A 51 year old woman presented with a one month history of progressive right sided neck swelling, throat and ear pain, and dysphagia. This was accompanied by worsening of a chronic cough, intermittent fevers and weight loss. Over these weeks, the patient received empiric courses of clindamycin, amoxicillin, penicillin VK, prednisone and acyclovir for presumed tonsillar cellulitis that were ineffective.
She had a history of Crohn's Disease diagnosed 6 years prior to presentation, for which she was receiving 6-mercaptopurine and infliximab for the past 3 years. She had been diagnosed with sarcoidosis based on cervical lymph node histology with sclerotic granulomas; lung nodules with mediastinal adenopathy; hypercalciuria and vitamin D dysregulation. She was a native of Germany, residing in upstate New York for the past 13 years. Her only travel outside New York was to Europe. Remote screening for latent tuberculosis had been negative. She was a current smoker and averaged about one pack per day for 34 years.
On physical examination, she was afebrile. Her right neck was tender to touch without a palpable mass. There was no cervical or supraclavicular adenopathy. Examination of the oropharynx revealed an enlarged necrotic right tonsil without odor. No lesions of the tongue, buccal mucosa or palate were identified. Chest auscultation was normal. There was no abdominal hepatosplenomegaly.
Complete blood count showed white blood cell count 4100/muL, hemoglobin 13.5 gm/dL and platelet count 167,000/muL. Computed tomography (CT) of the thorax showed bilateral diffuse micronodules. CT scan of the neck (Fig. 1) showed an enlarged right tonsil with asymmetric thickening of the aryepiglottic fold, the right side of the epiglottis, right tonsillar pillar, and right lingual tonsil.
Infliximab was discontinued with her most recent dose being three weeks prior to presentation. One week later, bronchoalveolar lavage (BAL) and transbronchial biopsy were performed, but histology and microbiology were non-diagnostic. BAL cytology and flow cytometry did not suggest lymphoma or malignancy. Tonsillar biopsy (Fig. 2A) demonstrated granulomas and multinucleated giant cells with suppurative inflammation. Diastase-resistant periodic acid Schiff (DPAS) stain showed intracytoplasmic yeast forms, consistent with histoplasmosis (Fig. 2B). Two weeks after the biopsy, the urine Histoplasma antigen was negative. Serum Histoplasma antibody quantitative immunodiffusion analysis was obtained an additional two weeks later, and was positive for M antigen with a titer of 1:128, but was negative for H antigen. The formalin fixed tonsillar biopsy tissue was sent to the Mycology Laboratory, Wadsworth Center, Albany, NY, which was confirmed to contain H. capsulatum DNA with a cycle threshold (Ct) of 35.5 (positive <40) by real-time polymerase chain reaction (rt-PCR) assay.
Itraconazole was administered at a dose of 200mg three times daily for three days and continued at 200mg twice daily. Within two weeks of starting therapy, her throat pain and cough greatly improved. Within one month of therapy, her tonsil had healed, and follow up CT of the chest at 3 months was normal.