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Objectives To evaluate long-term outcomes, impact of maintenance therapy and potential curability of patients with mycosis fungoides (MF) treated with psoralen plus UV-A (PUVA) monotherapy. Design Single-center retrospective cohort analysis. Setting Academic referral center for cutaneous lymphoma. Patients A total of 66 of 104 patients with clinical stages IA to IIA MF who achieved complete remission (CR) after PUVA monotherapy between 1979 and 1995. Main Outcome Measures Kaplan-Meier actuarial survival and disease-free survival curves were compared between stage IA and IB/IIA cases. Patients were stratified into relapse and nonrelapse groups based on whether their MF relapsed during study follow-up. Baseline characteristics and treatment were compared between these groups. Results Median follow-up time was 94 months (range, 5-242 months). Thirty-three patients maintained CR for 84 months (range, 5-238 months), and 33 patients experienced relapse with a median disease-free interval of 39 months (range, 2-127 months). There was no significant difference in baseline characteristics between patients in the nonrelapse and relapse groups. Those in the nonrelapse group received a higher cumulative dosage to CR ( P = .03) and required longer treatment periods to achieve CR ( P = .03). Disease-free survival rates at 5 and 10 years for all patients with stage IA were 56% and 30%, respectively, and for stage IB/IIA, 74% and 50%. Actuarial survival rates at 5, 10, and 15 years were 94%, 82%, and 82%, respectively, in patients with stage IA, and 80%, 69%, and 58% in patients with stage IB/IIA. The overall survival rate for the nonrelapse and relapse groups did not show any statistical difference. One third of the patients developed signs of chronic photodamage and secondary cutaneous malignancies. Conclusions Psoralen UV-A is an effective treatment for MF, inducing long-term remissions and perhaps in some cases disease “cure.” Thirty percent to 50% of patients remain disease free for 10 years, but late relapses occur. Long-term survival is not affected by relapse status, and the risk of photodamage needs to be measured against the possible benefit of greater disease elimination.

Objective To summarize the current state of evidence for combination topical and systemic therapies for mild to severe psoriasis. Data Sources We performed a systematic search for all entries in PubMed, CINAHL, Cochrane Review, and EMBASE related to combination treatments for psoriasis through July 2010. Study Selection We included randomized controlled trials that reported proportion of disease clearance or mean change in clinical severity score (or provided these data through communication with study authors) for efficacy of a combination treatment for psoriasis compared with 1 or more corresponding monotherapies. Data Extraction Study data were extracted by 3 independent investigators, with disagreement resolved by consensus. The proportion of patients who achieved clearance, definition of clearance, means and standard deviations for baseline disease symptom score and final disease symptom score, and major design characteristics were extracted for each study. Data Synthesis Combination treatments consisting of vitamin D derivative and corticosteroid, vitamin D derivative and UV-B, vitamin A derivative and psoralen–UV-A, vitamin A derivative and corticosteroid, vitamin A derivative and UV-B, corticosteroid and hydrocolloid occlusion dressings, UV-B and alefacept, and vitamins A and D derivatives were more effective than 1 or more monotherapies using the likelihood of clearance as the outcome. Blinding status and potency of the corticosteroid treatment used were significant sources of heterogeneity between studies. Conclusions The results demonstrate the need for additional long-term trials with standardized outcome measures to evaluate the efficacy and adverse effects of combination therapies for psoriasis and highlight the possible effects of trial design characteristics on results.

Background Stiff skin syndrome is a sclerodermalike disorder that presents in infancy or early childhood with rock-hard skin, limited joint mobility, and mild hypertrichosis in the absence of visceral or muscle involvement, immunologic abnormalities, or vascular hyperreactivity. Observations We describe 6 children who fit criteria for stiff skin syndrome. A review of the clinical range of this disorder and discussion of the differential diagnosis is presented. The age at onset in our cases ranged from infancy to 6 years of age. Stony-hard skin was noted mostly on the thighs, buttocks, and lower back with shoulder and arm involvement in 2 cases. There was associated hypertrichosis in 3 of 6 cases. Extracutaneous manifestations consisted primarily of joint restriction, and several patients had resulting postural and thoracic wall irregularities. Histopathologically, our cases showed areas of fascial sclerosis or showed increased fibroblast cellularity with thickened, sclerotic, horizontally oriented collagen bundles in the deep reticular dermis and/or subcutaneous septa without associated inflammation. Conclusions Stiff skin syndrome is characterized by an early, insidious onset of stony-hard skin, often with associated contracturelike joint restriction, hypertrichosis, and postural and thoracic wall abnormalities. Supportive histopathologic findings consisting of either fascial sclerosis or increased fibroblast cellularity with sclerotic collagen bundles in the deep reticular dermis and/or subcutaneous septa may help to confirm this diagnosis.

