Psoralen Plus Ultraviolet A Therapy Research Articles

Treatment Response to Phototherapy in Patients with Mycosis Fungoides and Parapsoriasis

Background: Early stage mycosis fungoides (MF) and parapsoriasis are treated by phototherapy techniques. In this study, we aimed to assess treatment responses to narrow-band ultraviolet B (NB-UVB) and psoralen plus ultraviolet A (PUVA) therapies in patients with MF and parapsoriasis in a comparative manner. Materials and Methods: We retrospectively reviewed patients with early-stage MF and parapsoriasis who underwent phototherapy in Phototherapy Unit of our clinic between 2008 and 2018. In all groups, data regarding phototherapy were recorded and evaluated statistically. Results: In this study, 127 patients including 46 patients with early-stage MF, 48 patients with small plaque psoriasis and 33 patients with large plaque psoriasis received phototherapy. PUVA therapy session rate was significantly higher in patients with MF while NB-UVB therapy rate was significantly higher in patients with SPP. Number and duration of sessions to achieve complete remission were significantly higher in patients with MF when compared to those with SPP while no significant correlation was found between MF and LPP. In addition, the number and duration of sessions to achieve complete remission were significantly higher in patients with LPP than those with SPP. When patients groups were assessed according to phototherapy type given, it was seen that the complete remission rate was significantly higher in MF patients received PUVA therapy than patients received NB-UVB therapy (p

SOAP PUVA.

Psoralen plus ultraviolet A (PUVA) photochemotherapy combines the use of psoralen and long-wave ultraviolet A (UVA) radiation. The phototherapeutic effects of PUVA result from photochemical reactions. PUVA therapy can be administered in various methods such as conventional UV chambers, psoralen with sunlight as source of UV light PUVASOL, bath PUVA, bath suit PUVA, soak PUVA, and turban PUVA. The advantage of using topical psoralen is that it avoids the adverse effects associated with the oral PUVA therapy and is being increasingly used in the treatment of psoriasis. However, it is known to cause increased phototoxicity, and in conditions like vitiligo, the spotty repigmentation is not cosmetically acceptable. Psoralen bath plus UVA therapy is known as bath PUVA therapy. Bath PUVA treatment for psoriasis was first reported by Fischer and Alsins in 1976. Bath PUVA is administered by mixing 37.5 mL of 1% 8-methoxypsoralen in 100 Lof water to obtain a concentration of 3.75 mg/L.[1] In bath suit PUVA, bathing suit of flannel material (stitched to suit the patient) is dipped in this solution for 5 min and worn for 15 min with a raincoat over it to prevent evaporation of the solution, and the patient is then immediately exposed to UVA in a whole-body phototherapy chamber. Bath PUVA needs plenty of water. Bath tub is not easily available and bath suit needs special suit, and treatment is cumbersome. We planned to modify the therapy by mixing psoralen with cleansing lotion and coined it as SOAP PUVA. The choice is due to the solubility factor as 8-MOP being insoluble in water. We reported a novel method of delivering 8-MOP uniformly all over the skin within a short time and on subsequent exposure to UV light. Because8-MOP was not soluble in water, we tried to dissolve it in commercially available moisturizing lotion (cetaphil) and synthetic detergent (cetaphil cleansing lotion). As it dissolved well in cleansing lotion, we decided to use it for our study [Figure 1]. As the method was new, we initially tried to standardize the procedure and determine the minimal pigmentation dose (MPD). The project was done in a single healthy subject with no existing dermatological disease requiring phototherapy. We started by using 1:100 dilution of methoxsalen that was prepared by mixing 0.1 mL of methoxsalen with 9.9 mL of cleansing lotion. The mixture was applied over the back [Figure 2]. The paste was left over for 5 min after which it was wiped with water-soaked gauze. The template cloth was worn along with goggles to protect the eyes. The area was exposed to UVA light (0–3J) with 0.5-J increments. The plan was to observe for MPD after 48 h and delayed pigmentation upto 7 days. No erythema and pigmentation was observed upto 7 days. We increased the concentration to 1:80, and the same procedure was repeated with no erythema or pigmentation. The concentration was increased to 1:60 and the same procedure was repeated. Erythema was observed at 2.5 J after 48 h [Figure 3] and pigmentation was observed after 5 days.Figure 1: Psoralen completely soluble in cleansing lotionFigure 2: Psoralen and cleansing lotion mixture applied over the backFigure 3: Erythema observed after 48 h at 2.5 JOral PUVASOL is effective but is time-consuming because the exposure to UV light occurs after 2 h and the intensity of sunlight varies. It also becomes difficult for children and working women. To overcome these issues bath PUVA was introduced, but it requires consumption of a large quantity of water. Pai and Srinivas introduced bathsuit tPUVA [2] to overcome this but the suit had to be worn for 15 min and was practically difficult. The main purpose of this study was to identify the method and use it with exposure to sunlight. The plan was to increase the concentration of psoralen rather increase the exposure time because we wanted to deliver it in a shorter period and the irradiance of sunlight was much lower than the irradiance of UV light in artificial chambers. The limitation was that it was done on a single subject, and the results might have varied. We plan to conduct further studies on a larger scale to determine the ideal dilution and use it as a viable alternative for delivering PUVA therapy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Blocking or enhancing effects of some basic emollients in UVA penetration

