The successful treatment of hand dermatitis (HD) depends less on the selection of the proper topical steroid or a particular systemic agent than on addressing any underlying cause or perpetuating factor. Thus, innovative treatment is based on comprehensively addressing the patient’s problem. Aggressive approaches may be required for the most severe forms of HD.
Severe HD is pragmatically defined as that which does not respond to simple preventive measures, barrier repair and protection, topical steroids, or brief courses of systemic steroids, or that which recurs rapidly after the foregoing measures are tapered or discontinued, having protracted episodes and a chronic, relapsing course. Intuitively, severe hand dermatitis (HD) also has lesion-related symptoms that limit function and adversely affect the quality of life (QoL).
HD is a comprehensive term that, for the purpose of this review, encompasses all skin inflammatory disorders involving the hands. It includes hand eczema (HE) and a long list of inflammatory dermatoses ranging from atopic dermatitis (AD) and psoriasis to other reactions, many of external causation, such as allergic and irritant contact dermatitis (ICD), infections, and reactions of internal etiology such as drug eruptions, auto and heteroimmunity conditions.
In this article, the term HE is reserved for the clinical syndrome characterized by pruritus, pale erythematous to violaceous hues, scaling, vesiculation or bulla formation, erosion, exudation and crusting, lichenification, fissuring, and excoriation, that typically results in a genetically determined faulty barrier function plus a dysregulated response of the immune system to common antigens, often involving immunoglobin E (IgE), predominantly affecting the hands. A connection between the filaggrin gene and HE is questionable.
There are several ways to classify HD, most reflect the pathogenesis or the clinical pattern. Classification schemes address extrinsic aspects of contact dermatitis (CD) such as nonallergic, irritant, nutritional, physical or chemical burns, and allergic CD (ACD) to intrinsic factors (genetic or inherited, metabolic, age related, neoplastic, dyskeratotic or acantholytic, autoimmune), and infectious causes as well as multifactorial conditions such as psoriasis, pityriasis rubra pilaris, AD, PsEmA (psoriasis/eczema overlap syndrome), lichen planus, and reactive arthritis.
Patterns involving specific selected areas of the hands, such as dorsal, ventral (palmar or volar), junctional (webs, finger sides, and canthal), and miscellaneous (ring, pulpitic, apron, lenticular, unilateral, and onychial), may be sufficiently characteristic as to suggest a diagnosis. Allergic reactions to ingredients in protective gloves are often limited to the back of the hands and wrists; isolated lesions localized to the fingertips of the dominant hand suggest acrylate allergy (particularly in dental personnel), plant or vegetable dermatitis, or chromate allergy. Changing patterns, such as webs to fingertips or volar to dorsal, should alert the physician to consider patch testing.
Other classifications use signs that best correlate with the natural history of HD, dividing it into acute, subacute, or chronic. These may be differentiated into wet, intermediate, dry, and less common/harder to categorize. Wet typically corresponds with acute, oozing, macerated, ulcerated, excoriated, pompholyx (dishydrotic), or relapsing forms. Dry typically corresponds to scaly, hyperkeratotic, or lichenified, usually chronic forms. Less common/harder to categorize may correspond with follicular, pustular, bullous, ulcerative, purpuric, lichenoid, dyspigmented, and erythema exsudativum multiforme-like, eruptions.
Dyshidrotic eczema (DE) or pompholyx merits separate attention. DE is a chronic, recurrent HD characterized by flares that start as tiny, tense, pruritic vesicles that may coalesce into large blisters and evolve into pustular lesions usually affecting the palms and volar and lateral aspects of the fingers. Although DE may be totally idiopathic, it may be associated with underlying atopy, contactants, and fungal or bacterial infection with hypersensitivity.
