Editor's Note: Please see the PDF attached on this page for the tables mentioned in this article.
Foot dermatitis can be a chronic, recalcitrant condition associated with disability, a weakened cutaneous barrier and occupational implications. Avoidance of specific allergens in footwear and use of alternative products are crucial for resolution.
Allergic Contact Dermatitis (ACD) is an important disease that notably affects 14.5 million Americans each year.1 The economic impact of this disease is high in terms of both patient morbidity and loss of income, school and work, not to mention significant expenditures for visits to healthcare providers and for medicaments.1 Once patch testing is performed and a culprit has been identified, education becomes critical to ensure adherence to an avoidance regimen. With allergen avoidance, remission of the dermatitis ensues. If patients are unable to comply with the avoidance regimen, they become at risk for recurrent or sustained dermatitis or progression to a systematized presentation.2,3 In fact, education of the patient often begins before the diagnostic patch test is ever placed. This ensures that the patient has an appropriate understanding of potential outcomes, including his or her central role in both the disease and treatment.
In the initial consultation, patients are often taught about the pathophysiology of ACD: its delayed presentation; its relationship with the immune system (sensitization to a chemical and then elicitation of a dermatitis with re-exposure); and its occurrence at any point in time, even to something the patient has been using regularly for a short period of time or even intermittently for years. In certain cases, the topics of the other key players, such as irritant contact dermatitis (ICD) and contact urticaria, may be explained, as history (not patch testing) can point to these as the correct diagnosis for the patient. It is important to note that ICD, the most prevalent form of contact dermatitis, can, at times, precede or be a concomitant diagnosis with ACD.4,5 Unlike ACD, ICD is not immune-mediated but occurs secondary to contact with an irritating or abrasive substance. Contact urticaria (wheal and flare reaction), on the other hand, represents the least prevalent form of contact dermatitis. It is important to note that it is an immune-mediated phenomenon whose hallmark is an IgE and mast cell-mediated, immediate-type hypersensitivity reaction. We acknowledge this form of hypersensitivity due to the severity of the potential deleterious anaphylactic-type reactions and direct the reader to key sources.6,7,8
In this column, we highlight ACD and explore top relevant allergens, regional- and topic-based dermatitis presentations and clinical tips and pearls for diagnosis and treatment.
Allergic Contact Dermatitis of the Foot
Foot dermatitis can be a chronic and recalcitrant condition. Disability from painful fissures and impaired gait may be seen. Active dermatitis may lead to a weakened cutaneous barrier, which increases the potential risk for infection. Occupational implications also exist, in that many patients require protective footwear for employment. If an allergy to this protective barrier equipment develops, the patient may be forced to seek other employment.
When discussing ACD of the foot, there is a relatively stable microenvironment of contactants, composed principally of rubber compounds and accelerators, chromates, adhesives, dyes and retained contaminants, such as topical medicaments.9-13 Table 1 highlights the most common of these allergens. In cultures that tend to favor the use of footwear, the shoe and sock encapsulate this microenvironment and are the source of potential allergens. Studies have estimated that the prevalence of foot dermatitis due to shoes ranges from 3.3% to 11.7% of patch-test patients.14 The development of ACD of the foot is favored by friction and the hot, humid environment within the shoe.15
While this may initially appear straightforward, one realizes on closer inspection that the anatomy of footwear is quite complex. The approach to footwear can be simplified by considering five separate systems: (1) uppers or straps, (2) soles, (3) insoles, (4) adhesives and (5) heel and toe stiffeners.16
The upper or strap is the component of the footwear that attaches to the sole and covers the dorsal foot. Leather is commonly utilized and may therefore be a source of chromate exposure, depending on how the leather was tanned. Some types of leather undergo a multi-step tanning process. This process may start with chromate tanning and involve subsequent tanning with formaldehyde or glutaraldehyde.12,16 In a retrospective analysis published in 2007 by the North American Contact Dermatitis Group (NACDG), potassium dichromate was found to be the second-most frequent shoe-related allergen. Only the adhesive p-tert-butylphenol-formaldehyde resin (PTBFR) was more frequently positive on patch testing.14
The sole of a shoe is the base. The chemical composition of the sole depends on the type of shoe; leather, neoprene, polyurethane and various types of rubber are commonly used. Neoprene is oil-resistant and commonly found in the sole of occupational footwear.16 While overall the single most common shoe allergen in North America appears to be PTBFR followed by chromate, taken as a group, rubber additives cause a greater number of reactions.14 In other words, rubber-related chemicals are the most common shoe allergen category overall. This group includes carba mix, thiuram mix, mercaptobenzothiazole (MBT), mercapto mix, mixed dialkyl thioureas, dithiodimorpholine (DTDM) and black rubber mix.
The insole provides cushion and arch support. The composition of the insole may be leather, polyurethane, neoprene or a composite of rubber or paper fibers. Composite fiber insoles are cheaper and may be found in less expensive footwear. These fibers are typically held together by a resinous glue. To prevent microbial degradation of these fibers, a biocides (preservative) is also typically added.16 Insoles of a shoe come in direct contact with the sock and plantar foot region. While the plantar foot is innately resistant to ACD (because to the relatively thick skin of this region), there are several key factors that can lead to sensitization. Potential sensitizing haptens of the insole may be released with heat, friction and sweat over time. Because most socks are porous, potential allergens leached from the insole infiltrate the textile matrix easily. This creates a reservoir of potential allergens in direct contact with the skin of the foot for prolonged periods of time. The normally robust cutaneous barrier of the plantar foot may also be diminished because of other conditions like eczema or dermatophyte infection.
