Dyshidrotic Eczema (Pompholyx)

Background

Dyshidrotic eczema is a type of eczema (dermatitis) that is characterized by a pruritic vesicular eruption (bullae, or blisters) on the fingers, palms, and soles; typically these intensely itchy blisters develop on the edges of the fingers, toes, palms, and soles of the feet. (See the image below.) This skin condition affects teenagers and adults and may be acute, recurrent, or chronic. A more appropriate term for this vesicular eruption is pompholyx, which means bubble. Some have suggested that the terms pompholyx and dyshidrosis are both obsolete and that acute and recurrent vesicular hand dermatitis is a better term for this condition.

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Dyshidrotic eczema (pompholyx). Multiple tense vesicles on palm.

The etiology of dyshidrotic eczema is unresolved and is believed to be multifactorial. Dyshidrotic eczema is considered to be a reaction pattern caused by various endogenous conditions and exogenous factors.

The clinical course of dyshidrotic eczema can range from self-limited to chronic, severe, or debilitating. The skin condition's unresponsiveness to treatment can be frustrating for the patient and physician.

Signs and symptoms

Signs and symptoms of dyshidrotic eczema include the following:

• Symmetric crops of clear vesicles and/or bullae (blisters)
• Intensely pruritus (itchiness)
• Typically present on the palms and soles, as well as the lateral aspects of fingers and toes
• Deep-seated vesicles with a tapiocalike appearance
• May become large, form bullae, and become confluent
• In chronic disease, fingernails may reveal dystrophic changes
• Vesicles typically resolve without rupturing, followed by desquamation

Diagnosis

Diagnosis of dyshidrotic eczema includes the following:

• Typically a clinical diagnosis
• Bacterial culture and sensitivity can rule out secondary infection
• Patch testing to exclude allergic contact dermatitis
• Recalcitrant cases warrant systemic evaluation
• Potassium hydroxide (KOH) wet mount to exclude dermatophyte infection
• Punch biopsy for direct immunofluorescence to exclude bullous pemphigoid

Treatment

Treatments for dyshidrotic eczema include the following:

• First-line treatment - High-strength topical steroids and cold compresses; systemic steroids are also used
• Treatment for bullae (blisters) - Compresses with Burow solution or 1:10.000 solution of potassium permanganate; drainage of large bullae with a sterile syringe, with the roof left intact; systemic antibiotic therapy covering Staphylococcus aureus and group A streptococci
• Ultraviolet A (UVA) or UVA-1 light therapy, alone or with oral or topical psoralen (PUVA); UVB therapy has also shown utility
• Topical calcineurin inhibitors
• OnabotulinumtoxinA injections
• For severe refractory pompholyx - Azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, or etanercept
• Nickel chelators (eg, disulfiram) occasionally used in nickel-sensitive patients
• Alitretinoin (9-cis retinoic acid)
• Dietary avoidance of nickel and cobalt for nickel- and cobalt-sensitive patients

• References

Etiology

The hypothesis of sweat gland dysfunction as the cause of dyshidrotic eczema was refuted on the grounds that vesicles have not been shown to be associated with sweat ducts. A 2009 case report provided clear histopathologic evidence that sweat glands do not play a role in dyshidrosis.^[1] However, hyperhidrosis is an aggravating factor in 40% of patients with dyshidrotic eczema. Improvement in pruritus, erythema, vesicles, and hand dermatitis with fewer or no signs of relapse has been obtained after onabotulinumtoxinA injection.^[2]

Dyshidrotic eczema may be associated with atopy and familial atopy. Of patients with dyshidrosis, 50% have atopic dermatitis.

Exogenous factors (eg, contact dermatitis to nickel, balsam, cobalt; sensitivity to ingested metals; dermatophyte infection; bacterial infection) may trigger episodes. These antigens may act as haptens with a specific affinity for palmoplantar proteins of the stratum lucidum of the epidermis. The binding of these haptens to tissue receptor sites may initiate pompholyx.

Evidence shows that the ingestion of metal ions such as cobalt can induce type I and type IV hypersensitivity reactions. In addition, they can also act as atypical haptens, activating T lymphocytes through human leukocyte antigen (HLA)-independent pathways, causing systemic allergic dermatitis in the form of dyshidrotic eczema.^{[3, 4]}

Emotional stress^[5] and environmental factors (eg, seasonal changes, hot or cold temperatures, and humidity) have been reproted to exacerbate dyshidrosis.

