Rheumatology Module July 2022 MRCP Part-1

Hint

Iritis is associated with conditions such as Reactive arthritis, Behcet’s, psoriatic arthropathy (about 20%) and inflammatory bowel disease.

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A chronic iritis is rarely described in association with Lyme disease.

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Osteogenesis imperfecta is associated with blue sclera.

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Keratoconus, meaning “cone shaped,” describes a condition in which the cornea (the clear front window of the eye) becomes thin and protrudes. This abnormal shape can cause serious distortion of visual images. It is not associated with iritis.

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Refsum’s disease is associated with retinitis pigmentosa.

Hint

Joint aspiration is the best option in this context. It is a simple procedure with a high diagnostic yield. A destructive septic arthritis is a potential diagnosis and it must be excluded as a matter of urgency. Joint aspirate is the most crucial step in excluding a septic arthritis, and allows the timely commencement of surgical management and appropriate antibiotics.

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Sending the joint aspiration for M/C/S in a blood culture bottle may increase yield. Whilst joint washout is appropriate management of septic arthritis, a diagnosis must be made prior to this being considered.

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The risk of introducing infection into the knee joint during simple aspiration by non-experts is 1 in 10,000 procedures, so the procedure is safe.

Hint

According to the National Institute for Health and Care Excellence (NICE) guidelines, the statement about infliximab that is most true is: C. Is licensed for the treatment of rheumatoid arthritis.

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Infliximab is indeed licensed for the treatment of rheumatoid arthritis, among other conditions. It is a tumour necrosis factor (TNF)-alpha inhibitor used in the management of autoimmune diseases by reducing inflammation.

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Now, let us address the other options:

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1. Must not be used in combination with methotrexate due to increased toxicity: This statement is incorrect. Infliximab is often used in combination with methotrexate to reduce the formation of anti-drug antibodies and increase the efficacy of treatment in conditions like rheumatoid arthritis.

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2. Is first line treatment for ulcerative colitis: Infliximab is not the first line of treatment for ulcerative colitis. It is considered for patients with moderate to severe ulcerative colitis when conventional therapy is not suitable or has not worked.

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3. Is a monoclonal antibody to the glycoprotein IIb-IIIa receptor: This statement is incorrect. Infliximab is a monoclonal antibody against TNF-alpha, not the glycoprotein IIb-IIIa receptor.

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4. It prevents relapse of Crohn’s disease in patients who are in remission: While infliximab is used in the management of Crohn’s disease, the National Institute for Health and Care Excellence (NICE) guidelines specifically recommend it for treating severe active Crohn’s disease and not explicitly for preventing relapse in patients who are in remission.

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In summary, option C is the most accurate statement regarding infliximab according to the National Institute for Health and Care Excellence (NICE) guidelines.

Hint

The correct option for a recognized feature of polymyalgia rheumatica (PMR) is:

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1. Weight loss.

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Weight loss is a recognized systemic symptom associated with polymyalgia rheumatica (PMR), along with other constitutional symptoms like fever and fatigue.

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Now, let us rule out the incorrect options:

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1. Elevated serum creatine phosphokinase activity: This is incorrect because polymyalgia rheumatica (PMR) typically does not involve elevated creatine phosphokinase levels, which would suggest muscle damage rather than the inflammation characteristic of polymyalgia rheumatica (PMR).

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2. An association with bronchial carcinoma: There is no recognized association between PMR and bronchial carcinoma. Polymyalgia rheumatica (PMR) is primarily an inflammatory condition affecting the shoulders, hip girdle, and neck.

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3. A peak incidence in the fourth decade of life: Polymyalgia rheumatica (PMR) most commonly affects individuals over the age of 50, with the peak incidence occurring between ages 70 and 80.

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4. Weakness of distal muscle groups: Polymyalgia rheumatica (PMR) is characterized by aching and morning stiffness in the proximal muscle groups, such as the shoulders and hips, rather than weakness in the distal muscles.

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In summary, weight loss is a recognized feature of polymyalgia rheumatica (PMR), reflecting the systemic nature of the disease. The other options listed do not accurately represent the features of polymyalgia rheumatica (PMR).

Hint

Montelukast works as a leukotriene receptor antagonist and is used in the treatment of asthma.

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Etanercept and infliximab inhibit TNF and are licensed in the treatment of rheumatoid arthritis.

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Infliximab is given with methotrexate and is associated with the development of tuberculosis.

Hint

A recessive gene is responsible for the activity of hepatic N-acetyl transferase resulting in slow or fast (intermediate and fast groups get lumped together) acetylation.

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45% of the United Kingdom population are slow acetylators.

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Drugs affected include:

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• isoniazid

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• hydralazine

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• dapsone

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• procainamide, and

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• sulphasalazine.

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Slow acetylators have increased risk of isoniazid-induced peripheral neuropathy, and hydralazine or procainamide-induced systemic lupus erythematosus (SLE).

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At least 38 drugs currently in use can cause DILE. However, most cases have been associated with these three:

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• procainamide

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• hydralazine, and

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• quinidine.

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The risk for developing lupus-like disease from any of the other 35 drugs is low or very low; with some drugs only one or two cases have been reported.

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• Isoniazid (INH) – low risk

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• Sulfasalazine – low risk.

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Hint

The specific cause of SLE is unknown, but multiple genetic predispositions and environmental factors have been identified. The underlying mechanism is thought to be associated with a deficiency in immune clearance, which results in autoimmunity. 

Patients with HLA-DR3, HLA-A1, and HLA-B8 are throught to have an innate susceptibility, as are those with abnormal complement levels (especially congenital deficiencies of C4 or C2) or specific immunoregulatory genotypes (mainly related to B-cell receptor pathway signalling). UV exposure, microbial response and drugs can then interact with this innate susceptibility to result in the development of SLE. 

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There is an increased risk in relatives of those affected, with 40% concordance in monozygotic twins. 

The role of infection in the aetiology of SLE has been extensively investigated, and it has been found that patients have higher antibody titres against EBV than the general population which is postulated to result in a T-cell abnormality with causes failure of the normal regulation of the B-cell response. In addition, chronic infections can result in anti-DNA antibodies and bacterial infections can precipitate a flare of SLE symptoms. 

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Environmental factors are more complex, but some associations have been found:
Silica dust, exogenous oestrogen administration and cigarette smoking may increase the risk of developing SLE.
Breastfeeding seems to decrease the risk of developing SLE.
UV light is a clear precipitant of skin disease, by stimulating keratinocytes resulting in overexpression of surface nuclear ribonucleoproteins and cytokine secretion with subsequent increased autoantibody production.  
Vitamin D deficiency may also result in increased autoantibody production. 

Hint

This boy has Henoch-Schönlein purpura (HSP). HSP is more commonly seen in infants, but may also be seen in older individuals.

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The buttock rash seen here is characteristic as is the blood and proteinuria. Creatinine may be elevated, although progression to renal failure is rare. Platelet count can be low, normal or elevated. IgA levels are elevated and the patient may also have an eosinophilia.

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HSP is usually managed with supportive measures only. There is no evidence that steroid therapy impacts on progression to renal failure.

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Non-steroidals may be of value in treating joint pain.

Hint

This lady has developed symptoms suggestive of drug-induced lupus erythematosus (DILE) after starting minocycline for her acne treatment. The autoantibody test that would help to confirm the diagnosis is E. Antihistone.

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Antihistone antibodies are the hallmark of drug-induced lupus. In the context of minocycline use, these antibodies are frequently present and can help confirm the diagnosis of drug-induced lupus erythematosus (DILE). Minocycline is a well-known trigger for this condition, and the presence of antihistone antibodies in this scenario would be supportive of drug-induced lupus erythematosus (DILE).

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The other options are incorrect for the following reasons:

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1. Anti-dsDNA: Anti-double-stranded DNA (dsDNA) antibodies are highly specific for systemic lupus erythematosus (SLE) rather than drug-induced lupus. While they may be present in some cases of drug-induced lupus erythematosus (DILE), they are not the primary antibodies used for confirmation of the diagnosis.

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2. Anti-RNP: Anti-ribonucleoprotein (RNP) antibodies are associated with mixed connective tissue disease (MCTD) and are not typically seen in drug-induced lupus erythematosus (DILE). They are also not specific for the condition and would not be the best choice for confirming a diagnosis of drug-induced lupus erythematosus (DILE).

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3. Anti-Scl-70: Anti-Scl-70 antibodies, also known as anti-topoisomerase I antibodies, are associated with systemic sclerosis (scleroderma) and are not indicative of drug-induced lupus erythematosus (DILE). These antibodies are not relevant to this lady’s presentation and would not be useful in confirming a diagnosis of drug-induced lupus erythematosus (DILE).

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4. Anti-Jo-1: Anti-Jo-1 antibodies are specific for polymyositis and dermatomyositis and are not associated with drug-induced lupus erythematosus (DILE). They would not be appropriate for confirming a diagnosis in a patient with suspected drug-induced lupus erythematosus (DILE) following minocycline therapy.

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In summary, the clinical presentation of fever, myalgia, arthralgia, and a characteristic rash, along with the recent use of minocycline, points towards a diagnosis of drug-induced lupus erythematosus (DILE). The detection of antihistone antibodies would be the most confirmatory test for this diagnosis, making option E the correct answer. The other options listed are associated with different autoimmune conditions and are not the best tests for confirming drug-induced lupus erythematosus (DILE) in a patient with this clinical presentation and drug history. The diagnosis of drug-induced lupus erythematosus (DILE) is further supported by the resolution of symptoms upon cessation of the offending drug, which in this case would be minocycline.

Hint

NICE have published guidance on the diagnosis and management of Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) (CG53). To confirm a diagnosis of fatigue the following main features need to be present:

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• It must be new in onset, persistent or recurrent and unexplained by other conditions.

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• It should be characterised by post-exertional malaise.

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• It should result in a substantial reduction in activity level.

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Associated symptoms include:

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• Hypersomnia or insomnia

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• Muscle or joint pain without inflammation 

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• Painful lymph nodes without lymphadenopathy

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• Headaches

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• Cognitive dysfunction.

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Red flag symptoms which suggest another diagnosis include:

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• Significant weight loss

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• Inflammatory arthropathy or connective tissue disease

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• Localising or focal neurological signs.

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The diagnosis of CFS is one of exclusion, and features must have been present for at least four months in an adult.

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Clinicians should check:

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• Full blood count (FBC)

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• Urea and electrolytes (U&Es)

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• Urinalysis

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• Liver function tests (LFTs)

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• Thyroid function

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• Erythrocyte sedimentation rate (ESR)

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• C reactive protein (CRP)

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• Blood glucose

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• Creatinine

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• Gluten sensitivity calcium

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• Creatinine kinase, and

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• Ferritin.

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Initial treatment should focus on management of symptoms, and minimising their impact on daily activities. Patients must be encouraged to continue work and studies. Any therapy should be person-centred and should aim to improve the patient’s capacity to manage their symptoms.

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The majority of research evidence is for cognitive behavioural therapy (CBT) and/or graded exercise therapy and these should be offered to all people with mild or moderate CFS.

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In addition, patients should be given tailored sleep management advice including how to introduce rest periods into their daily routine. Relaxation techniques should be offered for the management of pain, sleep problems, stress and anxiety.

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There is no research evidence to support the experience of some patients with CFS that they are more intolerant of drug treatment. In addition, there is insufficient evidence to recommend the use of complementary therapies or vitamin supplementation.

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The following drugs should not be used:

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• Monoamine oxidase inhibitors

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• Glucocorticoids

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• Mineralocorticoids

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• Dexamphetamine

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• Thyroxine

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• Antivirals.

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Referral to specialist CFS care should be offered within six months of presentation to people with mild CFS, within three to four months for moderate CFS and immediately for severe CFS.

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If chronic pain is a predominant feature, referral to a pain management clinic should be considered. Amitriptlyline should be considered for patients with poor sleep or pain.

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Patients should be advised that relapses and setbacks are to be expected.

Hint

Erythema nodosum is commonly idiopathic.

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It can also be related to streptococcal infections, acute sarcoidosis or related to drugs such as the oral contraceptive pill, sulphonamides and penicillins.

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Rarer causes include inflammatory bowel disease, tuberculosis, Behçet’s disease and other connective tissue disorders.

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In this case, a chest x ray would be the most helpful investigation as this may identify bilateral hilar lymphadenopathy which together with a bilateral ankle arthropathy would strongly support a diagnosis of acute sarcoidosis.

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Investigation of the bowel is unlikely to help in the absence of any bowel symptoms.

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Viral titres and ESR are non-specific.

Hint

The correct answer is D. Minocycline.

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Minocycline is a tetracycline antibiotic that is used to treat acne and other bacterial infections. It is one of the drugs that can cause drug-induced lupus erythematosus (DIL), a condition that mimics the symptoms of systemic lupus erythematosus (SLE), such as polyarthritis, fatigue, serositis, and positive antinuclear antibodies (ANA).

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The other options are incorrect for the following reasons:

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• A. Erythromycin is a macrolide antibiotic that is also used to treat acne and other infections. It is not associated with drug-induced lupus erythematosus (DIL), but it can cause liver toxicity, especially when combined with other drugs that are metabolized by the liver.

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• B. Oxytetracycline is another tetracycline antibiotic that is used to treat acne and other infections. It is also not associated with drug-induced lupus erythematosus (DIL), but it can cause photosensitivity, gastrointestinal disturbances, and tooth discolouration.

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• C. Isotretinoin is a retinoid that is used to treat severe acne that does not respond to other treatments. It is not associated with drug-induced lupus erythematosus (DIL), but it can cause teratogenicity, depression, dryness, and elevated liver enzymes.

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• E. Trimethoprim is a folate antagonist that is used to treat urinary tract infections and other infections. It is not associated with drug-induced lupus erythematosus (DIL), but it can cause megaloblastic anaemia, hyperkalaemia, and rash.

