Combining PUVA therapy with systemic immunosuppression to treat progressive diffuse morphoea

Cyclosporin and mycophenolate mofetil (MMF) are immunosuppressant agents now used frequently in the field of organ transplantation. More recently cyclosporin has been used for the treatment of a number of dermatological conditions, including severe psoriasis and eczema. Extensive diffuse morphoea is very difficult to treat. PUVA, UVA and a number of immunomodulating drugs have been used to attempt improvement but are most beneficial only in early disease. Combination treatments are often used in psoriasis, for example, but are not reported in morphoea. We present the case of a patient treated initially with cyclosporin and PUVA and subsequently with MMF and PUVA, with considerable improvement in his condition.     

Multiple squamous cell carcinomas in a psoriatic patient following high–dose photochemotherapy and cyclosporin treatment: response to long–term acitretin maintenance

Cumulative toxicity is a well known limitation of antipsoriatic treatments. In particular, the induction of multiple squamous cell carcinomas following long–term PUVA treatment is well established. In the present report, a psoriatic patient is described who was treated for more than 14 years with photochemotherapy (PUVA) and who received excessive amounts of topical corticosteroids. The patient developed, in total, 34 squamous cell carcinomas. In all, three squamous cell carcinomas developed during long–term PUVA treatment, and 21 carcinomas appeared during 16 months of treatment with cyclosporin. Subsequently, a marked inhibition of the occurrence of new tumours occurred during prolonged treatment with acitretin, and no new tumours have appeared during the last 4 years of continuous treatment with this retinoid at a dose of 60mg/day. Modulation of the expression of PUVA–induced squamous cell carcinomas by cyclosporin and acitretin are discussed. The present report lends support to the hypothesis that cyclosporin causes an increased occurrence of PUVA–induced carcinomas, whereas acitretin (60mg/day) is of value in preventing the occurrence of new squamous cell carcinomas in patients who were treated with long–term PUVA.     

Controlled study of PUVA and adjunctive topical therapy in the management of psoriasis

In a random study of 116 patients with psoriasis vulgaris, oral psoralen photochemotherapy (PUVA) used alone was compared to PUVA plus adjunctive topical therapy with tar, dithranol, or topical corticosteroids. PUVA plus topical corticosteroids produced more rapid clearing of psoriasis but despite maintenance therapy, the frequency of recurrences of the disease during the early phase of follow-up was significantly higher with that treatment, as compared to all other treatments. Dithranol plus PUVA also cleared psoriasis quicker than PUVA alone but patient acceptability for that regimen was low. The addition of tar to PUVA therapy appeared to have little influence on results.     

Treatment of the acute graft versus host skin reaction with cyclosporin and PUVA

Acute graft-versus-host reaction is usually managed by immunosuppressive therapy, and cyclosporin is one drug of choice. In some patients, cyclosporin alone cannot always control the evolution. The use of other immunosuppressive drugs could be considered but their toxicity and side-effects are such that a vital risk is introduced for the patient. Conversely, when the disease primarily affects the skin, photochemotherapy (PUVA) associated with cyclosporin appears to be effective and safe.     

The efficacy of localized PUVA therapy for chronic hand and foot dermatoses

The response to treatment of all patients enrolled over an 18-month period for localized oral or topical psoralen photochemotherapy (PUVA) of chronic hand and foot dermatoses was retrospectively reviewed. There were broadly similar success rates for the two groups for complete clearance: 61.5% (eight of 13 patients who completed therapy)—oral PUVA, 47.8% (11 of 23 patients who completed therapy)—topical PUVA, and for significant improvement: 23.1% (three of 13 patients)—oral PUVA, 30.4% (seven of 23 patients)—topical PUVA; there were no significant differences in response when diagnostic subgroupings of the hand dermatoses were taken into account. The mean number of treatments (22 for oral PUVA and 24 for topical), treatment durations (122 and 129 days), maximum UVA doses (11.2 and 12.3J/cm²) and to a lesser extent cumulative UVA doses (189.3 and 237.0 J/ cm²) for the therapies were similar in the two groups; adverse effects were minimal for both treatment protocols. However, at least five of the eight patients in the oral PUVA group and five of the 11 in the topical group who cleared completely relapsed after a mean 86 (range 19.245) and 174 (range 23-596) days, respectively. These findings are in broad agreement with those of previous studies. Therefore to avoid generalized photo-sensitivity and a higher likelihood of adverse effects with systemic therapy, as well as a possible slower relapse rate, topical therapy seems preferable.     

