Adult Onset Still’s Disease Presenting with Acute Respiratory Distress Syndrome: Case Report and Review of the Literature
A 26-year-old African-American female with a history of type 2 diabetes mellitus presented to her primary care physician with sore throat and cough. She was noted to have a “viral exanthem”, and was started on amoxicillin-clavulanate. Her symptoms did not improve and she went to the emergency department (ED) for shortness of breath, cough and myalgias. Her vital signs were as follows: temperature 36.7 C, pulse rate 112, respiratory rate 18, and blood pressure 100/56 mm Hg. Physical examination was notable for coarse breath sounds bilaterally over lung fields with scattered crackles at the bases and tachycardia. Radiograph of the chest showed bilateral interstitial infiltrates suggestive of ARDS. Arterial blood gas (ABG) showed pH 7.28, pCO2 38 mmHg and pO2 58 mmHg. Her respiratory status worsened and she underwent endotracheal intubation requiring ventilator support, and was started on broad-spectrum antibiotics for presumed pneumonia.\nTwo days after admission to the intensive care unit (ICU), the patient developed daily spiking fevers up to 40.0 C. She became more difficult to oxygenate with increasing ventilator requirements. She became hypotensive to 70/49 mmHg and required vasopressors. Antibiotic therapy was broadened and changed multiple times, including treatment with vancomycin, ceftriaxone, azithromycin, piperacillin/ tazobactam, imipenem, metronidazole and fluconazole, without any clinical improvement.\nLaboratory analysis included an initial white blood cell (WBC) count of 20 x 103/mm3 (which increased to 49 x 103/mm3 within one week) with 91.8% neutrophils. Hemoglobin (Hb) was initially 10 g/dL (and dropped to 8.3 g/dL within one week), and platelet count 407,000/mL. Aspartate aminotransferase (AST) was 88 IU/L, alanine aminotransferase (ALT) 44 IU/L, and lactate dehydrogenase (LDH) 530 units/L. Autoimmune panel was negative for anti-nuclear antibodies (ANA) and rheumatoid factor (RF). C-reactive protein (CRP) was elevated at 7.19 nmol/L and erythrocyte sedimentation rate (ESR) was 39 mm/h. The ferritin level was 4,022 ng/mL.\nThe patient underwent further extensive evaluation during the first ten days of her admission. All cultures during fever spikes were negative, including seven sets of blood cultures. Computerized axial tomography (CT) scans of her neck and sinus were unremarkable. CT of the chest revealed bilateral pleural effusions and diffuse, patchy airspace opacities and interstitial infiltrates. She underwent bronchoscopy which was negative for bacterial, viral (including cytomegalovirus) or fungal infection. Hepatitis panel, urine legionella, serum histoplasma antigen, cryptococcal antigen, Clostridium dificile toxin, and acid fast bacilli were all negative. Transthoracic echocardiogram was normal with an ejection fraction of 55-65%. Bone marrow biopsy and flow cytometry were normal.\nShe was diagnosed with AOSD based on fulfillment of the Yamaguchi criteria with major criteria of fevers lasting greater than one week, leukocytosis with neutrophilia, and minor criteria of abnormal liver enzymes, sore throat, and negative RF and ANA []. In addition, she had hyperferritinemia and no evidence of infection or malignancy after extensive investigation. She was started on methylprednisolone 60 mg intravenously (IV) every 6 hours on day 13 of her hospital admission, and the next day, her maximum temperature improved to 38.2 C, down from 39.4 C. On day 16 she was given pulse methylprednisolone 1000mg daily for 3 days, followed by prednisone 60mg daily. She remained afebrile until her discharge on hospital day 19. She was weaned off vasopressors, antibiotics were discontinued, mental status was at baseline, and WBC count improved prior to discharge. She had developed an ICU polyneuropathy during her hospital course and required tracheostomy and transfer to a ventilator facility for weaning from ventilator support. At the ventilator facility she was continued on prednisone 60 mg daily except for one missed dose of prednisone the week prior to re-admission.\nTwo weeks after her discharge, she was re-admitted to the ICU with spiking fevers to 39.4 C, and again, broad-spectrum antibiotic therapy with vancomycin, tobramycin, and metronidazole was initiated. Two days after admission, she had a seizure followed by hypotension to 87/43 mmHg and required vasopressor support. Seizures were treated with lorazepam and phenytoin. Imipenem, metoclopramide, and metronizadole were discontinued, and meropenem and oral vancomycin were initiated. Laboratory testing revealed a WBC count of 15.1 x 103/mm3, Hb 6.9 g/dL, platelets 61,000/mL, AST 627 IU/L, ALT 507 IU/L, LDH 2,080 units/L, ferritin 110,065 ng/mL, fibrinogen 170 g/L, normal coagulation studies and ESR 16 mm/h.\nShe continued to have seizure activity, electromyogram showed moderate to severe axonal sensorimotor polyneuropathy, and electroencephalogram revealed epileptiform activity over the right parietal region and prominent sharp waves over bilateral temporal regions. Magnetic resonance imaging of the brain revealed multifocal stenosis of bilateral posterior cerebral arteries and a segment of the left anterior cerebral arteries. CT chest showed bilateral large pleural effusions with consolidation and airspace opacities consistent with ARDS. The patient was started on methylprednisolone 1000 mg IV daily for three days followed by prednisone 60 mg daily and cyclosporine 3mg/kg/day for presumed macrophage activation syndrome (MAS). Because of her continued deteriorating course, a repeat bone marrow biopsy was done over two weeks after cyclosporine therapy was begun and showed positive staining for cytomegalovirius (CMV) without evidence for hemophagocytosis. CD 163 staining to look for activated histiocytes was not performed. In addition, the cerebrospinal fluid (CSF) was positive for CMV by PCR and the patient was started on gancyclovir. The patient’s presentation was felt to meet criteria for CMV infection and secondary hemophagocytic syndrome despite bone marrow absence of true hemophagocytosis. The patient died despite treatment and supportive care measures six weeks after her initial presentation with ARDS and AOSD.