Cutaneous Alternariosis in Immunosuppressed Patients Treated with Photodynamic Therapy and Oral Antifungals, a Synergistic Strategy.

Cutaneous alternariosis is a rare condition, more frequently presented in immunocompromised patients, which usually requires long courses of systemic antifungals that may interact with other medications. The presented series shows three cases of cutaneous alternariosis in immunocompromised patients and organ transplant recipients that were successfully treated with photodynamic therapy and oral antifungals, allowing a reduction in the systemic treatment duration and therefore decreasing the risk of side effects and drug interactions.

Intricate isavuconazole therapy of a subcutaneous nodule caused by Alternaria infectoria in a heart transplant recipient.

Invasive fungal infections have appeared to be increasingly emergent in immunocompromised patients, especially in solid organ transplant (SOT) recipients. The Alternaria genus encompasses more than 80 dematiaceus species. Among them, Alternaria alternata and Alternaria infectoria are the most frequent isolated as responsible for infection in humans. To our knowledge, we report the first case of a heart transplant recipient suffering from subcutaneous nodule caused by Alternaria infectoria and who was treated with isavuconazole. Despite all the promises of this new azole drug, one should keep in mind the potential great variability of the inter-individual responses for such complex patients. We demonstrate herein how it can be challenging to manage Alternaria infection in SOT recipients. More comprehensive studies and recommendations are expected in the context of Alternaria infections.

Unusual location of cutaneous alternariosis in an immunocompetent patient.

Alternaria is a dematiaceous fungus ubiquitously found in nature. It can cause infections, especially in immunocompromised patients. We report a periorbital location of Alternaria infection in an immunocompetent woman with a confusing clinical presentation. The diagnosis was confirmed by a cutaneous biopsy of the cheek. PCR sequencing identified Aternaria alternata species. The evolution was fatal despite antifungal treatment.

Clinical analysis of three cases of disseminated cutaneous alternariosis caused by Alternaria / 中华皮肤科杂志

Objective:To analyze clinical manifestations, histopathological and pathogenic fungus characteristics as well as treatment of 3 cases of disseminated cutaneous alternariosis caused by Alternaria. Methods:Clinical data were collected from 3 cases of disseminated cutaneous alternariosis caused by Alternaria, who were diagnosed in Department of Dermatology, Xijing Hospital from 2019 to 2021, and clinical and histopathological features, fungal culture, strain identification and treatment results were retrospectively analyzed. Results:The 3 patients were aged 55, 41 and 46 years respectively, including 1 male and 2 females. Two patients were previously diagnosed with nephrotic syndrome and 1 with systemic lupus erythematosus. All the patients had a history of taking glucocorticoids and tacrolimus for different durations, and experienced chronic infections. Histopathological examination with hematoxylin and eosin (HE) staining showed double-contour thick-walled spores and knot-shaped thick-walled septal hyphae, but no melanin in skin lesions. Sequencing of the fungal internal transcribed spacer region confirmed that 2 cases were infected with Alternaria alternate, and 1 with Alternaria infectoria. Fungal culture at different temperatures showed that the growth ability of Alternaria markedly decreased at the temperature over 35 ℃. To treat these patients, the dose of tacrolimus was reduced to less than 1/3 of the standard dose, or tacrolimus was switched to other immunosuppressants, and systemic antifungal therapy was also given at the same time. After 7-month treatment, good clinical outcomes were achieved in the 3 patients. Conclusion:Disseminated cutaneous alternariosis is characterized by bilateral hematogenous dissemination and lymphatic distribution in unilateral limbs, and the skin lesions are characterized by verrucous plaques covered with scabs, nodules and/or sinuses.

Polyphasic identification of three new species in Alternaria section Infectoriae causing human cutaneous infection.