Adhesives are necessary in the majority of footwear for assembly. These glues are used to attach the insole to the sole and to bind various components of the shoe top together. They are a major source of shoe allergy. As mentioned, the primary relevant shoe adhesive found on patch testing to cause foot dermatitis is the phenolic resin PTBFR. PTBFR has been shown to account for 10% to 20% of allergic reactions to footwear.15,16 It has been used as an additive in rubber glues since the 1950s and is ideally suited for footwear manufacturing due to its strong adhesion to both leather and rubber.17
Heel and toe stiffeners are also known as counters. This component of the shoe is meant to retain the overall shape of the shoe while strengthening the heel and toe. Stiffeners have a spectrum of complexity, ranging from a simple layer of inert adhesive to a complex web of polyester or cotton. Similar to insoles, stiffeners can be a source of exposure to rubber compounds, adhesives and biocides.16
Differential Diagnosis
The differential diagnosis for an eczematous eruption of the foot can be clinically challenging. A categorical approach is helpful. The majority of cases can be sorted into one of the following principle categories: (1) exogenous dermatitis, (2) endogenous dermatitis, (3) acral papulosquamous entities, (4) infectious entities and (5) hybrid dermatitis.18,19 Table 2 highlights this differential diagnosis.
Exogenous dermatitis includes both irritant and allergic contact dermatitis. The morphology of this group is the prototypical spectrum of acute, subacute and chronic eczematous eruptions. It is typical to see a poorly demarcated, spreading, erythematous and edematous, papulovesicular eruption. However, as the lesions progress along the spectrum to a more chronic state, there is more scaling and lichenification, which can cause some confusion clinically with the papulosquamous eruptions. Symptomatology is useful in that pruritus favors an allergic etiology and burning and stinging are more often seen with irritant etiologies. Finally, regional distribution is important to note. The classic “shoe pattern dermatitis” on the foot is suggestive of allergic contact dermatitis (Figure 1, above). This pattern shows an eczematous process involving the dorsal foot and ankle with notable sparing of the inter-digital spaces. There is often a relative symmetry, but one side may be more heavily affected than the other. Spreading of the process up the ankles over time is also a clue to ACD. This is particularly true in the setting of a chronic, stable, well-localized dermatitis that then shifts to become poorly localized and spreading.
Endogenous dermatitis is often the most difficult to separate from allergic contact dermatitis. This category includes atopic foot dermatitis, nummular foot dermatitis, juvenile plantar dermatosis and the pompholyx-dyshidrosis spectrum. In many cases, the diagnosis of endogenous dermatitis is one of exclusion, made only after a negative patch test has been performed to help rule out allergic contact dermatitis.
Acral papulosquamous entities may be easily diagnosed if typical stigmata are seen elsewhere on the patient. However, if involvement is limited to the feet, there can be significant morphologic overlap with chronic eczematous processes. Acral psoriasis, palmoplantar pustulosis and pityriasis rubra pilaris fall into this category. In a study in the International Journal of Dermatology, 70 patients suspected of having allergic contact dermatitis of the foot underwent patch testing; 30 were given a final diagnosis of psoriasis.20
Infectious entities of the feet are typically less likely to be misdiagnosed as contact dermatitis, with one major exception. Dermatophyte infection can easily be missed and should always be considered in the differential diagnosis of a patient with a possible contact dermatitis of the foot.
Hybrid dermatitis is a clinically useful term that takes into account the fact that many patients have multifactorial disease. It is often the case that a patient may be atopic with a component of irritant dermatitis and superimposed allergic contact dermatitis. Utilizing the term “hybrid dermatitis” brings into focus the need to address all underlying factors to ensure clinical success. Similar to the endogenous group, this diagnosis is typically only made after the completion of a full work-up, including comprehensive patch testing.
Practical Aspects of Patch Testing
As discussed above, the differential diagnosis of foot dermatitis can be a challenge. Patch testing is the gold standard for making the diagnosis of allergic contact dermatitis. Most patch test experts advocate an approach that utilizes an expanded series, including testing components of the patient’s own footwear and socks. The most common allergens have been listed in Table 1.
While management of ACD of the foot can be challenging, the majority of patients should be able to attain sustained improvement or resolution of their symptoms if proper patch testing is carried out and relevant allergens are avoided.12 To maximize the yield of patch testing, it is important to recognize which patterns of foot dermatitis are most likely to show relevant positive reactions. For example, the previously mentioned “classic shoe dermatitis pattern” with dorsal foot involvement is the foot pattern most likely to show relevant positive reactions on patch testing.21 Conversely, some patterns are important to recognize because of their relatively low yield on patch testing. One such pattern is symmetric involvement of both the central palms and plantar feet. This pattern is more likely to be an endogenous eczema or psoriasis and has a lower yield on patch testing for relevant positive reactions.