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Hint

The most likely cause of this gentleman’s knee effusion, given the history of a sexually transmitted disease and the current presentation, is B. Neisseria gonorrhoeae. This organism can cause gonococcal arthritis, which is a rare complication of gonorrhoea and presents with symptoms such as a swollen, painful joint, and in this case, a large effusion in the knee. The synovial fluid analysis showing an elevated white cell count without bacterial growth in culture is also consistent with gonococcal arthritis, as the bacteria are fastidious and may not grow in standard cultures.

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Now, let us rule out the other options:

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1. Trichomonas vaginalis is a protozoan that causes trichomoniasis, primarily affecting the urogenital tract. It does not typically cause joint effusions or systemic manifestations.

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2. Herpes simplex virus causes mucocutaneous infections and can lead to severe complications like encephalitis and neonatal herpes, but it is not known to cause joint effusions or septic arthritis.

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3. Treponema pallidum, the causative agent of syphilis, can cause a variety of symptoms including musculoskeletal manifestations in tertiary syphilis. However, the presentation of knee effusion in the context of recent sexually transmitted disease (STD) treatment makes acute syphilis less likely.

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4. Human papilloma virus (HPV) is associated with warts and certain cancers, but it does not cause joint effusions or septic arthritis.

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Given the clinical context and the available information, Neisseria gonorrhoeae is the most likely cause of this gentleman’s condition.

Hint

Given the clinical presentation and laboratory findings, the most likely diagnosis for this gentleman is D. Drug-induced systemic lupus erythematosus (SLE). This gentleman’s symptoms and the strongly positive antinuclear antibody (ANA) test, along with a negative anti-dsDNA, suggest systemic lupus erythematosus (SLE). However, the history of being well-controlled on minocycline, which is known to potentially induce systemic lupus erythematosus (SLE), points towards drug-induced systemic lupus erythematosus (SLE).

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The other options are less likely as discussed below:

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• A. Systemic lupus erythematosus (SLE): While this gentleman’s symptoms and laboratory results could suggest systemic lupus erythematosus (SLE), the history of minocycline use makes drug-induced systemic lupus erythematosus (SLE) more likely.

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• B. Seronegative spondyloarthropathy: This group of disorders typically presents with negative rheumatoid factor and antinuclear antibody (ANA) tests, which does not align with this gentleman’s strongly positive antinuclear antibody (ANA).

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• C. Fibromyalgia: This condition is characterized by widespread pain and tenderness but does not usually present with significant laboratory abnormalities such as elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels.

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• E. Rheumatoid arthritis: This gentleman’s negative rheumatoid factor and the absence of symptoms typical of rheumatoid arthritis, such as symmetric joint pain, make this diagnosis less likely. Additionally, rheumatoid arthritis would not explain the high IgG levels or the strongly positive antinuclear antibody (ANA) test.

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In conclusion, this gentleman’s clinical and laboratory findings are most consistent with D. Drug-induced systemic lupus erythematosus (SLE), likely related to the use of minocycline.

Hint

The most likely diagnosis is E. Takayasu’s arteritis. This is a rare type of vasculitis that affects the large arteries, especially the aorta and its branches. It can cause symptoms such as fatigue, fever, weight loss, abdominal pain, arm claudication, pulselessness, hypertension, and joint inflammation. The diagnosis is supported by the presence of a blood pressure difference between the arms, the diminished or absent radial pulses, the elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and the young age and female gender of the patient.

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The other options are less likely for the following reasons:

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• A. Fibromuscular dysplasia: This is a condition that causes narrowing or enlargement of medium and large arteries. It can affect the renal, carotid, mesenteric, coronary, and peripheral arteries, and cause symptoms such as high blood pressure, headache, tinnitus, neck pain, abdominal pain, chest pain, and limb pain. However, this condition does not cause fever, weight loss, joint inflammation, or elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). It is also more common in older adults than in young people.

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• B. Temporal arteritis: This is a form of vasculitis that affects the temporal arteries and other cranial arteries. It can cause symptoms such as headache, scalp tenderness, jaw pain, vision loss, and fever. However, this condition does not affect the aorta or its branches, and does not cause blood pressure difference, pulselessness, or joint inflammation. It is also very rare in young people, and more common in people over 50 years of age.

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• C. Juvenile chronic arthritis: This is a term for several types of arthritis that affect children under 16 years of age. It can cause joint inflammation, stiffness, pain, and swelling. However, this condition does not affect the large arteries, and does not cause blood pressure difference, pulselessness, or abdominal pain. It may cause fever, weight loss, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but these are usually mild and transient.

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• D. Kawasaki’s disease: This is a rare condition that causes inflammation of the blood vessels, especially the coronary arteries. It mainly affects children under 5 years of age. It can cause symptoms such as fever, rash, red eyes, swollen lymph nodes, red lips and tongue, and peeling skin. However, this condition does not cause blood pressure difference, pulselessness, or joint inflammation. It may cause abdominal pain, but this is usually mild and transient. It is also very unlikely to affect young adults.

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Hint

Given the history of treatment for acute lymphoblastic leukaemia (ALL) and the presentation of acute left hip pain, the most likely diagnosis is avascular necrosis of the femoral head. Avascular necrosis (AVN) is a condition where bone tissue dies due to a lack of blood supply, and it is a known complication of acute lymphoblastic leukaemia (ALL) treatment due to the use of corticosteroids and chemotherapy, which can affect blood supply to the bones.

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The other options are incorrect for the following reasons:

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1. Pseudogout – This condition involves the deposition of calcium pyrophosphate crystals within the joint. It typically presents with sudden, painful swelling in a joint, often the knee, rather than the hip. It is associated with metabolic conditions like hypercalcaemia and is less likely to be related to acute lymphoblastic leukaemia (ALL) treatment.

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2. Gout – Gout is caused by the deposition of uric acid crystals in the joint, leading to inflammation. It most commonly affects the big toe and is associated with high levels of uric acid in the blood. While gout can cause acute joint pain, it is not typically associated with acute lymphoblastic leukaemia (ALL) treatment.

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3. Septic arthritis – This is an infection within the joint space that causes severe pain, redness, swelling, and fever. It can occur after joint surgery or in immunocompromised individuals but is less likely in this scenario without evidence of an overlying infection or penetrating injury.

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4. Osteoarthritis – This is a degenerative joint disease that typically affects older adults and is characterized by the gradual wearing down of joint cartilage. It presents with chronic joint pain and stiffness, particularly with activity, and is unlikely in a young gentleman without a history of joint trauma or chronic stress on the joint.

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In conclusion, the history of acute lymphoblastic leukaemia (ALL) treatment and the acute presentation of hip pain strongly suggest avascular necrosis of the femoral head as the most likely diagnosis.

Hint

Swelling and burning sensation over the thumb in a young individual with positive Finklestein’s test is characteristic of De Quervain’s tenosynovitis. Finklestein’s test is performed by grasping the thump and ulnar deviating the hand sharply. It is positive if sharp pain occurs along the distal radius. 

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De Quervain’s is caused by overuse of the thumb, as is the case here with this patient’s job. Thickening of the synovial sheaths surrounding extensor pollicis brevis and abductor polices longus leads to pain and reduced movement.

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Osteoarthritis is a possibility but would be associated more commonly in older individuals, and tenderness is classically at the base of the thumb.

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Carpal tunnel presents with pain and paraesthesia of the thumb, index, middle and half of the ring fingers on the affected side.

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Radial tunnel syndrome presents with pain in the dorsal aspect of the upper forearm, and is caused by pressure on the radial nerve possibly from compression by the muscles of the forearm.

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Rheumatoid arthritis presents with joint swelling and pain, with subsequent hand deformity if left untreated. It is classically symmetrical.

Hint

This question aims to cover the following learning points:

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• Distinguishing features of chronic inflammatory back pain

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• Population specific HLA association

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• Common differentials for ankylosing spondylitis.

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This man has ankylosing spondylitis (AS).

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The commonest subtype HLA associations are HLA B*2705 (Caucasians), B*2704 (Chinese, Japanese) and B*2702 (Mediterranean). The B*2706 subtype is weakly associated and commonly found in normal south east Asian individuals.

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Chronic (more than three months) back pain characteristics that favour a spondyloarthritic aetiology include:

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• Age of onset before 40 years

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• Insidious onset

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• Amelioration with exercise

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• Refractory with rest

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• Night pain (with improvement upon arising).

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His associated extra-articular manifestations include enthesitis of the Achilles and supraspinatus tendons.

Hint

The correct answer is B. Anti-Ro (SSA) antibody. This is because maternal anti-Ro/SSA antibodies are the most common and specific autoantibodies associated with foetal congenital heart block (CHB). These antibodies cross the placenta and cause inflammation, cell death, and scarring of the fetal cardiac conduction system, leading to a block in signal transmission at the atrioventricular (AV) node.

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The other answer options are incorrect because:

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• A. Anti-dsDNA antibody: This option is incorrect because anti-dsDNA antibodies are not associated with foetal congenital heart block (CHB). Anti-dsDNA antibodies are specific for systemic lupus erythematosus (SLE) and are involved in the pathogenesis of lupus nephritis, but they do not affect the foetal heart.

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• C. Anti-mitochondrial antibody (AMA): This option is incorrect because anti-mitochondrial antibodies (AMA) are not associated with foetal complete heart block (CHB). Anti-mitochondrial antibodies (AMA) are specific for primary biliary cirrhosis, a chronic liver disease, but they do not cross the placenta or target the foetal heart.

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• D. Anti-Jo 1 antibody: This option is incorrect because anti-Jo 1 antibodies are not associated with foetal congenital heart block (CHB). Anti-Jo 1 antibodies are specific for polymyositis and dermatomyositis, inflammatory muscle diseases, but they do not cross the placenta or target the foetal heart.

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• E. Anti-La (SSB) antibody: This option is incorrect because anti-La/SSB antibodies are not as specific as anti-Ro/SSA antibodies for foetal congenital heart block (CHB). Anti-La/SSB antibodies are often found together with anti-Ro/SSA antibodies in systemic lupus erythematosus (SLE) and Sjögren syndrome, but they are less frequently detected in mothers of children with congenital heart block (CHB). Moreover, anti-La/SSB antibodies alone are not sufficient to cause congenital heart block (CHB), and they may have a protective role against the development of congenital heart block (CHB).

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Hint

The most likely maternal antibody linked to the newborn’s illness, given the history of systemic lupus erythematosus (SLE) in the mother and the symptoms of an erythematous rash and bradycardia, is B. Anti-Ro/SSA. Neonatal lupus is a condition that can occur when maternal anti-Ro/SSA antibodies are passed to the foetus, leading to symptoms such as skin rash and cardiac issues like bradycardia.

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Now, let us rule out the other options:

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• A. c-anti-neutrophil cytoplasmic antibodies (cANCA): These antibodies are associated with vasculitis, not neonatal lupus, and would not explain the newborn’s symptoms.

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• C. Anti-smooth muscle: These antibodies are typically associated with autoimmune hepatitis and are not linked to neonatal lupus or the symptoms described.

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• D. Rheumatoid factor: This antibody is associated with rheumatoid arthritis and other autoimmune conditions but not specifically with neonatal lupus or the symptoms observed in the newborn.

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• E. Anti-LKM antibodies: These are associated with autoimmune hepatitis type 2 and are not related to the symptoms of neonatal lupus described in the newborn.

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In conclusion, the presence of anti-Ro/SSA antibodies is the most likely cause of the newborn’s condition, consistent with neonatal lupus. The other antibodies listed are not typically associated with the symptoms described in the newborn.

Hint

The correct answer is C. Systemic lupus erythematosus (SLE). This is a chronic autoimmune disease that can affect any organ in the body, but mainly involves the skin, joints, kidneys, and blood. The symptoms and signs that have been described are consistent with this diagnosis, such as:

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• Fatigue, which is one of the most common and disabling symptoms of lupus, affecting up to 90% of people with the condition.

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• Arthralgia, or joint pain, which affects about 95% of people with lupus at some point, especially in the wrists and ankles.

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• Rash, which can take various forms, but the most characteristic one is a butterfly-shaped (malar) rash that appears over the bridge of the nose and on both cheeks, affecting about 50% of people with lupus.

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• Hair loss, which can be caused by inflammation of the scalp, medications, or hormonal changes, affecting about 45% of people with lupus.

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The other options are incorrect for the following reasons:

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• A. Porphyria cutanea tarda is a condition that affects the production of heme, a component of haemoglobin and other proteins. It causes skin blisters, itching, and increased hair growth on the face and hands, especially after exposure to sunlight. It does not cause fatigue, joint pain, or hair loss on the scalp.

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• B. Scleroderma, or systemic sclerosis, is a condition that causes hardening and tightening of the skin and connective tissues. It can affect the fingers, hands, face, and other parts of the body, causing skin thickening, ulcers, Raynaud’s phenomenon, and calcinosis. It does not cause a butterfly-shaped rash or hair loss on the scalp.

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• D. Hypothyroidism, or an underactive thyroid, is a condition that affects the metabolism and energy levels of the body. It can cause fatigue, weight gain, dry hair and skin, muscle aches, cold sensitivity, and feelings of depression. It does not cause joint pain, a butterfly-shaped rash, or kidney problems.

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• E. Dermatomyositis is a condition that affects the muscles and the skin. It can cause muscle weakness, pain, and inflammation, as well as a distinctive skin rash on the eyelids, knuckles, elbows, knees, and chest. It does not cause hair loss on the scalp or kidney problems.

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Hint

All of these can be causes of back pain. The key differentiators in this case are the age of the patient and the detailed history of the type of back pain.

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Patients often present with ankylosing spondylitis (AS) in their 20s and 30s with a history of chronic back pain and stiffness. Key features of the pain include:

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• Early morning stiffness of more than 30 minutes

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• Alternating buttock pain

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• Waking in the second half of the night

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• Pain easing with non-steroidal anti-inflammatory drugs (NSAIDs)

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• Pain which is worse with rest and eases with exercise

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In the advanced stages of AS, patients develop loss of lumbar lordosis, buttock atrophy and an exaggerated thoracic kyphosis. This results in a posture commonly referred to as ‘question mark’.

