Invasive phaeohyphomycosis co-infection with Alternaria spp. and Curvularia spp. in a neutropenic host.

Phaeohyphomycoses are infections caused by dark-walled dematiaceous fungi. Alternaria and Curvularia are two genera of dematiaceous molds known to cause invasive fungal rhinosinusitis, particularly in immunocompromised patients. Co-infection with two dematiaceous fungi is rarely reported in the literature. This report describes a case of biopsy proven invasive fungal rhinosinusitis with Alternaria spp. and Curvularia spp. co-infection in a neutropenic host. The infection characteristics, microbiologic findings, and treatment are described.

COX Inhibition Increases Alternaria-Induced Pulmonary Group 2 Innate Lymphoid Cell Responses and IL-33 Release in Mice.

The cyclooxygenase (COX) metabolic pathway regulates immune responses and inflammation. The effect of the COX pathway on innate pulmonary inflammation induced by protease-containing fungal allergens, such as Alternaria alternata, is not fully defined. In this study, we tested the hypothesis that COX inhibition augments Alternaria-induced pulmonary group 2 innate lymphoid cell (ILC2) responses and IL-33 release. Mice were treated with the COX inhibitors indomethacin, flurbiprofen, or vehicle and challenged intranasally with Alternaria extract for four consecutive days to induce innate lung inflammation. We found that indomethacin and flurbiprofen significantly increased the numbers of ILC2 and IL-5 and IL-13 expression by ILC2 in the lung. Indomethacin also increased ILC2 proliferation, the percentages of eosinophils, and mucus production in the lung. Both indomethacin and flurbiprofen augmented the release of IL-33 in bronchoalveolar lavage fluid after Alternaria challenge, suggesting that more IL-33 was available for ILC2 activation and that a COX product(s) inhibited IL-33 release. This is supported by the in vitro finding that the COX product PGE2 and the PGI2 analogs cicaprost decreased Alternaria extract-induced IL-33 release by human bronchial epithelial cells. Although contrasting effects of PGD2, PGE2, and PGI2 on ILC2 responses have been previously reported, the overall effect of the COX pathway on ILC2 function is inhibitory in Alternaria-induced innate airway inflammation.

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 phaeohyphomycosis in a hematopoietic stem cell transplant patient caused by Alternaria rosae: First case report.

Alternaria species have been reported as a rare cause of fungal infection in organ and stem cell transplant recipients, but to date, no reports have been published of infection in humans caused by Alternaria rosae. Here, we report cutaneous A. rosae infection in a 66-year-old farmer with a history of primary myelofibrosis who had undergone allogeneic unrelated donor hematopoietic stem cell transplantation. Forty-nine days post transplant, he presented with a nodule on the thumb with no findings suggestive of disseminated infection. Pathology, culture, and molecular speciation showed the nodule was caused by cutaneous A. rosae. He had been on voriconazole as antifungal prophylaxis, but was found to have a subtherapeutic voriconazole level. He was switched to posaconazole based on published in vitro data showing its superior efficacy in Alternaria treatment. Susceptibility testing showed that the A. rosae isolate was indeed susceptible to posaconazole. His cutaneous lesion remained stable, but he died from respiratory failure secondary to lobar pneumonia. At lung autopsy, A. rosae was not identified in the lungs. We believe this to be the first published report, to our knowledge, of A. rosae infection in humans.

[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.

Unusual fungal sepsis of Alternaria alternata in acute lymphoblastic leukaemia in an adult patient.

We report a case of unusual fungal sepsis of Alternaria alternata in a patient of acute lymphoblastic leukaemia in 62-year-old male who presented with complaints of 'off and on' fever with decreased oral intake. On evaluation, haemogram showed low platelet count and 68% blast cells in peripheral blood. On flow cytometry of peripheral blood, the gated blasts (approximately 55%) highly express CD45, CD10, CD19, CD22 and condition was diagnosed as acute lymphoblastic leukaemia. He was started on standard induction treatment along with supportive therapies. During the course of treatment, two sets of paired blood cultures were sent 48 h apart. All of blood cultures were done on Bac-T alert 3D system. All of them yielded fungus. The fungus was then grown on Sabouraud's Dextrose agar media. It was identified as A. alternata. The patient condition worsened and later had cardiac arrest in ICU and could not be revived.