Epidemiology
The most frequent causes of HD include soap, plain water, detergents, solvents, acidic and alkaline agents, repeated friction, mechanical abrasion, thermal trauma, exposure to metals, fragrances, preservatives, food proteins, animal dander, rubber, and latex proteins. Less common/unusual causes recently reported include white-stemmed gum moth, cercaria, shiitake mushroom, hydrangea, aspen bark, henna, hop, phytophotodermatitis, pierced ears and tongue, radiation, photoallergic eczema, posttraumatic eczema, drugs, topical steroid allergy and dependence, quaternium-15, newer biocides used as preservatives, parvovirus, and Papillon-Lefevre syndrome. Additional rare factors include asparagus, artichokes, Paeonia (peony), melamide formaldehyde resins (in a plywood worker), and a case of contact uticaria from raw potatoes. Although often implicated as causing or aggravating factor, smoking was recently found to be not clearly associated in a study involving 13,452 individuals.
In a retrospective study of 714 consecutive individuals with HD, the precise etiologic diagnosis of HE was not distinguishable by clinical pattern, prevalence of personal atopy, or nickel sensitivity.
During systemic treatment of cancer, methotrexate, 6-mercaptopurine, carbamazepine, multikinase inhibitors like sorafenib and sunitinib, and inhibitors of vascular endothelium growth factor signal transduction (eg, monoclonal antibodies bevacizumab and ranibizumab) may all produce a painful hand-foot syndrome requiring awareness by physicians caring for patients at risk.
HD represents 20% to 25% of all cases of eczematous dermatitis seen by dermatologists and 20% to 35% of all dermatitis affects the hands.
QoL
Effective therapy is needed because HD significantly affects QoL. Pertinent issues include occupational, domestic, social, psychological, and economic factors. Major livelihood changes, like job transfers, may not lead to QoL improvements, and substantially increase cost of care. One study found that medical costs translated to $70 per patient per month; a burden that may be an underestimation when adjusted for inflation and the omission of over-the-counter drugs and indirect expenses. In another study, the highest number of claims due to HD from latex gloves came from nurses (30.8%), nursing aides and orderlies (24.6%), dental assistants (13.8%), clinical laboratory technicians (9.2%), and institutional maids/housemen (4.6%). By contrast, food preparers, laundry workers, therapists, general office clerks, private household cleaners, cooks, and personal service occupations filed the fewest claims. The average claim cost was $8309.48. Preventing exposure to noxious chemicals is recommended to reduce claims and facilitate healing from occupation-related skin diseases of the hands.
Patients from the Danish National Board of Industrial Injuries Registry with newly recognized occupational HE (OHE) were assessed with 1-year follow-ups. Underlying AD, age greater than 40 years and a low socioeconomic status at baseline were predictors of severe OHE, prolonged sick leave, and job loss. Substantially greater severity was observed among those with irritant occupational CD and AD. Prolonged sick leave because of OHE was reported by 19.9% of patients and was associated with AD. Severe OHE occurred more often among those in food-related occupations (27.2%) compared with those in wet (20.1%) and other occupations (16.5%). Persons with childhood AD had a significantly increased risk for job change (9% of the cases vs 2% of controls) and sick leave (10% vs 2%), both being related to HD.
CD has a significant effect on emotional well-being when it affects the hands or face, or interferes with normal occupation. Itching, irritation, and chronicity are most bothersome. Patients who elect to change jobs because of their skin condition report significantly worse QoL than those who do not. CD and HE are associated with impaired health-related QoL. Early diagnosis and intervention are associated with QoL improvements. Contradicting reports exist where disease duration, AD, age, and gender do not seem to have significant effects.
Among hospital employees self-reporting HD, 75% observed symptom worsening in direct relation to work, 79% improved during leisure time, and 48% declared psychological distress from their lesions.
High subjective reactions (high-SR) to stress correlated with high HD severity and depression scores, more itching, and life events. High-SR subgroups were younger and had earlier onset of HD. Those with high-SR but negative patch-test results recorded significantly higher values for itching, helplessness, and search for information, suggesting a greater need for adjunctive mental health intervention and psychological care. Chronicity in ICD is an initiator of emotional, physical, and financial stress. The hardening phenomenon is a questionable and poorly understood part of the healing process in HD; elucidating it should lead to better treatments.
