<p>In a 34-year-old pregnant woman at 10 weeks’ gestation with a 3-week history

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MSt MRCGP.

Posted: 24 July 2026Updated: 24 July 2026 Guideline-Aligned (High Confidence) Clinically Reviewed

Most likely diagnosis: The presentation is most consistent with adult-onset Still’s disease (AOSD), with active systemic disease causing serositis (bilateral pleural and pericardial effusions). ,

Immediate disposition: This requires same-day emergency admission under maternal medicine/obstetrics, rheumatology, haematology and respiratory/cardiology input, with urgent assessment for infection and cardiorespiratory compromise. Pregnant adults meeting high-risk sepsis criteria require immediate senior assessment, blood gas including lactate, blood cultures, FBC, CRP, renal function, liver tests and clotting screen, and broad-spectrum antibiotics within 1 hour if sepsis remains suspected.

Clinical classification criteria: Apply Yamaguchi criteria after exclusion of infection, malignancy and other rheumatic disease: major criteria are fever at least 39°C lasting at least 1 week, arthralgia/arthritis lasting at least 2 weeks, typical evanescent salmon-pink rash, and leucocytosis at least 10,000/µL with at least 80% neutrophils. The diagnosis requires at least 5 criteria, including at least 2 major criteria, after the required exclusions.

She fulfils all four Yamaguchi major criteria: quotidian fever of 39.5°C for 3 weeks, arthralgia for 3 weeks, fever-associated evanescent salmon-pink rash, and WBC 24,000/µL with 88% neutrophils. She also fulfils minor criteria of sore throat, splenomegaly/lymphadenopathy, abnormal inflammatory markers, and negative RF and ANA.

Required investigations to support AOSD and exclude mimics: Repeat blood cultures before antimicrobials where feasible; FBC with differential and film; CRP/ESR; ferritin and serial ferritin; LFTs, U&E/creatinine, albumin, LDH and triglycerides; coagulation screen including fibrinogen and D-dimer; blood gas with lactate; urinalysis/culture; pregnancy-safe infection testing directed by exposure history; and assessment for haematological malignancy, including peripheral film and haematology-led marrow assessment if indicated. NICE recommends blood gas including lactate, blood culture, FBC, CRP, renal tests, liver tests and clotting screen in recently pregnant people with suspected high-risk sepsis.

Hyperferritinaemia emergency: Urgently screen for secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), a life-threatening hyperinflammatory syndrome associated with fever, hepatomegaly and cytopenias and high mortality if not recognised and treated early.

HLH/MAS investigations and thresholds: Obtain urgent serial FBC, LFTs, bilirubin, triglycerides, fibrinogen, ferritin, LDH, clotting tests, soluble IL-2 receptor (sCD25), NK-cell activity where locally available, and assess for haemophagocytosis on bone-marrow or other tissue examination if uncertainty persists. Use HLH-2004 criteria: 5 of 8 are required—fever; splenomegaly; cytopenias affecting at least 2 lineages (haemoglobin below 90 g/L, platelets below 100×10⁹/L, neutrophils below 1.0×10⁹/L); triglycerides at least 3.0 mmol/L and/or fibrinogen at most 1.5 g/L; haemophagocytosis; low/absent NK activity; ferritin at least 500 micrograms/L; and sCD25 at least 2400 U/mL. Her ferritin of 12,500 ng/mL warrants immediate haematology involvement and repeated surveillance for falling cell counts, hypofibrinogenaemia, hypertriglyceridaemia, hepatitis, coagulopathy and organ dysfunction. HLH is characterised by extreme systemic inflammation and should be evaluated immediately when manifestations of pathological immune activation occur.

First-trimester pharmacological plan:

  • 1. Stabilise and treat competing infection risk: Give oxygen and manage pleural/pericardial disease in hospital, obtain the urgent sepsis investigations above, and give maximum-dose broad-spectrum intravenous antimicrobials within 1 hour if high-risk sepsis cannot be confidently excluded.
  • 2. Start systemic glucocorticoid treatment promptly after cultures and specialist review: Prednisolone is the preferred systemic corticosteroid in pregnancy; for severe systemic AOSD/serositis use high-dose oral prednisolone or intravenous methylprednisolone in a monitored inpatient setting, then taper according to clinical response and serial CRP/ferritin. Short-term oral, intramuscular or intra-articular glucocorticoids are established bridging treatment for inflammatory rheumatic disease.
  • 3. Use paracetamol for antipyresis and analgesia: Avoid routine NSAID use in this unstable first-trimester systemic presentation until maternal-fetal medicine and rheumatology have assessed renal function, bleeding/coagulation status, infection risk and the pericardial/pleural disease.
  • 4. Add a pregnancy-compatible steroid-sparing conventional DMARD if persistent arthritis or steroid dependence develops: Hydroxychloroquine and sulfasalazine are the preferred conventional options in pregnancy under rheumatology supervision; use folic-acid supplementation with sulfasalazine. Rheumatology-led treat-to-target care and glucocorticoid bridging while a DMARD takes effect are standard principles.
  • 5. Escalate refractory or life-threatening systemic disease with specialist multidisciplinary agreement: Anakinra is generally the preferred IL-1 inhibitor when biologic therapy is required in pregnancy because of its shorter half-life and accumulating pregnancy experience; canakinumab or tocilizumab should not be routine first-trimester choices and require exceptional specialist risk-benefit review. Canakinumab has demonstrated efficacy in Still’s disease trials, and tocilizumab carries clinically important risks including serious infection, neutropenia, hypofibrinogenaemia and hepatic injury. ,
  • 6. If HLH/MAS is suspected or confirmed: Escalate immediately to haematology, rheumatology, maternal medicine and critical care; treat as a hyperinflammatory emergency with high-dose corticosteroids and specialist-directed immunomodulation while monitoring organ function and coagulation. HLH has high mortality when not recognised and treated early.

Strictly contraindicated in early pregnancy: Do not use methotrexate or leflunomide, because both are teratogenic conventional DMARDs and are contraindicated in pregnancy. Hydroxycarbamide is also potentially teratogenic and should be avoided in pregnancy. Potentially teratogenic medications should ideally be discontinued before conception. ,

Key practical point: The combination of AOSD phenotype, ferritin 12,500 ng/mL and new serositis is an inpatient rheumatological and haematological emergency rather than a condition for outpatient symptomatic management. HLH is explicitly described as life-threatening and requiring immediate evaluation when pathological immune activation is suspected.

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