BACKGROUND: Cutaneous phaeohyphomycosis is an emerging disease in immunocompromised patients, being Alternaria one of the most common genera reported as a causative agent. Species identification is not carried out mainly due to the complexity of the genus. Analysis of the ITS barcode has become standard for fungal identification, but in Alternaria it is only able to discriminate among species-groups or sections. METHODS: We present three cases of cutaneous infection caused by Alternaria isolates morphologically identified as belonging to section Infectoriae. They have been morphologically characterised and phylogenetically delineated with five molecular markers (ITS, ATPase, gapdh, rpb2 and tef1). RESULTS: Mycotic infections have been diagnosed by repeated cultures and histopathological examination in two of the cases. The polyphasic approach has allowed to delineate three new species of Alternaria section Infectoriae, that is A anthropophila, A atrobrunnea and A guarroi. ATPase has been the only locus able to discriminate most of the species (29 out of 31) currently sequenced in this section, including A infectoria the commonest reported species causing alternariosis. Susceptibility test showed different antifungal patterns for the three species, although terbinafine was the most active in vitro drug against these fungi. CONCLUSIONS: The ATPase gene is recommended as an alternative barcode locus to identify Alternaria clinical isolates in section Infectoriae. Our results reinforce the relevance of identification of Alternaria isolates at the species level and the necessity to carry out antifungal susceptibility testing to determine the most adequate drug for treatment.

Cutaneous alternariosis in a renal transplant patient successfully treated with posaconazole: Case report and literature review.

Cutaneous alternariosis is an uncommon fungal infection that most commonly presents in organ transplant patients on immunosuppressive therapy. There are no clinical trials or guidelines to guide treatment of this condition, however itraconazole is the most commonly used antifungal in published cases. Here we report on a case of cutaneous alternariosis in a renal transplant recipient treated with a newer antifungal, posaconazole. A review of published reports of cutaneous alternariosis since 2008 is also discussed.

Successful Posaconazole Therapy of Disseminated Alternariosis due to Alternaria infectoria in a Heart Transplant Recipient.

We report a case of phaeohyphomycosis caused by Alternaria infectoria in a 61-year-old heart transplant recipient with multiple skin lesions and pulmonary infiltrates. The infection spread via the haematogenous route from the primary cutaneous lesions into the lungs. The diagnosis was based on the histopathological examination, direct microscopy, skin lesion cultures and detection of Alternaria DNA in the bronchoalveolar lavage fluid using molecular methods. The treatment consisted of a combination of surgical excision and systemic antifungal therapy. Voriconazole was the first agent used but had a weak effect. Posaconazole was subsequently used to achieve a successful response. The isolate was identified as A. infectoria by sequencing of the rDNA ITS region and the partial ß-tubulin gene.

A case of pulmonary alternariosis complicated with aspergillosis / 中南大学学报(医学版)

A 61-year-old woman with pulmonary alternariosis and aspergillosis was reported.The patient presented with recurrent hemoptysis and cough for 3 years.Alternaria was identified by fungal culture.Biopsy specimen showed pulmonary aspergillosis.The patient had been treated with voriconazole at 400 mg/d through intravenous guttae for 7 days,and then switched amphotericin B at 25 mg/d through intravenous guttae for 11 days.The patient was treated with voriconazole at 400 mg through oral when she was discharged from hospital.After the treatment,the clinical symptoms ofhemoptysis and cough were recovered,and the lung CT examinations showed normal.

Cutaneous alternariosis in a renal transplant recipient: a case report and literature review.

Organ transplant recipients under immunosuppressive therapy have a highly increased risk of acquiring unusual opportunistic infections. Diagnosis of the etiology of infection may be difficult in clinical manifestations, which need further histological and biological investigations. We recently treated a male renal transplant recipient with a cutaneous phaeohyphomycosis due to Alternaria species. The diagnosis was based on microscopy and culture of the skin lesions. Treatment with oral itraconazole for 5 weeks was ineffective, then clinical improvement was achieved by combination of amphotericin B wet-packing and systemic antifungal therapy with oral voriconazole. Alternaria species are ubiquitous plant-inhabiting saprobes, which are increasingly associated with opportunistic phaeohyphomycosis in immunocompromised individuals. To the best of our knowledge, this is the second case report noting sporotrichoid pattern as the manifestation of cutaneous alternariosis. In this context, we reviewed recent renal-transplant-related cutaneous alternariosis reported in the English-language literature during 1995 to 2011 to summarize its clinical features and outcomes, and to guide clinicians in the care of kidney transplant patients with cutaneous alternariosis.

Cutaneous infection with Alternaria triticina in a Bilateral lung transplant recipient.