Dyshidrosislike eczematous eruptions with the use of intravenous (IV) immunoglobulin (IVIG) infusions have been reported.^[6] A 2011 search of the literature identified pompholyx as one of the most important cutaneous adverse effects of IVIG, being present in 62.5% of the patients reported, of whom 75% developed the lesions after just one IVIG treatment.^[7] The eruption tends to be mild and to wane over time. It usually responds very well to topical steroids,^{[8, 9, 10]}  but it may become recurrent and more aggressive after repeated doses of IVIG.

In some patients, a distant fungal infection can cause palmar pompholyx as an id reaction. In one study, one third of pompholyx occurrences on the palms resolved after treatment for tinea pedis. The factors believed to be associated with dyshidrotic eczema are discussed in more detail below.

Genetic factors

Monozygotic twins have been affected simultaneously by dyshidrotic eczema. The pompholyx gene has been mapped to band 18q22.1-18q22.3 in the autosomal dominant form of familial pompholyx.^[11]

Mutations on the filaggrin gene leading to loss of filaggrin, a structural protein of the stratum corneum involved in the barrier function of the skin, cause dyskeratinization, increased transepidermal water loss, and an increase in the transepidermal antigen transfer. Combined, these features have been associated with the development of ichthyosis and atopic dermatitis, and they may be involved in the development of irritant and allergic contact dermatitis, which are well-known skin conditions associated with dyshidrotic eczema.

Chronic hand dermatitis, including dyshidrotic eczema, has also been associated with defects in the skin barrier, and in a few cases, it has also been associated with mutations in the filaggrin gene; however, these have not reached statistical significance.^[12]

Aquaporins are known to be expressed in patients with atopic dermatitis, and such expression may also be related to exacerbation and chronicity of pompholyx. Aquaporins are channel proteins located on cell membranes that increase their permeability. Particular examples include the aquaglyceroporins, which can transport water and glycerol. Aquaporin-3 and aquaporin-10 are normally expressed in the basal layer of the epidermis, and immunohistochemical staining has demonstrated their presence in all epidermal layers in patients with pompholyx. These channels may participate in the increase of transepidermal water loss seen in atopic dermatitis and possibly in pompholyx.

Owing to osmotic gradients, among other factors, the direction of water and glycerol through aquaporins is from the skin to the environment, possibly contributing to skin dehydration, even immediately after hand washing. Hypothetically, topical or systemic inhibition of the expression of aquaporins in the epidermis could contribute with the preservation of water and glycerol, decreasing the frequency and severity of pompholyx exacerbations.^[13]

Atopy

As many as 50% of patients with dyshidrotic eczema have reportedly had personal or familial atopic diathesis (eg, eczema, asthma, hay fever, or allergic sinusitis). The serum immunoglobulin E (IgE) level frequently is increased, even in patients who do not report a personal or familial history of atopy. Occasionally, dyshidrotic eczema is the first manifestation of an atopic diathesis.

Nickel sensitivity

Nickel sensitivity may be a significant factor in dyshidrotic eczema. It was reported to be low in some studies of dyshidrosis patients but significantly elevated in others. Increased nickel excretion in the urine has been reported during exacerbations of pompholyx. Ingested metals have been found to provoke exacerbations of pompholyx in some patients.

Low-nickel diets have reportedly decreased the frequency and severity of pompholyx flares. A high palmoplantar perspiration rate has been suggested to result in a local concentration of metal salts that may provoke the vesicular reaction. Contact allergy has been documented in 30% of patients with dyshidrotic eczema.

Cobalt sensitivity

Oral ingestion of cobalt manifests systemic allergic dermatitis as dyshidrotic eczema less frequently than oral ingestion of nickel does. Much more common is the simultaneous occurrence of nickel and cobalt allergy seen in 25% of nickel-sensitive patients developing pompholyx. In these cases, the eczema is usually more severe. When suspected as the cause of the dyshidrotic eczema, high oral ingestion of cobalt should be taken into consideration, regardless of the patch test results.^[3]

A point-based low-cobalt diet has been proposed to help patients limit cobalt ingestion and to keep the serum level below the threshold for developing flares (approximately < 12 μg/day). This diet has demonstrated higher compliance than an avoidance diet list. In addition, this diet reduces the amount of nickel consumed.^[3]

Exposure to other sensitizing chemicals or metals

Dyshidrotic eczema outbreaks are sometimes associated with exposure to other sensitizing chemicals or metals (eg, chromium, carba mix, fragrance mix, diaminodiphenylmethane, dichromates, benzoisothiazolones, paraphenylenediamine, perfumes, fragrances, balsam of Peru, or Primula plant).

