Coexisting phaeohyphomycosis and tubercular central nervous system infections in an immunocompetent child: A case report

Abstract

BACKGROUND

Diagnosing chronic meningitis is a clinical challenge. Infection with cerebral phaeohyphomycosis, caused by dematiaceous (melanized) fungi, is extremely rare but is a life-threatening cerebral abscess. It presents with non-specific signs and symptoms and carries a poor prognosis, regardless of the patient’s immune status. In endemic regions, it closely mimics common conditions such as tuberculous meningitis or intracranial tuberculomas, complicating timely diagnosis and management.

CASE SUMMARY

We present the case of 10-year-old immunocompetent child who was admitted with fever, headache, and meningeal signs. Initial neuroimaging revealed multiple ring-enhancing, conglomerated lesions with perilesional oedema in left temporo-parietal region. Cerebrospinal fluid analysis showed pleocytosis with lymphocytic predominance and highly raised protein levels. Based on clinical-radiological findings and the regional prevalence of tuberculosis (TB), child was initially diagnosed and treated as a case of central nervous system TB with standard anti-tubercular therapy (ATT) & adjunctive steroids. After 5-6 weeks, the patient was readmitted with worsening raised intracranial pressure. Repeat neuroimaging revealed an increase in abscess size along with oedema. Craniotomy with evacuation of the abscess was performed. Direct microscopy of aspirated pus showed pigmented, septate fungal hyphae consistent with phaeohyphomycosis. Histopathological examination also demonstrated features of coexisting tubercular pathology. Child was treated with combined antifungal therapy (liposomal amphotericin B) for 6 weeks and ATT, resulting in clinical and radiological improvement.

CONCLUSION

Case highlights the diagnostic dilemma posed by cerebral phaeohyphomycosis, particularly in regions endemic for TB. It emphasizes the need to consider alternative or dual infections in paediatric patients with poor response to standard treatments. Early suspicion, prompt surgical intervention, and targeted medical therapy are critical for improving outcomes.

Key Words: Cerebral phaeohyphomycosis; Central nervous system tuberculosis; Dematiaceous fungi; Chronic meningitis; Pediatric neuroinfection; Ring-enhancing lesions; Antifungal therapy; Case report

Core Tip: This report describes a rare dual central nervous system infection with phaeohyphomycosis and tuberculosis in an immunocompetent child. The case highlights diagnostic challenges, the importance of considering mixed infections even in healthy hosts, and the need for early combined antifungal and antitubercular therapy and surgical therapy to improve outcome.

INTRODUCTION

Tuberculosis (TB) is highly prevalent in India and commonly presents with intracranial tuberculomas or meningitis in children. The standard approach to such cases is empirical initiation of anti-tubercular therapy (ATT). However, non-responsiveness to ATT is a diagnostic red flag, raising suspicion for drug resistance or alternative aetiologies. Cerebral phaeohyphomycosis has been misdiagnosed as tuberculoma in several reports, leading to delays in correct treatment and high mortality.

We report a case of coexisting tubercular meningitis and cerebral phaeohyphomycosis in child without immunodeficiency, managed with combined medical and surgical therapy.

CASE PRESENTATION

Chief complaints

A case of 10-year-old immunocompetent child who was admitted with fever, headache, and meningeal signs. Intermittent low-grade fever for three months, headache for two months, and on & off vomiting for 2 months without any neurological deficit.

History of present illness

Intermittent low-grade fever for three months, almost on most days, evening rise. Headache for two months, bilateral temporal-parietal region, not associated with any diurnal variation, seizures. And on & off vomiting for 2 months, predominantly early morning.

History of past illness

No history significant past history. No previous history of tubercular infection, recurrent loose stools, recurrent pneumonia, ear discharge.

Personal and family history

Previously healthy child. No significant personal history. No family history of TB, and other significant illness.

Physical examination

General physical examination was normal. No lymphadenopathy noted. Central nervous system (CNS) examination was unremarkable except for positive neck rigidity, Kernig’s and Brudzinski’s sign.

Laboratory examinations

Initial evaluation during 3^rd week of illness revealed a normal haematological workup (haemoglobin = 13 g/dL, total leukocyte counts = 10800/mm³, with 35% polymorphs and 56% mononuclear & platelet count = 3.7 Lakhs/mm³). Cerebrospinal fluid (CSF) analysis showed 730 cells/mm³ (70% lymphocytes and 30% polymorphs), with a sugar 2.72 mmol/L and protein of 1.79 mmol/L.

CSF analysis during 3^rd month of illness revealed 100 cells/mm³ (80% lymphocytes), sugar = 36 mg/dL, and protein = 270 mg/dL. CSF gram’s stain, acid-fast bacilli smear true nucleic acid amplification test (Truenat) were negative. Culture of the CSF on mycobacterium growth indicator tube medium yielded no growth. Antibodies for human immunodeficiency virus (HIV) 1 & 2 was non-reactive. Immunoglobulin levels by quantitative assay were within normal limits for age. Antibodies for HIV 1 & 2 was non-reactive.

Imaging examinations

Non-contrast computed tomography (CT) scan of the brain during 3^rd week of illness demonstrated multiple ring-enhancing lesions along with surrounding oedema in the left temporo-parietal region, and magnetic resonance imaging (MRI) revealed ring-enhancing lesions in left temporal lobe (2 cm × 2 cm) and left caudate lobe (1.8 cm × 1 cm).

One month later, a repeat contrast-enhanced MRI of the brain demonstrated multiple nodular ring-enhancing lesions in the left temporal lobe measuring 3.4 cm × 2.8 cm (increased in size), with basal exudates and perilesional oedema (Figure 1). Magnetic resonance spectroscopy showed choline, lipid, and lactate peaks. Contrast-enhanced computed tomography brain during 3^rd month of illness demonstrated multiple conglomerate ring-enhancing lesions in the left temporal lobe.