We report the case of a 60-year-old man who was receiving immunosuppressive therapy for a bilateral lung transplant and presented with a crusted, violaceous plaque on the left hand. Based on histopathology and microbiological culture the patient was diagnosed with infection by Alternaria species. Treatment with itraconazole led to complete resolution of the skin lesion. Forty months later he developed four reddish, nodular, skin lesions on the left leg. Analysis of a biopsy from one of these lesions using histopathologic and molecular techniques identified a mold that shared 98% homology with a strain of Alternaria triticina. Alternaria species belong to a group of dematiaceous fungi that cause opportunistic infections in humans. The incidence of these infections is increasing, mainly in transplant centers. To the best of our knowledge, this is the first reported case of a human infection caused by A. triticina.

A Case of Cutaneous Infection by Alternaria alternata / 대한의진균학회지

Alternaria(A.) species are common saprophyte found in the environment such as soil, air, and plants. They are not usually pathogenic in humans but recently, infections by these fungi have occasionally been reported, occurring mostly in immunocompromised patients. They can cause hypersensitivity pneumonitis, bronchial asthma, or allergic rhinitis and rarely skin infection. A 76-year-old man presented with multiple erythematous papules, plaque and pustules with purpuric patches on both forearms and dorsal hands for 6 months. He had been treated for Parkinson's disease and dementia for 3 years but had not been taking any immunosuppressants. Direct smear with KOH was negative. Histopatholoigically, neutrophilic abscess, suppurative granulomatous inflammation and round spores were observed in the dermis. Periodic acid-Schiff and Methenamine silver stains revealed round to oval shaped spores. The biopsy specimen was cultured in potato dextrose agar and a cottony olive green to gray colored colony with black to brown reverse grew at 7 days of culture. The slide culture stained with lactophenol-cotton blue showed brown septated hyphae and obclavate conidia with brown muriform septation. The nucleotide sequences of the ribosomal internal transcribed spacer region of cultured colonies and paraffin blocks of biopsy specimen were identical to that of A. alternata. He was treated with topical ketoconazole cream application for 4 months, and healed leaving hyperpigmentation with scales.

Cutaneous Alternariosis Caused by Alternaria infectoria: Three Cases in Kidney Transplant Patients.

The genus Alternaria has more than 80 species. Alternaria alternata and Alternaria infectoria are the most frequent species associated with infections in humans. Their clinical importance lies in the growing number of cases reported in immunocompromised patients. Herein, we report three cases of kidney-transplanted patients with different clinical presentations of cutaneous alternariosis and we discuss the treatment options.

Two Cases of Cutaneous Infection by Alternaria alternata on Senile Purpura Site / 대한의진균학회지

Genus Alternaria is a species of dematiaceous fungi that is commonly found in the atmosphere or in the soil. It can cause hypersensitivity pneumonitis, bronchial asthma, or allergic rhinitis in immunocompromised host such as patient with organ transplantation or long-term steroid using patient. It can rarely cause skin infection. Case 1 was a 74-year-old man with well demarcated and elevated erythematous plaque with irregular scattered pustules on his right forearm. Case 2 was a 77-year-old woman with well demarcated elevated erythematous nodules within erythematous patch on her right forearm. In both cases, the lesions started at the senile purpura site. Herein, we report 2 rare cases of Alternaria alternata on senile purpura site to share the experience.

A Case of Cutaneous Alternariosis Treated with Fluconazole / 대한의진균학회지

Alternaria is a common saprophytic fungus found in the environment such as soil, air, and a variety of objects. The cutaneous infection caused by this fungus occurs more frequent in patients with immunocompromission than in immunocompetent people. We report a case of cutaneous alternariosis in a 63-year-old woman presented with a tender erythematous patch on the right forearm. She was on medication only for hypertension. Histopathologic examination showed a dermal mixed-cell infiltrate including multinucleated giant cells. PAS staining revealed fungal elements in the dermis. Microscopic examination of the colonies showed muriform conidia. A diagnosis of cutaneous infection due to Alternaria species was made on the basis of the above mentioned findings. Oral administration of fluconazole revealed resolution of her cutaneous lesion.

