Epidermal Barrier Dysfunction

Epidermal Barrier Dysfunction: Beyond Atopic Dermatitis Specialists describe how a disrupted barrier contributes to common dermatoses and offer strategies for treatment.

nderstanding of the structure and function A majority of research related to epidermal bar- of the epidermal barrier has expanded great- rier function has focused on classic atopic dermati- ly over the course of the last two decades.1 tis, which has come to be seen as the quintessen- UPrimary functions of the epidermal barrier tial disease of barrier dysfunction. However, are to protect against the entry of foreign sub- research continues to show that impaired barrier stances (antigens, irritants, and microbes). In addi- function contributes to a host of inflammatory der- tion to these primarily defensive roles, the epider- matoses, including rosacea,3 acne,4 and psoriasis.5 mis traps moisture and regulates hydration, and it The following provides a closer look at the diagno- synthesizes vitamin D.2 The epidermal barrier is sis and management of two cutaneous conditions not a passive structure. As keratinocytes mature to influenced by barrier dysfunction: juvenile plantar horny corneocytes, the epidermis is in a constantly dermatitis or wet-to-dry foot syndrome, and head active self-proliferating phase. In addition to physi- and neck dermatitis. cally blocking entry of most foreign substances, the barrier coordinates an immunologic defense Take-Home Tips. Juvenile Plantar Dermatitis tends to be chronic; against pathogens that manage to bypass the barri- typical interventions may be palliative but not curative. The dif- er. ferential diagnosis includes keratolysis exfoliativa and tinea The structure of the stratum corneum has been pedis. Topical corticosteroids are a standard treatment. An anti- described as a bricks-and-mortar structure. The inflammatory barrier repair therapy may represent a suitable “bricks” are covalently bonded corneocytes option for primary or adjunctive treatment in children with JPD. • arranged in compact, overlapping layers to hold When a dermatitic presentation on the head and neck of a patient moisture in while keeping allergens, pathogens, and environmental toxins (such as UV radiation) out. with a current or past history of AD does not respond well to stan- The “mortar” consists of ceramides, cholesterol, dard therapies, consider the potential influence of Malassezia, and lipids. Together, these elements form lipid for which antifungal therapy is beneficial. Airborne pattern AD bilayers that fill the spaces between the corneo- simulates photodermatitis with subtle distinctions and responds cytes. This extracellular matrix provides necessary to avoidance plus barrier repair therapy. ● permeability of moisture to the stratum corneum.

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Barrier Disease Beyond Eczema: Management of Juvenile Plantar Dermatitis with a Physiologic Barrier Repair Cream

By Joseph Bikowski, MD

uvenile plantar dermatosis (JPD), also known fissuring and cracking. In some cases, the skin of as wet-to-dry foot syndrome or sweaty socks the affected areas desquamates. Although general- syndrome, is a poorly understood and under- ly associated with hyperhidrosis, ironically, JPD Jstudied condition whose presentation may may be associated with anhidrosis.9 mimic that of numerous other common der- The desquamation of the skin can mimic kera- matoses. Due to a lack of published data on the tolysis exfoliativa, but this typically presents ini- condition, its prevalence is not well known. tially as pin-size white dots that coalesce.8 However, the condition may be somewhat com- Furthermore, keratolysis exfoliativa tends to affect mon. There is some evidence that JPD may be a the palms of the hands more often than the feet presentation of childhood atopic dermatitis and and is often asymptomatic.10 that it can persist into adulthood. The differential diagnosis of JPD also includes Clinical Presentation. Although juvenile plantar tinea pedis. However, tinea pedis typically involves dermatosis was first described more than three the fourth and fifth toe web spaces, whereas JPD decades ago,7 a literature search returns relatively generally spares the toe webs. Although tinea few publications on the condition. Taken together, pedis rarely affects small children, clinicians information from these few publications suggests should not assume based on a patient’s younger that the condition tends to be chronic with an age that a questionable presentation is JPD rather extended course of two to four years and that typi- than tinea pedis. A potassium hydroxide (KOH) cal interventions may be palliative but not cura- preparation can confirm or rule out tinea. tive.2,8 JPD may be misdiagnosed as classic atopic der- JPD typically presents as an erythematous rash matitis (AD) of the foot, given the young age of of the weight-bearing plantar aspects of the feet; affected individuals. While there is evidence of an the distal one-third of the plantar surface of the association between JPD and AD, they are distinct feet and toes tend to be involved more frequently. diagnoses. In a 10-year follow-up of patients diag- The postal two-thirds of the plantar surface are not nosed with JPD, researchers found that 52 percent involved. Areas of involvement generally are of JPD patients were atopic, and that JPD was smooth and shiny with a high incidence of painful often associated with hand eczema in adulthood.