QoL
Effective therapy is needed because HD significantly affects QoL. Pertinent issues include occupational, domestic, social, psychological, and economic factors. Major livelihood changes, like job transfers, may not lead to QoL improvements, and substantially increase cost of care. One study found that medical costs translated to $70 per patient per month; a burden that may be an underestimation when adjusted for inflation and the omission of over-the-counter drugs and indirect expenses. In another study, the highest number of claims due to HD from latex gloves came from nurses (30.8%), nursing aides and orderlies (24.6%), dental assistants (13.8%), clinical laboratory technicians (9.2%), and institutional maids/housemen (4.6%). By contrast, food preparers, laundry workers, therapists, general office clerks, private household cleaners, cooks, and personal service occupations filed the fewest claims. The average claim cost was $8309.48. Preventing exposure to noxious chemicals is recommended to reduce claims and facilitate healing from occupation-related skin diseases of the hands.
Patients from the Danish National Board of Industrial Injuries Registry with newly recognized occupational HE (OHE) were assessed with 1-year follow-ups. Underlying AD, age greater than 40 years and a low socioeconomic status at baseline were predictors of severe OHE, prolonged sick leave, and job loss. Substantially greater severity was observed among those with irritant occupational CD and AD. Prolonged sick leave because of OHE was reported by 19.9% of patients and was associated with AD. Severe OHE occurred more often among those in food-related occupations (27.2%) compared with those in wet (20.1%) and other occupations (16.5%). Persons with childhood AD had a significantly increased risk for job change (9% of the cases vs 2% of controls) and sick leave (10% vs 2%), both being related to HD.
CD has a significant effect on emotional well-being when it affects the hands or face, or interferes with normal occupation. Itching, irritation, and chronicity are most bothersome. Patients who elect to change jobs because of their skin condition report significantly worse QoL than those who do not. CD and HE are associated with impaired health-related QoL. Early diagnosis and intervention are associated with QoL improvements. Contradicting reports exist where disease duration, AD, age, and gender do not seem to have significant effects.
Among hospital employees self-reporting HD, 75% observed symptom worsening in direct relation to work, 79% improved during leisure time, and 48% declared psychological distress from their lesions.
High subjective reactions (high-SR) to stress correlated with high HD severity and depression scores, more itching, and life events. High-SR subgroups were younger and had earlier onset of HD. Those with high-SR but negative patch-test results recorded significantly higher values for itching, helplessness, and search for information, suggesting a greater need for adjunctive mental health intervention and psychological care. Chronicity in ICD is an initiator of emotional, physical, and financial stress. The hardening phenomenon is a questionable and poorly understood part of the healing process in HD; elucidating it should lead to better treatments.
Diagnostic techniques
Diagnostic methods include appropriate direct examinations and cultures to exclude bacterial, fungal, and viral causes. Biopsies for routine histology or immunofluorescence and special stains, confocal microscopy, and other imaging techniques, when necessary, may help characterize HD. Extensive or focused patch testing remains the gold standard to identify responsible antigens. A comprehensive occupational and recreational history may identify irritant exposures.
Severity assessments
The Hand Eczema Severity Index (HECSI) was developed in response to a need for a standardized clinical grading system, mostly for research purposes. Agreement for inter- and intraobserver reliability was achieved, but the inclusion of patient-rated symptoms is suggested to add value to this tool. A severity assessment tool developed for palmar eczema collated 3 standardized tools (the global assessment of severity, a standard eczema severity scale (grading erythema, edema/induration/papulation, excoriation, oozing/weeping, scaling, and lichenification), and a scale that integrates body surface area, course, and itch) and gave a near-linear score distribution without end clustering, suggesting that it is accurate.