It is also important to know how to interpret positive results. For example, nickel is a commonly tested and frequently positive allergen, but the relevance of nickel allergy is somewhat unclear when considering foot dermatitis. Dimethylglyoxime-positive metal snaps, fasteners, buckles or islets may be relevant in a patient with foot dermatitis and a positive patch test to nickel. Some reports also suggest that systemic nickel exposure in an allergic patient can present as a dyshidrotic hand and foot eczema.22,23 Outside of these two settings, a positive nickel patch test may only represent past sensitization without current relevance. Similarly, a positive reaction to fragrance, neomycin, bacitracin or corticosteroid may or may not currently be relevant. Evaluation of relevance for allergens that are not core components of footwear like the above allergens requires that the presence of retained allergens be excluded. For example, odor-eliminating powders and sprays may be a source of fragrance retention in footwear. Similarly, topical medicaments are frequently applied to the feet and it is possible for these medicaments to become embedded into the sock and footwear.24,25
When determining what allergens to test, a standard series to screen for common shoe allergens and occult allergens, such as those described in the previous paragraph, is useful. However, it is also important to expand testing beyond this standard series. It has been shown that, in 12.7% of patients with foot dermatitis, the NACDG standard series failed to identify any relevant allergens.14 This number of non-reactors is reduced when testing includes samples taken directly from the patient’s socks and shoes.12,14 Samples can be taken from footwear with an 8-mm punch, thereby yielding pieces equal in size to a standard 8-mm Finn chamber. In addition, it is often helpful to utilize an expanded shoe series. A good series will adequately screen for sensitivity to adhesives, dyes, rubber components and leather tanning agents, which may not be included on some standard series. Table 3 highlights an example of an expanded shoe series for patch testing. Several suppliers offer prepared expanded shoe series for patch testing; for more information, see Table 4.
Pearls of Treatment: Every Dose Counts
As alluded to in the preface, one may be exposed to, and subsequently sensitized to, a contact allergen like chromates in shoes for days to years before demonstrating the clinical picture of ACD. With every exposure, there is an increasing risk of reaching a point at which the immune system meets its metaphorical “threshold” and subsequent exposures at this point can lead to elicitation of a cutaneous response, such as foot dermatitis.4,26 Just as repeated contact over time led to this immune response, repeated avoidance will be required to induce remission.
Avoidance of specific allergens in footwear can prove to be a tedious task; however, there are programs available to aid in this endeavor. Both the Contact Allergen Management Program (CAMP),27 a service offered through the American Contact Dermatitis Society (ACDS), and the Contact Allergen Replacement Database (CARD),28 developed by Mayo Clinic, allow a provider to enter a patient’s known contact allergens and produce a “shopping list” of products void of those particular chemicals. The programs can also exclude cross-reactors. These services are particularly invaluable in the case of occult shoe and sock allergens from retained personal products or topical medicaments.
Another valuable resource available through the ACDS is the Hand and Foot Dermatitis Alternatives section.18 This information is accessible through the ACDS website and includes information on management pearls. Several companies who offer hypoallergenic footwear are also listed.
Dr. Sheehan is with the departments of dermatology at Indiana University School of Medicine and Richard L. Roudenbusch Veterans Hospital in Indianapolis, IN, and Dermatology Physicians, Inc in Columbus, IN.
Disclosure: Dr. Sheehan has no conflicts of interest to disclose.
Dr. Jacob, the Section Editor of Allergen Focus, is Associate Clinical Professor of Medicine and Pediatrics WOS (Dermatology) at the University of California, San Diego.
Disclosure: Dr. Jacob is an investigator for Smartchoice USA PREA-2 trial.
Editor's Note: Please see the PDF attached on this page for the tables mentioned in this article.
Foot dermatitis can be a chronic, recalcitrant condition associated with disability, a weakened cutaneous barrier and occupational implications. Avoidance of specific allergens in footwear and use of alternative products are crucial for resolution.
Allergic Contact Dermatitis (ACD) is an important disease that notably affects 14.5 million Americans each year.1 The economic impact of this disease is high in terms of both patient morbidity and loss of income, school and work, not to mention significant expenditures for visits to healthcare providers and for medicaments.1 Once patch testing is performed and a culprit has been identified, education becomes critical to ensure adherence to an avoidance regimen. With allergen avoidance, remission of the dermatitis ensues. If patients are unable to comply with the avoidance regimen, they become at risk for recurrent or sustained dermatitis or progression to a systematized presentation.2,3 In fact, education of the patient often begins before the diagnostic patch test is ever placed. This ensures that the patient has an appropriate understanding of potential outcomes, including his or her central role in both the disease and treatment.
In the initial consultation, patients are often taught about the pathophysiology of ACD: its delayed presentation; its relationship with the immune system (sensitization to a chemical and then elicitation of a dermatitis with re-exposure); and its occurrence at any point in time, even to something the patient has been using regularly for a short period of time or even intermittently for years. In certain cases, the topics of the other key players, such as irritant contact dermatitis (ICD) and contact urticaria, may be explained, as history (not patch testing) can point to these as the correct diagnosis for the patient. It is important to note that ICD, the most prevalent form of contact dermatitis, can, at times, precede or be a concomitant diagnosis with ACD.4,5 Unlike ACD, ICD is not immune-mediated but occurs secondary to contact with an irritating or abrasive substance. Contact urticaria (wheal and flare reaction), on the other hand, represents the least prevalent form of contact dermatitis. It is important to note that it is an immune-mediated phenomenon whose hallmark is an IgE and mast cell-mediated, immediate-type hypersensitivity reaction. We acknowledge this form of hypersensitivity due to the severity of the potential deleterious anaphylactic-type reactions and direct the reader to key sources.6,7,8
In this column, we highlight ACD and explore top relevant allergens, regional- and topic-based dermatitis presentations and clinical tips and pearls for diagnosis and treatment.
