Toxic epidermal necrolysis complicated with primary cutaneous aspergillosis: A report of four cases.

Primary cutaneous aspergillosis (PCA) is a rare opportunistic infection caused by Aspergillus that can be life-threatening. PCA is mainly reported in immunocompromised hosts such as patients with AIDS, those with hematologic malignancy, or infants with occlusive dressings. However, no study has previously reported PCA associated with toxic epidermal necrolysis (TEN). This study reports four cases of TEN complicated with PCA, presenting with discrete gray or black spots over newly formed epithelia. Risk factors of PCA in patients with TEN include host factors, iatrogenic factors, indoor environment, and wound care. Two of the four cases eventually died, highlighting the importance of further exploring PCA in patients with TEN.

Mucocutaneous mycoses in people living with human immunodeficiency virus in Indonesia.

BACKGROUND: To date, integrated care for people living with human immunodeficiency virus (PLHIV) has improved. However, although the management of mucocutaneous mycosis cases has improved, disease progression might be different in immunocompromised patients, which leads to variable clinical manifestations. OBJECTIVES: To describe the characteristics of mucocutaneous mycosis cases in the PLHIV population and its associated factors in Indonesia. METHODS: This retrospective study was conducted from January 2014 to December 2018 in four academic hospitals. Data were acquired from medical records with the inclusion of mucocutaneous mycosis patients with concurrent HIV infection. Analysis with the chi-squared test was performed using Statistical Package for the Social Sciences (SPSS) version 20.0. RESULTS: A total of 1,796 cases of mucocutaneous mycoses were identified in 1782 PLHIV. The most common types of infection were candidiasis (63%), followed by dermatophytosis (35.1%), and malasseziosis (1.9%), which were significantly higher in PLHIV with CD4 level <200 cells/mm3 . The proportions of male gender (78.6% vs. 56.3%, p < .001), high level of education (48.0% vs. 64.1%, p < .001), office workers (73.8% vs. 64.1%, p < .001), combination of topical and systemic antifungal agents (59.1% vs. 48.5%, p = .006) and not receiving antiretroviral therapy (63.2% vs. 7.8%, p < .001) were significantly higher in PLHIV with a CD4 level <200 cells/mm3 . CONCLUSION: In Indonesia, the most common fungal infection in PLHIV is candidiasis. This study also addressed the important matters regarding mucocutaneous mycoses in PLHIV. Education is an important measure to prevent the incidence of cutaneous mycoses in PLHIV, especially in high-risk groups.

Histoplasma capsulatum var. duboisii: A KwaZulu-Natal, South Africa public sector perspective.

BACKGROUND: Histoplasma capsulatum var. duboisii (H. duboisii) causes potentially fatal disease in the immunocompromised patient, and the literature on these cases is limited. The study was undertaken to describe the cases of H. duboisii seen in a resource-limited setting. METHODS: A 5-year retrospective, laboratory-based histopathologic review of all H. duboisii cases. RESULTS: A total of 24 patients were diagnosed with cutaneous H. duboisii infection. The male-to-female ratio was 1.4. All the patients were human immunodeficiency virus (HIV) positive, and 70.83% (17 of 24 patients) were on antiretroviral therapy. The clinically identified lesions were as follows: plaques, nodular plaques, papules, papulo-pustules, and umbilicated papules. Histopathological appraisal revealed organisms typical of H. duboisii. The commonest epidermal alterations were interface change, parakeratosis, spongiosis, ulceration, acanthosis, hyperkeratosis, transepidermal elimination, and exocytosis in decreasing order. The dermal changes included histiocytic pattern (n = 14), neutrophil-rich (n = 13), non-necrotizing granulomatous inflammation (n = 9), and karyorrhexis (n = 6). Histoplasma was confirmed in 53% (8 of 15 samples) of the tissue samples submitted for routine fungal culture. CONCLUSION: This study showed the demographics, clinical and histopathology features of H. duboisii infection in a resource-limited setting. Further research on histopathological features of this rare infection is essential to expand on the knowledge base and support findings in this study.