Differences between self-rated severity (visual analog scale [VAS], 0–10) and The Danish National Board of Industrial Injury severity rating based on morphology, extent of eczema, and frequency of eruptions, suggest that researchers should include ratings from patients and physicians. A guide composed of 5 severity levels, with 4 photographs per level, showed high interrater reliability and test-retest reproducibility. Asking “Do you have hand eczema?” had a higher sensitivity and specificity than grading erythema, papules or vesicles, scaling, and fissuring/lichenification.
Patients with HE were followed for 6 months from their first visit to identify factors associated with severe initial disease and poor prognosis using the HECSI and a self-administered photographic guide; overall improvement occurred by 6 months, but many symptoms remained noteworthy. Older age, AD, frequent flares, and being an unskilled worker (presumably exposed to sundry irritants or allergens) were predictors of a poor prognosis.
Patch testing
Patch testing is an effective and relevant method for determining the cause of allergic reactions. Patch testing with ammonia-preserved natural rubber latex (NRL) identifies patients in whom delayed-type hypersensitivity needs to be differentiated from IgE type 1 response. The addition of methyldibromo glutaronitrile, a preservative in liquid soaps and cosmetics, to the European standard patch test resulted in its ban after many cases of HD attributable to it were detected.
A study that patch tested 644 patients with suspected textile-induced ACD identified a typical distribution pattern that included areas of friction on the trunk and extremities, with the hands being affected less frequently. Allergic reactions to dye or resin were experienced by 12.9% of those patients. The highest incidence of sensitization was from disperse blue (DB) (30.6%), DB 106 (27%), DB 85 (8.1%), and melamine formaldehyde (20.7%). In the resin group, ethyleneurea melamine formaldehyde (20.7%) and urea formaldehyde (18.3%) caused the most reactions.
A patch-tested population that included students, farmers, housewives engaged in farming, laborers, paramedical workers, salesmen, teachers, and photographers, with pompholyx, revealed 40% of subjects reacting to 1 or more allergens; nickel sulfate was the most common (14%), followed by potassium dichromate, phenylenediamine and dinitrofurazone (8%), fragrance mix (FM; 6%), and cobalt chloride (4%).
Among patch-test–positive gold allergic individuals, total avoidance of gold jewelry on hands and wrists benefited a subgroup with facial and eyelid dermatitis who wore powder, eye shadow, or foundation on those areas. Titanium dioxide may adsorb gold particles from jewelry.
Patch testing patients with discoid eczema found hands and feet (44%), hands and forearms (30%), legs and feet (12%), and trunk and limbs (12%) to be the most common distribution patterns. Potassium dichromate, (20%) was followed by nickel, (16%) cobalt chloride, and fragrances (12%) as the most common allergens.
Comparing the FM in the European standard series with a novel selection of 14 fragrance allergens to which hand exposure would likely occur, 10.2% of 658 consecutive HD patients reacted to at least 1 allergen; the most common reactions to fragrances not in the FM series were to citral, hydroxyisohexyl-3-cyclohexene carboxaldehyde, and 1-limonene; more than half would have been missed by the FM.
Compositae dermatitis is 1 of the top 10 contact sensitivities in Europe with a prevalence of 0.7% to 1.4% in the general population. Patch testing with sesquiterpene lactone mix, Compositae extracts screening mix, and Compositae plant extract is recommended. Because of the frequency of positive responses and an annual increase in propolis allergy, it is recommended that it be excluded from topical products used by children.
The hands were the most frequently affected area in 82% of 281 packing station and field workers evaluated by physical examination, standard patch tests, and pesticide patch tests. Reactions to chlorothalonil (51.4%), thiabendazole (12.8%), imazalil (10.2%), and aluminum hydroxide (10.2%) were the most common.
Contact hypersensitivity was less common in patients with HD than in those without (46.7% vs 63.2% respectively) among 105 consecutive adult HD patients (vs 361 suspected nonhand ACD) patch tested. Irritant factors may explain these results.
In summary, several common allergens have been identified and should be sought as a cause of HD in patients who have an occupation or lifestyle that could conceivably place them at high risk for ACD. Randomly chosen patients with HD who undergo extensive patch testing may occasionally be found to have a reversible exposure to an unsuspected allergen.
