Review of diagnosis and management of dyshidrotic eczema (a/k/a pompholyx)

8/13/2019 Review of diagnosis and management of dyshidrotic eczema (a/k/a pompholyx)

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The aim of this article is to review the clinical features, dif-ferential diagnosis, and management of pompholyx. A l i tera-ture search was conducted using the MEDLINE database andthe terms 'pompholyx' and 'dyshidrotic eczema' f rom January2000 to April 2010.

1 Ciinicai FeaturesPompholyx or dyshidrotic eczema is a common disease

affecting palmoplantar skin.f Since palmoplantar skin is r ichin eccrine sweat glands, it had been suggested that there wasa relationship between the vesicles and these glands.'- ' Today,the disease is considered to be a special type of eczema, with apronounced spongiosis and accumulation of edema fluid inregions with a thick epidermis and an even thicker overlyinghorny layer. The spongiotic vesicle is intraepidermal. The acro-syringium of the sweat glands is not altered by the disease,'^'which makes the term 'dyshidrosis ' a misnomer.

Acco rding to Fo x,'- ' pomp holy x is characterized by vesiclesand bullae on nonerythematous palmoplantar skin. Based onnonadherence of many authors to the original clinical de-scription of this skin condition, Storrs' *' has recently proposedthe use of the term acu te and recurren t vesicular handderm atit is . I am not sure whether the terminology will changein practice or not.

Happ le'^' suggested the term par ap tic eczem a for thiscondit ion, when pompholyx is el ici ted by the hematogenousaction of an antigen that has already initiated a T-cell-mediatedeczema response on the skin.

There are two clinical types of presentation: bullous(figure 1) and vesicular (figure 2 ). Vesicular pom pho lyx isknown as dyshidrotic eczema in German-speaking countr ies,whereas the bullous tyjje is named cheiropodop omph olyx. '^ '

Pom pho lyx is associated with itching and bu rning sensa-t ions. Secondary infection with staphylococci is not in-frequent. The disease is more common during the warmseasons.'^'

2 PathogenesisPompholyx is seen all over the world, but seems to be less

common among Asians.'**' In rare cases, there is a geneticbackground. In a study from China, a gene locus on chromo-some 18q22.1-18q22.3 between markers D18S465 andD18S1362 could be identified in a large family with an auto-somal dominant type of pompholyx.'**' However, most cases ofpompholyx are sporadic.

Patien ts with pom pho lyx show highly significant differein autonomie vagal modulation under deep respirationspiration and expiration) , but cardiac autonomie modula

Fig. 1 . Bullous cheiropom pholyx: a) early presentation; b) later prestion; and c) secondary hemorrhagic bullae in bullous cheiropom phocontrast to primary hemorrhagic bullae in autoimmune bulious disease


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2. Vesicular pompholyx.

Pomp holyx can be associated with atopic dermatit is , contact

30%.''^*' In the case of nickel

In another study involving 120 patients with pomp holyx, of patients had allergic contact dermatitis, and 10% had

mycosis. ' ' ' Other authors have questioned the role of nickelsensitization. In a study of 398 patients, the relative risk forvesiculation in nickel-positive individuals was 0.45 comparedwith 3.58 for tinea pedis.'-*'' In a study to identify factorsassociated with the disease in 100 pompholyx patients in Togo,West Africa, the odd s ratios were 15.6 for tinea, 12.6 for ato py ,and 4.5 for hyperhidrosis. richophyton ruhnim was the mostcommon etiology of the tinea pedis.'-*' '

The blisters and vesicles on the palms do not containinfectious material. Their formation is thought to be mediatedby an allergic reaction to the p atho gen , called the id reaction.'-^'

Pompholyx has been observed as a manifestation of infect-ion with HIV . In this case, antiretro viral therap y w as beneficialfor the skin disease as well.''^'*'