Background:Topical agents used in combination with phototherapy or photochemotherapy may have both blocking or enhancing effects in ultraviolet rays. Objective:In this in vivo study, the effects of topical petrolatum, basis cream, glycerine, and olive oil on the transmission of ultraviolet A radiation were investigated. Methods:A test was performed to determine the minimal phototoxic dose on 29 volunteers with only psoralen plus ultraviolet A (PUVA) and then the same test was repeated with white petrolatum, basis cream, glycerine, olive oil, and sunscreen (0.3cc/25cm2). The effects of each agent on the minimal phototoxic dose were determined after 72 h. Results:When compared to pure PUVA, there was a statistically significant increase in the mean minimal phototoxic dose values by the application of white petrolatum (P = 0.011), but there was no significant increase or decrease in the mean minimal phototoxic dose values after the application of basis cream (P = 0.326), glycerine (P = 0.611) or olive oil (P = 0.799). Study limitations:Low number of patients Conclusion:The application of white petrolatum, which has a blocking effect, and also of basis cream immediately before PUVA therapy should not be recommended. Although we specify that glycerine and maybe olive oil can be used before photochemotherapy, there is a need for further research in larger series.

Erythema action spectrum of topical 8-methoxypsoralen-sensitized skin re-evaluated: implications for routine clinical practice.

Published methodology used to determine psoralen plus ultraviolet A (PUVA) erythemal action spectrum does not reflect current clinical practice for psoralen sensitization. We re-evaluated the PUVA action spectrum using aqueous 8-methoxypsoralen (8-MOP) 2·6mgL(-1) as used routinely in current clinical practice. To determine the UVA erythema action spectrum of topical 8-MOP-sensitized normal skin. Twenty healthy volunteers with skin phototypes I-V were recruited. Forearms were psoralen-sensitized at 37°C for 10min. Six UVA irradiations at 10-nm intervals between 325 and 375nm were randomly allocated to forearm sites and were applied using a 10-nm bandwidth irradiation monochromator. The visual minimal phototoxic dose (MPD) was recorded on each site at 96h. Volunteer Boston phototypes were: I, n=2; II, n=6; III, n=6; IV, n=5 and V, n=1. The mean MPD (Jcm(-2) ) for all subjects at each wavelength was as follows: 325nm, 0·64 (SD 0·37); 335nm, 0·80 (SD 0·58); 345nm, 0·96 (SD 0·55); 355nm, 1·50 (SD 0·85); 365nm, 2·19 (SD 0·90); and 375nm, 2·89 (SD 1·06). Therefore, the relative sensitization at each wavelength (erythemal action spectrum) was: 1, 0·83, 0·67, 0·43, 0·29 and 0·22. There were significant differences between the PUVA erythemal effectiveness at different wavelengths but none between skin types. This study has established the erythemal action spectrum for bath/soak PUVA therapy as is currently performed. In all volunteers, the peak sensitivity was at 325nm. All volunteers showed a similar trend across the wavelengths studied irrespective of skin type. The determination of the action spectrum for PUVA-induced erythema is important as it permits reliable estimates of erythemal efficacy of any UVA source where the emission spectrum of the lamp is known or can be measured.