Chronic cutaneous graft-vs-host disease (GVHD) is generally classified by whether lesions have a lichenoid or sclerodermatous morphology. Other unusual clinical forms have been reported that exhibit the features of dermatomyositis and lupus erythematosus. Within a large population of individuals who underwent allogeneic stem cell transplantation because of hematologic malignancy, a group of patients was identified in whom severe and persistent eczema developed.We prospectively evaluated 10 adult patients with unexplained eczematous dermatosis after allogeneic hematopoietic stem cell transplantation. The dermatosis developed between 2 and 18 months (mean, 7.5 months) after receipt of the transplant, exhibited the typical clinical features of dermatitis, and became erythrodermic in each case. The patient group had strong risk factors for chronic cutaneous GVHD: 8 had received a transplant from an unrelated donor, 7 had evidence of extracutaneous GVHD, and 7 had a history of acute cutaneous GVHD. Sampling of lesional skin revealed the histologic features of GVHD coexisting with the changes of dermatitis. The patients were treated with topical corticosteroid and systemic immunosuppressive agents. Six patients also received psoralen-UV-A. Four patients achieved prolonged remission. Six patients died, 5 of infective complications and 1 of relapsed leukemia.The eczematous dermatosis observed represents a novel form of chronic cutaneous GVHD that we named eczematoid GVHD. Eczematoid GVHD is an aggressive, chronic dermatosis that requires substantial immunosuppression therapy to achieve control. It is associated with a poor prognosis. Although atopy can be transmitted to an individual from a hematopoietic stem cell transplant, none of the donors in this series gave a history of an atopic disorder. Therefore, other factors must be implicated in provoking the expression of an eczematous phenotype in individuals with underlying chronic graft-vs-host activity.

Objective To compare characteristics of patients enrolled in a long-term multicenter cohort trial who had used biological therapies for treatment of psoriasis with those who had not used these agents. Design Retrospective analysis of users vs nonusers of biological therapies. Setting Database from the PUVA Follow-up Study, a multicenter, 30-year study of patients originally treated with psoralen UV-A (PUVA) for moderate to severe psoriasis. Patients A total of 521 patients who completed the last cycle of follow-up of the PUVA Follow-up Study. Main Outcome Measures Demographic data, severity data (physician global assessment), type of biological therapy used, patients' opinions about their therapy, and their best treatment. Results Seventy-four of 521 patients (14%) used biological therapies: 65% etanercept (n = 48), 22% infliximab (n = 16), 11% efalizumab (n = 8), and 8% alefacept (n = 6). Users of biological therapies were younger, had more formal education, and were more likely to have had a greater extent of psoriasis at entry than the other cohort members. In 1998, those who used biological treatments were more likely than other cohort members to have been assessed as having severe psoriasis. In 2004, no significant difference was noted. Users of etanercept considered this agent to be as effective as methotrexate and more effective in clearing their skin and having fewer adverse effects than PUVA or UV-B. The proportion of patients originally enrolled in the 16 centers who had used biological agents varied greatly (0%-33%). Conclusion After short durations of therapy, patients' opinions about biological agents tended to be positive.

Objective To assess the risk of lymphoma in patients with psoriasis. Design Prospective cohort study that spans 30 years and a systematic review of the literature. Setting Sixteen university medical centers. Patients A total of 1380 patients with psoriasis who were initially treated with psoralen–UV-A (PUVA) from 1975 through 1976 and who underwent periodic interviews and physician examinations irrespective of their use of any treatment. Main Outcome Measure Incidence of lymphoma relative to that expected in the general US population (original primary end point of the study). Results The incidence of lymphoma in patients who received PUVA and were not exposed to high levels of methotrexate was comparable to that expected in the general population (incidence rate ratio, 0.85; 95% confidence interval, 0.37-1.67) but was elevated among those exposed to high levels of methotrexate (≥36 months) (incidence rate ratio, 4.39; 95% confidence interval, 1.59-12.06). Conclusion Unless exposed to high levels of methotrexate, the risk of lymphoma among members of the PUVA Follow-up Study was comparable to that observed in the general population.

