Histoplasmosis-a great invader, even in immunocompetent patient

Abstract

Disseminated histoplasmosis (DH) is a rare deep fungal infection caused by Histoplasma capsulatum and it usually occurs in immunocompromised patients like in acquired immunodeficiency syndrome (AIDS) or patients getting any immunosuppressive therapy. Histoplasmosis usually remains unrecognized in immunocompetent individuals. Here we are reporting a case of a 55-year-old immunocompetent man with DH who presented to us with dysphagia, occasional vomiting, slurred speech with left sided hemipaeresis, weight loss and after hospital admission he developed fever, but no cough. On investigations, he was found to have bilateral adrenal mass, rim enhancing lesion in the brain, nodular lesions in duodenum and soft tissue mass in lung. DH was confirmed by the presence of Histoplasma capsulatum in the cytopathology of adrenal mass and histopathology of tissue from duodenum which revealed PAS positive yeasts. He was treated with itraconazole rather than recommended choice of liposomal amphotericin B as he could not afford this expensive drug. After getting itraconazole on subsequent follow up at 4 months, he was found to be clinically improving, gained weight about 10 kg with disappearance of other symptoms. DH may present with atypical symptoms like dysphagia, slurred speech with hemiparesis rather than common presentation with fever, cough or weight loss. Though DH is more common in immunocompromised patients, if multisystem involvement occurs in immunocompetent patients, we should always consider deep fungal infection as one of the differentials.

Introduction

Histoplasmosis, a deep fungal infection which is caused by a dimorphic fungus named Histoplasma capsulatum [1,2,5]. It spreads to humans by inhalation of microconidia and mycelial fragments of this organism. Usually, the immunocompromised patients such as HIV affected patients or patients receiving immunosuppressive agents are more vulnerable to this fungal infection [2,6]. The morbidity and mortality are also higher among these individuals [3].

Though Histoplasmosis is a widespread fungal disease, it usually remains asymptomatic in immunocompetent persons [4]. But it can also produce various types of symptoms in immunocompetent patients which depends on the involvement of the organ by the fungus. Histoplasmosis can be classified into acute pulmonary histoplasmosis, disseminated histoplasmosis and chronic pulmonary histoplasmosis [1]. We are presenting a case of Disseminated Histoplasmosis (DH) involving duodenum, brain, lungs and adrenal glands in an immunocompetent patient.

Case summary

A 55-year-old male businessman with no known history of hypertension, diabetes, or HIV presented with progressive dysphagia affecting both solids and liquids, accompanied by intermittent vomiting. Initial upper gastrointestinal endoscopy showed no abnormalities, and he was prescribed proton pump inhibitors (PPIs) and prokinetic agents, though these interventions yielded no improvement in symptoms.

Approximately two months after initial presentation, the patient developed acute neurological symptoms, including dysarthria, right-sided facial deviation, and left-sided hemiparesis. He was evaluated by a neurologist and was diagnosed with cerebrovascular disease with left-sided hemiparesis. Due to financial constraints, imaging was deferred, and he was managed conservatively with physiotherapy, achieving partial improvement in motor function.

Three months from symptom onset, the patient reported ongoing dysphagia, anorexia, episodic vomiting, and persistent left-sided weakness, resulting in significant weight loss of approximately 10 kg. Following admission to the hospital for re-evaluation, he exhibited a low-grade, intermittent fever with an evening rise in temperature but denied chills, rigors, or night sweats. He reported no contact with individuals with smear-positive tuberculosis.

Physical examination revealed mild anemia and a febrile state (101°F), while other vital parameters were within normal limits. Systemic examination of the gastrointestinal, cardiovascular, and respiratory systems was unremarkable. Neurological examination indicated left-sided hemiparesis with exaggerated deep tendon reflexes and a positive Babinski sign.

Routine laboratory investigations, including complete blood count, liver function tests, renal function tests, serum glucose, and electrolytes, were within reference ranges. HIV serology was negative. Cranial CT scan demonstrated a ring-enhancing space-occupying lesion in the right capsuloganglionic region. Repeat upper GI endoscopy revealed approximately ten ulcerated nodular lesions of varying sizes in the second portion of the duodenum. Histopathologic analysis of duodenal biopsies revealed PAS-positive, encapsulated, uniform oval yeasts with eccentric nuclei within and outside histiocytes, consistent with Histoplasma capsulatum. High-resolution computed tomography (HRCT) of the chest displayed a right hilar mass with associated right hilar lymphadenopathy and multiple micro-nodules within the right lung. Abdominal CT demonstrated bilateral adrenal gland enlargement (right: 56.2 × 42.8 mm; left: 50.4 × 36.8 mm) with heterogeneous enhancement (Fig. 1, Fig. 2). FNAC from the adrenal glands revealed necrotic material with abundant histiocytes and sparse polymorphonuclear leukocytes containing numerous Histoplasma capsulati. An ACTH stimulation test confirmed partial adrenal insufficiency. Tuberculosis was excluded via Mantoux and Gene Xpert tests.