Effective Oral Psoralen Plus Ultraviolet A Therapy for Digital Ulcers with Revascularization in Systemic Sclerosis

Systemic sclerosis (SSc) is a heterogeneous disorder characterized by excessive fibrosis and microvascular damage to the skin and various internal organs, including the lungs, kidneys, oesophagus and heart. Raynaud’s phenomenon is an almost universal symptom of SSc; 95% of patients are affected. Digital ulcers are observed frequently, especially in intractable cases with severe Raynaud’s phenomenon, and there is considerable morbidity, with gangrene and amputations (1). To date, there is no promising treatment for severe cases of SSc that are complicated by digital ulcers. Apart from immunosuppressive drugs, administration of oral psoralen plus ultraviolet A (PUVA) therapy has been used in patients with SSc with progressive skin sclerosis complications, with some improvement (2). We report here the first case of successful oral PUVA therapy in a patient with SSc complicated by progressive skin sclerosis and digital ulcers.

Catechol-O-methyltransferase activity in psoriasis patients treated with psoralen plus ultraviolet A therapy

Catechol-O-methyltransferase (COMT) activity is increased in patients with mild/moderate psoriasis. Narrowband ultraviolet B (nbUVB) phototherapy decreases COMT activity. However, the effect of psoralen plus ultraviolet A (PUVA) on this enzyme activity is unknown, and it remains to be clarified if the nbUVB-induced effect in COMT activity is related to clinical response. The aim of this study is to evaluate COMT activity in moderate/severe psoriasis and assess whether PUVA therapy modifies this activity. An observational study was conducted on 18 patients with moderate/severe psoriasis and 13 matched controls. Patients were treated with PUVA twice weekly during 6 weeks, and they were evaluated for Psoriasis Area and Severity Index (PASI) and COMT activity before photochemotherapy, at the end of it and 4 weeks after stopping. Before PUVA therapy, S(soluble)-COMT activity was significantly (P < 0.05) higher in psoriasis patients than in controls. After photochemotherapy, no significant differences were found in S-COMT activity at all end points. Photochemotherapy significantly decreased PASI but COMT activity values remained higher than those of control population. Psoriasis patients with moderate/severe disease present higher S-COMT activity than controls. Although a good clinical response was observed, PUVA therapy does not change S-COMT activity. This differential COMT effect of PUVA and nbUVB suggests a wavelength-specific regulation.

Phototherapy for pityriasis lichenoides: our experience

Pityriasis lichenoides is a benign disease that includes a continuous spectrum with two polar ends: pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). Although its benign and self-limited character, treatment is required, both for itch relief and for cosmetic issues. The present study is a retrospective analysis of 13 patients (11 PLC and 2 PLEVA) treated in our institution with psoralen plus ultraviolet A (PUVA) or ultraviolet A combined with ultraviolet B (UVA/UVB) during the period 1998–2011. In the PUVA group, complete response was achieved in five patients and partial response in two. Total cumulative UVA dose was 84.4 J/cm2. One patient quit therapy without therapeutic response. In the UVA/UVB group, complete response was achieved in two patients and partial response in an equal number of patients. One patient did not reach a significant improvement. Total cumulative doses were: 26.1 J/cm2 for UVA and 3.62 J/cm2 for UVB. There were no acute side effects in either therapeutic group. In the present study, PUVA phototherapy was preferred for patients with more widespread or long-evolving disease, while UVA/UVB was selected for patients who presented more recent disease or contraindications for PUVA therapy. Regardless of the absence of clinical guidelines, both therapeutic options proved to be successful, ascertaining phototherapy as an effective and safe option for pityriasis lichenoides patients.