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Fig. 1a Fig. 1b Photos courtesy of Joseph Bikowski, MD Fig. 1a. Juvenile plantar dermatitis at baseline. Fig. 1b. Patient shown following two weeks of twice-daily application of EpiCeram (Promius).

About 26 percent of individuals who had JPD as over extended periods of time (either through children experienced hand eczema as adults.6 hyperhidrosis occlusion of the foot via footwear Pathogenesis. The etiology and pathogenesis of made of non-breathable synthetic materials), high JPD are not well understood, though it is generally levels of surface moisture develop. However, it is accepted that excessive moisture of the feet con- well established that exposure to water does not tributes. There is no evidence for a fungal compo- induce skin hydration; in fact, persistent water nent to the disease. While there is no conclusive exposure is shown to disrupt epidermal barrier evidence implicating bacterial mediators, hypothe- function.11 Furthermore, there is recent evidence ses suggest that bacterial colonization may be a that TEWL increases as temperature increases,12 a factor in the pathogenesis.9 There is histopathologi- finding that may be relevant because non-breath- cal documentation of inflammation at the junctions able footwear may be associated with higher foot of sweat-gland ducts and acrosyringia in affected temperatures. individuals.9 As the disrupted barrier permits excessive evap- Irritants/allergens are not shown to contribute to oration of subcutaneous moisture (transepidermal the etiology of JPD. In the case of recalcitrant JPD, water loss or TEWL) beyond normal evaporation of patch testing may be indicated; data show that in moisture on the surface of the skin (skin surface one study population, half of patients diagnosed water loss, SSWL), a cycle of further degradation with non-atopic plantar dermatoses ultimately had and dysfunction ensues. With lack of hydration, positive patch reactions to at least one tested item. desiccated corneocytes on the epidermal layer The process of skin fissuring and desquamation shrink. It is likely that in the presence of depleted in JPD is not fully understood, but it may be lipids and epidermal proteins, corneocyte adhesion likened loosely to the formation of syneresis is diminished, and fissures develop. cracks in dried mud puddles (See Sidebar). As Another theory posits that in the hot, humid water evaporates out of the puddle, shrinkage environment of the shoe, sweat becomes “trapped” occurs, leading to the formation of cracks and fis- in the skin, producing corneocyte edema and exag- sures in the mud crust. gerated shearing stress.7 In JPD, when the foot is exposed to moisture Treatment Strategies. There is no specific treat-

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ment for JPD. Management strategies include avoidance of excess moisture through the selection Syneresis Cracks of breathable footwear and the avoidance of Derived from the Greek synairesis,meaning to contract, syneresis footwear when possible. This may help to reduce is the physical process of separation of liquid from a gel through the amount of sweating and also minimizes the contraction, and is even used in food chemistry to describe the effects of occlusion and friction that promote cuta- making of jelly. The term is used as an adjective to describe the neous peeling and cracking. Topical corticosteroids cracks that commonly form in desiccated mud puddles, which are are frequently used to diminish acute inflammation but do not seem to directly affect the patho- also sometimes called sun cracks. As water evaporates from the genesis. Therefore recurrence is common upon dis- muddy composite, fine sediment contracts and the “shrinkage continuation of corticosteroid therapy. cracks” form. Given that inflammation and barrier dysfunction are primary components of JPD, an anti- inflammatory barrier repair therapy may represent a suitable option for primary or adjunctive treatment in children with the condition. In clinical experience, twice-daily application of a barrier repair cream (EpiCeram) was associated with sig- nificant improvement in the appearance of the foot at the end of two weeks. Peeling and cracking were significantly reduced, and the patient report- ed reduced discomfort (Figs. 1a, 1b).

