Vesicular palmoplantar eczema

Background

Vesicular palmoplantar eczema is a term used to describe a group of diseases

characterized by vesiculobullous eruption involving mainly the hands and feet.

Clinical presentations vary from acute dermatitis to more chronic relapsing and

remitting disease patterns. The diversity of presentation has created challenges in

classifying hand eczema. A 2011 publication assembled an algorithm for chronic

hand eczema based on etiology, morphology and clinical features.[1]

Although considerable overlap exists in the various forms of vesicular

palmoplantar eczema, the disease can be roughly divided into 4 distinct

categories: pompholyx, subacute or chronic relapsing vesiculosquamous eczema,

chronic vesiculohyperkeratotic or hyperkeratotic eczema, and id reactions.

Pompholyx ("blister" or "bubble" in Greek) may be further subdivided into

vesicular and bullous forms, in which patients present with acute severe

eruptions of blisters over their palms and, less commonly, the soles.

Chronic vesiculosquamous eczema, also called dyshidrotic eczema, was initially

thought to be caused by abnormal functioning of the sweat glands. This

association has since been disproved, but the term dyshidrotic eczema is still

used. Patients with this variant present with small (1-2 mm) vesicles on

nonerythematous skin involving the inner sides of the fingers or on the palms

and soles. The vesicles are pruritic, last 1-2 weeks, desquamate, and then recur

at unpredictable intervals.

The chronic hyperkeratotic variety involves mainly the central palms, where it

causes thickening and fissures. This category is notoriously the most difficult to

treat.

An id reaction refers to vesicular eruption of the hands, caused by a distal focus

of infection, with fungal infections being the most common.

Despite the wide range of clinical presentations, all 4 types of vesicular

palmoplantar eczema are histologically characterized by features of dermatitis,

such as spongiosis and exocytosis.

Pathophysiology

Vesicular palmoplantar eczema is often thought to have an unidentified intrinsic

cause. Although many etiologic factors are described, the underlying pathology of

vesicular palmoplantar eczema is unknown. Similarly, although certain triggers

have been associated with the development or worsening of symptoms, how these

triggers cause flares has not been elucidated.

Vesicular palmoplantar eczema results in histologic evidence of dermatitis, such

as spongiosis, which is often accompanied by lymphocytic infiltrates.

Epidemiology

Frequency

United States

The frequency of vesicular palmoplantar eczema in the United States is unknown.

International

The true incidence is unknown, but vesicular palmoplantar eczema is probably

responsible for 5-20% of all cases of eczema of the hand. A 2012 study found

pompholyx accounted for 14% of all cases of hand eczema.[2]

Mortality/Morbidity

Patients with mild cases of pompholyx have an excellent prognosis. The more

severe chronic hyperkeratotic variety of vesicular palmoplantar eczema often

requires lifelong treatment and results in considerable disability.

Sex

The male-to-female ratio for vesicular palmoplantar eczema is 1:1.

Age

Pompholyx most commonly occurs in patients aged 20-40 years, but it may occur

in individuals of any age. Onset in patients younger than 10 years is unusual. The

frequency of recurrent episodes of pompholyx decreases after middle age,

although this is not true of chronic vesicular and hyperkeratotic variants.

History

The severity of vesicular palmoplantar eczema symptoms varies, ranging from

mild discomfort to acute severe episodes. Patients rarely require hospitalization.

Classically, itching, burning, and prickling sensations of the palms and soles

precede the eruption of vesicles.

Thereafter, small (1- to 2-mm) vesicles form, most commonly on the lateral

sides of the fingers. In pompholyx, the central areas of the palms and soles may

or may not be involved.

Large vesicles can develop on the palms and soles and may coalesce to form

confluent bullae.

The lesions last for 2-3 weeks, after which spontaneous resolution generally

occurs. Occasionally, large bullae may need to be aspirated. This phase is

followed by desquamation.

Chronic forms typically recur, and episodes are more frequent during the spring

and summer than in the fall and winter.

The chronic hyperkeratotic variety results in severe itching accompanied by

thickening and fissuring of the palm. This effect may decrease the mobility of

the affected hand.

Physical

Clinical signs depend on the stage of vesicular palmoplantar eczema. An absence

of erythema is often an important clinical feature in the acute and chronic forms.

Pompholyx of the palms.

Acute episodes are characterized by a sudden onset of small, clear vesicles or

bullae that are said to be sagolike or tapiocalike in appearance (see the image

above).

Vesicles and/or bullae are accompanied by severe, occasionally painful pruritus.

Small vesicles may enlarge or become more confluent and present as large

bullae (especially on the palms and soles).