A Case of Cutaneous alternariosis due to Alternaria alternata / 대한의진균학회지

Alternaria is a common saprophyte that is not usually pathogenic in humans. However, infections by the fungus have occasionally been documented, occurring mostly in immunocompromised patients. We report a case of cutaneous alternariosis caused by Alternaria alternata in a 64-year-old woman presenting with a coin-sized, slightly elevated, dark red plaque on the right wrist without systemic immunosuppression. Macroscopic and microscopic morphology of fungal culture and histopathological differentiation offered diagnostic possibility. Systemic roxithromycin and itraconazole were administered with a dramatic resolution of the lesion.

A Case of Cutaneous Alternariosis in Liver Transplant Patient / 대한의진균학회지

A case of cutaneous alternariosis is reported in a 61-year-old female who underwent liver transplantation one year earlier. The infection manifested as a crusted papule about 1 cm in diameter on the right knee. Histological examination with silver methenamine and periodic acid-Schiff diastase revealed fungal spores and hyphae with chronic granulomatous inflammation. Biopsy fragments inoculated on Sabouraud-glucose agar with chloramphenicol produced colonies which were identified as Alternaria species on the basis of macroscopic and microscopic characters. Complete excision and treatment with 250 mg/day oral terbinafine for one month resulted in a satisfactory course with no signs of local recurrence over follow-up period of one year.

A Case of Cutaneous Alternariosis / 대한피부과학회지

Alternaria species belong to the group of dematiacious fungi that have increasingly been reported as pathogens in immunocompromised patients, although cutaneous infection is regarded as a rare opportunistic infection. We describe a case of cutaneous alternariosis in a 66 year-old woman with rheumatoid arthritis. The lesions showed asymptomatic, edematous, violaceous scaly patches on both forearms. Histopathologic findings revealed chronic granulomatous inflammation, and PAS staining identified hyphae and spores. The organism was finally isolated as alternaria species by repeated fungal cultures of the tissue. Treatment with 200mg/day oral itraconazole for three months resulted in a marked regression of the skin lesions.

A Case of Primary Cutaneous Alternariosis in a Renal Transplant Recipient / 대한이식학회지

Alternariosis is a genus of dematiaceous fungi frequently found in air, soil and plants, but not usually pathogenic in humans. Most reports of alternariosis are immunosuppressed hosts, including solid-organ transplant recipients. We report a case of cutaneous alternariosis in a 53-year-old renal transplant recipient, which was successfully treated with local excision without concomittant reduction of immunosuppressive agents and antifungal therapy.

A Case of Cutaneous Alternariosis / 대한의진균학회지

Alternaria species are common plant pathogens and saprophytic fungi. Cutaneous alternariosis is rare and an opportunistic infection in both healthy and immunosuppressed hosts. We report a case of cutaneous alternariosis developed in a 60-year-old female with iatrogenic Cushing syndrome. She had several various sized confluent suppurative ulcers on erythematous plaques on the both forearm clinically. Histology showed mixed-cell granulomatous infiltration with epithelioid cells, lymphocytes, neutrophils and a few plasma cells in the dermis. Many branching septate hyphae and spores were noted within the granulomatous tissue stained with PAS. A fungal culture from biopsy specimen revealed Alternaria species; pigmented hyphae and cornidia which had both transverse and longitudinal septae. The cutaneous lesions treated with terbinafine, 250 mg daily, for 3 months and 1 year later there is no evidence of recurrence.

A Case of Cutaneous Alternariosis / 대한의진균학회지

Alternaria species are common plant pathogens and saprophytic fungi. Cutaneous alternariosis is rare and an opportunistic infection in both healthy and immunosuppressed hosts. We report a case of cutaneous alternariosis developed in a 60-year-old female with iatrogenic Cushing syndrome. She had several various sized confluent suppurative ulcers on erythematous plaques on the both forearm clinically. Histology showed mixed-cell granulomatous infiltration with epithelioid cells, lymphocytes, neutrophils and a few plasma cells in the dermis. Many branching septate hyphae and spores were noted within the granulomatous tissue stained with PAS. A fungal culture from biopsy specimen revealed Alternaria species; pigmented hyphae and cornidia which had both transverse and longitudinal septae. The cutaneous lesions treated with terbinafine, 250 mg daily, for 3 months and 1 year later there is no evidence of recurrence.