Finding and Treating the Causes of Head and Neck Dermatitis

By Matthew Zirwas, MD

ead and neck dermatitis can be a treatment ants can aid diagnosis and treatment. challenge for both patients and clinicians. Malassezia-exacerbated. When a dermatitic Importantly, variants of the condition have presentation on the head and neck of a patient Hbeen identified. Familiarity with these vari- with a current or past history of atopic dermatitis

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does not respond well to standard therapies, con- immunotherapy are usually not helpful. In suscep- sider the potential influence of Malassezia, which is tible patients, the proteins induce barrier dysfunc- known to exacerbate AD.13 Adolescent and adult tion and itch independent of IgE binding. patients with a history of typical flexural atopic Mite avoidance is simple, cheap, and often help- dermatitis—and often a history of mucosal aller- ful. Mite-preventing mattress and pillow covers, gies, as well—seem to be at increased risk for head when used properly, can be helpful. High quality and neck dermatitis. As sebum production increas- covers cost around $100 and can be found on the es in adolescence, Malassezia populations increase. Internet. Less expensive (and less comfortable) cov- At any time after that, even into the 30s or 40s, ers cost around $30 and can be found at Target or the patient can become IgE +/- CD4 sensitized to Walmart. These covers encase the mattress and pil- Malassezia, and the presence of the yeast will lead lowcase, and the normal sheets and pillowcases go to new onset of atopic dermatitis on the face, neck, over them. Frequently changing bed linens is rec- and upper chest, where sebum production and ommended. Weekly vacuuming of the home, and Malassezia counts are highest. especially the bedroom, is the only other interven- Malassezia-exacerbated head and neck dermatitis tion shown to be helpful. tends to be extremely recalcitrant to standard AD Patients should be instructed to shower twice therapies. However, itraconazole 100mg twice-daily daily to remove proteins from the skin. for two months generally yields clearance. When Immediately following the shower, patients should the acute flare is resolved after the initial two apply a physiologic moisturizer. Showering before months of therapy, a maintenance regimen of itra- bedtime may be especially helpful; patients should conazole 100mg once- or twice-daily on two days dress in freshly laundered nightclothes before get- per week may be continued indefinitely. ting into bed (re-wearing protein laden pajamas It is essential to recognize that patients have defeats the purpose of bathing). Allergen-specific underlying atopic dermatitis and require treatment immunotherapy may be helpful in some patients, beyond targeting Malassezia. Standard topical thera- but as noted above, is often not effective. pies for AD in other areas, including a physiologic Treatment consists of regular use of a physiolog- moisturizer, are indicated. ic moisturizer, CeraVe (Coria Laboratories) or Airborne Pattern. Another variant of AD is air- EpiCeram (Promius), whose mechanism—increasing borne pattern atopic dermatitis, which simulates production of endogenous stratum corneum lipids— photodermatitis with subtle distinctions. Airborne is completely unrelated to traditional moisturizers pattern AD tends to flare during the height of and likely leads to decreased penetration of these mucosal allergen seasons, unless dust mites—which airborne proteases. Topical corticosteroid therapy is are ubiquitously present—are involved. Data indi- indicated to manage acute flares. One of the most cate that certain recognized allergens have prote- effective and relatively inexpensive treatment olytic effects on the stratum corneum, activating options is a 50mL bottle of clobetasol solution com- Protease-activated receptor-2 (PAR-2). Activated pounded into a 16oz jar of CeraVe cream. This has PAR-2 directly causes itch and causes inflammatory been found to be extremely safe, highly effective, cytokine release from keratinocytes.14 Potentially and much better accepted by patients than tradi- causative airborne proteins so far identified include tional topical steroids. dust mite (the allergen most frequently associated with such reactions), cockroach, ragweed, birch, Keys to Success cedar, cypress, and juniper.14-16 It is extremely For successful management of any form of face and important to remember that this variant of AD is neck dermatitis or atypical atopic dermatitis, sever- not related to the allergenic effects of these pro- al principles guide patient care and support long- teins, and therefore, antihistamines and term efficacy. First and foremost is compliance:

