eMedicine Specialties > Dermatology > Fungal Infections

Candidiasis, Chronic Mucocutaneous

Author: David T Robles, MD, PhD, Resident Physician, Department of Internal Medicine, Division of Dermatology, University of Washington School of Medicine
Coauthor(s): Jonathan M Olson, BS, University of Washington School of Medicine; Robin L Hornung, MD, MPH, Assistant Professor, Division of Dermatology, Department of Pediatrics, University of Washington School of Medicine; Director, Department of Pediatric Dermatology, Children's Hospital and Regional Medical Center, Seattle; Michael G Bryan, MD, Staff Dermatologist, Las Vegas Skin and Care Clinics; Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Contributor Information and Disclosures

Updated: Jan 15, 2008

Introduction

Background

Chronic mucocutaneous candidiasis (CMC) refers to a heterogeneous group of disorders characterized by recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida organisms, usually Candida albicans. These disorders are confined to the cutaneous surface, with little propensity for systemic dissemination. CMC does not represent a specific disease, but rather a phenotypic presentation of a spectrum of immunologic, endocrinologic, and autoimmune disorders. The unifying feature of these heterogeneous disorders is impaired cell-mediated immunity against Candida species.

Pathophysiology

C albicans is an opportunistic yeast that is part of the normal flora of the gastrointestinal tract, skin, and mucous membranes. The fungus can exist in the yeast, the mycelial (pseudohyphal), or the chlamydospore phase. Invasive disease is rare; however, when it occurs, it is usually associated with mycelial elements. Several host factors are important in defending against infection by candidal organisms. Healthy, intact skin that continuously desquamates and regenerates is usually an effective initial barrier. An intact immune system is critical for keeping this opportunistic organism at bay.

CMC is associated with a defect in cell-mediated immunity that may either be limited to Candida antigens or be part of a more general immune abnormality. Recent data suggest alterations in cytokine production in response to Candida antigens. These alterations include decreased interleukin 2 and interferon-gamma levels (T_H 1 cytokines) and increased interleukin 10 levels in some studies.^1,2 Patients who lack T-cell immunity (eg, those with severe combined immune deficiency syndrome or DiGeorge syndrome) or patients with severely impaired T-cell function (eg, patients with AIDS) are susceptible to chronic candidal infections. Defects in humoral immunity are not commonly observed in patients with CMC, and patients with antibody deficiencies are not particularly prone to candidiasis.

Mortality/Morbidity

CMC is not associated with a high degree of mortality because disseminated invasive candidal infections are rare. In isolated CMC, the prognosis is good; however, significant morbidity is related to chronic and persistent skin, nail, and mucous membrane candidal infections. The risk of mycotic aneurysms, while low, remains a real possibility.³ In a subset of patients, malignant thymomas or cancers of the oral cavity and digestive tract may occur. Patients with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED) have significant morbidity from endocrinopathies or other autoimmune diseases associated with this condition. Several cases of Pneumocystis carinii pneumonia in patients with CMC are reported in the literature.

Race

No racial predilection is reported for CMC, although APECED is most prevalent in Finnish, Sardinian, and Iranian Jewish populations.

Sex

The male-to-female ratio for CMC is equal.

Age

CMC usually manifests in infancy or early childhood (60-80% of cases), with a mean age of onset of 3 years. Delayed or adult onset of the disease is reported and can be associated with thymoma, myasthenia gravis, and bone marrow abnormalities.

Clinical

History

Patients present with recurrent or persistent superficial candidal infections of the oral cavity (thrush) or intertriginous or periorificial areas. Infants often present with recalcitrant thrush, candidal diaper dermatitis, or both. More extensive scaling of skin lesions and thickened nails and red, swollen periungual tissues can follow these infections.

Systemic candidiasis and invasive fungal dermatitis, although rare, usually occur in premature infants, particularly those with extremely low birth weight.