Id reaction

Controversy has surrounded the possible existence of an id reaction, which is considered to be a distant dermatophyte infection (tinea pedis, kerion of scalp) triggering a palmar pompholyx reaction (also termed pompholyx dermatophytid).

Fungal infection

Pompholyx occasionally resolves when a tinea pedis infection is treated, then relapses when the fungal infection recurs, supporting the existence of this reaction pattern. Of patients who have a vesicular reaction to intradermal trichophytin testing, fewer than one third have experienced a resolution of pompholyx after treatment with antifungal agents.

Emotional stress

This is a possible factor in dyshidrotic eczema. Many patients report recurrences of pompholyx during stressful periods. Improvement of dyshidrotic eczema with the use of biofeedback techniques for stress reduction supports this hypothesis.

Other factors

Isolated reports have described other possible causative factors (eg, aspirin ingestion, oral contraceptive use, cigarette smoking, and the presence of implanted metals). A 3-year prospective study (N = 120) of the causes of dyshidrotic eczema found causes of pompholyx related to contact exposure (67.5%), including to cosmetic products (31.7%) and metals (16.7%); interdigital-plantar intertrigo (10%); and internal factors (6.7%); an additional 15% of patients had undiagnosed (idiopathic) causes probably related to atopic factors.^[14]

Contact allergy was found in 89 (74.2%) of the 120 patients.^[14] The most frequent allergens were nickel, shower gel, chromium, fragrance, shampoo, and balsam of Peru; less frequent allergens were lanolin, cobalt, thiuram, lauryl sulfate, fresh tobacco, p-phenylenediamine (PPD), formaldehyde, parabens, and octyl gallate. In 97 of 193 positive patch test results, application of the agent was correlated with pompholyx recurrence. The relevance of the analysis was confirmed in 81 (67.5%) of the 120 patients. In summary, the most frequent causes of pompholyx related to contact with substances were hygiene product intolerance (46.7%), metal allergy (25%), and others (28.3%).

Intertrigo occurred in 19 (15.8%) of the 120 patients.^[14] Of those individuals, 80% presented with dermatophytosis and 20% presented with candidiasis. After 3 weeks of antifungal therapy, 13 of 19 patients remained asymptomatic of pompholyx.

With regard to internal causes, 30 patients presented with a positive patch test result for metals, but only two presented with exacerbations of the lesions after a challenge test.^[14]

Of 58 patients with a history of smoking tobacco, five presented with a positive reaction on a tobacco patch test, and two of those were considered relevant.^[14] Drug allergy was determined to be the causative agent in 3 patients (amoxicillin in 2 and intravenous immunoglobulin in 1). Food-related pompholyx was detected in 4 patients, and, after a challenge test, reactivation occurred in 3 of these patients (2 for paprika and 1 for orange juice).

Ultraviolet A light

In a case series, five patients with prior diagnosis of pompholyx developed lesions morphologically and histologically consistent with a vesicular dermatitis after provocation with long-wavelength UVA light.^[15] Further workup ruled out contact dermatitis, polymorphous light eruption, and heat as the culprit, confirming that the reaction was due to true photosensitivity rather than to photoaggravation.

Pompholyx caused by UVA exposure may possibly be considered a variation of seasonal (summer) pompholyx. In the United States, dyshidrotic eczema is more commonly seen in warmer climates and during the spring and summer months. A study in Turkey also revealed a higher prevalence of dyshidrotic eczema in the summer months.^[16]

In a case series, three patients with frequent pompholyx exacerbations, mostly during summer (ie, photoaggavated pompholyx), were subjected to photoprovocation testing, with positive development of pompholyx lesions in two.^[17] Lesions occurred after exposure to solar-simulated UV radiation and broadband UVA. Treatment included photoprotective measures in addition to standard treatment and led to decreased frequency and severity of exacerbations. The authors suggested that this condition may be underdiagnosed and recommended recognition and early detection to institute sun protection as soon as possible and to avoid starting phototherapy or photochemotherapy in this subset of pompholyx patients.