Advances in ultraviolet A1 phototherapy and psoralen plus ultraviolet A (PUVA) photochemotherapy for localized scleroderma

Localized scleroderma (LS) is a connective tissue disease characterized by localized or diffused sclerosis of skin with or without the fibrosis of various internal organs.The management of LS includes physical treatment,drugs and phototherapy.Because of high efficiency and few side effects,phototherapy has become a hot spot of recent researches.Numerous clinical and basic researches have proved that phototherapy can block fibrosis progression,induce softening of already existing sclerotic lesions by suppressing inflammatory cell infiltration.In particular,long wave ultraviolet A1 (340-400 nm) and photochemotherapy (PUVA) have shown a satisfactory effect.However,no uniform standard is available for the design of trials and evaluation of efficacy. Key words: Scleroderma,localized; Ultraviolet; PUVA therapy

Probiotic supplementation: an alternative in the treatment of mycosis fungoides?

Editor The current treatment strategies for patients with mycosis fungoides and Sézary syndrome had been published in the EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome.1 In the early stages of cutaneous T-cell lymphoma (CTCL; mycosis fungoides, stages IA, IB and IIA), skin-directed therapies like topical corticosteroids, BCNU (carmustine), nitrogen mustard, bexarotene gel or systemic psoralen plus ultraviolet A (PUVA) phototherapy, UVB broad- or narrow-band phototherapy, localized radiotherapy or total skin electron beam therapy are recommended for first-line treatment. Here, we report a case of early-stage annular mycosis fungoides. A 38-year-old woman had been diagnosed with annular mycosis fungoides at the age of 19. Previous therapy included X-ray radiation (Dermopan) of the left flank and intermittent local corticosteroids. For 17 months, she received low-dose interferon alpha-2a, 6 million IU subcutaneously three times per week in combination with PUVA therapy, resulting in a complete response for 1 year. A flare-up was noticed around the irradiated skin area on the left flank. A 15 × 20 cm polycyclic annular erythematous plaque with fine scaling was seen (Fig. 1). The local treatment with corticosteroids had no benefit and the lesion grew larger centrifugally. A skin re-biopsy of the erythematous annular plaque was done. The biopsy showed a dense infiltrate of atypical lymphocytes, some forming groups within the epidermis (Pautrier micoabscesses) with a CD3+, CD4+ phenotype. The TCR-γ-PCR GeneScan analysis of the tissue showed a monoclonal T-cell population. The diagnosis of mycosis fungoides was confirmed. A 15 × 20 cm polycyclic annular erythematous plaque with fine scaling surrounding an area of post-irradiation hypo- and hyperpigmentation on the left flank. We discussed the therapeutic options such as localized PUVA therapy and systemic treatment with bexarotene with the patient. Radiotherapy was not recommended due to previous irradiation therapy leading to scaring. The patient preferred a wait-and-see strategy and refused the offered treatment options. At the same time, she started probiotic supplementation with Lactobacillus gasseri (8 × 108 to 8 × 109 KBE/g) and Bifidobacterium longum (8 × 108 to 8 × 109 KBE/g) daily for the prevention of intestinal infection. Probiotic supplements are generally well tolerated because the contained microorganisms are identical to those found in the human gastrointestinal tract. Interestingly, after 8 weeks of treatment with probiotic supplementation, the annular plaques changed colour to reddish-brown, and after 6 months, the lesions were almost gone (Fig. 2). The patient reported that she was not using any other ointment or therapy to treat the mycosis fungoides skin lesion. It could be speculated whether the complete regression of the annular mycosis fungoides skin lesion was induced by probiotic supplementation. However, clinical regression of annular mycosis fungoides lesions without therapy2 and a complete regression of CTCL, unspecified after skin biopsy, were described.3 Complete clearance of the mycosis fungoides lesion on the left flank after 6 months treatment with probiotic supplementation; only the irradiated skin was seen. Recent clinical trials have evaluated the clinical effectiveness of probiotics in the treatment and prevention of a wide range of acute and chronic gastrointestinal diseases,4,5 such as infectious diarrhoea, antibiotic associated diarrhoea, irritable bowel syndrome, inflammatory bowel disease and Helicobacter pylori infection. Several studies have also evaluated their efficacy in reducing the incidence of atopic clinical symptoms with promising results6 and other non-gastrointestinal diseases, such as respiratory infections, urogenital tract infections vaginitis and hypercholesterolaemia.5 There are various randomized studies and reports in the literature for the recommendation of probiotic supplementation in cancer prevention, particularly in colon,7 bladder, breast8 and liver cancer. Nevertheless, the clinical evidence for probiotic use in cancer prevention is insufficient. However, no successful treatment of cancer was reported. A recent study investigated the molecular mechanisms of pro-apoptotic effects of the probiotic Lactobacillus reuteri.9 They showed that L. reuteri promotes tumour necrosis factor–induced apoptosis in human myeloid leukaemia-derived cells by modulation of nuclear factor-kappa B (NK-kappaB) and mitogen-activated protein kinase signalling. This could be a possible explanation for the observed clinical effect because CTCL tumour cells are resistant to apoptosis by various mechanisms including constitutive activation of NF-kappaB.10 This might be the target of the probiotic bacteria in the tumour cells of our patient. However, it remains an open question if probiotics are able to induce apoptosis in CTCL tumour cells, and if sufficient dosages might reach the CTCL tumour cells in the skin. In conclusion, we present a patient with mycosis fungoides in whom probiotic supplementation may have lead to clearance of mycosis fungoides skin lesions.

