Chronic mucocutaneous candidiasis

What is chronic mucocutaneous candidiasis?

Chronic mucocutaneous candidiasis is a rare genetic condition occurring in childhood that affects skin, nails and mucosal sites. It is characterised by persistent and widespread candida infection. It is also called chronic mucocutaneous candidosis.

What causes chronic mucocutaneous candidiasis?

Chronic mucocutaneous candidiasis is due to primary immune deficiency. It is associated with various syndromes and laboratory abnormalities.

• There is a genetic predisposition with either autosomal dominant inheritance (an abnormal gene inherited from one parent) or autosomal recessive inheritance (an abnormal gene inherited from each parent).
• Autosomal dominant chronic mucocutaneous candidiasis is associated with gain-of-function STAT1 mutations resulting in IL-17 deficiency.
• Chronic mucocutaneous candidiasis is associated with certain endocrine conditions: hypoparathyroidism, hypothyroidism, hypoadrenalism, diabetes mellitus (autoimmune polyendocrinopathy type 1, or APECED syndrome, in which there is a mutation of the AIRE gene).
• It is also associated with immune defects, include malfunctioning T lymphocytes and low levels of immunoglobulin.

Rarely, chronic mucocutaneous candidiasis develops in adult life. This is often as a result of a thymoma (tumour of the thymus gland) and is associated with internal diseases such as myasthenia gravis or myositis, or bone marrow defects such as aplastic anaemia, neutropenia and hypogammaglobulinaemia.

Human immunodeficiency virus (HIV) infection and hyper-IgE syndrome may also present with chronic mucocutaneous candidiasis.

Clinical features of chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis usually presents before the age of 3 years, with one or more of the following:

• Chronic oral candidiasis (thrush)
• Napkin (diaper) dermatitis
• Paronychia and candidal onychomycosis (nail infection)
• Widespread crusted plaques on the scalp, trunk, hands and feet
• Scarring alopecia (hair loss)
• Granulomas in the mouth, on the skin and/or nails
• Stenosis of oesophagus, larynx or vagina
• Iron deficiency.

Affected patients are also susceptible to infection with dermatophyte fungi (tinea) and human papillomavirus (warts).

Complications from chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis may result in premature death due to disseminated candida infection, sepsis, pneumonia, or mycotic aneurysms.

Patients have an increased risk of skin cancer, and ear, nose, and oesophageal cancers.

How is chronic mucocutaneous candidiasis diagnosed?

The diagnosis of chronic mucocutaneous candidiasis is made on clinical grounds.

Microscopy and culture of skin swabs and skin scrapings confirm the presence of organisms.

Genetic testing may reveal a specific mutation.

How is chronic mucocutaneous candidiasis treated?

The underlying defect is not as yet treatable.

General measures

To reduce the incidence and severity of candida infection:

• Practice good oral hygiene (tooth brushing, oral rinsing, mouthwashes)
• Avoid smoking and alcohol.

Antifungal treatment

Treatment depends on repeated or prolonged courses of oral antifungal medications, often in higher doses than is normally necessary for candida infections.  Oral antifungal medications used for chronic mucocutaneous candidiasis include:

• Fluconazole
• Itraconazole
• Posaconazole
• Voriconazole
• Liposomal amphotericin B
• Terbinafine (usually used to treat tinea infections)
• Echinocandins (caspofungin, micafungin, anidulafungin).

Drug resistance may occur.

Immunological therapy

Options to improve immune status include:

• Transfer factor
• JAK1/2 tyrosine kinase inhibitors, such as ruxolitinib
• Intravenous immunoglobulin G (IVIg G)
• Granulocyte-macrophage colony-stimulating factor (GM-CSF) infusions
• Interferon-α. 

Evaluation and treatment of associated endocrinopathies should be undertaken in consultation with an endocrinologist.