Vesicles and bullae subsequently dry out and resolve, usually without rupturing.

In most individuals, desquamation occurs 2-3 weeks after the onset of vesicles

and bullae.

In some patients, a milder recurrence follows the initial severe episode.

Secondary infections, such as impetigo, cellulitis, or lymphangitis, are possible

in patients with recurrent hand eczema.

Secondary nail changes (eg, dystrophic nails, irregular transverse ridging,

pitting, thickening, discoloration) can also occur.

Subacute vesicular eczema tends to have a chronic relapsing course with more

vesiculation and more erythema in the acute phases than in later phases.

Residual erythema or some dryness or scaling occurs in the less-active phases.

Fissures are common and painful sequelae.

A form of microvesicular palmar eczema also occurs in association with dry

nummular (discoid) eczema.

When they occur on the hands, id reactions typically involve the lateral sides of

the fingers. These reactions often resolve when the primary infection is treated.

Causes

The etiology of hand eczema is unknown, but most observers suggest that

intrinsic changes in the skin are responsible for vesicular palmoplantar eczema. A

study of an autosomal dominant form of pompholyx found a genetic linkage on

chromosome 18.[3] Whether other forms have a similar genetic linkage is not clear.

However, several exogenous factors have been implicated in the causation or

worsening of vesicular palmoplantar eczema.[4]

Coexisting atopy is common in patients with palmoplantar eczema. A recent

study found a strong association between pompholyx and atopic status.[2]However, this is by no means the only causal relationship because many

patients have no history of atopy.

Emotional stress may also trigger episodes.

Seasonal changes seem to be directly related to relapses, as episodes are most

common in the spring and summer months. Warm weather has been known to

initiate episodes, with several cases reporting photo-induced pompholyx.

o Although dysfunction of the sweat glands is no longer accepted as the cause of

dyshidrotic eczema, increased sweating seems to exacerbate the condition and

many patients with palmar hyperhidrosis also have coexisting dyshidrotic

eczema.

o Photosensitivity to ultraviolet A (UVA) has been reported as an etiologic

factor in a small subset of patients with eczema.[5, 6] Therefore, worsening of the

disease in summer months may be due to the increase in exposure to sunlight.

Conversely, UVA therapy is a widely accepted form of treatment for

palmoplantar eczema.[7]

Sensitivity to certain metals, particularly nickel and cobalt, has been linked to

vesicular palmoplantar eczema.

Exogenous factors causing allergic contact pompholyx include balsams and

cosmetic and hygiene products.[8]

Drugs responsible for inducing episodes include oral contraceptive pills and

aspirin. Palmoplantar eczema occurring after intravenous immunoglobulin

(IVIG) therapy is reported.[9] One case report describes occurrence in the

pediatric population after IVIG administration for Kawasaki syndrome.[10] A

review of eczematous reactions linked with IVIG therapy cited pompholyx as

occurring in 62.5% of the cases reported to have an eczematous reaction

associated with IVIG.[7]

Fungal infections, particularly tinea pedis, are most commonly implicated in id

reactions. Bacterial infections play a role in both causation and in secondarily

infecting lesions.

Cigarette smoking may reduce the efficacy of topical therapy with psoralen and

UVA (PUVA) and has been itself, linked to pompholyx.

HIV infection has been associated with pompholyx, with response to

antiretroviral therapy; conversely, one case report describes of 2 HIV-positive

patients who developed severe dyshidrotic eczema after starting antiretroviral

treatment, thought to be due to an immune reconstitution inflammatory

syndrome

Differential Diagnoses

Contact Dermatitis, Allergic

Contact Dermatitis, Irritant

Lichen Planus

Pityriasis Rubra Pilaris

Psoriasis, Pustular

Syphilis

Laboratory Studies

The diagnosis of palmoplantar eczema is essentially a clinical one, and laboratory

tests are not routinely performed. However, laboratory studies may be helpful in

excluding other disorders.

Elevated serum immunoglobulin E levels or positive results on prick tests may

suggest an atopic tendency.

Skin scrapings can be used to exclude the presence of a fungus.

Skin swabs may exclude bacterial infection.

Other Tests

Perform KOH staining of skin scrapings to rule out fungal infection, especially in

hyperkeratotic forms of the disease.

Swab and culture suspected lesions to exclude secondary bacterial infection.

Procedures

Perform patch tests to exclude contact dermatitis or a systemic reaction to contact

allergen.

Perform biopsy to distinguish eczema from psoriasis or some forms of

palmoplantar hyperkeratoses.