Fig. 1.

(A) Involvement of adrenal glands with heterogenous contrast enhancement. (B) CT scan of chest showing soft tissue density mass lesion. (C) CT scan of head showing ring enhancing lesion with perilesional oedema at right capsuloganglionic region.

Fig. 2.

(A) Endoscopy of Upper GIT showing multiple nodular lesions in the duodenum. (B) PAS staining shows lamina propria is densely infiltrated with acute and chronic inflammatory cells. Collection of capsulated small uniform oval, budding yeasts with eccentric nuclei clusters within and outside histiocytes.

A diagnosis of disseminated histoplasmosis involving the duodenum, adrenal glands, central nervous system, and lungs, with secondary partial adrenal insufficiency, was established. Treatment with Itraconazole was initiated at 200 mg three times daily for three days, followed by twice daily for 12 months, alongside Hydrocortisone 15 mg daily for adrenal insufficiency. The patient's condition gradually improved over the following months, with an 8 kg weight gain, resolution of systemic symptoms, and recovery from neurological deficits. During follow-up, the patient developed new-onset hypertension, which was successfully managed with antihypertensive therapy.

Discussion

This case report sheds light on the diagnostic and management complexities of disseminated histoplasmosis (DH), particularly in an endemic setting like Bangladesh, where it often goes unrecognized [7]. Histoplasmosis arises from Histoplasma capsulatum, a fungus found in soil contaminated by bird and bat excreta. Inhalation of microconidia or direct invasion leads to infection, with immunocompromised individuals most at risk. While DH is relatively rare in immunocompetent hosts, it may present as a self-limiting flu-like illness in up to 90% of such cases. [8]. However, about 10% of these individuals may experience dissemination, which can complicate diagnosis and treatment, especially in regions with high tuberculosis prevalence due to the overlapping clinical and histopathological features [7,8].

A distinctive aspect of this case is the unusual involvement of the upper gastrointestinal (GI) tract, specifically the duodenum, in an immunocompetent patient. GI involvement in histoplasmosis is typically seen in the ileum and colon, with duodenal involvement observed in fewer than 4% of cases, even in immunocompromised patients such as those with AIDS [9]. This rarity underscores the atypical nature of our case, where the patient exhibited upper GI symptoms despite an intact immune system. Approximately 10% of DH cases may show GI symptoms, yet the duodenum as a primary site is unusual, making this case clinically significant [10].

The respiratory system is often the first point of infection in DH, with hematogenous dissemination following initial pulmonary involvement [10]. Interestingly, our patient did not display respiratory symptoms, although a CT scan later revealed lung involvement, indicating asymptomatic dissemination. This finding emphasizes the importance of imaging for early detection of DH in patients with systemic symptoms, as this can allow for prompt intervention and prevent further complications.

Central nervous system (CNS) involvement occurs in roughly 5%-10% of DH cases, often presenting as headache, confusion, or focal deficits [11]. In rare instances, patients may exhibit stroke-like symptoms. In our case, the patient presented with left-sided hemiparesis, and imaging revealed a space-occupying lesion in the right capsuloganglionic region. This underscores the potential severity and varied presentations of DH, which may impact critical organ systems.

Adrenal involvement is more common in immunocompetent DH patients, with or without hypoadrenalism [12]. These patients may experience adrenal insufficiency, leading to symptoms such as fatigue, weight loss, nausea, and postural dizziness [13,14]. Although our patient lacked typical signs of adrenal insufficiency, imaging revealed bilateral adrenal masses, and fine needle aspiration cytology (FNAC) confirmed Histoplasma capsulatum. A partial adrenal insufficiency was documented via a short synacthen test, emphasizing the need to assess adrenal function in DH cases with adrenal involvement.

Treatment for DH usually includes amphotericin B or liposomal amphotericin B, followed by itraconazole [[15], [16], [17]]. However, due to the high cost and nephrotoxicity of these treatments, itraconazole alone was administered in this case. This approach proved successful as in other cases, as the patient showed weight gain and symptom resolution during follow-up, without systemic upset or new focal signs [14].

This case illustrates the importance of a high index of suspicion for DH in patients with multi-organ involvement and constitutional symptoms, even among immunocompetent individuals. Clinicians should remain mindful of DH's acute and chronic forms and routinely assess adrenal function in DH cases with adrenal gland involvement. Treatment with itraconazole alone can be a viable and effective option in immunocompetent patients, offering a favorable outcome with fewer side effects.

Author contribution

Banik SK, Tania-Tofail wrote the article, revised the article for intellectual content, approved the final article. Tania-Tofail is involved in the concept, writing, review of draft and data acquisition. Arafat SM, Arefin MS reviewed the literature and were involved in the investigation. Arefin MS provided the images and descriptions. All authors contributed to the article.

Ethical approval

Patient information was anonymized to the full extent of our ability.

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