Occupation
Professions reported to have an increased risk of developing HD include hairdressers; musicians; food industry, agricultural, factory, and electronics workers; cleaners/washers and housekeepers; printers; builders; and medical and dental personnel. Estimates of HD in individuals with work-related skin diseases ranged from 80% to 88% in the 1980s, although recent figures suggest a decrease to 10% to 15%. Biocides are frequent hand irritants in medicine, agriculture and forestry, and industry.
The hands were the primary body part affected in 64% of ACD cases and 80% of ICD among 5839 patients who were patch tested. Frequently encountered allergens include carba mix, thiuram mix, epoxy resin, formaldehyde, and nickel. ACD and ICD of the hands were work related in 16.5% and 44.4% of 360 consecutive health care workers with HCD. Among 59 workers with HE, 72.8% had positive patch tests, 30.5% of which had a strong relationship to occupation; significantly less than was observed with other types of eczema (55% of 160 patients). The rate of atopic history did not differ. Among electronic workers, HD was found most frequently with wafer bonding, cutting, printing/photomasking, softening/degluing, impregnation, and tin plating; 35.5% had ICD and 3.8% ACD.
HD was associated with contact allergy to epoxy resin among 325 patch-tested workers in the wind turbine industry. Although women washed their hands more often and used more moisturizers/protection creams at work than men, no gender differences were found. This suggests that some common-sense maneuvers may not be effective at preventing HD or HE, even when clear-cut exposures are identified. Among 1355 metal workers, of whom 96.7% were men, implementation and acceptance of recommended skin protection at a German factory was shown to be low, even though barrier creams and moisturizers were highly recommended as a potentially effective means to prevent dermatitis.
Prolonged or repeated contact with gasoline caused hyperkeratosis, dryness, onychosis, fissuring, and dermatitis among 52 exposed workers in a matched epidemiologic study in the solvent industry. Prevalence of nickel allergy among older female hairdressers, who use scissors and crochet hooks, was higher than among younger individuals, probably as result of regulations to exclude nickel from such instruments. In large cohort studies that included a clinical examination, the prevalence of HD among hairdressers was 16.4%, compared with 80% in smaller questionnaire-based studies. Among 209 hairdressers, paraphenylenediamine caused the greatest number of positive patch tests, followed by paratoluenediamine sulfate, monthioglycolate, and ammonium persulphate. Total avoidance of these materials is difficult because they are essential to the hairdressing trade.
HD was more prevalent in intensive care unit (ICU) nurses (65%) than among in-patient clinic nurses (50%) at a hospital in the United States. Twelve-month prevalence data (from a self-reporting questionnaire) showed a correlation between history of allergic rash, increased hand washing, and HD, in a cohort of 148 Australian hospital nurses. The period prevalence was higher than in other reports. The rate of HD among Chinese nursing students was similar to that of their Japanese counterparts, but higher than that of nursing students from Germany, Holland, and Australia.
In the dental vocation, among 107 nurses examined, 29 cases of ACD, 15 of contact urticaria, and 12 of ICD, were found. Rubber chemicals, NRL in protective gloves, and methacrylates (dental-restorative materials) were the most common causes of allergy. In a recent questionnaire-based investigation, 17.4% of Norwegian orthodontists reported occupational dermatoses of the hands and fingers (vs 40% in 1987), a reduction explained by changes in hygiene factors such as soaps and detergents, as biomaterial-related reactions persisted unchanged. Prospective data from the National Board of Industrial Industry Registry and a self-administered questionnaire found OHE as a result of ICD to be the most frequent work-related disease in Denmark. The prevalence of AD was low (16.4%) and men had a greater rate of ACD. OHE occurred frequently among bakers, hairdressers, and dental surgery assistants.
Hand and mouth dermatitis among musicians was most frequent in string and wind instrument players; colophony, exotic woods, nickel sulfate, varnishes, and propolis (bee glue) were the most common allergens. As with hairdressers, total avoidance of true allergens might be difficult for those who must come in contact with these materials to play their instruments.
