Dermatology

Erythrasma

Are You Confident of the Diagnosis?

Characteristic findings on physical examination

Erythrasma is a superficial cutaneous infection characterized by red-brown, wrinkling, possibly scaling, possibly pruritic, well demarcated plaques in flexural areas, including the interdigital (most common form), axillary, inguinal, intergluteal, and submammary folds. Lesions often begin as pink or red (Figure 1) and over time develop a brown discoloration. A nummular or disciform variant can be seen outside flexural folds, generally in the setting of diabetes or immunodeficiency. This form can clinically simulate pityriasis rotunda or parapsoriasis.

Figure 1.

Axillary erythrasma.

Expected results of diagnostic studies

Erythrasma is commonly mistaken for mycotic infections. Confirmation of the diagnosis can be quickly achieved using a Wood's lamp, which demonstrates the characteristic “coral red” fluorescence. A false negative Wood's lamp examination could be due to the removal of bacteria-derived coproporphyrin III. Ask the patient if he/she showered within 12 hours before the visit. Do not wipe the area with alcohol before the Woods lamp examination. Gram stain of the scale will reveal gram positive filamentous rods. Direct KOH examination is helpful in ruling out dermatophytosis.

Skin biopsy may be useful if the diagnosis is unclear, though identifying the filaments and rods in the stratum corneum with hematoxylin and eosin (H&E) staining can sometimes be difficult (Figure 2, Figure 3) Erythrasma is often considered a microscopically “invisible dermatosis,” as the epidermis and dermis may appear normal on routine histology. Special stains such as periodic acid-Schiff (PAS) and Giemsa can aid in visualization.

Figure 2.

Coccobacilli and filaments of Corynebacterium minutissimum in the stratum corneum (H&E, 60x).

Figure 3.

Coccobacilli and filaments of Corynebacterium minutissimum in the stratum corneum (H&E, 60x)

Bacterial culture is rarely warranted but can be accomplished in a modified tissue culture medium 199.

Diagnosis confirmation

Differential diagnosis includes the following:

For intertiginious involvement

--Allergic or irritant contact dermatitis: Erythematous, potentially vesiculated (in the acute form), potentially scaling and fissured plaques. Distribution and configuration are key to diagnosis as contact dermatitis is caused by some outside offending agent.

--Inverse psoriasis: Pink to red, often minimally scaling, potentially very pruritic, plaques involving the body folds. More common in obese patients.

--Seborrheic dermatitis: Scaly, possibly greasy appearing pink plaques specifically involving hair bearing areas including the scalp, post-auricular skin, brow and glabellar region, nasolabial folds, and chest

--Tinea cruris: Annular, pink-red plaques extending/advancing away from the genitocrural fold down the medial thigh; positive KOH examination with hyphae.

--Candidiasis: Bright erythematous plaques and papules with satellite lesion and positive KOH examination demonstrating pseudohyphae and buds.

--Tinea versicolor: Brown or white macules/patches and thin plaques involving predominantly the front of the chest, neck, and back. Positive KOH examination with pseudohyphae and spherical yeast.

For interdigital involvement

--Tinea pedis: Scaling, macerated in the toe clefts; possible bullous lesions; positive KOH examination with hyphae

--Polymicrobial toe web infections: Moist, potentially green maceration in toe clefts extending to the dorsal or plantar portions of the toes or foot.

Microbiologic examinations for appropriate antimicrobial therapy.

Who is at Risk for Developing this Disease?

--Patients with diabetes: It is recommended that patients with recurrent erythrasma be evaluated for diabetes.

--Obese patients

--Elderly patients

--Immunocompromised patients

--Athletes

--Patients with hyperhidrosis

--Patients with poor hygeine

--Patients living in humid, moist environments

What is the Cause of the Disease?

Etiology

Pathophysiology

Erythrasma is caused by Corynebacterium minutissimum, a gram positive, catalase positive aerobe that is considered part of the normal skin flora. Local environmental changes, such as increased heat or occlusion, stimulates C minutissimum to proliferate in the upper levels of the stratum corneum. Proliferation stimulates thickening of the stratum corneum, in which the bacteria inserts itself intracellularly through keratin degradation.

