Approach Considerations
In dyshidrotic eczema, typical first-line treatment includes high-strength topical steroids and cold compresses. Short courses of oral steroids are the second line of treatment for acute flares, and other immunosuppressants have also been tried. Corticosteroids are cornerstones of topical therapy. Guidelines have been established by the National Institute of Clinical Evidence. [32] Calcineurin inhibitors may also be effective. [33]
Variable effects have been reported using oral administration of psoralen and subsequent exposure to long-wavelength UV light (PUVA) therapy. Topical photochemotherapy with 8-methoxypsoralen is probably as effective as systemic photochemotherapy or high-dose UVA-1 irradiation. For recalcitrant cases, corticosteroids are combined with immunosuppressants.
An evolving treatment seems to be the intradermal injection of onabotulinumtoxinA. Probiotics have been suggested as a potential treatment for eczema. [34] Topical khellin and natural sunlight therapy have been suggested for patients with recalcitrant palmoplantar pompholyx. [35] Tap water iontophoresis with pulsed direct current may be helpful as adjuvant treatment. [36]
Excellent results have been reported with the use of oxybutynin in two patients with coexistent hyperhidrosis and dyshidrotic eczema. [37] Further studies are needed before recommending this treatment modality.
Identification of the causes of stress and the use of stress management techniques as adjuncts may be helpful in some patients. Biofeedback therapy for stress reduction has succeeded in some individuals.
Treatment for bullae (blisters)
The following treatment is appropriate if bullae are present:
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Use compresses with Burow solution (10% aluminum acetate) in a 1:40 dilution until bullae resolve (usually within a few days)
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Compresses with a 1:10.000 solution of potassium permanganate are also effective
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Drain large bullae with a sterile syringe, and leave the roof intact
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Prescribe systemic antibiotics that cover Staphylococcus aureus and group A streptococci
Activity
Bed rest may be necessary if bullae develop on the feet. Additionally, if palmar bullae develop, patients may not be able to work or perform the activities of daily living.
Deterrence
Advise dyshidrotic eczema patients to avoid known contact irritants or allergens, to reduce stress (may help some patients), to follow a hand care regimen, and to use regular prophylactic emollients.
Consultations
Consultation with a psychologist may be helpful for stress reduction using biofeedback therapy and other techniques. [38] Consultation with an allergist may be helpful for oral provocation tests for nickel, cobalt, or chromium salts. Oral challenges occasionally are positive in patients who demonstrate negative patch tests to these metals. The test is considered positive if a patient's dyshidrotic eczema flares after metal is ingested.
Ultraviolet A Light
Paradoxically, although sometimes linked as a possible cause, UVA or UVA-1 alone or with oral or topical psoralen has been used in treatment. Hand and/or foot UVA therapy (UVA or UVA-1 alone or with oral or topical psoralen) improves the eruption and pruritus when administered 2-3 times per week. The dose typically starts at 0.5 J per treatment and is increased by 0.5 J at every other or every third treatment. [39, 40]
Topical application of 8-methoxypsoralen plus UVA (bath-PUVA) has been demonstrated to be the preferred method for the treatment of dyshidrotic eczema, compared with oral PUVA. [41] Local, narrow-band UVB has been shown to be as effective as bath-PUVA in patients with chronic hand eczema of dry and dyshidrotic types. [42]
Corticosteroids
Topical corticosteroids are the mainstay of treatment. Typically, use class I steroids initially, then class II or III steroids. Ointments penetrate the skin better than creams do, although patients may prefer creams during the day. Topical antipruritics with pramoxine are useful.
Systemic corticosteroids can also be used. Either oral prednisone or intramuscular triamcinolone suspension may be administered for severe episodes. Tapering of prednisone can follow intramuscular treatment. Schedule follow-up and check blood pressure 1 week after initiating prednisone.
Calcineurin Inhibitors
Topical calcineurin inhibitors may be helpful. Some patients may benefit from topical tacrolimus or pimecrolimus. Several studies have demonstrated their efficacy and tolerability in the treatment of chronic hand dermatitis, [43] and long-term occlusive therapy has also been determined to be efficacious, particularly in persons with severe dyshidrotic eczema. [43]
Advantages of topical calcineurin inhibitors over topical corticosteroids include the lack of development of tachyphylaxis, telangiectasias, and thinning and atrophy of the skin. [44] Personal experience of the coauthor has shown effective control with topical calcineurin inhibitor therapy alone in several patients followed in her practice. Note that topical calcineurin inhibitors can exacerbate irritant hand dermatitis.
OnabotulinumtoxinA
OnabotulinumtoxinA injections may be helpful in some patients. OnabotulinumtoxinA intradermal injections as an adjuvant to topical corticosteroids has been tested in a study in which 6 patients who completed an 8-week trial achieved significant reductions in their Dyshidrotic Eczema Area and Severity Index scores and faster reductions of pruritus and vesiculation. [44] In another study, 7 of 10 vesicular pompholyx patients achieved good to very good responses after the injection of OnabotulinumtoxinA alone, with a reduction of pruritus. [45]
Immunosuppressive Agents
For severe refractory pompholyx, azathioprine, methotrexate, [46] mycophenolate mofetil, cyclosporine, [47] or etanercept may be helpful. In one study, etanercept was administered subcutaneously to a patient with recalcitrant hand pompholyx at a dose of 25 mg twice a week. The patient achieved complete remission for 4 months, after which the patient had a relapse. The etanercept dose was increased to 50 mg twice a week without improvement. [48] Consider measuring thiopurine methyltransferase levels, which may help to guide azathioprine therapy. Accurate dosing avoids toxicity and underdosing.
