Deep cutaneous fungal infections in solid-organ transplant recipients.

BACKGROUND: Deep cutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs). OBJECTIVE: To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs. METHODS: A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed. RESULTS: Overall, 46 s-OTRs developed DCFIs (median delay, 13 months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs. LIMITATIONS: Due to the retrospective observational design of the study. CONCLUSIONS: Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams are helpful for optimal diagnosis and management.

Subcutaneous phaeohyphomycosis caused by a black pigmented mould (Rhytidhysteron species) in rural north-western New South Wales, Australia.

Invasive fungal infections are becoming increasingly more prevalent in clinical practice. This corresponds with more patients living with immunosuppression and improved techniques to identify fungal infections. Subcutaneous fungal masses can often masquerade and imitate common dermatological lesions such as cysts. Querying a fungal aetiology of a mass is important, as fungal elements can be missed on histological examination, and special stains may be needed to identify spores and hyphae to make the diagnosis. Skin trauma with inoculation of fungal elements contained in soil and vegetable matter is the most common source of subcutaneous fungal masses. While traditionally considered a disease of the tropics, subcutaneous fungal masses can present worldwide in both immunosuppressed and immunocompetent patients. This case study describes a subcutaneous knee mass in a 53-year-old immunosuppressed farmer in Australia. A subcutaneous phaeohyphomycosis was diagnosed with a black pigmented mould, Rhytidhysteron species. A latent period of 12 years was observed between traumatic inoculation with farm soil and wheat dust in north-western New South Wales and development of the knee mass. Rhytidhysteron is considered a disease of the tropics, most commonly reported in India. This case, to the author's knowledge, is the first case report of pathogenic Rhytidhysteron from Australia. Surgery and antifungal therapy are recommended to treat Rhytidhysteron infection. This patient's recommended antifungal treatment was shortened due to severe hepatic disease. The clinical course was complicated by three localised recurrences in the patient's knee over 14 months. At the time of the third localised recurrence, this patient could tolerate posaconazole therapy for a month only. Surgical excision using general anaesthesia, use of diathermy for excision and wound lavage with iodine, hydrogen peroxide and saline has coincided in remission of clinical disease for 3 years at the time of writing.

The Phytopathogenic Fungus Pallidocercospora crystallina-Caused Localized Subcutaneous Phaeohyphomycosis in a Patient with a Homozygous Missense CARD9 Mutation.

PURPOSE: In the past decade, an increasing number of otherwise healthy individuals suffered from invasive fungal infections due to inherited CARD9 mutations. Herein, we present a patient with a homozygous CARD9 mutation who was suffering from localized subcutaneous phaeohyphomycosis caused by the phytopathogenic fungus Pallidocercospora crystallina which has not been reported to cause infections in humans. METHODS: The medical history of our patient was collected. P. crystallina was isolated from the biopsied tissue. To characterize this novel pathogen, the morphology was analyzed, whole-genome sequencing was performed, and the in vivo immune response was explored in mice. Whole-exome sequencing was carried out with samples from the patient's family. Finally, the expression and function of mutated CARD9 were investigated. RESULTS: A dark red plaque was on the patient's left cheek for 16 years and was diagnosed as phaeohyphomycosis due to a P. crystallina infection. Whole-genome sequencing suggested that that this strain had a lower pathogenicity. The in vivo immune response in immunocompetent or immunocompromised mice indicated that P. crystallina could be eradicated within a few weeks. Whole-exome sequencing revealed ahomozygous missense mutation in CARD9 (c.1118G>C p.R373P). The mRNA and protein expression levels were similar among cells carrying homozygous (C/C), heterozygous (G/C), and wild-type (G/G) CARD9 alleles. Compared to PBMCs or neutrophils with heterozygous or wild-type CARD9 alleles, however, PBMCs or neutrophils with homozygous CARD9 alleles showed impaired anti-P. crystallina effects. CONCLUSION: Localized subcutaneous phaeohyphomycosis caused by P. crystallina was reported in a patient with a homozygous CARD9 mutation. Physicians should be aware of the possibility of a CARD9 mutation in seemingly healthy patients with unexplainable phaeohyphomycosis.

Cutaneous infections by dematiaceous opportunistic fungi: Diagnosis and management in 11 solid organ transplant recipients.

