Photodermatol Photoimmunol Photomed 1999: 15: 87–89 Copyright C Munksgaard 1999Printed in Denmark ¡ All rights reserved

ISSN 0905-4383

Communication

Treatment of severe recalcitrant dermatoses ofthe palms and soles with PUVA-bath versusPUVA-cream therapy

Grundmann-Kollmann M, Behrens S, Peter RU, Kerscher M. Treatment M. Grundmann-Kollmann1,2,of severe recalcitrant dermatoses of the palms and soles with PUVA- S. Behrens2, R. U. Peter2,bath versus PUVA-cream therapy. Photodermatol Photoimmunol M. Kerscher2

Photomed 1999: 15: 87–89. C Munksgaard, 1999.Departments of Dermatology, 1Johann WolfgangGoethe University, Frankfurt/Main, 2University of

PUVA-bath therapy developed into a first line topical PUVA therapy, and Ulm, Ulm, Germanygel and cream preparations have been described as alternative modes oftopical 8-MOP application. Because bath-PUVA can be difficult to man-age, topical PUVA therapy using 8-MOP gel or cream preparations maybecome an important alternative when treating localised skin diseases.However, controlled comparisons of efficacy with this alternative topical Key words: 8-methoxypsoralen; PUVA bath;

PUVA cream; palmoplantar dermatosesPUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant Marcella Grundmann-Kollmann, MD, Departmentdermatoses of the palms and soles using a left/right trial design. These of Dermatology, Johann Wolfgang Goethe

University, Theodor Stern Kai 7,patients responded well to both treatment modalities, meaning that both60590 Frankfurt, Germanycould be used successfully to treat recalcitrant dermatoses of the palms

and soles. Accepted for publication December 29, 1998

Recalcitrant dermatoses of the palms and solesoften are difficult to treat. Systemic treatment withglucocorticosteroids and etretinate or immunosup-pressive agents, although effective, is limited byside effects. Oral photochemotherapy with 8-me-thoxypsoralen (8-MOP) and long-wave ultravioletlight (PUVA) is often effective in treating severepalmoplantar dermatoses and may produce long-lasting remissions. Unfortunately, systemic PUVAtherapy is accompanied by a range of unwantedside effects (1). In order to reduce such side effects,alternative modes of application were developed,including PUVA-bath and PUVA-cream or geltherapy (2–5). PUVA-bath therapy avoids systemicside effects, offers better bioavailability of the pso-ralen, and requires much smaller amounts of UVAfor the induction of its therapeutic effect (2, 3).However bath-PUVA may be difficult to manage,e.g. it requires bath tubs. Therefore, 8-MOP con-taining cream or gel preparations are a relevantalternative mode of topical application. Thus far,two preparations have been described: a 0.005%8-MOP gel and a 0.0006% 8-MOP cream (4, 5).

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However, no data are available about the relativeefficacies of these preparation.

Recently PUVA-cream has been shown to be ef-fective in treating palmoplantar dermatoses (5).We, therefore, decided to compare the efficacy ofPUVA-cream therapy with PUVA-bath therapy in12 patients with severe recalcitrant dermatoses ofthe palms and soles, using a randomised left/righttrial design.

Patients and methodsPatients

Twelve patients (7 female and 5 male; ages 20 to65; mean duration of disease 3.6 years) with severeplaque-type psoriasis (4), severe atopic eczema (4)and severe hyperkeratotic eczema (4), who hadbeen resistant to prior topical treatment were in-cluded into the study after given informed consent.Comparative efficacies of PUVA-bath and PUVA-cream were assessed after random assignment (seeTable 1), treating one hand and/or foot withPUVA-bath and the other hand and/or foot with

Grundmann-Kollmann et al.

Table 1. Patient diagnosis and treatment

PUVA Bath PUVA Cream

Cum. Dose Cum. DosePatient Diagnosis Side Score (J/cm2) Side Score (J/cm2)

1 Ae L 1 33.8 R 1 61.72 Ae R 9 26.8 L 9 31.33 Ae R 5 27.0 L 6 28.64 Ae R 17 45.3 L 15 46.25 Pso L 0 51.5 R 2 63.76 Pso R 15 41.2 L 16 49.87 Pso L 0 29.8 R 15 34.28 Pso L 3 28.0 R 6 36.09 He R 18 53.3 L 18 67.6

10 He L 18 55.0 R 9 48.411 He R 3 42.0 L 2 46.412 He L 5 48.1 R 7 52.4

Ae: atopic eczema; He: hyperkeratotic eczema; Pso: Psoriasis.

PUVA-cream. No additional therapy except anemollient ointment was permitted during the studyperiod of 8 weeks.

PUVA-cream and PUVA-bath therapy

Psoralen-cream (final concentration 0.0006% 8-MOP containing water in oil emulsion (30% H2O))was prepared as previously described (5). Psoralensolution was prepared by dissolving 0.5 g, of 8-MOP in 100 ml 96% ethanol. To control the finalconcentration of 8-MOP in the cream and stocksolution, high-performance liquid chromatogra-phy (HPLC) with UV detection was performed (6).Four times a week (Monday, Tuesday, Thursday,Friday) 8-MOP-cream was applied in an even layerfor 1 h to the assigned hands and/or feet or theywere soaked for 20 min at 37æC in warm water con-taining 0.5 mg per litre 8-MOP (2, 3, 5). Appli-cation of PUVA-cream or PUVA-bath was fol-lowed directly by UVA-administration with in-creasing doses (initial dose 0.3–0.5 J/cm2). UVAdoses were gradually increased at each third treat-ment, according to the individual photosensitivityin order to avoid phototoxic reactions, up to amaximum single UVA-dose of 3.5–6.0 J/cm2. In-crements were allowed until mild erythema wasseen.