Persistent and refractory candidal infections, which characterize CMC, must be distinguished from the more common and treatment-responsive overgrowth of Candida that occurs in the setting of systemic antibiotic therapy, local/systemic corticosteroid treatment, or hyperglycemia in persons with diabetes mellitus.

Physical

CMC is diagnosed based on physical examination findings, potassium chloride (KOH) preparation results, fungal culture, and a history of recurrent and refractory candidiasis infections. Oral examination may reveal the white adherent plaques of thrush or the angular cheilitis of perlèche. Oral involvement may extend to the esophagus, but further extension is extremely uncommon. Nails may be markedly thickened, fragmented, and discolored, with significant edema and erythema of the surrounding periungual tissue, simulating clubbing (see Media File 1). Skin lesions more frequently are acral and characterized by erythematous, hyperkeratotic, serpiginous plaques (see Media File 2). The scalp may be involved with similar hyperkeratotic plaques, which can result in scarring alopecia (see Media File 3).

A subset of CMC patients has recurrent or severe noncandidal infections,⁴ including those from viral, bacterial, and other fungal pathogens. Some patients with CMC have low serum iron levels and decreased iron stores, possibly related to decreased iron absorption. Iron replacement should be initiated in these patients. Several patients reportedly have improved after parenteral iron therapy.

Several classifications exist for CMC. The authors categorize CMC based on its association with other conditions.

• CMC without endocrinopathy
  • This category comprises a spectrum of clinical presentations.
  • Inheritance may be autosomal recessive or dominant, but many cases are sporadic.
  • Onset is in childhood, and no associated endocrine or autoimmune disorders are observed.
• CMC with endocrinopathy
  • CMC may occur as part of autoimmune polyendocrinopathy syndrome type 1 (Online Mendelian Inheritance in Man #240300), also known as APECED.⁵
    • APECED is characterized by at least 2 of the following: CMC, hypoparathyroidism, and Addison disease. Other autoimmune disorders may be associated, such as, type 1 diabetes, autoimmune thyroiditis, Graves disease, alopecia areata, vitiligo, hypogonadism, biliary cirrhosis, hepatitis, idiopathic thrombocytopenic purpura, and pernicious anemia.
    • APECED is inherited in an autosomal recessive fashion and usually manifests early in childhood. It is caused by mutations in the autoimmune regulator gene (AIRE) on 21q22.3, which encodes a protein that plays an important role in establishing and maintaining tolerance in the thymus.⁶
    • A recent study found that APECED patients have defective receptor-mediated Candida internalization, leading to altered Candida -specific immune responses.⁵
    • Candidiasis is often the first manifestation of APECED, appearing before age 5 years in most cases, followed by manifestations of the other endocrine and nonendocrine conditions, including ectodermal dysplasia. Ectodermal dysplasia manifestations include dental enamel hypoplasia and pitted nail dystrophy. Keratopathy and calcifications of the tympanic membrane also may occur.
    • A 2006 review of 18 APECED patients found candidiasis in all patients as the presenting symptom, and researchers concluded that ectodermal dystrophy usually only occurs as a secondary phenomenon.⁶
    • No correlation exists between the severity of the endocrinopathy and the severity of the candidal infections. Treatment of the underlying endocrinopathy does not usually improve candidal infections.
  • CMC may be associated with thyroid disease. An autosomal dominant CMC associated with thyroid disease has been mapped to 2p.⁷
• CMC with thymoma
  • Patients in this subgroup typically present after the third decade of life.
  • These patients are at increased risk of myasthenia gravis and bone marrow abnormalities.
• CMC with other conditions
  • CMC may be seen in patients with hyperimmunoglobulin E syndrome.
  • Recurrent oral candidiasis is not uncommon in patients with HIV infection.

Causes

CMC occurs in a heterogeneous group of patients with a wide spectrum of immune dysregulation, ranging from Candida -specific decreased immunity to a broader immune defect.

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