It is noteworthy that UVB phototherapy and photochemotherapy are well-known, efficient treatments for pompholyx.

• References

Epidemiology

US and international statistics

Dyshidrotic eczema occurs in 5-20% of US patients with hand eczema; it more commonly develops in warmer climates and during spring and summer months (seasonal or summer pompholyx).

In a 1-year study from Sweden, dyshidrotic eczema accounted for 1% of initial consultations. A study that included 107,206 Swedish individuals found that 51 (0.05%) were diagnosed with dyshidrosis.^[18] Of all hand dermatitis cases in that population, 3% had dyshidrosis. In a retrospective study reviewing records of 714 Portuguese patients during a 6-year period, Magina et al found dyshidrotic eczema to be the third most common type of hand dermatitis (20.3%).^[19]

Age- and sex-related demographics

Dyshidrotic eczema affects individuals over a broad age range (4-76 y; mean age, 38 y). The peak incidence of the skin condition occurs between the ages of 20 and 40 years. After middle age, the frequency of dyshidrotic eczema episodes tends to decrease.

The male-to-female ratio for dyshidrotic eczema has variably been reported as 1:1 or 1:2. 

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Prognosis

Dyshidrotic eczema follows a chronic, intermittent course, with fewer episodes occurring after middle age. Some mildly affected patients experience spontaneous resolution within 2-3 weeks. (See Treatment and Medication.)

• References

Patient Education

Individuals with dyshidrotic eczema should be educated about the difficulty of achieving successful treatment. They should be informed that the typical first-line treatments for the blisters of this condition are high-strength topical steroids and cold compresses and that additional treatments that might be helpful include stress reduction (possibly involving consultation with a mental health professional and potentially including biofeedback therapy) and hand care measures (eg, use of moisturizers and emollients).

Bed rest may be necessary if large blisters develop on the feet. Work activities or activities of daily living (ADLs) may be hampered by blisters on the hands.

Nickel- or cobalt-sensitive dyshidrotic eczema patients should be instructed to avoid contact with these allergens; this may involve avoidance of certain activities, foods, and beverages.

For patient education information, see the Skin Conditions and Beauty Center, as well as Eczema (Atopic Dermatitis).

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History

Patients with dyshidrotic eczema (pompholyx) report pruritus of the hands and feet with a sudden onset of vesicles. Occasionally, they may experience burning pain or pruritus before vesicles appear. Tiny vesicles erupt first along lateral aspects of the fingers and then on the palms or soles. Palms and soles may be red and wet with perspiration. The vesicles usually persist for 3-4 weeks. Vesicle outbreaks may occur in waves. A photoinduced form of hand dermatitis resembling dyshidrotic eczema has been described.^[15]

Dyshidrotic eczema episodes may range in frequency from once per month to once per year. Patients may report a variety of factors that possibly are related to eruptions, as follows:

• Emotional stress
• Personal or familial atopic diathesis (eg, asthma, hay fever, or sinusitis)
• Certain work exposures (eg, cobalt) or recreational exposures
• Recent exposure to contact allergens (eg, nickel, balsams, paraphenylenediamine, chromate, or sesquiterpene lactones) before condition flares
• Exposure to contact irritants before condition flares
• Recent exposure to costume jewelry (patients with palmar pompholyx and allergy to nickel)
• Recent treatment with intravenous (IV) immunoglobulin (IVIG) therapy^{[7, 20, 21]}
• HIV infection

Colebunders et al reported two cases of HIV-positive patients who developed dyshidrotic eczema as an immune reconstitution inflammatory syndrome shortly after highly active antiretroviral therapy.^[22] Pompholyx has also been described as a manifestation of symptomatic HIV infection, including in individuals who do not respond to topical and systemic therapies and whose condition resolves only after the initiation of combination antiretroviral therapy.^[23]

Immune checkpoint inhibitor-induced dyshidrotic eczema has been described with tremelimumab.^[24]

Molin et al described the development of an algorithm for the diagnosis of chronic hand dermatitis, which offered an easy way of classifying these skin conditions and thereby facilitating decision-making regarding the choice of treatment modalities.^[25]

• References

Physical Examination

Symmetric crops of clear vesicles, bullae (blisters), or both on the palms and lateral aspects of the fingers are characteristic of dyshidrotic eczema. The feet, the soles, and the lateral aspects of the toes also may be affected. (See the images below.)

