Update on Diagnosis and Topical Management of Erythrasma This under-diagnosed cutaneous infection is caused by a bacterium but may respond to anti-fungal therapies.

By Joseph Bikowski, MD

rythrasma is a frequently under-diagnosed cutaneous infection caused by ECorynebacterium minutissi- mum. It commonly affects body folds, particularly the groin, and has been identified as one of the leading causes of interdigital foot infections.1 Traditionally, ery- thrasma has been considered to more frequently affect individuals living in warmer climates, though it can occur at any lattitude. Along with , , candida , furunculosis, Photos courtesy of Joseph Bikowski, MD , and folliculitis, ery- thrasma has been reported to Erythrasma. The image above shows involvement of the right axilla at baseline (left) and occur with increased incidence improvement following four weeks of once-daily application of ketoconazole foam (right). among obese individuals2 and those with .1 However, the infection may tial diagnosis of erythrasma includes cutaneous also be common among athletes, particularly fungal infections, including pityriasis rotunda, when affecting the toe webs.3 tinea corporis/cruris,4 tinea pedis, and pityriasis Among other cutaneous diseases, the differen- versicolor.5 Importantly, erythrasma may coexist

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with cutaneous dermatophyte infections.6 Proper Erythrasma has been found to have a higher diagnosis of erythrasma and any concomitant skin prevalence in diabetics and the obese.1,2 infection(s) is essential to allow initiation of appropriate therapy targeted at all causative Treatment Options organisms. Topical anti-infective therapy, includ- Systemic antibiotics offer proven efficacy and ing broad-spectrum ketoconazole, is typically suf- have been used for the management of erythras- ficient to manage the condition, although systemic ma; 250mg four times daily for 14 antibiotics have traditionally been advocated for days has been recommended as the systemic erythrasma and may be indicated for severe or antibiotic treatment of choice.1 Yet systemic refractive cases. antibiotics are currently described as a third-line treatment option for erythrasma, and they are Presentation and Prevalence known to confer limited efficacy for affected toe- Erythrasma is a bacterially mediated scaly skin webs.9,10 As dermatologists and other physicians eruption typically localized to warm, moist skin have become increasingly aware of antibiotic folds. The rash tends to be deep red to brown in resistance and its potential long-term impact on color and is not typically associated with signifi- patient care, there have been efforts to reduce the cant pruritus. Erythrasma was once improperly use of systemic antibiotics. Furthermore, systemic considered a fungal infection, though research medications in general tend to present a greater over the past 50 years has confirmed the role of risk of side effects and/or drug interactions com- C. minutissimum in its pathogenesis. 7,8 These pared to topical agents. Given that erythrasma is a gram-positive bacteria are typically part of the generally benign condition, the use of systemic normal resident flora of human skin. In 1965, antibiotics as first-line therapy becomes question- Montes, et al. evaluated biopsied skin from able. patients with erythrasma absent any concomitant Topical antimicrobial therapies are second-line fungal etiology.8 They found C. minutissimum dis- choices for erythrasma management.9 Topical persed over the skin surface, between and pene- preparations containing antibiotics have not been trating superficial cornified cells, and within kera- shown in the published literatureto be very effec- tinized cells. Their investigation showed that the tive for treating erythrasma. However, antimicro- stratum corneum of affected patients was hyperk- bial ointment 2% has demonstrated eratotic and identified likely keratolytic processes efficacy, as has Whitfield’s ointment (salicylic acid associated with the presence of intracellular bac- and benzoic acid).1,9 Whitfield’s ointment reported- teria. ly has similar efficacy to systemic erythromycin Erythrasma generally is diagnosed through for erythrasma affecting the axillae and groin and visualization, but it may be mistaken for candidia- is superior to the oral agent in the interdigital sis, intertrigo, , seborrheic dermatitis, areas.1 contact dermatitis, or .1 Despite the potential efficacy of the topical Luminecescence with a Wood’s Lamp reveals a antimicrobial ointment preparations, they are not coral pink fluorescence that confirms the presence ideal in the clinical setting. They may lack cos- of C. minutissimum and supports the diagnosis. metic elegance and thus be associated with low The diagnosis may be missed if the patient has compliance. Most patients are unwilling to apply bathed within the preceeding 24 hours; bathing thick, greasy preparations to intertriginous areas may wash away coproporphyrin III, the pigment or toe webs. produced by C. minutissimum that causes fluores- Although a role for dermatophytes, yeasts, and cence. Fungal culture may be used to rule out molds in the pathogenesis of pure erythrasma has concomitant fungal infection. been disproven, topical antifungal formulations