Nickel Chelators and Khellin
Nickel chelators, such as disulfiram (Antabuse), occasionally are used in nickel-sensitive patients who demonstrate a positive oral provocation test. [49]
Khellin, a furanochromone similar to methoxypsoralen, may be used in combination with photochemotherapy (sun exposure) for recalcitrant palmoplantar cases. [35] Khellin, unlike other psoralens, does not induce skin phototoxicity (erythema) and hyperpigmentation of healthy skin after UVA radiation therapy.
Alitretinoin
Alitretinoin (9-cis retinoic acid) activates the retinoid X receptor and all retinoic receptors. In one study, alitretinoin treatment produced significant clinical improvements in patients with chronic hand dermatitis, but it was not effective specifically against dyshidrotic eczema. The randomized, double-blind, placebo-controlled, multicenter trial involved 319 patients with chronic hand dermatitis (70 with pompholyx) that was refractory to standard therapy. Oral alitretinoin was administered at doses of 10 mg, 20 mg, or 40 mg once daily for 12 weeks. Although alitretinoin induced a significant clinical improvement in a dose-dependent fashion (53% improvement in disease status and 70% reduction in clinical features) in the patient group as a whole, no difference was noted in the patients with pompholyx compared with placebo. [44, 50]
However, evidence from another study indicated that alitretinoin is effective against dyshidrotic eczema In this investigation, another randomized, double-blind, placebo-controlled, multicenter trial, oral alitretinoin showed a response rate of 33% at a dose of 30 mg/d, compared with 23% at a dose of 10 mg/d and 16% with placebo, in 377 patients with pompholyx. [51]
Headache and mucocutaneous adverse events, including dry skin, rash, alopecia, exfoliative dermatitis, and hyperlipidemia, were the most common adverse events in these trials.
Alitretinoin 1% gel has been evaluated for the treatment of classic Kaposi sarcoma, [52] photoaging, [53] pyogenic granuloma, [54] and cutaneous T-cell lymphoma. [55] Currently, alitretinoin 1% gel has not been used for the topical treatment of pompholyx.
Three phase III studies (1 open-label study and 2 double-blind, randomized, controlled trials) evaluated the safety [56] and efficacy [57] of once-daily oral alitretinoin at 10 mg or 30 mg versus placebo in 1032 patients with chronic hand eczema, including pompholyx, in whom treatment with potent topical corticosteroids had failed.
According to physician assessment, "clear" or "almost-clear" status was achieved in up to 48% of patients in the alitretinoin groups and 17% in the placebo group. Median percentage reduction in disease symptoms was 75%. Alitretinoin at 30 mg had faster responses (median 85 d) than did placebo (median 141 d). Among complete responders who relapsed, 80% in the alitretinoin groups responded to the same alitretinoin dose and 8-10% of patients in the placebo group responded to retreatment with placebo.
Common adverse effects included headache, flushing, erythema, and xerosis. Headache was the most common adverse effect with alitretinoin at 30 mg. Also in the treatment group, dry skin, dry eyes, dry mouth, dry lips, and cheilitis were reported in 10% of patients, compared with 4% of patients in the placebo group. Lipid abnormalities were similar to those seen with other retinoids.
Additional Agents
Potential agents for the treatment of pompholyx, such as topical bexarotene, systemic alitretinoin, leukotriene receptor antagonists, leukotriene synthesis inhibitors, phosphodiesterase-4 inhibitors, and monoclonal antibodies, have been shown to be effective for the treatment of chronic hand dermatitis and other inflammatory conditions, including atopic dermatitis. Controlled studies need to be conducted to establish their efficacy and safety for the treatment of dyshidrotic eczema (pompholyx). Recalcitrant dyshidrotic eczema may be treated with dupilumab. [58]
Diet
For nickel-sensitive patients, consider a low-nickel diet for 3-4 weeks. However, the diet regimen is only rarely successful and is difficult for patients to follow. The diet requires avoiding foods rich in nickel, such as canned foods, foods cooked using nickel-plated utensils, herring, oysters, asparagus, beans, mushrooms, onions, corn, spinach, tomatoes, peas, whole grain flour, pears, rhubarb, tea, cocoa, chocolate, and baking powder. A list of additional nickel-containing foods has been reported by Lofgren and Warshaw. [18]
For cobalt-sensitive patients, consider a low-cobalt diet that avoids apricots, beans, beer, beets, cabbage, cloves, cocoa, chocolate, coffee, liver, nuts, scallops, tea, and whole grain flour. A point-based, low-cobalt diet has been described by Stuckert and Nedorost. [3] Some patients have reported improvement by avoiding foods rich in heavy metal salts.
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Dyshidrotic eczema (pompholyx). Tense vesicles and bullae on the palm. Courtesy of Norman Minars, MD, University of Miami, Department of Dermatology & Cutaneous Surgery.
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Dyshidrotic eczema (pompholyx). Close-up view of tense vesicles and bullae of the palm. Courtesy of Norman Minars, MD, University of Miami, Department of Dermatology & Cutaneous Surgery.
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Dyshidrotic eczema (pompholyx). Discrete yellow pustules on the sole of the foot. Courtesy of Norman Minars, MD, University of Miami, Department of Dermatology & Cutaneous Surgery.
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Dyshidrotic eczema (pompholyx). Multiple tense vesicles on the palm.
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Dyshidrotic eczema (pompholyx). Small tense vesicles on the fingers.
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Dyshidrotic eczema (pompholyx). Small, discrete, coalesced vesicles on the dorsal hand.
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Dyshidrotic eczema (pompholyx). Small, discrete, coalesced vesicles on the fingers.
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Dyshidrotic eczema (pompholyx). Palms and soles of a patient with a dyshidrosis flare. The patient unroofed a large bulla on the right sole.
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Dyshidrotic eczema (pompholyx). Small discrete vesicles of the lateral fingers.