Figure 1 Serial neuroimaging of the child. A: Non contrast-computed tomography (CT) head during 3^rd week of illness showing multiple ring-enhancing lesions with surrounding oedema in the left temporo-parietal region; B: Magnetic resonance imaging (MRI) brain at 3^rd week of illness showing ring-enhancing lesions in the left temporal lobe (2 cm × 2 cm) and left caudate lobe (1.8 cm × 1 cm); C: MRI brain during 9^th week of illness showing nodular ring-enhancing lesions in the left temporal lobe measuring 34 cm × 2.8 cm (increased in size), with basal exudates and perilesional oedema; D: Magnetic resonance spectroscopy during 9^th week of illness showed choline, lipid, and lactate peak; E: Non contrast CT head multiple during 3^rd month of illness showing conglomerate ring-enhancing lesions in the left temporal lobe; F: Non contrast CT head at same time showing left temporal lobe abscess.

FINAL DIAGNOSIS

Coexisting phaeohyphomycosis and tubercular central nervous system infections in an immunocompetent child.

TREATMENT

ATT initially taken for around 6 weeks (isoniazid, rifampicin, pyrazinamide, ethambutol) along with corticosteroids (prednisolone at 2 mg/kg/day in 2 divided doses), which was continued at admission at our unit. Left temporo-parietal craniotomy on Day 6 of hospitalisation, with excision of the lesion. Injection liposomal amphotericin B (5 mg/kg/day) for total six weeks.

OUTCOME AND FOLLOW-UP

Complete resolution of symptom safter 6 weeks of therapy, and repeat MRI of the brain showed radiological improvement.

DISCUSSION

Phaeohyphomycosis represents infections caused by dematiaceous fungi possessing melanin-rich cell walls. These are opportunistic fungi and can cause brain abscesses and chronic meningitis even in immunocompetent hosts. It can cause intracranial space occupying lesion mimicking tuberculoma or tumor[1]. Both immunocompetent and immunocompromised individuals can be affected, however, a marginally higher prevalence has been noted among immunocompetent individuals, with a predominance in males[2]. This organism is a ubiquitous soil saprophyte, and infection occurs through inhalation of airborne conidia, with subsequent hematogenous spread to the brain and other organs[3]. Extension from the paranasal sinuses or dissemination from a subcutaneous site after traumatic inoculation has also been seen. The presence of melanin in the hyphal wall protects against oxidative damage and promotes central nervous system invasion. It manifests clinically as chronic fever, vomiting, headache, seizures, hemiparesis, altered mental status, dysarthria, and vision disturbances[2], where in our case, child only had symptoms of chronic meningitis without any other features or focal deficits.

Diagnostic delays are common due to rarity of the disease, clinical and radiological similarities with tuberculoma. As occurred in our case, child continued to have symptoms despite adequate doses and good compliance to standard first line anti-tubercular drugs with oral steroids. Chakrabarti et al[4], in a retrospective analysis of 124 cases, reported a delayed diagnosis with a mean duration of 115 days from the onset of symptoms.

Diagnosing cerebral phaeohyphomycosis by laboratory means is difficult due to lack of serological tests or biomarkers. Hence, definitive diagnosis is based on the identification of pigmented fungal hyphae on microscopy and/or culture isolation of the organism. The use of fungal polymerase chain reaction with universal fungal primers allows rapid detection of fungal infections directly from clinical specimens, with a reported sensitivity of 90% and specificity of 100%[5].

There have been no definitive guidelines for the management of phaeohyphomycosis until 2020. Recently (in February 2021), European Confederation of Medical Mycology and International Society for Human and Animal Mycology and the American Society for Microbiology provided recommendations for diagnosis and treatment of these rare infections[6]. Complete excision of abscess by surgical means along with antifungal therapy is the treatment of choice. Additional care should be taken to avoid the seeding of CSF during surgical removal of the lesion and its contents. No drug has been found to be independently associated with improved survival. Monotherapy with liposomal amphotericin-B or in combination with a triazole and/or echinocandin or 5-flucytosine with voriconazole with are recommended as the first-line treatment[6]. Review conducted by Kantarcioglu et al[2] showed a survival rate of 40.8% in patients receiving Amphotericin-B monotherapy.

Mortality rate of cerebral phaeohyphomycosis abscess remains very high (65%-70%)[7,8] even with aggressive medical and surgical interventions. A significant proportion of deaths occur within the first six months of hospitalization, regardless of treatment[1,3], and are associated with delayed diagnosis, antifungal susceptibility of the fungus, and disease extent.

In current case, a fungal cause was not in the initial diagnostic consideration as the clinic-radiological features resembled tuberculoma, a leading cause of intracranial space-occupying lesions in India[9] (Figure 2). Moreover, CNS TB cannot be ruled out based on a negative CSF TrueNat because of its low sensitivity of the assay (50%-65%). Hence, possibility of CNS TB could not be completely ruled out.

Figure 2 Microscopy of abscess material and a post therapy repeat magnetic resonance imaging brain. A: Pigmented fungal hyphae on direct microscopy of aspirated pus (arrow); B: Necrotizing granulomatous inflammation with central necrosis with multinucleate giant cell (arrow); C: Follow up contrast-enhanced magnetic resonance imaging brain after 6 weeks of amphotericin B showing resolution of abscess.

CONCLUSION

It can be concluded that cerebral phaeohyphomycosis is a rare condition with a severe and often poor prognosis. Therefore, early diagnosis is crucial to enable prompt treatment and improve patient survival. Consequently, CP should be considered in the differential diagnosis of brain abscess.