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Metastatic cancer can affect the spine and cause back pain. This is usually associated with ‘red flag’ signs suggesting malignancy. This diagnosis is less common in younger patients.

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Muscular strain is the commonest cause of back pain in general practice but chronic pain for more than three months may indicate AS and should be investigated.

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Reactive arthritis can cause inflammatory back pain with similar symptoms to AS but there is no history of preceding genitourinary or gastrointestinal infection.

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Scheuermann’s disease generally presents in teenagers with thoracic back pain and increased thoracic kyphosis, and therefore does not fit with this scenario.

Hint

This question recognises the importance of using conservative management before embarking on potentially long term medication with risks of side effects, and the recognition of the vasospastic effect of cigarette smoking.

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The prostaglandin iloprost is useful in the treatment of Raynaud’s phenomenon and can be considered if the patient does not respond to nifedipine Retard or has developed digital ulceration or ischaemia.

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Raynaud’s phenomenon responds well to calcium channel blockers such as nifedipine but given that this gentleman has so many factors that can be altered in his lifestyle, such as smoking and working in a cold environment, more simple measures to change these could avoid daily medication with its side effects.

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Digital sympathectomy should be considered as a last resort when drug therapy has failed or has not been tolerated.

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Capillaroscopy is useful especially when serum antibodies are positive but it would not change the management at this stage.

Hint

Current United Kingdom guidance suggests that during the first three months of treatment with sulfasalazine, full blood count (FBC) should be monitored monthly for the first three months.

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Sulphasalazine should be withheld until discussion with the specialist team if:

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• the white cell count is less than 3.5

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• neutrophils is less than 2, or

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• platelets are less than 150.

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If mean corpuscular volume (MCV) is more than 105 fl, vitamin B12, folate and thyroid-stimulating hormone (TSH) should be checked and treated if found to be abnormal. If these are all normal it should be discussed with the specialist team.

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If counts remain normal within the first three months, full blood count can be checked three monthly.

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Liver function tests (LFTs) should also be checked monthly for the first three months. If either the aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are more than twice the upper limit of normal sulfasalazine should be withheld until discussion with the specialist team. If the LFTs remain normal for the first three months, monitoring can be decreased to three monthly.

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If, following the first year, the dose has not been increased and blood results have been stable, the frequency of monitoring can be reduced to every six months for the second year of treatment. Thereafter monitoring is not required, although FBC and LFTs should be checked one month after any dose increase.

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Side effects of sulfasalazine include myelosuppression, macrocytosis, hypersensitivity and azoospermia in males.

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There are numerous signs of sulfasalazine toxicity. Rash and oral ulceration should be asked about and, if severe, the drug should be withheld until specialist advice has been sought. Nausea, dizziness and headache can be common and sometimes necessitate dose reduction. If patients present with abnormal bruising or sore throat an urgent FBC should be done, and sulfasalazine withheld until results are available.

Hint

The most likely diagnosis for this gentleman is E. Discoid lupus erythematosus. This is a chronic autoimmune skin condition that causes red, scaly, and sometimes atrophic patches on the face and other sun-exposed areas. The plugging of hair follicles with keratin and the diminution of the skin are characteristic features of discoid lupus erythematosus.

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The other options can be ruled out as follows:

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• A. Polymorphic light eruption is a type of sun allergy that causes itchy, red, and sometimes blistering rashes on the skin after sun exposure. However, it does not cause plugging of hair follicles or skin atrophy.

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• B. Porphyria cutanea tarda is a disorder of heme metabolism that causes photosensitivity, blisters, erosions, and hyperpigmentation on the skin. It does not cause scaly plaques or hair follicle plugging.

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• C. Psoriasis is a common inflammatory skin condition that causes red, scaly, and sometimes pustular patches on the skin. It can affect the face, but it usually spares the central part of the face and involves the hairline and ears. It does not cause hair follicle plugging or skin atrophy.

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• D. Atopic eczema is a chronic allergic skin condition that causes dry, itchy, and inflamed skin. It can affect the face, but it usually involves the eyelids, perioral area, and nasolabial folds. It does not cause scaly plaques, hair follicle plugging, or skin atrophy.

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Hint

Based on the presence of back pain, raised inflammatory markers and reduced spinal mobility, this patient has ankylosing spondylitis (AS).

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Ankylosing spondylitis (AS) is a chronic, potentially disabling, form of seronegative spondyloarthropathy which primarily involves the axial skeleton. The aetiology is not clearly understood, but it involves the interaction of genetic and environmental factors. The pathology mainly affects the entheses, where ligaments, tendons and capsules are attached to the bone.

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Current British Society for Rheumatology recommendations state that the modified New York criteria should be used to diagnose ankylosing spondylitis:

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Clinical criteria:

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• Low back pain, present for more than three months, improved by exercise but not relieved by rest

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• Limitation of lumbar spine motion in both the sagittal and frontal planes

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• Limitation of chest expansion relative to normal values for age and sex

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Radiological criteria:

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• Sacroiliitis on x ray

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Diagnosis:

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• Definite AS if the radiological criterion is present plus at least one clinical criterion

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• Probable AS if three clinical criteria are present alone or if the radiological criterion is present but no clinicial criteria are present.

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It is widely accepted that making the diagnosis early is difficult because the onset is insidious, and there is no definitive diagnostic test. One study has stated that the average time from onset to diagnosis ranges from three to 11 years. Timely diagnosis therefore requires a high index of suspicion.

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HLA-B27 is found in 90% patients with AS but also 8% of the general population and therefore should not be relied upon in making a diagnosis.

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MRI can visualise sacroiliitis in patients with typical symptoms of AS but normal radiographs, and it is evolving as the most important diagnostic imaging tool in early disease.  However, as yet a diagnosis of ankylosing spondylitis cannot be made on MRI findings alone and these cases are currently termed non-radiographic axial spondyloarthritis (SpA).

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Both HLA-B27 and sacroiliitis on MRI play a major role in the recently proposed Assessment of SpondyloArthritis International Society (ASAS) diagnostic algorithm. This may replace the modified New York criteria in the future.

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An x ray of the lumbar spine may show bridging syndesmophytes between the vertebral bodies in keeping with ankylosing spondylitis but this is not part of the diagnostic criteria, and it is a late sign.

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Radiographic sacroiliitis is a requirement for patients to be eligible for anti-TNF treatment for AS.

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The sacroiliitis is usually bilateral and symmetrical. It progresses from blurring of the subchondral bone plate to irregular erosions of the margins of the sacroiliac joints to sclerosis, narrowing, and finally fusion.

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Erosions of the sacroiliac joint are generally seen earlier in the lower portion due to its synovial lining, and on the iliac side due to the thinner cartilage covering this side of the joint.

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As x ray is not available as an option here, MRI of the sacroiliac joints is the most appropriate answer.

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PET-CT and bone scans do not have a role in the diagnosis and investigation of ankylosing spondylitis.

Hint

The most likely diagnosis for this lady with a history of swinging fever, weight loss, erythematous nodular lesions on the shin, bilateral hilar adenopathy, and non-caseating granulomas is E. Sarcoidosis. Sarcoidosis is characterised by the presence of non-caseating granulomas and can present with Löfgren’s syndrome, which includes erythema nodosum (erythematous nodular lesions), fever, bilateral hilar lymphadenopathy, and arthralgia. The absence of peripheral adenopathy and organomegaly also aligns with sarcoidosis, which typically presents with bilateral hilar lymphadenopathy without peripheral lymph node involvement.

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The other options are less likely for the following reasons:

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• A. Lymphoma: While lymphoma can present with lymphadenopathy, it usually causes peripheral adenopathy and may show caseating granulomas if associated with tuberculosis. The absence of peripheral adenopathy and the presence of non-caseating granulomas make lymphoma less likely.

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• B. Histoplasmosis: This fungal infection can mimic sarcoidosis radiologically, but it is more commonly associated with caseating granulomas and often has a history of exposure to bird or bat droppings in endemic areas, which is not mentioned in this case.

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• C. Tuberculosis: Tuberculosis typically presents with caseating granulomas, and this lady would likely have a positive tuberculin skin test or interferon-gamma release assay, which is not mentioned here.

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• D. HIV infection: Human immunodeficiency virus (HIV) can cause generalized lymphadenopathy and can be associated with various opportunistic infections. However, the presentation of non-caseating granulomas and the specific symptoms described are more indicative of sarcoidosis.

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In summary, based on the clinical presentation and biopsy findings, sarcoidosis is the most likely diagnosis for this lady.

Hint

The first management step to be taken for this lady presenting with bilateral wrist pain, generalized aching, morning stiffness, fever, and a worsening of acne over her nasal bridge and cheeks, along with a positive autoimmune screen, should be A. Stop minocycline. Minocycline is known to cause drug-induced lupus erythematosus (DILE), which can present with symptoms similar to systemic lupus erythematosus (SLE), including musculoskeletal pain, fever, and a positive antinuclear antibody (ANA) test. The worsening of her acne and the presence of anti-DNA Histone antibodies, which are associated with drug-induced lupus, further support this decision.

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Let us discuss why the other options are less appropriate:

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• Methylprednisolone 80 mg: While corticosteroids like methylprednisolone are used to reduce inflammation, they are not the first step in management without a definitive diagnosis and especially if the symptoms may be drug-induced.

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• Methotrexate 15 mg: Methotrexate is a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis and other autoimmune conditions. However, it is not the first-line treatment for suspected drug-induced lupus erythematosus (DILE) and should not be used without a definitive diagnosis.

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• Naproxen 500 mg twice daily: Naproxen is a non-steroidal anti-inflammatory drug (NSAID) that can help with pain and inflammation. However, if a patient’s symptoms are due to drug-induced lupus erythematosus (DILE), the priority is to remove the offending agent rather than to treat the symptoms with non-steroidal anti-inflammatory drugs (NSAIDs).

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• Hydroxychloroquine 400 mg: Hydroxychloroquine is used in the treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis. However, if a patient’s condition is related to minocycline use, the appropriate step is to discontinue the drug rather than start treatment with hydroxychloroquine.

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In conclusion, the first step should be to stop minocycline to see if the symptoms improve, which would support a diagnosis of drug-induced lupus erythematosus (DILE).

Hint

This lady has ankylosing spondylitis (AS), based on the history of back pain and stiffness which improves with activity.

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The aim of treatment of AS is symptom control and maintenance of function. Physiotherapy is critical, and should be undertaken daily. There is limited evidence regarding any medication’s ability to alter the course of disease.

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Non-steroidal anti-inflammatory drugs (NSAIDs) should be started in all cases, unless contraindicated. Where symptoms are not controlled additional analgesics (for example, amitriptyline), corticosteroid injections or oral corticosteroids can be used. She is already on them PRN and should be started on regular NSAIDs with a PPI.

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Current NICE guidelines state that etanercept, golimumab and adalimumab can be used in patients with severe AS: 

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• That satisfy the modified New York criteria

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• Have confirmed, sustained active spinal disease over at least 12 weeks

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• In whom maximal conventional treatment with two or more NSAIDs has failed

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• Where there are no contraindications present.

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Infliximab is not recommended. The evidence for the use of other disease modifying antirheumatic drugs is weak.

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Surgery is occasionally useful to correct spinal or joint deformities.

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In the last few years evidence for additional agents has been growing. Another anti-TNF alpha agent, certolizumab, is under investigation. Rituximab is also being studied as a treatment.

Hint

HAO is characterised by deficiency of C1 esterase inhibitor.

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This leads to persistent activation of the classical complement pathway and C4 levels are frequently low secondary to activation and consumption.

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If treatment fails to normalise the C4 levels and they remain persistently low, these patients are at an increased risk of developing SLE

Hint

The most likely diagnosis for this lady is C. Adult onset Still’s disease (AOSD). This is a rare inflammatory disorder that causes high fever, arthritis, rash, sore throat, and elevated inflammatory markers. The exact cause of adult onset Still’s disease (AOSD) is unknown, but it may be triggered by infections, genetic factors, or environmental factors. Adult onset Still’s disease (AOSD) can affect any organ system and may have serious complications such as macrophage activation syndrome, amyloidosis, or organ failure. Adult onset Still’s disease (AOSD) is diagnosed by excluding other causes of fever and inflammation, and by applying certain criteria that include clinical and immunologic features.

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The other options are less likely for the following reasons:

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• A. Seronegative rheumatoid arthritis: This is a type of rheumatoid arthritis that does not have positive rheumatoid factor or anti-citrullinated peptide antibodies. It causes chronic and symmetrical joint inflammation, especially in the hands and feet. However, it does not usually cause high fever, rash, sore throat, or very high serum ferritin levels.

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• B. Rheumatic fever: This is a complication of streptococcal pharyngitis that can cause fever, arthritis, carditis, chorea, erythema marginatum, and subcutaneous nodules. However, it is uncommon in adults and usually occurs within two to four weeks of the initial infection. It also requires evidence of recent streptococcal infection, such as positive throat culture, rapid antigen test, or elevated ASO titre.

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• D. Polymyositis: This is an inflammatory myopathy that causes progressive and symmetrical muscle weakness, especially in the proximal muscles of the limbs and trunk. It may also cause muscle pain, dysphagia, interstitial lung disease, or skin rash. However, it does not usually cause fever, arthritis, sore throat, or leukocytosis. It also requires evidence of muscle damage, such as elevated creatine kinase, abnormal electromyography, or muscle biopsy.

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• E. Systemic lupus erythematosus (SLE): This is a chronic autoimmune disease that can affect multiple organ systems and cause various manifestations, such as fever, arthritis, rash, oral ulcers, serositis, nephritis, or neuropsychiatric disorders. However, it usually requires positive ANA or other specific autoantibodies, such as anti-dsDNA, anti-Sm, or anti-phospholipid antibodies. It also has different criteria for diagnosis and classification, which include clinical and immunologic features.