Histologic Findings

Histologic features vary according to the stage of the evolution vesicular

palmoplantar eczema. Usually, evidence suggests intracellular edema or

spongiosis, lymphocytic infiltration of the epidermis, and intraepidermal vesicles

or bullae in acutely affected persons. In chronically affected persons, spongiosis is

present and often associated with epithelial proliferation and/or hyperkeratosis or

psoriasiform epidermal hyperplasia. Dermis is often edematous, with a mixed

perivascular inflammatory cell infiltrate

Medical Care

Several modalities of therapy are available for the treatment and control of

vesicular palmoplantar eczema. Therapy should be chosen according to the type

and severity of the condition. Whenever possible, eliminate known triggers. If

pruritus is a problem, antihistamines (eg. hydroxyzine) can relieve some

symptoms.

Preventative measures

Regular use of hand emollients and avoidance of frequent contact with irritants

are important means to prevent flare-ups of vesicular palmoplantar eczema.

Contact allergy has been noted in one study to be responsible for 67.5% of

pompholyx eczema, and all patients should be considered for patch testing to

identify relevant allergens.[8]

Topical therapy

Topical therapy for vesicular palmoplantar eczema includes high-potency

glucocorticoids, Burow solution (aluminum acetate 1% or potassium

permanganate solution [1:8000 dilution]), tacrolimus, and/or psoralen plus UVA

(PUVA).

Topical high-potency glucocorticoids, such as betamethasone dipropionate and

clobetasol propionate, are first-line therapies. Application of these medications

under plastic and vinyl occlusion enhances their efficacy. However, this method

may predispose the patient to secondary bacterial or fungal infection and to both

local and systemic adverse effects of corticosteroids. Therefore, it should be

used only intermittently and should never be used in the presence of coexisting

infection.

Patients with mild vesicular palmoplantar eczema may be controlled with the

use of less potent corticosteroids such as betamethasone valerate, triamcinolone,

or mometasone.

Acute, severe episodes of pompholyx benefit from rest, and bland applications

with wet soaks and compresses and with drying agents such as Burow solution.

Occasionally, large blisters may need to be aspirated.

Newer agents, such as topical tacrolimus and pimecrolimus, have been shown to

be as effective as mometasone furoate in the treatment of chronic relapsing

eczema of the hands.[14] These topical immunomodulators may be used as

steroid-sparing agents to treat resistant palmar eczema, with minimal systemic

absorption or systemic effect.[15] Use of other agents should be considered when

plantar eczema is being treated because this therapy is less effective on the soles

of the feet than on the hands. The use of occlusion with these agents has also

been shown to increase their efficacy.

A small open-label study demonstrated efficacy of topical vitamin D-3

derivatives (ie, calcipotriol, maxacalcitol) for the control of hyperkeratotic

palmoplantar eczema.[16]

Systemic therapy

Systemic therapy includes steroids, immunosuppressive agents (eg, azathioprine,[17] cyclosporine), retinoids (eg, acitretin, alitretinoin), and PUVA.

Consider the use of systemic glucocorticoids or intralesional steroids in acute

episodes of vesicular palmoplantar eczema when local therapy fails. These

agents are not helpful for long-term treatment because of a potential for severe

adverse effects.

Cyclosporine, mycophenolate mofetil, and methotrexate either alone or in

combination with steroids may be used for severe, recalcitrant cases of vesicular

palmoplantar eczema.[18, 19] These therapies have also been tried as steroid-

sparing agents in chronic relapsing eczema.

For hyperkeratotic eczema, consider the use of aromatic retinoids, such as

acitretin, which help control hyperkeratosis. These agents are best used in

relatively low doses because of adverse effects. Therapy may need to be

continued indefinitely in cases of hyperkeratotic eczema and is often

accompanied by topical occlusive therapy, with combined or alternating steroids

and keratolytics (5-20% salicylic acid) or tar preparations.

Increasingly, the retinoid alitretinoin has been shown to be a favorable option for

severe hand eczema. One randomized, double-blind, placebo-controlled

multicenter trial examining severe chronic hand eczema found alitretinoin

superior to placebo, with 48% of patients achieving full or almost full resolution

of signs and symptoms.[20] A 2012 observational study noted alitretinoin

improved vesicular eczema in 47.9% of patients.[21]

The use of etanercept in a case study achieved a 4-month remission of vesicular

palmoplantar eczema, which was followed by relapse.[22]