To compare the efficacy of oral psoralen-UV-A (PUVA) therapy with that of narrowband UV-B (NB-UVB) therapy in patients with chronic plaque psoriasis.Double-blind randomized study.Phototherapy unit in a university hospital. Patients Ninety-three patients with chronic plaque psoriasis. Interventions Twice-weekly NB-UVB or PUVA therapy, starting at 70% of the minimum phototoxic or erythema dose, with 20% incremental increases. Patients were treated until clearance, up to a maximum of 30 sessions; those with clearance were followed up until relapse or for 12 months.Proportion of patients achieving clearance, number of treatments to clearance, and, among those with clearance, the proportion remaining in remission at 6 months.Patients with skin types V and VI had a lower rate of clearance than those with skin types I through IV (24% vs 75%; P = .001). In patients with skin types I through IV, PUVA was significantly more effective than NB-UVB at achieving clearance (84% vs 65%; P = .02). The median number of treatments to clearance was significantly lower in the PUVA group (17.0 vs 28.5; P.001). More patients treated with PUVA vs NB-UVB were reported to have erythema at some stage during treatment (49% vs 22%; P = .004), although this difference may have been due to ascertainment bias. Six months after the cessation of therapy, 68% of PUVA-treated patients were still in remission vs 35% of NB-UVB-treated patients. Conclusion Compared with NB-UVB, PUVA achieves clearance in more patients with fewer treatment sessions and results in longer remissions.

Patients with psoriasis treated with psoralen-UV-A (PUVA) are at increased risk of skin cancer; however, the exact causes of this increased incidence are not well understood. It has been suggested that PUVA may increase expression of the tumorigenic agent human papillomavirus (HPV) in skin by directly stimulating virus replication, immune suppression, or both, thereby leading to skin cancer formation.To determine whether HPV DNA prevalence in the skin is increased after long-term PUVA treatment.Screening for the presence of HPV sequences in DNA isolated from plucked body hairs of patients with psoriasis with a history of PUVA exposure and a history of skin cancer (group A), PUVA exposure and no history of skin cancer (group B), and no PUVA exposure and no history of skin cancer (group C).University hospital.Hair samples were obtained from 81 patients with psoriasis (56 men and 25 women; mean age, 52 years), including 16 in group A (mean number of PUVA exposures, 702), 35 in group B (mean number of PUVA exposures, 282), and 30 in group C. DNA was isolated from the hair samples and analyzed by polymerase chain reaction with the use of 2 nested primer systems specific for epidermodysplasia verruciformis-associated or related and genital or mucosal virus types, respectively.The rate of HPV DNA positivity was significantly higher in groups A (73% [11/15]) and B (69% [24/35]) than in group C (36% [10/28]) (A + B vs C, P =.009; chi(2) test; age adjusted). Conclusion The prevalence of HPV in the skin (hair follicles) is increased in patients with psoriasis who have a history of PUVA exposure.

Background Multimodality biological response–modifier therapy that includes photopheresis, interferon, and bexarotene is the standard of care in our institution for advanced cutaneous T-cell lymphoma with peripheral blood involvement. We added psoralen plus long-wave UV-A (PUVA) to this regimen in 5 patients with Sezary syndrome. Observations All patients responded with decreased Sezary counts, resolution of lymphadenopathy, and clearing of skin disease after the addition of PUVA. Adverse effects were well tolerated and managed via close clinical and laboratory follow-up. Conclusions The addition of PUVA to a multimodality immunomodulatory regimen in patients with Sezary syndrome can result in rapid and sustained remission of both skin and blood-borne disease. Further in vitro and in vivo studies are needed.

Objective To assess whether psychological distress affects treatment outcome in psoriasis. Design Cohort study of patients with psoriasis receiving psoralen–UV-A (PUVA) photochemotherapy. Setting Two university hospital dermatology departments. Patients One hundred twelve patients with chronic plaque psoriasis. Main Outcome Measures We assessed clinical severity of psoriasis, psychological distress, and other potential confounders of treatment outcome such as skin phototype, family history of psoriasis, and alcohol intake before starting PUVA therapy. Clinical severity of disease and response to therapy were assessed at every fourth appointment. Results Pathological or high-level worry was the only significant ( P = .01) predictor of time taken for PUVA to clear psoriasis. Event curves of time to clearance significantly differed between high- and low-level worry groups (log rank test, 6.64; df = 1; P = .01). Patients in the high-level worry group cleared with PUVA treatment at a rate 1.8 times slower than that of the low-level worry group (ExpB = 1.81; 95% confidence interval, 1.13-2.90). Fiftieth percentile time to clearance of psoriasis in the high- and low-level worry groups showed a median difference of 19 days. Conclusions Psychological distress, in the form of excessive worrying, has a significant and detrimental affect on treatment outcome in patients with psoriasis. Patients with psoriasis who are classified as high-level worriers may benefit from adjunctive psychological intervention before and during treatment. These findings provide further evidence of the existence of a brain-skin axis.