Successful sequential treatment with itraconazole and ALA-PDT for chromoblastomycosis because of Alternaria alternata.

Alternaria alternata is a rare etiology of phaeohyphomycosis in immunocompromised patients, which has never been reported to cause chromoblastomycosis. As far as we know, this is the first chromoblastomycosis case successfully treated with a short course of systemic antifungals and subsequent 5-aminolevulinic acid-photodynamic therapy.

Cutaneous alternariosis in a renal transplant recipient.

Alternariosis is a fungal infection that is usually described in immunocompromised patients. We report a case of cutaneous alternariosis in a renal transplant recipient caused by Alternaria tenuissima. The diagnosis was supported by histopathologic (ie, yeastlike cells, filamentous structures) and mycologic findings from a cutaneous biopsy. Cutaneous lesions regressed 1 month following a decrease in the dosage of immunosuppressive therapy. The patient also was treated with intravenous amphotericin B followed by oral fluconazole without improvement. Cryotherapy remarkably accelerated healing of the lesions.

Alternaria-derived serine protease activity drives IL-33-mediated asthma exacerbations.

BACKGROUND: The fungal allergen Alternaria alternata is implicated in severe asthma and rapid onset life-threatening exacerbations of disease. However, the mechanisms that underlie this severe pathogenicity remain unclear. OBJECTIVE: We sought to investigate the mechanism whereby Alternaria was capable of initiating severe, rapid onset allergic inflammation. METHODS: IL-33 levels were quantified in wild-type and ST2(-/-) mice that lacked the IL-33 receptor given inhaled house dust mite, cat dander, or Alternaria, and the effect of inhibiting allergen-specific protease activities on IL-33 levels was assessed. An exacerbation model of allergic airway disease was established whereby mice were sensitized with house dust mite before subsequently being challenged with Alternaria (with or without serine protease activity), and inflammation, remodeling, and lung function assessed 24 hours later. RESULTS: Alternaria, but not other common aeroallergens, possessed intrinsic serine protease activity that elicited the rapid release of IL-33 into the airways of mice through a mechanism that was dependent upon the activation of protease activated receptor-2 and adenosine triphosphate signaling. The unique capacity of Alternaria to drive this early IL-33 release resulted in a greater pulmonary inflammation by 24 hours after challenge relative to the common aeroallergen house dust mite. Furthermore, this Alternaria serine protease-IL-33 axis triggered a rapid, augmented inflammation, mucus release, and loss of lung function in our exacerbation model. CONCLUSION: Alternaria-specific serine protease activity causes rapid IL-33 release, which underlies the development of a robust TH2 inflammation and exacerbation of allergic airway disease.

Alternaria keratitis and hypopyon after clear-cornea phacoemulsification.

UNLABELLED: We report a case of Alternaria keratitis and hypopyon following clear-corneal cataract surgery. A 66-year-old woman presented with a painful red left eye several months after uneventful self-sealing clear-corneal phacoemulsification that was unresponsive to prolonged treatment with topical/oral quinolones and topical corticosteroids. A full-thickness stromal white dense infiltrate in the area of the intrastromal tunnel incision and a 2.0 mm hypopyon were observed. Culture from corneal scrapings revealed Alternaria species. Treatment included topical and subconjunctival injections of amphotericin-B (5 mg/mL) and 200 mg of oral ketoconazole. Complete resolution of the corneal infiltration and hypopyon was observed after 30 days of treatment, with no recurrence during 6 years of follow-up. To our knowledge, this is the first report of Alternaria species keratitis complicating self-sealing clear-corneal cataract surgery. Topical and subconjunctival injections of amphotericin-B and oral ketoconazole were effective in resolving the corneal abscess and anterior chamber inflammatory reaction. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Alternaria alternata in a case of mass in the lung.