There is a variety of other aggravating factors, such asirritants, prolonged use of protective gloves, smoking, stress,and even endoscopie thoracic sympathectomy for palmarhyperhidrosis. '-^' Am ong 120 pom pho lyx patients from Franc e,one-third had hyperhidrosis. ' ' ' Smoking also has a negative in-fluence on the efficacy of phototherapy, such as bath-psoralcnplus UVA irradiation (bath-PUVA). ' ' -^ ' However, diseaseswith disturbed sweating such as Parkinson disease are notassociated w ith an increased risk of pomp holy x.'- ' In rarecases, pompholyx can be photoinduced.'-*- '

The cou rse is often chro nic or chronic-cyclic, even in p atientsin whom the aggravating factors can be avoided. There mightbe longer periods of remission in these patients, but whenpom pholyx relapses there is no quick response to treatment.

Contact allergens and drugs associated with pompholyx

immunoglobulins

ilk

=highly active antiretroviral therapy;

AllergenResorcinolDiphencyproneBalsam of Peru, fragrancesunknownUnknownNickelCobaltChromium from food

RagweedPiroxicamp-phenylenediamineRubber vulcanizerSorbic acid

IV=intravenous.

FrequencyRareRare


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Table II.Differential diagnoses of pomphoiyxDiseaseAcropustuiosis of infancyAduit T-celi leukemia/iympfiomaBuilous impetigoBullous T-cell iymphomaDyshidrosiform pemphigoidLinear IgA disease with hemorrhagic) pompholyxEpidermolysis buliosaErythema muitltormeHand-toot-and-mouth diseaseHerpes intectionHTLV-1 infection aduit cutaneou sT celi iymphoma)Fixed drug eruptionFriction blistersPemphigus vulgarisPolymorphic dermatitis in pregnancyPsoriasis pustulosaSAPHO syndromeScabiesSubcorneal pustular dermatosisVasculitis allergica cutaneous sma ll vessel vasculitis)

Reference333435363738394041424344454647484933506

HTLV 1= human T-lymph otrophic virus human T-cell leukem ia virus)-1;SAPHO=synovitis, acne, pustulosis, hyperostosis, and os teitis.

3. Differential DiagnosisThere are several important differential diagnoses that have

to be excluded by careful history, clinical evaluation, histo-pathology, patch testing, microbiologie, and mycologie in-vestigations (tab le II; figure 3).

Hemorrhagic blisters are suspicious for autoimmune bullousdisease and Iymphoma'- ' - '- ' but may occur in pompholyx aswell (figure lc).

4. ManagementManagement is not simple and relapses occur frequently.

Aggravating factors, such as smoking, should be avoided.Medical treatment ranges from topical to systemic thera-pies. The targets for treatment are 3-fold: (i) suppression ofblister formation and inflammation; (ii) relief from itch; and(iii) prevention or treatment of infection.f^

As a standardized assessment method for the severity ofpompholyx, the Dyshidrotic Eczema Area and Severity Index(DASI) has been developed. It is based on the number of

vesicles per square centimeter, erythema, desquamation, and the extension of the affected area.'^-*' Th e DA SI ca n alsused to monitor treatment effects.

Management needs to be adapted to etiopathogenesipatients with tinea pedis, antifungal therapy is necesPatients with contac t allergies should avoid identified aller

Fig. 3 . Differential diagnoses of pomp holyx; a) pustular psoriasis; blous pemp higoid; and c) vasculitis allergica cutaneous small vesseculitis).


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4.1 Topical Therapy

4 CortlcosteroldsTopical corticosteroids are the cornerstone of treatment.ever, pub lished evidence is limited. Veien etal.'-'''*'reported

120 patien ts with chro nic han d eczema, including 13 with

than palmar or dorsal and palmar.t took to contro l the dermatitis. ' ' '* ' Imp rovem ent h as been

ol loid dress ing for a l imi ted t i t ^ ^ ' * '4 2 alcineurinInhibitorsTopical tacrolimus was as effective as mometasone furoate

ointment in a randomized, observer-blind trial in 16

Pimecrolimus 1 cream has been used in combination with

treated w ith topical pimecro limus 1% cream und er

l significance in this stud y (p = 0.068).'''*'

