Clinicopathological Features of Seborrheic-Like Dermatitis in HIV-Infected Adults: A Single Institutional Descriptive Cross-Sectional Study.

BACKGROUND: Atypical and severe clinical presentations of seborrheic-like dermatitis (SLD) are associated with HIV infection, correlating with advanced disease or low CD4 counts. Previous studies documented histological findings characteristic of seborrheic dermatitis in HIV-positive patients. OBJECTIVE: To expand current knowledge of the clinicopathological characteristics of SLD in South African HIV-seropositive individuals. METHODS: This prospective study included HIV-seropositive adult patients presenting with SLD to a dermatology clinic from March 2017 to April 2018. A dermatologist established the diagnosis of SLD and the severity of the disease. Detail about antiretroviral therapy (ART), the latest CD4 count, and the viral load was retrieved from the patients' clinical records. Histopathological assessment of the patients' skin biopsies was recorded using standardized data sheets and semiquantifiable grades. RESULTS: This study included 13 women and 17 men. Fifty percent of patients showed severe or very severe SLD. Six (20.0%) patients presented with erythroderma. Statistical analysis did not show a significant correlation between severity of disease and CD4 count, viral load, or ART, respectively. This study confirmed that the presence of confluent parakeratosis, necrotic keratinocytes, plasma cells, neutrophils with leukocytoclasia, and leukoexocytosis are histopathological clues to SLD occurring in HIV-seropositive patients. CONCLUSION: SLD in HIV patients may present with varying clinical severity, including erythroderma. The association between the prevalence and severity of SLD with CD4 count, viral load, and ART requires further studies with larger patient populations. The presence of specific histopathological features in a skin biopsy of SLD is a clue to the diagnosis of HIV.

An update on the microbiology, immunology and genetics of seborrheic dermatitis.

The underlying mechanism of seborrheic dermatitis (SD) is poorly understood but major scientific progress has been made in recent years related to microbiology, immunology and genetics. In light of this, the major goal of this article was to summarize the most recent articles on SD, specifically related to underlying pathophysiology. SD results from Malassezia hydrolysation of free fatty acids with activation of the immune system by the way of pattern recognition receptors, inflammasome, IL-1ß and NF-kB. M. restricta and M. globosa are likely the most virulent subspecies, producing large quantities of irritating oleic acids, leading to IL-8 and IL-17 activation. IL-17 and IL-4 might play a big role in pathogenesis, but this needs to be further studied using novel biologics. No clear genetic predisposition has been established; however, recent studies implicated certain increased-risk human leucocyte antigen (HLA) alleles, such as A*32, DQB1*05 and DRB1*01 as well as possible associations with psoriasis and atopic dermatitis (AD) through the LCE3 gene cluster while SD, and SD-like syndromes, shares genetic mutations that appear to impair the ability of the immune system to restrict Malassezia growth, partially due to complement system dysfunction. A paucity of studies exists looking at the relationship between SD and systemic disease. In HIV, SD is thought to be secondary to a combination of immune dysregulation and disruption in skin microbiota with unhindered Malassezia proliferation. In Parkinson's disease, SD is most likely secondary to parasympathetic hyperactivity with increased sebum production as well as facial immobility which leads to sebum accumulation.

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.

Increased IL-17-expressing γδ T cells in seborrhoeic dermatitis-like lesions of the Mpzl3 knockout mice.

Seborrhoeic Dermatitis (SD) is a common inflammatory skin disorder, but its molecular pathogenesis remains elusive. Previously, we have established the Mpzl3 knockout (-/-) mice as a model for SD. In this study, we focused on early phases of skin inflammation and determined the cytokine profiles and identified immune cell types in the lesional skin in the Mpzl3 -/- mice. Using flow cytometry, we detected a significant increase of CD45+ leucocytes, CD3+ T lymphocytes and especially γδ T cells but not αß T cells in the lesional skin compared to control. We also detected high levels of IL-17 and determined that the γδ T cells were a major contributing source. CD3+ and γδ T cell localization in the skin was verified by indirect immunofluorescent staining. Since neither γδ T cells nor IL-17 had been implicated in SD, our study provides novel insights into the role of MPZL3 in the pathogenesis of SD-like skin inflammation.

Dermatologic manifestations among human immunodeficiency virus patients in Morocco and association with immune status.

