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.