BACKGROUND: The incidence of cutaneous infections by dematiaceous fungi is rising in our environment due to the high number of solid organ transplant recipients (SOTR). OBJECTIVE: To review our experience in the management of cutaneous phaeohyphomycoses in a Spanish reference centre for dermatological care of SOTR. METHODS: Retrospective clinical, histopathological and microbiological review of all SOTR diagnosed of a phaeohyphomycosis in a 7-year period. RESULTS: Eleven SOTR were identified (8 lung and 3 kidney). The lesions were solitary in six patients and multiple in five, affecting mostly the lower extremities. Early lesions showed epidermal hyperplasia and a diffuse dermal suppurative granulomatous infiltrate that was progressively substituted by fibrosis when the lesions were treated. Septated fungal structures with refractile walls were identified. DNA sequencing confirmed the presence of Alternaria spp (8 cases), Cladosporium cladosporioides, Microsphaeropsis arundinis and Exophiala oligosperma. Three patients with single lesions were treated with surgery, while the other 8 required long-term antifungal therapy, including itraconazole, voriconazole and/or terbinafine, combined with surgery and reduction in tacrolimus doses. CONCLUSION: A clinical, histopathological and microbiological correlation is essential to corroborate this diagnosis. Solitary lesions are easily treated with surgery, but larger or multiple lesions may require long medical treatments combined with surgery and modification of immunosuppressive medication. The list of dematiaceous fungi implicated in cutaneous infections is expanding, in line with the availability of more sophisticated identification methods and the increasing number of immunosuppressed patients.

Exophiala dermatitidis Endophthalmitis: Case Report and Literature Review.

We report a case of a 59-year-old male patient with a postoperative fungal infection of the left eye. A dark-pigmented yeast, Exophiala dermatitidis (previously known as Wangiella dermatitidis), was identified from the culture of the biopsy taken from the posterior capsule. The infection was successfully eradicated by a combination of surgical and medical (i.e., voriconazole and fluconazole) treatment. This is the first report of successfully treated E. dermatitidis endophthalmitis, which demonstrates that a prompt and aggressive antifungal therapy combined with surgical intervention is necessary to prevent vision loss in cases of endophthalmitis due to Exophiala species. Beside the case description, we also aim to provide a literature review of previously reported eye infections caused by Exophiala species in order to help the future diagnosis and management of the disease.

[Sinonasal fungal infections are not exclusively due to mucorales and Aspergillus!]. / Les infections fongiques nasosinusiennes ne sont pas uniquement liées aux mucorales et aux Aspergillus !

Rhino-sinusal infections are serious diseases and possibly lethal. When they are invasive, we easily discuss apergilloses and mucormycoses. The confirmation of the diagnosis of mucormycosis need an extensive surgery for precise histopathological and mycological evaluation. The pathologist may be faced to other rare mycoses such as phaeohyphomycoses, which present different morphological features than mucormycoses and Aspergillus. Once the diagnosis is established, an appropriate antifungal treatment is quickly started. The aim of our work is to report two observations of phaeohyphomycoses, to describe their histopathological features, to discuss complementary diagnostic methods and to present the main differential diagnoses.

NOCARDIA BEIJINGENSIS PSOAS ABSCESS AND SUBCUTANEOUS PHAEOHYPHOMYCOSIS CAUSED BY PHAEOACREMONIUM PARASITICUM IN A RENAL TRANSPLANT RECIPIENT: THE FIRST CASE REPORT IN THAILAND.

We describe the first case of a psoas muscle abscess caused by Nocardia beijingensis and subcutaneous phaeohyphomycosis caused by Phaeoacremonium parasiticum in a renal transplant recipient. The patient was treated for nocardiosis with percutaneous drainage and intravenous trimethoprim/sulfamethoxazole (TMP/SMX) combined with imipenem for 2 weeks, followed by a 4-week course of intravenous TMP/SMX and then oral TMP/SMX. During hospitalization for the psoas muscle abscess the patient developed cellulitis with subcutaneous nodules of his right leg. Skin biopsy and cultures revealed a dematiaceous mold, subsequently identified as P. parasiticum by DNA sequencing. The subcutaneous phaeohyphomycosis was treated with surgical drainage and liposomal amphotericin B for 4 weeks followed by a combination of itraconazole and terbinafine. The patient gradually improved and was discharged home after 18 weeks of hospitalization.

Phaeohyphomycosis fungal infections in solid organ transplant recipients: clinical presentation, pathology, and treatment.

