Allergic coNtAct DermAtitis of the foot - The Dermatologist

Allergen FocusIn this column, we highlight ACDand explore top relevant allergens, regional-and topic-based dermatitis presentationsand clinical tips and pearls fordiagnosis and treatment.Allergic Contact Dermatitis of the FootFoot dermatitis can be a chronic andrecalcitrant condition. Disability frompainful fissures and impaired gait maybe seen. Active dermatitis may lead to aweakened cutaneous barrier, which increasesthe potential risk for infection.Occupational implications also exist, inthat many patients require protectivefootwear for employment. If an allergyto this protective barrier equipment develops,the patient may be forced to seekother employment.When discussing ACD of the foot,there is a relatively stable microenvironmentof contactants, composed principallyof rubber compounds and accelerators,chromates, adhesives, dyes andretained contaminants, such as topicalmedicaments. 9-13 Table 1 highlightsthe most common of these allergens.In cultures that tend to favor the useof footwear, the shoe and sock encapsulatethis microenvironment and arethe source of potential allergens. Studieshave estimated that the prevalence offoot dermatitis due to shoes ranges from3.3% to 11.7% of patch-test patients. 14The development of ACD of the foot isfavored by friction and the hot, humidenvironment within the shoe. 15While this may initially appearstraightforward, one realizes on closerinspection that the anatomy of footwearis quite complex. The approach tofootwear can be simplified by consideringfive separate systems: (1) uppers orstraps, (2) soles, (3) insoles, (4) adhesivesand (5) heel and toe stiffeners. 16The upper or strap is the componentof the footwear that attaches to the soleand covers the dorsal foot. Leather isTable 1. Top Allergens 14,18AllergenMercaptobenzothiazoleMercapto MixThiuram MixCarba MixMixed Dialkyl ThioureasDithiodimorpholineBlack Rubber MixPotassium DichromateGlutaraldehydeFormaldehydep-tert-butylphenol formaldehyde resin (PTBFR)ColophonyEthyl/Methyl AcrylateDiaminodiphenylmethanecommonly utilized and may thereforebe a source of chromate exposure, dependingon how the leather was tanned.Some types of leather undergo a multisteptanning process. This process maystart with chromate tanning and involvesubsequent tanning with formaldehydeor glutaraldehyde. 12,16 In a retrospectiveanalysis published in 2007 by the NorthAmerican Contact Dermatitis Group(NACDG), potassium dichromate wasfound to be the second-most frequentshoe-related allergen. Only the adhesivep-tert-butylphenol-formaldehyde resinFoot dermatitis can be a chronic and recalcitrant condition.Disability from painful fissures and impaired gait may be seen.Active dermatitis may also lead to a weakened cutaneousbarrier, which increases the potential risk for infection.Occupational implications also exist, in that many patientsrequire protective footwear for their employment.NickelPreservatives(PTBFR) was more frequently positiveon patch testing. 14The sole of a shoe is the base. Thechemical composition of the sole dependson the type of shoe; leather, neoprene,polyurethane and various types ofrubber are commonly used. Neopreneis oil-resistant and commonly foundin the sole of occupational footwear. 16LocationRubberRubberRubberRubberRubberRubberRubberLeatherLeatherLeatherAdhesivesAdhesivesAdhesivesPolyurethaneLace eyelets, bucklesBiocidesWhile overall the single most commonshoe allergen in North America appearsto be PTBFR followed by chromate,taken as a group, rubber additives causea greater number of reactions. 14 In otherwords, rubber-related chemicals are themost common shoe allergen categoryoverall. This group includes carba mix,thiuram mix, mercaptobenzothiazole(MBT), mercapto mix, mixed dialkylthioureas, dithiodimorpholine (DTDM)and black rubber mix.The insole provides cushion and archsupport. The composition of the insolemay be leather, polyurethane, neopreneor a composite of rubber or paper fibers.Composite fiber insoles are cheaperand may be found in less expensivefootwear. These fibers are typically heldtogether by a resinous glue. To preventmicrobial degradation of these fibers, abiocides (preservative) is also typicallyadded. 16 Insoles of a shoe come in directcontact with the sock and plantarfoot region. While the plantar foot is innatelyresistant to ACD (because to therelatively thick skin of this region), thereare several key factors that can lead tosensitization. Potential sensitizing haptensof the insole may be released withheat, friction and sweat over time. Becausemost socks are porous, potentialallergens leached from the insole infil-November 2012 | The Dermatologist ® | www.the-dermatologist.com 21