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Dyshidrotic eczema (pompholyx). Small tense vesicles on fingers.

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Dyshidrotic eczema (pompholyx). Small, discrete, coalesced vesicles on dorsum of hand.

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Dyshidrotic eczema (pompholyx). Small, discrete, coalesced vesicles on fingers.

In mildly affected patients, vesicles are present only on the lateral aspects of the fingers and occasionally involve feet and toes. (See the image below.)

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Dyshidrotic eczema (pompholyx). Small discrete vesicles of lateral fingers.

Vesicles are deep-seated and have a tapiocalike appearance, without surrounding erythema. They may become large, form bullae, and become confluent. Resolution without rupturing, followed by desquamation, is typical. (See the images below.)

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Dyshidrotic eczema (pompholyx). Tense vesicles and bullae on palm. Image from Norman Minars, MD, University of Miami, Department of Dermatology & Cuta....

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Dyshidrotic eczema (pompholyx). Close-up view of tense vesicles and bullae of palm. Image from Norman Minars, MD, University of Miami, Department of D....

In 80% of patients, only the hands are involved, whereas in 10% of patients, the disease affects only the feet, and in another 10%, the hands and feet are involved together. (See the images below.)

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Dyshidrotic eczema (pompholyx). Discrete yellow pustules on sole of foot. Image from Norman Minars, MD, University of Miami, Department of Dermatology....

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Dyshidrotic eczema (pompholyx). Palms and soles of patient with dyshidrosis flare. Patient unroofed large bulla on right sole.

With long-standing disease, patients' fingernails may reveal dystrophic changes (eg, irregular, transverse ridging; pitting; thickening; discoloration). Interdigital maceration and desquamation of the interdigital spaces often are present, despite the possible absence of a dermatophyte infection. Vesicles and bullae may become infected secondarily, and pustular lesions may be present. Cellulitis and lymphangitis may develop.

Severity index

The Dyshidrotic Eczema Area and Severity Index (DASI) was developed on the basis of severity grades for the number of vesicles per square centimeter, erythema, desquamation, itch, and the extent of affected areas.^[26] The index was found to be a simple standardized method for assessing the condition and was used to assess disease severity and treatment effectiveness in two clinical studies. Further evaluation with larger patient groups is warranted.

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Complications

Secondary bacterial infection of dyshidrotic eczema vesicles or bullae can result in cellulitis, lymphangitis, and bloodstream infection (rare). Dystrophic nail changes may develop, with the occurrence of transverse ridging, thickening, discoloration, and pitting. Dyshidrotic eczema has no associated mortality, though some severe cases can become debilitating. A 2015 study determined that dyshidrosis is a risk factor in the development of herpes zoster.^[27]

• References

Approach Considerations

A 2023 S2k guideline from a group of German medical societies made recommendations for the diagnosis of hand eczema (HE), including the following^[33] :

• Epicutaneous patch testing should be performed if HE persists for more than 3 months, if there is no response to an adequate therapy, or if contact allergy is clinically suspected. Testing should be done with the standard series but may be extended to additional tests, depending on exposure.
• Before epicutaneous patch testing and prick testing, an exposure assessment using all available sources should be performed to identify potential allergens in the surroundings that should be included in the tests.
• Any positive/allergic patch test reaction should be assessed with respect to its clinical relevance. In cases where patch test reactions are negative or doubtful and there is continuing suspicion of contact allergy, strip patch testing should be performed to exclude false negatives and establish sensitization.
• After a positive prick test or epicutaneous patch test, a qualitative and, if possible, quantitative assessment of exposure to allergens should be performed.

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Laboratory Studies

The diagnosis of dyshidrotic eczema (pompholyx) is usually a clinical one, though bacterial culture and sensitivity tests may be useful for excluding secondary infection. Blood tests are not usually ordered; however, immunoglobulin E (IgE) levels are commonly elevated.

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Other Tests

Substances used to systemically challenge patients with possible ingested allergens may trigger exacerbations. Vasculitis or erythema multiforme may develop during this testing.

