Chapter 16. Vesicular Palmoplantar Eczema

Vesicular palmoplantar eczema is a dermatitis of the hands and feet characterized by small to large blisters clinically and spongiotic vesicles histologically. It can manifest as either an acute or a chronic dermatitis, or both. Because clinical and histologic presentations of the variants of hand dermatitis, including vesicular palmoplantar eczema, often overlap, making a precise diagnosis can be difficult. For example, patients with pompholyx, the most acute form of vesicular palmoplantar eczema, have been noted to have higher incidence rates of both atopy and contact dermatitis than controls.

With the preceding caveat in mind, vesicular palmoplantar eczema can be divided into four categories: (1) pompholyx, (2) chronic vesiculobullous hand dermatitis, (3) hyperkeratotic hand dermatitis, and (4) id reactions (see Chapter 17). These conditions can be grouped under the category of endogenous hand dermatitis, in contrast to dermatitis clearly caused by exogenous factors such as contact allergy or irritation.

Pompholyx is a term best reserved for acute explosive outbreaks of small to large vesicles and bullae on the palms and soles. It tends to occur more often in the spring and fall, and may be associated with stress. Other etiologic factors are less well established. Cheiropompholyx and podopompholyx are terms occasionally used to describe cases affecting the palms or soles, respectively. Chronic vesiculobullous hand dermatitis, also known as dyshidrotic hand eczema or dyshidrotic hand dermatitis, is usually characterized by small vesicles on the lateral aspects of the fingers. “Dyshidrosis,” a dysfunction of the sweat gland, was long postulated to be a cause, but its role has been subsequently disproved. However, the terminology persists and is commonly used. A third category is chronic hyperkeratotic hand dermatitis, an entity that generally occurs on the central palms. Unlike the other classifications of vesicular palmoplantar eczema, vesicles do not dominate the clinical presentation. However, the spongiosis observed histologically is indistinguishable from the other categories. An id reaction is a vesiculobullous dermatitis, generally appearing on the lateral aspects of the fingers, elicited by an infection elsewhere in the body. The most common cause is a fungal infection. Treatment of the underlying causative factor usually leads to resolution. Endogenous hand dermatitis can be exacerbated by exogenous factors, most notably irritant dermatitis and allergic contact dermatitis. In addition, atopy may in some cases predispose to the development of vesicular palmoplantar eczema.

Differences in classification and definition have made it difficult to assess the true incidence of the endogenous hand disorders. Most studies have focused on the prevalence of exogenous hand disorders as seen in occupational settings. Pompholyx is the least common presentation of hand dermatitis; in one population study, the 1-year prevalence of pompholyx was estimated to be 0.5%.1 In the same study, hyperkeratotic hand dermatitis represented 2% of all hand dermatoses.1 Other studies have noted prevalence rates ranging from 1% to 5%, with the variation in the frequency of vesicular hand eczema attributable in part to the lack of a common condition.2,3,4

With the exception of the id reaction, a direct cause of vesicular palmoplantar eczema is rarely identified. A number of etiologic factors have been associated with pompholyx, including atopy (see Chapter 14), contact allergy (see Chapter 13), psychological stress, and hot weather.1 Pompholyx has also been reported after ingestion of piroxicam,5 after ingestion of certain metals in predisposed or sensitized patients most commonly nickel, cobalt, and chromate5 and after intravenous immunoglobulin therapy, with 39 cases reported to date.6,7 There has also been a report of five cases of photo-induced pompholyx in patients with a reported history of photo-induced disease that was reproduced when the patients were phototested with an ultraviolet A (UVA) source.5 Histologic evaluation confirmed the diagnosis of pompholyx and a true photosensitivity rather than photoaggravation. Additionally, there has been evidence of association of vesicular hand eczema following dermatophytid from tinea pedis.8 In a study of 398 patients with hand eczema, those with culture positive tinea pedis were found to have an increased relative risk of 3.58 (p < 0.05) for vesicular hand eczema.9

