Indian Journal of Paediatric Dermatology

: 2015  |  Volume : 16  |  Issue : 3  |  Page : 159--162

Successful treatment of chronic mucocutaneous candidiasis with oral antifungals and levamisole

Surabhi Sinha1, Rashmi Sarkar2, Vijay K Garg2,  
1 Department of Dermatology, S.T.D. and Leprosy, Dr. RML Hospital, New Delhi, India
2 Department of Dermatology, Venereology and Leprology, Maulana Azad Medical College, New Delhi, India

Correspondence Address:
Surabhi Sinha
C 403, Sabka Ghar C.G.H.S., Plot No. 23, Sector 6, Dwarka, New Delhi - 110 075


Chronic mucocutaneous candidiasis is a group of diseases in which patients have recurrent or persistent infections of the skin, nails or mucosae, caused by Candida, most commonly by Candida albicans. These patients may also develop noncandidal infections, mostly dermatophytoses and viral infections of the skin. Treatment of this condition is a dilemma as there is no sustained improvement on antifungals alone. This is attributable to the basic cause of the syndrome, which is a primary defect in the cellular immunity of skin. Three siblings, born out of a nonconsanguineous marriage, presented with persistent candidal infections since early childhood and had never been completely lesion-free. Two of them also had lesions of molluscum contagiosum and scarring reminiscent of herpes zoster infection. They were started on azole antifungal therapy, but they continued to develop recurrent skin and oral lesions over the next 3 months. Levamisole was then added as an immunomodulator and a sustained remission was observed over a follow-up period of 6 months. The addition of levamisole to the antifungal drugs led to a sustained clinical improvement which was maintained over the next 6 months. This suggests immunomodulators like levamisole could be a useful adjunct in such patients and their role needs to be investigated in larger trials.

How to cite this article:
Sinha S, Sarkar R, Garg VK. Successful treatment of chronic mucocutaneous candidiasis with oral antifungals and levamisole.Indian J Paediatr Dermatol 2015;16:159-162

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Sinha S, Sarkar R, Garg VK. Successful treatment of chronic mucocutaneous candidiasis with oral antifungals and levamisole. Indian J Paediatr Dermatol [serial online] 2015 [cited 2021 Jan 22 ];16:159-162
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Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of immune disorders with a primary defect of T-lymphocyte responsiveness to Candida. The disorder is characterized by chronic skin, nail and mucous membrane infections with Candida along with dermatophytes. Cutaneous viral infections may also occur; however, systemic candidiasis rarely occurs. Endocrinopathies (e.g., hypoparathyroidism, thyroid abnormalities, Addison disease) and autoimmune disorders may sometimes be associated. Topical and oral antifungal therapy may provide limited improvement early in the course of the disease, but repeated courses of these drugs for recurrences may lead to the development of resistance later in the course of the disease. Due to the primary defect in cellular immunity, immunomodulatory drugs have the ability to produce long-term remissions and are a promising mode of treatment in these patients, as demonstrated in our patients.


Three siblings, two girls aged 14 years and 10 years, and a boy aged 8 years, born out of a nonconsanguineous marriage, presented to our dermatology outpatient department with their mother. All three children had a history of oral thrush since around the age of 3 years. The younger two siblings also had a history of thickening and discoloration of the nails that developed around the age of 4 years. The elder sister and her brother had a history of recurrent painful oral aphthae. The boy also had few umbilicated raised lesions over both the knees and abdomen at presentation. However, the eldest sibling, a 17-year-old girl, was asymptomatic. Their mother was unaffected but gave a history of similar recurrent oral aphthae and persistent oral thrush in their father and a paternal aunt.

Examination of the children revealed oral candidiasis and perleche in all three [[Figure 1]a]. They also had multiple minor oral aphthae [[Figure 2]a]. The two younger children had onychomycosis [[Figure 1]b]. The boy had skin colored umbilicated papules of molluscum contagiosum over both the knees and filiform warts on his abdomen [[Figure 1]c]. Two of the siblings also had scarring reminiscent of herpes zoster over the trunk.{Figure 1}{Figure 2}

Microscopic examination of the scrapings from the oral cavities suspended in 10% Potassium hydroxide revealed pseudohyphae and epithelial cells. Fungal culture of the nails clippings yielded soft creamy colonies on Sabouraud’s Dextrose Agar medium [Figure 3]. Gram staining from these colonies showed budding yeast cells, thus confirming the organism to be Candida. Hemogram, liver, and kidney function tests, blood sugar, thyroid function tests, parathormone levels, cortisol levels, serum electrolytes, serum calcium and phosphorous and antinuclear antibodies were within normal limits. HIV antibody testing was negative and CD4 counts were normal. Immunoglobulins A, E, and M were normal for the three children. The Mantoux test for tuberculin sensitivity was significant as it was 0, 2, and, 0 mm, respectively.{Figure 3}

