Chronic Mucocutaneous Candidiasis

Background

• Chronic mucocutaneous candidiasis (CMCC) refers to selective susceptibility to persistent or recurrent candidal infections (most commonly C. albicans) affecting nails, skin, and oral and genital mucosa, associated with congenital immunodeficiency disorders.
• CMCC is rare, although exact incidence and prevalence are not known.
• CMCC is associated with a variety of congenital disorders affecting CD4 T helper 17 (Th17) immunity that include:
  • Signal transducer and activator of transcription 1 (STAT1) gain-of-function variants (most commonly reported)
  • Inborn errors of interleukin 17 (IL-17) signaling such as IL-17 cytokine subunits, receptors, or signaling adaptor deficiencies
  • Retinoid-related orphan receptor (ROR)-gamma T (RORC) deficiency
  • IL-12R beta 1 (IL12RB1) or IL-12 p40 (IL12B) deficiency
  • STAT3 or dedicator of cytokinesis 8 (DOCK8) deficiency (see also hyper IgE syndrome)
  • Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

Evaluation

• Carefully examine, skin, nails, and mucosal surfaces for signs of candidal infection, as patients with CMCC may present with:
  • Oropharyngeal mycosis (thrush, glossitis, and/or cheilitis)
  • Cutaneous mycosis (pustules, annular plaques, intertrigo)
  • Esophageal/genital mycosis
  • Onychomycosis
  • Aphthous stomatitis
  • Scalp mycosis
• Depending on the underlying disorder, other manifestations may include:
  • Bacterial, viral, mycobacterial, and invasive fungal infections
  • Autoimmune manifestations
  • Vascular aneurysm
  • Malignancy
• Consider confirming candida infection with special stains, cultures or biopsy of involved areas.
• Immunologic evaluation may include:
  • Complete blood count with differential
  • Serum immunoglobulins
  • Flow cytometry to enumerate T cell, B cell, and natural killer (NK) cell counts and function
  • Cutaneous delayed hypersensitivity reaction
  • Tests of phagocyte function
• Genetic testing is required for definitive diagnosis of underlying primary immunodeficiency associated with CMCC.

Management

• Antifungal agents are cornerstone of therapy.
  • Initial treatment typically fluconazole, with dose and duration dependent on site involved.
  • Many patients will require chronic suppressive therapy with fluconazole.
  • Assess for development of resistance to fluconazole and treat with alternative antifungal agent if necessary.
• Ruxolitinib, granulocyte colony stimulating factors, and hematopoietic cell transplantation have been successful in limited case reports.
• Complications and prognosis are highly variable and dependent upon the underlying disorder.