Contact allergy is common in patients affected with vesicular palmoplantar eczema, especially the chronic type, but the causal relationship is not always clear. There are cases in which contact allergy has exacerbated preexisting hand dermatitis and also reports that ingestion of certain metals, including nickel, cobalt, and chromium, have caused flares. However, in other cases, the causal relationship may be the reverse. The skin's impaired barrier function in vesiculobullous hand dermatitis (see Chapter 47) may in some cases lead to sensitization and a higher prevalence of contact dermatitis in the affected population. Investigations into the role of atopy (see Chapter 14) have yielded mixed results. Some studies have shown levels of personal or familial atopy as high as 50% in affected subjects, compared to 11.5% of controls, but other studies have demonstrated no difference in the prevalence in people with vesiculobullous hand dermatitis versus controls.10

Pompholyx

Figure 16-1 is an algorithm showing the approach to the patient with vesicular palmoplantar eczema. Pompholyx can even be severe enough to necessitate hospitalization. In true acute pompholyx, there is an explosive outbreak of deep-seated vesicles on the palms, the lateral aspects of the fingers (Fig. 16-2), and sometimes the soles, usually in a symmetric pattern. Discomfort and itching usually precede the development of the blisters, which have been described as having a “tapioca” appearance (see Fig. 16-3). Blisters may coalesce then desiccate and resolve without rupture (Fig. 16-4). Intact, large blisters can be drained, but should not be unroofed. However, large blisters may rupture spontaneously, leaving oozing or dried up erosions (Fig. 16-5).

This acute phase is generally followed by desquamation of the affected areas. Individual outbreaks are usually self-limited over 2–3 weeks, although they may recur. Secondary bacterial infection is common, often resulting in a local cellulitis, and can sometimes potentiate the development of lymphatic damage, resulting in lymphedema. Attacks are most common among adolescents and young adults and seem to be more common in the spring and summer months. Outbreaks have been shown to be associated with dermatophyte infection, contact dermatitis, in particular cosmetic and hygiene products, metals and internal reactivation from drugs, foods, or metals.

Chronic Vesiculobullous Dermatitis

Chronic vesiculobullous hand dermatitis is more common than pompholyx and more difficult to manage because of its relapsing course. The clinical presentation includes small 1- to 2-mm vesicles filled with clear fluid localizing to the lateral aspects of the fingers, palms, and soles as in pompholyx (see Fig. 16-3). As the condition becomes more chronic, the clinical appearance may evolve and subsequently appear more fissured and hyperkeratotic (as in Figs. 16-2 and 16-6). A clear history of vesicles or exacerbations characterized by blistering may help to narrow the classification of a given presentation of hand dermatitis.

Hyperkeratotic Hand Dermatitis

Patients with hyperkeratotic hand dermatitis are usually male and generally present with chronic keratotic pruritic plaques, sometimes with fissures on the central palm (see Fig. 16-6). This condition may be the end result of contact allergy, excoriation, and irritation, but generally the cause is not identifiable, and contact allergy does not seem to play an important role. This hand dermatitis commonly occurs in middle-aged to elderly men and is often very refractory to treatment. Friction in lichen simplex chronicus may be an important factor in some cases. Plantar involvement is present in a minority of cases.

ID Reaction

(See Chapter 17)

In an id reaction, erythematous vesicles usually are seen on the lateral aspects of the fingers and the palms and are typically pruritic (Fig. 16-7). This eruption of vesicles is usually sudden and classically occurs in response to an intense inflammatory process, especially fungal infections, taking place somewhere else on the body. The id reaction is thought to be an allergic reaction to fungi or to some antigen created during inflammation. Treatment of the underlying infection results in resolution.

