Chronic Mucocutaneous Candidiasis Clinical Presentation

  • Author: David T Robles, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Sep 29, 2011
 

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.

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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 first image below). Skin lesions more frequently are acral and characterized by erythematous, hyperkeratotic, serpiginous plaques (see second image below). The scalp may be involved with similar hyperkeratotic plaques, which can result in scarring alopecia (see third image below).

Thickened, fragmented, hyperkeratotic nails and erThickened, fragmented, hyperkeratotic nails and erythematous periungual skin. Courtesy of Walter Reed Army Medical Center. Crusted hyperkeratotic plaques on and around the nCrusted hyperkeratotic plaques on and around the nose. Courtesy of Walter Reed Army Medical Center. Crusted hyperkeratotic plaques on eyebrow, foreheaCrusted hyperkeratotic plaques on eyebrow, forehead, and scalp. Courtesy of Walter Reed Army Medical Center.

A subset of CMC patients has recurrent or severe noncandidal infections,[5] 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.[6]
      • 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.[7]
      • A recent study found that APECED patients have defective receptor-mediated Candida internalization, leading to altered Candida -specific immune responses.[6]
      • 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.[7]
      • 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.[8]
  • 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.
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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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Contributor Information and Disclosures
Author

David T Robles, MD, PhD  Dermatologist, Chaparral Medical Group

David T Robles, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

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

Robin L Hornung, MD, MPH is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Jonathan M Olson, MD  Resident Physician, Division of Dermatology, University of Washington Medical Center

Jonathan M Olson, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Carrie L Kovarik, MD  Assistant Professor of Dermatology, Dermatopathology, and Infectious Diseases, University of Pennsylvania School of Medicine

Carrie L Kovarik, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD  Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Michael G. Bryan, MD and Lester F. Libow, MD to the development and writing of this article.

References

  1. Lilic D. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr Opin Infect Dis. Apr 2002;15(2):143-7. [Medline].

  2. Lilic D, Gravenor I, Robson N, Lammas DA, Drysdale P, Calvert JE, et al. Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis. Infect Immun. Oct 2003;71(10):5690-9. [Medline].

  3. van de Veerdonk FL, Plantinga TS, Hoischen A, et al. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med. Jul 7 2011;365(1):54-61. [Medline].

  4. Marazzi MG, Bondi E, Giannattasio A, Strozzi M, Savioli C. Intracranial aneurysm associated with chronic mucocutaneous candidiasis. Eur J Pediatr. Apr 19 2007;[Medline].

  5. Herrod HG. Chronic mucocutaneous candidiasis in childhood and complications of non-Candida infection: a report of the Pediatric Immunodeficiency Collaborative Study Group. J Pediatr. Mar 1990;116(3):377-82. [Medline].

  6. Brännström J, Hässler S, Peltonen L, Herrmann B, Winqvist O. Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens. Clin Immunol. Dec 2006;121(3):265-73. [Medline].

  7. Collins SM, Dominguez M, Ilmarinen T, Costigan C, Irvine AD. Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Br J Dermatol. Jun 2006;154(6):1088-93. [Medline].

  8. Atkinson TP, Schäffer AA, Grimbacher B, Schroeder HW Jr, Woellner C, Zerbe CS, et al. An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family. Am J Hum Genet. Oct 2001;69(4):791-803. [Medline].

  9. Patiroglu T, Tahan F. Chronic mucocutaneous candidiasis with agammaglobulinaemia. J Eur Acad Dermatol Venereol. Jul 2007;21(6):833-4. [Medline].

  10. Meager A, Visvalingam K, Peterson P, Möll K, Murumägi A, Krohn K, et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. Jul 2006;3(7):e289. [Medline].

  11. Masi M, De Vinci C, Baricordi OR. Transfer factor in chronic mucocutaneous candidiasis. Biotherapy. 1996;9(1-3):97-103. [Medline].

  12. Abuzakouk M, Feighery C. Primary immunodeficiency disorders in the Republic of Ireland: first report of the national registry in children and adults. J Clin Immunol. Jan 2005;25(1):73-7. [Medline].

  13. Chiu SJ, Tsao CH, Chen LC, Kao CC, Lue KH, Huang JL. Chronic mucocutaneous candidiasis in a 6-year-old boy. J Microbiol Immunol Infect. Jun 2004;37(3):196-9. [Medline].

  14. Ee HL, Tan HH, Ng SK. Autosomal dominant familial chronic mucocutaneous candidiasis associated with acne rosacea. Ann Acad Med Singapore. Oct 2005;34(9):571-4. [Medline].

  15. Guidelines/Outcome Committee, American Academy of Dermatology. Guidelines of care for superficial mycotic infections of the skin: mucocutaneous candidiasis. J Am Acad Dermatol. Jan 1996;34(1):110-5. [Medline].

  16. Kirkpatrick CH. Chronic mucocutaneous candidiasis. Pediatr Infect Dis J. Feb 2001;20(2):197-206. [Medline].

  17. Mangino M, Salpietro DC, Zuccarello D, Gangemi S, Rigoli L, Merlino MV, et al. A gene for familial isolated chronic nail candidiasis maps to chromosome 11p12-q12.1. Eur J Hum Genet. Jun 2003;11(6):433-6. [Medline].

  18. Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. Aug 2006;91(8):2843-50. [Medline].

 
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Thickened, fragmented, hyperkeratotic nails and erythematous periungual skin. Courtesy of Walter Reed Army Medical Center.
Crusted hyperkeratotic plaques on and around the nose. Courtesy of Walter Reed Army Medical Center.
Crusted hyperkeratotic plaques on eyebrow, forehead, and scalp. Courtesy of Walter Reed Army Medical Center.
 
 
 
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