4 3 exaroteneGelBexarotene is a retinoid X receptor agonist that has been

a. The compou nd is contraindicated in premen opausa l I-II randomized,

1% gel alone and in combina-on with a hydrocortisone 1% ointment or a mom etasone

e 0.1% ointm ent, 55 patients with severe chronic ha nddaily. The response ra te of patients achieving at least 50%SI) was 79% for bexarotene gel alone, 85% for the com-

n with hydrocortison e. An improvem ent of the HEA SI score

tene alone, in 38% of patients treated with bexaroten e an dmom etasone furoate, and in 14% of patients with the combi-nation of bexarotene and hydrocortisone. In a subgroup of'other types of eczema/dyshidrotic eczema,' the clearance ratewith bexarotene gel monotherapy was 50%. Adverse effectsrelated to bexarotene gel included burning, stinging, irritation,and flare of dermatitis. '* ' This study reveals that the combi-nation of bexarotene gel with a topical mid-potency cortico-steroid such as mometasone furoate is beneficial, whereasweaker corticosteroids do not add any benefit in such a com-bination. It has not been evaluated systematically whether morepotent corticosteroids in combination with bexarotene gelwould further improve the outcome in pompholyx.

4.2 Systemic Therapy ;4 2 CorticosteroidsThe basic systemic therapy in bullous pom pholy x consists of

systemic corticosteroids. Depending on the severity and thearea affected, initial dosages between 40 and lOOmg/day areemplo yed.' ' ' ' The dosage is gradu ally tapered after blister for-mation ceases. Other authors recommend the use of intra-muscular tr iamcinolone acetonide 40-80 mg . ' ' ' However, thistreatment has never been investigated by randomized, pro-spective trials. Systemic corticosteroids are rarely advisable forlong-term use because of undesirable adverse effects.

4 2 2ImmunosuppressantsIn the case of recalcitrant pompholyx, other immuno-

suppressive drugs have occasionally been used, such as aza-thiop rine 100 -150 mg /day,'^ ' ' low-dose metho trexa te (initially15-2 5m g once a week), ' - ' and m ycoph enolate mofeti

Cyclosporine (ciclosporin) was used in four patients withvesicular pompholyx. A star t ing dosage of at least2.5 mg/kg /day w as necessary to induce a respo nse. R elapse iscommon after withdrawal of the treatment. '^ ' These data arenot sufficient to recommend any of the systemic therapiesahead of any of the others based on their efficacy and safetyprofile.

4 2 3RetmoidsAlitretinoin (9-cis-retinoic acid) is a retinoid for systemic

use. I t has been described as a panagonist since the compoundactivates retinoid X receptors as well as all retinoic acid re-ceptors. Headach e and m ucocu taneous adverse effects are seenas with other oral retinoids. Because of teratogenicity, all oral


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retinoids are strictly contraindicated in premenopausal w omenwho are not using sufficient contraception.'^^l

In a European, randomized, double-blind, placebo-controlled, multicenter trial, 319 patients with chronic handdermatitis refractory to standard therapy were evaluated.'^^'In a four-armed study design, patients received either placeboor alitretinoin at dosages of lOmg,20mg,or40 mgonce dailyfor 12 weeks. Responders were followed up for another3 months. Alitretinoin led to a significant, dose-dependentimprovement of the disease status in up to53%of patien ts, withan up to 70% reduction in disease symptom s and signs. In thistrial, a group of70patients w ith pompholyx was included; theresponse rate in this subgrou p was not statistically differentbetween placebo and alitretinoin.t^^'A recent paper repo rted the results of a randomized, do uble-blind, placebo-controlled, multicenter trial in ten Europeancountries and in Canada.'''^' A total of 1032 patients withrefractory chronic hand derma titis (eczema) were included. Thetreatment was organized in three arms, i.e. alitretinoin 10 mgor30 mgor placebo once a day for 24 weeks. Clear or almost clearhands were achieved in 48% of alitretinoin-treated patientsversus17%of placebo recipients. There were mo re responses inthe 30 mg group compared with the lOmg group. The studyincluded a grou p of377patients with pompholyx. In this group,the response rate was 16%in the placebo recipients,23%in thepatients receiving alitretinoin lOmg/day, and33%in the gro upreceiving alitretinoin 30mg/day.t^^l