In the diagnostic workup of vesicular palmoplantar eczema, it is important to first examine the feet to exclude a dermatophytid. Secondly, a potassium hydroxide examination of the hand should be performed to rule out tinea manuum. Finally, patch testing should be performed to rule out a contact dermatitis or a systemic reaction to a contact allergen. There are no specific laboratory findings characteristic of vesicular palmoplantar eczema, although IgE levels may be elevated in atopic patients.

The histology of these entities depends on the chronicity of the disease. The primary vesicle appears as an intraepidermal spongiotic vesicle that does not involve the acrosyringia on either conventional and electron microscopy. Lymphocytic infiltration is common in the epidermis, with a mixed infiltrate observed in the dermis. In more chronic cases, the epidermis may show hyperproliferation, hyperkeratosis, or even psoriasiform epidermal hyperplasia. Periodic acid-Schiff staining can be helpful in excluding fungal elements.

The diagnosis of vesiculobullous hand dermatitis is usually made on the basis of clinical presentation, history, and sometimes histology. Patch testing may be useful in helping to distinguish this entity from other palmoplantar disorders or in eliminating other exacerbating factors such as irritant exposure and contact allergy.

There are many other skin conditions of the hands and feet that can be difficult to distinguish from vesiculobullous hand dermatitis. Several of the diagnoses may also coexist.

(Box 16-1)

Allergic contact dermatitis (see Chapter 13) may be clinically indistinguishable from other forms of hand eczema, and patch testing should be considered for those with recurrent, atypical, or persistent forms of the disease. In a recent study of 422 patients with hand eczema, the ten most common allergens with positive patch testing were nickel, cobalt, thiuram mix, balsam of Peru (Myroxylon pereirae resin), formaldehyde, colophony, potassium dichromate, benzoyl peroxide, fragrances methylchloroisothiazolinone/methylisothiazolinone, and sesquiterpene lactone mix.11,12 Although frequently considered, laundry detergents rarely cause allergic contact dermatitis. Irritants (see Chapter 48) are by far the most common causes of hand dermatitis that are often exacerbated by occupational exposures. The irritant dermatitis is usually symmetric and chronic, and affects the dorsal fingertips and web spaces.

Atopic hand dermatitis (see Chapter 14) is associated with a number of factors: hand dermatitis before age 15 years, persistent eczema on the body, dry or itchy skin in adult life, and widespread atopic dermatitis in childhood. The backs of the hands, particularly the fingers, are affected with erythema, vesiculation, crusting, excoriation, and scale.

Infections, most commonly from tinea, can mimic endogenous hand dermatitis. In cases of asymmetric or atypical cases, or in cases of small vesicles confined to the feet, a potassium hydroxide examination may be useful in ruling out primary tinea infection. In chronic cases of hand dermatitis, fungal and bacterial infections may be superimposed, and treatment may result in improvement of clinical symptoms. Herpes simplex may, in unusual cases, present as blisters on the hands.

Psoriasis and psoriasiform hand dermatitis (see Chapter 18) are most prominent over pressure points. Psoriasis can normally be distinguished by its sharply marginated, nummular, or circinate scaly plaques; relative lack of itching; silvery scales; and the presence of psoriasis elsewhere. Psoriasiform hand dermatitis can occur without a family or personal history of psoriasis. It is a diagnosis made primarily on clinical and histologic presentation. At times, however, it appears as though eczematous, hyperkeratotic, and psoriatic diatheses coexist. Repeated pressure or friction may cause hyperkeratosis in some individuals.

Pustular eruptions of the palms and soles (see Chapter 21) are generally easy to distinguish because, unlike the presentation of clear fluid-filled blisters and bullae of hand dermatitis, pustules are the primary lesions. For example, in pustular psoriasis, the vesicles are cloudy and painful.

Keratolysis exfoliativa (recurrent focal palmar peeling) is a chronic, asymptomatic, and noninflammatory peeling of the palms and soles, most commonly seen during the summer months. It is thought to occur more frequently in people with hyperhidrosis in these areas. Scaling usually starts from one to two fine points and expands outward to larger circular areas. The condition is usually self-limited and asymptomatic, requiring only emollients.