Systemic Implications and Complications

Erythrasma is typically a non–life-threatening cutaneous infection. Recurrent infections may indicate underlying diabetes mellitis.

Concurrent corynebacterium infections, such as trichomycosis axillaris (caused by C tenuis) and pitted keratolysis (Micrococcus sedentarius) should be ruled out.

Barrier disruption due to ongoing erythrasma may put the patient at risk for co-bacterial and fungal infections. There are a few reports in the literature of erythrasma infections in immunocompromised hosts resulting in cellulitis, septicemia, pyelonephritis, and endocarditis.

Treatment Options

--MEDICAL

Topical

--Clindamycin 1% solution or lotion

--Ketoconazole 2% cream or foam

--Oxiconazole cream

--Miconazole cream/lotion

--Clotrimazole cream

--Econazole cream

--Whitfield's ointment (salicylic acid + benzoic acid)

--Fusidic acid 2%

Systemic

--Erythromycin

--Clarithromycin

--Tetracycline

Physical

--Photodynamic therapy (red light)

Optimal Therapeutic Approach for this Disease

Although there is limited evidence available to compare treatment options, erythrasma fortunately responds to various topical and systemic therapies. Therefore choice of treatment depends on extent of disease, tolerability, and drug cost.

MEDICAL THERAPY

Local disease

The ideal treatment for local disease is a topical therapy with a low side-effect profile, patient tolerability, and low risk of bacterial resistance. For example, foams, solutions, or lotions are generally preferred over creams and ointments in the intertriginous areas, whereas creams and ointments may be better tolerated in flexural disease.

--Clindamycin 2% solution or lotion applied twice a day for 1-2 weeks is highly effective in treating erythrasma. Thorough washing with an antibacterial soap or benzoyl peroxide wash in conjunction with this therapy can accelerate infection clearance as well as limit bacterial resistance to clindamycin. Topically applied clindamycin can be absorbed in sufficient amounts to induce a systemic effect.

--Azole antifungals

The frequency of a concomitant fungal component (especially in the setting of interdigital disease) and the known anti-inflammAtory properties, as well as the previously demonstrated efficacy of azole antifungals, make this class of treatment a comparable first-line therapy to clindamycin.

Ketoconazole, miconazole, oxiconazole, and econazole have similar efficacy. Application is twice a day for 2 to 3 weeks. Oxiconazole demonstrated efficacy with once-daily dosing.

Ketoconazole is available in a foam preparation, which may be more cosmetically elegant and therefore better tolerated by patients with interdigital or intertriginous disease.

--Whitfield's ointment (benzoic acid 6%, salicylic acid 3%): Clearance with twice daily application for 2 weeks has been reported. Demonstrated similar efficacy to systemic erythromycin for axillary or groin erythrasma and superior efficacy to oral tetracycline. Irritation is a common side effect and has thus limited this author's use of this therapy.

--Fusidic acid 2%: Fusidic acid 2% ointment twice a day for 2 weeks has demonstrated complete resolution of erythrasma in the literature. Fusidic acid is not approved in the United States and therefore this author has minimal experience with this medication.

Diffuse disease

Erythromycin is the treatment of choice for diffuse or extensive erythrasma, but considered second line for limited infection. Treatment is dosed at either 250mg 4 times a day or 500mg twice a day for 7 to 14 days (depending on site of infection; interdigital infection may require the longer course). Dosing choice may depend on tolerability of gastrointestinal side effects associated with erythromycin use. Pediatric patients should be dosed at 30 to 50mg/kg/day, split into two doses, for 14 days.

Considerations:

--Erythromycin is pregnancy category B.

--Erythromycin is a potent inhibitor of the cytochrome P450 system, and therefore concomitant use with other medications metabolized by this pathway may increase serum concentrations. Examples include: cyclosporine, cisapride (risk of arrhythmias), carbamazepine, digoxin, warfarin, ergot alkaloid, HMG CoA-reductase inhibitors.

--The estolate formulation may cause cholestatic jaundice. Erythromycin is contraindicated in patients with hepatic disease.

Clarithromycin: Clarithromycin is considered a third-line therapy as the evidence of efficacy is limited and anecdotal. A single dose of clarithromycin 1gm demonstrated clearance of erythrasma within 2 weeks. Pediatric dosing is 15mg/kg once.