Randomized, double-blind, placebo-controlled evaluation of the efficacy of oral psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the Psoriasis Area Severity Index score (improvement of 75% or greater) at 12 weeks

Psoralen plus ultraviolet A (PUVA) for the treatment of psoriasis has never been evaluated using the Psoriasis Area Severity Index (PASI) in a randomized, double-blind, placebo-controlled trial. The lack of such data limits our capacity to estimate PUVA's efficacy relative to other treatment options that are available today. The purpose of this study was to evaluate the efficacy of PUVA therapy for patients with plaque-type psoriasis. This study involved 40 patients with psoriasis; 30 received PUVA and 10 received UVA with placebo. PASI scores were assessed at baseline and every 4 weeks thereafter for 12 weeks. By nonresponder imputation, 60% (18 of 30) in the PUVA group achieved 75% or more improvement in PASI score after 12 weeks of treatment compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). Using intent to treat with last observation carried forward analysis, 63% (19 of 30) in the PUVA group achieved 75% or more improvement in PASI score compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). By per protocol analysis, 86% (18 of 21) in the PUVA group as compared with 0% (0 of 7) in the UVA plus placebo group reached 75% or more improvement in PASI score after 12 weeks (P < .0001). The study was relatively small with only 40 patients enrolled and 28 patients who completed the protocol. Further studies that involve head-to-head comparison of PUVA with other treatment modalities are needed. Nonresponder imputation, last observation carried forward with intent to treat, and per protocol analyses each have separate advantages and limitations when determining clinical significance. This study supports the observation that PUVA is a highly efficacious treatment for chronic plaque psoriasis.

Patterns of repigmentation in two cases of hypopigmented type of vitiligo

It has been observed that depigmentation in vitiligo passes through two stages; patches of light brown hypopigmentation which gradually changes into milky white patches. In this work, we studied two cases of hypopigmented vitiligo regarding the melanocytes and keratinocytes' changes before and after 7 months of psoralen plus ultraviolet A (PUVA) therapy. Skin biopsies were taken from the vitiliginous lesions before and after 7 months of PUVA therapy and were examined using haematoxylin and eosin and Masson Fontana stains, L-3,4-dihydroxyphenylalanine reaction, immuno-histochemical stains and ultrastructural examination. In the pretreated patients, the melanocytes present were inactive and degenerative changes were detected in both melanocytes and keratinocytes. After PUVA therapy, obvious histopathological improvement was detected. Clinically, the initial response to PUVA therapy was increased hypopigmentation indicating that degenerated cells in the vitiliginous patches might have continued the process of degeneration and did not recover. Meanwhile, the perifollicular and marginal pigmentation suggested that pigmentation occurred from those areas and not from activation of already degenerated melanocytes.