Bazex acrokeratosis paraneoplastica is a rare, acute, erythematous, scaling, vesiculobullous hand dermatitis with nail dystrophy associated with neoplasia, usually squamous carcinomas of the upper digestive or respiratory tracts, although there have been some reports of similar findings in patients with colon cancer and genitourinary tumors.

Other blistering diseases, such as pemphigoid, pemphigus, or epidermolysis bullosa, may affect the hands and feet, but usually do so in the setting of blisters elsewhere on the body.

Secondary bacterial infection of the vesicles can result in cellulitis, lymphedema, and, in rare instances, septicemia.13

Pompholyx tends to occur as intermittent explosive outbreaks and becomes less frequent in middle-aged individuals. The more chronic forms of vesicular palmoplantar eczema, however, are much more persistent and frustrating to manage and often require multiple therapeutic approaches over time.

(Box 16-2)

Treatment of vesiculobullous hand dermatitis should be based on the acuity of the condition, the severity of the disease, the prominence of blisters versus chronic changes, and any relevant history that reveals possible cofactors.

Topical Therapy

Topical steroids, typically high potency (class 1 or 2), are usually first-line agents. They are often more effective if used under occlusion, although this approach may increase the chance of infection. Topical drying agents, such as Domeboro soaks, Burow's solutions (aluminum subacetate), or dilute potassium permanganate solution (1–8,000) may be useful in acute forms with a predominance of vesicles.

Nonsteroidal topical immunomodulating agents, such as tacrolimus and pimecrolimus, have been studied for treatment of individuals with mild to moderate chronic hand dermatitis with improvements from baseline.5 Topical tacrolimus was shown to be as effective as momethasone furoate 0.1% ointment in a randomized, blinded trial in patients with vesicular pompholyx of the palms. After 2 weeks of treatment, the Dyshidrotic Eczema Area and Severity Index (DASI) was reduced by more than 50%.14

Hyperkeratotic palmar eczema is notoriously difficult to manage. Topical retinoids and calcipotriene, both of which act to regulate epidermal cell maturation, have anecdotally been shown to improve this category of hand dermatitis.1

Systemic Therapy

For recurrent pompholyx and chronic vesicular dermatitis, oral prednisone may be required and is often effective if treatment is initiated early, at the onset of the itching prodrome. However, because of significant side effects, systemic glucocorticoids are typically inappropriate for long-term management. Intralesional and intramuscular steroid injections can also be considered for short-term use in acute episodes when intensive topical therapy fails.

Cyclosporine has been studied at dosing levels of 3 mg/kg/day and 5 mg/kg/day in the treatment of chronic vesicular dermatitis. Although patients showed improvement with treatment, relapses occurred shortly after discontinuation of cyclosporine.15

Mycophenolate mofetil has been used in the treatment of chronic vesicular dermatitis at dosing levels of 2–3 g/day (in divided doses). It has been anecdotally shown to improve chronic vesicular dermatitis that has been otherwise recalcitrant to corticosteroids, iontophoresis, and phototherapy. However, it has also been anecdotally shown to induce biopsy-proven dyshidrotic eczema.

Methotrexate has proven a useful therapy of a wide range of skin diseases. In chronic vesicular eczema, it has been reported to partially or completely clear lesions at low doses ranging from 12.5 to 22.5 mg/week.15 However, its wide spectrum of potential side effects remains a limiting factor to its use in this particular skin disease.