Phototherapy has been shown to be effective in dyshidrotic eczema, in particular

PUVA. However, the use of psoralen has been associated with carcinogenic risk

of the skin. Although conventionally used with psoralen for its photosensitizing

effects, UVA-1 alone has also shown success in treating palmoplantar eczema,

with the advantage that it does not require psoralen.[23, 24] PUVA can be

administered orally or topically. In a study comparing the effectiveness of the 2

modalities, dyshidrotic eczema responded well to both oral and topical (bath)

treatment, while hyperkeratotic eczema cleared significantly better with oral

therapy than with topical (bath) PUVA.[25] Narrowband UVB therapy has been

shown to be equally efficacious as PUVA therapy and can be used as an

alternative to PUVA, with fewer adverse effects.[26]

Other therapies

Other treatment options[27] for vesicular palmoplantar eczema that have been

reported include treatment with intradermal injections of botulinum toxin A, x-ray

therapy, disulfiram for nickel-induced disease, and, in patients with obstructive

sleep apnea, continuous positive airway pressure (CPAP).

Botulinum toxin A is a potent neurotoxin that blocks the autonomic cholinergic

fibers.[28, 29] It has been shown to improve symptoms of itching and vesicular

formation in a controlled left-right hand comparison study with 8 subjects.[30] This

therapy may be used alone or in combination with topical steroids. However, the

mechanism of action in reducing the severity of palmoplantar eczema is disputed.

Some proposed mechanisms are a disruption of the afferent nerve supply of the

skin, which may reduce sweating, because sweat is known to exacerbate the

condition. Another mechanism is the possible effect of the toxin on afferent nerve

fibers. Blockade of the inflammatory process and inhibition of neuropeptides such

as substance P via toxic effects may explain the reduction of pruritus in treated

patients.

The inflammatory cells functioning in eczema are highly radiosensitive, and,

therefore, x-ray irradiation has been used in some patients with resistant chronic

eczema of the hand when other treatments have not been successful.

Grenz rays and superficial radiotherapy were popular treatments for chronic

severe hand eczema in the 1980s; however, they have currently decreased in

popularity, mostly because of a lack of availability than because of the risk for

potential carcinogenesis. Superficial radiation therapy appears to have a higher

success rate than grenz ray therapy because of its deeper penetration into the

skin.[31]

One study revealed excellent results with the use of superficial radiation for

palmoplantar eczema, while others have not.[32, 33] However, the potential risk of

irradiation for a benign non–life-threatening disease must be recognized, and

care must be taken not to exceed the maximum safe cumulative lifetime dose by

using dosimetry. External-beam megavoltage radiation therapy was reportedly

successful in treatment of this condition in one patient.

Disulfiram may be administered as a nickel-chelating agent in patients with

known nickel sensitivity, but this should not be used in thiuram-sensitive patients.

One case report describes a patient with obstructive sleep apnea and dyshidrotic

palmar eczema whose dermatitis resolved after being placed on a CPAP machine.

The authors speculated the resolution of the eczema may reflect the effects of

increased tissue oxygenation and decreased circulating inflammatory factors

associated with better sleep quality.[34]

Id reactions tend to resolve with treatment of the primary infection. Consider

systemic antibiotics if secondary infection is suspected, and culture suspicious

lesions.

Consultations

Refer patients to a dermatologist because vesicular palmoplantar eczema is likely

to be a lifelong disease (albeit intermittent in some patients).

Diet

Maintaining a low-cobalt diet has been suggested to decrease the number of

dyshidrotic eczema flares.[35]

Patients with established nickel sensitivity may benefit from nickel-free diets.

Medication Summary

The goals of pharmacotherapy for vesicular palmoplantar eczema are to reduce

morbidity and to prevent complications.

The dyshidrotic eczema severity index (DASI), a standardized severity scale for

palmoplantar eczema, has made it easier to compare the efficacy of various

therapies in controlled clinical trials.[36]

Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied

metabolic effects. They modify the immune response of the body to diverse

stimuli.

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Betamethasone topical (Diprolene, Luxiq)

 

For inflammatory dermatoses responsive to steroids. Decreases inflammation by

suppressing migration of polymorphonuclear leukocytes and reversing capillary

permeability. Affects production of lymphokines and has inhibitory effect on

Langerhans cells.

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Clobetasol (Temovate, Olux-E, Temovate E, Cormax)

 

Class I superpotent topical steroid; suppresses mitosis and increases synthesis of

proteins that decrease inflammation and cause vasoconstriction.

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Prednisone

 

Immunosuppressant to treat autoimmune disorders; may decrease inflammation

by reversing increased capillary permeability and suppressing PMN activity.

Stabilizes lysosomal membranes and suppresses lymphocytes and antibody

production.

Immunosuppressants

Class Summary

These agents are used for severe acute episodes and as steroid-sparing agents in

the chronic forms of the disease.

