Pulmonary arterial hypertension in adult onset Still’s disease: a case report of a severe complication

A 19 year-old female presented with persistent fever, evanescent rash (Fig. 1), sore throat and polyarthralgia without synovitis (bilateral knees, shoulders, elbows and metatarsophalangeal joints). Physical examination showed axillary and inguinal lymphadenopathy (diameter < 1 cm). Investigations revealed a high erythrocyte sedimentation rate (87 mm/first hour) and high C-reactive protein (CRP) (116 mg/L). Serum creatinine, liver enzymes, CPK, granulocytes and platelet levels were all normal. Rheumatoid factor, anti CCP, antinuclear antibodies and antineutrophil cytoplasm antibodies were negative. Blood cultures were negative. Serological tests for virus (EBV, CMV, HSV and HIV) were negative. Ferritin level was high (8140 μg/L) and glycosylated ferritin was low (rate: 9 %). Computed tomography (CT) scan of chest, abdomen and pelvis was normal (Fig. 2a). The presentation suggested a systemic rheumatic disease and the investigations excluded alternative auto-immune diagnoses. AOSD was finally proposed, as a diagnosis of exclusion, based on the association of arthritis, rash, fever, elevated acute phase reactants and low glycosylated ferritin.

She received oral steroids (1 mg/kg), which led to clinical and laboratory improvement. Symptoms reappeared during the tapering-off phase (25 mg.d⁻¹) and the dose was increased again to 1 mg/kg with the addition of a 10 mg methotrexate dose once a week. Despite methotrexate therapy, the patient experienced a second relapse when the steroid dose was decreased (25 mg.d⁻¹). Methotrexate dose was increased to 15 mg once per week, with a steroid dose at 25 mg.d⁻¹. Decision was made to introduce anakinra (100 mg.d⁻¹) as a steroid sparing agent. Steroid dosage was decreased and methotrexate was discontinued but subsequently reintroduced due to a reappearance of skin rash.

Two years after AOSD diagnosis, the patient presented with NYHA class III dyspnea associated with polyarthritis, fatigue and ferritin increase. At that time, therapy was methotrexate (15 mg once per week), corticosteroids (25 mg.d⁻¹) and anakinra. There was no sign of right-sided heart failure and the electrocardiogram was normal. The patient walked 462 m with oxygen desaturation (SpO2 : 87 %) on a 6-min walk test (6MWT). Vital capacity was 1.6 L (49 %), and total pulmonary capacity 2.44 L (59 %). Carbon monoxide diffusion capacity was low (22 %). We did not have any reference values as the patient had no previous pulmonary function tests available. Arterial blood gas analysis revealed hypoxemia (pO2 : 71 mm.Hg⁻¹) and hypocapnia (pCO2 : 34 mm.Hg⁻¹). BNP, troponin, serum uric acid, creatinin and CRP were normal. Chest HRCT showed a dilated pulmonary trunk (PT) (31 mm); the PT/Aorta trunk index was 1.4 and the right ventricle/left ventricle (RV/LV) index was 1.26 (Fig. 2b). There was no pleural or parenchymal involvement of the lungs; no signs of pulmonary vasculitis, and no pulmonary embolism as confirmed by a ventilation/perfusion scan. Doppler echocardiography showed a systolic pulmonary artery pressure of 65 mm.Hg⁻¹. Pulmonary hypertension was confirmed by right heart catheterization with a mean pulmonary artery pressure (mPAP) of 33 mm.Hg⁻¹ and normal PCWP (4 mm.Hg⁻¹). The cardiac output was 4.0 L.mn⁻¹ and pulmonary resistance was 7.25 UWood. A Nitric oxide test was negative.

The patient was included in a clinical trial and received ambrisentan and tadalafil associated with ongoing anakinra and corticosteroids. Methotrexate was removed to avoid adverse effects on the lungs or liver. Ambrisentan was rapidly discontinued due to cytolytic hepatitis. One month later, she was admitted to ICU for right-sided heart failure; a thrombotic thrombocytopenic purpura was observed (low platelets at 5G/L, anaemia at 6.7 g/dL, LDH: 905 UI/L ADAMTS13: 31 % with N: 50–150 %). Dobutamine and intraveinous (IV) prostacycline were administered, with a progressive improvement. The patient showed a clinical improvement with a distance of 696 m on 6MWT under IV protacycline, tadalafil, anakinra and corticosteroids. One month later, she was admitted again to intensive care for septic shock with a staphylococcus epidermidis infection. The tunneled catheter was removed and bacteriological analyses found staphylococcus epidermidis. Evolution was poor and she passed away despite antibiotic treatment (piperacillin/amikacin) and vasoactive drug support.

Not applicable.

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Data are not available for obvious reasons of patient confidentiality.