Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature

Makino, Jun; Koshy, Sanjana; Bajaj, Sonal; Jeong, Young-Gwang; Perlman, David C.

On physical examination, the patient had a temperature of 35.3 C, blood pressure of 117/75 mmHg, pulse rate of 112 beats/ min, respiratory rate of 29 breaths/min, and an oxygen saturation of 96% on room air. There were bilateral lung wheezes, and multiple painful ecchymosis with several hemorrhagic bullae over his trunk and extremities (Fig. 1 ). CBC on admission showed WBC 9000/mm3 (87% neutrophils) and Hemoglobin 13.4 g/dL, and comprehensive metabolic panel including electrolytes, liver and renal function was all within normal range. The significant laboratory data included high lactate dehydrogenase of 799 IU/L, erythrocyte sedimentation rate of 81 mm/h, and C-reactive protein level of 38.5 mg/dL. The Xray and computed tomography (CT) of the chest showed multifocal alveolar infiltrates; there was no evident pulmonary embolism on a CT angiogram (Fig. 2 ). Empiric treatment with intravenous ceftriaxone and oral azithromycin was initiated for community acquired pneumonia (CAP). The ecchymoses appeared to worsen on the following day, and the possibility of an adverse drug reaction was raised. Ceftriaxone and azithromycin were switched to levofloxacin, and vancomycin was added. On the second day after admission, a punch biopsy of an ecchymotic lesion on the right arm was performed. The histopathological findings revealed a superficial and deep dermal thrombotic paucicellular vasculitis/vasculopathy involving skin appendages without significant neutrophils or leukocytoclasia (Fig. 3) . Tests for cryoglobulin, serum protein electrophoresis (SPEP), protein C, protein S, b-2 glycoprotein IgM and IgG, rheumatoid factor, CCP IgG, ds DNA Ab IgG, complement levels, ANCA, GBM Ab IgG, Scl-70 IgG, SSA,B Ab, Jo-1 IgG Ab were negative. Tests for ANA 1:160, lupus anticoagulant 82 (normal range: 27-41 s), cardiolipin Ab IgM 64 (normal range: 0-12), and phosphatidylserine Ab IgM > 100 (normal range: <10) were positive. A nasal swab for MRSA and a sputum respiratory culture for bacteria were negative, and vancomycin was discontinued on the fourth day. Nasopharyngeal swabs for influenza antigen, streptococcal antigen, and urine for legionella antigen were negative. Nasal swab for the FilmArray Respiratory Panel (BioFire) was positive for RSV, but adenovirus, coronavirus, human metapneumovirus, rhinovirus, enterovirus, influenza virus, parainfluenza virus, Bordetella pertussis, chlamydophilia pneumoniae, mycoplasma pneumoniae were negative. Also, other possible infectious etiologies associated with APS were investigated, and EBV DNA PCR was positive (8696 copies/mL), but HIV, CMV, hepatitis A, B and C were negative. The patient's respiratory symptoms gradually improved, and a repeat CT of the chest done on the seventh day post admission showed interval improvement of the diffuse bibasilar opacities. A transbronchial lung biopsy performed on day 6 showed intraalveolar hemorrhage, interstitial fibrosis and intra-capillary megakaryocytes. Lung tissue culture grew Actinomyces odontoyiticus and Staphyloccous sacchalolyticus which were considered contaminants. The patient completed a 7-day course of levofloxacin with significant improvement of his respiratory symptoms. His skin lesions also gradually improved. The patient improved and was discharged on hospital day 10, and he has remained in a good health. It was subsequently found that the patient's 3-year old son had been diagnosed with acute RSV infection one week prior to the patient's admission. A lupus anti