A 50-year-old woman, an agriculture worker with diabetes and asthma presented to us with complaints of fever with chills, cough with scanty, mucopurulent sputum and dull aching chest pain in right mammary area radiating to axilla. Chest X-ray and computed tomography scan revealed mass in the right lung. Ultrasound guided fine-needle aspiration cytology was done and the greenish fluid on direct wet mount and inoculation on Sabouraud's dextrose agar isolated Alternaria species. Serum specimen was evaluated for immunoglobulin E specific titres for Alternaria species which was high. Patient was treated with fluconazole for 6 weeks after which the symptoms disappeared and chest X-ray was normal.

Cutaneous alternariosis with trichosporon infection in a heart transplant recipient: a case report.

Cutaneous alternariosis infection occurs mainly in immunocompromised individuals. The incidence of alternariosis in a heart transplant recipient is infrequent. Coincidence of the aforementioned infection with additional fugal agents is rare. We describe a case of alternariosis with Trichosporon fungal infection in a patient who was successfully treated with combined antifungal therapy, modulation of immunosuppressive regimen, and blood glucose management. The patient had a good response to treatment, and has had an uneventful 1-year follow-up at the time of this writing.

A rare case of allergic bronchopulmonary mycosis caused by Alternaria alternata.

A rare case of allergic bronchopulmonary mycosis (ABPM), caused by Alternaria alternata, is reported in an immunocompetent resident of Delhi. Her complaints included a generalized, urticarial skin rash and occasional pain in the right lower chest. Her differential count showed eosinophils, 22%; absolute eosinophil count (AEC), 2400 cells/µl; and total IgE, 4007 IU/ml. The computerised tomogram (CT) scan of her thorax showed an enhancing lesion with surrounding ground glass haziness in the right lower lobe. Histopathologic examination of the resected lung revealed a necrotizing granulomatous inflammation, parenchymal infiltration by eosinophils, lymphocytes, neutrophils, plasma cells and some exudative bronchiolitis suggestive of ABPM. Observation of KOH wet mounts of repeat sputum and BAL samples demonstrated the presence of septate, brownish hyphae and cultures of these specimens yielded A. alternata (identified by sequencing of the ITS region). Her serum showed a three-fold higher specific IgE to A. alternata antigens than control levels, and the type I cutaneous hypersensitivity response to antigens of A. alternata was strongly positive. She was treated successfully with oral glucocorticoids and itraconazole. To our knowledge, ABPM due to Alternaria alternata has not been reported previously.

Cutaneous alternariosis microscopically mimicking blastomycosis.

A 57-year-old man status post several myocardial infarcts and heart transplantation presented with a slowly growing violaceous plaque on his lateral left knee at the site of prior minor trauma. A biopsy revealed a suppurative dermatitis with associated pseudocarcinomatous epithelial hyperplasia. There were multiple non-pigmented eosinophilic organisms with clear cytoplasmic halos within the infiltrate. A methenamine silver stain showed round to ovoid organisms of slightly variable size. Rare uni-polar budding, some of which was broad based, was apparent. A few short hyphae with indeterminate septa were also noted. Fontana-Masson, mucicarmine, Alcian blue and Fite stains were all negative. These findings suggested a diagnosis of blastomycosis. However, a fungal culture grew colonies of Alternaria species. Alternariosis has been previously shown to possess morphologic characteristics that can simulate other fungal infections. To our knowledge, a striking similarity to blastomycosis, as seen in our case, has not been previously reported. Dermatopathologists should be aware that alternariosis may mimic blastomycosis, especially when hyphal forms are rare or absent in tissue specimens. Culture is necessary for definitive classification.