Chronic Mucocutaneous Candidiasis Research Articles

Qualitative Immunoglobulin Deficiency Causes Bacterial Infections in Patients with STAT1 Gain-of-Function Mutations.

STAT1 is a transduction and transcriptional regulator that functions within the classical JAK/STAT pathway. In addition to chronic mucocutaneous candidiasis, bacterial infections are a common occurrence in patients with STAT1 gain-of-function (GOF) mutations. These patients often exhibit skewing of B cell subsets; however, the impact of STAT1-GOF mutations on B cell-mediated humoral immunity remains largely unexplored. It is also unclear whether these patients with IgG within normal range require regular intravenous immunoglobulin (IVIG) therapy. Eleven patients (harboring nine different STAT1-GOF mutations) were enrolled. Reporter assays and immunoblot analyses were performed to confirm STAT1 mutations. Flow cytometry, deep sequencing, ELISA, and ELISpot were conducted to assess the impact of STAT1-GOF on humoral immunity. All patients exhibited increased levels of phospho-STAT1 and total STAT1 protein, with two patients carrying novel mutations. In vitro assays showed that these two novel mutations were GOF mutations. Three patients with normal total IgG levels received regular IVIG infusions, resulting in effective control of bacterial infections. Four cases showed impaired affinity and specificity of pertussis toxin-specific antibodies, accompanied by reduced generation of class-switched memory B cells. Patients also had a disrupted immunoglobulin heavy chain (IGH) repertoire, coupled with a marked reduction in the somatic hypermutation frequency of switched Ig transcripts. STAT1-GOF mutations disrupt B cell compartments and skew IGH characteristics, resulting in impaired affinity and antigen-specificity of antibodies and recurrent bacterial infections. Regular IVIG therapy can control these infections in patients, even those with normal total IgG levels.

A novel mutation site in STAT in a chronic mucocutaneous candidiasis pediatric patient with disseminated cryptococcosis: Case report and review of the literature

A novel mutation site in STAT in a chronic mucocutaneous candidiasis pediatric patient with disseminated cryptococcosis: Case report and review of the literature

STAT1 Mutations in Chronic Mucocutaneous Candidiasis Diagnosed in an Adult.

A 30-year-old man presented with oral candidiasis and a history of lung abscess. He experienced recurring oral and skin candidiasis in childhood but spent long periods without any infections. Therefore, immunodeficiency was suspected. T and B lymphocyte and natural killer cell counts as well as immunoglobulin levels were normal. Human immunodeficiency virus test results were negative. Therefore, we suspected chronic mucocutaneous candidiasis (CMC). The signal transducer and activator of transcription (STAT) mutation, the leading cause of CMC, was detected by exome sequencing. Most cases of STAT1 mutations are diagnosed in childhood, but a few are diagnosed in adulthood because Candida infections may not be severe.

Patients with STAT1 Gain-of-function Mutations Display Increased Apoptosis which is Reversed by the JAK Inhibitor Ruxolitinib

IntroductionThe signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity.MethodsIn our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation.ResultsSTAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment.ConclusionIn STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

Mucocutaneous Candidiasis: Insights Into the Diagnosis and Treatment.

Recent progress in the methods of genetic diagnosis of inborn errors of immunity has contributed to a better understanding of the pathogenesis of chronic mucocutaneous candidiasis (CMC) and potential therapeutic options. This review describes the latest advances in the understanding of the pathophysiology, diagnostic strategies, and management of chronic mucocutaneous candidiasis.

Early recognition of the APECED rash can accelerate the diagnosis of APECED

Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) is a monogenic autoimmune disease most often resulting from biallelic loss-of-function variants in the autoimmune regulator (AIRE) gene. Although typically characterized by the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, we have recently reported that the clinical spectrum of the syndrome is far broader that previously described and that incorporation of an adjunct triad of APECED rash, autoimmune enteritis-associated intestinal dysfunction, and enamel hypoplasia in the classic triad manifestations could lead to earlier diagnosis. Among the adjunct triad manifestations, APECED rash occurs in 66 % of American APECED patients by age 3, most often developing in the first year of life. Here, we describe the clinical and histological features of protracted APECED rash manifesting together with recurrent mucocutaneous candidiasis as the first two disease components of APECED in a 10-month-old girl.