In conclusion, although oral alitretinoin is effective in re-calcitrant hand eczema in general, it is of limited efficacy inpompholyx. A combination therapy with topical cortico-steroids could achieve higher response rates; however, this hasyet not been evaluated in a controlled clinical trial.

4 2 4 iologiesA 40-year-old woman with a 6-yearhistory of recalcitrant

atopic cheiropompholyx was treated with subcutaneous inject-ions of the tumor necrosis factor-a inhibitor etanercept25mgtwice weekly.'^ ' At a 6-week follow-up, the pompholyx hadcleared. Remission was sustained for 4 months, after whichtime the patient experienced a flare-up. The dosage of etaner-cept was doubled, but was ineffective and was, therefore,eventually discontinued.I^**' Further investigations are neededwith the use of biologies for p ompho lyx.

4 2 5 AntihistaminesAntihistamines have been used to control accompanyingpruritus, although there is no proof of their efficacy in pom-

pholyx. Sodium cromoglicate (disodium cromoglycatefound to be more effective in the treatment and preventinickel-sensitive pompholyx than a low-nickel diet by dishing the intestinal nickeluptake.t ** Th euseof sodium cglicate raises several questions. First, since only a prtion of pompholyx patients are nickel sensitized, woulddrug be ineffective in the other patients? Second, howshould sodium cromoglicate be used for secondary prevein nickel-sensitized patients? Probably as a life-long treatbut there are no scientific data to support long-term pre ve

4.3 Botulinum Toxin

Botulinum toxin A (BTXA) shows potent anhidrotitivity, and sweatingisan aggravating factor in pompholypilot study with left-right c omp arison, intrac utaneo us injofBTXA(100UofBotox[AUergan, Inc., Irvine, CA, Uone palm on day 1) was used in addition to topical costeroids. Among the six patients who completed the 8-trial, the DASI was significantly lower, and itching and vlation disappeared earlier in the hand treated with BTXA

Ano ther study involving ten patients compared the effBTXA alone (mean dose of 162 U of Botox per palm ohand) with the untreated side as contro l. Seven ofte n paexperienced a good to very good effect on vesicular pompand a decrease in itching.'^'' Other reports also mentioneability of BTXA to improve itch, vesiculation, andthema.t -- - ' Pain on injection is a comm on adverse effeclimits the use of BTXA in general.

4.4 Phototherapy and PhotochemotherapySelective UVB phototh erapy (300-320 nm) combined

balneotherapy was found to be more effective in palmopdermatoses, including pompholyx, than broad-spectrum (280-320nm .t 41 Narrow-band UVB (311nm) and U(340-400 nm) irradiation have been proven to be superbroad-band UVB for certain indications.'^^'

Systemic photochemotherapy with PUVA (320-^00 neffective in vesicular pompholyx, although it has theadvantage of generalized photosensitivity and adverse eon the gastrointestinal tract by the photosensitizer methox(8-methoxypsoralen; 8-MOP). To reduce the risk of unwadverse effects, there have been modifications to the clasystemic PUVA therapy, such as bath-PUVA and cPUVA. For bath-PUVA,8-MOPis used in a water bathto irradiation. Cream-PUVA employs a cream containinphotosensitizer applied 20 minutes prior to UV exposure


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Bath-PUVA is an effective treatment modality for palmo-

Cream-PUV A is as effective as bath-PUVA in the treatmentTopical PUVA with8 MOPhas been compared with UVA

UVA-1 irradiation was found to be effective in vesicular

27patients with vesicular

III Evidence-based medicine in pompholyx

num toxin A

inhibitors

Evidence level^3^4a' '

224a332222

Levels of evidence-base d medicine in clinical studies. Level :evidence isavailable for meta-analysis from several randomized controlled studies;level 2: evidence is available from at least one random ized controlledtrial;level 3: evidence is available from good mthodologie studies withoutrandomization; level 4a: evidence is available from clinical case reports;level 4b: this represents a consensus of respected experts or expertcommittees.Mostly with topical corticosteroids.