Patch testing is performed to exclude allergic contact dermatitis. Measurement of thiopurine methyltransferase levels allows accurate dosing of azathioprine. In recalcitrant cases, systemic evaluation is recommended, including serology for human T-cell lymphotrophic virus type 1 (HTLV1), which can rule out the dyshidrosislike variant of adult T-cell leukemia/lymphoma.^[34]  Potassium hydroxide (KOH) wet mount preparation is performed to exclude dermatophyte infection.

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Procedures

Punch biopsy for hematoxylin and eosin (H&E) staining is usually unnecessary. Punch biopsy for periodic acid-Schiff (PAS) staining may help exclude dermatophytosis in patients with unresponsive disease. Punch biopsy for direct immunofluorescence (DIF) is used to exclude bullous pemphigoid.

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Histologic Findings

Spongiosis with an epidermal lymphocytic infiltrate and intraepidermal vesicles or bullae are present. The vesicles are not associated with sweat glands.

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Approach Considerations

Treatment of dyshidrotic eczema (pompholyx) can be quite challenging, both because of the severe inflammatory process that can be involved and because of the frequency of recurrences. The economic burden of this chronic eczema has been stressed.^[35]

In dyshidrotic eczema, typical first-line treatment includes high-strength topical steroids and cold compresses. Corticosteroids are cornerstones of topical therapy. Short courses of oral steroids are the second line of treatment for acute flares, and other immunosuppressants have also been tried. Calcineurin inhibitors may also be effective.^[36]

Variable effects have been reported using oral administration of psoralen and subsequent exposure to long-wavelength ultraviolet A (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.

Intradermal injection of onabotulinumtoxinA has received interest as a treatment for this condition. Probiotics have been suggested as a potential treatment for eczema.^[37] Topical khellin and natural sunlight therapy have been suggested for patients with recalcitrant palmoplantar pompholyx.^[38] Tapwater iontophoresis with pulsed direct current may be helpful as adjuvant treatment.^[39]

Markantoni et al reported excellent results from the use of oxybutynin in two patients with coexistent hyperhidrosis and dyshidrotic eczema.^[40] Further studies would be needed before this treatment is recommended.

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.

If bullae (blisters) are present, the following measures are appropriate:

• Apply compresses with Burow solution (10% aluminum acetate) in a 1:40 dilution until bullae resolve (usually within a few days)
• Compresses with a 1:10.000 solution of potassium permanganate are also effective
• Drain large bullae with a sterile syringe, and leave the roof intact
• Prescribe systemic antibiotics that cover Staphylococcus aureus and group A streptococci

Guidelines for treatment of hand eczema

A 2023 S2k guideline from a group of German medical societies made recommendations for the treatment of hand eczema (HE), including the following^[33] :

• Topical glucocorticoids (with low atrophogenic potential) should be used as short-term first-line therapy for the treatment of HE. Intermittent topical glucocorticoid therapy may be employed for maintenance therapy.
• Tacrolimus ointment (0.1%) may be used as short-term therapy for HE and may be used proactively for maintenance therapy.
• In adults with moderate-to-severe chronic HE (CHE) that is refractory to topical glucocorticoids, phototherapy should be administered; however, it should not be used for long-term treatment.
• Alitretinoin should be used to treat moderate-to-severe CHE if topical therapy and phototherapy alone are not sufficiently effective.
• In individual cases with acute and severe inflammation, an oral glucocorticoid pulse may be used in combination with other therapies as part of a treatment plan.
• Cyclosporine should be used to treat moderate-to-severe CHE that is refractory to first-line and second-line therapies or for which such therapies are contraindicated.
• Azathioprine or methotrexate may be used to treat moderate-to-severe CHE that is refractory to first-line and second-line therapies or for which such therapies are contraindicated.
• Acitretin may be used to treat moderate-to-severe CHE for which other therapeutic options are contraindicated or unavailable.

• References

Pharmacologic Therapy

Corticosteroids

Topical corticosteroids are the mainstay of treatment. Typically, class I steroids are administered initially, followed by class II or III steroids. Ointments penetrate the skin better than creams do, though 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. Patients should be followed and their blood pressure checked 1 week after initiation of prednisone.

