1,047 results match your criteria Candidiasis Chronic Mucocutaneous

Gene Mutation Presenting at Age 2 Years With Autoimmune Retinopathy and Steroid-Responsive Acute Liver Failure: A Case Report and Literature Review.

Front Immunol 2021 28;12:687280. Epub 2021 May 28.

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic autosomal recessive disorder caused by mutation in the autoimmune regulator (AIRE) gene. Patients usually are diagnosed at ages between 5 and 15 years when they show 3 or more manifestations, most typically mucocutaneous candidiasis, Addison's disease, and hypoparathyroidism. APECED-associated hepatitis (APAH) develops in only 10% to 40% of patients, with severity varying from subclinical chronic active hepatitis to potentially fatal acute liver failure (ALF). Read More

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Chronic Demodicosis in Patients with Immune Dysregulation: An Unexpected Infectious Manifestation of Signal Transducer and Activator of Transcription (STAT)1 Gain-of-Function.

Clin Exp Immunol 2021 Jun 11. Epub 2021 Jun 11.

Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Signal transducer and activator of transcription (STAT)1 heterozygous gain-of-function (GOF) mutations are known to induce immune dysregulation and chronic mucocutaneous candidiasis (CMCC). Previous reports suggest an association between demodicosis and STAT1 GOF. However, immune characterization of these patients is lacking. Read More

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Case Report: Rituximab Improved Epileptic Spasms and EEG Abnormalities in an Infant With West Syndrome and Anti-NMDAR Encephalitis Associated With APECED.

Front Neurol 2021 20;12:679164. Epub 2021 May 20.

Department of Paediatrics, St Mary's Hospital, Kurume, Fukuoka, Japan.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder caused by a mutation in the autoimmune regulator gene. Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy typically exhibit hypoparathyroidism, adrenocortical failure, and chronic mucocutaneous candidiasis. There are only a few case reports of autoimmune encephalitis during autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, but not as an initial manifestation. Read More

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Report of two siblings with APECED in Serbia: is there a founder effect of c.769C>T AIRE genotype?

Ital J Pediatr 2021 Jun 2;47(1):126. Epub 2021 Jun 2.

Endocrine Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.

Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) or autoimmune polyglandular syndrome Type 1 is a rare autosomal recessive syndrome. The disorder is caused by mutations in the AIRE (AutoImmune Regulator) gene. According to the classic criteria, clinical diagnosis requires the presence of at least two of three main components: chronic mucocutaneous candidiasis, hypoparathyroidism and primary adrenal insufficiency. Read More

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Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

J Endocrinol Invest 2021 May 18. Epub 2021 May 18.

FIRS Laboratories RSR Ltd, Cardiff, UK.

Background: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD).

Methods: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23. Read More

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Clinical, immunological, and genetic features in 938 patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a systematic review.

Expert Rev Clin Immunol 2021 Jun 3:1-11. Epub 2021 Jun 3.

Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP), and adrenal insufficiency (ADI).: Literature search was conducted in PubMed, Web of Science, and Scopus databases using related keywords, and included studies were systematically evaluated.: We reviewed 938 APECED patients and the classic triad of APECED was detected in 57. Read More

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Atypical presentation of autoimmune polyglandular syndrome type 1 in the fifth decade.

BMJ Case Rep 2021 Apr 26;14(4). Epub 2021 Apr 26.

Endocrinology, Sri Ramachandra University Medical College, Chennai, Tamil Nadu, India.

A 45-year-old woman presented to us with a short-term history of nausea, vomiting and giddiness. On arrival at our hospital, examination revealed postural hypotension. Fluid resuscitation with intravenous normal saline was commenced. Read More

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A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis.

J Clin Immunol 2021 Apr 7. Epub 2021 Apr 7.

Primary Immunodeficiencies Unit, Hospital Dona Estefânia-CHLC, EPE, Rua Jacinta Marto, 1169-045, Lisbon, Portugal.

Inborn errors of the IL-17-mediated signaling have been associated with chronic mucocutaneous candidiasis (CMC). We describe a patient with CMC, atopic dermatitis, enamel dysplasia, and recurrent parotitis harboring a novel compound heterozygous mutation of TRAF3IP2, leading to autosomal recessive ACT1 deficiency and deficient IL-17 signaling. Read More

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Clinical Relevance of Gain- and Loss-of-Function Germline Mutations in STAT1: A Systematic Review.

Front Immunol 2021 11;12:654406. Epub 2021 Mar 11.

Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China.

Germline mutations in signal transducer and activator of transcription 1 (STAT1), which lead to primary immunodeficiency, are classified as defects in intrinsic and innate immunity. To date, no comprehensive overview comparing GOF with LOF in early-onset immunodeficiency has been compiled. To collect and systematically review all studies reporting STAT1 GOF and LOF cases, and to describe the clinical, diagnostic, molecular, and therapeutic characteristics of all the conditions. Read More

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Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature.

Rev Soc Bras Med Trop 2021 22;54:e0008-2021. Epub 2021 Mar 22.

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clinicas, Departamento de Dermatologia, Ambulatório das Manifestações Cutâneas das Imunodeficiências Primárias, São Paulo, SP, Brasil.

We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Read More

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Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence.

Front Immunol 2021 26;12:606860. Epub 2021 Feb 26.

Section of Internal Medicine and Endocrinological and Metabolic Sciences, Department of Medicine, University of Perugia, Perugia, Italy.

The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator () gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Read More

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February 2021

Transcriptional Profiling of STAT1 Gain-of-Function Reveals Common and Mutation-Specific Fingerprints.

Front Immunol 2021 17;12:632997. Epub 2021 Feb 17.

Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

STAT1 gain-of-function (GOF) is a primary immunodeficiency typically characterized by chronic mucocutaneous candidiasis (CMC), recurrent respiratory infections, and autoimmunity. Less commonly, also immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX)-like syndromes with CMC, and combined immunodeficiency without CMC have been described. Recently, our group and others have shown that different mutation-specific mechanisms underlie STAT1 GOF , including faster nuclear accumulation (R274W), and reduced mobility (R321, N574I) to near immobility in the nucleus (T419R) upon IFNγ stimulation. Read More

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February 2021

Late-onset autoimmune polyendocrine syndrome type 1: a case report and literature review.

Feixia Zhan Li Cao

Immunol Res 2021 Apr 18;69(2):139-144. Epub 2021 Feb 18.

Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China.

Autoimmune polyendocrine syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare monogenic disorder, is classically characterized by a triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. The identified causative gene is autoimmune regulator (AIRE), which encodes a critical transcription factor and is essential for self-tolerance. Here, we describe a late-onset Chinese case who presented with symptoms of persistent tetany due to hypocalcemia. Read More

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An AIREless Breath: Pneumonitis Caused by Impaired Central Immune Tolerance.

Front Immunol 2020 27;11:609253. Epub 2021 Jan 27.

Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by biallelic mutations in the gene, has historically been defined by the development of chronic mucocutaneous candidiasis together with autoimmune endocrinopathies, primarily hypoparathyroidism and adrenal insufficiency. Recent work has drawn attention to the development of life-threatening non-endocrine manifestations such as autoimmune pneumonitis, which has previously been poorly recognized and under-reported. In this review, we present the clinical, radiographic, autoantibody, and pulmonary function abnormalities associated with APECED pneumonitis, we highlight the cellular and molecular basis of the autoimmune attack in the AIRE-deficient lung, and we provide a diagnostic and a therapeutic roadmap for patients with APECED pneumonitis. Read More

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January 2021

Inborn Error of Immunity or Atopic Dermatitis: When to be Concerned and How to Investigate.

J Allergy Clin Immunol Pract 2021 04 3;9(4):1501-1507. Epub 2021 Feb 3.

Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany. Electronic address:

Around 20% of all children worldwide suffer from atopic dermatitis. Therefore, eczematous skin lesions and elevated serum immunoglobulin E (IgE) levels are common findings. Inborn errors of immunity (IEI) may be missed in the context of atopic dermatitis, and management and prognosis of these conditions can be substantially different. Read More

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Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy in Two Siblings: Same Mutations but Very Different Phenotypes.

Genes (Basel) 2021 01 26;12(2). Epub 2021 Jan 26.

Pediatric Endocrinology Unit, Regina Margherita Children's Hospital, 10126 Turin, Italy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), caused by mutations in the gene, is mainly characterized by the triad of hypoparathyroidism, primary adrenocortical insufficiency and chronic mucocutaneous candidiasis, but can include many other manifestations, with no currently clear genotype-phenotype correlation. We present the clinical features of two siblings, a male and a female, with the same mutations in the gene associated with two very different phenotypes. Interestingly, the brother recently experienced COVID-19 infection with pneumonia, complicated by hypertension, hypokalemia and hypercalcemia. Read More

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January 2021

Primary immunodeficiency and chronic mucocutaneous candidiasis: pathophysiological, diagnostic, and therapeutic approaches.

