Gastrointestinal histoplasmosis presenting as a small bowel obstruction in an immunocompetent patient

Abstract

The clinical presentation of gastrointestinal histoplasmosis (GIH) is often non-specific, mimicking several other gastrointestinal diseases, making diagnosis difficult. We present a case of GIH, causing bowel obstruction in an immunocompetent patient. A woman in her 80s presented with anorexia and a distended abdomen. A CT scan of the abdomen and pelvis (CTAP) showed ileal thickening. Endoscopy was performed and ileal biopsies were taken. A diagnosis of histoplasmosis was made by histopathology, and she began treatment with liposomal amphotericin and itraconazole. Despite presenting well at her routine follow-up appointments, she presented 4 months after diagnosis with worsening symptoms of anorexia and abdominal distention. CTAP showed the ileal stricture causing bowel obstruction. She underwent itraconazole and steroid treatment while having nasogastric tube decompression. Subsequent gastrografin follow through showing partial obstruction and surgical resection was planned. Unfortunately, her condition deteriorated, her kidney function worsened and she suffered from aspiration pneumonia with eventual demise.

Background

Prompt diagnosis of gastrointestinal histoplasmosis (GIH) is important as mortality is high if left untreated.^{1 2} Although GIH is commonly reported in patients who are immunocompromised, particularly patients living with HIV,^3–8 it can also occur in patients without underlying HIV infection⁸ and in the immunocompetent.^{8 9} A low index of suspicion by the attending clinician or delayed diagnosis can lead to complications and fatal outcomes.^{1 8} Our case affirms the need to consider GIH in an immunocompetent patient presenting with features of gastrointestinal disease.

Case presentation

A woman in her 80s initially presented with a 2-month history of postprandial epigastric pain, nausea, anorexia and weight loss. Her comorbidities include hypertension, chronic kidney disease (baseline eGFR~46 mL/min/1.73 m²), fatty liver disease and vitamin D deficiency. She is immunocompetent with no history of HIV infection or diabetes and does not take any immunosuppressants. She has no history of alcohol intake, smoking or intravenous drug use. Her only risk factor for histoplasmosis disease was frequent travel to southeast Asia.

A CT scan of the abdomen and pelvis (CTAP) showed mid-segmental ileal thickening and fat stranding. An outpatient colonoscopy was performed which showed three patchy areas of ulceration in her terminal ileum. Biopsies revealed fungal microorganisms consistent with histoplasmosis (figure 1). Advice from the infectious diseases unit was sought and she was treated with 150 mg intravenous liposomal amphotericin (3 mg/kg) once daily for 14 days before progressing to 200 mg oral itraconazole two times per day, planned to be taken for 12 months.

Figure 1.

CT scan of the abdomen and pelvis showing stricture at the mid-ileum, circled.

While on amphotericin therapy, the patient’s kidney function and electrolytes were monitored. Her kidney function remained stable at her baseline of chronic kidney disease, maintaining a stable eGFR of around 46 mL/min/1.73 m², and she was not found to be hypokalaemic.

Three months later, she was reviewed at a routine infectious disease outpatient clinic. She had completed her liposomal amphotericin induction course and was taking itraconazole. She reported ongoing weight loss and constipation. On examination, her abdomen was not distended, soft on palpation with no tenderness. Her random serum itraconazole level was found to be subtherapeutic at 159 µg/L, and a random concentration of >1000 µg/L is required for itraconazole to be effective against histoplamosis.¹⁰ Antacids or proton pump inhibitors can reduce gastric acidity, which can reduce itraconazole absorption.¹¹ It is unclear what caused the subtherapeutic itraconazole levels in this patient, as she was not administered any of these medications regularly. Her dose of oral itraconazole was increased to 400 mg two times per day.

A month following her outpatient appointment, she presented to the emergency department with worsening anorexia and fatigue. She was not nauseated or vomiting and had no abdominal pain. She was passing stool and flatus. On examination, she appeared cachectic, lethargic and had severe abdominal distention. She had no areas of abdominal tenderness on palpation and did not have peritonitis.

Investigations

Blood tests on admission showed the patient was malnourished with a serum albumin concentration of 17 g/L (normal range 35–50 g/L) and her kidney function was at her baseline, with an eGFR at 46 mL/min/1.73 m² (normal range <59 mL/min/1.73 m²). The patient had stable haemoglobin during her admission and her white cell count was within the reference interval at 5.3×10⁹ /L (normal range 4.0–11.0×10⁹/L), with all subgroups of differentiated white cells within reference limits (table 1). Her C reactive protein was elevated on admission at 58 mg/L (normal reference range 0–10 mg/L), suggestive of inflammation. HIV antibodies and antigens were not detected in her bloodwork.