Increased type 1 inflammation in gynecologic cervicovaginal samples in patients with APS-1

Inborn errors of immunity offer important insights into mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1), chronic mucocutaneous candidiasis has been ascribed to neutralizing IL-17 autoantibodies. Recent evidence implicates excessive T-cell IFN-γ secretion and ensuing epithelial barrier disruption in predisposition to candidiasis, but these results remain to be replicated. Whether IL-17 paucity, increased type I inflammation, or their combination underlies susceptibility to chronic mucocutaneus candidiasis in APS-1 is debated. Our aim was to characterize the immunologic features in the cervicovaginal mucosa of females with APS-1. Vaginal fluid was collected with a flocked swab from 17 females with APS-1 and 18 controls, and cytokine composition was analyzed using Luminex (Luminex Corporation, Austin, Tex). Cervical cell samples were obtained with a cervix brush from 6 patients and 6 healthy controls and subjected to transcriptome analysis. The vaginal fluid samples from patients with APS-1 had IFN-γ concentrations comparable to those of the controls (2.6 vs 2.4 pg/mL) but high concentrations of the TH1 chemokines CXCL9 and CXCL10 (1094 vs 110 pg/mL [P< .001] and 4033 vs 273 pg/mL [P= .001], respectively), whereas the IL-17 levels in the samples from the 2 groups were comparable (28 vs 8.8 pg/mL). RNA sequencing of the cervical cells revealed upregulation of pathways related to mucosal inflammation and cell death in the patients with APS-1. Excessive TH1 cell response appears to underlie disruption of the mucosal immune responses in the genital tract of patients with APS-1 and may contribute to susceptibility to candidiasis in the genital tract as well.

Progress in molecular diagnosis and treatment of chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membrane. It is a rare and severe disease resulting from autoimmune defects or immune dysregulations. Nonetheless, the diagnosis and treatment of CMC still pose significant challenges. Erroneous or delayed diagnoses remain prevalent, while the long-term utility of traditional antifungals often elicits adverse reactions and promotes the development of acquired resistance. Furthermore, disease relapse can occur during treatment with traditional antifungals. In this review, we delineate the advancements in molecular diagnostic and therapeutic approaches to CMC. Genetic and biomolecular analyses are increasingly employed as adjuncts to clinical manifestations and fungal examinations for accurate diagnosis. Simultaneously, a range of therapeutic interventions, including Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), cytokines therapy, novel antifungal agents, and histone deacetylase (HDAC) inhibitors, have been integrated into clinical practice. We aim to explore insights into early confirmation of CMC as well as novel therapeutic options for these patients.

Cutaneous Manifestations in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED): A Comprehensive Review.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), or polyglandular autoimmune syndrome type 1 (PAS-1/APS-1), is a rare autosomal recessive disorder linked to mutations in the autoimmune regulator (AIRE) gene. This review provides a detailed analysis of cutaneous manifestations in APECED, focusing on chronic mucocutaneous candidiasis (CMC), alopecia areata (AA), and vitiligo. The classic triad of hypoparathyroidism, adrenal insufficiency, and CMC serves as a diagnostic cornerstone. However, the varied clinical spectrum of APECED, particularly its cutaneous presentations, poses a diagnostic challenge. CMC, often an early sign, varies in prevalence across populations, including Finnish (100%), Irish (100%), Saudi Arabian (80%), Italian (60-74.7%), North American (51-86%), and Croatian (57.1%) populations. Similarly, AA prevalence varies in different populations. Vitiligo also exhibits variable prevalence across regions. The review synthesizes the current knowledge arising from a narrative analysis of 14 significant human studies published in English up to October 2023. Moreover, this paper underscores the importance of early detection and monitoring, emphasizing cutaneous manifestations as key diagnostic indicators. Ongoing research and clinical vigilance are crucial for unraveling the complexities of this rare autoimmune syndrome and enhancing patient care.

Plaque Patterned Cutaneous Candidiasis on the Lower Legs: A Case Report

Diabetes mellitus (DM) is a metabolic disorder that causes chronic hyperglycemia, leading to immune dysfunction and increased vulnerability to infections. As a result, patients with DM are more susceptible to fungal infections, including Candida species, due of their weakened immune systems. Cutaneous candidiasis is a fungal infection that appears as a red plaque with peripheral satellite papules and pustules around the periphery. Patients with chronic mucocutaneous candidiasis may have erythematous plaques and thickened skin thickening with an overlying scale, which can mimic plaque psoriasis. Therefore, fungal infections should be considered when assessing chronic refractory psoriasiform lesions that are difficult to treat, especially in patients with DM. This report describes a case of cutaneous candidiasis in both lower legs, which was initially misdiagnosed as psoriasis.