Narrowband UVB and PUVA in the Treatment of Mycosis Fungoides: A Retrospective Study

Psoralen plus ultraviolet A (PUVA) is widely used as first-line therapy for treatment of mycosis fungoides. Narrowband ultraviolet B (NB-UVB) has also been shown to be effective for treatment of early mycosis fungoides. The aim of this retrospective study was to analyse the response to treatment and relapse-free interval for PUVA and NB-UVB therapies in mycosis fungoides. Forty patients were treated with PUVA or NB-UVB between 1980 and 2003. All patients had failed to respond to topical therapy or were unwilling to use it. PUVA therapy was used between 1980 and 1997. Thereafter, the choice between PUVA (twice a week) and NB-UVB therapy (three times a week) depended on stage and extent of the disease as well as on how far patients had to travel). Twelve patients (stage IA-IIB) were treated with NB-UVB and 28 patients (stage IA-IVA) with PUVA. No maintenance therapy was given. Six patients (50%) had a complete response, 4 (33%) had a partial response and 2 (16%) had a failed response to NB-UVB but had stable disease. PUVA led to a complete response in 18 (64%), a partial response in 6 (21%) and a failed response in 4 (14%) patients. The median relapse-free interval was 11.5 months in the NB-UVB treated group and 10 months in the PUVA group. The majority of the patients (79%) had stage IA and IB disease. Of these, 6 of 10 (60%) in the NB-UVB group and 13/21 (62%) in the PUVA group had a complete response to treatment. These results show that PUVA and NB-UVB are effective treatments for early mycosis fungoides.

CD30+ large cell transformation of mycosis fungoides after psoralen plus ultraviolet A photochemotherapy

Psoralen plus ultraviolet A (PUVA) photochemotherapy is widely used for the therapy of mycosis fungoides (MF). Clinical progression of MF is often associated with an increase in the size of tumour cells known as transformation. We report two patients with CD30+ large cell transformation that appeared after low-dose PUVA therapy for MF. Clinical data, histopathology, immunohistopathology and T-cell receptor gene rearrangement were studied. Nodules consisted of atypical large cells that expressed CD30. Monoclonal rearrangement of T-cell receptors was observed in one case. Low-dose PUVA therapy may be associated with CD30+ large cell transformation in patients with MF.

Endothelin-1 is significantly elevated in plasma of patients with vitiligo treated with psoralen plus ultraviolet A1

Recent evidence suggests that systemic psoralen plus ultraviolet A (PUVA) therapy may have a stimulatory effect on melanocytes, not only locally but also systemically. Aim. We aimed to assess endothelin-1 (ET-1), a potent melanocyte mitogen, in plasma of PUVA-treated paients with vitiligo. ET-1 was sequentially assessed (using ELISA) in patients with nonsegmental vitiligo treated with PUVA (n = 20), at 8, 16 and 24 h following the PUVA session. Evaluations took place at 0, 1 and 3 months of therapy. Patients with psoriasis (n = 15) treated identically and healthy subjects not receiving any therapy (n = 15) served as controls. Vitiligo Area Scoring Index (VASI) and Psoriasis Area Severity Index (PASI) scores were simultaneously evaluated. ET-1 was significantly lower in vitiligo than in psoriasis at month 0 (8.2 +/- 3.6 vs. 13.7 +/- 5.4 pg/mL; P = 0.03) and it was significantly higher in both than in healthy controls at all time points of the PUVA sessions (P < 0.001). In vitiligo, it significantly increased at month 3 at 8 (8.2 +/- 3.6 vs. 10.8 +/- 2.7 pg/mL; P = 0.02) and 16 h (8.2 +/- 3.6 vs. 11.5 +/- 3.9 pg/mL; P < 0.01), whereas in psoriasis, it significantly decreased at month 3 at 8 (13.7 +/- 5.4 vs. 3.5 +/- 0.4 pg/mL; P < 0.01) and 16 h (13.7 +/- 5.4 vs. 6.3 +/- 4 pg/mL; P = 0.01). In contrast to psoriasis, sequential values of vitiligo revealed insignificant variance (P > 0.05). VASI score significantly decreased at month 3 (19 +/- 9.6 vs. 11.9 +/- 7.3; P < 0.01), whereas PASI score significantly decreased at months 1 (38.2 +/- 16.1 vs. 13.8 +/- 3; P < 0.05) and 3 (38.2 +/- 16.1 vs. 7 +/- 2.6; P = 0.03). There was a significant indirect correlation of ET-1 with VASI score (P < 0.01) and a significant direct correlation with PASI score (P < 0.01). Systemic PUVA therapy in vitiligo may have a generalized mitogenic effect on melanocytes through the release of ET-1 into the circulation.