Allergic Contact Dermatitis of the Foot
Foot dermatitis can be a chronic and recalcitrant condition. Disability from painful fissures and impaired gait may be seen. Active dermatitis may lead to a weakened cutaneous barrier, which increases the potential risk for infection. Occupational implications also exist, in that many patients require protective footwear for employment. If an allergy to this protective barrier equipment develops, the patient may be forced to seek other employment.
When discussing ACD of the foot, there is a relatively stable microenvironment of contactants, composed principally of rubber compounds and accelerators, chromates, adhesives, dyes and retained contaminants, such as topical medicaments.9-13 Table 1 highlights the most common of these allergens. In cultures that tend to favor the use of footwear, the shoe and sock encapsulate this microenvironment and are the source of potential allergens. Studies have estimated that the prevalence of foot dermatitis due to shoes ranges from 3.3% to 11.7% of patch-test patients.14 The development of ACD of the foot is favored by friction and the hot, humid environment within the shoe.15
While this may initially appear straightforward, one realizes on closer inspection that the anatomy of footwear is quite complex. The approach to footwear can be simplified by considering five separate systems: (1) uppers or straps, (2) soles, (3) insoles, (4) adhesives and (5) heel and toe stiffeners.16
The upper or strap is the component of the footwear that attaches to the sole and covers the dorsal foot. Leather is commonly utilized and may therefore be a source of chromate exposure, depending on how the leather was tanned. Some types of leather undergo a multi-step tanning process. This process may start with chromate tanning and involve subsequent tanning with formaldehyde or glutaraldehyde.12,16 In a retrospective analysis published in 2007 by the North American Contact Dermatitis Group (NACDG), potassium dichromate was found to be the second-most frequent shoe-related allergen. Only the adhesive p-tert-butylphenol-formaldehyde resin (PTBFR) was more frequently positive on patch testing.14
The sole of a shoe is the base. The chemical composition of the sole depends on the type of shoe; leather, neoprene, polyurethane and various types of rubber are commonly used. Neoprene is oil-resistant and commonly found in the sole of occupational footwear.16 While overall the single most common shoe allergen in North America appears to be PTBFR followed by chromate, taken as a group, rubber additives cause a greater number of reactions.14 In other words, rubber-related chemicals are the most common shoe allergen category overall. This group includes carba mix, thiuram mix, mercaptobenzothiazole (MBT), mercapto mix, mixed dialkyl thioureas, dithiodimorpholine (DTDM) and black rubber mix.
The insole provides cushion and arch support. The composition of the insole may be leather, polyurethane, neoprene or a composite of rubber or paper fibers. Composite fiber insoles are cheaper and may be found in less expensive footwear. These fibers are typically held together by a resinous glue. To prevent microbial degradation of these fibers, a biocides (preservative) is also typically added.16 Insoles of a shoe come in direct contact with the sock and plantar foot region. While the plantar foot is innately resistant to ACD (because to the relatively thick skin of this region), there are several key factors that can lead to sensitization. Potential sensitizing haptens of the insole may be released with heat, friction and sweat over time. Because most socks are porous, potential allergens leached from the insole infiltrate the textile matrix easily. This creates a reservoir of potential allergens in direct contact with the skin of the foot for prolonged periods of time. The normally robust cutaneous barrier of the plantar foot may also be diminished because of other conditions like eczema or dermatophyte infection.
Adhesives are necessary in the majority of footwear for assembly. These glues are used to attach the insole to the sole and to bind various components of the shoe top together. They are a major source of shoe allergy. As mentioned, the primary relevant shoe adhesive found on patch testing to cause foot dermatitis is the phenolic resin PTBFR. PTBFR has been shown to account for 10% to 20% of allergic reactions to footwear.15,16 It has been used as an additive in rubber glues since the 1950s and is ideally suited for footwear manufacturing due to its strong adhesion to both leather and rubber.17
Heel and toe stiffeners are also known as counters. This component of the shoe is meant to retain the overall shape of the shoe while strengthening the heel and toe. Stiffeners have a spectrum of complexity, ranging from a simple layer of inert adhesive to a complex web of polyester or cotton. Similar to insoles, stiffeners can be a source of exposure to rubber compounds, adhesives and biocides.16
Differential Diagnosis
The differential diagnosis for an eczematous eruption of the foot can be clinically challenging. A categorical approach is helpful. The majority of cases can be sorted into one of the following principle categories: (1) exogenous dermatitis, (2) endogenous dermatitis, (3) acral papulosquamous entities, (4) infectious entities and (5) hybrid dermatitis.18,19 Table 2 highlights this differential diagnosis.
Exogenous dermatitis includes both irritant and allergic contact dermatitis. The morphology of this group is the prototypical spectrum of acute, subacute and chronic eczematous eruptions. It is typical to see a poorly demarcated, spreading, erythematous and edematous, papulovesicular eruption. However, as the lesions progress along the spectrum to a more chronic state, there is more scaling and lichenification, which can cause some confusion clinically with the papulosquamous eruptions. Symptomatology is useful in that pruritus favors an allergic etiology and burning and stinging are more often seen with irritant etiologies. Finally, regional distribution is important to note. The classic “shoe pattern dermatitis” on the foot is suggestive of allergic contact dermatitis (Figure 1, above). This pattern shows an eczematous process involving the dorsal foot and ankle with notable sparing of the inter-digital spaces. There is often a relative symmetry, but one side may be more heavily affected than the other. Spreading of the process up the ankles over time is also a clue to ACD. This is particularly true in the setting of a chronic, stable, well-localized dermatitis that then shifts to become poorly localized and spreading.
Endogenous dermatitis is often the most difficult to separate from allergic contact dermatitis. This category includes atopic foot dermatitis, nummular foot dermatitis, juvenile plantar dermatosis and the pompholyx-dyshidrosis spectrum. In many cases, the diagnosis of endogenous dermatitis is one of exclusion, made only after a negative patch test has been performed to help rule out allergic contact dermatitis.
Acral papulosquamous entities may be easily diagnosed if typical stigmata are seen elsewhere on the patient. However, if involvement is limited to the feet, there can be significant morphologic overlap with chronic eczematous processes. Acral psoriasis, palmoplantar pustulosis and pityriasis rubra pilaris fall into this category. In a study in the International Journal of Dermatology, 70 patients suspected of having allergic contact dermatitis of the foot underwent patch testing; 30 were given a final diagnosis of psoriasis.20
Infectious entities of the feet are typically less likely to be misdiagnosed as contact dermatitis, with one major exception. Dermatophyte infection can easily be missed and should always be considered in the differential diagnosis of a patient with a possible contact dermatitis of the foot.
Hybrid dermatitis is a clinically useful term that takes into account the fact that many patients have multifactorial disease. It is often the case that a patient may be atopic with a component of irritant dermatitis and superimposed allergic contact dermatitis. Utilizing the term “hybrid dermatitis” brings into focus the need to address all underlying factors to ensure clinical success. Similar to the endogenous group, this diagnosis is typically only made after the completion of a full work-up, including comprehensive patch testing.
Practical Aspects of Patch Testing
As discussed above, the differential diagnosis of foot dermatitis can be a challenge. Patch testing is the gold standard for making the diagnosis of allergic contact dermatitis. Most patch test experts advocate an approach that utilizes an expanded series, including testing components of the patient’s own footwear and socks. The most common allergens have been listed in Table 1.
While management of ACD of the foot can be challenging, the majority of patients should be able to attain sustained improvement or resolution of their symptoms if proper patch testing is carried out and relevant allergens are avoided.12 To maximize the yield of patch testing, it is important to recognize which patterns of foot dermatitis are most likely to show relevant positive reactions. For example, the previously mentioned “classic shoe dermatitis pattern” with dorsal foot involvement is the foot pattern most likely to show relevant positive reactions on patch testing.21 Conversely, some patterns are important to recognize because of their relatively low yield on patch testing. One such pattern is symmetric involvement of both the central palms and plantar feet. This pattern is more likely to be an endogenous eczema or psoriasis and has a lower yield on patch testing for relevant positive reactions.
It is also important to know how to interpret positive results. For example, nickel is a commonly tested and frequently positive allergen, but the relevance of nickel allergy is somewhat unclear when considering foot dermatitis. Dimethylglyoxime-positive metal snaps, fasteners, buckles or islets may be relevant in a patient with foot dermatitis and a positive patch test to nickel. Some reports also suggest that systemic nickel exposure in an allergic patient can present as a dyshidrotic hand and foot eczema.22,23 Outside of these two settings, a positive nickel patch test may only represent past sensitization without current relevance. Similarly, a positive reaction to fragrance, neomycin, bacitracin or corticosteroid may or may not currently be relevant. Evaluation of relevance for allergens that are not core components of footwear like the above allergens requires that the presence of retained allergens be excluded. For example, odor-eliminating powders and sprays may be a source of fragrance retention in footwear. Similarly, topical medicaments are frequently applied to the feet and it is possible for these medicaments to become embedded into the sock and footwear.24,25
When determining what allergens to test, a standard series to screen for common shoe allergens and occult allergens, such as those described in the previous paragraph, is useful. However, it is also important to expand testing beyond this standard series. It has been shown that, in 12.7% of patients with foot dermatitis, the NACDG standard series failed to identify any relevant allergens.14 This number of non-reactors is reduced when testing includes samples taken directly from the patient’s socks and shoes.12,14 Samples can be taken from footwear with an 8-mm punch, thereby yielding pieces equal in size to a standard 8-mm Finn chamber. In addition, it is often helpful to utilize an expanded shoe series. A good series will adequately screen for sensitivity to adhesives, dyes, rubber components and leather tanning agents, which may not be included on some standard series. Table 3 highlights an example of an expanded shoe series for patch testing. Several suppliers offer prepared expanded shoe series for patch testing; for more information, see Table 4.
Pearls of Treatment: Every Dose Counts
As alluded to in the preface, one may be exposed to, and subsequently sensitized to, a contact allergen like chromates in shoes for days to years before demonstrating the clinical picture of ACD. With every exposure, there is an increasing risk of reaching a point at which the immune system meets its metaphorical “threshold” and subsequent exposures at this point can lead to elicitation of a cutaneous response, such as foot dermatitis.4,26 Just as repeated contact over time led to this immune response, repeated avoidance will be required to induce remission.
Avoidance of specific allergens in footwear can prove to be a tedious task; however, there are programs available to aid in this endeavor. Both the Contact Allergen Management Program (CAMP),27 a service offered through the American Contact Dermatitis Society (ACDS), and the Contact Allergen Replacement Database (CARD),28 developed by Mayo Clinic, allow a provider to enter a patient’s known contact allergens and produce a “shopping list” of products void of those particular chemicals. The programs can also exclude cross-reactors. These services are particularly invaluable in the case of occult shoe and sock allergens from retained personal products or topical medicaments.
Another valuable resource available through the ACDS is the Hand and Foot Dermatitis Alternatives section.18 This information is accessible through the ACDS website and includes information on management pearls. Several companies who offer hypoallergenic footwear are also listed.
Dr. Sheehan is with the departments of dermatology at Indiana University School of Medicine and Richard L. Roudenbusch Veterans Hospital in Indianapolis, IN, and Dermatology Physicians, Inc in Columbus, IN.
Disclosure: Dr. Sheehan has no conflicts of interest to disclose.
Dr. Jacob, the Section Editor of Allergen Focus, is Associate Clinical Professor of Medicine and Pediatrics WOS (Dermatology) at the University of California, San Diego.
Disclosure: Dr. Jacob is an investigator for Smartchoice USA PREA-2 trial.
Editor's Note: Please see the PDF attached on this page for the tables mentioned in this article.
Foot dermatitis can be a chronic, recalcitrant condition associated with disability, a weakened cutaneous barrier and occupational implications. Avoidance of specific allergens in footwear and use of alternative products are crucial for resolution.
Allergic Contact Dermatitis (ACD) is an important disease that notably affects 14.5 million Americans each year.1 The economic impact of this disease is high in terms of both patient morbidity and loss of income, school and work, not to mention significant expenditures for visits to healthcare providers and for medicaments.1 Once patch testing is performed and a culprit has been identified, education becomes critical to ensure adherence to an avoidance regimen. With allergen avoidance, remission of the dermatitis ensues. If patients are unable to comply with the avoidance regimen, they become at risk for recurrent or sustained dermatitis or progression to a systematized presentation.2,3 In fact, education of the patient often begins before the diagnostic patch test is ever placed. This ensures that the patient has an appropriate understanding of potential outcomes, including his or her central role in both the disease and treatment.
In the initial consultation, patients are often taught about the pathophysiology of ACD: its delayed presentation; its relationship with the immune system (sensitization to a chemical and then elicitation of a dermatitis with re-exposure); and its occurrence at any point in time, even to something the patient has been using regularly for a short period of time or even intermittently for years. In certain cases, the topics of the other key players, such as irritant contact dermatitis (ICD) and contact urticaria, may be explained, as history (not patch testing) can point to these as the correct diagnosis for the patient. It is important to note that ICD, the most prevalent form of contact dermatitis, can, at times, precede or be a concomitant diagnosis with ACD.4,5 Unlike ACD, ICD is not immune-mediated but occurs secondary to contact with an irritating or abrasive substance. Contact urticaria (wheal and flare reaction), on the other hand, represents the least prevalent form of contact dermatitis. It is important to note that it is an immune-mediated phenomenon whose hallmark is an IgE and mast cell-mediated, immediate-type hypersensitivity reaction. We acknowledge this form of hypersensitivity due to the severity of the potential deleterious anaphylactic-type reactions and direct the reader to key sources.6,7,8
In this column, we highlight ACD and explore top relevant allergens, regional- and topic-based dermatitis presentations and clinical tips and pearls for diagnosis and treatment.
Allergic Contact Dermatitis of the Foot
Foot dermatitis can be a chronic and recalcitrant condition. Disability from painful fissures and impaired gait may be seen. Active dermatitis may lead to a weakened cutaneous barrier, which increases the potential risk for infection. Occupational implications also exist, in that many patients require protective footwear for employment. If an allergy to this protective barrier equipment develops, the patient may be forced to seek other employment.
When discussing ACD of the foot, there is a relatively stable microenvironment of contactants, composed principally of rubber compounds and accelerators, chromates, adhesives, dyes and retained contaminants, such as topical medicaments.9-13 Table 1 highlights the most common of these allergens. In cultures that tend to favor the use of footwear, the shoe and sock encapsulate this microenvironment and are the source of potential allergens. Studies have estimated that the prevalence of foot dermatitis due to shoes ranges from 3.3% to 11.7% of patch-test patients.14 The development of ACD of the foot is favored by friction and the hot, humid environment within the shoe.15
While this may initially appear straightforward, one realizes on closer inspection that the anatomy of footwear is quite complex. The approach to footwear can be simplified by considering five separate systems: (1) uppers or straps, (2) soles, (3) insoles, (4) adhesives and (5) heel and toe stiffeners.16
The upper or strap is the component of the footwear that attaches to the sole and covers the dorsal foot. Leather is commonly utilized and may therefore be a source of chromate exposure, depending on how the leather was tanned. Some types of leather undergo a multi-step tanning process. This process may start with chromate tanning and involve subsequent tanning with formaldehyde or glutaraldehyde.12,16 In a retrospective analysis published in 2007 by the North American Contact Dermatitis Group (NACDG), potassium dichromate was found to be the second-most frequent shoe-related allergen. Only the adhesive p-tert-butylphenol-formaldehyde resin (PTBFR) was more frequently positive on patch testing.14
The sole of a shoe is the base. The chemical composition of the sole depends on the type of shoe; leather, neoprene, polyurethane and various types of rubber are commonly used. Neoprene is oil-resistant and commonly found in the sole of occupational footwear.16 While overall the single most common shoe allergen in North America appears to be PTBFR followed by chromate, taken as a group, rubber additives cause a greater number of reactions.14 In other words, rubber-related chemicals are the most common shoe allergen category overall. This group includes carba mix, thiuram mix, mercaptobenzothiazole (MBT), mercapto mix, mixed dialkyl thioureas, dithiodimorpholine (DTDM) and black rubber mix.
The insole provides cushion and arch support. The composition of the insole may be leather, polyurethane, neoprene or a composite of rubber or paper fibers. Composite fiber insoles are cheaper and may be found in less expensive footwear. These fibers are typically held together by a resinous glue. To prevent microbial degradation of these fibers, a biocides (preservative) is also typically added.16 Insoles of a shoe come in direct contact with the sock and plantar foot region. While the plantar foot is innately resistant to ACD (because to the relatively thick skin of this region), there are several key factors that can lead to sensitization. Potential sensitizing haptens of the insole may be released with heat, friction and sweat over time. Because most socks are porous, potential allergens leached from the insole infiltrate the textile matrix easily. This creates a reservoir of potential allergens in direct contact with the skin of the foot for prolonged periods of time. The normally robust cutaneous barrier of the plantar foot may also be diminished because of other conditions like eczema or dermatophyte infection.
Adhesives are necessary in the majority of footwear for assembly. These glues are used to attach the insole to the sole and to bind various components of the shoe top together. They are a major source of shoe allergy. As mentioned, the primary relevant shoe adhesive found on patch testing to cause foot dermatitis is the phenolic resin PTBFR. PTBFR has been shown to account for 10% to 20% of allergic reactions to footwear.15,16 It has been used as an additive in rubber glues since the 1950s and is ideally suited for footwear manufacturing due to its strong adhesion to both leather and rubber.17
Heel and toe stiffeners are also known as counters. This component of the shoe is meant to retain the overall shape of the shoe while strengthening the heel and toe. Stiffeners have a spectrum of complexity, ranging from a simple layer of inert adhesive to a complex web of polyester or cotton. Similar to insoles, stiffeners can be a source of exposure to rubber compounds, adhesives and biocides.16
Differential Diagnosis
The differential diagnosis for an eczematous eruption of the foot can be clinically challenging. A categorical approach is helpful. The majority of cases can be sorted into one of the following principle categories: (1) exogenous dermatitis, (2) endogenous dermatitis, (3) acral papulosquamous entities, (4) infectious entities and (5) hybrid dermatitis.18,19 Table 2 highlights this differential diagnosis.
Exogenous dermatitis includes both irritant and allergic contact dermatitis. The morphology of this group is the prototypical spectrum of acute, subacute and chronic eczematous eruptions. It is typical to see a poorly demarcated, spreading, erythematous and edematous, papulovesicular eruption. However, as the lesions progress along the spectrum to a more chronic state, there is more scaling and lichenification, which can cause some confusion clinically with the papulosquamous eruptions. Symptomatology is useful in that pruritus favors an allergic etiology and burning and stinging are more often seen with irritant etiologies. Finally, regional distribution is important to note. The classic “shoe pattern dermatitis” on the foot is suggestive of allergic contact dermatitis (Figure 1, above). This pattern shows an eczematous process involving the dorsal foot and ankle with notable sparing of the inter-digital spaces. There is often a relative symmetry, but one side may be more heavily affected than the other. Spreading of the process up the ankles over time is also a clue to ACD. This is particularly true in the setting of a chronic, stable, well-localized dermatitis that then shifts to become poorly localized and spreading.
Endogenous dermatitis is often the most difficult to separate from allergic contact dermatitis. This category includes atopic foot dermatitis, nummular foot dermatitis, juvenile plantar dermatosis and the pompholyx-dyshidrosis spectrum. In many cases, the diagnosis of endogenous dermatitis is one of exclusion, made only after a negative patch test has been performed to help rule out allergic contact dermatitis.
Acral papulosquamous entities may be easily diagnosed if typical stigmata are seen elsewhere on the patient. However, if involvement is limited to the feet, there can be significant morphologic overlap with chronic eczematous processes. Acral psoriasis, palmoplantar pustulosis and pityriasis rubra pilaris fall into this category. In a study in the International Journal of Dermatology, 70 patients suspected of having allergic contact dermatitis of the foot underwent patch testing; 30 were given a final diagnosis of psoriasis.20
Infectious entities of the feet are typically less likely to be misdiagnosed as contact dermatitis, with one major exception. Dermatophyte infection can easily be missed and should always be considered in the differential diagnosis of a patient with a possible contact dermatitis of the foot.
Hybrid dermatitis is a clinically useful term that takes into account the fact that many patients have multifactorial disease. It is often the case that a patient may be atopic with a component of irritant dermatitis and superimposed allergic contact dermatitis. Utilizing the term “hybrid dermatitis” brings into focus the need to address all underlying factors to ensure clinical success. Similar to the endogenous group, this diagnosis is typically only made after the completion of a full work-up, including comprehensive patch testing.
Practical Aspects of Patch Testing
As discussed above, the differential diagnosis of foot dermatitis can be a challenge. Patch testing is the gold standard for making the diagnosis of allergic contact dermatitis. Most patch test experts advocate an approach that utilizes an expanded series, including testing components of the patient’s own footwear and socks. The most common allergens have been listed in Table 1.
While management of ACD of the foot can be challenging, the majority of patients should be able to attain sustained improvement or resolution of their symptoms if proper patch testing is carried out and relevant allergens are avoided.12 To maximize the yield of patch testing, it is important to recognize which patterns of foot dermatitis are most likely to show relevant positive reactions. For example, the previously mentioned “classic shoe dermatitis pattern” with dorsal foot involvement is the foot pattern most likely to show relevant positive reactions on patch testing.21 Conversely, some patterns are important to recognize because of their relatively low yield on patch testing. One such pattern is symmetric involvement of both the central palms and plantar feet. This pattern is more likely to be an endogenous eczema or psoriasis and has a lower yield on patch testing for relevant positive reactions.
It is also important to know how to interpret positive results. For example, nickel is a commonly tested and frequently positive allergen, but the relevance of nickel allergy is somewhat unclear when considering foot dermatitis. Dimethylglyoxime-positive metal snaps, fasteners, buckles or islets may be relevant in a patient with foot dermatitis and a positive patch test to nickel. Some reports also suggest that systemic nickel exposure in an allergic patient can present as a dyshidrotic hand and foot eczema.22,23 Outside of these two settings, a positive nickel patch test may only represent past sensitization without current relevance. Similarly, a positive reaction to fragrance, neomycin, bacitracin or corticosteroid may or may not currently be relevant. Evaluation of relevance for allergens that are not core components of footwear like the above allergens requires that the presence of retained allergens be excluded. For example, odor-eliminating powders and sprays may be a source of fragrance retention in footwear. Similarly, topical medicaments are frequently applied to the feet and it is possible for these medicaments to become embedded into the sock and footwear.24,25
When determining what allergens to test, a standard series to screen for common shoe allergens and occult allergens, such as those described in the previous paragraph, is useful. However, it is also important to expand testing beyond this standard series. It has been shown that, in 12.7% of patients with foot dermatitis, the NACDG standard series failed to identify any relevant allergens.14 This number of non-reactors is reduced when testing includes samples taken directly from the patient’s socks and shoes.12,14 Samples can be taken from footwear with an 8-mm punch, thereby yielding pieces equal in size to a standard 8-mm Finn chamber. In addition, it is often helpful to utilize an expanded shoe series. A good series will adequately screen for sensitivity to adhesives, dyes, rubber components and leather tanning agents, which may not be included on some standard series. Table 3 highlights an example of an expanded shoe series for patch testing. Several suppliers offer prepared expanded shoe series for patch testing; for more information, see Table 4.
Pearls of Treatment: Every Dose Counts
As alluded to in the preface, one may be exposed to, and subsequently sensitized to, a contact allergen like chromates in shoes for days to years before demonstrating the clinical picture of ACD. With every exposure, there is an increasing risk of reaching a point at which the immune system meets its metaphorical “threshold” and subsequent exposures at this point can lead to elicitation of a cutaneous response, such as foot dermatitis.4,26 Just as repeated contact over time led to this immune response, repeated avoidance will be required to induce remission.
Avoidance of specific allergens in footwear can prove to be a tedious task; however, there are programs available to aid in this endeavor. Both the Contact Allergen Management Program (CAMP),27 a service offered through the American Contact Dermatitis Society (ACDS), and the Contact Allergen Replacement Database (CARD),28 developed by Mayo Clinic, allow a provider to enter a patient’s known contact allergens and produce a “shopping list” of products void of those particular chemicals. The programs can also exclude cross-reactors. These services are particularly invaluable in the case of occult shoe and sock allergens from retained personal products or topical medicaments.
Another valuable resource available through the ACDS is the Hand and Foot Dermatitis Alternatives section.18 This information is accessible through the ACDS website and includes information on management pearls. Several companies who offer hypoallergenic footwear are also listed.
Dr. Sheehan is with the departments of dermatology at Indiana University School of Medicine and Richard L. Roudenbusch Veterans Hospital in Indianapolis, IN, and Dermatology Physicians, Inc in Columbus, IN.
Disclosure: Dr. Sheehan has no conflicts of interest to disclose.
Dr. Jacob, the Section Editor of Allergen Focus, is Associate Clinical Professor of Medicine and Pediatrics WOS (Dermatology) at the University of California, San Diego.
Disclosure: Dr. Jacob is an investigator for Smartchoice USA PREA-2 trial.
Allergic Contact Dermatitis (ACD) is an important disease that notably affects 14.5 million Americans each year.1 The economic impact of this disease is high in terms of both patient morbidity and loss of income, school and work, not to mention significant expenditures for visits to healthcare providers and for medicaments.1 Once patch testing is performed and a culprit has been identified, education becomes critical to ensure adherence to an avoidance regimen. With allergen avoidance, remission of the dermatitis ensues. If patients are unable to comply with the avoidance regimen, they become at risk for recurrent or sustained dermatitis or progression to a systematized presentation.2,3 In fact, education of the patient often begins before the diagnostic patch test is ever placed. This ensures that the patient has an appropriate understanding of potential outcomes, including his or her central role in both the disease and treatment.