Isolated Chronic Mucocutaneous Candidiasis due to a Novel Duplication Variant of IL17RC.

Inborn errors of the IL-17A/F-responsive pathway lead to chronic mucocutaneous candidiasis (CMC) as a predominant clinical phenotype, without other significant clinical manifestations apart from mucocutaneous staphylococcal diseases. Among inborn errors affecting IL-17-dependent immunity, autosomal recessive (AR) IL-17RC deficiency is a rare disease with only three kindreds described to date. The lack of an in vitro functional evaluation system of IL17RC variants renders its diagnosis difficult. We sought to characterize a 7-year-old Japanese girl with CMC carrying a novel homozygous duplication variant of IL17RC and establish a simple in vitro system to evaluate the impact of this variant. Flow cytometry, qPCR, RNA-sequencing, and immunoblotting were conducted, and an IL17RC-knockout cell line was established for functional evaluation. The patient presented with oral and mucocutaneous candidiasis without staphylococcal diseases since the age of 3 months. Genetic analysis showed that the novel duplication variant (Chr3: 9,971,476-9,971,606 dup (+131bp)) involving exon 13 of IL17RC results in a premature stop codon (p.D457Afs*16 or p.D457Afs*17). Our functional evaluation system revealed this duplication to be loss-of-function and enabled discrimination between loss-of-function and neutral IL17RC variants. The lack of response to IL-17A by the patient's SV40-immortalized fibroblasts was restored by introducing WT-IL17RC, suggesting that the genotype identified is responsible for her clinical phenotype. The clinical and cellular phenotype of the current case of AR IL-17RC deficiency supports a previous report on this rare disorder. Our newly established evaluation system will be useful for the diagnosis of AR IL-17RC deficiency, providing accurate validation of unknown IL17RC variants.

Human STAT1 gain of function with chronic mucocutaneous candidiasis: A comprehensive review for strengthening the connection between bedside observations and laboratory research.

Germline human heterozygous STAT1 gain-of-function (GOF) variants were first discovered a common cause of chronic mucocutaneous candidiasis (CMC) in 2011. Since then, numerous STAT1 GOF variants have been identified. A variety of clinical phenotypes, including fungal, viral, and bacterial infections, endocrine disorders, autoimmunity, malignancy, and aneurysms, have recently been revealed for STAT1 GOF variants, which has led to the expansion of the clinical spectrum associated with STAT1 GOF. Among this broad range of complications, it has been determined that invasive infections, aneurysms, and malignancies are poor prognostic factors for STAT1 GOF. The effectiveness of JAK inhibitors as a therapeutic option has been established, although further investigation of their long-term utility and side effects is needed. In contrast to the advancements in treatment options, the precise molecular mechanism underlying STAT1 GOF remains undetermined. Two primary hypotheses for this mechanism involve impaired STAT1 dephosphorylation and increased STAT1 protein levels, both of which are still controversial. A precise understanding of the molecular mechanism is essential for not only advancing diagnostics but also developing therapeutic interventions. Here, we provide a comprehensive review of STAT1 GOF with the aim of establishing a stronger connection between bedside observations and laboratory research.

FRI054 Partial Lipodystrophy As A Manifestation Of Autoimmune Polyglandular Syndrome 1

Abstract Disclosure: S. Agarwal: None. C. Xing: None. M.S. Anderson: Stock Owner; Self; Medtronic Diabetes, Merck. A. Garg: None. Background: Autoimmune polyglandular syndrome 1 (APS1) is a rare autosomal recessive disorder due to mutations in AIRE gene that manifests mainly with chronic mucocutaneous candidiasis, primary hypoparathyroidism and adrenal insufficiency. We report an extremely rare APS1 patient who developed partial lipodystrophy during adulthood. Clinical Case: This 39-year-old white female developed frequent diaper rashes, oral thrush and tetany at the age of one year due to candidiasis and hypoparathyroidism. At 6 years, she developed hypothyroidism. At 11 years, she developed fatigue, excessive thirst, and anorexia due to primary adrenal insufficiency. At 13 years of age, she had thelarche and adrenarche but never attained menarche. At 14 years, she underwent a sibling matched allogenic bone marrow transplant due to multiple antibiotic-refractory fungal infections. At 35 years, her serum triglycerides level was 904 mg/dL and loss of subcutaneous fat from the upper and lower extremities and hips was noted but she had increased subcutaneous fat on the chest and abdomen as well as buffalo hump. Thigh skinfold thickness was 8 mm (&amp;lt;10th percentile of normal). A whole-body dual-energy X-ray absorptiometry revealed a total body fat of 38% with lower extremity fat of 25%-27% (&amp;lt;1st percentile of normal). Whole exome sequencing on DNA extracted from saliva revealed two pathogenic variants in AIRE gene; c.83T&amp;gt;C; p.Leu28Pro and c.769C&amp;gt;T; p.Arg257* confirming the diagnosis of APS1. No other pathogenic variants were noted in the known lipodystrophy genes. Serum was negative for anti-perilipin 1 autoantibody. Discussion: Biallelic mutations in the AIRE hinder the process of selective apoptosis of T-cells in the thymic medulla that have a strong affinity to self-antigens leading to autoimmunity manifesting as APS1. Previously, a 5-year-old boy with APS1 was reported to develop generalized lipodystrophy and his serum was positive for anti-perilipin 1 autoantibody. Recently, serum anti-perilipin-1 autoantibodies have also been reported in the Aire gene knock out mice. In contrast, our patient has partial lipodystrophy and was negative for anti-perilipin 1 autoantibody. This suggests that patients with APS1 may harbor many different autoantibodies against adipocyte expressed proteins and develop different patterns of autoimmune lipodystrophies. Presentation: Friday, June 16, 2023