OBJECTIVE: The objective was to determine if the type and number of skin diseases can be clinical indicators of underlying immune status in HIV1 disease by estimating and correlating with the CD4 count and CDC stage. MATERIALS AND METHODS: This was a retrospective cross-sectional descriptive study. All consecutive patients infected with HIV1 followed at the Dermatology Department of Rabat Military Hospital between January 2008 and January 2017 were studied for dermatological manifestations, CD4 count and CDC clinical stage. RESULTS: A total of 170 patients with 304 dermatological manifestations were included. The most common dermatoses were fold dermatophytic infections (67%), genital warts (43%), herpes zoster (21%), xerosis (21%), and oral candidiasis (12%). The number of dermatologic manifestations was significantly greater in patients with CD4 count less than 200/mm3 or in stage C of the CDC classification. Five types of skin diseases (dermatophyte infections of the folds, genital warts, shingles, oral candidiasis, and seborrheic dermatitis) were significantly associated (P < 0.05) with CD4 count <200/mm3 . Seborrheic dermatitis was the only one skin disease significantly associated with AIDS stage. In multivariate analysis, genital warts (OR = 0.3, 95% CI 0.10-0.92) are independently associated with CD4 count less than 200 CD4/mm3 . CONCLUSIONS: Skin manifestations not only act as markers but also reflect the underlying immune status. Seborrheic dermatitis and genital warts appear to be a marker of immune status, and seborrheic dermatitis appears to be associated with CDC stage C, especially in their chronic and severe forms.

Mucocutaneous manifestations in human immunodeficiency virus (HIV)-infected patients in Nouakchott, Mauritania.

BACKGROUND: Mucocutaneous manifestations are one of the first clinical signs in patients infected with human immunodeficiency virus (HIV). To the best of our knowledge, there has been no previous study describing dermatologic manifestations in Mauritanians infected with HIV. The aim of the present study was to determine the profiles of mucocutaneous manifestations in relation to CD4 T cell count in HIV-positive Mauritanian patients. METHODS: A total of 86 adult patients aged > 18 years old attending the Ambulatory Treatment Center of the National Hospital of Nouakchott, Mauritania, with newly diagnosed HIV and who were not under antiretroviral treatment were included in the study in 2015. Dermatologic manifestations were documented before initiating antiretroviral treatment. RESULTS: Most of the included patients were in clinical stage 3 of the World Health Organization classification at initial diagnosis, with the mean CD4 T cell count (± SD) of 514 ± 319 cells/mm3 (range, 2-1328 cells/mm3 ), and 19 of 86 (22.1%) patients had CD4 T cell counts below 200 cells/mm3 . More than half (64%) of newly diagnosed HIV-infected patients had dermatoses, including the following: pruritic papular eruption (44.2%), seborrheic dermatitis (4.7%), Kaposi's sarcoma (3.5%), extensive xerosis cutis (2.3%), drug-induced skin reactions (1.2%), and various infectious dermatoses (dermatophyte infections [16.3%], oral candidiasis [11.6%], herpes zoster [8.1%], and scabies [2.3%]). A low CD4 T cell count (< 200 cells/mm3 ) was significantly correlated (P < 0.05) with the presence of following dermatoses: dermatophytosis, oral candidiasis, Kaposi's sarcoma, seborrheic dermatitis, and extensive xerosis cutis. CONCLUSION: Mucocutaneous lesions occur throughout the course of HIV infection, and dermatologic findings in Mauritanian HIV-positive patients are similar to those of patients in other countries. Early detection of skin disorders in some patients may help establish the diagnosis of HIV and management of HIV-associated diseases, limiting the cost of care in low-resource countries.

Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis.

BACKGROUND: Previous studies have shown the expression of histamine H4 receptor (H4R) on CD4+ T cells, especially human CD4+ Th2-polarized T cells. OBJECTIVE: This study aimed to investigate the role of H4R on these effector T cells in psoriasis. METHODS: We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4+ T cells. Then, we identified H4R expression in dermal CD4+ T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4+ T cells with several inflammatory cytokines. RESULTS: The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to Th17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4+ T cells were polarized into Th17 cells, we observed a tendency toward suppressed IL-17 secretion. CONCLUSIONS: Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4+ T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis.

Spectrum of mucocutaneous manifestations in human immunodeficiency virus-infected patients and its correlation with CD4 lymphocyte count.