Successful treatment of solar urticaria by extracorporeal photochemotherapy (photopheresis)--a case report

Solar urticaria is characterized by erythema and whealing immediately after exposure to ultraviolet radiation and/or visible light. We report about a patient with severe solar urticaria, who was highly sensitive to both UVA radiation and visible light with a Minimal Urticaria Dose (MUD) of 7 J/cm2 UVA. Management of this patient was extremely difficult because standard treatment with oral antihistamines, hardening with UVA, UVB, visible light or oral PUVA and even oral cyclosporin A were completely ineffective. We therefore decided to perform extracorporeal photochemotherapy (photopheresis, ECP). After nine treatment cycles with photopheresis the MUD increased from 7 J/cm2 UVA before treatment to 22 J/cm2 UVA. This hardening effect was associated with a significant decrease of the frequency and severity of whealing and the accompanying symptoms (pain, fatigue, pruritus). CONCLUSION: Photopheresis might be of some benefit in selected patients with otherwise intractable solar urticaria.     

Cutaneous malignancy related to cyclosporin A therapy

A 61-year-old, male, psoriatic patient, previously treated with methotrexate and PUVA, subsequently developed five basal cell carcinomas and a squamous cell carcinoma related to cyclosporin A therapy.     

Treatment of PUVA- and retinoid-PUVA-resistant severe psoriasis with systemic cyclosporin A

Twenty patients with severe psoriasis were treated with the oral administration of 5 mg/kg/day of cyclosporin A (CyA) for 12 weeks. These patients had either failed to respond to or had become unresponsive to conventional treatments including PUVA, UVB, or combinations of etretinate and PUVA or UVB. Complete clearance and marked improvement were observed in 12 (60%) and 4 patients (20%), respectively. The average score of the Psoriasis Area and Severity Index (PASI) was 26.2 before treatment, decreasing to 18.3 in 2 weeks, 8.2 in 6 weeks, and 5.1 in 12 weeks of CyA treatment. There was a tendency for patients with lower blood levels of CyA to show smaller decreases in their PASI scores. In four patients who received skin biopsies, histological improvement was noted within 10 days of treatment; epidermal thickness had decreased by 32%, intraepidermal mitoses by 66%, and parakeratosis had disappeared almost completely. No clinical side effects or alterations in laboratory values were observed that required cessation of CyA. Exacerbations of psoriasis occurred in 11 of 16 patients within 6 weeks after stopping treatment. These results suggest that CyA could be the first choice of treatment for resistant severe psoriasis.     

PUVA therapy for chronic cutaneous graft-vs-host disease

Chronic graft-vs-host disease (GVHD) is an immunologic disorder frequently occurring as a late sequelae of allogeneic bone marrow transplantation and characterized in the skin with lichenoid or sclerodermoid lesions. Systemic immunosuppressive agents such as corticosteroids or cyclosporine are usually required to control the disease. Therapy with psoralen and UVA (PUVA) has recently been shown to be effective for skin and oral mucosa in a few cases of GVHD. We present our experience with PUVA in six patients, five with lichenoid and one with sclerodermoid GVHD. None of these patients had significant systemic involvement. All five patients with lichenoid GVHD showed clinical improvement after PUVA therapy. Three of these patients had complete clearance of skin lesions. Clinical clearance of the disease was accompanied by microscopic clearance. The patient with sclerodermoid GVHD did not respond to therapy. No significant complications or exacerbation of systemic disease occurred. We confirm that PUVA is an effective and safe therapy for the cutaneous manifestations of lichenoid chronic GVHD. We postulate that PUVA therapy clears chronic lichenoid GVHD by selective cytotoxicity for the activated lymphoid cells in the inflammatory infiltrate.     

Comparison of the relative therapeutic efficacy of 7-methyl pyridopsoralen and 8-methoxypsoralen in photochemotherapy in psoriasis treatment

A newly-synthesized, monofunctional psoralen derivative, 7-methyl pyrido (3,4-C) psoralen (MPP) was compared with 8-methoxypsoralen (8MOP) with respect to their therapeutic efficacy in photochemotherapy of psoriasis. Psoriatic lesions of six patients were treated with topical application of MPP plus UVA (MPP PUVA) or with 8MOP plus UVA (8MOP PUVA). The UVA doses used in each treatment were 7.5 or 10 J/cm² with MPP and from 1.2 to 3.6 J/cm² with 8MOP. In every patient, marked improvement was observed after 2 to 6 treatments with MPP PUVA or 8MOP PUVA. Three patients showed clearance of each psoriatic lesion treated 9 to 17 times with MPP or 8MOP PUVA. Althought MPP required much higher UVA doses than 8MOP, MPP PUVA was as effective as 8MOP PUVA in treating psoriasis. When irradiating with identical doses of UVA, MPP PUVA appeared to be less active than 8MOP PUVA. None of the patients developed any severe dermatitis reactions during 20 exposures to MPP PUVA, indicating that the probability of inducing allergic contact and photocontact dermatitis may be extremely low. Erythemogenic and pigmentogenic activities of MPP and 8MOP were also compared. The data demonstrated that 8MOP is more than 8 times as effective as MPP for both activities. With the UV doses used in this study, however, every patient produced marked pigmentation after MPP PUVA therapy. Finally, the UVA dose-dependency of MPP PUVA was studied with an additional patient. Both therapeutic and pigmentogenic effects increased as a function of the UVA dose; it appeared impossible to clear psoriasis without producing pigmentation.     