Seborrheic dermatitis-Looking beyond Malassezia.

Seborrhoeic Dermatitis (SD) is a very common chronic and/or relapsing inflammatory skin disorder whose pathophysiology remains poorly understood. Yeast of the genus Malassezia has long been regarded as a main predisposing factor, even though causal relationship has not been firmly established. Additional predisposing factors have been described, including sebaceous activity, host immunity (especially HIV infection), epidermal barrier integrity, skin microbiota, endocrine and neurologic factors, and environmental influences. Genetic studies in humans and mouse models-with particularly interesting insights from examining the Mpzl3 knockout mice and their SD-like skin phenotype, and patients carrying a ZNF750 mutation-highlight defects in host immunity, epidermal barrier and sebaceous activity. After synthesizing key evidence from the literature, we propose that intrinsic host factors, such as changes in the amount or composition of sebum and/or defective epidermal barrier, rather than Malassezia, may form the basis of SD pathobiology. We argue that these intrinsic changes provide favourable conditions for the commensal Malassezia to over-colonize and elicit host inflammatory response. Aberrant host immune activity or failure to clear skin microbes may bypass the initial epidermal or sebaceous abnormalities. We delineate specific future clinical investigations, complemented by studies in suitable SD animal models, that dissect the roles of different epidermal compartments and immune components as well as their crosstalk and interactions with the skin microbiota during the process of SD. This research perspective beyond the conventional Malassezia-centric view of SD pathogenesis is expected to enable the development of better therapeutic interventions for the management of recurrent SD.

Angioinvasive fungal infections impacting the skin: Diagnosis, management, and complications.

As discussed in the first article in this continuing medical education series, angioinvasive fungal infections pose a significant risk to immunocompromised and immunocompetent patients alike, with a potential for severe morbidity and high mortality. The first article in this series focused on the epidemiology and clinical presentation of these infections; this article discusses the diagnosis, management, and potential complications of these infections. The mainstay diagnostic tests (positive tissue culture with histologic confirmation) are often supplemented with serum biomarker assays and molecular testing (eg, quantitative polymerase chain reaction analysis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry) to ensure proper speciation. When an angioinvasive fungal infection is suspected or diagnosed, further workup for visceral involvement also is essential and may partially depend on the organism. Different fungal organisms have varied susceptibilities to antifungal agents, and knowledge on optimal treatment regimens is important to avoid the potential complications associated with undertreated or untreated fungal infections.

Angioinvasive fungal infections impacting the skin: Background, epidemiology, and clinical presentation.

Angioinvasive fungal infections cause significant morbidity and mortality because of their propensity to invade blood vessel walls, resulting in catastrophic tissue ischemia, infarct, and necrosis. While occasionally seen in immunocompetent hosts, opportunistic fungi are emerging in immunosuppressed hosts, including patients with hematologic malignancy, AIDS, organ transplant, and poorly controlled diabetes mellitus. The widespread use of antifungal prophylaxis has led to an "arms race" of emerging fungal resistance patterns. As the at-risk population expands and new antifungal resistance patterns develop, it is critical for dermatologists to understand and recognize angioinvasive fungal pathogens, because they are often the first to encounter the cutaneous manifestations of these diseases. Rapid clinical recognition, histopathologic, and culture confirmation can help render a timely, accurate diagnosis to ensure immediate medical and surgical intervention. Superficial dermatophyte infections and deep fungal infections, such as blastomycosis and histoplasmosis, have been well characterized within the dermatologic literature, and therefore this article will focus on the severe infections acquired by angioinvasive fungal species, including an update on new and emerging pathogens. In the first article in this continuing medical education series, we review the epidemiology and cutaneous manifestations. The second article in the series focuses on diagnosis, treatment, and complications of these infections.