CD is common among beekeepers, due to allergy to propolis, an ingredient in some toothpastes, ointments, and cosmetics. The most frequent hand problems in paddy field workers were nail dystrophy, paronychia, and hyperkeratosis, 73% reporting work-related itch. Repetitive trauma to the hands caused nodules and plaques in 150 carpet weavers.
Risk factors
Of 50 consecutive patients with HE, most had a personal history of atopy; 58% had known contact allergy, 67.4% hay fever, 25.6% asthma, 82% other eczema/dermatitis, 44% fungal infection, and 52% familial atopy. AD and contact allergy were confirmed as important risk factors for HE but did not adequately account for the aggregation. HE in a population-based study involving 1076 individual twins suggests an unrecognized independent genetic risk factor. Skin atopy, previous HD, and flexural dermatitis were predictive for the development of HD. By contrast, there was no association with respiratory atopy among food industry apprentices suffering HD. Among 59 workers with DE, 72.8% had positive patch tests and 30.5% a strong relationship to occupation, much less than with other types of eczema (55% of 160 patients); the rate of atopic history did not differ. A perplexing relapsing case of HD after connubial contact between husband and wife with the same occupation (gardening) is described.
In a retrospective study of 3000 individuals from the general Swedish population, there was no gender difference in the incidence rates of HE in those older than 30 years. Female sex, childhood eczema, and asthma/hay fever were associated with HE in those less than 30 years. HD in psoriasis occurred with similar frequency in men and women, and a higher number of female patients had HE in an analysis of treatment practices in a dermatology outpatient clinic. More frequent and intense therapy was provided to men; women used more topical preparations.
The retrospective analysis of a patch-tested population at a dermatologic referral clinic found that 32% had HD, 56% of it was occupational, 54.4% allergic, and 27.4% irritant. Among women, the prevalence of ACD remained constant between the ages of 21 and 60 years, whereas ICD peaked in the third decade; the prevalence of ICD and ACD peaked in the fifth decade for men. Among 502 (458 men, 44 women) patch-test–negative subjects, analyzed retrospectively, 8.8% had adult-onset AD, and the hands were the most frequently affected area; 5.6% were pure adult-onset, whereas 3.2% had prior contact sensitization.
Laboratory
Laboratory evaluations may be used to measure the effect of various media that can cause sensitization of hand skin. The release of cobalt, nickel, and chromium from hard metal alloys was tested in cobalt-sensitized patients; cobalt concentration was high enough to generate ACD in sensitized patients. Because the materials in the discs are used in wear parts of hard metal tools, individuals with contact allergy to cobalt can develop HE when handling them.
Manipulation tests simulating everyday coin handling provide a reliable means to evaluate contamination. The introduction of the Euro has led to a decrease in nickel exposure; coins are now an unlikely cause of nickel allergy, unless a simultaneous increase in copper exposure causes synergistic sensitization. A newly designed, more reliable method of quantifying nickel on the skin in occupationally exposed individuals consists in immersing thumbs and indexes into tubes containing ultrapure water. In 15 patients with patch-test–positive eczema to a given fragrance, there was no concordance between immersion in a solution containing the fragrance and patch-test results.
African American skin proved superior to White skin in terms of barrier function, stratum corneum disruption, and presence of parakeratosis and spongiosis in a study of ICD on hands evaluated by confocal microscopy, fluorescence, and transepidermal water loss.
Therapy
In all cases, a thorough exploration of environmental factors, many of which were discussed earlier, is appropriate. The trigger of HD, when known from a carefully obtained history and dermatologic examination, should be addressed first, be it by discontinuing a drug or contactant, or by treating a specific cause. When the trigger is not known, or the condition does not respond to conventional therapy, a series of steps must be considered.
Prevention
Regardless of HD type, education and lifestyle modification are essential. Measures contributing to a successful treatment include avoidance of irritants, use of protective gloves, application of protective creams and foams, appropriate moisturization, and use of barrier-restorative materials. Some oil-containing lotions or barrier creams help to protect the hands against dryness, chemical irritation, and skin breakdown.