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Azathioprine (Azasan, Imuran)

 

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and

proteins. May decrease proliferation of immune cells, resulting in low

autoimmune activity. Used in transplant recipients and some autoimmune

conditions.

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Cyclosporine (Gengraf, Neoral, Sandimmune)

 

Calcineurin inhibitor. Potent immunosuppressant; nonmyelotoxic but markedly

nephrotoxic. Widely used in organ and tissue transplantation and skin diseases

(eg, psoriasis, atopic dermatitis).

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Methotrexate (Rheumatrex, Trexall)

 

Antimetabolite; inhibits enzyme dihydrofolate reductase, which is essential for

purine and pyrimidine synthesis. Unknown mechanism of anti-inflammatory

action. Folinic acid after MTX administration helps prevent MTX-induced

mucositis or myelosuppression.

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Mycophenolate (CellCept, Myfortic)

 

Immunosuppressant to prevent acute rejection of renal or cardiac transplants.

Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo

purine synthesis by lymphocytes, inhibiting their proliferation. Inhibits antibody

production.

Retinoid-like Agents

Class Summary

Beta-carotene derivatives have marked effects on keratinizing epithelia. Etretinate

often helps control hyperkeratosis in hyperkeratotic palmar eczema. Therapy may

have to be continued indefinitely. The incidence of adverse effects tends to be

high.

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Acitretin (Soriatane)

 

Retinoic acid analog, like etretinate and isotretinoin. Etretinate is main metabolite

and has clinical effects similar to those of etretinate. Mechanism of action

unknown.

Chelators

Class Summary

These drugs split into 2 molecules of sodium diethyldithiocarbamate after

absorption, which, in turn, chelates divalent metal ions (eg, Ni++) and results in the

increased urinary excretion of nickel. Effective in the treatment of vesicular

palmoplantar dermatitis in nickel-hypersensitive patients whose eczema is

aggravated by oral challenge with nickel.

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Disulfiram (Antabuse)

 

Thiuram derivative that interferes with aldehyde dehydrogenase. Chelating effect

helpful in reducing the nickel burden in patients allergic to nickel.

Dermatologics, Other

Class Summary

PUVA therapy is used to treat many skin conditions, including psoriasis, eczema,

urticaria, mycosis fungoides, vitiligo, and palmoplantar pustular dermatoses.

The drug 8-methoxypsoralen (8-MOP) is taken 2 h before exposure to UVA

irradiation. The initial UVA irradiation dose of 2.5 J/cm2 is usually increased by

0.5 J/cm2 for approximately 6 treatments, then by 1 J/cm2 per treatment for a total

of 25-35 treatments.

Local bath-PUVA therapy has been successful in treating palmoplantar eczema

and psoriasis. Compared with systemic PUVA, local-bath therapy has several

advantages, particularly the absence of phototoxicity, severe hyperpigmentation,

and protracted photosensitivity. The drug 8-MOP in a 0.15% alcoholic solution is

added to tap water (37°C) at a concentration of 1 mg 8-MOP/L (0.0001%). After a

15-minute bath, the palms or soles are exposed to UVA radiation.

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Methoxsalen (Oxsoralen-Ultra, Uvadex, 8-MOP)

 

Inhibits mitosis by covalently binding to pyrimidine bases in DNA when

photoactivated by UV-A.

Immunosuppressants

Class Summary

Topical immunosuppressive agents, such as tacrolimus, have been successfully

used to decrease the severity of chronic palmar eczema. These drugs may be used

as steroid-sparing agents.

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Tacrolimus topical (Protopic)

 

Reduces itching and inflammation by suppressing release of cytokines from T

cells; inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and

TNF-alpha (all involved in early T-cell activation).

May inhibit release of preformed mediators from skin mast cells and basophils;

may down-regulate FCeRI expression on Langerhans cells. Can be used in

patients as young as 2 y. Drugs of this class more expensive than topical

corticosteroids

Deterrence/Prevention

Elimination of known exacerbating factors, although often difficult to accomplish,

is crucial in preventing relapses of vesicular palmoplantar eczema.

Prognosis

Acute vesicular eczema (pompholyx) in both major and minor forms tends to

occur intermittently or sporadically and becomes less common as patients age.

Episodes are less frequent from middle age onward.

The prognosis is less satisfactory for subacute and chronic forms of vesicular and

hyperkeratotic eczema, which often persist for years, than for other forms.

Patient Education

For excellent patient education resources, visit eMedicineHealth’s Skin

Conditions and Beauty Center. Also, see eMedicineHealth’s patient education

articleEczema.