Unsuspected Dematiaceous Fungal Infection Causing Subcutaneous Nodules in a Diabetic Patient

Lauren Fontana; Marcel E. Curlin

Unsuspected Dematiaceous Fungal Infection Causing Subcutaneous Nodules in a Diabetic Patient

Lauren Fontana¹, Marcel E. Curlin^2*

¹Division of Infectious Diseases, University of Minnesota, Minneapolis, MN, USA

²Department of Medicine, Division of Infectious Diseases, Oregon Health and Science University, Portland, USA

*Corresponding author: Marcel E. Curlin, Department of Medicine, Division of Infectious Diseases, Oregon Health and Science University, Portland, USA

Received Date: 29 September 2022

Accepted Date: 03 October 2022

Published Date: 05 October 2022

Citation: Fontana L, Curlin ME (2022) Unsuspected Dematiaceous Fungal Infection Causing Subcutaneous Nodules in a Diabetic Patient. Ann Case Report 7: 976. DOI: https://doi.org/10.29011/2574-7754.100976

Abstract

Melanised dematiaceous fungi are environmental saprophytes that can cause subcutaneous phaeohyphomyosis. We describe a case of coincident subcutaneous phaeohypomycosis due to Medicopsis romero and Cryptococcus neoformans meningitis in a Cambodian native female with uncontrolled diabetes mellitus and seropositive non-erosive rheumatoid arthritis receiving chronic steroids. Both organisms are dematiaceous environmental fungi but M. Romero infrequently causes invasive disease, occurring most commonly in the setting of immune suppression. We discuss the clinical significance, diagnosis and treatment of phaeohyphomycosis in an immunocompromised host.

Case Report

A 65 y/o Cambodian native female, who immigrated to the United States 30 years ago, presented with an 18-month history of persistent painless right knee swelling, and six days of acute fever and progressive confusion. Her medical history included poorly controlled type II diabetes mellitus, and seropositive rheumatoid arthritis (RA) diagnosed two years prior to admission. On initial rheumatologic evaluation, she was prescribed oral methotrexate 15mg weekly for 11 months and prednisone 10mg daily. The prednisone dose was increased to 20mg for ongoing generalized arthralgia one year later. However, ten months after starting therapy, she developed persistent painless right knee swelling, and eight months later experienced new spontaneous drainage from a nodular lesion overlying the patella. A home remedy of vinegarsoaked bread was applied but swelling and drainage persisted. Admission vital signs revealed a fever of 103oC, HR of 110 bpm, BP of 85/51 mmHg, and oxygen saturation of 88% on room air. Examination confirmed confusion without focal neurologic deficits. The right knee was swollen with multiple fluctuant prepatellar lesions (Figure 1, panel A) from which abundant cream-colored pus was expressed. The serum WBC count was 12 K/mm. Lumbar puncture opening pressure was 22 cm H2O. Cerebral spinal fluid (CSF) contained 32 WBC with 87% lymphocytes, protein and glucose values of 263mg/dL and 135mg/dL, respectively. CSF Cryptococcus antigen was positive (titer 1:320) and fungal culture grew Cryptococcus neoformans. Testing for HIV and tuberculosis was negative.

Manually expressed knee drainage revealed 3+ fungal spectated pseudo hyphae (Figure 1, panels D, E). Right knee MRI revealed multiple subcutaneous rim-enhancing prepatellar collections but no knee joint abnormalities (Figure 1, panels B, C). Pathology from a prepatellar bursectomy demonstrated an organizing abscess with surrounding fibrosis, and multinucleated histiocytic. No macroscopic granules were observed. Groote’s methoxamine silver stain showed darkly pigmented spores and hyphae within inflammatory zones (Figure 1, panel F). Mucicarmine stain was negative for Cryptococcus. Surgical culture revealed fungal hyphae and sequencing of 28S ribosomal DNA yielded a final diagnosis of Medicopsis romero. The patient’s hospital course was complicated by prolonged encephalopathy due to Cryptococcal meningitis requiring serial lumbar punctures. She received liposomal amphotericin and flu cytosine for 28 days, followed by consolidation therapy with voriconazole and was ultimately discharged in stable condition.

Discussion

Melanised dematiaceous fungi are environmental saprophytes characterized by their ability to produce melanin creating a dark pigmented appearance in tissue [1,2]. There are over 150 species of medically relevant dematiaceous fungi distributed across at least nine phylogenetic orders and 70 genera.1 The isolate reported here is closely related to other M. Romero strains from various geographic regions worldwide (Figure 1 panel G). Darkly pigmented dematiaceous fungi can cause eumycetomic (slowly growing painless cutaneous masses characterized by tumefaction, the presence of mycolic granules and development of sinus tracts), chromoblastomycosis (slowly progressive hypertrophic verrucous plaques which may ulcerate or spread, and contain sclerotic “Medlar bodies”) and phaeohyphomycosis involving superficial infection of skin structures presenting as an encapsulated mass or nodule commonly seen on the extremities, deep organ infection such as pulmonary and central nervous system infections, or disseminated infection [1-3]. Medicopsis romero (previously Pyrenochaeta romero) typically causes phaeohyphomycosis in warmer climates, affecting immunocompromised individuals including those with acquired immunodeficiency syndrome, hematologic malignancies, diabetes mellitus, transplant recipients, and patients requiring prolonged steroid use [4-9]. M. Romero infrequently causes disease in normal hosts [10]. Infection occurs after minor traumatic skin inoculation precipitating dermatologic phaeohyphomycosis. In tissue, organisms appear as yeast-like cells or pseudo hyphal elements [11]. With darkly-pigmented conidia, spores and hyphae [1,5]. Grossly, colonies appear velvety, greyish, and green [12]. Microscopic identification of M. Romero is challenging, and molecular methods including ribosomal gene sequencing and matrix-assisted laser desorption ionization time-offlight mass spectrometry are helpful in establishing the diagnosis [9,13,14]. Phaeohyphomycotic lesions are often cured by surgical excision alone, though antifungal therapy may be indicated in patients with extensive or refractory infections [5,6]. Limited antifungal susceptibility data suggest that M. Romero is relatively resistant to echinocandins, flu cytosine, fluconazole, but sensitive to Iitraconazole, isavuconazole, and posaconazole [5,6,15]. Susceptibility data are inconsistent with respect to voriconazole and amphotericin [6,14,15]. Diabetes mellitus, corticosteroid use, and residence in Southeast Asia likely influenced her risk of acquiring both infections. The demographic history initially prompted concerns for other diagnoses including penicilliosis, sporotrichosis and histoplasmosis. M. Romero infection in this case likely originated from a remote asymptomatic inoculation followed by reactivation during immune suppression. Clinicians should remain vigilant for atypical infections in patients with a history of residence in areas endemic for unusual fungal pathogens, and should have a low threshold for utilizing sequencebased molecular tools to make a timely diagnosis. Treatment of dematiaceous fungal infections remains challenging especially in those with invasive infections.