Allergol Immunopathol (Madr) 2021 2;49(1):118-127. Epub 2021 Jan 2.

Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain.

Chronic mucocutaneous candidiasis (CMC) is characterized by a chronic or recurrent non-invasive infection, mainly due to , in skin, nails, and mucous membranes, associated in some cases with autoimmune manifestations. The key immune defect is a disruption of the action of cytokine IL-17, whose most common genetic etiology is gene gain-of-function (GOF) mutations. The initial appropriate treatment for fungal infections is with azoles. Read More

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January 2021

Stepwise Reversal of Immune Dysregulation Due to STAT1 Gain-of-Function Mutation Following Ruxolitinib Bridge Therapy and Transplantation.

J Clin Immunol 2021 May 21;41(4):769-779. Epub 2021 Jan 21.

Division of Allergy and Immunology, Marmara University, Istanbul, Turkey.

Purpose: Patients with heterozygous gain-of-function (GOF) mutations in STAT1 frequently exhibit chronic mucocutaneous candidiasis (CMC), immunodeficiency and autoimmune manifestations. Several treatment options including targeted therapies and hematopoietic stem cell transplantation (HSCT) are available for STAT1 GOF patients but modalities and outcomes are not well established. Herein, we aimed to unravel the effect of ruxolitinib as a bridge therapy in a patient with sporadic STAT1 T385M mutation to manage infections and other disease manifestations. Read More

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Aberrant type 1 immunity drives susceptibility to mucosal fungal infections.

Science 2021 01;371(6526)

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. Read More

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January 2021

Palmoplantar keratoderma with deafness phenotypic variability in a patient with an inherited GJB2 frameshift variant and novel missense variant.

Mol Genet Genomic Med 2021 02 14;9(2):e1574. Epub 2021 Jan 14.

Department of Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Variants in the GJB2 gene encoding the gap junction protein connexin-26 (Cx26) can cause autosomal recessive nonsyndromic hearing loss or a variety of phenotypically variable autosomal dominant disorders that effect skin and hearing, such as palmoplantar keratoderma (PPK) with deafness and keratitis-ichthyosis-deafness (KID) syndrome. Here, we report a patient with chronic mucocutaneous candidiasis, hyperkeratosis with resorption of the finger tips, profound bilateral sensorineural hearing loss, and normal hair and ocular examination. Exome analysis identified a novel missense variant in GJB2 (NM_004004. Read More

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February 2021

Bronchiectasis and Bronchiolectasis With Severe Herniating Pattern Associated With Gain-of-Function Mutation: Detailed Clinicopathological Findings.

Pediatr Dev Pathol 2021 Mar-Apr;24(2):131-136. Epub 2021 Jan 13.

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.

gain-of-function (GOF) mutations are associated with a rare autosomal dominant immunodeficiency disorder with main clinical manifestations including chronic mucocutaneous candidiasis (CMC) and bronchiectasis. In addition, these patients show higher incidences of cerebral and extracerebral aneurysm, malignancies and various autoimmune conditions compared to the general population. Although previous publications have reported clinical findings in patients with GOF mutation, they did not include histopathologic features. Read More

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January 2021

Hypoparathyroidism as the single major component for decades of autoimmune polyglandular syndrome type 1.

Endocrinol Diabetes Metab Case Rep 2020 Dec 24;2020. Epub 2020 Dec 24.

Endocrinology Department, Hospital Pedro Hispano, Matosinhos Local Health Unit, Matosinhos, Portugal.

Summary: Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison's disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. Read More

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December 2020

STAT 1 mutation associated with chronic mucocutaneous candidiasis and pancytopenia.

Pediatr Allergy Immunol 2021 May 25;32(4):798-800. Epub 2021 Jan 25.

Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India.

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Chronic Candida infection, bronchiectasis, immunoglobulin abnormalities, and stunting: a case report of a natural mutation of STAT1 (c.986C>G) in an adolescent male.

BMC Infect Dis 2021 Jan 7;21(1):38. Epub 2021 Jan 7.

Department of Hematology, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuchang District, Wuhan City, Hubei Province, China.

Background: Chronic mucocutaneous candidiasis (CMC) is the most common clinical symptom of singer transducer and signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations. Bronchiectasis is a chronic lung disease that is characterized by permanent bronchiectasis, causing cough, expectoration, and even haemoptysis. The underlying pathogeny is not yet clear. Read More

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January 2021

Two patients with chronic mucocutaneous candidiasis caused by TRAF3IP2 deficiency.