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have been used with success to manage the condition and are described as first-line treatment options.9 Topical miconazole,11,12 clotrimazole,12 and econazole9 have all been shown effective for erythrasma. In one trial involving 61 patients with fungal infection or erythrasma, subjects were randomized to use topical tioconazole base 1% w/w or econazole nitrate 1% creams for a mean treatment period of 40 and 38 days respectively.13 All but two patients in each arm achieved clinical and mycologic Photos courtesy of Joseph Bikowski, MD cure and described treatment as The patient above is shown at baseline (left) and following 10 days of once-daily application generally acceptable, though of ketoconazole foam. mild intermittent pruritus was reported with econazole. Again, creams may not with hydrocortisone acetate 1%, no therapy, oint- be ideal for use in skin folds and interdigital ment vehicle alone, or hydrocortisone acetate spaces. alone. For the killed bacteria (i.e., no infection) In my clinical experience, a new ketoconazole groups, topical ketoconazole had anti-inflammato- foam 2% formulation (Extina, Stiefel), has been a ry activity comparable to that of hydrocortisone welcome new treatment option for erythrasma. acetate. For infected animals, ketoconazole was The foam vehicle (VersaFoam HF) is a superior to hydrocortisone. Combination therapy hydroethanolic formulation that is neither hydrat- was beneficial in both groups. ing nor drying. It is designed to rapidly dissolve at An added benefit of topical ketoconazole for the skin temperature leaving little to no residue. As management of erythrasma is that the broad-spec- such, it is ideal for application to skin folds. The trum antifungal will address any concomitant fun- foam can be easily applied to various body sites gal component of the presentation, eliminating the large and small and is readily applied to hair-bear- need for culture and optimizing the likelihood of ing skin, making it suitable for use in the axilla complete cutaneous clearance. and hair-bearing chest and abdomen. It is also easily and comfortably applied to the toe webs. Prevention Ketoconazole has long been recognized as hav- To reduce the likelihood of recurrence of erythras- ing a broad spectrum of activity.14 It confers docu- ma, patients must make efforts to reduce bacterial mented anti-inflammatory and antibacterial colonization and minimize moisture in the skin effects.15 Researchers demonstrated the agent’s folds. The use of antibacterial washes has been anti-inflammatory and antibacterial properties in a recommended, though no published data are guinea pig model.12 First, either living or killed available. Advise patients to thoroughly dry the Staphylococcus aureus was applied to the backs of skin after bathing. the animals, which then received either ketocona- Although standard laundering practices are zole 0.5% ointment alone or with hydrocortisone expected to prevent bacterial colonization of cloth- acetate 1%, ketoconazole 2% ointment alone or ing, bacteria may, like dermatophytes, colonize