BACKGROUND: Dematiaceous, or dark-pigmented, fungi are known to cause infections such as phaeohyphomycosis, chromoblastomycosis, and mycetoma. These fungi are becoming increasingly important opportunistic pathogens in solid organ transplant recipients (SOTR). We present a retrospective chart review of 27 SOTR who developed phaeohyphomycosis infections post transplant from 1988 to 2009. METHODS: Cases were reviewed for fungal species isolated, date and source of culture, immunosuppressive and fungal therapy used, and outcome. The majority of isolates obtained were from the skin and soft tissue, with 3 pulmonary and brain abscesses. RESULTS: The time from transplantation to onset of infection ranged from 2 months to 11 years. The species isolated were Exophiala (11), Ochroconis (3), Alternaria (2), Phoma (2), Wangiella (1), Cladosporium (1), Aureobasidium (1), Chaetomium (1), Coniothyrium (1), and non-sporulating fungi (2). An additional 4 patients had infections confirmed by pathology, but no cultures were done. Most of the affected skin lesions were surgically debrided and treated with itraconazole; 2 patients were treated with voriconazole and 2 with amphotericin D. Death from fungal disease occurred only in patients with pulmonary and brain abscesses. CONCLUSIONS: As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.

Dematiaceous fungi mimicking a conjunctival melanoma.

An 85-year-old, immunocompetent man was referred to the authors due to the presence of an enlarging, pigmented mass of the conjunctiva concerning for a conjunctival melanoma. Wide excision of the mass revealed a pigmented or "dematiaceous" fungus. He was treated with topical natamycin, and the lesion healed well without any evidence of recurrence. Dematiaceous fungi should be considered in the differential for pigmented conjunctival lesions.

Ocular Phaeohyphomycosis Caused by Veronaea botryose: A Novel Fungal Infection in Human Beings.

PURPOSE: To describe an aggressive, refractory case of Veronaea botryosa-associated mycokeratitis progressing to endophthalmitis. METHODS: Observational case report and review of relevant literature. RESULTS: An 80-year-old man with a history of lung cancer and diabetes mellitus type 2 presented as an emergent referral to the corneal service with a corneal ulcer and associated endothelial plaque that responded initially to topical steroid and antiviral therapy but subsequently progressed to fungal endophthalmitis. The patient underwent an emergent penetrating keratoplasty and pars plana vitrectomy. Despite multiple negative Grocott methenamine silver smears, gram stains, eye cultures (aerobic, anaerobic, and fungal), and inconclusive confocal microscopy, the host corneal tissue pathology revealed melanin-containing fungi (phaeohyphomycosis). Further speciation of the pathology specimen revealed mold and phenotypic characterization and DNA sequencing confirmed V. botryose. CONCLUSIONS: Veronaea botryose is a rare fungal infection with previously reported human cutaneous, subcutaneous, and submucosal infections. This is the first documented case of phaeohyphomycosis caused by V. botryosa infection in human ocular tissue.

Cutaneous infection by Phaeoacremonium parasiticum.

BACKGROUND: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. CASE REPORT: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding ß-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. CONCLUSIONS: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown.

Cutaneous phaeohyphomycosis.

BACKGROUND: Phaeohyphomycosis is an infrequent infection in human beings. However, in recent years, its prevalence has augmented in immunosuppressed patients (mostly in solid organ transplanted patients). Infection can be mucocutaneous or disseminated. In the former, the fungus inoculation occurs mainly through traumatism. Lesions may be polymorphic and asymptomatic, isolated or multiple, and are usually localized in exposed areas of the limbs and head. Treatment is not standardized. When possible, surgical resection of the lesion is combined with systemic antifungals. METHODS: We communicate three phaeohyphomycosis cases with cutaneous compromise. RESULTS: The cases we present show diverse clinical characteristics and varied severity and evolution. CONCLUSION: It is important for dermatologists to recognize this cutaneous fungus infection because the diagnosis using microscopic examination and mycological culture depends on the clinical suspicion.

Subcutaneous Phaeohyphomycosis Caused By Pyrenochaeta Romeroi in a Kidney Transplant Recipient: A Case Report.

Infections are Achilles heel of kidney transplant recipients. Opportunistic fungal infections are increasingly recognized in these patients. We report a case of kidney transplant recipient with skin and soft tissue infection caused by Pyrenochaeta romeroi, a dematiaceous fungi. Infection by this organism is rare.

Phaeohyphomycosis in renal transplantation: report of two cases.

Phaeohyphomycosis is an infection caused by a filamentous fungus that contains pigment melanin in its cell wall. We report two cases caused by Exophiala sp. emphasizing the clinical variability of the disease, as well as diagnostic and therapeutic difficulties of this opportunistic infection in immunosuppressed patients (kidney transplant).