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Therefore, the correct answer is C. Adult onset Still’s disease (AOSD).

Hint

The majority of cases of congenital heart block are due to the presence of anti-Ro/SSA antibodies in the maternal serum.

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The mother may have no evidence of a connective tissue disorder.

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The risks of congenital heart block in mothers with anti-Ro/SSA antibodies remains very small (<3%) but the correlation between the presence of anti-Ro/SSA antibodies and congenital heart block is very strong.

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The heart block is generally permanent (unlike other features of neonatal lupus) and insertion of a permanent pacemaker is frequently required.

Hint

Methotrexate is teratogenic and, according to the British National Formulary (BNF), the manufacturers advise effective contraception during, and for at least three months, after stopping methotrexate. Fertility may be reduced during treatment, but this usually reverses upon stopping. Advice regarding reduced fertility and potential teratogenicity applies to both females and males who are taking methotrexate.

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There is little published information on the potential teratogenicity following paternal exposure to methotrexate. There have, however, been reports of alterations of the spermatozoa and oligospermia following exposure to methotrexate. These seem to be reversible on cessation of treatment.

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The National Patient Safety Agency (NPSA) state on their patient held record that: “It is recommended that men wait six months after finishing their treatment, before trying to father a child as sperm can be affected”. Paternal exposure to methotrexate is not regarded as an indication for termination of pregnancy, however

Hint

The correct answer is C. T-score −2.5. This is a measurement of bone mineral density (BMD) that compares the person’s bone mineral density (BMD) with the average bone mineral density (BMD) of a young, healthy adult of the same sex. A T-score of −2.5 or lower indicates osteoporosis, which means the person has low bone mineral density (BMD) and a high risk of fractures.

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The other options can be ruled out as follows:

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• A. T-score −1.5 is a measurement of bone mineral density (BMD) that indicates osteopenia, which means the person has below normal bone mineral density (BMD) but not low enough to be diagnosed with osteoporosis.

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• B. Z-score −1.5 is a measurement of bone mineral density (BMD) that compares the person’s bone mineral density (BMD) with the average bone mineral density (BMD) of people of the same age, sex, and body size. A Z-score of −1.5 or lower is considered below the expected range for the person’s age group and may indicate secondary osteoporosis, which is caused by an underlying medical condition or medication.

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• D. Z-score −2.0 is a measurement of bone mineral density (BMD) that is also below the expected range for the person’s age group and may indicate secondary osteoporosis. However, Z-scores are not used to diagnose osteoporosis in adults over 50 years old, as bone density naturally decreases with age. T-scores are more useful for diagnosing primary osteoporosis, which is caused by aging and hormonal changes.

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• E. None of the above is not a correct answer, as T-score −2.5 is a valid measurement that indicates a diagnosis of osteoporosis.

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Hint

The correct option for a diagnosis of tennis elbow is: D. Pain on wrist extension against resistance.

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Tennis elbow, or lateral epicondylitis, is characterized by pain on the lateral side of the elbow, which can be exacerbated by extending the wrist against resistance. This is due to the overuse of the extensor muscles of the forearm, particularly where they attach to the lateral epicondyle of the elbow.

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Now, let us address why the other options are incorrect:

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1. Pain on extension of the elbow: This is not specific to tennis elbow, as pain on elbow extension can be associated with various elbow pathologies and does not specifically indicate the involvement of the extensor tendons of the forearm.

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2. Pain on pronation of the forearm: Pain during pronation of the forearm is not typical for tennis elbow, which primarily affects the extensor muscles that are involved in wrist extension, not pronation.

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3. Pain on flexion of the fingers against resistance: This would more likely suggest an issue with the flexor tendons, which is not characteristic of tennis elbow.

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4. Pain on pressure over the medial epicondyle: Pain over the medial epicondyle would suggest golfer’s elbow, or medial epicondylitis, which affects the flexor tendons of the forearm, not the extensor tendons affected in tennis elbow.

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In summary, the most consistent sign of tennis elbow is pain on the lateral side of the elbow when the wrist is extended against resistance, due to the involvement of the extensor muscles of the forearm.

Hint

The next step in the long-term management of this lady with longstanding psoriasis and persistently swollen, painful, and tender left knee, who has partial relief from non-steroidal anti-inflammatory drugs (NSAIDs) and a normal x-ray, would be to consider disease modifying antirheumatic drugs (DMARDs) (option C). Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or leflunomide, are often used when symptoms do not sufficiently improve with non-steroidal anti-inflammatory drugs (NSAIDs) alone. They can slow the progression of psoriatic arthritis and prevent joint damage.

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The other options are incorrect for the reasons as discussed below:

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• Anti-TNF alpha agents (A): These are typically used for moderate to severe psoriatic arthritis and may be considered if there is an inadequate response to disease-modifying antirheumatic drugs (DMARDs). They are not usually the first line of treatment due to their cost and potential side effects.

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• Intra-articular corticosteroids (B): These can provide relief for acute flare-ups but are not generally used for long-term management due to potential joint damage with repeated use.

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• Oral corticosteroids (D): These are not commonly used for long-term management of psoriatic arthritis due to the risk of significant side effects, especially with long-term use.

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• Alternative non-steroidal anti-inflammatory drugs (NSAIDs) (E): While other non-steroidal anti-inflammatory drugs (NSAIDs) could be tried, if one non-steroidal anti-inflammatory drug (NSAID) does not provide adequate relief, it is unlikely that another will have a significantly different effect. Additionally, non-steroidal anti-inflammatory drugs (NSAIDs) do not prevent disease progression.

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Therefore, disease-modifying antirheumatic drugs (DMARDs) are the most appropriate next step in her management, aiming to control the disease activity and prevent joint damage.

Hint

The combination of lower back pain and stiffness makes ankylosing spondylitis (AS) the most likely diagnosis in this scenario.

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Ankylosing spondylitis is a chronic, potentially disabling, form of seronegative spondyloarthropathy which primarily involves the axial skeleton. The aetiology is not clearly understood, but it involves the interaction of genetic and environmental factors. The pathology mainly affects the entheses, where ligaments, tendons and capsules are attached to the bone.

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Current British Society for Rheumatology recommendations state that the modified New York criteria should be used to diagnose ankylosing spondylitis:

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Clinical criteria:

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• Low back pain, present for more than three months, improved by exercise but not relieved by rest

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• Limitation of lumbar spine motion in both the sagittal and frontal planes

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• Limitation of chest expansion relative to normal values for age and sex

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Radiological criteria:

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• Sacroiliitis on x ray

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Diagnose:

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• Definite AS if the radiological criterion is present plus at least one clinical criterion

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• Probable AS if three clinical criteria are present alone or if the radiological criterion is present but no clinicial criteria are present.

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It is widely accepted that making the diagnosis early is difficult because the onset is insidious, and there is no definitive diagnostic test. One study has stated that the average time from onset to diagnosis ranges from three to 11 years. Timely diagnosis therefore requires a high index of suspicion.

_x000D_

HLA-B27 is found in 90% patients with AS but also 8% of the general population and therefore should not be relied upon in making a diagnosis.

_x000D_

MRI can visualise sacroiliitis in patients with typical symptoms of AS but normal radiographs and it is evolving as the most important diagnostic imaging tool in early disease. 

_x000D_

However, as yet a diagnosis of ankylosing spondylitis cannot be made on MRI findings alone and these cases are currently termed non-radiographic axial spondyloarthritis (SpA).

_x000D_

Both HLA-B27 and sacroiliitis on MRI play a major role in the recently proposed Assessment of SpondyloArthritis International Society (ASAS) diagnostic algorithm. This may replace the modified New York criteria in the future.

_x000D_

An x ray of the lumbar spine may show bridging syndesmophytes between the vertebral bodies in keeping with ankylosing spondylitis but this is not part of the diagnostic criteria, and it is a late sign.

_x000D_

Radiographic sacroiliitis is a requirement for patients to be eligible for anti-TNF treatment for AS. The sacroiliitis is usually bilateral and symmetrical. It progresses from blurring of the subchondral bone plate to irregular erosions of the margins of the sacroiliac joints to sclerosis, narrowing, and finally fusion.

_x000D_

Erosions of the sacroiliac joint are generally seen earlier in the lower portion due to its synovial lining, and on the iliac side due to the thinner cartilage covering this side of the joint.

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Discitis is inflammation of the vertebral disc space, often related to infection. It typically presents with an insidious onset of pain and localised tenderness, which is worsens with activity (unlike the stiffness described here).

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Mechanical back pain and osteoarthritis pain also improve with NSAIDs. However, they cause low back pain that is worse with activity, and relieved with rest.

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Spondylolisthesis is the movement of one vertebra due to instability. It presents with pain which is worse with activity, and may be associated with nerve root compression.

Hint

The next step in the management of the lady’s symptoms should be E. Oral non-steroidal anti-inflammatory drugs (NSAIDs). Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated for relief of pain and swelling in cases of inflammatory arthritis when infection has been ruled out, as in this case where the knee aspirate showed no organisms.

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Let us consider why the other options are less appropriate:

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A. Intra-articular corticosteroids: These are typically used for inflammatory arthritis but should be avoided until infection has been definitively excluded, as corticosteroids can worsen an existing infection.

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B. Oral antibiotics for six weeks: Long-term antibiotics are prescribed for confirmed infectious arthritis, which is not indicated here due to the absence of organisms on Gram stain or culture.

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C. Commence disease modifying antirheumatic drug (DMARD): Disease-modifying antirheumatic drugs (DMARDs) are used for chronic inflammatory conditions like rheumatoid arthritis, which is not indicated here without a definitive diagnosis and persistent inflammatory signs.

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D. Oral antibiotics for five days: Short-term antibiotics might be considered if there was suspicion of a bacterial infection, but again, the knee aspirate did not show any organisms, making this option inappropriate.

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In conclusion, given the absence of infection and the presence of inflammation indicated by the effusion and leucocytes, E. Oral non-steroidal anti-inflammatory drugs (NSAIDs) is the most appropriate next step for symptom management.

Hint

Raynaud’s phenomenon is a common clinical presentation, which may be primary or secondary to underlying disease.

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It can be diagnosed if there is a history of clearly demarcated pallor of the digit(s) followed by at least one other colour change (cyanosis and/or erythema). Symptoms are usually precipitated by cold (or less commonly emotion). Vasospasm without endothelial damage is thought to be the main cause for primary RP. The pathogenesis of secondary forms is probably initiated primarily by endothelial damage.

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Physical examination, nailfold capillaroscopy and immunological tests can differentiate between primary and secondary Raynaud’s.

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One should suspect secondary Raynaud’s phenomenon if any of the following are present:

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• Onset at more than 30 years of age

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• Intense, painful or asymmetrical episodes

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• Presence of additional clinical features suggestive of underlying disease

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• Positive anti-nuclear antibody

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• Abnormal nail-fold capillaries

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• Digital ulcers, gangrene or severe ischaemia of one or more digits.

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Primary Raynaud’s can be diagnosed if all the following are present:

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• No suspicion of underlying disease

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• Symmetrical episodes affecting both hands, but not necessarily all fingers

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• No tissue necrosis, ulceration, gangrene or severe ischaemia

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• Normal nail-fold capillaries

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• Normal ESR and negative anti-nuclear antibodies.

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Treatment involves prevention so that permanent ischaemic damage can be avoided. Patients should avoid exposure to the cold.

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The mild forms of primary RP can be controlled by non-pharmacological approaches alone. If insufficient, the first choice therapy is calcium channel blockers. In severe forms, intravenous prostaglandin, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors are used.

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Future treatment options may include selective alpha-2c adrenergic receptor blockers, tyrosine and Rho-kinase inhibitors and calcitonin gene-related peptide.

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Differential diagnosis of Raynaud’s phenomenon includes:

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• Chilblains (perniosis): erythematous itchy swellings on fingers and toes in response to cold

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• Acrocyanosis: continuous blueness of the extremities aggravated by cold

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• Erythromelalgia: painful erythema caused by paroxysmal dilatation of blood vessels

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• Vascular embolism

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• Livedo reticularis

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• Mottled, cyanotic discolouration of skin.

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Whilst it is not a strict criteria given in the current guidance, it is recognised that episodes do tend to be longer in secondary Raynaud’s. Episodes typically terminate within 15 minutes following warming in primary disease, but can often be prolonged in secondary disease. All the other features described here would be consistent with a diagnosis of primary Raynaud’s disease.

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Whilst miscarriage can be associated with connective tissue disease, in particular antiphospholipid syndrome, it is common in the population especially in early pregnancy.

Hint

The correct answer is B. Inflammatory bowel disease (IBD).

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This gentleman’s clinical presentation of weight loss, chronic diarrhoea, and mono/oligo-arthropathy is indicative of inflammatory bowel disease (IBD)-associated arthropathy, which is a recognized extraintestinal manifestation of inflammatory bowel disease (IBD). This form of arthritis is typically non-erosive and may correlate with the activity of the intestinal disease. The lack of correlation between axial arthritis and gastrointestinal symptoms further supports the diagnosis of inflammatory bowel disease (IBD) over other forms of spondyloarthropathy.

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The other options are incorrect for the following reasons:

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1. Tuberculosis: Tuberculous arthritis typically presents with pain, swelling, and reduced range of motion in the affected joint, and is now rare in Europe. This gentleman’s symptoms do not align with the common presentation of tuberculous arthritis, which often includes fever and weight loss, and there is no mention of a history of tuberculosis or risk factors associated with it.

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2. Thyrotoxicosis: Thyrotoxicosis generally presents with symptoms such as rapid heart rate, weight loss, anxiety, and sweating due to an overactive metabolism. While diarrhoea and arthralgia can occur, the presentation of monoarthritis is uncommon, making thyrotoxicosis an unlikely diagnosis in this case.