Oral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema

Background: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. However, most studies were retrospective and did not include longer follow-up periods.
Aim: To compare the therapeutic efficacy, tolerability and duration of remission after oral vs. bath PUVA using 8-MOP in patients with chronic palmoplantar eczema.
Methods: Twenty-nine patients were randomly allocated to treatment with oral or bath PUVA. Treatment was given thrice weekly for a maximum of 20 weeks. The primary outcome measure was the improvement in eczema score at the end of treatment. After clearing patients were followed up until relapse or up to 40 months.
Results: Overall, both PUVA modalities appeared comparably effective. However, after stratifying according to eczema type, significant differences in therapeutic outcome in general as well as in response to the two regimes were found. Dyshidrotic eczema responded better to both treatments ( P =0.048) and remained longer in remission than hyperkeratotic eczema. Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA ( P =0.03).
Conclusion: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.     

Comparison of efficacy and side‐effect profile of oral PUVA vs. oral PUVA sol in the treatment of vitiligo: a 36‐week prospective study

Background Both Oral PUVA and PUVA sol have been successfully used in vitiligo treatment. However, there is paucity of studies comparing the two therapies, especially under subtropical conditions of abundant sunlight where PUVA sol is more feasible. Objectives To compare the efficacy and side effects of oral PUVA versus oral PUVA sol therapy in generalized vitiligo. Methods Comparative prospective clinical trial conducted on consecutive patients of generalized vitiligo. Response to treatment was assessed using change in Lund & Browder (L & B) score for assessment of reduction in body surface area of involvement, patient global assessment (PGA) of improvement in vitiligo, investigator’s global assessment (IGA) of extent of repigmentation, and quality of life (QOL) assessment using Tjioe et al questionnaire. Results Thirty five patients were recruited‐ 18 in PUVA and 17 in PUVA sol group. Mean percentage change in L & B score at 36 weeks was 46.4% in PUVA and 26.1% in PUVA sol group (P = 0.06), mean PGA score in PUVA was 4.58 ± 2.23 and in PUVA sol group was 6 ± 2.08 (P = 0.13), mean IGA score was 3.08 ± 1.68 in PUVA and 1.79 ± 0.57 in PUVA sol group (P = 0.11). QOL scores were significantly higher in PUVA group as compared to the PUVA sol group (P = 0.04). Side effects were comparable in two groups except for phototoxic side effects which were significantly more in PUVA group. Conclusions PUVA is more efficacious than PUVA sol and also provides greater psychological benefit in treatment of generalized vitiligo but is associated with more phototoxic adverse effects.     

Acute myelomonocytic leukaemia developing in a patient with psoriasis treated with oral 8–methoxypsoralen and longwave ultraviolet light

Acute myelomonocytic leukaemia developed in a patient with psoriasis treated with oral 8–methoxypsoralen and longwave ultraviolet light (PUVA). The possibility that PUVA may induce haematological malignancies by damaging the DNA of cirulating multipotential haemopoietic stem cells is discussed. We advise increased attention to the haemopoietic system of patients treated with PUVA.     

PUVA and PUVB in vitiligo – are they equally effective?

BACKGROUND/AIMS: The combination of psoralens with different types of ultraviolet (UVL) sources in the treatment of vitiligo has led to different reports of success. The purpose of this trial is to compare in a random right-left comparison study the efficacy and side effects of oral 8-MOP plus UVA (PUVA) and oral 8-MOP plus UVB (broadband, 290-320 nm P-UVB) in the treatment of vitiligo. METHODS: The study included 24 cases of extensive vitiligo involving more than 30% of the body surface area in a bilateral symmetrical distribution. Each patient received 0.7 mg/kg 8-MOP orally 2 h before the light session. The right side of the body was exposed to UVA (320-400 nm), while the left half was exposed to UVB (290-320 nm). The patients received 3 sessions/week for a total of 30 sessions. RESULTS: Both PUVA and PUVB produced moderate (50-60%) improvement, with similar incidences of phototoxic reaction and skin thickening. However, the study revealed a significant difference in the number of sessions needed to improve produce erythema and perifollicular pigmentation as well as a moderate response, the response on the UVA side always being earlier. Furthermore, the amount of joules needed to achieve the same response was 10 times greater on the UVA side than on the UVB side. CONCLUSION: The use of psoralen plus broadband UVB is as effective as PUVA in the treatment of vitiligo. However, the long-term side effects of psoralen plus UVB are unknown.     

