Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
This article have been viewed 2203 times
Caroline Halverstam and Steven R. Cohen
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Cutaneous candidiasis is typically caused by Candida albicans, which exists as normal flora of human skin as well as in the gastrointestinal and genitourinary systems. Overgrowth of Candida species is suppressed by normal bacterial flora. Other Candida species occasionally cause mucocutaneous infections, the second most common being Candida tropicalis. Under certain conditions, these Candida species overgrow and become pathogens. Warmth and moisture of the intertriginous skin (axilla, inguinal folds, abdominal creases, inframammary creases), an increased skin pH, and the administration of antibiotics can disrupt the normal bacterial flora, allowing Candida to proliferate. Clinically, candidiasis presents as scaly erythematous patches with satellite papules and pustules. The diagnosis is made either microscopically, with a potassium hydroxide (KOH) preparation revealing spores and pseudohyphae, or by culture.
Topical antifungal agents include, but are not limited to, polyenes, azoles, allylamines, and ciclopirox olamines. Most studies required therapy twice daily for 4 weeks to ensure complete clearance in all patients. Notably, microscopic cure was often present before complete clinical clearance.
Topical corticosteroids are a source of controversy. Although the addition of corticosteroids to local antifungal therapy may reduce local inflammation in acute candidiasis, their use should be limited to 1 or 2 days because of their immunosuppressant properties.
Systemic therapy may be appropriate for cutaneous infections in immunosuppressed patients, in the setting of extensive disease not responding to topical therapy, or in patients non-compliant with topical therapy. Fluconazole 150 mg weekly appears to be as efficacious as fluconazole 50 mg daily or ketoconazole 200 mg daily. As in topical therapy, microscopic cure often precedes complete clinical clearance.
KOH
Culture
Diagnosis of superficial mycoses by direct microscopy: a statistical evaluation.
Mohanty JC, Mohanty SK, Sahoo RC, Sahoo A, Prahara. Indian J Dermatol Venereol Leprol 1999; 65: 72–4.
Scrapings and cultures were taken from 250 patients with superficial mycotic infections including 18 cases of candidiasis. Scrapings were cultured and examined by direct microscopy in 10% KOH solution . Eleven of the candidiasis cases showed pseudohyphae and blastospores on microscopic examination with KOH solution. Nine of the 18 cases of candidiasis had a positive culture. The overall sensitivity of a KOH test to detect any of the above mycoses was 89%, and was found to be as good at detecting mycoses as culture.
A multicenter, open-label study to assess the safety and efficacy of ciclopirox topical suspension 0.77% in the treatment of diaper dermatitis due to Candida albicans.
Gallup E, Plott T. J Drugs Dermatol 2005; 4: 29–34.
A multicenter, open-label study which included 44 male and female subjects aged 6–29 months with diaper dermatitis due to C. albicans. The study medication was applied topically to the affected area twice daily for 1 week. Subjects were clinically evaluated at baseline and at days 3, 7, and 14. The results showed a statistically significant improvement in both the rate of mycological cure and the reduction of severity score at each time point compared to baseline.
Topical treatment of dermatophytosis and cutaneous candidiasis with flutrimazole 1% cream: double-blind randomized comparative trial with ketoconazole 2% cream.
Del Palacio A, Cuetara S, Perez A, Garau M, Calvo T, Sánchez-Alor G. Mycoses 1999; 42: 649–55.
A double-blind, randomized study in which the efficacy and tolerance of flutrimazole 1% cream was compared with ketoconazole 2% cream, applied once daily for 4 weeks, in 60 patients with culture-proven dermatophytosis (47 patients) or cutaneous candidiasis (13 patients). The results of this study showed that flutrimazole 1% cream is as safe and effective as ketoconazole 2% cream for Candida and dermatophyte skin infections.
Naftifine cream in the treatment of cutaneous candidiasis.
Zaias N, Astorga E, Cordero CN, Day RM, de Espinoza ZD, DeGryse R, et al. Cutis 1988; 42: 238–40.
In a double-blind, parallel-group clinical trial, 60 patients with cutaneous candidiasis were randomly assigned to receive naftifine cream 1% or its vehicle twice a day for 3 weeks. Two weeks after the end of therapy, 77% of the naftifine-treated patients were mycologically cured (negative results on KOH preparations and culture) and had no clinically apparent disease, compared to only 3% of patients treated with vehicle alone.
A comparison of nystatin cream with nystatin/triamcinolone acetonide combination cream in the treatment of candidal inflammation of the flexures.
Beveridge GW, Fairburn E, Finn OA, Scott OL, Stewart TW, Summerly R. Curr Med Res Opin 1977; 4: 584–7.