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Cutaneous Infections Associated with out greasy residue, supporting patient compliance ■ ❑✔ Common cutaneous Less common infections: with therapy. infections: Dr. Bikowski has served on the advisory board, Candidiasis served as a consultant, received honoraria, and/or Intertigo Gas served on the speaker’s bureau for Allergan, Barrier, Candida folliculitis CollaGenex, Coria, Galderma, Intendis, Medicis, Furunculosis OrthoNeutrogena, PharmaDerm, Quinnova, Ranbaxy, Erythrasma Sanofi-Aventis, SkinMedica, Stiefel, UCB, and Tinea cruris Warner Chilcott. —Scheinfeld NS Folliculitis Clin Dermatol. 22(4):303-9 1. Holdiness MR. Management of cutaneous erythrasma. Drugs. 2002;62(8):1131-41. 2. Scheinfeld NS. Obesity and dermatology. Clin Dermatol. 2004 Jul- Aug;22(4):303-9. moist footwear.3 Patients with erythrasma involv- 3. Conklin RJ. Common cutaneous disorders in athletes. Sports Med. 1990 ing the toe webs may need to disinfect or replace Feb;9(2):100-19. shoes to eliminate exposure to bacteria. Once 4. Gupta S. Pityriasis rotunda mimicking tinea cruris/corporis and erythrasma in clear, patients should be advised to allow their an Indian patient. J Dermatol. 2001 Jan;28(1):50-3. shoes to thoroughly dry between wearing, perhaps 5. Aste N, Pau M, Aste N. Pityriasis versicolor on the groin mimicking erythras- alternating footwear every-other-day, if needed, to ma. Mycoses. 2004 Jun;47(5-6):249-51. allow drying. 6. Karakatsanis G, Vakirlis E, Kastoridou C, Devliotou-Panagiotidou D. Coexistence of pityriasis versicolor and erythrasma. Mycoses. 2004 Patients with a history of recalcitrant or recur- Aug;47(7):343-5. rent erythrasma may be directed to prophylacti- 7. Marks R, Ramnarain ND, Bhogal B, Moore NT. The erythrasma microorganism in cally apply topical ketaconozole foam to previous- situ: studies using the skin surface biopsy technique. J Clin Pathol. 1972 ly affected areas once daily. Sep;25(9):799-803. 8. Montes LF, McBride ME, Johnson WP, Owens DW, Knox JM. Ultrastructural study of the host-bacterium relationship in erythrasma. J Bacteriol. 1965 Multi-Targeted Intervention Nov;90(5):1489-91. The ability to manage a generally benign, bacteri- 9. Barkham MC, Smith AC. Erythrasma in Treatment of Skin Disease: ally-mediated cutaneous eruption with a topical Comprehensive Therapeutic Strategies, Lebwohl MG, et al., eds. 2005 Mosby, formulation that poses minimal risk of side effects Incorporated and no risk of bacterial resistance is ideal. As 10. Seville RH, Somerville DA. The treatment of erythrasma in a hospital for the mentally subnormal.Br J Dermatol. 1970 May;82(5):502-6 with all dermatologic presentations, therapeutic outcomes are optimized when patients are compli- 11. Pitcher DG, Noble WC, Seville RH. Treatment of erythrasma with miconazole. Clin Exp Dermatol. 1979 Dec;4(4):453-6. ant with therapy. In light of these considerations, 12. Clayton YM, Knight AG. A clinical double-blind trial of topical miconazole and ketoconazole foam 2% represents a new treatment clotrimazole against superficial fungal infections and erythrasma. Clin Exp option for the management of erythrasma that Dermatol. 1976 Sep;1(3):225-32. may increase compliance. 13. Grigoriu D, Grigoriu A. Double-blind comparison of the efficacy, toleration Topical ketoconazole provides both anti-inflam- and safety of tioconazole base 1% and econazole nitrate 1% creams in the treat- ment of patients with fungal infections of the skin or erythrasma. Dermatologica. matory and antibacterial properties that directly 1983;166 Suppl 1:8-13. target the underlying bacterial cause of erythras- 14. Van Tyle JH. Ketoconazole. Mechanism of action, spectrum of activity, phar- ma. It also provides broad-spectrum antifungal macokinetics, drug interactions, adverse reactions and therapeutic use. effects that eradicate the fungal component that Pharmacotherapy. 1984 Nov-Dec;4(6):343-73. frequently co-exists with erythrasma. The foam 15. Van Cutsem J, Van Gerven F, Cauwenbergh G, Odds F, Janssen PA. The antiin- flammatory effects of ketoconazole. A comparative study with hydrocortisone vehicle is particularly suited for application to acetate in a model using living and killed Staphylococcus aureus on the skin of skin folds, toe webs, and hair-bearing skin with- guinea-pigs. J Am Acad Dermatol. 1991 Aug;25(2 Pt 1):257-61.

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