Allergen FocusTable 2. Differential Diagnosis of Allergic Contact Dermatitis of the Foot 18,19Diagnosis Clinical Presentation CommentsACD of the foot (upper/strap) Dorsal foot dermatitis sparing the interdigital spaces. Classic “shoe pattern dermatitis”ACD of the foot (insole) Plantar dermatitis sparing the plantar arch and proximal creases of the toes. Typically spares areas most involved in palmoplantar pustulosis.ACD of the foot (sole)Can present as plantar dermatitis or as localized plaques of dermatitis on thethighs/buttock in patients with a habit of sitting with their legs folded andtheir feet underneath them.ACD of the foot (stiffeners) Dermatitis involving the dorsal toes and heels. Major differential for heel involvement is irritant dermatitis.ACD of the foot (adhesives)Irritant dermatitisMay present with dorsal foot dermatitis, plantar dermatitis or heel and toedermatitis.Parched and glazed appearance of skin with fine scaling that favors the heelsor bridges the dorsal toes and foot in an “apron pattern.”Heel irritant dermatitis is seen more often with frequent wearingof open back shoes such as flip flops. The apron pattern ismore often seen with atopic dermatitis.Atopic Dermatitis Favors the dorsal foot in childhood and the palmoplantar skin in adulthood. Look for other atopic stigmata such as Dennie-Morgan lines,allergic shinners, and hyperlinear thenar eminences.Nummular DermatitisJuvenile Plantar DermatosisPompholyxDyshidrotic EczemaPsoriasisPalmoplantar pustulosisPityriasis rubra pilarisTinea pedisDiscrete, coin-shaped crusted plaques on the dorsal foot.Smooth and glazed appearance with fine scaling localized to the plantar aspectof the forefoot and toes with sparing of the interdigital spaces.Severe sudden outbreaks of intensely pruritic vesicles symmetrically on thepalms, soles and lateral aspects of the digits.Similar to pompholyx but more of a subacute to chronic clinical presentationrather than an acute sudden outbreak.Well-demarcated, erythematous plaques with micaceous scale can be seen onthe dorsal foot. Plantar lesions tend to be more hyperkeratotic and often havea pustular quality. Nail pitting.Bilateral and symmetric erythematous plaques studded with minute pustuleson the central palms and soles.Salmon-orange appearing hyperkeratosis of the plantar foot extending up thesides in the so-called “sandal pattern.” Rarely associated with nail pitting.Dull erythema and fine scale on the sole and sides of the feet in a “moccasinor sandal pattern.” May see similar fine scaling on one palm giving a “onehand, two feet pattern.”Also known as dermatitis plantaris sicca or “sweaty sockdermatitis.”Keratoderma blenorrhagicum is a plantar eruption characteristicof reactive arthritis (Reiter Syndrome).Associated with smoking and thyroid disorders. Likely a localizedacral variant of psoriasis.KOH positive for dermatophyte hyphae is diagnostic.T. mentagrophytes can produce a bullous tinea that favors theplantar arch.trate the textile matrix easily. This createsa reservoir of potential allergens indirect contact with the skin of the footfor prolonged periods of time. Thenormally robust cutaneous barrier ofthe plantar foot may also be diminishedbecause of other conditions like eczemaor dermatophyte infection.Adhesives are necessary in the majorityof footwear for assembly. Theseglues are used to attach the insole tothe sole and to bind various componentsof the shoe top together. They area major source of shoe allergy. As mentioned,the primary relevant shoe adhesivefound on patch testing to causefoot dermatitis is the phenolic resinPTBFR. PTBFR has been shown toaccount for 10% to 20% of allergic reactionsto footwear. 15,16 It has been usedas an additive in rubber glues since the1950s and is ideally suited for footwearmanufacturing due to its strong adhesionto both leather and rubber. 