Guidelines for topical steroid use in atopic eczema have been established by the National Institute of Clinical Evidence.^[41]

Calcineurin inhibitors

Topical calcineurin inhibitors (eg, tacrolimus and pimecrolimus) may be helpful. Some patients may benefit from this therapy. Several studies have demonstrated the efficacy and tolerability of calcineurin inhibitors in the treatment of chronic hand dermatitis. Long-term efficacy of occlusive therapy with pimecrolimus was reported in patients with severe dyshidrosiform hand and foot eczema.^[42]

Advantages of topical calcineurin inhibitors over topical corticosteroids include the lack of development of tachyphylaxis, telangiectasias, and thinning and atrophy of the skin.^[43]  In the personal experience of one of the coauthors, effective control has been achieved with topical calcineurin inhibitor therapy alone in several patients. It should be kept in mind that topical calcineurin inhibitors can exacerbate irritant hand dermatitis. The authors recommend caution in the extended use of calcineurin inhibitors.

OnabotulinumtoxinA

Intradermal injection of onabotulinumtoxinA may be helpful in some patients. The use of this treatment as an adjuvant to topical corticosteroid therapy was tested in a study in which six patients who completed an 8-week trial period achieved significant reductions in their Dyshidrotic Eczema Area and Severity Index (DASI) scores and faster alleviation of pruritus and vesiculation.^[43]  In another study, seven of 10 vesicular pompholyx patients achieved good to very good responses after the injection of onabotulinumtoxinA alone, with a reduction of pruritus.^[44]

Immunosuppressants

For severe refractory pompholyx, azathioprine, methotrexate,^[45]  mycophenolate mofetil, cyclosporine,^[46]  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 weekly. The patient achieved complete remission for 4 months, after which a relapse occurred.^[47] The etanercept dose was increased to 50 mg twice weekly, without yielding improvement.^[47]  Measurement of thiopurine methyltransferase levels should be considered, these may help guide azathioprine therapy.

Nickel chelators and khellin

Nickel chelators (eg, disulfiram) occasionally are used in nickel-sensitive patients who demonstrate a positive oral provocation test.^[48] ​

Khellin, a furanochromone similar to methoxypsoralen, may be used in combination with photochemotherapy (sun exposure) for recalcitrant palmoplantar cases.^[38]  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 multicenter double-blind randomized controlled trial (RCT; N = 319; pompholyx, n = 70), alitretinoin (10 mg, 20 mg, or 40 mg once daily for 12 wk) produced significant clinical improvements in patients with chronic hand dermatitis that was refractory to standard therapy, but it was not effective specifically against dyshidrotic eczema.^[49]  Although alitretinoin induced a significant clinical improvement in a dose-dependent fashion (53% improvement in disease status, 70% reduction in clinical features) in the patient group as a whole, it did not differ significantly from placebo in the patients with pompholyx.

Headache and mucocutaneous adverse events, including dry skin, rash, alopecia, exfoliative dermatitis, and hyperlipidemia, have been the most common adverse events in these trials.^{[43, 50]}

Alitretinoin 1% gel has been evaluated for the treatment of classic Kaposi sarcoma,^[51]  photoaging,^[52]  pyogenic granuloma,^[53]  and cutaneous T-cell lymphoma.^[54]  It has not been generally used for the topical treatment of pompholyx.

Three phase III studies (one open-label study and two double-blind RCTs) evaluated the safety^[55]  and efficacy^[56]  of once-daily oral alitretinoin at 10 mg or 30 mg vs placebo in 1032 patients with chronic hand eczema (including pompholyx) in whom treatment with potent topical corticosteroids had failed.

A physician assessment of "clear" or "almost clear" was achieved in as many as 48% of patients in the alitretinoin groups and in 17% of participants in the placebo group.^{[55, 56]} Median percentage reduction in disease symptoms was 75%. Alitretinoin 30 mg yielded faster responses (median, 85 d) than 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.^{[55, 56]} Headache was the most common adverse effect with alitretinoin 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

Various other potential agents (eg, topical bexarotene, systemic alitretinoin, leukotriene receptor antagonists, leukotriene synthesis inhibitors, phosphodiesterase [PDE]-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 are required to establish their efficacy and safety for the treatment of dyshidrotic eczema (pompholyx).