Considerations:

--Clarithromycin is pregnancy category C.

--As clarithromycin is in the macrolide family along with erythromycin, similar risks are associated with its use.

--Improved gastrointestinal side effect profile as compared with erythromycin.

--Co-administration with pimozide and fluconazole can increase the toxicity of clarithromycin.

--Increased risk of pseudomembranous collitis has been documented.

Tetracycline is considered a third-line therapy. Tetracycline 250mg 4 times daily for 14 days is the recommended dosing. Tetracycline has demonstrated similar efficacy to macrolides in treating interdigital erythrasma, though less so with respect to axillary or groin disease. Tetracycline may be considered in patients who can not tolerate erythromycin.

Considerations:

--Tetracycline is pregnancy category D.

--Should not be used in pediatric patients.

--Risks associated with tetracycline that should be discussed with patients include phototoxicity, pseudotumor cerebri, vestibular effects, and renal toxicity.

Mechanical therapy

Photodynamic therapy (red light): In theory, targeting the bacteria-generated porphyrins to induce bactericidal oxidative stress as a means of treating erythrasma appears plausible. Clinical data to date, however, do not support the use of this technology in the treatment of erythrasma.

Patient Management

Patients generally respond to therapy within 2 to 4 weeks.

Patients with refractory disease, specifically in the interdigital spaces, may require a combination of topical and systemic therapy. In both the setting of extensive, progressive, or frequently recurrent disease, a workup for diabetes or an underlying debilitating disease is warranted. As the diagnosis of erythrasma may sometimes be both clinically and histologically difficult, and providers may empirically treat cutaneous findings, a biopsy may be helpful in the setting of persistent disease.

To reduce the risk of recurrence, patients should be instructed to minimize bacterial colonization by using antibacterial washes or benzoyl peroxide gel/wash. Patients with recurrent disease may benefit from a daily prophylactic application of a topical azole antifungal rather than topical clindamycin (to reduce the risk of antibiotic resistance).

Reduction of chronic moisture exposure secondary to excessive sweating may be useful in preventing disease. Advocate weight loss if indicated. Anecdotal evidence using aluminum chloride to limit sweating demonstrated efficacy in preventing recurrences.

Dry skin thoroughly after bathing. Appropriately clean exposed clothing. This is of the utmost importance in the setting of foot interdigital erythrasma as bacteria and fungi can colonize moist footwear. Patients should be advised to allow their shoes to fully dry before wearing them. Alternating foot wear throughout the week may also limit recurrence.

Patients with known immunodeficiencies should be made aware of the high risk of recurrence as well as the potential for systemic involvement.

Unusual Clinical Scenarios to Consider in Patient Management

In the setting of immunodeficiency, cutaneous infection with C minutissimum can present as severe cellulitis, suppurative nodules or abscesses. Biopsy and tissue cultures can aid in the diagnosis. Treatment with oral erythromycin is curative. Local propylaxis in these patients should be considered.

Algorithm 1

If non-intertriginous areas are involved, start erythromycin 250 mg orally 4 times daily for 14 days

Tetracycline 250 mg orally 4 times daily for 14 days when erythromycin is contraindicated or not tolerated.

If intertriginous areas are involved, a topical agent in addition to systemic therapy is suggested in the following order: clindamycin 2% 3 times daily, Whitfield's ointment twice daily, or sodium fusidate 2% ointment twice daily, all of which would be for 14 days.

The concomitant use of antibacterial soap is also suggested.

Minimal information on the use of topical antifungals was provided.)

What is the Evidence?

Blaise, G, Nikkels, A, Hermanns-Le, T, Nikkel-Tassoudji, N, Pierard, GE. "Corynebacterium-associated skin infections". Int J Dermatol. vol. 47. 2008. pp. 884-90.

(A 2-year, two-center, prospective study was conducted to assess the demographics of pitted keratolysis, which included the association of concomittant erythrasma infection: 3.7% of participants reported erythrasma in association with pitted keratolysis. A review of the common and rare clinical presentations, diagnosis, and treatment of erythrasma is provided.The authors comment that there are no adequate evidence-based studies indicating the best therapeutic option. The authors recommend erythromycin 250mg orally 4 times daily for 14 days as the treatment of choice, with the recommendation for topical therapies in the setting of treatment failure or contraindication for systemic therapy.)