Erythema multiforme following polymorphic light eruption: a report of two cases

We report two patients in whom episodes of polymorphic light eruption were followed by recurrent erythema multiforme on exposed and nonexposed sites. Treating the polymorphic light eruption with prophylactic PUVA and/or oral prednisolone or cyclosporin prevented the development of erythema multiforme, suggesting that the two events are related. It is possible that erythema multiforme develops as a response to the same causative antigen as polymorphic light eruption.     

Oral methoxsalen photochemotherapy of extensive pityriasis alba. Preliminary report

Six patients with extensive pityriasis alba were treated with oral methoxsalen, followed by exposure to midday summer sun or exposure to long-wave ultraviolet radiation in a psoralens plus ultraviolet A (PUVA) cabinet. Complete clearing or marked improvement was obtained in five patients in less than 4 weeks of treatment. The patient with the most extensive skin involvement and the longest duration of the disease achieved a marked degree of improvement after 15 weeks of therapy. A long-term follow-up is still required to define the maintenance treatment and its efficacy.     

Oral PUVA and topical steroids for treatment of oral manifestations of chronic graft-vs.-host disease

BACKGROUND: Oral manifestations of chronic graft-vs.-host disease (cGVHD) can significantly affect the quality of life and severity often does not correlate with systemic manifestations. We evaluated the use of topical corticosteroids and the intraoral application of psoralen-UVA (PUVA) for treatment of oral manifestations of cGVHD. METHODS: Overall, 18 patients with oral manifestations of cGVHD were treated with either intraoral PUVA (n=7) or with topical corticosteroids (n=16). Four patients received intraoral PUVA after failure of topical steroids and one patient was treated with topical corticosteroids after failing treatment with intraoral PUVA. A glass fiber extension of an UVA source was used for manual intraoral application. Treatment with topical corticosteroids consisted of 0.1 mg/ml dexamethasone mouth wash four times a day in combination with antifungal prophylaxis. RESULTS: Four patients showed complete local response (CR) due to intraoral PUVA, two improved and one did not respond. Topical corticosteroids resulted in nine patients in CR, two improved and five did not respond. CONCLUSION: Intraoral PUVA as well as topical corticosteroids are effective in treatment of oral manifestations of oral GVHD with few side-effects and improve quality of life in patients with cGVHD.     

Cutaneous carcinoma and PUVA lentigines in Thai patients treated with oral PUVA

A total of 113 Thai patients who were treated with oral PUVA from 1979 to 1992 were examined for long-term cutaneous side effects of PUVA. Two psoriatic patients developed PUVA keratosis on non-sun-exposed areas. Both were skin type IV and had had phototherapy with UVB and sunlight previously. The total doses of UVA were 909 J/cm² and 242 J/cm² respectively. One psoriatic patient developed Bowen's disease. He had had a cumulative dose of UVA 2207 J/cm². He also had a past history of arsenic intake and phototherapy with UVB and sunlight. PUVA lentigines were seen in 58 patients (51.4%). It was associated with older age at starting PUVA, higher cumulative UVA dose and greater number of PUVA treatment. This study suggests that previous exposure to other risk factors is important for inducing skin cancer in populations with skin phototype III, IV and V treated with oral PUVA.     

Persistent light reaction. Successful treatment with cyclosporin A

A 53-year-old male patient who had suffered for several years from severe persistent light reaction possibly due to tribromsalan photosensitivity was treated with cyclosporin A after long-term low-dose administration of corticosteroids which had to be discontinued. PUVA therapy was impracticable due to the extraordinarily high UVA sensitivity. When cyclosporin A blood concentrations between 100 and 200 ng/ml were reached, the patient was nearly free from symptoms; the excellent clinical response was also documented by phototesting performed prior to and during therapy. Cyclosporin A may be a valuable therapeutic alternative to systemic corticosteroids for severe cases of persistent light reaction which cannot be controlled by photoprotective measures.     

Topical psoralen photochemotherapy (PUVA) and superficial radiotherapy in the treatment of chronic hand eczema

The therapeutic efficacy of conventional superficial radiotherapy and topical psoralen photochemotherapy (topical PUVA) administered over a 6 week period was compared in a double-blind study of 21 patients with chronic bilateral constitutional hand eczema. One hand was treated with conventional superficial radiotherapy and the other with topical 8-methoxy-psoralen and long-wave ultraviolet light (topical PUVA). Significantly better clinical improvement was seen in superficial radiotherapy treated hands over topical PUVA treated hands after 6 weeks of treatment, but this difference was not maintained at 9 or 18 weeks. There was no significant difference in symptom severity between the two treatments after 6 weeks, but superficial radiotherapy produced significantly more symptomatic improvement at 9 and 18 weeks. Superficial radiotherapy is a less time consuming procedure than topical PUVA and leads to more rapid improvement.