17Heel and toe stiffeners are alsoknown as counters. This component ofthe shoe is meant to retain the overallshape of the shoe while strengtheningthe heel and toe. Stiffeners have aspectrum of complexity, ranging from asimple layer of inert adhesive to a complexweb of polyester or cotton. Similarto insoles, stiffeners can be a source ofexposure to rubber compounds, adhesivesand biocides. 16Differential DiagnosisThe differential diagnosis for an eczematouseruption of the foot can beclinically challenging. A categorical approachis helpful. The majority of casescan be sorted into one of the followingprinciple categories: (1) exogenousdermatitis, (2) endogenous dermatitis,(3) acral papulosquamous entities, (4)infectious entities and (5) hybrid dermatitis.18,19 Table 2 highlights this differentialdiagnosis.Exogenous dermatitis includes bothirritant and allergic contact dermatitis.The morphology of this group is theprototypical spectrum of acute, subacuteand chronic eczematous eruptions. Itis typical to see a poorly demarcated,spreading, erythematous and edematous,papulovesicular eruption. However, asthe lesions progress along the spectrumto a more chronic state, there is morescaling and lichenification, which cancause some confusion clinically withthe papulosquamous eruptions. Symptomatologyis useful in that pruritusfavors an allergic etiology and burningand stinging are more often seen withirritant etiologies. Finally, regional distributionis important to note. The clas-22 November 2012 | The Dermatologist ® | www.the-dermatologist.com

sic “shoe pattern dermatitis” on the footis suggestive of allergic contact dermatitis(Figure 1). This pattern shows aneczematous process involving the dorsalfoot and ankle with notable sparing ofthe inter-digital spaces. There is oftena relative symmetry, but one side maybe more heavily affected than the other.Spreading of the process up the anklesover time is also a clue to ACD. Thisis particularly true in the setting of achronic, stable, well-localized dermatitisthat then shifts to become poorly localizedand spreading.Endogenous dermatitis is often themost difficult to separate from allergiccontact dermatitis. This category includesatopic foot dermatitis, nummularfoot dermatitis, juvenile plantar dermatosisand the pompholyx-dyshidrosisspectrum. In many cases, the diagnosisof endogenous dermatitis is one of exclusion,made only after a negative patchtest has been performed to help rule outallergic contact dermatitis.Acral papulosquamous entities maybe easily diagnosed if typical stigmataare seen elsewhere on the patient. However,if involvement is limited to thefeet, there can be significant morphologicoverlap with chronic eczematousprocesses. Acral psoriasis, palmoplantarpustulosis and pityriasis rubra pilarisfall into this category. In a study inthe International Journal of Dermatology,70 patients suspected of having allergiccontact dermatitis of the foot underwentpatch testing; 30 were given a finaldiagnosis of psoriasis. 20Infectious entities of the feet aretypically less likely to be misdiagnosedas contact dermatitis, with one majorexception. Dermatophyte infection caneasily be missed and should always beconsidered in the differential diagnosisof a patient with a possible contact dermatitisof the foot.Hybrid dermatitis is a clinically usefulterm that takes into account the factthat many patients have multifactorialdisease. It is often the case that a patientmay be atopic with a component of irritantdermatitis and superimposed allergiccontact dermatitis. Utilizing theterm “hybrid dermatitis” brings intofocus the need to address all underlyingfactors to ensure clinical success. Similarto the endogenous group, this diagnosisis typically only made after the completionof a full work-up, including comprehensivepatch testing.Practical Aspects of Patch TestingAs discussed above, the differential diagnosisof foot dermatitis can be a challenge.Patch testing is the gold standardfor making the diagnosis of allergic contactdermatitis. Most patch test expertsadvocate an approach that utilizes anexpanded series, including testing componentsof the patient’s own footwearand socks. The most common allergenshave been listed in Table 1.While management of ACD of thefoot can be challenging, the majorityof patients should be able to attainsustained improvement or resolutionof their symptoms if proper patch testingis carried out and relevant allergensare avoided. 