Antifungal activity of silver nanoparticles loaded oregano oil nano-emulsion for topical treatment of mucocutaneous candidiasis

Oregano essential oil (OEO) possesses antimicrobial, antioxidant, and preservative properties, making it a promising candidate for various biotechnological and biomedical applications. However, the inherent volatility, hydrophobicity, and susceptibility to external factors such as light, heat, and oxygen can compromise its stability and bioactivity. To overcome these limitations, silver nanoparticles (AgNPs) were incorporated into an oregano oil nanoemulsion, enhancing both its antimicrobial efficacy and mechanical properties. Chronic Mucocutaneous candidiasis, often associated with recurrent unexplained fungal infections, is characterized by inherited T-cell defects and typically requires prolonged antifungal treatment. The approved oral imidazole derivative, ketoconazole, is commonly used for the treatment of candidiasis, chronic Mucocutaneous candidiasis, and oral thrush. However, non-compliance, therapy failure, and systemic side effects have been reported with prolonged use of ketoconazole. In this study, we developed a silver nanoparticle-loaded oregano oil nanoemulsion as a potential alternative. Our results demonstrated that the prepared nanoemulsion exhibited enhanced antimicrobial activity, as indicated by larger zones of inhibition compared to the standard ketoconazole and oregano oil combination, as confirmed by the disc diffusion method. This novel formulation holds great promise for the treatment of Mucocutaneous candidiasis, providing an effective and potentially safer alternative to current therapies.

Knowledge mapping of COVID-19 and autoimmune diseases: a visual and bibliometric analysis

BackgroundMany studies have shown an association between COVID-19 and autoimmune diseases (ADs). Studies on COVID-19 and ADs have also increased significantly, but there is no bibliometric analysis to summarize the association between COVID-19 and ADs. The purpose of this study was to perform a bibliometric and visual analysis of published studies related to COVID-19 and ADs.MethodsBased on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools Co-Occurrence13.2 (COOC13.2), VOSviewer, CiteSpace, and HistCite for analysis.ResultsA total of 1736 related kinds of papers were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, the author is Yehuda Shoenfeld from Israel, and the journal is Frontiers in Immunology. Research hotspots include immune responses (such as cytokines storm), multisystem ADs (such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis), treatment modalities (such as hydroxychloroquine, rituximab), vaccination and autoimmune mechanisms (such as autoantibodies, molecular mimicry). The future research direction may be the mechanisms and treatment ideas of the association between ADs and COVID-19 (such as NF-κB, hyperinflammation, antiphospholipid antibodies, neutrophil extracellular traps, granulocyte-macrophage colony-stimulating factor), other cross-diseases of COVID-19 and ADs (such as inflammatory bowel disease, chronic mucocutaneous candidiasis, acute respiratory distress syndrome).ConclusionThe growth rate of publications regarding ADs and COVID-19 has risen sharply. Our research results can help researchers grasp the current status of ADs and COVID-19 research and find new research directions in the future.

Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria). We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms. Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome. Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.

