Dematiaceous Fungal Infection Research Articles

Clinicopathological study of pigmented fungal lesions with special reference to subcutaneous phaeohyphomycosis: A 3-year study in a tertiary care hospital of Eastern India

Background: Fungal infections are predominantly opportunistic infections in immunocompromised patients and in immunocompetent adults with a history of trauma. Recently, there is an increase in trends of fungal infections in immunocompetent individuals also without any history of trauma. Pigmented fungi are a group of fungi that have pigment in their cell wall and also known as dematiaceous fungi. These pigmented fungi include phaeohyphomycosis with a differential diagnosis of chromoblastomycosis, cryptococcosis, mycetoma, and aspergillus. Phaeohyphomycosis is a subcutaneous or systemic infection characterized histologically by dark-colored fungal hyphae and yeast forms (black yeast). Aims and Objectives: The aim of the present study is to analyze the clinicopathological features of pigmented fungal infections in biopsy specimen based on their histomorphology. Materials and Methods: This was a prospective study in which we have analyzed the dematiaceous fungal species by their histomorphological characteristics in biopsy specimens. Results: A total of 21 cases of biopsy specimens (with the clinical presentation of cutaneous/subcutaneous lesions) were studied histologically which showed 13 cases of phaeohyp homycosis, seven cases of eumycotic mycetoma, and one case of chromoblastomycosis. There was male predominance (17, 80.95%) and the majority of the patients were >60 years (16, 76.19%). Most common site of infection was foot with predominant clinical presentation as subcutaneous mass lesion. Conclusion: All the cases of dematiaceous fungal infections were diagnosed by histopathological examination. Melanin in the cell wall of dematiaceous fungi is the pathogenic factor. Phaeohyphomycosis is no longer considered as a rare infection rather there is an increasingly incidence of recognized infection. Although culture and histopathological study remain important tools for final diagnosis, various molecular studies might be helpful for accurate diagnosis.

Unsuspected Dematiaceous Fungal Infection Causing Subcutaneous Nodules in a Diabetic Patient

Unsuspected Dematiaceous Fungal Infection Causing Subcutaneous Nodules in a Diabetic Patient

P264 Brain phaeohyphomycosis secondary to immunosuppressant therapy due to Rhinocladiella mackenziei

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Two cases of Rhinocladiella mackenziei have been noted in our institute, the first case in 2015 (post-renal transplant) and the second case in 2021 (post-COVID infection). Both the patients had received immunosuppressants for varying duration. Both the cases presented to the hospital with neurological deficit secondary to brain abscess. On initial assessment, the melanized fungus was noted which was later identified as Rhinocladiella on culture and further confirmed with molecular methods. Both the cases were treated with injection of L AmB, voriconazole and 5FC for a prolonged duration and later discharged when the condition improved. The renal transplant patient was advised lifelong voriconazole since he would continue to be on immunosuppressants. To our knowledge, the second patient diagnosed post-COVID could be the first case report of invasive dematiaceous fungal infection in an apparently immunocompetent individual. Both cases also highlight the challenges in management such as designing an appropriate regimen, deciding the optimum duration of antifungal therapy, and managing the toxicities associated with long-term antifungal use. R. mackenziei is a frequently fatal melanized neurotropic fungus known to carry almost 100% mortality despite the combination of antifungal agents and surgery. Central nervous system infections due to R. mackenziei have been exclusively reported from the Middle East, except for cases recently reported from India.

Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta-analysis.

Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR). We searched PubMed database (last searched 1/6/2022) for English-language reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm. We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation. We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.

Verruconus gallopava CNS Infection in a Heart-Kidney Transplant Recipient

Introduction Dematiaceous fungal infections are uncommon and have diverse clinical manifestations. CNS involvement is among the rarest manifestations and typically presents as a brain abscess. Verruconus gallopava has been isolated in cases and appears to be associated with immunocompromised hosts, particularly the post-transplant population. There is no standardized treatment regimen for dematiaceous fungal CNS infections. Recommendations are largely based on in-vitro data and studies derived from case reports. Anti-fungal agents and complete excision of brain abscesses portends the best survival, although prognosis remains poor, with overall mortality >70%. Case Report Ms. H was a 50 yo F with a PMH of NICM c/b cardiorenal syndrome s/p combined heart-kidney transplant (on mycophenolate, tacrolimus and prednisone) who was brought to the ED 4 months post-transplant with altered mental status (AMS). 1 week prior to presentation, Ms. H developed intermittent headaches and progressive AMS. Vital signs WNL. Physical exam significant only for confusion and lethargy. Labs unremarkable. MRI brain revealed a L frontal lobe abscess w/ surrounding vasogenic edema and L-to-R midline shift. Ms. H underwent emergent L frontal craniectomy for abscess D&C. Empiric antibiotics were started and mycophenolate held. She worsened clinically and radiographically, compelling a L frontal lobectomy. Initial cultures grew mold, so liposomal amphotericin B (L-AmB) was added and antibiotics eventually discontinued. CT chest revealed a fungal abscess in the RLL, which was determined to be the primary source of infection. Cultures eventually speciated Verruconus gallopava, and voriconazole was added. Susceptibilities showed MICs of 2mcg/ml for AmB and 0.50 mcg/ml for voriconazole. However, she continued to decline, and voriconazole was switched to posaconazole (MIC of 0.25mcg/ml). Ms. H gradually improved and, after an 8-month hospital course, was discharged in stable condition on lifelong posaconazole monotherapy. At 1-year post-transplant f/u, L/RHC/biopsy showed hemodynamics WNL, CAV0, and no evidence of acute cellular rejection. Summary High clinical suspicion for dematiaceous fungi in brain abscesses is needed as these are rarely seen in practice. For Ms. H, a combination of posaconazole, L-AmB, and surgical intervention treated her life-threatening V. gallopava CNS infection.