12 To maximize the yield ofpatch testing, it is important to recognizewhich patterns of foot dermatitisare most likely to show relevant positivereactions. For example, the previouslymentioned “classic shoe dermatitis pattern”with dorsal foot involvement is thefoot pattern most likely to show relevantpositive reactions on patch testing. 21Conversely, some patterns are importantto recognize because of their relativelylow yield on patch testing. One suchpattern is symmetric involvement ofboth the central palms and plantar feet.This pattern is more likely to be an endogenouseczema or psoriasis and has alower yield on patch testing for relevantpositive reactions.It is also important to know how tointerpret positive results. For example,nickel is a commonly tested and frequentlypositive allergen, but the relevanceof nickel allergy is somewhatunclear when considering foot dermatitis.Dimethylglyoxime-positive metalsnaps, fasteners, buckles or islets may berelevant in a patient with foot dermatitisand a positive patch test to nickel.Some reports also suggest that systemicnickel exposure in an allergic patientcan present as a dyshidrotic hand andfoot eczema. 22,23 Outside of these twosettings, a positive nickel patch test mayonly represent past sensitization withoutcurrent relevance. Similarly, a positivereaction to fragrance, neomycin,bacitracin or corticosteroid may or mayTable 3. ExPanded Shoe Series 15Allergen FocusAdhesivesp-tert-butylphenol-formaldehyde resinColophonyEpoxy ResinBenzoyl PeroxideDyesParaphenylendiamineDisperse Blue 106 or 124Rubber ComponentsBlack Rubber MixCarba MixMercaptobenzothiazole or Mercapto MixThiourea MixThiuram MixDithiodimorpholineLeather Tanning AgentsPotassium DichromateGlutaraldehydeFormaldehydenot currently be relevant. Evaluationof relevance for allergens that are notcore components of footwear like theabove allergens requires that the presenceof retained allergens be excluded.For example, odor-eliminating powdersand sprays may be a source of fragranceretention in footwear. Similarly, topicalmedicaments are frequently applied tothe feet and it is possible for these medicamentsto become embedded into thesock and footwear. 24,25When determining what allergensto test, a standard series to screen forcommon shoe allergens and occult allergens,such as those described in theprevious paragraph, is useful. However,it is also important to expand testingbeyond this standard series. It has beenshown that, in 12.7% of patients withfoot dermatitis, the NACDG standardseries failed to identify any relevantallergens. 14 This number of non-reactorsis reduced when testing includessamples taken directly from the patient’ssocks and shoes. 12,14 Samplescan be taken from footwear with an8-mm punch, thereby yielding piecesequal in size to a standard 8-mm Finnchamber. In addition, it is often helpfulto utilize an expanded shoe series.A good series will adequately screenfor sensitivity to adhesives, dyes, rubbercomponents and leather tanningagents, which may not be included onsome standard series. Table 3 high-November 2012 | The Dermatologist ® | www.the-dermatologist.com 23

Allergen FocusTable 4. Additional ResourcesFor more information about suppliers who offer preparedexpanded shoe series for patch testing, the followingresources may be helpful.1. Allergeaze is an international company that offersindividual & series allergens, patch-test chambers andancillary products. Their website, www.allergeaze.com,can be accessed in English, German and Japanese.2. Chemotechnique is the self-described “world leaderin patch testing.” For information about their products,distributors and more, visit www.chemotechnique.se.3. Dormer Laboratories, Inc. offer information on sites andsources of allergen exposure, patch test kits and more.Visit www.dormer.ca/Phy_Pages/PatchTesting.aspx tolearn more.lights an example of an expanded shoeseries for patch testing. Several suppliersoffer prepared expanded shoe seriesfor patch testing; for more information,see Table 4.Pearls of Treatment: Every Dose CountsAs alluded to in the preface, one maybe exposed to, and subsequently sensitizedto, a contact allergen like chromatesin shoes for days to years beforedemonstrating the clinical picture ofACD. With every exposure, there is anincreasing risk of reaching a point atwhich the immune system meets itsmetaphorical “threshold” and subsequentexposures at this point can lead toelicitation of a cutaneous response, suchas foot dermatitis. 