Successful treatment of psoriasis improves psoriasis-specific but not more general aspects of patients' well-being

Psoriasis has a detrimental effect on patients' quality of life. However, there is a relative dearth of information on which aspects of a patient's well-being are affected by successful treatment. To investigate whether, and to what extent, improvement in the clinical severity of psoriasis induced by photochemotherapy with psoralen plus ultraviolet A (PUVA) translates into meaningful changes in beliefs about psoriasis, coping, stress, distress or disability. In a prospective study, 72 patients were assessed before PUVA therapy and again when they had achieved clearance of their psoriasis. Patients demonstrated significant reductions in psoriasis-related disability, psoriasis-related stress or daily hassles and in the frequency of psoriasis-related symptoms. By comparison, there were no significant differences in levels of anxiety, depression or worrying. Similarly, patients' perceptions about cure, potential chronicity, causes, consequences and coping also remained unchanged. These results suggest that while clearance of psoriasis produces a significant reduction in factors specific to psoriasis (disability and stress), it does not impact upon psychological distress, on patients' beliefs about psoriasis or on coping. This observation highlights the complex features of patients' psychological experience of psoriasis and may provide further impetus for integration of psychological interventions into standard care protocols.

Effect of ethnicity on the risk of developing nonmelanoma skin cancer following long‐term PUVA therapy

Research demonstrating an increased incidence of skin cancer with psoralen plus ultraviolet A (PUVA) therapy has reflected the Caucasian experience. Our objective was to review the literature on skin cancer risk associated with long-term PUVA therapy in non-Caucasians. Our analysis included 4,294 long-term PUVA patients in Japan, Korea, Thailand, Egypt, and Tunisia with a follow-up period of at least 5 years. The relative risk of PUVA patients developing nonmelanoma skin cancer relative to general dermatology outpatients was 0.86 [CI 0.36-1.35]. There does not appear to be an increased risk of nonmelanoma skin cancer with long-term PUVA therapy in Asian and Arabian-African populations. Therefore, in phototherapy risk assessment, it is important to consider the patient's skin phototype and the potential protection that more pigmented skin may confer.

Eumelanin and phaeomelanin contents of depigmented and repigmented skin in vitiligo patients.

There are two chemically distinct types of melanin: the red-yellow phaeomelanin and the brown-black eumelanin. Both types of melanin have been detected in human hair, epidermis and cultured melanocytes. In a preliminary study, to quantify levels of both eumelanin and phaeomelanin in depigmented as well as repigmented patches of vitiligo following psoralen plus ultraviolet A (PUVA) therapy. We enrolled five patients with vitiligo for this study. We took biopsies from depigmented as well as repigmented lesions after PUVA therapy. The eumelanin and phaeomelanin contents of the skin biopsies were quantified by high-performance liquid chromatography. The mean concentrations in depigmented lesions were 229.4 ng per piece for phaeomelanin and 572 ng per piece for eumelanin (mean phaeomelanin/eumelanin ratio 0.36). In repigmented lesions, the mean concentration of phaeomelanin was 74.8 ng per piece and that of eumelanin was 1657.6 ng per piece (mean phaeomelanin/eumelanin ratio 0.049). Depigmented lesions showed both types of melanin, and contained a substantial amount of phaeomelanin, whereas repigmented lesions after PUVA showed predominantly eumelanin. We detected melanin in depigmented lesions of vitiligo of 5 years duration, suggesting that some residual melanocytes are still active in depigmented lesions.

A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis

Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis. To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments. Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse. Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene. Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.

Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin infiltrates and lymphomatoid papulosis.