Through the implementation of an evidence-based prevention program that included frequent use of protective gloves, cotton gloves worn underneath rubber or plastic gloves, and increased discussion of skin problems, the frequency of HE at a European factory was significantly reduced from 56.2% at baseline to 41.0% at the 1-year follow up. HD symptoms can be diminished by reducing the exposure to irritants through training, frequent but short-duration hypoallergenic glove use, and limited hand washing with soap.
A guideline from the Centers for Disease Control and Prevention promotes alcohol-based hand rubs containing emollients instead of irritating soaps and detergents to reduce skin damage, dryness, and irritation. Frequency of ICD was highest with preparations containing 4% chlorhexidine gluconate, less with nonantimicrobial soaps, and least with alcohol-based hand rubs containing emollients. Washing after application of an alcohol-based hand rub is not recommended. A summary of the evidence justifying recommendations of glove occlusion during wet activities and of alcohol rub as the preferred hand disinfectant is available. Another article reviews hand-hygiene practices emphasizing promotion programs and provides guidelines for hand antisepsis for health care workers.
Hand contact dermatitis (HCD) usually results from exposures to monomers and additives in the occupational setting. Resin- and additive-induced direct CD usually affects the hands, fingers, and forearms, whereas indirect exposure affects the face and neck. Industrial hygiene prevention techniques are essential when handling resin systems.
The low irritation index (IrIn) of some soaps and cleansers was established for White Dove, Dove Baby, Dove liquid cleanser for hands, Dove Pink (Lever Pond’s, Toronto, Ontario, Canada), Cetaphil bar (Galderma Laboratory, Forth Worth, TX, USA), and Aderma (Pierre Fabre, Dermo-Cosmetique, Boulagne, France). Camay Classic (Procter & Gamble, Cincinnati, OH, USA) had the lowest IrIn. Prevention of HD with general skin protective measures seems to be more effective than UV light hardening.
Topical Agents
Corticosteroids remain first-line agents for HD. Topical calcineurin inhibitors have been studied for chronic eczematous skin diseases, and are particularly favored to treat the dorsal aspect of the hands, and as steroid-sparing agents. Recently introduced device creams for eczema, containing glycyrrhetinic acid and telmesteine or palmitoylethanolamide, alginate, and trolamine, await testing to prove their value in HD. Refractory chronic pruritic eruptions hydrated for 20 minutes before bedtime followed by the application of mid- to high-strength corticosteroids led to clearing or dramatic symptom improvement in a retrospective study of 28 patients.
Statistically significant improvement is obtained in mild to moderate and moderate to severe chronic HD with pimecrolimus 1% cream applied twice daily under occlusion. Pimecrolimus blood concentrations remain below the limit of quantitation. Most patients with hand and foot dermatitis improved significantly in erythema, scaling, induration, fissuring, and pruritus with tacrolimus 0.1% ointment applied to affected areas 3 times daily for 8 weeks.
Bexarotene gel was well tolerated and showed a good clinical effect in an open-label randomized study of 55 patients comparing its use alone versus in combination with low- and midpotency corticosteroids. Alitretinoin also seems promising for refractory HD.
Botulinum toxin may be an alternative or an adjunctive therapy for vesicular eczema. In 39% of patients with pompholyx, itch improvement occurred on the treated side (compared with a 52% increase in symptoms on the untreated side). A mean decrease in Dyshidrotic Eczema Area and Severity Index (DASI) from 36 to 3 on the hand treated with topical corticosteroids plus intradermal botulinum (compared with a mean decrease from 28 to17 with topical therapy alone) was reported in another study.