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give patients one therapy to use in addition to appropriate skincare. Equally important is to avoid or minimize any additional damage to the barrier. If using topical steroids, for example, the patient must also be using a physiologic lipid-based moisturizer, which may reverse much of the barrier dysfunction caused by topical steroids. Finally, avoid ointments, which may be associated with decreased delivery of active ingredients, less compliance, and increased risk of infections. ■ Dr. Bikowski is a consultant and has served on the Advisory Board and Speakers Bureau for Promius Pharma. Services Include Dr. Zirwas is on the Speaker’s Bureau for Coria Laboratories and Astellas Pharma. Dermatology Practice Start-ups 1. Harding CR. The stratum corneum: structure and function in health and disease. Practice Management Consultation Services Dermatol Ther. 2004;17 Suppl 1:6-15. 2. Exp Dermatol. 2005 Oct;14(10):719-26. Interactions among stratum corneum Coding Presentations defensive functions. Elias PM, Choi EH. HIPAA Support 3. Meyer-Hoffert U. Reddish, scaly, and itchy: how proteases and their inhibitors contribute to inflammatory skin diseases. Arch Immunol Ther Exp OSHA Compliance (Warsz). 2009 Sep-Oct;57(5):345-54 4. Arch Dermatol Res. 1995;287(2):214-8. Impaired water barrier function in Bi-Monthly Newsletter acne vulgaris. Yamamoto A, Takenouchi K, Ito M. Lectures on Practice Management Issues 5. Zeeuwen PL, de Jongh GJ, Rodijk-Olthuis D, Kamsteeg M, Verhoosel RM, van Rossum MM, Hiemstra PS, Schalkwijk J. Genetically programmed differences in Insurance Credentialing Services epidermal host defense between psoriasis and atopic dermatitis patients. PLoS One. 2008 Jun 4;3(6):e2301. 6. Svensson A. Prognosis and atopic background of juvenile plantar dermatosis and gluteo-femoral eczema. Acta Derm Venereol. 1988;68(4):336-40. Book Store 7. Gibbs NF. Juvenile plantar dermatosis: Can sweat cause foot rash and peeling? Dermatology Nursing and Medical Assisting Manual Postgraduate Medicine 2004. 115(6):73. 8. Kalia S, Adams SP. Dermacase. Juvenile plantar dermatosis. Can Fam Medical Office Response to Emergency Physician. 2005 Sep;51:1203, 1213. 9. van Diggelen MW, van Dijk E, Hausman R. The enigma of juvenile plantar der- E/M Documentation Package matosis. Am J Dermatopathol. 1986 Aug;8(4):336-40. HIPAA Security Compliance Manual 10. Lee YC, Rycroft RJ, White IR, McFadden JP. Recurrent focal palmar peeling. Australas J Dermatol. 1996 Aug;37(3):143-4. HIPAA Privacy Compliance Manual 11. Perry AD, Trafeli JP. Hand dermatitis: review of etiology, diagnosis, and treatment. J Am Board Fam Med. 2009 May-Jun;22(3):325-30. Risk Management for Physician Offices 12. Cravello B, Ferri A. Relationships between skin properties and environmental Audit Tools parameters. Skin Res Technol. 2008 May;14(2):180-6. 13. Sugita T, Suto H, Unno T, Tsuboi R, Ogawa H, Shinoda T, Nishikawa A. Employee Policy Manual Molecular analysis of Malassezia microflora on the skin of atopic dermatitis patients and healthy subjects. J Clin Microbiol. 2001 Oct;39(10):3486-90. Getting Paid! 14. Gunawan H, Takai T, Ikeda S, Okumura K, Ogawa H. Protease activity of allergenic pollen of cedar, cypress, juniper, birch and ragweed. Allergol Int. 2008 Mar;57(1):83-91. 15. Roelandt T, Heughebaert C, Hachem JP. Proteolytically active allergens cause barrier breakdown. J Invest Dermatol. 2008 Aug;128(8):1878-80. 16. Jeong SK, Kim HJ, Youm JK, et al. Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery. J Invest Dermatol. 2008 Aug;128(8):1930-9.

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