In this study, 100 HIV-positive cases (63 men, 37 women) with skin findings were included. The mean CD4 T cell count was 253 cells/mm(3). A total of 235 dermatological manifestations were seen. The common infectious dermatoses were candidiasis (21%), Staphylococcal skin infections (20%), dermatophytoses (14%) and herpes zoster (6%). Among the non-infectious dermatoses were papular pruritic eruptions (20%), xerosis/ichthyosis (20%) and seborrhoeic dermatitis (16%). Statistically significant association (p < 0.05) with CD4 T cell count was seen in pyodermas, dermatophytoses and papular pruritic eruptions. Adverse drug reactions, diffuse hair loss, straightening of hairs and pigmentary changes were also noted. Although there was an absence of Kaposi's sarcoma in our study, a case of verrucous carcinoma of penis was noted.

Malassezia infections: a medical conundrum.

Malassezia yeasts have long been considered commensal fungi, unable to elicit significant damage. However, they have been associated with a diversity of cutaneous diseases, namely pityriasis versicolor, Malassezia folliculitis, seborrheic dermatitis, atopic dermatitis, psoriasis, and confluent and reticulate papillomatosis. Several hypotheses have been proposed to explain the pathogenic mechanisms of these fungi, but none have been confirmed. More recently, such organisms have been increasingly isolated from bloodstream infections raising serious concern about these fungi. Given the difficulty to culture these yeasts to proceed with speciation and antimicrobial susceptibility tests, such procedures are most often not performed and the cutaneous infections are treated empirically. The recurring nature of superficial skin infections and the potential threat of systemic infections raise the need of faster and more sensitive techniques to achieve isolation, identification, and antimicrobial susceptibility profile. This article reviews and discusses the latest available data concerning Malassezia infections and recent developments about diagnostic methods, virulence mechanisms, and susceptibility testing.

Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.

Seborrheic dermatitis (SD) is a common skin condition seen frequently in clinical practice. The use of varying terms such as sebopsoriasis, seborrheic dermatitis, seborrheic eczema, dandruff, and pityriasis capitis reflects the complex nature of this condition. Despite its frequency, much controversy remains regarding the pathogenesis of SD. This controversy extends to its classification in the spectrum of cutaneous diseases, having being classified as a form of dermatitis, a fungal disease, or an inflammatory disease, closely related with psoriasis. Some have postulated that SD is caused by Malassezia yeasts, based on the observation of their presence in affected skin and the therapeutic response to antifungal agents. Others have proposed that Malassezia is incidental to a primary inflammatory dermatosis that resulted in increased cell turnover, scaling, and inflammation in the epidermis, similar to psoriasis. The presence of host susceptibility factors, permitting the transition of M furfur to its pathogenic form, may be associated with immune response and inflammation. Metabolites produced by Malassezia species, including oleic acid, malssezin, and indole-3-carbaldehyde, have been implicated. SD also has been traditionally considered to be a form of dermatitis based on the presence of Malassezia in healthy skin, the absence the pathogenic mycelial form of Malassezia yeasts in SD, and its chronic course. As a result, proposed treatments vary, ranging from topical corticosteroids to topical antifungals and antimicrobial peptides.

Investigations of seborrheic dermatitis. Part I. The role of selected cytokines in the pathogenesis of seborrheic dermatitis.

INTRODUCTION: The etiology of seborrheic dermatitis is not fully understood. It has been observed that a number of anascogenic yeasts of Malassezia spp. is related to the intensity of the symptoms. The aim of the study is to measure the concentration of selected inflammatory factors IL-2, IL-4, IFN-γ and TNF-α in the serum by an immunoenzymatic method, as well as to confirm the relationship between the studied factors and the clinical condition of the patients (sex, the intensity of skin lesions according to the Scaparro scale) and, finally, to compare the results with the control group. MATERIAL/METHODS: The total number of subjects who participated in the study was 66. The control group (C) consisted of 30 volunteers (23 females and 7 males), with no clinical disorders, aged 24-65 (37.41±6.08 years). Thirty-six patients with seborrheic dermatitis (16 females and 20 males), aged 19-76 (38.61±13.77), made up the study group. The determination of IL-2, IL-4, IFN-γ and TNF-α was performed by ELISA using a Human High Sensitivity kit (Diaclone, France). Clinically, the intensity of the disease process was evaluated on the Scaparro et al. scale, as modified by Kaszuba. RESULTS: We observed statistically significantly higher levels of IL-2 and IFN-γ in patients with seborrheic dermatitis compared to the control group. CONCLUSIONS: We conclude that seborrheic dermatitis is a dermatosis characterized by a cell type immune response with an important role of IFN-γ and IL-2.

The LINA cohort: indoor chemical exposure, circulating eosinophil/basophil (Eo/B) progenitors and early life skin manifestations.