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3. Reactive arthritis: Reactive arthritis is commonly associated with the triad of urethritis, conjunctivitis, and arthritis, often following infections with organisms like Salmonella or Chlamydia. The chronic diarrhoea described does not fit the acute presentation typically associated with reactive arthritis, and there is no mention of urethritis or conjunctivitis.

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4. Behçet’s disease: Behçet’s disease is characterized by recurrent oral and genital ulcers and ocular involvement. While arthropathy can occur, this gentleman’s symptoms do not include the hallmark features of Behçet’s disease, and bowel habit disturbances are not expected, making this an unlikely diagnosis.

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In summary, this gentleman’s symptoms and the correlation of arthritis with intestinal disease activity strongly suggest inflammatory bowel disease (IBD) as the most likely diagnosis. The other options are less consistent with this gentleman’s presentation and lack supporting clinical evidence or characteristic features.

Hint

The combination of thrombophilia, recurrent miscarriage, thrombocytopenia and leucopenia in this patient indicates a diagnosis of antiphospholipid syndrome, probably in associated with systemic lupus erythematosus.

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Antiphospholipid syndrome is a common cause of acquired thrombophilia and characterised by arterial and/or venous thrombosis and pregnancy mortality in association with circulating antiphospholipid antibodies. These are a heterogenous group of approximately twenty autoantibodies directed against phospholipid binding plasma proteins. Three of the most clinically important are the lupus anticoagulant, anti-beta-2 glycoproetin I antibodies and the anticardiolipin antibodies. They can be detected either by phospholipid-dependent coagulation test for lupus anticoagulant or ELISA test for anticoagulation and anti-β2GPI antibodies. Antibodies should be demonstrated on at least two occasions separated by 12 weeks. Antiphospholipid syndrome may be primary, or associated with other conditions (such as systemic lupus erythematosus).

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Antiphospholipid syndrome is the most important treatable cause of recurrent miscarriage, defined as the loss of three or more consecutive pregnancies. 15% of women with recurrent miscarriage have persistently positive tests for either lupus anticoagulant or anticardiolipin antibodies, compared to 2% with an uncomplicated obstetric history. In future untreated pregnancies, women with recurrent miscarriage and persistently positive anticardiolipin antibodies have a miscarriage rate of 90%. The majority of miscarriages occur between 7 and 12 weeks gestation, and foetuses are typically chromosomally normal. It is thought the antibodies affect trophoblast invasion and placentation.

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Antiphospholipid syndrome is also an important cause of early onset pre-eclampsia and intra-uterine growth restriction.

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Aspirin and low-dose heparin is the treatment of choice to reduce the risk of miscarriage in confirmed antiphospholipid syndrome. This combination has been showed to lead to a 70% live birth rate in future pregnancies. Intravenous immunoglobulin can also be used.

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Elevated levels of circulating homocysteine increase the risk of developing coronary artery disease, peripheral vascular disease and cerebrovascular disease but they are not commonly associated with pregnancy loss.

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An indium white blood cell scan is a nuclear medicine study in which leucocytes are removed from the patient, tagged with Indium-111 and reinjected into the patient. They can then be used to localise areas of infection and inflammation, such as thrombophlebitis and osteomyelitis.

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Platelet function studies measure the platelet’s ability to adhere and aggregate. They are not particularly reliable or accurate, and therefore do not have a central role in clinical practice.

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Protein C is one of the major inhibitors of the coagulation system. Deficiency is associated with an increased risk of venous thrombosis, but not classically an increase rate of miscarriage.

Hint

The most likely diagnosis for this gentleman is E. Behçet’s syndrome. Behçet’s syndrome is a rare disorder that causes blood vessel inflammation throughout the body, leading to various signs and symptoms that can seem unrelated at first. Some of the characteristic features of Behçet’s syndrome are:

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• Recurrent oral and genital ulcers

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• Eye inflammation (uveitis or conjunctivitis)

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• Skin lesions (erythema nodosum, pustular vasculitis, or pyoderma gangrenosum)

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• Arthritis or arthralgia, usually affecting the knees, ankles, wrists, or elbows

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• Positive pathergy test (skin reaction to minor trauma)

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The gentleman in this case has oral and genital ulcers, eye irritation, and arthritis, which are consistent with Behçet’s syndrome. Additionally, he has a high white blood cell count and C-reactive protein (CRP), indicating inflammation, and a negative rheumatoid factor, ruling out rheumatoid arthritis. The diagnosis of Behçet’s syndrome is based on clinical criteria, as there is no specific laboratory test for it.

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The other options are less likely because:

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• A. Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation of the digestive tract, such as ulcerative colitis or Crohn’s disease. Inflammatory bowel disease (IBD) can cause extraintestinal manifestations, such as arthritis, mouth ulcers, eye inflammation, and skin lesions, but these are usually associated with active bowel inflammation. The gentleman in this case does not have any gastrointestinal symptoms, such as diarrhoea, abdominal pain, or blood in stool, which makes inflammatory bowel disease (IBD) unlikely.

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• B. Psoriatic arthritis is a type of arthritis that affects some people who have psoriasis, a chronic skin condition that causes red, scaly patches. Psoriatic arthritis can cause joint pain and swelling, nail changes, eye inflammation, and skin lesions, but it usually affects the distal joints of the fingers and toes, the spine, or the sacroiliac joints. The gentleman in this case does not have psoriasis or nail changes, and has bilateral wrist and knee involvement, which are not typical of psoriatic arthritis.

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• C. Reactive arthritis is a form of arthritis that develops in response to an infection in another part of the body, usually the intestines or the genitals. Reactive arthritis can cause joint pain and swelling, eye inflammation, urethritis, and skin lesions, but it usually occurs within a few weeks of the triggering infection. The gentleman in this case has a four-month history of symptoms, which is too long for reactive arthritis. Moreover, he does not have any history of infection or urethritis, which are common triggers of reactive arthritis.

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• D. Sjögren’s syndrome is an autoimmune disorder that affects the moisture-producing glands of the eyes and mouth, causing dryness. Sjögren’s syndrome can also affect other organs, such as the joints, skin, lungs, kidneys, and nerves, causing various symptoms. The gentleman in this case has mouth ulcers, not dryness, and does not have any other symptoms of Sjögren’s syndrome, such as fatigue, dry eyes, dry cough, or neuropathy.

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Hint

The most appropriate bedside test to indicate an underlying connective tissue disorder in this case is C. Nailfold capillaroscopy. This non-invasive test is used to examine the small blood vessels (capillaries) at the base of the fingernail and is particularly useful in diagnosing conditions like systemic sclerosis and distinguishing primary from secondary Raynaud’s phenomenon. Abnormalities such as capillary dilation, haemorrhages, or avascular areas can suggest the presence of a connective tissue disease.

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Now, let us rule out the other options:

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A. Capnography measures the concentration of carbon dioxide in exhaled air and is primarily used to monitor ventilation in various settings, such as during anaesthesia or in critical care. It is not used to diagnose connective tissue disorders and would not be relevant to the symptoms described.

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B. Finger systolic pressure can help in the diagnosis of vascular diseases affecting the fingers, such as Raynaud’s phenomenon, but it does not specifically indicate an underlying connective tissue disorder.

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D. Digital artery closing temperature is not a standard bedside test for connective tissue disorders. While temperature changes can affect blood flow and may be relevant in Raynaud’s phenomenon, this test does not provide specific information about connective tissue disease involvement.

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E. Cold water challenge is a test that can trigger a Raynaud’s phenomenon episode and is used to diagnose Raynaud’s syndrome. However, it does not provide direct evidence of an underlying connective tissue disorder and can be non-specific.

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Given the lady’s history and symptoms, nailfold capillaroscopy is the most suitable test to perform for a probable diagnosis of a connective tissue disorder.

Hint

This lady has antiphospholipid antibody syndrome which is a non-inflammatory pro-thrombotic state in vivo, in the presence of laboratory tests suggesting an anticoagulant state.

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The antiphospholipid antibodies (anticardiolipin and lupus anticoagulant) cause coagulation defect in-vitro (raised aPTT which fails to correct after the addition of normal human plasma). However, despite the coagulation defects and thrombocytopenia, the lupus anticoagulant causes arterial and venous thromboses in vivo.

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Disseminated intravascular clotting and thrombotic thrombocytopenic purpura are severe systemic illnesses, where bleeding may occur due to consumption of clotting factors, and platelets by an overactive clotting cascade.

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Idiopathic thrombocytopenic purpura does not cause raised aPTT.

Hint

The most likely conclusion is D. Spontaneous improvement. This gentleman has a classic presentation of Löfgren syndrome, which is an acute form of sarcoidosis that manifests with erythema nodosum, polyarthropathy, hilar lymphadenopathy, and sometimes fever, uveitis, and parotitis. Löfgren syndrome has a good prognosis and usually resolves spontaneously over six to eight weeks without treatment.

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The other options are less likely because:

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• A. Chronic arthritis is not a typical outcome of Löfgren syndrome, as most patients recover completely without joint damage. Chronic arthritis may occur in other forms of sarcoidosis that involve noncaseating granulomas in the joints, but this is not the case for this gentleman.

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• B. Skin ulceration is not a common feature of Löfgren syndrome, which is characterized by erythema nodosum, a type of panniculitis that causes tender nodules on the lower limbs. Skin ulceration may be seen in other cutaneous manifestations of sarcoidosis, such as lupus pernio or scar sarcoidosis, but this is not the case for this gentleman.

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• C. Pulmonary fibrosis is a possible complication of chronic sarcoidosis, but it is rare in Löfgren syndrome, which usually has a benign course and does not cause significant lung damage. Pulmonary fibrosis may result from persistent inflammation and granuloma formation in the lung parenchyma, leading to scarring and reduced lung function.

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• E. Renal failure is not a frequent complication of Löfgren syndrome, which does not affect the kidneys. Renal failure may occur in sarcoidosis due to granulomatous interstitial nephritis, nephrocalcinosis, or renal stones, but these are uncommon and usually associated with hypercalcaemia or hypercalciuria.

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Hint

The correct answer is C. She should continue the OCP for at least three months after stopping methotrexate. This is because methotrexate is a teratogenic drug, which means it can cause harm to the developing foetus if taken during pregnancy. According to the British National Formulary (BNF) and the National Patient Safety Agency (NPSA), both men and women should avoid conception for at least three months after stopping methotrexate, as it may take some time for the drug to be cleared from the body and the tissues. Fertility may be temporarily reduced during treatment, but it usually returns to normal after stopping the drug.

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The other options are not correct for the following reasons:

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• A. She should continue the OCP for at least two weeks after stopping methotrexate: This is incorrect because two weeks is not a sufficient period of time to ensure that methotrexate is completely eliminated from the body and that the risk of foetal anomalies is minimized. Methotrexate has a variable elimination half-life, which means it can stay in the body for different lengths of time depending on the individual and the dose. It can also accumulate in some organs, such as the liver and the kidneys, and cause damage. Therefore, a longer period of contraception is recommended by the British National Formulary (BNF) and the National Patient Safety Agency (NPSA).

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• B. She can stop the OCP at the same time as she stops methotrexate: This is incorrect because stopping the OCP at the same time as methotrexate can increase the chance of ovulation and conception before methotrexate is fully cleared from the body. This can expose the developing embryo to the harmful effects of methotrexate, which can cause miscarriage or congenital malformations. The British National Formulary (BNF) and the National Patient Safety Agency (NPSA) advise that women should wait for at least one ovulatory cycle, and men should wait for at least three months, before trying to conceive after stopping methotrexate.

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• D. She should continue the OCP for at least one year after stopping methotrexate: This is incorrect because one year is much longer than necessary to prevent pregnancy after stopping methotrexate. There is no evidence that methotrexate has a long-term effect on fertility or pregnancy outcomes after it is discontinued. A shorter period of contraception, such as three months, is sufficient to reduce the risk of methotrexate exposure during pregnancy, as recommended by the British National Formulary (BNF) and the National Patient Safety Agency (NPSA).

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• E. She should continue the OCP for at least one month after stopping methotrexate: This is incorrect because one month is shorter than necessary to prevent pregnancy after stopping methotrexate. Although the British National Formulary (BNF) and the National Patient Safety Agency (NPSA) state that women should wait for at least one ovulatory cycle before trying to conceive, this may not be enough time to ensure that methotrexate is completely eliminated from the body and that the risk of foetal anomalies is minimized. Methotrexate has a variable elimination half-life, which means it can stay in the body for different lengths of time depending on the individual and the dose. It can also accumulate in some organs, such as the liver and the kidneys, and cause damage. Therefore, a longer period of contraception, such as three months, is recommended by the British National Formulary (BNF) and the National Patient Safety Agency (NPSA). 

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Hint

The most likely diagnosis for the gentleman described is D. Fibromyalgia. This condition is characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory, and mood issues. The symptoms mentioned, such as chronic pain that varies in location, tenderness in multiple areas, and normal blood tests, align with fibromyalgia. Additionally, the lack of restorative sleep and gastrointestinal symptoms like constipation and diarrhoea are common in fibromyalgia.

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The other options are incorrect for the following reasons:

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1. Somatoform disorder: This disorder involves patients having physical symptoms that are not explained by a medical condition. However, the chronic nature of the pain and its specific characteristics in this case are more indicative of fibromyalgia.

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2. Schizophrenia: This is a severe mental disorder characterized by distortions in thinking, perception, emotions, language, sense of self, and behavior. Chronic pain is not a typical feature of schizophrenia.

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3. Hypothyroidism: While hypothyroidism can cause muscle pain and weakness, it is usually accompanied by other symptoms like weight gain, cold intolerance, and changes in skin and hair. Moreover, routine blood tests would typically show abnormalities in thyroid function tests, which is not the case here.

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4. Depressive disorder: Depression can cause physical symptoms, including pain, but it is primarily characterized by persistent feelings of sadness and loss of interest. The physical examination findings and the variety of symptoms presented are more consistent with fibromyalgia.

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In conclusion, based on the symptoms and examination findings provided, fibromyalgia is the most likely diagnosis.