=psoralen plus UVA.

Table IV General advice for hand an d foot care for patients with pom pholyxWash hands and feet as infrequently as possibleAvoid soaps, and direct contact with household cleansers, fresh fruits,and fresh meatDry hands an d feet carefullyUse protective gloves for hair care, including shampooingUse protective plastic gloves only with white cotton gloves beneathUse cotton socks and change them regularlyStop smoking

4.5 RadiotherapyGrenz rays and conventional superficial x-rays have beenused either alone or in comb ination w ith topical corticosteroids

for refractory hand dermatitis (eczema). In a double-blindstudy, conventional x-rays (300 rad) were superior to Grenzrays.'^''Complete remission of pompholyx is also possible withlow-dose external beam m egavoltage radiation.' ^'

4.6 Tap V^ater lonotophoreslsTap water iontophoresis is an effective measure to control

excessive sweating ofpalmsand soles. In a study of2 patientswith pomph olyx, it was more effective than corticosteroid-freetopical treatment alone.'**-^'

In a study with 20 pompholyx patients, tap water ionto-phoresis resulted in faster relief of symptoms, particularly itch,than topical corticosteroids alone. There was a statisticallysignificant difference in the relapse-free interval, i.e. 6 versus2 '***

5 ConclusionIt is surprising that although pompholyx is a common dis-

ease,relatively few randomized controlled trials of its treatm enhave been performed and published. For an overview onevidence-based medicine for pompholyx see table III. Thecurrent best treatment for pompholyx is a combination oftopical and systemic therapy. In practice, the most commoncombination used is topical and short-term systemic cortico-steroids. However, no randomized study has been published inthe international medical literature for such a treatment. Goodproof ofevidenceis available for topical d rugs such as corticosteroids, calcineurin inhibitors, and bexarotene.

Among phototherapies, PUVA and high-dose UVA-1 seemto be equal in efficacy, with probably a more balanced risk-


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benefit ratio for UVA-1.However, the long-term risks are notwell known, and the equipment is more expensive, for high-doseUVA-1.Systemic PUVA does not offer any benefit com-pared with topical PUVA andUVA-1.

Ifthereis aggravation ofthedisease by focal hyperhidrosis,tap water iontophoresis and BTXA have been proven to notonly improve abnormal sweating but also to have beneficialeffects on pompholyx. A better understanding of the mechan-isms of action of botulinum toxin may be helpful in developinga new class of anti-inflammatory drugs.

In systemic therapy, corticosteroids remain the cornerstoneof treatment, although alitretinoin has recently shown efficacy.In recalcitrant cases, a combination of corticosteroids withimmunosuppressants or a complete switch to immunosup-pressants may be useful but none of the systemic pharma-cotherapies (including biologies) has been evaluated incontrolled trials.

Pharmacologie treatment (and other treatments as well)should be accompanied by general advice for patients withpompholyx (table IV).

The current situation in pompholyx dem onstrates the urgentneed for controlled trials, in particular for systemic treatmentoptions.

cknowledgmentsNo sources of funding were used to assist in the preparation of this

review. The author has no conflicts of interest that are directly relevant tothe content of this review.

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Correspondence: Prof Dr Uwe Wollina Department of Dermaand Allergology, Academic Teaching Hospital Dresden FriedricFriedrichstrasse 41 ,01067 Dresden, Germany.E-mail: [email protected]

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Review of diagnosis and management of dyshidrotic eczema (a/k/a pompholyx)