Alitretinoin, (9-cis-retinoic acid) is a novel retinoid with anti-inflammatory properties and one of the newer therapies under study for palmoplantar vesicular eczema. It is the only medication specifically approved for the treatment of adults with hand eczema unresponsive to topical steroids in some countries outside of the United States.19 In a large controlled study with over 1,000 patients it was successful in the treatment of chronic hyperkeratotic hand eczema and offers another treatment option for patients refractory to treatments with corticosteroids, radiation therapy, tretinoin, isotretinoin, and acitretin.20

UVB, systemic, topical, and bathwater psoralen and UVA light with or without PUVA have been used in severe cases of chronic vesicular hand eczema. Studies evaluating the use of UVA-1 compared localized high-dose UVA-1 irradiation against topical cream psoralen UVA for the treatment of dyshidrotic eczema demonstrated that UVA-1 irradiation and topical PUVA showed similar beneficial responses.23,24 In addition, the potential side effects noted with PUVA, such as phototoxic reactions and long-term carcinogenic risk, are theoretically reduced with UVA-1 therapy. UV therapy is thought to work by induction of apoptosis of T and B lymphocytes.

Other Therapies

Iontophoresis, sympathectomy, and intradermal botulinum toxin are effective therapies for hyperhidrosis and have been studied as treatments for chronic vesicular dermatitis.15 Tap water iontophoresis with pulsed direct current showed no benefit for subjects with hand dermatitis over controls in time to improvement, but those who were treated had much longer remissions, by a factor of months.6 Intradermal botulinum toxin A was shown to have a beneficial effect in patients with treatment-refractory vesicular dermatitis, especially in those patients whose condition was aggravated by hyperhidrosis.25 This therapy may also be used in conjunction with topical corticosteroids.26

Future Therapies

Radiation Therapy and Immunotherapy

The use of etanercept has also been shown in a case report to be successful in treatment of recalcitrant dyshidrotic eczema for a 4-month period before relapse occurred.16

Azathioprine has been shown to be efficacious in a study that included six patients with pompholyx; however, a separate case study of its use reported development of myelotoxicity.17,18

Superficial radiotherapy (Grenz ray) is still sometimes used at a few centers. This condition may be one of the last indications for this treatment modality, and has been shown to be successful in some patients with resistant chronic eczema of the hand in a double-blind study.14 Megavoltage radiation therapy (1,200 cGy) has also been tried in patients with severe chronic vesicular hand dermatitis with moderate success in long-term remission.21,22

Leuokotriene Inhibitors

Leukotriene receptor antagonists and inhibitors are oral medications that act by inhibiting proinflammatory mediators in the 5-lipoxygenase pathway and have been shown to block the effects of leukotrienes successfully in asthma, allergic rhinitis, and recently in atopic dermatitis. No specific trial has been reported yet with these medications on pompholyx.

Phosphodiesterases-4 (PDE4) modulate the release of inflammatory mediators and have recently been investigated as a novel therapeutic approach in the treatment of inflammation-associated diseases. Animal models of PDE4 inhibitors have displayed strong anti-inflammatory action in models of allergic contact dermatitis. The safety and efficacy in pompholyx has yet to be evaluated.

Tumor necrosis factor inhibitors (e.g., infliximab) have been successful for treatment of psoriatic arthritis and psoriasis, among other chronic inflammatory diseases. No data is available on pompholyx.

Two severity indices, (1) the dyshidrosis area and severity index and (2) the total sign and symptoms score, have been validated and may prove useful in clinical trials to better assess the effectiveness of these and future therapies.

Prevention is a critical part of therapy in most cases, especially when known exacerbating factors are present. Avoidance of commonly encountered allergens, such as foods and plants, and irritants, such as soaps, solvents, acids, and alkalis, can be helpful. Vinyl gloves, rather than latex, are recommended because of the risk of either having an underlying allergy or of developing one in the setting of impaired barrier function. Patch testing may be considered for patients to identify relevant allergens. Modification of environmental exposure to exacerbating factors, such as friction and cold air, may also help with persistent or refractory disease. Frequent use of emollients, specifically novel barrier creams or ointments, help to preserve the normal skin-barrier function. Maintaining a low-cobalt diet has been suggested to decrease the number of dyshidrotic flares.28