In Vitro Activities of Ravuconazole and Isavuconazole against Dematiaceous Fungi

The in vitro activities of 11 antifungals against 84 dematiaceous fungi were tested. For most tested fungal species, the MIC values of ravuconazole and isavuconazole were lower than those obtained with itraconazole, voriconazole, and posaconazole. Ravuconazole and isavuconazole appear to be more efficient against most dematiaceous fungal infections than the other triazoles. However, some pigmented fungi, such as Bipolaris spicifera and Veronaea botryosa, remain more susceptible to other triazoles or to echinocandins.

Impaired Specific Antifungal Immunity in CARD9-Deficient Patients with Phaeohyphomycosis

Phaeohyphomycosis is a group of severe infections caused by dematiaceous fungi. We previously identified CARD9 deficiencies in four Chinese patients with phaeohyphomycosis caused by Phialophora verrucosa. In this study, we sought to identify the genetic and immunological mechanisms underlying rare dematiaceous fungal infections in three otherwise healthy patients with phaeohyphomycosis caused by Exophiala spinifera, Ochroconis musae, and Corynespora cassiicola. CARD9 sequencing in these patients showed one mutation (p.S23X) that, to our knowledge, has not been characterized and two previously characterized mutations (p.D274fsX60 and p.L64fsX59) that led to lack of CARD9 protein expression. Patient-derived CARD9-deficient cells showed a selective impairment of proinflammatory cytokine and chemokine production, NF-κB activation, and T helper type 22- and T helper type 17-associated responses upon fungus-specific stimulation, whereas phagocytosis and reactive oxygen species production were intact. Consistently, Card9-knockout mice were highly susceptible to phaeohyphomycosis and exhibited immune deficiencies similar to those of patients, including diminished NF-κB and p38 MAPK activation in local and invitro functional studies. This work clarifies the association between inherited CARD9 deficiencies and phaeohyphomycosis, and furthers current knowledge on the spectrum and pathophysiology of diseases resulting from CARD9 deficiencies.

Impairment of Immune Response against Dematiaceous Fungi in Card9 Knockout Mice.

Dematiaceous fungi are a large group of pathogens that can cause a wide range of diseases in both immunocompetent and immunocompromised hosts. Based on our previous finding of caspase recruitment domain-containing protein 9 (CARD9) mutations in patients with subcutaneous phaeohyphomycosis caused by Phialophora verrucosa (P. verrucosa), we further investigated the exact role of CARD9 in the pathogenesis of phaeohyphomycosis using Card9 knockout (Card9 KO) mice. We showed that Card9 KO mice are profoundly susceptible to P. verrucosa infection compared with wild-type mice, reflected by significantly more severe footpad swelling, higher fungal burden, lower survival, and systemic dissemination. The inability of Card9 KO mice to control P. verrucosa infection was associated with lack of Th17 differentiation and reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A levels in footpad homogenates. In vitro experiments showed a defect of fungal conidia killing and pro-inflammatory cytokine production in Card9 KO bone marrow-derived macrophages and dendritic cells. Furthermore, ex vivo coculture and in vitro T cell differentiation assay demonstrated that Card9 signaling pathway acts indispensably on differentiation of Th17 cells. In conclusion, our findings suggest that CARD9 mediate the innate immune and Th17-mediated adaptive immune responses against dematiaceous fungal infections at the early stage of infection.

Molecular typing using polymorphisms of the polyketide synthase gene (PKS1) of strains in Japan morphologically identified as Fonsecaea pedrosoi.