In cutaneous T-cell lymphoma (CTCL) lesions, both reactive T cells and malignant T cells intermingle. The disease progression is mostly slow. Recent evidence suggests that even if clinical remission is reached, malignant cells persist and a relapse follows sooner or later. To wha extent tumour cell apoptosis occurs in the skin lesions either due to the reactive T cells or t therapeutic efforts is not known. To determine the extent of tumour cell apoptosis and the expression of proapoptotic an antiapoptotic markers in serial skin lesion samples from patients with CTCL, and to compare th findings with those in patients with lymphomatoid papulosis (LyP). Thirty-four skin samples were obtained from 12 patients with CTCL at the time o diagnosis and at a mean of 1.6, 3 and 6 years later. The patients received psoralen plus ultraviolet (PUVA), electron beam or cytostatic treatments. In addition, fresh post-treatment samples fro three patients with CTCL undergoing PUVA therapy were obtained. For comparison, skin biopsies o five patients with LyP were studied. Immunohistochemical demonstration of the expression of th following markers was performed on formalin-fixed skin sections: Fas (CD95), Fas ligand (FasL) bcl-2, granzyme B, the tumour-suppressor protein PTEN and the effector caspase, caspase-3. Th malignant cells were identified morphologically, and apoptotic cells were identified with th terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method on parallel sections. In untreated CTCL lesions, apoptotic lymphocytes were extremely rare, and no increase in the number of apoptotic cells was observed after any of the treatments used. In LyP, apoptotic cell were more frequent, comprising on average 5% of the infiltrate. The apoptosis-associated marker Fas, FasL, caspase-3 and granzyme B were expressed by morphologically neoplastic cells in CTCL and by large atypical cells in LyP, with no significant differences. However, only a few reactive cell in CTCL infiltrates expressed granzyme B while about 10% of the corresponding cells were positive in LyP. The expression of antiapoptotic bcl-2 was more frequent in CTCL than in LyP, while PTE expression was high in both instances. The number of bcl-2 + cells tended to decrease after therapy When comparing the findings between the first and the last samples, a decrease in the number of bcl-2+ cells and an increase in Fas+ cells was associated with disease progression, despite therapy, while the opposite was true for remissions. Apoptosis was found to be a rare event in CTCL lesions irrespective of precedin therapy During patient follow-up, no significant differences in the expression of apoptotic marker was observed while in most cases a lower level of antiapoptotic bcl-2 expression was observed after all types of therapies and in association with disease progression when compared with high expression in the untreated lesions. The absence of apoptosis and high expression of bcl-2 together with a low expression of apoptosis-inducing granzyme B in the reactive lymphocytes in CTC could explain the chronic nature of the disease and the poor response to therapy, while th more frequent occurrence of granzyme B and apoptosis together with a lower level of expressio of bcl-2 by the large atypical cells in LyP could contribute to the favourable outcome of the latter.

Hand and foot PUVA soaks: an audit of the Massachusetts General Hospital's experience from 1994 to 1998.

Palmoplantar psoriasis and eczema can be chronic recalcitrant dermatoses. Oral psoralen plus ultraviolet A (PUVA) has proven effective for these, but has a number of unwanted side effects. Previous studies have shown that regional PUVA therapy using the 8-methoxypsoralen (8-MOP) soak method followed by immediate UVA irradiation is also beneficial and well tolerated. The purpose of this audit was to determine the efficacy of hand and foot PUVA soaks by reviewing the experience of the Massachusetts General Hospital's Phototherapy Unit with this treatment modality. Phototherapy records of all patients who underwent hand and foot PUVA soaks from 1994 to 1998 were reviewed. Details regarding the treatment procedure, patient compliance, patient response and incidence of side effects were noted and summarized. Of the 56 patients who underwent at least 20 treatments, 29% had excellent response, 42% had minimal to moderate response, and 29% had poor response. The average number of treatments to induce clearing was 41. The average maximum treatment dose at clearing was 5.85 J/cm2, while the average cumulative dose to achieve clearing was 267.17 J/cm2. 8-MOP PUVA soak therapy is quite useful for chronic hand and foot dermatoses. Patient compliance must be emphasized to obtain favorable results.