Ionizing Radiation
Radiation therapy is often mentioned as useful in reviews on HE treatment. A comprehensive review of past studies using superficial x-rays and grenz rays, revealed contradictory findings. Of a subgroup of patients treated with grenz rays for CD (94% of them with HD), 64% stated that such radiation was worthwhile and 77% would choose it again if needed. Megavoltage equipment producing low-dose external beam radiation was used to induce long-term remission in a patient for whom conventional treatments, including systemic steroids, failed. Although few dermatologists still offer ionizing radiation therapy in the ambulatory setting, this modality is available in hospitals or medical centers.
Nonionizing Radiation
Topical and systemic psoralen combined with ultraviolet A irradiation (PUVA) has been used to treat patients with different forms of HD. UVA-psoralen gel is a potentially less expensive alternative to PUVA bath therapy in severe recalcitrant palmar-plantar dermatoses.
Preliminary results using 308-nm excimer laser light suggests its efficacy and safety in the treatment of HD. The palmar-plantar pustular form did better than plaque-type, chronic atopic, and non-AD.
A prospective open study of 30 patients with chronic hand dermatoses treated with hand UVB-TL01 found that psoriatics responded best; 9 of 11 patients improved after 20 to 38 treatments (compared with 11 of 16 patients with eczema who improved after 11–31 treatments).
UVA-1 irradiation for DE was superior to placebo, assessed by DASI and VAS, after 2 and 3 weeks in a randomized, double-blind, placebo-controlled study of 28 patients receiving irradiation 5 times per week for 3 weeks. There was no difference in response between individuals with increased and normal IgE levels.
Systemic Treatment
Antihistamines, leukotriene antagonists, corticosteroids, cyclosporine, methotrexate, mycophenolate mofetil, azathioprine, hydroxyurea, thalidomide, botulinum toxin, several retinoids, and biologics have all been used to treat HD. Nonetheless, a systematic review of 100 studies, including 31 randomized clinical trials, concluded that this body of evidence constituted an inadequate guide to proper clinical practice. Paradoxically, topical exposure to azathioprine and mycophenolate mofetil have been reported to induce HD.
Cyclosporine has been repeatedly found, in isolated case reports and in small series, to be effective. Acrodermatitis continua–type pustular psoriasis has also been reported to respond to low-dose cyclosporine. The theoretical risk of superinfection during cyclosporine therapy has also been confirmed.
Recent reports on retinoids suggest that oral alitretinoin, a panagonist of retinoid receptors, works well on chronic, severe HE unresponsive to potent topical corticosteroids. In a double-blind placebo-controlled study involving more than 1000 patients, 80% cleared or almost cleared on drug (compared with 8% on placebo).
The use of biologics has been successful in HD, particularly if related to psoriasis. Etanercept has been found to bring long-term control to acrodermatitis continua–type pustular psoriasis. A good response occurred in a patient previously refractory to infliximab, another anti-TNF-α agent. Inconsistent responses to etanercept are reported for pompholyx-type HD. A psoriasiform dermatitis to infliximab involving the hands has been reported. The successful use of adalimumab treating acrodermatitis continua of Hallopeau, and its use with acitretin in a patient who failed to respond to cyclosporine, acitretin, and infliximab, was recently reported. A literature search crossing HD and adalimumab failed to bring up any other reports of success or failure. Alefacept may be a treatment option for refractory chronic HD as suggested by a dramatic and lasting improvement in a patient who failed to respond to class I topical corticosteroids, topical calcineurin inhibitors, intralesional triamcinolone, and phototherapy. The benefit was noted 30 weeks after therapy was initiated, and was sustained for at least 28 weeks with the aid of a mild topical corticosteroid. Efalizumab, once considered to be a usable drug in palmoplantar pustular forms of dermatitis, particularly if associated with psoriasis, was involved in a serious adverse infectious event, requiring its withdrawal from the market.
Tetracycline, along with betamethasone valerate under occlusion, produced a dramatic improvement within a week in a patient with acrodermatitis continua.
Thalidomide combined with UVB therapy succeeded for an infant with acrodermatitis continua of Hallopeau.
Iatrogenic phytophotodermatitis occurred in a 56-year-old farmer after ingesting a herbal decoction prescribed for his chronic HD.
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