In a multicenter double-blind trial, 31 patients with bilateral candidal lesions of the flexures were treated for 14 days with nystatin cream on one side and with a combination of nystatin and triamcinolone acetonide cream on the other side. Both treatments proved equally effective in terms of mycological cure rate and clinical improvement. There was a weak trend by both patients and physicians to favor the combination preparation because symptoms resolved more rapidly.
Prospective aetiological study of diaper dermatitis in the elderly.
Foureur N, Vanzo B, Meaume S, Senet P. Br J Dermatol 2006; 155: 941–6.
Of 46 patients, all over 85 years of age with dermatitis of the diaper area, 24 were identified as candidiasis. Of these, eight (33%) were cured after 1 month of topical bifonazole therapy, three (12.5%) improved, and 13 (54%) were cured after the addition of oral fluconazole 100 mg once daily for 1 month. Although topical antifungal drugs represent the first line of treatment for diaper dermatitis in the elderly, more than half the patients in this study required an oral antifungal to achieve a complete cure.
Fluconazole versus ketoconazole in the treatment of dermatophytoses and cutaneous candidiasis.
Stengel F, Robles-Soto M, Galimberti R, Suchil P. Int J Dermatol 1994; 33: 726–9.
Patients were treated with either fluconazole 150 mg once weekly plus daily placebo, or ketoconazole 200 mg once daily plus weekly placebo for 2 to 6 weeks. Candida was present in 21 of the evaluable 150 infection sites. Both treatments were clinically effective, with sites of infection responding equally to treatment with fluconazole and ketoconazole. Mycologic cure rates were seen in 68 of 73 fluconazole-treated patients and in 70 of 77 ketoconazole-treated patients. There were no major differences noted in the eradication rates between the various organisms. However, fluconazole offered the advantage of once-weekly oral administration.
A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis.
Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silny W. Int J Dermatol 1998; 37: 703–5.
Patients received either fluconazole 150 mg/week or 50 mg/day until clinically cured or for a maximum of 4 weeks. Of the patients in this study with candidiasis, 10 of 11 patients receiving fluconazole 150 mg weekly had a positive response (microscopic cure with marked clinical improvement) and 12 of 13 taking fluconazole 50 mg daily had a positive response. Thus, weekly treatment was determined to be equivalent to daily dosing.
Clinical trials and double-blind studies of oral antifungals for cutaneous candidiasis are sparse.
Antifungal activity of Lavandula angustifolia essential oil against Candida albicans yeast and mycelial form.
D’Auria FD, Tecca M, Strippoli V, Salvatore G, Battinelli L, Mazzanti G. Med Mycol 2005; 43: 391–6.
The antifungal activity of the essential oil of Lavandula angustifolia (lavender oil) and its main components, linalool and linalyl acetate, was studied. Lavender oil showed both fungistatic and fungicidal activity against C. albicans strains.
Perianal candidosis: a comparative study with mupirocin and nystatin.
De Wet PM, Rode H, Van Dyk A, Millar AJ. Int J Dermatol 1999; 38: 618–22.
This clinical trial compares the efficacy and clinical outcome of 2% mupirocin in a polyethylene glycol base and nystatin cream for the treatment of diaper candidiasis. Eradication of all Candida organisms was achieved within 2 to 6 days (mean 2.6 days) in 10 patients receiving topical mupirocin therapy (three to four times daily or with each diaper change). The 10 patients who received topical nystatin cream successfully cleared within 5 days (mean, 2.8 days). While both agents eradicated Candida, a major difference was the marked response of the diaper dermatitis to mupirocin, presumably due to its well documented bacteriocidal effects. The authors conclude that mupirocin is an excellent antifungal agent and a superior therapy for diaper dermatitis because of its polymicrobial toxicity.
Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of disorders with progressive and recurrent infections of the skin, nails, and mucosal surfaces caused by Candida albicans. The clinical presentation in patients with CMC can range from recurrent or recalcitrant thrush with a mild rash and dystrophic nails to severe generalized crusted plaques. Affected individuals have a defect in T-cell-mediated immunity; specifically, Th17 cells have recently been implicated. CMC typically presents in childhood. Half of those affected are identified as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). APECED is caused by mutations in the AIRE gene, which plays a key role in immunotolerance. It is characterized by hypoparathyroidism, hypothyroidism, and adrenal or gonadal failure. Candida susceptibility in APECED is attributed to autoantibodies directed against IL-17 and IL-22. Malabsorption, gastric cell atrophy, or autoimmune hepatitis occurs in about a third of patients. Alopecia, vitiligo, dental enamel dysplasia, and keratitis are frequent associations.
Other subtypes of CMC include autosomal dominant CMC with or without thyroid disease and autosomal recessive, isolated CMC. Recently, mutations in the STAT1 gene were found to underlie autosomal dominant CMC and lead to defective Th1 and Th17 responses. Thymoma has been also associated with rare cases of IL-17 and IL-22 autoantibody positive CMC.