Holdiness, MR. "Management of cutaneous erythrasma". Drugs. vol. 62. 2002. pp. 1131-41.

(The impact on quality of life is discussed and a guideline for the diagnosis, treatment, and prevention is provided. Drug adverse effects and interactions for both topical and systemic therapies are reviewed. The authors recommended the following treatment algorithm following a confirmed diagnosis of erythrasma via Wood's lamp or microscopic examination:

Wharton, JR, Wilson, PL, Kincannon, JM. "Erythrasma treated with single dose clarithromycin". Arch Dermatol. vol. 134. 1998. pp. 671-2.

(In this case series, three patients with Wood's lamp-proven bilateral inguinal erythrasma were treated with a single dose of clarithromycin 1g. Oneof three patients reported mild gastrointestinal discomfort. Clinical and Wood's lamp examination 2 weeks following treatment were unremarkable. The authors suggested that single-dosed clarithromycin may be cost-effective and better tolerated. However, efficacy in interdigital erythrasma has yet to be demonstrated.)

Cochran, RJ, Rosen, T, Landers, T. "Topical treatment for erythrasma". Int J Dermatol. vol. 20. 1981. pp. 562-4.

(In this small case study, patients treated with clindamycin 2% solution 2 or 3 times daily for1 week demonstrated complete resolution. No recurrence of disease was noted 6 weeks following treatment.)

Seville, RH, Somerville, A. "The treatment of erythrasma in a hospital for the mentally subnormal". Br J Dermatol. vol. 82. 1970. pp. 502-6.

(In this 7-day comparative study, oral erythromycin was more effective than tetracycline in treating axillae and groin lesions (90% vs 70% respectively. Erythromycin was only slightly more efficacious than tetracycline in the treatment of interdigital disease. Topical Whitfield's ointment was shown to be equally as effective as erythromycin and superior to tetracycline.)

Clayton, YM, Knight, AG. "A clinical double-blind trial of topical miconazole and clotrimazole against superficial fungal infections and erythrasma". Clin Exp Dermatol. vol. 1. 1976. pp. 225-32.

(In this comparative study, six patients were treated with miconazole cream and five with clotrimazole cream, both twice daily. Patients in both groups were clear of infection at 4 weeks.)

Darras-Vercambre, S, Carpentier, O, Vincent, P, Bonnevalle, A, Thomas, P. "Photodynamic action of red light for treatment of erythrasma: preliminary results". Photodermatol Photoimmunol Photomed. vol. 22. 2006. pp. 153-6.

(In this study of 13 patients with erythrasma, red light (635nm) was employed to target the bacterial porphyrins as a means of eradicating the infection. Complete clearance was only noted in 3 of the 13 patients after a single treatment session.)

Ramelet, AA, Walker-Nasir, E. "One daily application of oxiconazole cream is sufficient for treating dermatomycoses". Dermatologica. vol. 175. 1987. pp. 293-5.

(In a double blind, randomized, multicenter study, daily application of oxiconazole cream was effective is treating erythrasma.)

Santos-Juanes, J, Galache, C, Martinez-Cordero, A, Curto, JR, Carrasco, MP, Ribas, A. "Cutaneous granulomas caused by Corynebacterium minutissimum in an HIV-infected man". J Eur Acad Venereol. vol. 16. 2002. pp. 643-5.

(A 22-year-old HIV-positive man presented with four painful, suppurative nodules on his lower extremities. Histology demonstrated abscess formation with a mixed cell infiltrate including neutrophils, lymphocytes and histiocytes. Tissue culture isolated Corynebacterium minutissimum. The patient responded to oral erythromycin.)

Halpern, AV, Heymann, WR, Bolognia, J, Jorizzo, J, Rapini, R. "Bacterial Infections". Dermatology e-edition. Elsevier Inc. 2008.

(This chapter reviews the breadth of cutaneous bacterial infections including gram postive and negative organisms as well as spirochetes. The section on erythrasma briefly reviews demographics, pathogenesis, clinical presentation, differential diagnosis, diagnostic modalities, and treatment options. The authors comment that oral erythromycin for 5 days is highly effective in more recalcitrant cases.)
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