Medical Care

Management can be difficult, and relapse is common following discontinuation of therapy. Topical therapies are not usually effective in patients with chronic mucocutaneous candidiasis (CMC). Treatment of oral involvement in CMC can be aided by therapy with clotrimazole troches or oral nystatin solution. Treatment falls into three main categories: antifungal agents, immunologic therapies, and combination therapy.

Systemic antifungal therapy is the mainstay of CMC therapy. It may be used alone or in combination with an immunomodulatory agent. The drawbacks of systemic antifungal therapy include the risk of adverse effects or toxicity, a failure to correct the underlying immune deficiency, relapse following the cessation of therapy, and antifungal resistance to some antifungal agents. It is estimated that 40% of patients receiving long-term antifungal treatment develop drug resistance, although lower frequency is observed with intermittent therapy.^[31]Patients with resistance to antifungals usually present with more severe phenotypes such as systemic infections and recurrent pneumonia. First-line antifungals include fluconazole, itraconazole, and posaconazole, while second-line therapy includes voriconazole, echinocandins, terbinafine, and liposomal amphotericin B.

Several immunologic therapies have been proposed in an effort to correct the underlying immune deficiency in persons with CMC. The most widely studied treatment is the use of transfer factor.^[34]Transfer factor is a cell-free protein extracted from the T lymphocytes of Candida-immune donors. Although the precise mechanism is unknown, it has been shown to transfer delayed-type hypersensitivity reactions to patients previously anergic to candidal skin testing. Candida-specific cell immunity may be transferred by this approach. It is not effective in all cases. Long-term remissions have occurred when combined with antifungal medications. Patients with CMC associated with autoimmune manifestations due to STAT1 mutations may show improvement with JAK1/2 tyrosine kinase inhibitors such as ruxolitinib.^{[35, 36]}Novel therapies such as JAK1/2 inhibitors have demonstrated sufficient potency to attenuate the increased STAT1 phosphorylation in CD4⁺ T lymphocytes, while enhancing IL-production, resulting in improvement of both the immunodeficiency and autoimmune disease processes.^[37]

Other systemic immunologic treatments include intravenous immunoglobulin G (IgG) or granulocyte macrophage colony-stimulating factor (GM-CSF) infusions and interferon-alfa.

Consultations

Refer patients to an endocrinologist if screening laboratory test results suggest an associated endocrine abnormality.

If familial chronic mucocutaneous candidiasis (CMC) is suspected, consultation with a geneticist should be obtained.

Patients with recurrent infections or pneumonia should be referred to an immunologist.

Long-Term Monitoring

Baseline studies and yearly screening for associated endocrinopathy should be performed. Long-term follow-up is necessary for identifying and addressing accompanying disorders.

Some authors suggest screening angio-MRI for all patients with diagnosed CMC to rule out aneurysm, but this is not a universal recommendation.^[6]Owing to chronic mucocutaneous candidiasis (CMC) and resultant chronic mucocutaneous inflammation, patients are at increased risk of skin and ear, nose, and throat cancers.^[38]Sequential biopsies of the esophagus to screen for tumors in patients presenting with recurrent esophagitis and associated dysphagia is recommended by some authors.^[31]

If the disease flares, patients may need to be seen on an urgent basis, particularly after a course of antifungals has been discontinued.

Guidelines

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Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 2010 Feb 15. 207 (2):291-7. [QxMD MEDLINE Link].
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. 2001 Oct. 69(4):791-803. [QxMD MEDLINE Link].
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Kisand K, Lilic D, Casanova JL, Peterson P, Meager A, Willcox N. Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications. Eur J Immunol. 2011 Jun. 41 (6):1517-27. [QxMD MEDLINE Link].
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Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, et al. Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med. 2009 Jun 8. 206 (6):1291-301. [QxMD MEDLINE Link].
de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, et al. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med. 2008 Jul 7. 205 (7):1543-50. [QxMD MEDLINE Link].
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Media Gallery

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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Author

Hassan I Galadari, MD Assistant Professor, Division of Dermatology, Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates (UAE) University, UAE

Hassan I Galadari, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, American Society for Dermatologic Surgery, Asian Dermatological Association, Dermatologic and Aesthetic Surgery International League, Emirates Medical Association, International Society for Dermatologic Surgery, International Society of Dermatology, Massachusetts Medical Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sasha Haddad, BS MD Candidate, Kirksville College of Osteopathic Medicine, AT Still University

Disclosure: Nothing to disclose.

Specialty Editor Board

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, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

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, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

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.

Neil Sandhu, MD, FAAD Dermatologist (Medical/Cosmetic) and Mohs Surgeon, Gulf Coast Dermatology

Neil Sandhu, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery

Disclosure: Nothing to disclose.

Blanca Anais Estupiñan University of Central Florida College of Medicine

Blanca Anais Estupiñan is a member of the following medical societies: American College of Physicians, American Medical Association, American Psychiatric Association

Disclosure: Nothing to disclose.

Acknowledgements

Michael G Bryan, MD Staff Dermatologist, Dermatology, Las Vegas Skin and Care Clinics