BACKGROUND: Hematopoietic progenitor cells, especially those committed to the Eo/B lineage, are known to contribute to allergic inflammation. OBJECTIVE: The aim of the present study was to investigate whether environmental factors are associated with changes in numbers of circulating Eo/B progenitors at 1 year of age. METHODS: Peripheral blood from 60 1-year-old children enrolled in the LINA (Lifestyle and environmental factors and their Influence on Newborns Allergy risk) birth cohort was assessed for Eo/B progenitor cells (Eo/B CFU) using standardized and validated methylcellulose assays. Frozen peripheral blood mononuclear cells (PBMC) were cultured in the presence of IL-3, IL-5 or GM-CSF, and Eo/B CFUs enumerated. Clinical outcomes and exposure to environmental tobacco smoke (ETS) were documented by standardized questionnaires, and indoor volatile organic compound (VOC) concentrations were assessed by passive sampling. RESULTS: Children with skin manifestations (atopic dermatitis or cradle cap) within the first year of life had higher numbers of circulating IL-3-, IL-5- or GM-CSF-stimulated Eo/B CFUs (P < 0.05) at 1 year. In children with cradle cap, a positive correlation was found between Eo/B CFUs and exposure to ETS-related VOCs during pregnancy or at 1 year of age (P < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: This is the first demonstration that environmental exposures are positively associated with levels of circulating Eo/B progenitors. The recruitment and differentiation of Eo/B progenitors in response to environmental triggers may play a role in the development of skin manifestations during the first year of life.

Dandruff/seborrhoeic dermatitis is characterized by an inflammatory genomic signature and possible immune dysfunction: transcriptional analysis of the condition and treatment effects of zinc pyrithione.

BACKGROUND: Dandruff/seborrhoeic dermatitis is a common scalp condition that is characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect tissue level events that are poorly understood at the molecular level. OBJECTIVES: The purpose of this work was: (i) to compare gene expression profiles in subjects with dandruff vs. those of subjects without dandruff to determine the key physiological disruptions manifest in the condition; and (ii) to determine the effect on this profile of treatment with a shampoo containing potentiated zinc pyrithione (ZPT). METHODS: In study 1, scalp biopsies were taken from 16 normal subjects and from involved and uninvolved sites in 15 subjects with dandruff. In study 2, 30 subjects with dandruff were treated for 3 weeks with a commercial ZPT shampoo (n = 15) or a vehicle (n = 15), and scalp lesional biopsies were collected at baseline and end of study for transcriptomic analysis. RNA was extracted from all biopsies and Affymetrix gene chips were used to analyse transcriptomic profiles, followed by bioinformatic analysis. RESULTS: Analysis of study 1 biopsies revealed more than 7000 individual probes differentially regulated in dandruff lesional skin relative to normal. Enriched Gene Ontology categories included: lipid metabolism, immune response, response to stimulus, apoptosis, cell proliferation, and epidermal development. The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. Induced inflammatory genes were also enriched in dandruff uninvolved skin, suggesting the existence of predisposing factors associated with inflammation. Many genes increased in lesional skin were increased at the level of protein in stratum corneum samples (e.g. IL-1RA, S100A8, S100A9, S100A11, IL-8). Under conditions known to improve overall scalp condition, the ZPT shampoo treatment in study 2 produced a transcriptomic profile resembling that of normal scalp skin. CONCLUSIONS: These data provide novel insights into the nature of dandruff and the therapeutic action of potentiated ZPT-containing shampoo, and provide a basis to explore many new mechanistic questions related to these topics.

Contact allergy to corticosteroids and Malassezia furfur in seborrhoeic dermatitis patients.

BACKGROUND: Seborrhoeic dermatitis (SD) is a chronic skin disease, requiring long-term treatment, which might promote sensitization. Malassezia furfur (Mf) plays an important role in seborrhoeic dermatitis. Objectives The aim of this study was to determine the frequency of contact sensitivity in SD patients. PATIENTS AND METHODS: A total of 100 patients and 20 healthy controls (HC) were investigated: 50 suffering from SD with no previous local corticosteroid treatment (SDN), 50 SD patients treated with local corticosteroids (SDC). Mycological examination for Mf was performed. All patients were patch tested with the baseline standard, corticosteroid series, with 12 commercial corticosteroid preparations frequently used in Croatia; and also with Mf. RESULTS: Malassezia furfur was found in 44 (88%) SDN, 37 (74%) SDC, and in 4 (20%) HC; patch test reaction to Mf was positive in one SDN and in three SDC. Positive patch tests to standard allergens were observed in 17 (34%) SDN, 33 (66%) SDC and 2 (10%) HC. Patch tests to the corticosteroid series revealed positive reactions in 4 SDC and to commercial corticosteroids in seven patients, i.e. 2 SD and 5 SDC. CONCLUSIONS: Patch tests to the baseline series and to both individual corticosteroid and commercial corticosteroid preparations should be performed in SD patients with persistent dermatitis, as contact-allergic reactions may complicate their dermatitis. Sensitization to Mf was found to be infrequent.

