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An 18-Year-Old Woman With Recurrent Skin, Nail, and Oral Mucosal Abnormalities

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

An 18-year-old woman presented to the dermatology clinic for evaluation of recurrent skin, nail, and oral mucosal abnormalities. At age 4 years, she developed white oral plaques that resolved with oral nystatin. Approximately 6 months later, the oral plaques recurred, her toenails became thickened and yellowed, and red plaques appeared on both feet and lower legs. After 3 months of daily oral itraconazole, her skin, nail, and oral mucosal abnormalities resolved for approximately 1 year. Over the following years, she received intermittent 3- to 6-month courses of daily itraconazole for recurrent skin, nail, and oral mucosal abnormalities, which typically recurred within 6 to 12 months of discontinuing itraconazole. Her last dose of itraconazole was approximately 2 years prior to presentation. On physical examination, the patient had white, moist, nonadherent plaques in the oral mucosa and moist red fissures at bilateral oral commissures (Figure, left panel). She also had thickened, yellowed toenails and scaly erythematous plaques on her lower legs and feet bilaterally (Figure, right panel). Results of complete blood cell count with differential were normal, as were results of measurement of serum IgG, IgA, IgM, and IgE levels and analysis of CD3, CD4, and CD8 T-cell subsets. Potassium hydroxide wet mount preparation of skin scrapings from the lower extremities demonstrated fungal elements. Fungal culture of the skin scrapings grew Candida albicans.

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Chronic mucocutaneous candidiasis (CMC)

C. Restart daily oral itraconazole

The key to the correct diagnosis is recognition that recurrent fungal infections of the oropharynx, skin, and nails are characteristic of CMC. Choices A and B are incorrect because antibiotics and steroid creams are not treatments for candidiasis and may worsen this condition. Although terbinafine (choice D) is an antifungal medication, it is not first-line therapy for CMC.

Chronic mucocutaneous candidiasis is a primary immunodeficiency disorder characterized by persistent or recurrent noninvasive infections of the skin, nails, oral cavity, and genital mucosa with Candida species, typically C albicans.1

The differential diagnosis of CMC includes other T-cell deficiency diseases that cause chronic candidiasis such as HIV, severe combined immunodeficiency, CARD9 (caspase recruitment domain-containing protein 9) deficiency, CD25 deficiency, and hyperimmunoglobulin E syndrome. Unlike CMC, these conditions are typically associated with invasive Candida infections.2

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Xiao-Yong Man, MD, PhD, Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 JF Rd, Hangzhou, Zhejiang 310000, China (manxy@zju.edu.cn).

Published Online: August 18, 2022. doi:10.1001/jama.2022.14460

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for providing permission to share her information.

References
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Okada  S , Puel  A , Casanova  JL , Kobayashi  M .  Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity.   Clin Transl Immunology. 2016;5(12):e114. doi:10.1038/cti.2016.71PubMedGoogle ScholarCrossref
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Depner  M , Fuchs  S , Raabe  J ,  et al.  The extended clinical phenotype of 26 patients with chronic mucocutaneous candidiasis due to gain-of-function mutations in STAT1.   J Clin Immunol. 2016;36(1):73-84. doi:10.1007/s10875-015-0214-9PubMedGoogle ScholarCrossref
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Okada  S , Asano  T , Moriya  K ,  et al.  Human STAT1 gain-of-function heterozygous mutations: chronic mucocutaneous candidiasis and type I interferonopathy.   J Clin Immunol. 2020;40(8):1065-1081. doi:10.1007/s10875-020-00847-xPubMedGoogle ScholarCrossref
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Toubiana  J , Okada  S , Hiller  J ,  et al; International STAT1 Gain-of-Function Study Group.  Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype.   Blood. 2016;127(25):3154-3164. doi:10.1182/blood-2015-11-679902PubMedGoogle ScholarCrossref
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Sharifinejad  N , Zaki-Dizaji  M , Tebyanian  S ,  et al.  Clinical, immunological, and genetic features in 938 patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a systematic review.   Expert Rev Clin Immunol. 2021;17(8):807-817. doi:10.1080/1744666X.2021.1925543PubMedGoogle ScholarCrossref
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Lévy  R , Okada  S , Béziat  V ,  et al.  Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency.   Proc Natl Acad Sci U S A. 2016;113(51):E8277-E8285. doi:10.1073/pnas.1618300114PubMedGoogle ScholarCrossref
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Pappas  PG , Kauffman  CA , Andes  DR ,  et al.  Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America.   Clin Infect Dis. 2016;62(4):e1-e50. doi:10.1093/cid/civ933PubMedGoogle ScholarCrossref
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Forbes  LR , Vogel  TP , Cooper  MA ,  et al.  Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations.   J Allergy Clin Immunol. 2018;142(5):1665-1669. doi:10.1016/j.jaci.2018.07.020PubMedGoogle ScholarCrossref
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Leiding  JW , Okada  S , Hagin  D ,  et al; Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium.  Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations.   J Allergy Clin Immunol. 2018;141(2):704-717. doi:10.1016/j.jaci.2017.03.049PubMedGoogle ScholarCrossref
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