Recalcitrant dyshidrotic eczema may be treated with dupilumab.^[57]  Two systematic reviews found it to be effective and well tolerated in the treatment of CHE, though further study would be needed to define its long-term effectiveness, optimal dosing strategies, cost-effectiveness, and applicability to specific subtypes of CHE.^{[58, 59]}  

Parmar reported a case of successful treatment of dyshidrotic palmoplantar eczema with tralokinumab.^[60]

The Janus kinase (JAK) inhibitor upadacitinib has also been tried in this setting.^{[61, 62]}

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Ultraviolet Light Therapy

Paradoxically, although UVA is sometimes linked as a possible cause of dyshidrotic eczema, it has also been used to treat this condition, either alone or in combination with oral or topical psoralen. Hand or foot UVA therapy (UVA or UVA-1 alone or with oral or topical psoralen) improves the eruption and pruritus when administered two or three times weekly. The dose typically starts at 0.5 J per treatment and is increased by 0.5 J at every other or every third treatment.^{[63, 64]}

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.^[65] Local narrowband UVB has been shown to be as effective as bath-PUVA in patients with chronic hand eczema of dry and dyshidrotic types.^[66]

In a retrospective study (N = 64) of adults with chronic hand dermatitis that was refractory to topical corticosteroids, Bednar et al assessed a combination regimen of narrowband UVB therapy three times weekly plus low-dose (10 mg) oral alitretinoin three times weekly (n = 33) against a regimen of high-dose (30 mg/day) oral alitretinoin alone (n = 31) over a period of 16 weeks.^[67]  The combination regimen was found to be both more effective and less likely to cause adverse effects than the high-dose oral alitretinoin regimen.

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Diet

For nickel-sensitive patients, a 3- to 4-week low-nickel diet should be considered. However, this diet regimen is only rarely successful and is difficult for patients to follow. It 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, it is worthwhile to 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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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.

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Prevention

Dyshidrotic eczema patients should be advised to avoid known contact irritants or allergens, to reduce stress, to follow a hand care regimen, and to use regular prophylactic emollients.

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Consultations

Consultation with a psychologist may be helpful for stress reduction with biofeedback therapy and other techniques. 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.

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Guidelines Summary

The following organizations have released guidelines for the management of hand eczema. Key diagnostic and treatment recommendations have been reviewed and integrated throughout the article:

• German Dermatological Society (DDG; including Working Group for Occupational and Environmental Dermatology [ABD] and German Contact Allergy Group [DKG])/Medical Association of German Allergologists (AeDA)/Professional Association of German Dermatologists (BVDD)/German Society for Allergology and Clinical Immunology (DGAKI) - S2k Guideline: Diagnosis, Prevention, and Therapy of Hand Eczema^[33]

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Hydroxyzine (Vistaril)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Loratadine (Alavert, Claritin, Claritin RediTabs)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Bexarotene (Targretin)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Pramoxine topical (Azo Itch Relief Maximum Strength Analgesic Cream, Eczemin, Itch-X Gel)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Pimecrolimus (Elidel)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Tacrolimus ointment (Protopic)

• Dosing, Interactions, etc.

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Cephalexin (Keflex, Panixine Disperdose)

• Dosing, Interactions, etc.

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Prednisone (Deltasone, Prednisone Intensol, Rayos)

• Dosing, Interactions, etc.

Clinical Context: 

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Betamethasone topical (Alphatrex, BetaVal, Dermabet)

• Dosing, Interactions, etc.

Clinical Context: 

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Clobetasol (Clobex, Clobex Spray, Cormax)

• Dosing, Interactions, etc.

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Fluocinonide (Lidemol, Lidex, Lyderm)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Triamcinolone topical (Kenalog Orabase, Kenalog topical, Pediaderm TA)

• Dosing, Interactions, etc.

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Azathioprine (Azasan, Imuran)

• Dosing, Interactions, etc.

Clinical Context: 

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Cyclosporine (Gengraf, Neoral, Sandimmune)

• Dosing, Interactions, etc.

Clinical Context: 

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Etanercept (Enbrel, Erelzi, Etanercept-szzs)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Methotrexate (Jylamvo, Otrexup, Rasuvo)

• Dosing, Interactions, etc.

Clinical Context: 

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Mycophenolate (CellCept, MMF, Myfortic)

• Dosing, Interactions, etc.

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Dupilumab (Dupixent)

• Dosing, Interactions, etc.

Clinical Context: 

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Erythromycin base (Ery-Tab, PCE Dispertab)

• Dosing, Interactions, etc.

Clinical Context: 

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Dicloxacillin

• Dosing, Interactions, etc.

Clinical Context: 

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Disulfiram (Antabuse)

• Dosing, Interactions, etc.

Clinical Context: 

• References