Once the etiology of the symptoms is confirmed with a positive culture for C. albicans, a work-up should be done to test for immunodeficiency. Patients should also be tested for endocrine dysfunction characteristic of APECED. If clinical suspicion for APECED is high, genetic analysis for the AIRE gene can be performed. An association of CMC with abnormalities in iron metabolism or thymoma has also been reported in adult patients, so iron and radiological studies may be warranted in HIV-negative patients with adult-onset CMC.
Treatment usually begins with an oral azole, most commonly fluconazole or ketoconazole 100–200 mg/day. Intermittent use is often advocated to prevent resistance. However, resistance in CMC patients to these first-line drugs is frequently encountered and alternative options include second-generation azoles such as voriconazole and posaconazole, as well as echinocandins such as caspofungin and micafungin. Amphotericin B can be administered orally with variable response but minimal side effects. Due to toxicity, intravenous amphotericin B should generally be limited to short treatment courses with a transition to alternative therapies. Relapse after withdrawal of these agents is the rule since the inherent immune defect remains. Therapeutic strategies that augment the immune response can be very beneficial, including transfer factor (orally or parenterally) or high-dose cimetidine.
Complete blood count with differential
HIV antibody test
Thyroid-stimulating hormone
Fasting blood glucose
Plasma cortisol level
Parathyroid hormone
Serum calcium
Serum iron and ferritin
Chest X-ray or CT scan if thymoma suspected
Genetic testing for AIRE gene if suspicious for APECED
Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines.
Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV, et al. J Exp Med 2010; 207: 299–308.
Patients with APECED were found to have severely reduced IL-17F and IL-22 responses to C. albicans antigens.
STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis.
van der Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C, et al. N Engl J Med 2011; 365: 54–61.
DNA sequencing identified missense mutations in STAT1.
Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole: experience with twenty-one patients.
Horsburgh CR Jr, Kirkpatrick CH. Am J Med 1983; 74: 23–29.
Of the 21 patients in the study, eight had APECED. Patients weighing less than 40 kg were treated with ketoconazole 100 mg/day and patients weighing more than 40 kg were treated with ketoconazole 200 mg/day. All patients responded to treatment. Mucosal lesions improved by a mean of 6.7 days, cutaneous lesions improved by a mean of 22.7 days, and nails responded by a mean of 92.4 days. Adverse effects were infrequent: one patient had drug-induced hepatitis which resolved on discontinuation of the drug and two patients became hypertensive (the relationship of the hypertension to the treatment was unclear). After 12 and 14 months of therapy, two patients remained in remission for at least 7 and 19 months, respectively (they were symptom-free at the time of publication). After an initial response, two patients had relapses while on treatment (one after 6 months, the other after 23 months) and were noted to have resistant isolates.
Itraconazole in the treatment of two young brothers with chronic mucocutaneous candidiasis.
Tosti A, Piraccini BM, Vincenzi C. Pediatr Dermatol 1997; 14: 146–8.
Two children with CMC involving the mouth and nails were successfully treated with itraconazole 200 mg/day for 2 months. A rapid cure rate of both infections was observed. No relapses of oral or nail candidiasis were identified at a follow-up examination more than a year later. The drug was very well tolerated.
Fluconazole in the management of patients with chronic mucocutaneous candidiasis.
Hay RJ, Clayton YM. Br J Dermatol 1988; 119: 683–4.
Eight patients with CMC (five idiopathic cases, three APECED cases) and oral candidiasis were treated with 50 mg of fluconazole daily for up to 4 weeks. Clinical and mycologic remissions were achieved in all patients after a mean of 10 days. Three patients relapsed within 4 months (mean 56 days), but all responded to fluconazole 50 mg daily for 3 days. The authors suggest intermittent oral antifungal therapy as the most appropriate method to manage patients with oral candidiasis in CMC after induction of remission.
Voriconazole: a broad spectrum triazole for the treatment of serious and invasive fungal infections.
Maschmeyer G, Haas A. Future Microbiol 2006; 1: 365–5.
This is an excellent review of voriconazole (a second-generation triazole) for treating life-threatening fungal infections. Voriconazole can be given intravenously (6 mg/kg every 12 hours for two doses and then 4 mg/kg every 12 hours for maintenance dosing) or orally (200 mg every 12 hours for individuals over 40 kg and 100 mg every 12 hours for individuals less than 40 kg). It is effective for fluconazole-susceptible and -resistant candidiasis. Voriconazole is well tolerated. Although transient visual disturbances, liver enzyme abnormalities, skin cancers and skin rashes are reported, these rarely lead to discontinuation of treatment.
Successful treatment of chronic mucocutaneous candidiasis caused by azole-resistant Candida albicans with posaconazole.