The color of skin: black diseases of the skin, nails, and mucosa.

Gradations in skin color are a consequence of differing amounts of melanin and their varying distribution. Although many darkly pigmented skin lesions are melanocytic and can be attributed to melanin content, the color of a black lesion can also be due to blood, necrotic tissue, or exogenous pigment. The source, pattern, and distribution of the color in black lesions usually offer important insight into its etiology. This contribution reviews conditions that can take on a black color, discussing the cause of the hue and any additional impact sun exposure may have.

A suppurative thyroiditis and perineal subcutaneous abscess related with aspergillus fumigatus: a case report and literature review.

BACKGROUND: Invasive aspergillosis is a complication in immunocompromised patients and commonly detected in patients with hematological malignancies, which mostly affect the lungs. Because of its high iodine content, rich blood supply and capsule, the thyroid is considered to be less prone to microbial invasion thus most infectious thyroiditis cases are caused by bacteria. However, a few case reports have described thyroid gland aspergilloses, most of which were due to disseminated invasive aspergillosis. CASE PRESENTATION: We first report a case of thyroid gland and subcutaneous labium majus aspergillosis in a Chinese patient who received long-term glucocorticoid treatment for systemic lupus erythematosus (SLE) and lupus nephritis, and then we reviewed 36 articles describing similar aspergillus infections in 41 patients. CONCLUSION: We included 29 cases of diagnosed aspergillus thyroiditis and analyzed clinical findings, treatments and outcomes to provide clinical information for diagnosis and prognosis of thyroiditis caused by Aspergillus fumigatus.

Fungal Osteomyelitis in Diabetic Foot Infections: A Case Series and Comparative Analysis.

Fungal osteomyelitis (OM) is relatively rare. There is scarce literature discussing fungal OM in diabetic foot infections (DFIs). This case series explores the clinical characteristics of patients treated at a large tertiary academic center for DFI and found to have a causative agent of fungal origin in their bone on surgical intervention. Between July 2017 and March 2018, a prospective longitudinal analysis was performed of patients with diabetes admitted to our institution who underwent operative management of OM. Demographic, clinical, radiographic, and laboratory data were collected for all patients. Data between bacterial and fungal OM cohorts was analyzed for differences and similarities in patient characteristics and outcomes. All patients were followed 20 weeks postoperatively. Five patients with fungal OM were identified from the 35 cases where OM was confirmed through podiatric surgical intervention. In each fungal case, a Candida species was isolated from operative bone culture which included subspecies Candida albicans, C parapsilosis, and C glabrata. A P value ⩾.05 was found in clinical characteristics between our cohorts. Wound healing was achieved in 40% of patients with fungal OM, and oral fluconazole successfully treated Candida OM in the cases that achieved healing. Diabetes can increase the risk of Candida OM. In DFIs, fungus can impede wound healing if not recognized and treated. Because Candida OM is typically indolent in nature, bone biopsy and mycological culture is recommended for definitive diagnosis and treatment.

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations.

Keratitis-ichthyosis-deafness syndrome accompanied by disseminated cutaneous fungal infection.

Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis. It is mostly associated with mutations of the connexin 26 gene, resulting in keratitis, erythrokeratoderma and neurosensory deafness. In addition to the clinical triad, the KID syndrome patients are at high risk for infectious complications, while the mechanisms are poorly understood. In the present article, we described an Asian case of KID syndrome accompanied by fungal infection. The present study was designed to define the mutation type, and further to explore the interaction between the innate immunity response and the infectious complication of KID syndrome. Genomic DNA was extracted from peripheral blood for mutation analysis. Isolation and identification of the species were carried out to confirm the infectious microorganism. Three biopsy specimens from different parts of the body (right thigh, abdomen and forehead, respectively) were carried out for histopathological and immunohistochemical analysis. Furthermore, quantitative polymerase chain reaction (PCR) was carried out to study the expression of Toll-like receptor 2 (TLR2) on the epidermis of the right thigh. We identified a mutation (p.G12R) in the GJB2 gene in this patient with Trichophyton rubrum infection. Immunohistochemistry staining revealed a lower expression of TLR2 and no significant difference in TLR4. Meanwhile, PCR showed a relatively slight increase of TLR2 RNA expression. These results indicated that GJB2 mutation (p.G12R) in this case of KID syndrome, which was susceptible to T. rubrum infection, might be attributed to a limited native immune response.

