Case Report
A 65-year-old female presented with left sided tongue necrosis (Figure 1). She had a past medical history significant for SLE on mycophenolate mofetil (MMF) 1000 mg twice daily and prednisone 5 mg daily, Factor V Leiden, and atrial fibrillation. The patient initially developed pain and numbness on the left side of her tongue which worsened over the course of several weeks and prompted her to see her primary care doctor. She was started on amoxicillin-clavulanate without improvement of her symptoms. A Computed Tomography (CT) scan was performed and revealed acute inflammatory phlegmonous changes of the left tongue without any abscess or fluid collection as well as left anterior lateral facial soft tissue and left submandibular space inflammation.
Physical exam of the oral cavity revealed a left sided area of tongue necrosis that extended medially and did not cross midline (Figure 1). There was also a fissure in the mouth posteriorly as well as erythema of the lateral lower lip. No thrush was noted.
Vasculitides including GCA, polyarteritis nodosa, ANCA-associated vasculitis and cryoglobulinemic vasculitis were considered as possible etiologies. PET-CT scan was obtained and did not show any evident signs of vessel inflammation. ANCA titers and cryoglobulin levels were also within normal limits. Laboratory examination revealed a soluble interleukin 2 receptor (sIL2r) 11,141 U/mL, ferritin 42,975 ng/mL, C-Reactive Protein (CRP) 19.5 mg/dL, fibrinogen <50 mg/dL.
Infectious work up was performed with bronchoalveolar lavage (BAL) confirming disseminated histoplasmosis. Histoplasma urine and blood antigens were positive at >25.0 ng/mL (N undetectable) and >20.0 ng/mL (N undetectable) respectively. Blood cultures were obtained and revealed fungemia with speciation showing histoplasma. Tongue and lip biopsies revealed necrotic tissue with neutrophilic inflammation and fungal organisms. Bone marrow biopsy was obtained and revealed hemophagocytosis and histoplasmosis.
Malignancy was also considered given the location of necrosis as well as severe leukocytopenia and thrombocytopenia, but flow cytometry and superficial tongue biopsies did not reveal evidence of malignancy. The patient’s medical history of Factor V Leiden and atrial fibrillation did raise concern for a thromboembolic event. COVID antibodies were also obtained with the spike antibody present, indicating vaccination, and the nucleocapsid antibody negative, indicating that she had not had a recent infection that could have resulted in a hypercoagulable state.
The patient was started on liposomal amphotericin for antibiotic coverage but continued to have fevers and rising levels of CRP and transaminases raising concern for cytokine storm given her underlying autoimmune disease and active systemic fungal infection. The patient was also noted to have low fibrinogen and dramatically rising ferritin in addition to her cytopenias. Serum soluble interleukin 2 receptor (sIL2r) was also markedly elevated. Flow cytometry of peripheral blood showed increased CD38++/HLA-DR/CD8+ which was highly suggestive of hemophagocytic lymphohistiocytosis (HLH). Bone marrow biopsy confirmed both hemophagocytosis and histoplasmosis. Laboratory markers and clinical picture initially did improve with the initiation of steroids, IVIG and Anakinra along with concurrent treatment of histoplasmosis. However, following stabilization for 2-3 days, she developed septic shock and passed away.