J Allergy Clin Immunol 2021 Jan 21. Epub 2021 Jan 21.

Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

Background: TRAF3 interacting protein 2 (TRAF3IP2) (Act1) is an adapter protein that interacts with IL-17R via its similar expression to fibroblast growth factor genes and IL-17R domain and coordinates 2 separate proinflammatory pathways following IL-17 cytokine stimulation.

Objective: We sought to elucidate the immunologic consequences of TRAF3IP2 homozygous mutations to improve treatments for immunodeficiency patients with chronic mucocutaneous candidiasis.

Methods: We describe 2 patients presenting with chronic mucocutaneous candidiasis who harbor biallelic nonsense mutations in TRAF3IP2. Read More

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January 2021

Novel Pathogenic Variants of the AIRE Gene in Two Autoimmune Polyendocrine Syndrome Type I Cases with Atypical Presentation: Role of the NGS in Diagnostic Pathway and Review of the Literature.

Biomedicines 2020 Dec 19;8(12). Epub 2020 Dec 19.

Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

. Autoimmune polyglandular syndrome type 1 (APS-1) with or without reversible metaphyseal dysplasia is a rare genetic disorder due to inactivating variants of the autoimmune regulator, gene. Clinical variability of APS-1 relates to pleiotropy, and the general dysfunction of self-tolerance to organ-specific antigens and autoimmune reactions towards peripheral tissues caused by the underlying molecular defect. Read More

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December 2020

A Patient With AIRE Mutation Who Presented With Severe Diarrhea and Lung Abscess.

Pediatr Infect Dis J 2021 01;40(1):66-69

From the Department of Pediatrics, Division of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (polyglandular endocrinopathy type 1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). The major clinical features of APECED are hypoparathyroidism, adrenal insufficiency (Addison disease), and chronic mucocutaneous candidiasis. This disease is also associated with multiple other and uncommon autoimmune (autoimmune hepatitis, autoimmune enteropathy, atrophic gastritis with or without pernicious anemia, gonadal failure, diabetes mellitus, hypothyroidism, functional hyposplenism), ectodermal (alopecia and vitiligo), and inflammatory (intestinal lung disease, nephritis) features. Read More

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January 2021

Chronic Mucocutaneous Candidiasis in Early Life: Insights Into Immune Mechanisms and Novel Targeted Therapies.

Front Immunol 2020 16;11:593289. Epub 2020 Oct 16.

Pediatrics Department A, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Children with chronic mucocutaneous candidiasis (CMC) experience recurrent infections with . Moreover, immune dysregulation in the early life of these patients induces various autoimmune diseases and affects normal growth and development. The adaptive and innate immune system components play a significant role in anti-fungal response. Read More

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October 2020

The pathogenic T387A missense mutation in the gene encoding signal transducer and activator of transcription 1 exhibits a differential gene expression profile.

Mol Immunol 2020 12 20;128:79-88. Epub 2020 Oct 20.

Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany; German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany. Electronic address:

Heterozygous gain-of-function (GOF) mutations in the interferon-driven transcription factor STAT1 (signal transducer and activator of transcription 1) cause chronic mucocutaneous candidiasis (CMC). In this study, we characterized the molecular basis of a CMC-associated missense mutation by introducing a threonine-to-alanine exchange in the STAT1 DNA-binding domain at position 387. This substitution had previously been described in a CMC patient with suppurative eyelid infection and cutaneous abscesses, which are both unusual symptoms in this immunodeficiency. Read More

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December 2020

A Case of Critical Lower-Limb Ischemia in a 29-Year-Old Man with Autoimmune Polyglandular Syndrome Type 1 (APS-1).

Am J Case Rep 2020 Oct 17;21:e924705. Epub 2020 Oct 17.

Department of Internal Medicine, Jordan University of Science and Technology, Irbid, Jordan.

BACKGROUND Autoimmune polyglandular syndrome type 1 (APS-1) is an extremely rare autoimmune disorder with an autosomal recessive inheritance pattern. Its manifestations present in chronological sequence of the components mucocutaneous candidiasis, Addison disease, and hypoparathyroidism. Vascular calcification is a very rare manifestation of the disease, and it may be severe, causing critical lower-limb ischemia and significant morbidity. Read More

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October 2020