Neutrophils in STAT1 Gain-Of-Function Have a Pro-inflammatory Signature Which Is Not Rescued by JAK Inhibition

STAT1 gain-of-function (GOF) mutations cause an inborn error of immunity with diverse phenotype ranging from chronic mucocutaneous candidiasis (CMC) to various non-infectious manifestations, the most precarious of which are autoimmunity and vascular complications. The pathogenesis centers around Th17 failure but is far from being understood. We hypothesized that neutrophils, whose functions have not been explored in the context of STAT1 GOF CMC yet, might be involved in the associated immunodysregulatory and vascular pathology. In a cohort of ten patients, we demonstrate that STAT1 GOF human ex-vivo peripheral blood neutrophils are immature and highly activated; have strong propensity for degranulation, NETosis, and platelet-neutrophil aggregation; and display marked inflammatory bias. STAT1 GOF neutrophils exhibit increased basal STAT1 phosphorylation and expression of IFN stimulated genes, but contrary to other immune cells, STAT1 GOF neutrophils do not display hyperphosphorylation of STAT1 molecule upon stimulation with IFNs. The patient treatment with JAKinib ruxolitinib does not ameliorate the observed neutrophil aberrations. To our knowledge, this is the first work describing features of peripheral neutrophils in STAT1 GOF CMC. The presented data suggest that neutrophils may contribute to the immune pathophysiology of the STAT1 GOF CMC.

A Novel Interleukin 17 Receptor A Mutation in a Child with Chronic Mucocutaneous Candidiasis and Staphylococcal Skin Infections.

Chronic mucocutaneous candidiasis leads to persistent or recurrent fungal infections of the nail, skin, oral, and genital mucosa. Impaired interleukin 17-mediated immunity is a cause of chronic mucocutaneous candidiasis. We aimed to show the pathogenicity of a novel interleukin 17 receptor A mutation through functional studies. After next-generation sequencing analysis showed the interleukin 17 receptor A variant, we confirmed the variant by Sanger sequencing and functional validation of the variant by flow cytometry. We present the case of a 6-year-old male patient who presented with recurrent oral and genital Candida infections and eczema. He had staphylococcal skin lesions, fungal susceptibility, and eczema. The patient carried a novel homozygous nonsense [(c.787C> T) (p.Arg263Ter)] mutation in the interleukin 17 receptor A gene. Sanger sequencing confirmed the variant and revealed the segregation of the variant in the family. We used flow cytometry to detect interleukin 17 receptor A protein expression in peripheral blood mononuclear cells from patients and measured Th17 cell percentage. We observed low interleukin 17 receptor A protein expression in patient peripheral blood mononuclear cells, decreased CD4+ interleukin 17+ cell percentage, and decreased interleukin 17F expression in CD4+ cells compared to healthy controls. Innate immune defects may lead to chronic recurrent fungal and bacterial infections of the skin, mucosa, and nails. Generally, genetic and functional analysis is needed in addition to basic immunological tests.

Formulation and Evaluation of Herbal Excipients-Based Ketoconazole Cream for Fungal Infection

The goals of the current studies were to create herbal excipients-based ketoconazole cream to enhance the efficacy against chronic mucocutaneous candidiasis. Ketoconazole, coconut oil and other herbal excipients namely shea butter, bees wax, Lanolin and Rose oil were used for the formulation. Each formulation was prepared with various concentrations of coconut oil. Every prepared formulations were evaluated successfully. Among all the formulations F4 was the best that exhibiting a higher in vitro diffusion rate 59.6 ± 0.10 % CDR within 480 min with maximum antifungal efficacy, compared with the marketed formulation. We might therefore say that herbal excipients-based cream improved patient compliance and is a superior alternative to oral preparation, easier administration, local bioavailability, and better results for individuals with persistent mucocutaneous candidiasis who are afflicted with fungi.

The Th17/IL-17 Axis and Host Defense Against Fungal Infections.

Chronic mucocutaneous candidiasis (CMC) was recognized as a primary immunodeficiency in the early 1970s. However, for almost 40 years, its genetic etiology remained unknown. The progressive molecular and cellular description of inborn errors of immunity (IEI) with syndromic CMC pointed toward a possible role of IL-17-mediated immunity in protecting against fungal infection and CMC. Since 2011, novel IEI affecting either the response to or production of IL-17A and/or IL-17F (IL-17A/F) in patients with isolated or syndromic CMC provided formal proof of the pivotal role of the IL-17 axis in mucocutaneous immunity to Candida spp, and, to a lesser extent, to Staphylococcus aureus in humans. In contrast, IL-17-mediated immunity seems largely redundant against other common microbes in humans. In this review, we outline the current knowledge of IEI associated with impaired IL-17A/F-mediated immunity, highlighting our current understanding of the role of IL-17A/F in human immunity.