Hint

The most anticipated diagnosis for the gentleman described is C. Diffuse cutaneous systemic sclerosis. This condition is characterized by rapidly progressing skin thickening involving areas proximal to the elbows and knees, and can include the trunk, which aligns with this gentleman’s symptoms of skin tightness and thickening to the shoulders. The presence of sclerodactyly, Raynaud’s phenomenon, and bi-basal crepitations are also indicative of systemic sclerosis. The positive Anti-Scl70 antibody is highly specific for systemic sclerosis, particularly the diffuse cutaneous subtype.

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Let us evaluate the other options:

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A. Mixed connective tissue disease (MCTD): Mixed connective tissue disease (MCTD) typically presents with features of several connective tissue diseases, including systemic lupus erythematosus, scleroderma, and polymyositis. Patients often have high titers of Anti-U1RNP antibodies, which this patient does not have, making mixed connective tissue disease (MCTD) less likely.

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B. Dermatomyositis: This inflammatory disease is characterized by muscle weakness and a distinctive skin rash. The absence of muscle weakness and the presence of Anti-Scl70 antibodies make dermatomyositis an unlikely diagnosis for this gentleman.

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D. Sjögren’s syndrome: Sjögren’s syndrome primarily presents with dry eyes and dry mouth due to lymphocytic infiltration of exocrine glands. This gentleman’s symptoms do not align with this diagnosis, and the serological markers (Anti-Ro/La antibodies) associated with Sjögren’s syndrome are negative.

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E. Limited cutaneous systemic sclerosis: This subtype of systemic sclerosis is associated with skin thickening that is limited to the hands, face, feet, and forearms. This gentleman’s extensive skin involvement beyond these areas suggests the diffuse cutaneous subtype rather than the limited form.

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In summary, the clinical presentation, serological findings, and the absence of features typical of the other conditions listed support the diagnosis of C. Diffuse cutaneous systemic sclerosis.

Hint

This lady has SAPHO syndrome. SAPHO is an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis. It is characterised by osteosclerotic bone lesions, sterile osteomyelitis, and a variety of skin lesions.

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• Synovitis – may be present rarely, and associates with erosions.

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• Acne – may be severe (conglobate or fulminans) and recur with new bony involvement.

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• Pustulosis – palmo-plantar pustulosis occurs in approximately 50% of patients, other skin lesions may include psoriasis, hidradenitis suppurativa, acne, and rarely Sweet’s syndrome.

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• Hyperostosis (increase in bone substance) and osteitis (inflammation of the bones) – the bony lesions typically involve the acromioclavicular, and sternoclavicular joints. Other sites include anterior chest wall, sternum, clavicle, pubic symphysis, spine, and mandible. These lesions are visualised on 99m technetium bone scan or MRI.

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The cause of the SAPHO syndrome is unknown. The skin lesions are characterised by neutrophilic pseudoabscesses. Bone biopsy can reveal sterile osteomyelitis.

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Diagnosis should be suspected when there is an association of rheumatic pain with a pustular skin disease.

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SAPHO has no specific treatment, and some cases remit spontaneously. Typical treatment can be used for the arthritic symptoms (i.e. non-steroidal anti-inflammatories and disease modifying anti-rheumatic agents). Isotretinoin and aciretin can be used to treat the skin disease. In the more severe cases corticosteroids, calcitonin, bisphosphonates and TNF-inhibitors can be used.

Hint

Prednisolone and hydroxychloroquine may be taken whilst breast-feeding. Azathioprine, cyclophosphamide, methotrexate and cyclosporin A are contraindicated in breast-feeding mothers.

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In general, SLE does not affect the fertility of patients. However, fertility may be adversely affected in specific subgroups of patients such as those with renal failure, cyclophosphamide treatment, very active disease or high dose corticosteroids.

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Anti-Ro and anti-La antibodies are associated with increased risk of congenital heart block. The risk is greater with anti-Ro positivity than anti-La positivity. The risk of congenital heart block in the presence of anti-Ro may be up to 5%.

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Stopping any unnecessary drugs is advisable in pregnancy, however use of azathioprine, hydroxychloroquine and prednisolone in pregnancy is considered safe if these are necessary for treatment of the mother’s disease.

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Risk of pre-eclampsia is increased in SLE. It may be difficult to differentiate between pre-eclampsia and renal flare of SLE, and both may coexist. Differentiating features include raised anti-dsDNA antibody, decreased complement levels (C3 and C4) and response to steroids in the case of renal flare.

Hint

Anti-Ro antibodies from a mother with SLE can cause fetal heart block as part of neonatal lupus. It affects only 3-5% of babies born to mothers with SLE, and the most common cause of heart block is anti-Ro antibodies.

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Anti-La antibodies are also a cause of fetal heart block, but less commonly than anti-Ro.

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dsDNA is used as a marker of disease activity in Lupus, but is not associated with neonatal heart block.

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pANCA is common in a number of vasculitides but is not specific to neonatal lupus.

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Anti-Jo1 antiboides are associated with dermatomyositis and polymyositis.

Hint

The correct diagnosis for this lady presenting with fever, urethritis, arthralgia, vaginal discharge, a swollen ankle, and a pustular rash is A. Disseminated gonorrhoea. Disseminated gonococcal infection (DGI) is a serious complication of gonorrhoea caused by the bacterium Neisseria gonorrhoeae. It can lead to various systemic symptoms, including dermatitis, tenosynovitis, migratory polyarthralgias, and, less commonly, septic arthritis.

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Let us address why the other options are less likely:

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• B. Staphylococcal arthritis: This condition typically presents with acute onset of symptoms and is associated with a more localized infection. It does not usually include urethritis or a pustular rash.

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• C. Tuberculous arthritis: This form of arthritis is caused by Mycobacterium tuberculosis and usually affects a single joint, leading to chronic pain and swelling. It is not characterized by urethritis or a pustular rash.

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• D. Lyme disease: Lyme disease, caused by the tick-borne bacterium Borrelia burgdorferi, typically presents with a distinctive erythema migrans rash and can affect various systems. However, this lady’s presentation does not align with the typical manifestations of Lyme disease.

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• E. Reactive arthritis: This condition is an autoimmune response to an infection, often presenting with conjunctivitis, urethritis, and arthritis. The skin rash described in this lady’s case is not typical for reactive arthritis.

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In conclusion, this lady’s symptoms align most closely with disseminated gonorrhoea, which is known to cause a pustular rash, fever, urethritis, and oligoarthritis, fitting the clinical picture described. The other conditions listed do not typically present with this combination of symptoms and are therefore less likely to be the correct diagnosis.

Hint

This gentleman has psoriatic arthritis. Synovitis is indicative of an inflammatory arthritis. The rash typically pre-dates the arthropathy by a number of years, but the opposite can be true. Small plaques should be looked for on the elbows and scalp.

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There are five patterns of disease:

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1. Symmetrical polyarthritis (‘rheumatoid pattern’) – affects wrists, hands, feet and ankles. The distal interphalangeal joints are more commonly affected than the metacarpophalangeal joints, which helps to distinguish it from rheumatoid arthritis.

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2. Asymmetrical oligoarticular arthritis – dactylitis.

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3. Distal interphalangeal joint disease – typically in men.

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4. Arthritis mutilans – rare.

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5. Spondylitis pattern with sacroileitis.

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Rheumatoid arthritis typically affects the metacarpophalangeal and proximal interphalangeal joints symmetrically. Psoriatic arthritis affects the distal interphalangeal joints and tends to be asymmetrical.

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Joint involvement in systemic lupus erythematosus occurs in the form of a polyarticular arthralgia, frequently symmetrical and episodic. Intense tendonitis is more common than synovitis and can lead to deforming reversible subluxation of joints without erosive disease (Jaccoud’s arthropathy).

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Osteoarthritis would be unusual in someone of this age group.

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Reactive arthritis is a sterile inflammatory arthritis which develops as a sequel to remote infection, usually of the gastrointestinal or urogenital tract. There is no history of such infection in this case. It also classically presents as a large joint oligoarthritis.

Hint

The correct answer is E. All of the above. All of these options are potential risks to the foetus of a woman with Sjögren’s syndrome, especially if she is positive for anti-Ro/La antibodies. These antibodies can cross the placenta and affect the development and function of the foetal heart, skin, liver, and blood cells. The possible complications include:

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• A. Complete heart block: This is a condition where the electrical impulses that control the heartbeat are blocked, resulting in a slow and irregular heart rate. This can lead to heart failure, hydrops foetalis, or death in utero or shortly after birth. The incidence of complete heart block in foetuses of women with anti-Ro/La antibodies is estimated to be 1-2%.

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• B. Hydrops foetalis: This is a condition where the foetus develops severe fluid accumulation in the body cavities, such as the chest, abdomen, or skin. This can cause respiratory distress, anaemia, organ failure, or death. The causes of hydrops foetalis in foetuses of women with anti-Ro/La antibodies include complete heart block, neonatal lupus, or haemolytic anaemia.

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• C. Neonatal lupus: This is a condition where the foetus develops skin rashes, liver problems, or blood cell abnormalities due to the exposure to anti-Ro/La antibodies. The symptoms usually appear within the first few weeks of life and resolve within 6-12 months as the antibodies clear from the baby’s system. The incidence of neonatal lupus in foetuses of women with anti-Ro/La antibodies is estimated to be 10-20%.

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• D. Congestive cardiac failure (CCF): This is a condition where the heart is unable to pump enough blood to meet the body’s needs, resulting in fluid retention, shortness of breath, fatigue, or death. The causes of congestive cardiac failure (CCF) in foetuses of women with anti-Ro/La antibodies include complete heart block, myocarditis, or cardiomyopathy.

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Hint

Diffuse staining ANA on immunofluorescence in high titre raises the possibility of systemic lupus erythematosus (SLE).

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Further tests are required to ascertain if the diffuse staining ANA is due to anti-dsDNA (pathogenic in SLE) or due to anti ss-DNA antibody (not thought to play a pathogenic role in SLE).

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Crithidialuciliae immunofluorescence is positive only in the presence of anti-dsDNA antibody. This is as Crithidialuciliae has a giant mitochondrion, with a circular dsDNA. It does not have ssDNA or any histones. In routine clinical practice, only anti-dsDNA are tested for. Diffuse staining ANA on immunofluorescence, in low titres (<1:160) is very common in the general population.

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Although not mutually exclusive, different ANA immunofluorescence patterns suggest different diseases:

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• Anti-centromere pattern: limited cutaneous systemic sclerosis

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• Cytoplasmic pattern: Sjögren’s syndrome, anti-synthetase syndrome

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• Nucleolar pattern: diffuse cutaneous systemic sclerosis

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• Speckled pattern: mixed connective tissue disease.

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This gentleman has no symptoms to support the diagnoses of

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• Discoid lupus erythematosus (scarring photosensitive skin ulceration)

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• Sjögren’s syndrome (dry eyes, dry mouth, fatigue)

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• Scleroderma (Raynaud’s phenomenon, skin thickening, tightness, telangiectasia), and

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• SLE (photosensitive rash).

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Anti-dsDNA antibodies are highly specific for diagnosis of SLE. However, they are neither necessary, nor sufficient in themselves for the diagnosis of SLE. At any one time only 50% patients with SLE have the anti-dsDNA antibody, while only 70% patients with SLE develop anti-dsDNA antibodies at any one time during the course of their illness.

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Raynaud’s phenomenon is a common clinical presentation, which may be primary or secondary to underlying disease. It can be diagnosed if there is a history of clearly demarcated pallor of the digit(s) followed by at least one other colour change (cyanosis and/or erythema). Symptoms are usually precipitated by cold (or less commonly emotion). Vasospasm without endothelial damage is thought to be the main cause for primary RP. The pathogenesis of secondary forms is probably initiated primarily by endothelial damage.

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Physical examination, nailfold capillaroscopy and immunological tests can differentiate between primary and secondary Raynaud’s.

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One should suspect secondary Raynaud’s phenomenon if any of the following are present:

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• Onset at more than 30 years of age

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• Intense, painful or asymmetrical episodes

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• Presence of additional clinical features suggestive of underlying disease

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• Positive anti-nuclear antibody

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• Abnormal nailfold capillaries

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• Digital ulcers, gangrene or severe ischaemia of one or more digits.

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Primary Raynaud’s can be diagnosed if all the following are present:

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• No suspicion of underlying disease

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• Symmetrical episodes affecting both hands, but not necessarily all fingers

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• No tissue necrosis, ulceration, gangrene or severe ischaemia

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• Normal nailfold capillaries

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• Normal ESR and negative anti-nuclear antibodies.

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Treatment involves prevention so that permanent ischaemic damage can be avoided. Patients should avoid exposure to the cold.

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The mild forms of primary RP can be controlled by non-pharmacological approaches alone. If insufficient, the first choice therapy is calcium channel blockers. In severe forms, intravenous prostaglandin, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors are used.

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Future treatment options may include selective alpha-2c adrenergic receptor blockers, tyrosine and Rho-kinase inhibitors and calcitonin gene-related peptide.

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Differential diagnosis of Raynaud’s phenomenon includes:

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• Chilblains (perniosis): erythematous itchy swellings on fingers and toes in response to cold

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• Acrocyanosis: continuous blueness of the extremities aggravated by cold

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• Erythromelalgia: painful erythema caused by paroxysmal dilatation of blood vessels

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• Vascular embolism

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• Livedo reticularis: mottled, cyanotic discolouration of skin.

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All the other features described here would be consistent with a diagnosis of primary Raynaud’s disease.

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Whilst miscarriage can be associated with connective tissue disease, in particular antiphospholipid syndrome, it is common in the population especially in early pregnancy.

Hint

This gentleman has symptoms that are consistent with tennis elbow (lateral epicondylitis), most probably due to excessive forearm extension as a result of his work as a woodworker.

