Life-saving treatment with anakinra in severe relapse of Still disease with perimyocarditis and aseptic pneumonia

A 27-year-old man with a history of systemic juvenile rheumatoid arthritis (sJRA), remaining in remission for 13 years (the Pouchot score of 0), presented urgently to a cardiology department due to myopericarditis with typical chest pain, pericardial effusion on transthoracic echocardiography (Figure 1A), reduction of the PQ segment on electrocardiogram, and high troponin T levels (up to 1352 pg/ml, reference range [RR] <⁠13 pg/ml). He also reported sore throat, a fever up to 39 ^oC, and arthralgia in shoulders and knees. Laboratory tests revealed severely elevated inflammatory parameters with ferritin up to 13 641 ng/ml (RR, 30–400 ng/ml) and leukocytosis up to 22 × 10³/µl (RR, 4.26–10.57 × 10³/µl), with 95% neutrophil predominance and a neutrophil / lymphocyte ratio of 32. Rheumatoid factor, antinuclear antibodies, and antineutrophil cytoplasmic antibody tests were negative. Viral infections and other triggers were excluded. Based on the Yamaguchi criteria¹ (the patient fulfilled all minor criteria and 3 major criteria besides rash), a suspicion of Still disease was raised by a consulting rheumatologist. Despite intravenous administration of methylprednisolone (1100 mg in a single dose) the patient condition deteriorated with sudden dyspnea, desaturation, fever (up to 41 ^oC) and a pink maculopapular rash (Figure 1B), with a computed tomography (CT) image showing left-sided pneumonia and left pleural effusion (Figure 1C). The patient was urgently transferred to a pulmonology department, where noninfectious lung involvement was confirmed by thoracentesis and bronchoscopy. After readmission to the rheumatology department, treatment with high doses of intravenous methylprednisolone pulses (cumulative 3 g), followed by oral prednisone 60 mg daily and methotrexate 15 mg per week orally were introduced. After initial temporary improvement, the patient condition deteriorated with recurrence of fever, sore throat, skin changes, and rising ferritin level. A CT scan revealed pleural, pericardial, and peritoneal effusion, splenomegaly, and right hilar lymphadenopathy (Figure 1D). Macrophage activation syndrome and leukemia were excluded based on bone marrow biopsy. Paroxysms of atrial flutter followed by bradycardia were observed. Echocardiography showed reduced left ventricular global longitudinal strain (Figure 1E), and cardiac magnetic resonance imaging showed enhancement of the thickened pericardium (Figure 1F). Life-saving therapy with anakinra (an interleukin-1 antagonist; 100 mg daily, subcutaneously) was administered, with rapid resolution of fever, pulmonary and skin lesions, normalization of the inflammatory parameters and ferritin level. The patient was discharged on maintenance treatment with anakinra, methotrexate, and tapered prednisone, and has remained asymptomatic at a 3-month follow-up.

Nowadays sJRA and adult-onset Still disease are considered a continuum of Still disease.² This rare (1–10 per million annually) autoinflammatory disorder may differ in its clinical manifestation and course from mild to life-threatening.³ Our case of glucocorticoid-resistant flare of Still disease with multiorgan involvement shows that a failure to respond to traditional treatment in Still disease should raise suspicion of its potentially life-threatening course and encourage implementation of biologic treatment without delay. From a diagnostic point of view, it also shows that Still disease should be taken into consideration in the initial workup of myopericarditis.