Psoralen cream plus ultraviolet A photochemotherapy (PUVA cream): our experience

BACKGROUND: Psoralen ultraviolet A (PUVA) bath photochemotherapy has been proved highly effective in the treatment of various dermatoses without potential side-effects of systemic therapy. Another form of topical PUVA therapy (PUVA cream) without the logistical requirements for bath tubs has recently been developed. OBJECTIVE: We sought to develop preparation and treatment standards to PUVA cream and to confirm its clinical efficacy in the treatment of various dermatoses. METHODS: In the first phase, the safety of a novel cream containing 0.002% 8-methoxypsoralen (8-MOP) was determined in six healthy volunteers. In a second phase, 40 patients with different dermatoses were treated with a minor concentration (0.001% 8-MOP), following the guidelines for topical PUVA of the British Photodermatology Group. RESULTS: Plasma levels of psoralen after the application of the novel cream containing 0.002% 8-MOP, were less than 34 ng/mL, the maximum 8-MOP concentration reported for topical PUVA. With a minor concentration (0.001% 8-MOP), important improvement or healing was found in 53.3% of the cycles, generally with a good response since the first month of treatment. Only mild side-effects were detected in 14 patients. CONCLUSIONS: Based on our data, PUVA cream photochemotherapy is well accepted by patients and may be a highly effective treatment even if previous therapy was unsuccessful. In addition, PUVA cream is easier to use than PUVA bath.     

Phototherapy and PUVA photochemotherapy in children

The use of phototherapy and photochemotherapy in children has been limited due to concerns over their long-term carcinogenic potential. Furthermore, the method of administration is disconcerting to some children, particularly as phototherapy treatment units are seldom rendered 'child-friendly'. Despite these reservations, ultra-violet therapies can be useful treatment options for children with selected dermatological conditions provided they are used under carefully controlled conditions.     

Narrow band Ultraviolet B 311 nm in the treatment of vitiligo: two right-left comparison studies

AIM: Evaluation of narrow band ultraviolet B (NB UVB 311 nm) in the treatment of vitiligo by two independent studies. The first study compared NB UVB with a well-established therapeutic modality, psoralen ultraviolet A (PUVA), and the second study was conducted to find out whether psoralen might add to its efficacy. METHODS: In the first study, 15 patients were exposed on the left half of their body to UVB 311 nm and then exposed on their right half to UVA after ingestion of psoralen. In the second study, 20 patients were exposed to UVB 311 nm on the left side of the body, followed by ingestion of psoralen and exposure to NB UVB 311 nm 90 min later to the right side of the body. In both studies, while exposing one side, the other was protected by an UV-proof gown. Thus two right-left comparative studies were carried out simultaneously, namely: UVB 311 nm vs. PUVA and UVB 311 nm vs. PUVB 311 nm. RESULTS: In the first study, comparison of PUVA and NB UVB 311 nm showed no difference either in the degree of response or in the incidence of complications. In the second study, comparison of PUVB and UVB showed equal clinical improvement on both sides. The cumulative dose needed to achieve the same response on the PUVB side was lower than that on the UVB side, but the difference was not statistically significant. The incidence of phototoxic reactions was significantly higher on the PUVB treated body half. CONCLUSION: NB UVB 311 nm has similar repigmentary effects as PUVA. The addition of psoralen does not increase its efficacy.     

Phototherapy and photochemotherapy of sclerosing skin diseases

The treatment of sclerosing skin diseases [systemic sclerosis, localized scleroderma, lichen sclerosus et atrophicus, sclerodermoid graft-vs.-host disease, scleredema adultorum (Buschke), scleromyxedema and necrobiosis lipoidica] is difficult and remains a great challenge. Numerous treatments, some with potentially hazardous side effects, are currently used with only limited success. The introduction of phototherapy and photochemotherapy for sclerosing skin diseases has considerably enriched the therapeutic panel and proven useful in a number of sclerosing skin diseases especially in localized scleroderma. Two phototherapeutic modalitites are used for the treatment of sclerosing skin diseases, long-wave ultraviolet A and psoralen plus ultraviolet A (PUVA). This article reviews current knowledge about the application of phototherapy and photochemotherapy to various sclerosing skin disorders.     

Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy

Eosinophilic fasciitis is a rare disorder which can markedly affect the quality of life in individual patients. So far, no generally accepted and effective treatment modality has been available. Although the precise nature of eosinophilic fasciitis is still unknown, it is often regarded as a variant of localized scleroderma (morphoea). Phototherapy and photochemotherapy have been shown to be effective in the treatment of sclerodermatous skin lesions. We report a patient with eosinophilic fasciitis which was successfully treated with psoralen plus ultraviolet A bath photochemotherapy within 6 months.     

Combination of photochemotherapy (PUVA) and ultraviolet B (UVB) in the treatment of psoriasis vulgaris

Nineteen patients with psoriasis vulgaris were treated with a combination of psoralen-ultraviolet A (PUVA) and ultraviolet B (UVB) on the right side of their bodies and with PUVA therapy alone on the left side. Herein is an analysis of the results. There were no significant differences in the mean number of treatments, the mean UVA dose at clearing, or the mean cumulative UVA dose between the PUVA-UVB side and the PUVA side. However, in 4 cases, the PUVA-UVB side cleared more rapidly than the PUVA side. Interestingly, patients who received PUVA-UVB on one side and PUVA on the other required fewer treatments, a lower ultraviolet (UV) dose at clearing, and a lower cumulative UV dose than did patients who were treated with only PUVA monotherapy or UVB monotherapy, following the same protocol. This combined method may be useful in the treatment of chronic psoriatic patients, because of rapid clearing and a marked reduction in the total cumulative UV radiation. However, further follow-up studies are indicated due to the long-term side effects of combined UV radiation.     