Progressive cutaneous Cryptococcosis complicated with meningitis in a myasthenia gravis patient on long-term immunosuppressive therapy - a case report.

BACKGROUND: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV-infected individuals, especially in the settings of very low CD4 count. Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare and usually signifies a marked immunodeficiency. Cryptococcosis in association with myasthenia gravis or thymoma has been previously documented in only very few cases in the literature. CASE PRESENTATION: We reported a complicated case of severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with myasthenia gravis on long-term immunosuppressive therapy. The patient presented with a five month history of recurrent and progressive skin lesions that later on progressed into cryptococcal meningitis. CONCLUSION: Through this case, we aimed to emphasize the importance of including cutaneous cryptococcosis in the differential diagnosis of cutaneous lesions in patients on chronic immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be the first clue for a disseminated disease, which makes early recognition crucial and life-saving.

Purple patches in an immunocompromised patient: a report of secondary disseminated cutaneous mucormycosis in a man with chronic lymphocytic leukemia.

A 60-year-old man with chronic lymphocytic leukemiadeveloped a deeply violaceous annular patchwith a halo of erythema on the right thigh duringhospitalization for neutropenic fever. Associatedsymptoms included chronic cough and fatigue.Bilateral lung opacities with hilar lymphadenopathywere noted on chest computed tomographyscan. Punch biopsy and tissue culture confirmeda diagnosis of secondary disseminated cutaneousmucormycosis. Although rare, physicians shouldinclude mucormycosis in the differential diagnosisof purpuric patches in immunosuppressed patients.Prompt skin biopsy and tissue culture may optimizethe success of treatment.

A Case Report of Widespread Majocchi's Granuloma in a Patient with Systemic Lupus Erythematosus.

Majocchi's granuloma is an intracutaneous or subcutaneous granulomatous inflammation caused by invasion of dermatophytic fungus, especially Trichophyton rubrum. This type of lesion is misdiagnosed frequently without proper auxiliary examination. Here, we report a case of widespread Majocchi's granuloma caused by T. rubrum in a 35-year-old woman with systemic lupus erythematosus for 9 years. The patient was initially misdiagnosed as SLE-associated skin lesions, which delayed her treatment and resulted in severe multiple disseminated lesions. After confirmed as Majocchi's granuloma, the patient was cured after 11-month treatment with terbinafine.

Skin lesion in a patient with acute myeloid leukemia.

We present the case of a 51-year-old man with acute myeloid leukemia who developed fevers with a skin lesion following the first cycle of induction chemotherapy. Skin biopsy showed evidence of invasive fungal infection. Cultures remained negative, but polymerase chain reaction on tissue detected Rhizopus oryzae complex. The patient was started on liposomal amphotericin B and underwent surgical debridement. He was switched to posaconazole, with plans for allogeneic hematopoetic stem cell transplant in the future.

Invasive cutaneous infection due to Scopulariopsis brevicaulis unsuccessfully treated with high-dose micafungin in a neutropenic patient.

Scopulariopsis brevicaulis onychomycosis with local cutaneous invasion was diagnosed in an acute leukemia patient and unsuccessfully treated with high-dose micafungin, based on antifungal susceptibility testing. This case should alert clinicians to the possible severe evolution of onychomycosis in neutropenic patients and suggests that surgery should be preferred in such a situation.

Primary cutaneous aspergillosis and idiopathic bone marrow aplasia.

We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients.