Research in Review

Hand Dermatitis Update

May 2017

Allergic contact dermatitis (ACD) is an important disease that is estimated to affect up to 18 million Americans each year.¹ The economic impact of this disease is high in terms of both patient morbidity as well as loss of income, school, and work—not to mention significant expenditures for visits to health care providers and for medicaments.¹

Patch testing—the gold standard for ACD diagnosis—is utilized to confirm relevant allergens. Once patch testing is performed and an inciting allergen has been identified, education of the patient is critical to ensure adherence to an avoidance regimen. With avoidance, remission of the dermatitis is possible. If the patient is unable to comply with the avoidance regimen, they are 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 conducted to make sure the patient has an appropriate understanding of potential outcomes and his or her central role in both disease and treatment. During the initial consultation, providers must educate patients about the pathophysiology of ACD, including its delayed presentation, its relationship with the immune system (sensitization to a chemical and then elicitation of dermatitis with re-exposure), and its frequent recurrence rate.

The differential diagnoses will also need to be considered, especially with hand dermatitis where there are often confounders. It is important to note that irritant contact dermatitis (ICD), the most prevalent form of contact dermatitis, can, at times, precede or be a concomitant diagnosis with ACD.^4,5 Unlike ACD, ICD does not require prior sensitization and occurs from direct contact with an irritating or abrasive substance. On the other hand, contact urticaria (a type I, IgE-meditated, wheal- and flare-type hypersensitivity reaction) represents the least prevalent form of contact dermatitis; one should note that contact urticaria has the potential to evolve into a fully systemic, anaphylactic reaction. Sources for supplementary reading on this topic are available.^6-8 This article highlights ACD and explores top relevant allergens, regional- and topic-based presentations, and clinical tips and pearls for diagnosisband treatment, with a focus on hand dermatitis including its clinical and etiologic subtypes with an emphasis on ACD.

Background
Hand dermatitis, also known as hand eczema, is a common dermatologic disorder that affects a significant number of people across a wide age range.⁹ The socioeconomic impact of hand dermatitis can be profound, affecting both a person’s ability to perform tasks at both home and in the workplace. Women have been reported to have a higher prevalence of hand dermatitis than men and this may reflect practices, such as water immersion/wet work or threshold to access care.¹⁰ Hand dermatitis often has a relapsing and remitting course, but if diagnosis and management are postponed, the dermatitis may become chronic.¹¹

Hand dermatitis is the most common occupational skin disease: one study found that 82.6% of patients with occupational dermatitis had hand involvement.¹² It is estimated that more than 30 million Americans¹³ experience hand eczema each year at a cost of $0.9 to $3.8 billion per year.¹⁴ Individuals at particular risk include homemakers, bartenders, food workers, construction workers, hair stylists, cosmetologists, housekeeping personnel, health care workers, gardeners, and metalworkers.^15-21

Clinical Evaluation and Morphologic Classification
History
When evaluating a patient for hand dermatitis, it is critical to elicit history-based information that will give insight into the etiology of the presentation and help to direct work-up and management. Specifically, the evaluation should review duration and temporal course, aggravating/alleviating factors, type of emollient and frequency of use, recreation and occupational exposures, medications, personal hygiene products, personal and family history of skin diseases (especially nickel allergy, atopic dermatitis, and psoriasis), and past medical history.

Wet Work
Wet work²² is another important risk factor for hand dermatitis, which may be defined as:
• Direct skin contact with water >2 hours/day
• Use of occlusive gloves >2 hours/day
• Hand washing >20 times/day

Smoking
A commonly overlooked important risk factor in hand dermatitis is a history of smoking. Lai and Yew²³ found that heavy smokers were 5 times more likely to have active hand dermatitis compared to the general population. A combination of ICD and ACD are thought to be the major factors in the increased prevalence of hand dermatitis in active smokers. Both nickel and formaldehyde allergies have been associated with cigarette smoking.^24,25 Furthermore, cigarette smoke contains nicotine, carbon monoxide, and hydrogen cyanide which impairs skin repair by causing vasoconstriction, tissue hypoxia, and disrupting cellular metabolism, respectively. Smoking also impairs white blood cell migration, which confers an increased risk of infection.²⁶

Filaggrin
A key inherited risk factor that predisposes patients to develop hand dermatitis is a mutation of filaggrin. Filaggrin is a protein found in the stratum corneum of the skin that is responsible for maintaining skin barrier function. Abnormal filaggrin function leads to increased transepidermal water loss and has been found to predispose patients to develop atopic dermatitis, ACD, and ICD.^27,28 Kaae and colleagues evaluated hand characteristics of patients with known filaggrin loss-of-function mutations and found this subset of patients typically have a combination of hyperkeratosis on the dorsal aspects of the hands and fingers in addition to palmar hyperlinearity.²⁹

In addition to an inherited defect of filaggrin, studies have shown that inflammatory cytokines decrease skin filaggrin expression, leading to an acquired filaggrin deficiency.³⁰ Emollients to maintain skin barrier function and topical steroids/calcineurin inhibitors for their anti-inflammatory effects to suppress these inflammatory cytokines would be conceptually helpful in the treatment of filaggin deficiency.

Etiology and Classifications
The etiology of hand dermatitis is often multifactorial. Although there is no universally accepted classification system, several authors have attempted to organize the disease based on its morphologic and etiologic characteristics. The commonly described clinical subtypes of hand dermatitis are summarized in Table 1. In practice, it is not unusual for a mixture of clinical subtypes to coexist.³¹ Categorizing the clinical type of hand dermatitis is helpful as the morphologic variant can point toward the etiology. For example, a prospective study of 508 patients with hand dermatitis found hand ICD was most frequently associated with fissured, pulpitis, and nummular clinical subtypes.³²

The subtypes are commonly grouped into ICD, ACD, atopic hand eczema, protein contact dermatitis, vesicular endogenous hand eczema, hyperkeratotic endogenous hand eczema, and unclassified (Table 2).^32-35Classification into these subgroups can be a challenge when there are different etiologic factors leading to the presentation of hand eczema. In a study of 427 patients that sought to classify each patient’s hand dermatitis, approximately 90% of patients were diagnosed to have more than one etiologic subtype as the cause of their hand dermatitis.³²

In addition to a thorough history and physical exam, a work-up for hand dermatitis should aim to identify or exclude other diagnoses on the differential. Skin biopsies, swabs for culture, and laboratory tests may be needed. Table 3 outlines the common causes for chronic hyperkeratotic endogenous and unclassified types of hand eczema,^34-45though uncommon causes like cutaneous T-cell lymphoma and bullous pemphigoid have also been reported.^36,46

ACD and ICD in Hand Dermatitis
ICD is the most common diagnosis among patients in the general population with hand dermatitis accounting for 35% of the cases, followed by ACD (22%) and atopic dermatitis (19%).⁴⁷ In the occupational setting, a greater proportion of hand dermatitis cases have been attributed to ICD (76%).⁴⁸ In the clinical setting, ACD and ICD, especially in the chronic state, may be indistinguishable. In the acute phase, both may demonstrate erythema, papules, vesicles, bullae, weeping, urticaria, excoriations, and/or crusts, though with ICD the patient may be able to recall a temporally associated event. In the chronic phase, dryness, scaling, lichenification, and/or fissures predominate. Both acute and chronic ACD and ICD may be associated with pruritus and/or pain, although typically pruritus is more prominent in patients with ACD, while burning or pain predominate in ICD.^49,50

ICD classically occurs within hours of the exposure to the inciting irritant, although with hand dermatitis it is frequently associated with repeated and/or prolonged exposure to inciting agents. Furthermore, mechanical trauma (ie, friction or thermal insults) may also complicate the diagnosis and management.^33,49

If mild irritants are involved, or if the irritant is only encountered intermittently, the dermatitis may take weeks or months to develop.³³ ICD has a predilection for the palm, ball of the thumb, and the finger web spaces, sometimes extending from the web spaces onto the dorsal and/or ventral surfaces of the hand in an “apron-like” pattern.³³

Alternatively, ACD favors the fingertips, nail folds, and dorsal aspects of the hand and fingers, generally sparing the palm.^10,11,33 Of note, both ICD and AD may predispose a patient to ACD, due to epidermal barrier compromise and/or overlap of inflammatory pathways.^33,51 Symptoms of ACD often begin within 48 hours of re-exposure to a pre-sensitized allergen and can take sometimes weeks to manifest themselves. If the allergen is exclusively encountered at work, weekends or holidays may initially improve the dermatitis, although this finding diminishes as the dermatitis becomes chronic, with only one exposure every 2 to 6 weeks required to propagate chronic dermatitis.^15,33

The importance of patch testing for diagnostic accuracy was demonstrated by Duarte and colleagues¹⁰: 250 patients with hand dermatitis were initially given a diagnosis of ICD, ACD, atopic dermatitis, or vesicular hand dermatitis based on clinical history and physical exam. Patch testing was then performed and the diagnoses were reevaluated. Of the 73 patients initially given a diagnosis of ICD, 61% maintained the diagnosis, while 39% were re-classified as having ACD. Similarly, of the 79 patients with an initial diagnosis of ACD, 53% maintained this diagnosis, while 47% with no positive patch tests were re-classified as having ICD.

Although patch testing is an essential evaluation for chronic hand dermatitis, care must be taken not to overdiagnose ACD in the setting of positive patch test results that do not correlate to the patient’s allergen exposure. Avoidance of irrelevant allergens leads to delays in clinical improvement and frustration on the part of the both the patient and provider. In a prospective study of 508 hand dermatitis patients, positive patch test results were found in approximately one-third of patients with a primary diagnosis other than ACD.³² This emphasizes the importance interpreting a patch test by taking a thorough exposure history and reviewing this at the final analysis to ascertain which allergens are clinically relevant. As stated earlier, with avoidance, remission of the dermatitis is possible, although interestingly, does not always occur. Patients unable to comply with the avoidance regimen are at risk for recurrent or sustained dermatitis.^2,3

General Relevant Allergens
The North American Contact Dermatitis Group (NACDG) performed a retrospective cross-sectional study9 of 22,025 patients who received patch testing between 1994 and 2004 to determine relevant allergens, irritants, and occupations associated with hand dermatitis. Results revealed that 31.6% (6953/22,025) of patients presenting for patch testing had disease involving the hands, with 15.7% (3456/22,025) having only hand involvement. Of these 3456 patients with hand involvement only, 959 (27.7%) had ACD as the sole causative factor. (Notably, for 1959 patients [56.7%], ACD was 1 of up to 3 etiologies underlying the hand dermatitis).⁹Table 4 (refer to page 2) summarizes the top 14 clinically relevant hand ACD allergens found through the NACDG standard series from 1994 to 2004.⁹

In this last decade, there has been a rapidly increasing prevalence of ACD to methylisothiazolinone (MI) with many cases involving the hands.⁵² The prevalence in hand dermatitis is due to the high utilization of this allergen in personal hygiene products, such as shampoos, cosmetics, soaps, and household cleaning products.⁵³ Quite notably, the mixture of the preservatives methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) was noted to cause a worldwide epidemic of contact-allergic reactions in the 1980s.⁵⁴ Since 2000, MI was allowed in industrial products as a stand-alone preservative, but it was not until 2005 that authorities gave the green light for its use in leave-on and rinse-off cosmetics. Notably, Gallo and colleagues⁵⁵found the prevalence of MI sensitization dramatically increased from 2.3% in 2012 to 6.9% in 2013. Yu and colleagues⁵⁶ also reported similar findings with MI allergy rates increasing over 100% from 2012 to 2014. In 2015, the European Commission began to address the second MI epidemic by banning MCI/MI in all leave-on body products.⁵⁷ There is no such ban in the United States.

Allergens in Occupational vs Nonoccupational Hand Dermatitis
Some overlap exists between allergens underlying occupational and nonoccupational ACD-related hand dermatitis.^9,58 Templet and colleagues⁵⁸ retrospectively reviewed the results of 329 patients with hand dermatitis who presented for patch testing and concluded that the most common substances causing sensitization in patients with either occupational or nonoccupational hand dermatitis were quaternium-15, formaldehyde, thiuram mix, and carba mix. The rubber accelerators thiuram and carba mix likely related to glove utilization.

Elston and colleagues⁵⁹ reviewed hand dermatitis and found that the most frequent occupational allergens include first aid medications, germicides, metallic salts (eg, chromate, nickel), organic dyes, plants, plastic resins, and rubber additives, while the most common nonoccupational allergens include fragrance, preservatives, and nickel. Furthermore, Goh⁴⁸ compared patch test results for 721 patients with occupational and nonoccupational hand dermatitis and showed that potassium dichromate and epoxy resin allergy occurred more frequently in the occupational group, whereas fragrance mix allergy was significantly more frequent in the nonoccupational group. Sun and colleagues⁶⁰ patch tested 68 patients with occupational ACD of the hand and found the most significant allergens were dichromate, nickel, cobalt, fragrance mix, epoxy resin, thiuram mix, and p-phenylenediamine; however, comparisons with nonoccupational allergens were not made.

Rubber additives (accelerators and antioxidants) are a frequent cause of occupational ACD. Both Warshaw and colleagues⁹ and Duarte and colleagues¹⁰ concluded that rubber allergens were the most common occupational hand dermatitis allergens. Indeed, workers with occupations requiring the regular use of gloves, such as health care workers, machine operators, technicians, and cleaning service employees, have been found to have the highest rates of ACD-related hand dermatitis.^9,58

Rubber allergens are a frequent source of sensitization in the general population as well. Bendewald and colleagues⁶¹ showed that 31.7% of 773 patients who underwent patch testing to a rubber series had a positive allergic reaction to at least one rubber allergen. Thus, when educating patients, it is critical to inquire about the use of gloves and other possible sources of rubber additive exposure, such as contact with neoprene or fungicides.⁶² Vinyl gloves with cotton liners should be worn when performing wet work, dusty work, or work in cold weather.³³ Table 5 reviews occupationally-related cases.^59,63-96

Patch Testing
Patch testing is often necessary to distinguish ACD from other causes of hand dermatitis and to identify the culprit allergen(s). Baseline screening series include the North American series and the American Contact Dermatitis Society Core 80 series.⁹⁷ Supplemental trays may also be needed to complete evaluation for specific exposures like dental materials, cosmetics, and occupation-specific exposures, which when used judiciously have been shown to improve detection rates.⁹⁸ Personal products should also be considered and in work-related cases consultation of materials safety data sheets to exclude toxic or irritating substances should be performed for all occupational materials prior to testing. These self-procured products can be tested “as is” or may require preparation prior to testing.⁹⁸

Treatment
The goal of treatment in hand dermatitis is to reduce clinical symptoms, improve quality of life, and prevent relapses. Lifestyle modifications are paramount, as avoidance of known irritants and allergens is key to preventing relapses and inducing remission for patients with ICD or ACD. Although complete avoidance is ideal, it is not always practical. There are programs to aid allergen avoidance. The Contact Allergen Management Program, a service offered through the American Contact Dermatitis Society,⁹⁹ and SkinSAFE (formerly Contact Allergen Replacement Database), developed in association with the Mayo Clinic,¹⁰⁰ allow the provider to enter a patient’s known contact allergens and provide personalized “shopping lists” of products free of those particular substances. These programs can also exclude cross-reactors.

Protection of the hands is also important, especially when irritants or allergens cannot be avoided. Gloves should be changed every 30 minutes, or worn over cotton liners, as sweating may exacerbate the dermatitis.³³ To determine the most appropriate glove for a specific chemical encountered in the occupational setting, SpecWare online chemical hand protection is an excellent resource (https://www.ansellpro.com/specware/).

Emollients
Emollient use is a critical factor in the treatment regimen of hand dermatitis and patients should undergo extensive emollient education. Thick cream/ointment based emollients should be recommended and moisturizing should be repeated many times throughout the day.³³ The aggressive use of emollients helps provide hydration to the skin and improves the skin’s barrier function.¹⁰¹

Patients should be educated about proper handwashing techniques. Lukewarm or cold water with nonalkaline gentle cleansers without fragrance, coloring, or antibacterial agents are recommended. Hands should be patted dry, especially between the fingers, and then immediate application of a generous amount of bland emollient ointment should follow.³³ The soak and smear technique, where patients soak their hands in a basin of water for 20 minutes before applying an ointment, has been found to enhance therapeutic efficacy.¹⁰² In addition, collodial oatmeal may be added to the hand soak. It has been shown to have anti-inflammatory properties and is efficacious in the treatment of atopic dermatitis and other eczematous processes.¹⁰³ Alternatively, patients may be instructed to soak 3 to 4 times per week for 15 minutes in dilute apple cider vinegar soaks (adjust to a pH of 4.5). The solution need not be rinsed, but should be followed by a generous application of emollient.

Ceramide-containing emollients are often recommended by dermatologists to aid in reestablishing skin barrier function. Ceramides are lipids within the stratum corneum of the skin and are important in maintaining the skin’s barrier function.¹⁰⁴ Studies in which atopic dermatitis patients were switched over to ceramide-containing emollients found a significant clinical improvement.^105,106 However, 2 blinded, randomized, controlled trials (one evaluating adult patients with hand dermatitis, the other evaluating children with atopic dermatitis) in which patients received ceramide-containing emollient or a nonceramide emollient showed no difference in dermatitis improvement between the treatment groups.^107,108

Topical Corticosteroids
Topical corticosteroids are a first-line therapy and the mainstay of treatment for hand dermatitis. Acute flares can be treated with high-potency topical corticosteroids to quickly decrease the inflammation. Side effects include skin atrophy, striae, delayed wound healing, risk of developing a steroid allergy, increased susceptibility to cutaneous infections, and rebound corticosteroid flare.¹⁰⁹ Once-daily application (in addition to emollients) is recommended as multiple double-blinded control trials have not found increased efficacy with twice-daily application.^29,110 For chronic hand dermatitis, the frequency of topical corticosteroid would optimally be decreased to allow for steroid-free days to decrease the risk of developing the above side effects. The American Academy of Dermatology recommends once-daily use of topical corticosteroids for 1 month followed by maintenance therapy 2 to 3 times per week.¹¹¹

Topical Calcineurin Inhibitors
The topical calcineurin inhibitors (TCI), tacrolimus and pimecrolimus, are approved for the treatment of atopic dermatitis but are often used together with topical steroids on alternating days for chronic dermatitis to decrease the risk of steroid side effects. The most common side effects to TCI include skin irritation, burning, and/or pruritus directly after application. Meta-analysis of randomized control trials comparing the efficacy of tacrolimus and pimecrolimus in the treatment of atopic dermatitis found that tacrolimus was more likely to have a good response. TCIs have a black box warning about the potential risk of lymphoma and skin malignancy that is associated with oral calcineurin inhibitors. Extensive postmarketing surveillance has been collected for more than 15 years and no increased risk of lymphoma or skin malignancy has been found.¹¹²

In refractory cases, systemic immunosuppressive therapies may be needed which include (but are not limited to) phototherapy, ionizing radiation, or systemic therapy with oral steroids, oral retinoids, or other immune-modulators (ie, methotrexate, cyclosporine). Additionally, 2 key papers have been published that further review these treatment modalities.^113,114

Dr Zumwalt is a resident with Loma Linda University Medical Center in Linda Loma, CA.
Dr Chen is a clinical assistant professor of dermatology at Stanford University School of Medicine in Redwood City, CA.
Dr Davis is professor and chair of the Department of Dermatology at Mayo Clinic Rochester, MN, and is an active participant in the clinical, educational, and research efforts in the department.
Dr Jacob, Section Editor of Allergen Focus, is professor of dermatology at Loma Linda University in Loma Linda, CA, and the founder and chief executive officer of the Dermatitis Academy public outreach education campaign.

Disclosure: The authors report no relevant financial relationships.

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