Fonsecaea pedrosoi sensu lato is a major causative agent of dematiaceous fungal infection in Japan. Recent sequence analysis of the internal transcribed spacer (ITS) regions of the ribosomal RNA gene has shown that this species can be separated into three species: F. pedrosoi sensu stricto, F. monophora and F. nubica. The cell walls of dematiaceous fungi including the genus Fonsecaea contain melanin, which is important for their virulence. Polyketide synthase (PKS1) is an enzyme required for melanin synthesis. This study analyzed the phylogeny of strains of F. pedrosoi sensu lato isolated in Japan by sequencing the PKS1 gene and ITS regions and identifying molecular polymorphism. Sixty strains morphologically identified as F. pedrosoi isolated worldwide, including 37 strains isolated in Japan, were analyzed. ITS regions of the ribosomal RNA gene and part of the PKS1 gene region were amplified, yielding sequences of approximately 600 and 450 bp, respectively. Polymerase chain reaction products were sequenced, and cluster analysis was performed. The proposed phylogenetic tree based on PKS1 sequences closely matched that based on the ITS regions. Sequencing of both regions showed that the isolates from Japan belonged to the clade of F. monophora. Molecular variations of these Japanese strains were evaluated by assessing both ITS and PKS1 sequences. The 37 isolates could be divided into at least seven molecular subtypes. The combination of these two molecular markers provides a most robust method for intraspecies subtyping and further epidemiological study of F. monophora.

Chromoblastomycosis caused by Phialophora verrucosa on the hand

The fungi that form black colonies on culture medium due to melanin pigment in the cell wall are collectively referred to as dematiaceous fungi. Dematiaceous fungal infections with a verrucous or plaque appearance and histopathologically sclerotic or muriform cells are classified as chromoblastomycosis. Phialophora verrucosa (P. verrucosa) is one of the chromoblastomycosis-causing fungi [1]. Itis common in the environment but infrequently causes an infection due to its low pathogenicity [2]. Here, [...]

Feohifomicosis subcutánea causada por Phaeoacremonium parasiticum

BackgroundFrom the available literature, it is demonstrated that dematiaceous fungal infections mostly affect immunosuppressed patients. These infections can occur in different forms, from subcutaneous infection to disseminated forms that may compromise the life of the patient. In many cases the infection is related to the inoculation of the microorganism by diverse traumatic mechanisms, which determines the course of the infection to be slower in some cases. Case reportWe describe two cases of phaeohyphomycosis caused by Phaeoacremonium parasiticum: A cancer patient with subcutaneous lesions affecting the left hand and forearm, and a patient who presented with subcutaneous abscesses in the left leg. ConclusionsThese cases confirm the presence of this type of fungus in Spain. In the second case a combination of amphotericin B lipid complex and posaconazole, together with several surgical resections, were necessary in order to overcome the infection.

骨髄異形成症候群に合併したExophiala jeanselmeiによるchromomycosisの1例：症例報告及び過去10年間における菌種別特徴

骨髄異形成症候群に合併したExophiala jeanselmeiによるchromomycosisの1例：症例報告及び過去10年間における菌種別特徴

Subcutaneous dematiaceous fungal infection

Subcutaneous dematiaceous fungal infections, which include chromoblastomycosis and phaeohyphomycosis, are a heterogeneous group of clinical entities that are caused by dematiaceous or pigmented fungi found in soil. These infections have a wide spectrum of clinical presentations that depend largely on the specific causative organism and on the integrity of the host's immune response. Treatment is challenging and involves a highly individualized plan that often combines both surgical and long-term medical treatment.

Dermoscopy improves diagnosis of tinea nigra: A study of 50 cases

Tinea nigra is a relatively uncommon dematiaceous fungal infection of the palms and soles, which clinically may mimic a melanocytic lesion. We sought to ascertain how frequently misdiagnosis of this infection occurred and whether the use of dermoscopy helped in its diagnosis. Fifty consecutive cases of tinea nigra diagnosed at a dermatopathology laboratory were examined with regard to the clinical diagnosis, use of dermoscopy and the mode of management. Of the 50 cases, 21 (42.0%) were treated by shave or surgical excision. The clinical diagnosis of tinea nigra was made in five cases (10.0%) and suggested along with other diagnoses in a further two cases (4.0%). The dermatologists (n = 9) gave the correct diagnosis in four patients (44.4%), the general practitioners (n = 38) gave the correct diagnosis in one patient (2.6%) and the three surgeons involved did not give the correct diagnosis. When dermoscopy was used, in seven of 13 (53.8%) cases tinea nigra was suggested as a probable diagnosis but when dermoscopy was not used (n = 37) tinea nigra was not clinically diagnosed (P < 0.001). The diagnosis of tinea nigra is significantly improved by dermoscopy, the disease should be considered as a cause of palmar or plantar pigmentation.