Phototherapy of mycosis fungoides

Background/purpose: Among the primary cutaneous T‐cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow‐ and broadband UVB and 8‐methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance.     

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy

PUVA-bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8-MOP application. Because bath-PUVA can be difficult to manage, topical PUVA therapy using 8-MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.     

Liver cytochrome P450 CYP1A2 is markedly inhibited by systemic but not by bath PUVA in dermatological patients

BACKGROUND: Methoxsalen (8-MOP) may cause important pharmacokinetic drug interactions as it has been shown to inhibit and/or induce several drug-metabolizing enzymes in vitro, in animal models and in humans. OBJECTIVES: In order to assess the clinical importance of acute and chronic 8-MOP effects on the liver cytochrome P-450 enzyme CYP1A2 in vivo, we measured caffeine clearance in dermatological patients before the onset of systemic or bath psoralen + ultraviolet A radiation (PUVA) (8-MOP + UVA) therapy, on the first day and after 1 week of treatment. METHODS: Data from four patients with systemic PUVA and seven patients with bath PUVA were available (age range 23-71 years, five women and six men). RESULTS: For all of the patients, individual pre-PUVA caffeine clearance values were above the lower limit of previously assessed reference ranges. Systemic PUVA markedly decreased caffeine clearance by factors of 0.17 [90% confidence interval (CI) 0.07-0.42] on the first day and 0.14 (90% CI 0.05-0.36) after 1 week of treatment, respectively, and values thus dropped below the reference ranges. In contrast, bath PUVA had no obvious effect on pre-PUVA clearance values as the latter changed by factors of 1.00 (90% CI 0.81-1.23) and 1.05 (90% CI 0.75-1.49) on the first day and after 1 week of treatment, respectively. CONCLUSIONS: Systemic PUVA causes pronounced inhibition of liver CYP1A2, while bath PUVA has no such effect. The extent of interaction makes a dose adjustment for most CYP1A2 substrates such as theophylline mandatory in patients undergoing systemic PUVA.     

Phototherapy in systemic sclerosis: Review

Systemic scleroderma—also known as systemic sclerosis (SSc)—is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis‐à‐vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.     

Lichen planus of the lower limbs: successful treatment with psoralen cream plus ultraviolet A photochemotherapy

Lichen planus (LP) classifies into different subtypes depending on morphology and localization. Localized LP of the lower limb (LPLL) manifests a great challenge due to persistent itching, therapeutic resistance and the risk to develop into SCC. We report two cases with LPLL refractory to standard topical therapy, which were successfully treated with psoralen cream plus UVA photochemotherapy (cream‐PUVA). We propose cream‐PUVA as an alternative therapeutic option effective for localized LP of the lower limbs.     

Phototherapy in the age of biologics

Dermatologists are presented with a diversity of therapeutic modalities for the treatment of inflammatory, sclerosing, and neoplastic conditions, but with the development of various new irradiation devices that utilize specific parts of the electromagnetic spectrum, phototherapy has become a more viable, accessible, and efficacious option in the treatment of these conditions. The ultraviolet (UV) range (10-400 nm) is further subdivided into UVA and UVB, each of which has been particularly useful in a number of skin conditions. The most commonly used forms of UV irradiation are UVA1, psoralen plus UVA (PUVA), and narrowband (NB) UVB. Each of these modalities differ in their mechanism of action, indications, and side effect profiles, and it is important that clinicians be familiar with these differences. Today, phototherapy is a valuable option in the treatment of many nonpsoriatic conditions including atopic dermatitis, sclerosing skin conditions such as morphea, vitiligo, and mycosis fungoides. Due to its relative safety, phototherapy may be used in most populations, including children and pregnant women. However, contraindications and side effects are known and should be considered before patients begin a phototherapeutic regimen.     

Bath psoralen+ultraviolet A photochemotherapy vs. narrow band‐ultraviolet B in psoriasis: a comparison of clinical outcome and effect on circulating T‐helper and T‐suppressor/cytotoxic cells

Background: Comparative success rates of bath psoralen+ultraviolet A (PUVA) and narrow band‐ultraviolet B (NB‐UVB) in psoriasis treatment are variably reported with no previous studies on the possible effect of bath PUVA on circulating CD4+ and CD8+ T cells. Objective: We aimed to compare the effect of bath PUVA and NB‐UVB clinically and on circulating T‐helper and T‐suppressor/cytotoxic cells in psoriasis. Patients and methods: Thirty‐four psoriatic patients divided into a bath PUVA‐treated group (18 patients) and a NB‐UVB‐treated group (16 patients) were compared regarding the disease severity by psoriasis area and severity index (PASI) score and percentage of circulating CD4+ and CD8+ T cells by flowcytometry before and after treatment. Results: After treatment, the bath PUVA group showed a significantly higher reduction of PASI score (85.44%) than the NB‐UVB group (58.72%). Mean peripheral CD4+ T‐cell percentage was significantly lower after [36.8; 95% confidence interval (CI) 33.80, 39.97] compared with before treatment (42.06; 95% CI 38.29, 45.83) (P<0.05) in the bath PUVA group while this difference was insignificant in the NB‐UVB group (P>0.05). Conclusion: Bath PUVA therapy is superior to NB‐UVB in the treatment of moderate and severe psoriasis with mild reversible side effects. Both modalities have a systemic effect decreasing peripheral CD4+ T cells, which is more with bath PUVA.