A 31-year-old woman presented to the Emergency Department (ED) with generalized fatigue and lethargy. Medical history was significant for type II diabetes mellitus, sickle cell trait and SLE complicated by lupus nephritis class III. SLE was diagnosed one-year prior following presentation with discoid cutaneous lesions and high ANA titers with initiation of hydroxychloroquine. Her lupus course was marked by flare manifesting as pericardial and pleural effusion treated with pulsed IV Methylprednisolone 100 mg daily for 3 days and transitioned to prednisone 20 mg. Before prednisone could be tapered, lupus nephritis developed with plans to start cyclophosphamide during which latent TB was diagnosed and she was started on isoniazid (INH) and rifampin (RFP). Labs on presentation showed leukopenia, thrombocytopenia, mild transaminitis and elevated inflammatory markers with mild atelectasis in bilateral lower lobes on a chest x-ray. Her symptoms were thought to be due to COVID-19 infection and she was sent home to self-quarantine while awaiting SARS-CoV-2 PCR test result. She returned two days later with abdominal pain, nausea, vomiting, diarrhea, and fevers. Vital signs revealed a temperature of 101 F, BP 110/82, HR 122, RR 24 and SpO2 100% on room air. Labs on the day of admission showed persistent leukopenia, thrombocytopenia, rising inflammatory markers and worsening transaminitis. Details of lab results from her initial ED visit and on the day of admission are shown in Table 1. In addition, CT chest, abdomen and pelvis was notable for bulky adenopathy in bilateral axilla, iliac, and inguinal regions.
The initial plan of treatment included broad spectrum antibiotics due to concern for an infection, discontinuation of rifampin and INH due to elevated transaminases and continuation of her home dose of prednisone and HCQ.
Given the presence of lymphadenopathy, abnormal laboratory results and her clinical presentation, extensive workup was performed for a broad differential diagnoses including infections, TB lymphadenitis, SLE flare and hemophagocytic lymphohistiocytosis (HLH). Blood cultures were negative for bacterial, fungal, and TB infections. ANA titers were elevated at 1:1280 with decreased C3 37 mg/dL (76-100 mg/dL), pointing to an autoimmune case. Tests for HLH revealed mildly elevated sIL-2R at 2137 pg/mL (532-1891 pg/mL) and low NK cell activity at 48 cells/uL (70-760 cells/uL). A lymph node biopsy was done which revealed necrotizing lymphadenitis without evidence of lymphoproliferative disorders or infections (Fig. 1). These findings were concerning for Kikuchi-Fujimoto disease (KFD) or lupus lymphadenitis. A bone marrow biopsy showed normocellular marrow without evidence of hemophagocytosis, favoring reactive changes from infection or autoimmune disease. With these findings, HLH and infection were thought less likely but rather lymphadenitis from a lupus flare or KFD. The patient's symptoms improved on her home dose of prednisone and HCQ after discontinuation of RFP and INH, suggesting that the most likely cause of her presentation was an SLE flare due to drug-drug interactions.
She was discharged in stable condition on her home medications except for INH and RFP. On rheumatology follow-up, she was started on immunosuppressive medicines. This allowed subsequent resumption of a course of isoniazid and rifampin and successful completion of treatment of latent TB.