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Disseminated Histoplasmosis Presenting with Intestinal Ulcers and Adrenal Insufficiency

      To the Editor:
      50-year-old white man from Arkansas who was referred to the endocrinology clinic for bilateral adrenal masses. The adrenal masses were noted on a computed tomography scan of the abdomen that was performed for evaluation of weight loss. The patient reported fatigue, decreased appetite, and weight loss of approximately 26 pounds in the last 7 years. The biochemical evaluation was negative for functional adenoma. The patient had an inappropriate cortisol response to an adrenocorticotropic hormone stimulation test with a baseline adrenocorticotropic hormone level of 17.5 pg/mL, cortisol level of 13.1 μg/dL, and 30- and 60-minute values of 16 and 16.9 μg/dL, respectively. Hydrocortisone replacement therapy was started, and an adrenal biopsy was planned.
      The patient reported worsening systemic symptoms along with painful oral lesions and diarrhea. The patient was admitted to the hospital. On admission, vital signs were normal. Physical examination revealed a cachectic male with diffuse oral thrush and a 1-cm ulcer in the dorsal part of the center of the tongue. Diffuse nontender anterior cervical lymphadenopathy was noted. Complete blood count and liver function test results were normal, and a human immunodeficiency virus and urine histoplasma antigen were negative. A repeat adrenocorticotropic hormone stimulation test was performed during admission after holding a morning dose of hydrocortisone. Baseline adrenocorticotropic hormone was 154.9 pg/mL, and baseline, 30-minute, and 60-minute cortisol levels were 8.7, 8.2, and 7.4 μg/dL, respectively. Colonoscopy was performed for evaluation of diarrhea and showed ulcerative lesions in the cecum and transverse colon. Biopsies from the colon and tongue were reported positive for intracellular fungal forms stained in the Gomori methenamine silver stain and Papanicolaou slides, consistent with Histoplasma capsulatum, and a positive fungal blood culture confirmed the diagnosis. Liposomal amphotericin B was administered to the patient, and constitutional symptoms markedly improved in the next few days. The patient was discharged from the hospital with oral itraconazole.

      Discussion

      Disseminated histoplasmosis is the most fatal presentation of histoplasmosis, with a mortality rate up to 80% without treatment.
      • Sarosi G.A.
      • Voth D.W.
      • Dahl B.A.
      • Doto I.L.
      • Tosh F.E.
      Disseminated histoplasmosis: results of long-term follow-up. A center for disease control cooperative mycoses study.
      Although most patients with histoplasmosis remain asymptomatic, a small proportion (<0.1%) may develop disseminated disease, particularly those with impaired T-cell immunity.
      • Goodwin Jr., R.A.
      • Shapiro J.L.
      • Thurman G.H.
      • Thurman S.S.
      • Des Prez R.M.
      Disseminated histoplasmosis: clinical and pathologic correlations.
      Of note, up to 40% of patients presenting with disseminated histoplasmosis do not have obvious risk factors.
      • Assi M.A.
      • Sandid M.S.
      • Baddour L.M.
      • Roberts G.D.
      • Walker R.C.
      Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients.
      Disseminated histoplasmosis may affect a number of organ systems, including the central nervous system, liver, spleen, adrenal glands, skin, and gastrointestinal tract.
      • Assi M.A.
      • Sandid M.S.
      • Baddour L.M.
      • Roberts G.D.
      • Walker R.C.
      Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients.
      More than one half of patients with disseminated histoplasmosis have adrenal involvement of the infection. Although clinically evident adrenal insufficiency seems to be less common, the most common cause of death in patients with disseminated histoplasmosis is acute adrenal crisis.
      • Sarosi G.A.
      • Voth D.W.
      • Dahl B.A.
      • Doto I.L.
      • Tosh F.E.
      Disseminated histoplasmosis: results of long-term follow-up. A center for disease control cooperative mycoses study.
      Involvement of the gastrointestinal tract by disseminated histoplasmosis seems to be common on autopsy.
      • Goodwin Jr., R.A.
      • Shapiro J.L.
      • Thurman G.H.
      • Thurman S.S.
      • Des Prez R.M.
      Disseminated histoplasmosis: clinical and pathologic correlations.
      However, clinically meaningful presentations are less than 10%.
      • Kahi C.J.
      • Wheat L.J.
      • Allen S.D.
      • Sarosi G.A.
      Gastrointestinal histoplasmosis.
      Intestinal lesions may present as ulcers or masses, causing abdominal pain, diarrhea, hematochezia, or bowel obstruction, mimicking the presentation of malignancies or inflammatory bowel diseases.
      • Kahi C.J.
      • Wheat L.J.
      • Allen S.D.
      • Sarosi G.A.
      Gastrointestinal histoplasmosis.
      Oral ulcers are particularly common.
      • Goodwin Jr., R.A.
      • Shapiro J.L.
      • Thurman G.H.
      • Thurman S.S.
      • Des Prez R.M.
      Disseminated histoplasmosis: clinical and pathologic correlations.
      The treatment strategy depends on the severity of the initial presentation. If the patient appears severely ill, liposomal amphotericin B is administered. Once a clinical response is observed or the patient is moderately ill, liposomal amphotericin B can be replaced by a prolonged course of itraconazole treatment.

      Conclusions

      This demonstrates a case of disseminated histoplasmosis in an otherwise healthy immunocompetent host. Therefore, a high index of suspicion is required to make a prompt diagnosis and provide appropriate treatment.

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