Table 1.

White cell differentiation

Differentiated white cell type	Result (x109 /L)	Normal range
Neutrophils	3.5	2.0–8.0
Lymphocytes	1.3	1.0–4.0
Monocytes	0.5	0.0–1.0
Eosinophils	0.0	0.0–0.5
Basophils	0.1	0.0–0.2

A repeat CTAP showed a stricture at the mid-ileum causing subacute small bowel obstruction (SBO) (figure 1).

Previous ileal biopsies stained with Alcian blue periodic acid-Schiff (AB/PAS) showed ovoid yeast cells suggestive of Histoplasma capsulatum (figure 2).

Figure 2.

Alcian blue periodic acid-Schiff staining of ileal tissue taken at colonoscopy, fungal elements shown by arrow.

Treatment

Given the infective nature of her stricture, she was continued on the increased dose of itraconazole and steroids while having nasogastric tube decompression. A subsequent gastrografin meal and follow through only showed partial resolution of this obstruction and therefore a surgical resection was planned. Dietician input was sought and parenteral nutrition was commenced to nutritionally optimise the patient prior to surgery due to her significant preoperative malnutrition. She was monitored for refeeding syndrome and her abdominal distension persisted.

Outcome and follow-up

While awaiting surgical treatment, her condition deteriorated. She developed refeeding syndrome, worsening renal impairment and aspiration pneumonia. Unfortunately, she died shortly after.

Discussion

Histoplasmosis is caused by inhalation of Histoplasma conidia and causes a self-limiting

respiratory illness often in the immunocompetent.^{3–7 12} In those who are immunocompromised (most commonly due to HIV infection), histoplasmosis infection can become disseminated, affecting extrapulmonary sites including the gastrointestinal tract.^{1 3–7} Untreated disseminated histoplasmosis has a significant mortality of approximately 80% but medical management can significantly reduce this to 30%.2 5 6 13 This case is unusual because GIH was diagnosed in an immunocompetent, HIV-negative patient.¹³

GIH is often difficult to diagnose as symptoms and signs are non-specific^{5–7 12} and can include weight loss, abdominal pain, fever, night sweats and rarely gastrointestinal bleeding.2 3 5 7 Strictures form in 6% of these patients and they mostly affect the small bowel, hence manifesting with SBO.2 4 5 9 12

Radiological findings include lesions which often exhibit a mass effect on adjacent structures³ and prominent lymphadenopathy.^{5 7} Consistent with our findings, endoscopic features were predominantly mucosal ulceration.2 5 7 12 Continuous or segmental pseudopolypoid and plaque-like lesions were also be seen in the terminal ileum and caecum,2–4 6–8 mimicking malignancy or inflammatory bowel disease.⁸ Histopathology would show caseated granulomas and Groccot-Gomori methenamine silver or AB/PAS staining techniques can be used to identify these fungal elements.^{2 5 6}

Targeted therapy to the gastrointestinal tract is limited and systemic treatment with antifungal medication is required. Amphotericin B is used for remission induction and azole therapy is used for maintenance.2 5 10 13 Conservative management of SBO prior to surgical intervention is possible in some situations but in those patients who fail conservative therapy, surgical intervention including balloon dilatation or bowel resection has been advocated.3–5 7 12

In conclusion, GIH also affects immunocompetent individuals with fatal outcomes especially following delayed diagnosis and/or treatment.⁸ Although medical management of stricturing lesions may improve symptoms, in most cases, surgical resection for SBO is necessary.⁹

Learning points.

• Histoplasmosis is a self-limiting condition caused by the inhalation of Histoplasma conidia.

• Histoplasmosis can become disseminated in some patients, involving multiple body systems.

• Gastrointestinal histoplasmosis is difficult to diagnose as radiological findings are non-specific and may appear as a mass effect with associated lymphadenopathy.

• Endoscopic findings include mucosal ulcerations that may resemble inflammatory bowel disease or malignancy, making diagnosis without biopsy difficult.

• Biopsy with Alcian blue periodic acid-Schiff staining can be used for histopathology diagnosis

Ethics statements

Patient consent for publication

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