Thus, a diagnosis of CMC (autosomal dominant) was made and treatment was started with clotrimazole cream twice daily and oral fluconazole 6 mg/kg weekly. This led to an initial improvement in the candidiasis lesions, but even after 12 weeks of this treatment, oral aphthae kept appearing along with oral thrush. Thus, the children were also started on tab. Levamisole 2.5 mg/kg twice weekly and capsule zinc sulfate (elemental zinc 50 mg) twice daily for 6 months. Fluconazole was continued at the same dose during this period. At the end of these 6 months, all the children had become lesion free and thus all treatment was discontinued [[Figure 2]b]. They were followed up for the next 6 months during which time they remained lesion free except for occasional oral aphthae in the youngest sibling. The mother too reported that this was the longest remission they ever had.


Chronic mucocutaneous candidiasis is a spectrum of disorders in which the patients have persistent or recurrent infections of the skin, nails or/and mucosal membranes caused by Candida. In nearly all cases, the infecting species is Candida albicans. However, they very rarely develop Candida sepsis.

Chronic mucocutaneous candidiasis was first reported by Thorpe and Handley in 1929. Non candidal infections in these patients include dermatophytoses, verruca, molluscum contagiosum, herpes zoster, and recurrent pyogenic infections of the skin. Other dermatoses reported in CMC include recurrent aphthous stomatitis, seborrheic dermatitis, alopecia areata, and vitiligo.

The reason why CMC remains confined to the skin and mucosae is the difference in the mechanisms involved in the susceptibility to systemic and mucocutaneous candidiasis. Innate immunity (neutrophils and complement system) which is instrumental in protecting against systemic involvement is intact in CMC. However, there is a failure in these patients to develop a cell-mediated immune response to Candida, which leads to persistent and recurrent colonization of the skin and mucosal surfaces by the organism.[1] The exact underlying defect is unknown. Only recently, interleukin-17-producing T-cells have been reported to be involved in clearing Candida infections.[2] Even in our patients, there was notable anergy to tuberculin detected by the Mantoux test (0, 2, and 0 mm, respectively). Thus, in these patients, drugs known to restore cellular immunity have the ability to produce long-term remissions.

In the light of the knowledge we have at present regarding the immunologic basis of CMC, immunostimulatory drugs are a logical and reasonable option for such patients. The role of topical and oral antifungals cannot be negated in that they produce definite clinical and microbiological improvement.[3],[4] However, patients of CMC have been shown to develop resistance to azole antifungals.[5] Kamai et al. had reported the development of resistance to Fluconazole in their patient and had attributed it to the increased efflux of the drug and to the reduced affinity of the target enzyme.[5] In view of the risk of antifungal resistance, long-term treatment with them is not recommended.

To prevent recurrences and to target the primary immunodeficiency in these patients, immunostimulatory drugs such as cimetidine, levamisole, zinc, and Vitamin C have been tried. Cimetidine, an H2 receptor antagonist, has been shown to enhance a variety of immunologic functions because of its inhibitory effects on suppressor T-cell function.[6] Patients receiving cimetidine exhibit enhanced cell-mediated immunity as evaluated by increased responses to skin test antigens and increased responses of lymphocytes to mitogen stimulation.[6][7][8] However, the safety of oral Cimetidine is not established in patients below the age of 16 years. Since all our patients were below the safe age limit, we did not prescribe cimetidine.

Levamisole is another immunomodulatory drug used in many patients with extensive viral infections such as verruca and molluscum contagiosum. Levamisole decreases cAMP and increases cGMP levels in cells, thus maintaining intracellular cGMP which is required for neutrophil and macrophage mobility.[9],[10] It also makes the macrophages more hydrophilic. Through both these mechanisms, it promotes chemotaxis by both these types of cells.[9],[10] It is prescribed in a dose of 2.5 mg/kg twice–thrice weekly.

Zinc is a cofactor for thymulin, a thymic hormone essential for T-cell maturation; thus it too acts as an immunomodulator. Oral zinc sulfate in a dose of 200 mg once daily has been reported to be useful in CMC by Polizzi et al.[8]


We present a potential therapeutic regimen for maintaining remissions in CMC. However, our observation needs to be confirmed in a larger cohort of patients.


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