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A 24-year-old man presents with a 3-week history of daily spiking fevers reaching 39.7 degrees C in the late afternoon/evening, an evanescent salmon-pink macular rash over his trunk that appears with the fevers and fades between them, arthralgia of the wrists and knees, and a sore throat. He has lost 4 kg and feels exhausted. He is otherwise previously well and takes no regular medications. On examination he is febrile (39.4 degrees C), has a faint salmon-pink rash on the trunk, mild cervical lymphadenopathy, a mildly enlarged spleen, and tender wrists and knees with small effusions; the throat is mildly erythematous but non-exudative. Investigations: WBC 18.2 (neutrophils 88 percent), Hb 108, platelets 480, CRP 212 mg/L, ESR 96, ferritin 5600 micrograms/L, ALT 95, ALP mildly raised, ANA negative, RF negative; blood cultures (three sets) negative; HIV, hepatitis B and C, EBV, CMV and parvovirus B19 serology negative; LDH normal; CT chest/abdomen/pelvis shows splenomegaly only.
Questions
a) What is the most likely diagnosis, and what is the key diagnostic principle? (2 marks)
Most likely adult-onset Still's disease (AOSD). The key principle is that it is a diagnosis of exclusion: the classical tetrad of quotidian spiking fever, evanescent salmon-pink rash, arthritis and sore throat with very high ferritin and negative ANA/RF is diagnostic only after infection, malignancy (lymphoma) and other rheumatic disease have been excluded (then applying the Yamaguchi or Fautrel clinical criteria).
b) Name four differential diagnoses that must be excluded and state how each is excluded. (3 marks)
- Sepsis / infective endocarditis — multiple blood cultures, echocardiography, and targeted imaging (excluded here).
- Lymphoma / malignancy — examine nodes, LDH, CT imaging, and lymph-node or bone-marrow biopsy if indicated (LDH normal and CT negative here).
- Systemic lupus erythematosus — ANA, anti-dsDNA, complement, urinalysis (ANA negative here).
- Acute rheumatic fever / reactive or viral arthritis — ASO titre, preceding infection history, viral serology, and migration pattern of arthritis.
c) Outline the management. (3 marks)
- First-line: NSAIDs (e.g. naproxen or indometacin) for fever and arthritis, plus glucocorticoids — oral prednisolone 0.5 to 1 mg/kg/day for systemic features (IV methylprednisolone pulses for severe/organ-threatening disease).
- Steroid-sparing: methotrexate (10 to 25 mg weekly with folic acid) for chronic articular disease or to taper steroids.
- Refractory/systemic: IL-1 inhibitors (anakinra 100 mg subcutaneously daily, or canakinumab) as the preferred first-line biologic; tocilizumab for the chronic articular pattern. Treat to remission, then taper.
- Multidisciplinary monitoring of inflammatory markers, ferritin, FBC and LFTs; screen for TB, hepatitis and HIV before biologics.
d) Name two complications, and describe the life-threatening complication including its earliest laboratory signature and treatment. (2 marks)
- Complications: chronic destructive arthritis and treatment-related toxicity (glucocorticoid and biologic adverse effects).
- The life-threatening complication is macrophage activation syndrome (secondary HLH). Its earliest laboratory signature is falling platelets and white cells with falling fibrinogen and rising ferritin, LDH, triglycerides and transaminases alongside persistent fever. Treat as an emergency with high-dose IV methylprednisolone pulses plus anakinra (IL-1 blockade), supportive care for cytopenias and coagulopathy, and ICU-level monitoring.