A Verrucous Plaque of the Eyebrow

Phaeohyphomycosis is a rare dematiaceous fungal infection requiring surgical excision or appropriate systemic antifungal therapy. The objective of this study is to report a case of phaeohyphomycosis of the right eyebrow successfully treated with surgical excision. We performed an excision of a dermal plaque of phaeohyphomycosis using 4-mm margins on the right brow extending onto the right forehead. An island pedicle flap was used to close the defect. Histopathologic evaluation confirmed the presence of numerous dematiaceous fungal organisms fully consistent with phaeohyphomycosis, and the margins were verified to be free of fungal organisms. Culture of a central portion of the excised lesion confirmed that the causative organism was a saprophytic fungus. Adjuvant systemic antifungal therapy was offered to the patient, but because of financial resources, the patient did not desire any further treatment. The patient remains free of the organism and has healed well, without complications. Phaeohyphomycosis can be effectively treated with excision alone, and when located in a risky anatomic location, such as near the orbit, adjuvant treatment with systemic antifungals may be warranted to prevent recurrence.

Sporotrichosis and Dematiaceous Fungal Skin Infections

Sporotrichosis is a chronic infectious granuloma of skin. The detection of fungal elements in pathological examination and the isolation of Sporothrix schenckii from the lesion are requisite for diagnosis. The sporotrichin test is useful as an auxiliary examination, but a false-negative reaction might occur in some cases. Oral potassium iodide is first choice of treatment, because of its modest cost and usefulness, although gastrointestinal disorder is a frequent side effect. Itraconazole should be the second selection, and then terbinafine. Local thermotherapy is also effective as an additional therapy. Dematiaceous fungal skin infections are divided into two groups by their parasitic form, chromoblastomycosis and phaeohyphomycosis. Chromoblastomycosis is also called chromomycosis in Japan. It is most important for clinical diagnosis to detect dark brown spores in the scale of chromoblastomycosis and dark brown hyphae in the pus of phaeohyphomycosis by microscopic examination. Both morphological and molecular biological approaches are recommended for identification of fungi. In treatment, the drug appropriate in each case should be selected, and the combination of surgical excision, local thermotherapy, laser therapy or cryotherapy must be considered.

Diagnosis of Cutaneous Fungal Infection

The Japanese Dermatological Association produced some guidelines for the management of cutaneous fungal infection in cooperation with the Japanese Society for Medical Mycology, in which the importance of an accurate diagnosis of the fungal infection before antifungal treatment is emphasized. Here I comment on conventional mycological tests including direct microscopic examination and fungal cultures, which have been listed in the guidelines. Sampling of the clinical specimen is the most important step in mycological tests, so dermatologists should be aware of how and where good specimens are obtained. Direct microscopic examination of a KOH (potassium hydroxide) mounted preparation is the most simple and important test for diagnosing superficial fungal infection and dematiaceous fungal infection, which requires that dermatologists be skilled. The fungal culture is important in determining the therapeutic strategy and prophylaxis of the fungal infection, especially in cases of tinea capitis, tinea corporis, and deep mycoses. It is imperative that dermatologists be fully trained and prepared in order to implement these procedures when the occasion demands.

Craniofacial dematiaceous fungal infection

A 48-year-old man with no history of immunosuppressive illness presented with generalised facial ulceration and crusting throughout the lower and middle face (Fig. 1). He had previously had a Curvularia infection of the left turbinate. After an endoscopic examination of the maxillary sinus and incisional biopsy of the facial skin, extensive debridement, and treatment with itraconazole 600 mg daily, orally for four weeks he was considerably better. Curvularia is a saprobic dematiaceous mould that is often associated with human infections of the paranasal sinus, skin, and soft tissue. Antifungal treatment with itraconazole has been reported to be successful.

Chronic craniofacial dematiaceous fungal infection: A case report

Curvularia is a saprobic dematiaceous mold that has been associated with a wide spectrum of human infection. In non-immunosuppressed patients, infections frequently involve the paranasal sinus, skin, and soft tissue, whereas systemic dissemination and endocarditis are extremely rare. The optimal antifungal therapy for Curvularia infection is not known, and responses to treatment with amphotericin B, miconazole, ketoconazole, terbinafine, and itraconazole have been reported. We describe a patient with an invasive dematiaceous fungal sinusitis who was immunocompetent and was infected with Curvularia. The patient was successfully treated with oral itraconazole by otolaryngology and the infectious disease service.

Allergic fungal sinusitis presenting as a paranasal sinus tumor.

We present a case of allergic fungal sinusitis (AFB) in a 20-year old man with few months' history of bilateral nasal obstruction and discharge with unilateral proptosis that underwent maxillary antrostomy due to the mass in paranasal sinuses. Histological examination of tissue showed branching fungal hyphae interspersed with allergic mucin without fungal invasion to soft tissue. The patient received local steroid for 4 months and had no problem during follow up. Fungal culture was performed and Bipolaris fungus grew. Although most dematiaceous fungal infections occur in immunocompetent patients, the incorrect diagnosis and insufficient treatment may be life threatening.