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Lateral epicondylitis occurs due to inflammation of the extensor forearm muscle origins, and causes lateral elbow and upper forearm pain and tenderness. On examination, patients have pain and tenderness over the lateral epicondyle of the humerus, radiating into the forearm and pain on resisted dorsiflexion of the wrist and middle finger. Pain is exacerbated by active and resisted movements of the extensor muscles of the forearm.

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Lateral epicondylitis is a self-limiting condition, and usually resolves within 6 months to 2 years. Whilst awaiting for resolution rest, ice, activity restriction and non-steroidal anti-inflammatory drugs can reduce symptoms. Physiotherapy has been shown to be beneficial. Steroids injections have been shown to be harmful in the long-term and are therefore not recommended. Glyceryl trinitrate patches over the painful area do improve outcome. 

Hint

The most likely diagnosis for this gentleman is pulmonary infection due to opportunistic pathogens. This is because he has a history of rheumatoid arthritis and is on etanercept, which is a tumour necrosis factor (TNF) blocker that increases the risk of serious infections. The gentleman also has symptoms and signs of systemic inflammation such as fever, chills, weight loss, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The chest X-ray shows diffuse bilateral infiltrates, which can be caused by various infectious and non-infectious causes.

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The most distinctive test to confirm the diagnosis and identify the causative organism is bronchoalveolar lavage (BAL). This is a procedure that involves inserting a bronchoscope into the lungs and collecting fluid samples from the alveoli. The fluid can then be analysed for microbiological cultures, stains, antigen tests, and cytology. Bronchoalveolar lavage (BAL) can help differentiate between bacterial, fungal, viral, and other opportunistic infections, as well as non-infectious causes of diffuse infiltrates such as pulmonary haemorrhage, oedema, or alveolar proteinosis.

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The other tests are less distinctive for the following reasons:

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• High resolution computed tomography (CT) scan: This is a more detailed imaging modality than chest X-ray, but it cannot provide a definitive diagnosis of the type of infection. It can only show the pattern and distribution of the pulmonary abnormalities, such as nodules, ground-glass opacities, consolidations, or cavities. These patterns can overlap among different infectious and non-infectious causes, and may not be specific for opportunistic pathogens.

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• Mycoplasma serology: This is a blood test that detects antibodies against Mycoplasma pneumoniae, a common cause of atypical pneumonia. However, this test is not very useful in the setting of immunosuppression, as the antibody response may be delayed, absent, or unreliable. Moreover, Mycoplasma pneumoniae is not a typical opportunistic pathogen, and it usually causes patchy rather than diffuse infiltrates on chest X-ray.

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• Aspergillus precipitin: This is a blood test that detects antibodies against Aspergillus species, a group of fungi that can cause invasive pulmonary aspergillosis in immunocompromised patients. However, this test has low sensitivity and specificity, and may not reflect the current infection status. Furthermore, Aspergillus species are not the only fungi that can cause opportunistic pulmonary infections, and they usually cause cavitary rather than diffuse infiltrates on chest X-ray.

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• Quantiferon: This is a blood test that measures the interferon-gamma release by T cells in response to Mycobacterium tuberculosis antigens. It is used to diagnose latent or active tuberculosis (TB) infection. However, this test may not be reliable in immunosuppressed patients, as the T cell response may be impaired or absent. Additionally, tuberculosis (TB) is not the only bacterial infection that can cause opportunistic pulmonary infections, and it usually causes apical rather than diffuse infiltrates on chest X-ray.

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Therefore, the correct answer is D. Bronchoalveolar lavage.

Hint

Still’s Disease is a febrile syndrome in young adults (16-35 years) which affects multiple organs.The diagnosis is mainly one of exclusion.

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The clinical features include:

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• High spiking fever (once a day, with return of temperature to normal)

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• Arthralgia/arthritis

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• Sore throat

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• Transient maculopapular rash (mildly pruritic in 1/3)

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• Lymphadenopathy

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• Hepatosplenomegaly, and

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• Pleuritis/pericarditis.

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Rarely there may be:

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• Aseptic meningitis

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• Cranial nerve palsies

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• Iritis, and

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• Peripheral neuropathy.

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There is often delay in diagnosis.

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Hyperferritinaemia (greater than five times normal) is present in 90% of cases.

Hint

This lady has psoriatic arthritis.

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Among people who develop psoriatic arthritis, two-thirds develop joint symptoms after skin involvement. In the absence of psoriasis, a positive family history of psoriasis in a first degree relative supports the diagnosis of psoriatic arthritis.

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RA is unlikely as there is asymmetrical joint involvement – with predominant involvement of the distal interphalangeal (DIP) joints in the hands. DIP joint involvement is a distinctive feature of psoriatic arthritis. DIP joint involvement associates with dactylitis, nail pitting and onycholysis (separation of nail from nail bed).

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The absence of preceding infection makes reactive arthritis unlikely.

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Gout is unlikely.

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The alcohol intake is not excessive, and except for male gender, there is no other risk factor, for example,  age greater than 40 years, diuretic use, renal failure and solid organ transplant.

Hint

Common manifestations of Granulomatosis with polyangiitis include:

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• Constitutional symptoms like fevers, night sweats, fatigue, lethargy, weight loss, arthralgia

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• Ocular involvement including conjunctivitis, episcleritis, uveitis, optic nerve vasculitis, and proptosis

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• ENT symptoms like chronic sinusitis, rhinitis, otitis media and hearing loss, subglottic stenosis (leading to stridor and features of extrathoracic airway obstruction on flow-volume loop)

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• Pulmonary disease, for example, pulmonary infiltrates, cough, haemoptysis, chest discomfort, and dyspnoea

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• Renal disease manifests as crescentic necrotising glomerulonephritis

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• Nervous system involvement manifests as mononeuritis multiplex, sensorimotor polyneuropathy, cranial nerve palsies, vasculitis of small to medium-sized vessels of the brain or spinal cord, and granulomatous masses that involve the orbit, optic nerve, meninges or brain

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• Skin involvement can lead to palpable purpura or skin ulcers.

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Hint

For this 39-year-old gentleman with systemic lupus erythematosus (SLE) and a new diagnosis of deep vein thrombosis (DVT), the presence of antiphospholipid antibodies (positive Anti-Cardiolipin Antibody) suggests an increased risk of recurrent thrombotic events. The most appropriate treatment plan would be:

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B. Warfarin for life.

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Patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), indicated by the presence of antiphospholipid antibodies, are at a higher risk for both arterial and venous thromboses. Lifelong anticoagulation with warfarin is recommended for patients with antiphospholipid syndrome (APS) and a history of thrombosis to prevent recurrence.

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Let us discuss why the other options are incorrect:

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A. Warfarin for 3 months, followed by aspirin 75 mg/day: This option is incorrect because aspirin alone is not sufficient for the secondary prevention of thrombosis in patients with antiphospholipid syndrome (APS). Lifelong anticoagulation is necessary due to the high risk of recurrence.

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C. Warfarin for 3 months: This duration is too short for this gentleman with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) who has already experienced a thrombotic event. Lifelong anticoagulation is typically required.

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D. Warfarin, and aspirin 75 mg/day for life: The combination of warfarin and aspirin is not routinely recommended due to the increased risk of bleeding without evidence of added benefit in preventing recurrent thrombosis over anticoagulation alone.

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E. Warfarin for 3 months, followed by aspirin 75 mg/day: Similar to option A, this option is incorrect because it does not provide adequate long-term prevention of thrombotic events in a patient with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

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In summary, lifelong anticoagulation with warfarin is the most appropriate treatment to prevent recurrent thrombotic events in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Hint

This gentleman is most likely to have psoriatic arthritis.

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Psoriatic arthritis has been subclassified according to different patterns of arthritis.

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The rash typically predates the arthropathy by a number of years, but the opposite can be true. Small plaques should be looked for on the elbows and scalp.

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There are five patterns of disease:

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• Symmetrical polyarthritis (‘rheumatoid pattern’) – affects wrists, hands, feet and ankles. The distal interphalangeal joints are more commonly affected than the metacarpophalangeal joints, which helps to distinguish it from rheumatoid arthritis

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• Asymmetrical oligoarticular arthritis: dactylitis

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• Distal interphalangeal joint disease: typically in men

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• Arthritis mutilans (rare)

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• Spondylitic pattern with sacroileitis.

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Osteoarthritis in this age group is unlikely.

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Rheumatoid arthritis is a symmetrical arthritis typically affecting the metacarpophalangeal joints.

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Arthritis does occur in systemic lupus erythematosus, however there are several other clinical features that form part of the diagnositic criteria, none of which are present here.

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Reactive arthritis occurs following a gastrointestinal or genitourinary infection. It commonly affects the large joints.

Hint

The correct option is D. De Quervain’s tenosynovitis. This is a condition that affects the tendons of the thumb and causes pain and inflammation at the base of the thumb and the radial side of the wrist. The symptoms and signs described are consistent with this diagnosis, such as:

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• Dorsoradial wrist pain that worsens with thumb movement or grasping.

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• Tenderness and swelling over the first dorsal compartment of the wrist, which contains the abductor pollicis longus and extensor pollicis brevis tendons.

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• Crepitus or a grating sensation when moving the thumb.

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• Positive Finkelstein’s test, which involves flexing the thumb into the palm and then ulnarly deviating the wrist. This test reproduces the pain and confirms the diagnosis.

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The other options are incorrect for the following reasons:

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• A. Tennis elbow, or lateral epicondylitis, is a condition that affects the tendons of the elbow and causes pain and tenderness at the lateral epicondyle of the humerus. It is usually associated with repetitive wrist extension or forearm supination, such as in racquet sports. It does not affect the thumb or the radial side of the wrist, and Finkelstein’s test is negative.

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• B. Carpal tunnel syndrome is a condition that affects the median nerve and causes pain, numbness, tingling, and weakness in the thumb, index, middle, and ring fingers. It is usually associated with repetitive wrist flexion or compression of the wrist, such as in keyboard use or driving. It does not cause inflammation or crepitus at the radial side of the wrist, and Finkelstein’s test is negative.

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• C. Golfer’s elbow, or medial epicondylitis, is a condition that affects the tendons of the elbow and causes pain and tenderness at the medial epicondyle of the humerus. It is usually associated with repetitive wrist flexion or forearm pronation, such as in golf or throwing sports. It does not affect the thumb or the radial side of the wrist, and Finkelstein’s test is negative.

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• E. Ulnar tunnel syndrome, or Guyon’s canal syndrome, is a condition that affects the ulnar nerve and causes pain, numbness, tingling, and weakness in the little and ring fingers. It is usually associated with compression of the ulnar nerve at the wrist, such as in cycling or using crutches. It does not cause inflammation or crepitus at the radial side of the wrist, and Finkelstein’s test is negative.

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Hint

The most specific antibody for systemic lupus erythematosus (SLE) is Anti-Sm antibody (C). Anti-Sm antibodies are highly associated with systemic lupus erythematosus (SLE) and are considered a hallmark of the disease. They are not typically found in other diseases, which makes them quite specific for systemic lupus erythematosus (SLE).

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Let us review the other options:

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• c-Anti-neutrophil cytoplasmic antibodies (c-ANCA) (A): These are primarily associated with vasculitis, particularly granulomatosis with polyangiitis, and not specific for systemic lupus erythematosus (SLE).

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• Anti-Ro antibody (B): While these antibodies can be present in systemic lupus erythematosus (SLE), they are also found in other autoimmune conditions like Sjögren’s syndrome and are not as specific as Anti-Sm antibodies for systemic lupus erythematosus (SLE).

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• Antinuclear antibody (ANA) (D): Antinuclear antibody (ANA) is a sensitive screening test for systemic lupus erythematosus (SLE) but is not specific as it can be positive in a variety of other autoimmune diseases and even in some healthy individuals.

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• Rheumatoid factor (E): This antibody is associated with rheumatoid arthritis and other autoimmune diseases, but it is not specific for systemic lupus erythematosus (SLE).

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In summary, while several antibodies can be present in systemic lupus erythematosus (SLE), the Anti-Sm antibody (C) is the most specific and is a key marker in the diagnosis of systemic lupus erythematosus (SLE).

Hint

This gentleman has clinical features of Behçet’s syndrome.

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Behçet’s syndrome is a systemic vasculitis with an unknown aetiology, which affects small and large vessels (venous and arterial).

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More than 60% of patients are HLA-B51, and there is an increased prevalence in the Mediterranean countries.

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It is commonly associated with mucocutaneous manifestations (oro-genital ulceration, erythema nodosum), ocular disease, gastrointestinal involvement and neurological features. Venous thrombosis is a common complication, and therefore there should be a high clinical suspicion of a left sided DVT in this case. The tenderness and erythema of the right leg is most likely due to erythema nodosum. 

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None of the other conditions listed above are commonly associated with Behçet’s syndrome.

Hint

This patient has reactive arthritis (a reactive illness with concurrent arthritis, non-infective urethritis, and conjunctivitis).

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Other manifestations of reactive arthritis include:

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• Psoriasiform skin

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• Nail and mucosal lesions

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• Keratoderma blenorrhagica (palmoplantar pustulosis), and

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• Circinate balanitis.

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Behcet’s disease is unlikely as there are no orogenital ulcers. Genital ulceration in Behcet’s disease affects the scrotum in men and labia in women.

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Peripheral arthropathy in inflammatory bowel disease (IBD) is oligoarticular, asymmetric, and predominantly involves the lower limbs. The lack of a history of diarrhoea and presence of urethritis, makes IBD unlikely.

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Sarcoidosis leads to ankle and ocular involvement but does not lead to urethritis.

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Similarly, Whipple’s disease manifests as:

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• Polyarticular symmetrical arthropathy

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• Diarrhoea

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• Weight loss

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• Lymphadenopathy, and

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• Fever.

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Whipple’s disease does not lead to urethritis.

Hint

This lady has Behçet’s disease. This is a clinical diagnosis. Recurrent scarring oro-genital ulcers are pathognomonic of Behçet’s disease. Recurrent oral ulcers occur in SLE but they are generally non-scarring.

