7. Life-threatening adult-onset Still’s disease
Authors: Arumalla Nikita , Coakley Gerald , Agarwal Sangita 
Published: September 2019

Abstract

Introduction
Adult-onset Still’s disease (AOSD) is a rare inflammatory disorder of unknown aetiology with systemic involvement. The presentation and severity is highly variable in affected individuals and requires a clinical diagnosis, commonly using the Yamaguchi classification criteria. The majority of patients with AOSD develop non-specific symptoms associated with a systemic inflammatory response including fever, rash and arthralgia; however, a few patients with AOSD develop life-threatening complications. Here, we describe a case of newly diagnosed AOSD who rapidly deteriorated with myo-pericarditis, cardiogenic shock and multi-organ failure requiring ECMO, despite treatment with high dose oral corticosteroids.

Case description
A 27-year old female presented with a 6-month history of joint pain, fever, sore throat, evanescent red rash, night sweats and weight loss. On examination she had florid synovitis in most of her small and large joints. Laboratory tests showed a DAT positive (IgG positive) haemolytic anaemia with haemoglobin 60g/L, raised ESR 98mm/hr and CRP 261mg/L and an elevated Ferritin level of 14,892ug/L. ANA, dsDNA and RF were negative; anti-cardiolipin IgM was initially positive, but negative on repeat. CT scan of the chest, abdomen and pelvis (CTCAP) showed diffuse lymphadenopathy, hepatomegaly and mild pericardial effusion. A likely diagnosis of AOSD was made and she rapidly improved clinically and biochemically on oral prednisolone 60mg daily. Her ferritin fell to 5,500ug/L and she was discharged with outpatient follow-up.
2-weeks later she re-presented feeling non-specifically unwell with new orthopnoea. She was tachycardic (HR 120bpm), hypotensive (BP 95/60mmHg), ECG showed widespread ST depression and she had significant hyperferritinaemia (50,695ug/L) with a raised Troponin-T level of 134ng/L. Despite treatment with intravenous methylprednisolone (IVMP) 1000mg, she rapidly deteriorated and 6-hours later had a brief period of cardiac arrest. Echocardiogram showed global hypokinesis and severe systolic dysfunction with ejection fraction of 15%. She had developed anuric renal failure, hyperlactataemia (Lactate 16) and profound shock in the setting of severe acute heart failure, and was started on VA-ECMO. Alongside supportive therapies this patient received 3 days of IVMP 1000mg/day, intravenous immunoglobulin (IVIg) 2mg/kg and intravenous anakinra 200mg daily. She made an excellent recovery – she was de-cannulated from VA-ECMO on day 4 and extubated on day 6. Ferritin level fell to 6439ug/L and troponin-T down to 64 ng/L. Due to hypoperfusive injury, the patient developed necrotic foot ulcers which required debridement; however the AOSD remains stable, with oral prednisolone weaned to 40mg daily and subcutaneous anakinra 100mg daily.

Discussion
Our patient fulfilled Yamaguchi classification criteria for AOSD with three major criteria (leucocytosis, rash, arthralgia) and four minor criteria (sore throat, lymphadenopathy, hepatomegaly and negative ANA and RF).
AOSD is an uncommon condition, with annual incidence estimated to be less than 1 case per 100,000 people. Cardiopulmonary disease can be observed in up to 40 percent of patients with AOSD including pericarditis and pleural effusions, with the more serious manifestations of myocarditis and acute respiratory distress syndrome (ARDS) being described as rare. Whilst myocarditis has been reported to have a prevalence of around 7% in AOSD, a recent systematic review looking at severe organ manifestations of AOSD (79 cases from 62 publications reviewed) found that 23% of studied cases had cardiac complications, with 15% having myocarditis and 6% having cardiogenic shock associated with this. 20% of cases had multi-organ failure. Organ complications mostly occurred at diagnosis (78% of cases studied). Another pooled case series reviewing myocarditis in AOSD found that myocarditis occurred early in the disease course with 80% occurring in the first year, with 54% having myocarditis at the onset of disease.
When AOSD patients with myocarditis were compared to a control group of AOSD without myocarditis, clinical features such as fever, rash and sore throat were similar in both groups; however, arthritis was less frequent in the myocarditis group (25% versus 42%) and total WCC was higher. Interestingly there was no significant difference in serum ferritin levels between these two groups. In all, 50% of cases in both groups required disease modifying treatment beyond corticosteroid therapy. Similarly, a review looking at life-threatening organ complications in AOSD demonstrated that 50% of these cases also required second-line therapies including IVIg or anakinra; however these patients had lower ferritin levels and less severe disease overall.

Key learning points
Literature so far suggests the key severe manifestations of AOSD leading to intensive care admission are cardiogenic failure secondary to myocarditis or cardiogenic shock, non-cardiogenic shock, respiratory failure from ARDS or pleural effusion and haematological complications including macrophage activation syndrome and disseminated intravascular coagulation. Treatment included corticosteroids, IVIg, cyclosporin, etoposide and anakinra, with an efficacy rate of 64% for steroids alone, 41% for IVIg and 89% for IL1-Ra anakinra.
We have described a case of AOSD complicated by myocarditis and multi-organ failure, which occurred early in the disease course. Despite these life-threatening complications, our patient responded well to combination treatment with corticosteroids, IVIg and anakinra. Published cases suggest that myocarditis remains an uncommon manifestation of AOSD, but tends to occur early in the course of the disease and can be further complicated by cardiogenic shock, as in our patient. At least half of AOSD patients with myocarditis and/or MOF require further therapies such as IVIg or Anakinra in addition to corticosteroids. Due to its heterogeneous presentation, it is important that general medical physicians, cardiologists and intensive care physicians as well as rheumatologists be aware of the condition and the potential for rapid deterioration. Further study is required to identify which patients with AOSD are at higher risk of developing life-threatening complications associated with this condition.

Conflict of interest
The authors declare no conflicts of interest.