Introduction
Exophiala (E.), a genus of saprotrophic black fungi, is widely found in the environment, growing on soil, wood, and decaying organic matter.1 Species associated with human diseases include E. jeanselmei, E. dermatitidis, and E. spinifera.2 It is commonly involved in cutaneous infections in immunocompromised hosts and seldom manifests as pneumonia.3 Since Barenfanger et al.4 documented the first case in 1989, only a few case reports of isolated pulmonary infections have been identified.5 To the best of our knowledge, we report the first case of pneumonia caused by E. jeanselmei from Pakistan. This case demonstrates that although the fungus is usually associated with cutaneous infections, it can also result in disseminated infections and severe pulmonary disease. Moreover, increased immunosuppression due to organ transplantation, malignancies, and corticosteroid therapy may be contributing to the rising prevalence of these infections. The identification of Exophiala requires a high degree of suspicion due to its rarity, and clinicians must consider Exophiala in the differential diagnoses for pneumonia in immunocompromised patients to avoid delays in treatment.
Case presentation
A 56-year-old female, a known case of type 2 diabetes mellitus and interstitial lung disease characterized clinically as idiopathic pulmonary fibrosis for 12 and eight years, respectively, presented with a two-week history of malaise and a cough productive of black sputum. She had been receiving intermittent corticosteroid therapy for interstitial lung disease over the past five years, comprising of prednisolone in doses ranging from more than 500 mg per day intravenously during acute exacerbations to a chronic oral dose of approximately 5 mg per day. In the present admission, following a five-day course of corticosteroids, she experienced significant fatigue and her condition deteriorated. She was admitted to the ward for subsequent workup and management. Upon admission, there was no rash or adenopathy. Her heart rate was 102 beats per minute, oxygen saturation was 95%, and auscultation revealed fine crackles in the bilateral posterior middle and lower lung fields. A complete blood count showed a white cell count of 9.7 × 109/L (4.2–10.2 × 109/L). Chest radiograph showed features of usual interstitial pneumonia with patchy and dense reticular opacities in the middle and lower lung lobes bilaterally. Empirically, oral levofloxacin and intravenous piperacillin/tazobactam were initiated. Bronchoalveolar lavage was sent to the microbiology laboratory for culture and sensitivity testing.
Gram stain revealed numerous pus cells, primarily neutrophils, and occasional septate hyphae, which were confirmed by potassium hydroxide staining. The results were communicated to the physician, and intravenous voriconazole was initiated, while levofloxacin and piperacillin/tazobactam were discontinued. After four days of incubation of culture plates at 25°C and 37°C, colonies of mold were observed on Sabouraud dextrose agar and potato dextrose agar plates, which matured after 10 days of incubation.
Gross morphology revealed brownish-black colonies with a suede-like texture (Fig. 1). Lactophenol Cotton Blue staining revealed septate hyphae with numerous conidiogenous cells that were slender, tubular, occasionally branched, and characteristically tapered to a narrow, elongated tip. The oval conidia were grouped at the tips, sides, and ends of the conidiophores, and at places along the hyphae (Fig. 2). The gross morphological and microscopic features of the isolate were consistent with Exophiala jeanselmei. The final report was communicated to the clinician. The patient improved clinically after one week of treatment and was discharged on oral voriconazole with advice for outpatient follow-up. Further clinical improvement was noted on follow-up outpatient visits, as evidenced by improvement in symptoms of cough and fatigue, and resolution of bilateral lung consolidations on chest radiograph. Oral voriconazole therapy was continued for three months after discharge, at which point it was stopped when the patient's symptoms had completely resolved.
Discussion
Exophiala species are rarely pathogenic in immunocompetent hosts; however, the frequency of infections is rising in immunocompromised patients.6 They are commonly implicated in skin infections and are rarely involved in pulmonary, sinus, and disseminated infections.7Exophiala pneumonia is a rare manifestation typically associated with immunocompromised states or underlying cystic fibrosis. There is ample evidence that Exophiala species colonize up to 19% of patients with cystic fibrosis; however, reports of pneumonia in this population are comparatively rare.6,8,9 Our patient was secondarily immunocompromised due to diabetes mellitus and corticosteroid therapy for the management of interstitial lung disease. Although there was no history or evidence of cystic fibrosis, she had interstitial lung disease with intermittent acute exacerbations, which contributed to the development of invasive infection.
A standardized treatment plan has not been established due to the rarity of pneumonia caused by Exophiala species. Antifungals such as amphotericin B, ketoconazole, itraconazole, flucytosine, and voriconazole have been used to treat pulmonary Exophiala infections; however, the efficacy of any antifungal has not been definitively proven, and appropriate treatment needs to be established.9–11 Though most studies suggest a duration of three to seven months, there is no consensus regarding the ideal length of therapy.9–11
Voriconazole is a well-tolerated triazole antifungal drug that has been shown to be effective against various fungal infections, including candidemia, esophageal candidiasis, and invasive aspergillosis. It is often used as a last-resort drug when no improvement is observed with other antifungals.12 Our patient showed a successful response to voriconazole therapy over the course of three months, which demonstrates that it might be a valuable option in treating pulmonary infections caused by Exophiala jeanselmei. Fungal infections are a major source of morbidity and mortality in immunocompromised individuals and should be treated with a high level of suspicion. Hence, it is crucial to request fungal cultures along with bacterial cultures whenever an infection is suspected, as invasive fungal infections are more likely to occur in immunocompromised individuals, including transplant recipients, those on immunosuppressive or chemotherapeutic agents, those living with HIV, premature infants, and the elderly.13 Moreover, fungal cultures improve the yield of fungi from clinical samples by employing specialized fungal media, media with added antibiotics to reduce bacterial overgrowth, and prolonged incubation time.14
Conclusions
Bronchoalveolar lavage with an elevated neutrophil count and abnormal pulmonary imaging should be considered characteristic of both bacterial and fungal pneumonia. Cultures must be sent not only for bacterial workup but also for fungal culture, as it employs special techniques and prolonged incubation for the isolation of fungi. Good microbiological acumen and enhanced communication between the lab and clinical teams facilitate appropriate diagnosis and early initiation of therapy.
Declarations
Ethical statement
The study was performed following the ethical standards of the institutions to which we are affiliated and in accordance with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report.
Data sharing statement
As a case report, all data generated or analyzed are included in this article.
Funding
The authors did not receive any funding for this work.
Conflict of interest
The authors declare no conflicts of interest.
Authors’ contributions
Data curation, visualization, writing – original draft (MK), investigation (MK, KS), supervision, resources (NK, FA), and writing – review & editing (NK, FA, KS). All authors have approved the final version and publication of the manuscript.