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Reactive arthritis and sarcoidosis do not associate with recurrent scarring oro-genital ulcers.

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Uveitis does not occur in Steven-Johnson’s syndrome.

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The International Study Group criteria for classification of Behçet’s disease require the presence of recurrent oral ulceration (minor aphthous, major aphthous or herpetiform ulceration observed by physician or patient, which have recurred at least three times in a 12 month period), and two of the following:

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• Recurrent genital ulceration – aphthous ulceration or scarring, observed by physician or patient

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• Eye lesions – anterior uveitis, posterior uveitis, or cells in vitreous on slit lamp examination; or retinal vasculitis observed by ophthalmologist

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• Skin lesions – erythema nodosum observed by physician or patient, pseudofolliculitis or papulopustular lesions; or acneiform nodules observed by the physician in post-adolescent patients not on corticosteroid treatment

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• Positive pathergy test – read by physician at 24-48 hours.

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Pathergy is the non-specific hyperreactivity of the skin following minor trauma, and is specific to Behçet’s disease. It involves intradermal injection of skin with a 20-gauge needle under sterile conditions. It is considered positive if an erythematous sterile papule develops within 48 hours.

Hint

The most likely diagnosis for this gentleman with bilateral knee pain, swelling, stiffness, and positive rheumatoid Factor (RF) and antinuclear antibody (ANA) is C. Rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is a chronic inflammatory disorder that can affect more than just the joints. In some people, the condition can damage a wide variety of body systems, including the skin, eyes, lungs, heart, and blood vessels. The morning stiffness lasting almost an hour, the positive rheumatoid factor (RF) and antinuclear antibody (ANA), and the absence of psoriasis or family history of chronic skin conditions support the diagnosis of rheumatoid arthritis (RA) over the other options.

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The other options are incorrect for the following reasons:

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1. Pseudogout: This condition, also known as calcium pyrophosphate deposition (CPPD), typically affects older adults and is characterized by the presence of calcium pyrophosphate crystals in the joint fluid. This gentleman’s age and the absence of crystal identification in the synovial fluid make this diagnosis less likely.

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2. Reactive arthritis: This form of arthritis develops in response to an infection in another part of the body (cross-reactivity). Given the lack of recent illness history and the chronic nature of the symptoms, reactive arthritis is less likely.

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3. Psoriatic arthritis: This type of arthritis occurs in some persons with psoriasis, a condition that features red patches of skin topped with silvery scales. This gentleman has no psoriasis or nail changes, which are common in psoriatic arthritis.

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4. Systemic lupus erythematosus (SLE): Systemic lupus erythematosus (SLE) is an autoimmune disease that causes widespread inflammation and tissue damage in the affected organs. It can present with joint pain and positive antinuclear antibody (ANA); however, the absence of other systemic symptoms makes this diagnosis less likely compared to rheumatoid arthritis (RA).

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In conclusion, based on the clinical presentation and serological findings, rheumatoid arthritis (RA) is the most probable diagnosis in this case.

Hint

Carpal tunnel syndrome is one of the most common entrapment neuropathies, and is a recognised occupational disease. The carpal tunnel is an anatomical compartment bounded on three sides by the carpal bones, and the transverse carpal ligament on the palmar side. Intermittent or sustained high pressure within this compartment produces ischaemia of the median nerve, resulting in the classical symptoms or paraesthesia and pain. If allowed to progress, weakness and wasting develop which eventually become irreversible.

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Nerve conduction studies are an important diagnostic test, and are the best predictor of symptom severity and functional status. Treatment depends on severity, and includes splinting, corticosteroid interventions or surgical decompression. In the future pulsed radio frequency may be used.

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Gout is caused by the deposition of monosodium urate crystals within a joint, leading to excruitiating pain and swelling. It is not a common cause of the symptoms described above.

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Hypertrophic osteoarthropathy may occur secondary to primary lung carcinoma. It presents with clubbing, arthralgia, arthritis and periostosis of the tubular bones. Pain is severe and is present throughout the day.

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Rheumatoid arthritis is a possibility in women of this age group, but more commonly presents with swelling and pain of the small joints of the hand.

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Toxic neuropathy presents with weakness, sensory loss and reduced reflexes secondary to diffuse nerve damage. This can be caused by a variety of agents but is much less common than carpal tunnel syndrome, making it a less likely answer in this case.

Hint

The correct answer is E. Inflammatory arthritis associated with inflammatory bowel disease.

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Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation of the gastrointestinal tract, such as Crohn’s disease and ulcerative colitis. Arthritis is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting 7 to 20 percent of patients. The arthritis can affect the large joints of the lower extremities, such as the knee, as well as the spine and sacroiliac joints. The arthritis usually correlates with the activity of the bowel disease, and may improve with treatment of the underlying inflammatory bowel disease (IBD).

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The other options are incorrect for the following reasons:

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• A. Carcinomatous arthropathy is a rare paraneoplastic syndrome that causes arthritis and periostitis in patients with malignancies, such as lung, breast, or prostate cancer. This gentleman has no history of cancer or other risk factors, and the arthritis is more likely related to the bowel disease.

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• B. Gout is a metabolic disorder that causes hyperuricaemia and deposition of monosodium urate crystals in the joints, leading to acute inflammatory arthritis. This gentleman has no history of gout attacks, tophi, or renal stones, and the stool cultures are negative for infection, which can trigger gout flares. The arthritis is more likely related to the bowel disease.

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• C. Psoriatic arthritis is a type of spondyloarthritis that affects patients with psoriasis, a chronic skin condition that causes scaly, red patches. This gentleman has no history or signs of psoriasis, and the arthritis is more likely related to the bowel disease.

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• D. Reactive arthritis is a type of spondyloarthritis that occurs after an infection, usually of the gastrointestinal or genitourinary tract. This gentleman has no history of recent infection, and the stool cultures are negative for pathogenic organisms. The arthritis is more likely related to the bowel disease.

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Hint

The answer is sarcoidosis. The clues here include the non-responsiveness of chest symptoms to the salbutamol inhaler, erythema nodosum, non-specific elevation in inflammatory markers, and hypercalcaemia.

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Patients with sarcoid frequently present with symptoms of hypercalcaemia after a holiday because increased sun exposure results in increased production of vitamin D. A chest radiograph, not reported here, may show a variety of abnormalities, including bilateral hilar lymphadenopathy. The mainstay of treatment of sarcoidosis is with oral corticosteroids, but patients with mild symptoms can be managed with surveillance alone.

None of the other options listed commonly causes hypercalcaemia, and the inflammatory markers are only mildly elevated, reducing the probability of her symptoms being due to a chronic infection such as tuberculosis.

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Granulomatosis with polyangiitis is associated with symptoms of sinusitis due to granuloma formation, and Churg-Strauss syndrome would explain the asthma-like symptoms but not the others.

Hint

The most likely organism responsible for the findings in this lady with sickle cell disease is Salmonella species (D). Patients with sickle cell disease are particularly susceptible to osteomyelitis caused by Salmonella due to their impaired splenic function. The clinical presentation of pain in the groin radiating to the thigh and knee, fever, and x-ray findings of irregular bony destruction are consistent with osteomyelitis, which is a known complication in sickle cell disease.

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Let us address the other options:

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• Group B Streptococcus (A): While Group B Streptococcus can cause bone infections, it is more commonly associated with neonatal infections and is less likely to be the cause of osteomyelitis in a patient with sickle cell disease.

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• Clostridium perfringens (B): This organism is typically associated with gas gangrene and is not a common cause of osteomyelitis.

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• Yersinia pestis (C): It is the causative agent of the plague and does not typically cause osteomyelitis.

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• Candida albicans (E): While Candida species can cause osteomyelitis, it is usually in the setting of an immunocompromised host or intravenous drug use and is less likely in this clinical scenario.

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In summary, the clinical presentation, along with the patient’s history of sickle cell disease, strongly suggests Salmonella species (D) as the causative organism for the osteomyelitis in the femoral head. The presence of sickled erythrocytes on peripheral blood smear and the haemoglobin electrophoresis results further support the diagnosis of sickle cell disease, which increases the risk of Salmonella infection.

Hint

The correct answer is D. CBC, LFT and U&E at baseline and then two weekly until on stable dose of methotrexate and then every month. This is based on the guidelines for monitoring methotrexate toxicity in rheumatoid arthritis patients, which recommend that complete blood count (CBC), liver function tests (LFT) and urea and electrolytes (U&E) should be measured at baseline and then every two weeks until the gentleman is on a stable dose of methotrexate, and then every month thereafter. This is to ensure that the drug is well-tolerated and does not cause any adverse effects on the blood cells, liver or kidneys.

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The other options are incorrect for the following reasons:

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• A. CBC, coagulation screen, LFT and ESR at baseline and then weekly until on stable dose of methotrexate and then every three months: This option is incorrect because it includes a coagulation screen and an erythrocyte sedimentation rate (ESR), which are not necessary for monitoring methotrexate toxicity. Coagulation screen is used to assess the clotting ability of the blood, and erythrocyte sedimentation rate (ESR) is a marker of inflammation, but neither of them are affected by methotrexate. Moreover, this option suggests testing every three months after reaching a stable dose, which is too infrequent and may miss early signs of toxicity.

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• B. CBC, coagulation screen, U&E and Rheumatoid Factor weekly, includes baseline levels: This option is incorrect because it also includes a coagulation screen, which is not required for monitoring methotrexate toxicity, as explained above. Additionally, this option includes rheumatoid factor (RF), which is an antibody that can be detected in some patients with rheumatoid arthritis, but is not affected by methotrexate. Rheumatoid factor (RF) is used to diagnose rheumatoid arthritis, but not to monitor methotrexate therapy. Furthermore, this option suggests testing weekly, which is too frequent and unnecessary, as methotrexate toxicity usually develops over weeks to months.

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• C. CBC, LFT and U&E monthly, including baseline levels: This option is incorrect because it suggests testing monthly from the start of methotrexate therapy, which is not frequent enough to detect early toxicity. Methotrexate toxicity can occur within the first few weeks of treatment, especially in patients with renal impairment, obesity, diabetes, or alcohol use. Therefore, testing every two weeks until a stable dose is achieved is recommended.

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• E. CBC, uric acid, folate levels, U&E and LFT at baseline and then weekly until on stable dose of methotrexate and then every two to three months: This option is incorrect because it includes uric acid and folate levels, which are not necessary for monitoring methotrexate toxicity. Uric acid is a waste product that can accumulate in the blood and cause gout, but methotrexate does not affect uric acid levels. Folate is a vitamin that is essential for DNA synthesis and cell division, and methotrexate inhibits folate metabolism, which can lead to folate deficiency. However, folate deficiency can be prevented by taking folic acid supplements, which are usually prescribed along with methotrexate. Therefore, measuring folate levels is not required for monitoring methotrexate therapy. Moreover, this option suggests testing every two to three months after reaching a stable dose, which is too infrequent and may miss early signs of toxicity.

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Hint

This is a slightly difficult question, but you may experience similar during the exam. It tests your ability to consider epidemiology as well as your knowledge of disease presentations.

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In this middle aged gentleman, the acute bilateral arthritis of shoulders and wrists together with synovitis and raised ESR are highly suggestive of acute rheumatoid arthritis. The features given do not fully satisfy the ACR criteria (see the reference for updated guidelines), but it is not unusual for this to be the case in clinical practice.

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Weakness and myalgia would be expected with polymyositis and a rash would be expected with systemic lupus erythematosus with less evidence of a synovitis.

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There is no prior precipitant to suggest a reactive arthritis, although it is important to consider this diagnosis in young patients.

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PMR would be less likely in this age group as it usually occurs in patients over 50 years of age

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Proximal weakness in the morning with the gel phenomenon would be expected, and synovitis in the wrists would be less likely in PMR.

Hint

It is important to be aware of the following teaching points:

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• Recommendations for biologic therapy in rheumatoid arthritis (RA)

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• Contraindications to biologic therapy, and

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• Basic disease scoring in RA.

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This lady has a DAS-28 score persistently greater than 3.2 and has failed on a combination of more than two disease modifying agents, thus fulfilling the criteria for consideration of anti-TNF (biologic) therapy.

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Patients receiving anti-TNF alpha treatment have an increased risk of clinical tuberculosis (TB) development. The current British Thoracic Society guidelines therefore recommend a clinical examination, chest radiograph and thorough history taken to check for prior TB.

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Any patient with an abnormal chest radiograph or previous history of TB should be referred for assessment by a specialist with an interest in TB. Those with symptoms raising a suspicion of TB should be thoroughly investigated to exclude active disease. Any patient with active TB, either pulmonary or non-pulmonary, should receive standard chemotherapy. They must complete two months full treatment before starting anti-TNF alpha treatment.

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Patients with an abnormal chest radiograph consistent with past TB, or a history or prior extrapulmonary TB but who have received previous adequate therapy can be started on anti-TNF alpha therapy but need to be monitored regularly.

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Where there is an abnormal chest radiograph, or a history of prior pulmonary or extrapulmonary TB not previously adequately treated, chemoprophylaxis should be given before commencing anti-TNF alpha treatment.

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For patients with a normal chest radiograph who have not started immunosuppressive threrapy, a tuberculin test is helpful.

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If a patient is already on immunosuppressive treatment, the result of the tuberculin test is dampened and it is therefore not useful. An individual risk assessment should be made: if the annual risk of TB is greater than that of drug-induced hepatitis then chemoprophylaxis should be given. If not, the patient should be monitored and investigated early if symptoms consistent with TB develop.

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Chemoprophylaxis is generally with isoniazid for 6 months.

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The BTS guidelines have not been updated to include recommendations regarding Quantiferon and Elispot tests. Practice does vary between individual NHS trusts regarding who to test with one of these, and which to use. However, the most accepted recommendations are that patients who test positive with either of these should be treated with chemoprophylaxis (either isoniazid for 6 months, or dual therapy for two months) at the same time as being started on anti-TNF alpha treatment.