Identification of Malassezia species from immunocompetent and immunocompromised patients with seborrheic dermatitis.

BACKGROUND AND OBJECTIVES: Differences in prevalence, clinical and histological manifestations between seborrheic dermatitis (SD) in immunocompetent and immunocompromised patients suggest that these two populations might also differ in a spectrum of isolated Malassezia species. The purpose of our study was to analyse the prevalence of Malassezia species in immunocompromised and non-immunocompromised patients with SD and to examine if the range of isolated yeasts varies between these two study groups. PATIENTS AND METHODS: Specimens were taken from 50 patients with SD: 30 without any underlying disease and 20 with confirmed immunosuppression. The samples were obtained by scraping the skin surface of the scalp and trunk lesions of all subjects and then incubated on modified Dixon agar. The yeasts isolated were identified by their morphological and physiological properties according to Guillot et al method. RESULTS: In both groups, the most commonly isolated species from the scalp lesions were Malassenzia restricta and Malassenzia globosa, the later being the most common species isolated from lesional trunk skin. No significant differences were found between immunocompromised and immunocompetent patients from both sampled sites. CONCLUSIONS: There is no difference in the distribution of Malassezia species isolated from SD lesions between immunocompetent and immunocompromised patients. However, the much higher percentage of positive cultures in immunocompromised patients confirms that impaired cellular immunity may facilitate fungal survival on the skin.

Distribution of Malassezia species in seborrhoeic dermatitis: correlation with patients' cellular immune status.

Malassezia species are implicated in the pathogenesis of seborrhoeic dermatitis (SD), but the relationship between each species and the disorder remains unclear. It is hypothesised that the pathogenesis of SD has an immune component, which is supported by the increased incidence in patients with immunosuppressive disorders. The purpose of our study was to analyse the prevalence of Malassezia species in lesional skin of SD, and to assess the distribution of the species according to severity of the disease and cellular immune status of the patients. Forty SD patients with scalp involvement were included in the study. The samples were obtained by scraping the skin surface of the scalp and then incubated on Sabouraud dextrose agar and modified Dixon agar. The yeasts isolated were identified by their morphological and physiological properties according to the method of Guillot et al. In addition, we performed two-colour flow cytometry analysis to investigate the lymphocyte subpopulations in the peripheral blood. The most commonly isolated species was Malassezia restricta (27.5%), followed by Malassezia globosa (17.5%) and Malassezia slooffiae (15%). We demonstrated low helper/suppressor ratios in 70% patients, because of an increase in the suppressor T-cell population, suggesting an impaired cellular immunity. However, we found no significant difference in the distribution of isolated Malassezia species according to the severity of the scalp involvement and changes in the peripheral blood lymphocyte subpopulations.

Malassezia species and seborrheic dermatitis.

Malassezia spp. are medically important dimorphic, lipophilic yeasts that form part of the normal cutaneous microflora of human. Seborrheic dermatitis is a multifactor disease that needs endogenous and exogenous predisposing factors for its development. Presence of these factors leads to reproduction of the saprophytic opportunistic pathogen Malassezia spp. and development of a disease. The inflammatory reaction against the yeast Malassezia is considered basic in the etiology of the seborrheic dermatitis. The pathogenesis and exact mechanisms via which these yeasts cause inflammation are still not fully elucidated. They are rather complex and subject of controversy in literature. Most probably Malassezia spp. cause seborrheic dermatitis by involving and combining both nonummune and immune mechanisms (nonspecific and specific). Which of these mechanisms will dominate in any single case depends on the number and virulence of the yeasts as well as on the microorganism reactivity. In the recent years a great interest have been aroused by the epidemiological investigations. Depending on the geographical place of the countries different Malassezia species in seborrheic dermatitis dominate in the different countries. In view of the etiology and pathogenesis of the seborrheic dermatitis comprehensive antifungal preparations have been recently introduced and are nowadays the basic therapeutic resource in the treatment of this disease.