4,26 Just as repeatedcontact over time led to this immuneresponse, repeated avoidance will be requiredto induce remission.Avoidance of specific allergens infootwear can prove to be a tedioustask; however, there are programsavailable to aid in this endeavor. Boththe Contact Allergen ManagementProgram (CAMP), 27 a service offeredthrough the American Contact DermatitisSociety (ACDS), and the ContactAllergen Replacement Database(CARD), 28 developed by Mayo Clinic,allow a provider to enter a patient’sknown contact allergens and producea “shopping list” of products void ofthose particular chemicals. The programscan also exclude cross-reactors.These services are particularly invaluablein the case of occult shoe andsock allergens from retained personalproducts or topical medicaments.Another valuable resource availablethrough the ACDS is the Hand andFoot Dermatitis Alternatives section. 18This information is accessible throughthe ACDS website and includes informationon management pearls. Severalcompanies who offer hypoallergenicfootwear are also listed. nDr. Sheehan is with the departments ofdermatology at Indiana University School ofMedicine and Richard L. Roudenbusch VeteransHospital in Indianapolis, IN, and DermatologyPhysicians, Inc in Columbus, IN.Disclosure: Dr. Sheehan has no conflicts of interestto disclose.References1. Bickers DR, Lim HW, Margolis D, et al. Theburden of skin diseases: 2004 a joint project ofthe American Academy of Dermatology and theSociety for Investigative Dermatology. J Am AcadDermatol. 2006;55(3):490-500.2. Hsu JW, Matiz C, Jacob SE. Nickel allergy: Localized,id and systemic manifestations in children.Pediatr Dermatol. 2011;28(3):276-280.3. Salam TN, Fowler JF Jr. Balsam-related systemiccontact dermatitis. J Am Acad Dermatol.2001;45(3):377-81.4. Nijhawen RI, Matiz C, Jacob SE. Contact dermatitis:From basics to allergodromes. Pediatr Ann.2009;38(2):99-108.5. Militello G, Jacob SE, Crawford GH. Allergiccontact dermatitis in children. Curr Opin Pediatr.2006;18(4):385–390.6. Valks R, Conde-Salazar L, Cuevas M. Allergiccontact urticaria from natural rubber latex inhealthcare and non-healthcare workers. 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Accessibility verifiedOctober 15, 2012.19. James WD, Berger TG, Elston DM, Odom RB.Andrews’ Diseases of the Skin: Clinical Dermatology.Philadelphia: Saunders Elsevier, 2006.20. Rani Z, Hussain I, Haroon TS. Common allergensin shoe dermatitis: Our experience in Lahore,Pakistan. Int J Dermatol. 2003:42(8):605–607.21. Lazzarini R, Duarte I, Marzagão C. Contactdermatitis of the feet: A study of 53 cases. Dermatitis.2004:15(3):125–130.22. Veien NK, Hattel T, Laurberg G. Low nickeldiet: An open, prospective trial. J Am Acad Dermatol.1993;29(6):1002–1007.23. Veien NK, Hattel T, Justesen O, Nørholm A.Dietary treatment of nickel dermatitis. Acta DermVenereol. 1985;65(2):138–142.24. Nedorost S, Kessler M, McCormik T.Allergens retained in clothing. Dermatitis.2007;18(4):212–214.25. Rietschel RL. Role of socks in shoe dermatitis.Arch Dermatol. 1984;120(3):398.26. Jacob SE, Herro EM, Taylor J. “Contact Dermatitis:Diagnosis and Therapy.” In: Elzouki AY,et al., eds. Textbook of Clinical Pediatrics, PediatricDermatology Section, 2nd Edition. Springer-Verlag,Berlin Heidelberg, 2012; Volume 3, Section 9,1467-1476.27. ACDS CAMP. American Contact DermatitisSociety. 2011. Available at: http://www.contactderm.org/i4a/pages/index.cfm?pageid=3489.Accessibility verified October 15, 2012.28. CARD: Contact Allergen ReplacementDatabase. 2012. Available at: http://www.preventice.com/card/.Accessibility verified October15, 2012.Sharon E. Jacob, MDDr. Jacob, the SectionEditor of Allergen Focus,is Associate ClinicalProfessor of Medicine andPediatrics WOS (Dermatology)at the Universityof California, San Diego.Disclosure: Dr. Jacob is an investigator for SmartchoiceUSA PREA-2 trial.24 November 2012 | The Dermatologist ® | www.the-dermatologist.com