Firinu D, Massidda O, Lorrai MM, Serusi L, Peralta M, Barca MP, et al. Clin Dev Immunol 2011; 283239.
A 39-year-old female patient with familial CMC who developed candidiasis that was resistant to multiple antifungal drugs was successfully treated with amphoteracin B. She was treated with amphotericin B 50 mg/day intravenously for 2 weeks followed by posaconazole 400 mg twice daily. After 2 months the dose was reduced to 200 mg/day without a relapse in symptoms. When posaconazole was discontinued, a relapse of oral candidiasis occurred after 2 weeks. She was thereafter maintained successfully on cycles of posaconazole 200 mg, three times per day, for a month with a 15-day discontinuation.
Activity of amphotericin B, anidulafungin, caspofungin, micafungin, posaconazole, and voriconazole against Candida albicans with decreased susceptibility to fluconazole from APECED patients on long-term azole treatment of chronic mucocutaneous candidiasis.
Rautemaa R, Richardson M, Pfaller MA, Perheentupa J, Saxen H. Diagn Microbiol Infect Dis 2008; 62: 182–5.
Forty-three isolates of C. albicans were taken from 23 patients with APECED and tested for resistance to various antifungals. Isolates were divided into two groups: fluconazole-susceptible dose-dependent and fluconazole-susceptible groups. All isolates were highly susceptible to amphotericin B and echinocandins. Posaconazole and voriconazole were active against all isolates, but more active in the fluconazole-susceptible group, suggesting a possibility that patients may develop some cross-resistance to these drugs when they take fluconazole.
Successful treatment of azole-resistant chronic mucocutaneous candidiasis with caspofungin.
Jayasinghe M, Schmidt S, Walker B, Rocken M, Schaller M. Acta Derm Venereol 2006; 86: 563–4.
An 18-year-old woman with CMC developed severe symptoms from an azole-resistant strain of C. albicans after 3 years of treatment with fluconazole. Following a 70 mg loading dose of intravenous caspofungin on the first day, the regimen was adjusted to 50 mg infusions four to seven times per week for almost 12 months. Clinical improvement of oral and cutaneous candidiasis was sustained during a follow-up period of 12 months. The treatment was well tolerated; the only side effect was a temporary elevation of hepatic enzyme levels that did not necessitate discontinuation of therapy.
Prolonged oral treatment of chronic mucocutaneous candidiasis with amphotericin B.
Montes LF, Cooper MD, Bradford LG, Lauderdale RO, Taylor CD. Arch Dermatol 1971; 104: 45–56.
Amphotericin B was given orally to four patients with CMC in doses of 1000–1800 mg/day. One patient had complete clearance of extensive candidal granulomas after 6 months of treatment; one patient had a slower but excellent response. Two other patients had minimal or no response; of these, one was hypothyroid and the other had a thymoma. Of note, the serum levels were significantly higher in the first two patients than the latter two. In all four patients the oral amphotericin B was free of side effects both clinically and in laboratory studies.
Chronic mucocutaneous candidiasis treated with amphotericin B. Case report.
Waweru HW, Owili DM. East Afr Med J 1983; 60: 588–91.
A 5-year-old girl with CMC was treated with intravenous amphotericin B at a dose of 1 mg/kg every other day for a cumulative dose of 200 mg. The crusts and plaques completely cleared, but with residual atrophy, hypopigmentation, and scarring alopecia. She remained free of recurrence for 2 years.
Case report: successful treatment with cimetidine and zinc sulphate in chronic mucocutaneous candidiasis.
Polizzi B, Origgi L, Zuccaro G, Matti P, Scorza R. Am J Med Sci 1996; 311: 189–90.
The clinical efficacy of high-dose cimetidine, 400 mg, three times daily, and zinc sulfate, 200 mg daily (subsequently adjusted to maintain blood zinc levels at the upper normal range), was evaluated in a patient with CMC for 16 months. An impressive reduction in infectious events was correlated with an increased CD4 (helper/inducer) cell count.
Transfer factor in chronic mucocutaneous candidiasis.
Masi M, De Vinci C, Baricrdi OR. Biotherapy 1996; 9: 97–103.
Fifteen patients with CMC were treated with an in vitro produced transfer factor (TF) specific for C. albicans antigens and/or with TF extracted from pooled buffy coats of blood donors: 400 million CEU per week for the first 2 weeks, followed by 100 million CEU per week for 6 to 12 months. All but one patient experienced significant improvement during treatment with specific TF.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
WhatsApp us
Topical antifungal
Topical antifungal combined with topical corticosteroids
Systemic azoles
Lavender oil
Topical mupirocin
Systemic azole antimycotics
Echinocandins
Oral amphotericin B
Intravenous amphotericin B
Transfer factor
Cimetidine and zinc sulfate