Equipment

The UVA irradiation equipment consisted of a‘‘PUVA 200’’-unit (Waldmann, Villingen-Schwen-ningen, Germany) and a ‘‘PUVA 180’’-unit (Wald-mann, Villingen-Schwenningen, Germany) emit-ting exclusively UVA in the range of 320–400 nmwith a peak at 365 nm.

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Clinical grading

In order to compare the therapeutic response toPUVA-cream and PUVA-bath, a special scoringsystem ranging from 0 to 20 was developed andused separately for each hand or foot: Erythema,scaling, infiltration, pustulation and hyperkera-tosis were graded from 0 (no symptoms) to 4(maximum) for each feature. Addition of thescores could reach a maximum of 20. Only patientswith a sum of at least 16 were included into thestudy. Improvement was defined as follows: Excel-lent (total score 0–4), good (total score 5–8), satis-factory (total score 9–12) and poor or no response(12–20). All patients were assessed by the samephysician before initiation of therapy, then weeklyand at the end of the study. After the end of studyfollow-up of each patient over a period of 8 weekswas performed.

Results

Efficacy was assessed separately for each hand orfoot. A total of 58% of lesions treated with thePUVA-bath and 50% of lesions treated with thePUVA-cream showed excellent or good improve-ment. The percentage of non-responders was 33%for both treatment modalities. While 50% of thepatients with chronic plaque-type psoriasis did notrespond to cream PUVA, only 25% of patientswith plaque-type psoriasis treated with PUVA-bath showed no response. However, 50% of pa-tients suffering from hyperkeratotic eczema treatedwith PUVA-bath showed no response, while only25% of patients with the same disease did not im-prove with cream PUVA therapy. Mean number ofirradiations for skin lesions treated with PUVA-bath was 18, whereas mean number of treatmentswith cream PUVA was 27 (for detailed results seeTable 1). Side effects such as blistering, severe ery-thema, pain or patchy hyperpigmentation did notoccur. A follow-up period of 8 weeks after end ofPUVA-bath or PUVA-cream therapy showed goodor excellent skin condition of the responders withno relapse.

Discussion

Photochemotherapy with 8-methoxypsoralen (8-MOP) combined with long-wave ultraviolet lighthas been widely used in treating a variety ofdermatoses. However, it is associated with a rangeof unwanted effects due to systemic absorption of8-MOP (1–3). Thus, as a therapeutic alternative,bath-PUVA therapy with bathwater delivery of 8-MOP was developed (2, 3). Recently, cream and gelpreparations containing 8-MOP (e.g. a 0.005% 8-

PUVA-bath vs PUVA-cream therapy

MOP gel and a 0.0006% 8-MOP cream) haveshown good clinical results in individual patients(12, 13). However, thus far no controlled clinicaltrial has been performed comparing cream-PUVAtherapy to bath-PUVA therapy, which is, at themoment a first line topical PUVA therapy for pa-tients with palmoplantar dermatoses. Therefore,we investigated the efficacy of cream-PUVA ther-apy in comparison to bath-PUVA therapy in thetreatment of recalcitrant dermatoses of the palmsand soles using a left/right trial.

Our data suggest that cream-PUVA therapy maybe an efficient alternative to bath-PUVA therapy.Like bath-PUVA therapy, cream-PUVA therapy in-duces a homogeneous sensitivity to UVA, but se-lected body regions can be excluded from the ther-apy. Therefore, it is possible to limit photosentis-ation strictly to lesional skin, while this is notpossible with bath-PUVA.

Although the number of patients treated in thisstudy is too small to make judgement on the effi-cacy of cream-PUVA therapy in comparison toPUVA-bath therapy, our initial results indicatethat both treatment protocols may be effectiveeven in severe recalcitrant dermatoses of the palms

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and soles which have responded poorly to othertopical therapies. Therefore cream-PUVA therapymight develop into a useful alternative to PUVA-bath, especially for those dermatologists who findPUVA-bath difficult to organise.

References

1. Morison WL, Parrish JA, Fitzpatrick TB. Oral methoxsal-en photochemotherapy of recalcitrant dermatoses of thepalms and soles. Br J Dermatol 1978: 99: 297–302.

2. Kerscher M, Plewig G, Lehmann P. PUVA-Bad Therapiezur Behandlung von palmoplantaren Dermatosen. ZHautkr 1994: 69: 110–112.

3. Luftl M, Degitz K, Plewig G, Rocken M. Psoralen bathplus UVA therapy: Possibilities and limitations. ArchDermatol 1997: 133: 1597–1603.

4. De Rie MA, Eendenburg van JP, Versnick AC et al. A newpsoralen containing gel for topical PUVA therapy: develop-ment, and treatment results in patients with palmoplantarand plaque-type psoriasis, and hyperkeratotic eczema. Br JDermatol 1995: 132: 964–969.

5. Stege H, Berneburg M, Ruzicka T, Krutmann J. Cream-PUVA-Phototherapy. Hautarzt 1997: 48: 89–93.

6. Susanto F, Humfeld S, Reinauer H, Meschig R. High per-formance liquid chromatography measurement of 8-me-thoxypsoralen in plasma. Chromatographia 1986: 21: 443–446.