(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more .)
Chronic mucocutaneous candidiasis is a primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more that involves T cell defects Cellular immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more . Inheritance may be
Autosomal dominant: Involving a mutation in the signal transducer and activator of transcription 1 gene (STAT1)
Autosomal recessive: Involving a mutation in the autoimmune regulator gene (AIRE)
In the recessive form (autoimmune polyendocrinopathy–candidosis-ectodermal dystrophy), autoimmune manifestations typically develop; they include endocrine disorders (eg, hypoparathyroidism Hypoparathyroidism Hypocalcemia is a total serum calcium concentration 8.8 mg/dL ( 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration 4.7 mg/dL ( 1.17... read more , adrenal insufficiency Addison Disease Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more , hypogonadism Male Hypogonadism Hypogonadism is defined as testosterone deficiency with associated symptoms or signs, deficiency of spermatozoa production, or both. It may result from a disorder of the testes (primary hypogonadism)... read more , thyroid disorders Overview of Thyroid Function The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones... read more , diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ), alopecia areata Alopecia Areata Alopecia areata is typically sudden patchy nonscarring hair loss in people with no obvious skin or systemic disorder. (See also Alopecia.) This photo shows patchy loss of scalp hair in alopecia... read more , pernicious anemia Evaluation of Anemia Anemia is a decrease in the number of red blood cells (RBCs—as measured by the red cell count, the hematocrit, or the red cell hemoglobin content). In men, anemia is defined as hemoglobin read more , and hepatitis Causes of Hepatitis Hepatitis is an inflammation of the liver characterized by diffuse or patchy necrosis. Hepatitis may be acute or chronic (usually defined as lasting > 6 months). Most cases of acute viral hepatitis... read more . Mutations may also occur in genes that encode various proteins involved in the innate immune response to fungi—notably, the following:
PTPN22 (protein tyrosine phosphatase, non-receptor type 22 [also called LYP, or lymphoid tyrosine phosphatase], which is involved in T-cell–receptor signalling)
Dectin-1 (an innate pattern recognition receptor essential for the control of fungal infections)
CARD9 (caspase recruitment domain-containing protein 9, which is an adaptor molecule important in the production of interleukin (IL)-17 and for protection against fungal invasion)
Patients have cutaneous anergy to Candida, absent proliferative responses to Candida antigen (but normal proliferative responses to mitogens), and intact antibody response to Candida and other antigens. Mucocutaneous candidiasis Candidiasis (Mucocutaneous) Candidiasis is skin and mucous membrane infection with Candida species, most commonly Candida albicans. Infections can occur anywhere and are most common in skinfolds, digital web spaces, genitals... read more recurs or persists, usually beginning during infancy but sometimes during early adulthood. Life span is not affected. Some patients also have deficient humoral immunity (sometimes called antibody deficiency), characterized by abnormal antibody responses to polysaccharide antigens despite normal immunoglobulin levels.
Symptoms and Signs
Thrush is common, as are infections of the scalp, skin, nails, and gastrointestinal and vaginal mucosa. Severity varies. Nails may be thickened, cracked, and discolored, with edema and erythema of the surrounding periungual tissue, resembling clubbing. Skin lesions are crusted, pustular, erythematous, and hyperkeratotic. Scalp lesions may result in scarring alopecia.
Infants often present with refractory thrush, candidal diaper rash, or both.
Candidal lesions are confirmed by standard tests (eg, potassium hydroxide wet mount of scrapings).
Diagnosis of chronic mucocutaneous candidiasis is based on the presence of recurrent candidal skin or mucosal lesions when no other known causes of candidal infection (eg, diabetes, antibiotic use) are present.
Patients are screened for endocrine disorders based on clinical suspicion.
If an AIRE mutation is detected, screening can be offered to the patient's siblings and children.
Treatment of endocrine and autoimmune manifestations
Usually, the infections of chronic mucocutaneous candidiasis can be controlled with a topical antifungal, If patients have a poor response to topical antifungals, long-term treatment with a systemic antifungal drug (eg, amphotericin B, fluconazole, ketoconazole) may be needed. Immune globulin should be considered if patients have antibody deficiency.
Autoimmune (including endocrine) manifestations are treated aggressively.
Hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers (leukemias, lymphomas, myeloma) and other hematologic disorders... read more has rarely been successful and could be considered as last-line treatment in severe cases.
Inheritance of chronic mucocutaneous candidiasis is autosomal dominant or recessive.
Patients with the recessive form can have autoimmune (including endocrine) manifestations.
Diagnose the disorder by confirming mucocutaneous candidiasis and excluding other causes.
Treat candidiasis with antifungal drugs (using a systemic drug if needed), and treat autoimmune manifestations.