Background: Limited data exist in the literature concerning the characteristics of erythema following psoralen UV-A (PUVA) treatment using topical methoxsalen. To optimize the phototherapeutic regimen and reduceshort-andlong-termrisks,knowledgeofsuchbasic information is essential. Observations: The characteristics of PUVA erythema following 15- and 5-minute immersion in methoxsalen was determined. The PUVA erythema after 15-minute methoxsalenimmersionexhibitedabroadpeak,withthe lowest median minimal phototoxic dose (MPD) at 96, 120, and 144 hours after UV-A irradiation. Seventythree percent of subjects experienced peak erythema at 120 hours compared with only 45% at 72 hours. From the dose-response data, an increase in the erythema index of 0.025 (equivalent to the MPD) was significantly lower when determined at 120 hours after UV-A irradiation than at 72 hours (P=.03). The median maximum slope of the dose-response curve occurred at 144 hours. After 5-minute immersion, PUVA erythema displayed a broad peak from 72 hours. Erythema summation scores followed a trend similar to that of 15-minute immersion, but the intensity was significantly reduced. Conclusions:Methoxsalen–UV-Aerythemaexhibiteda broadplateaubetween96and144hours,withmostsubjectsatpeakerythemaat120hours.Reductionofmethoxsalen immersion time significantly lowered the erythemal intensity. Minimum phototoxic dose reading at 72 hours underestimates the phototoxic effect of topical methoxsalen PUVA, and a change in the MPD assessment time should be considered.

Context Each year tens of thousands of patients in the United States are treated with UV-B radiation or psoralen plus UV-A radiation (PUVA) for a variety of skin disorders. Although PUVA is generally considered more effective, it is also more toxic and more expensive. The degree of consensus among experts in prescribing these alternative treatments has not been quantified. Objectives To quantify variation among specialty clinics in the type of ultraviolet therapy used to treat specific skin conditions and assess factors associated with the use of specific treatments. Design Survey conducted during two 2-week periods in the late fall of 1994 and early spring of 1995. Setting Thirty-nine specialty clinics in 17 US geographic areas in 14 states and Washington, DC. Participants A total of 3401 patients treated with UV radiation one or more times. Outcome Measures Type of UV therapy used and indications for treatment, age, sex, number of patients treated, and geographic location of each clinic. Results The proportion of patients at each center treated with PUVA ranged from 0% to 93% (mean, 41%). Clinic size and geographic location, demographic characteristics of the patients, and diagnosis did not explain these large intercenter differences. Conclusions Among specialized clinics, there is little consistency in the use of alternative therapies, which differ substantially in safety and cost, but whose relative efficacy is not well quantified. There is a lack of consensus among experts about the circumstances in which the greater risks and costs of PUVA are outweighed by its possibly greater efficacy, especially in the treatment of psoriasis.

Background Dihydroxyacetone (DHA), a colorless sugar in "sunless" tanning lotions, binds to stratum corneum to form a UV-A–protective brown pigment. Bound DHA polymer is shed faster from hyperproliferative skin sites such as psoriatic plaques. We tested the hypothesis that selective shedding of DHA pigment during psoralen–UV-A (PUVA) treatment of psoriasis may allow higher UV-A doses, thus accelerating clearing while protecting uninvolved skin. Concurrent use of lactic acid was investigated as an aid in removing scale and residual DHA from psoriatic plaques. Observations Thirty psoriatic patients with more than 20% body surface area involvement were recruited. The 6 PUVA study groups were (1) standard American style, (2) American style plus lactic acid, (3) DHA-PUVA or "topical ultraviolet-resisting barrier to optimize PUVA" (Turbo-PUVA), (4) Turbo-PUVA with lactic acid, (5) European style, and (6) European style plus DHA. Combinations of lactic acid and European-style treatment were not studied. Each subject received up to 30 oral PUVA treatments twice weekly 3 days apart. The DHA-PUVA groups used 15% DHA lotion twice weekly. Lactic acid groups used 7% lotion daily except on treatment days. Psoriasis area and severity index scores were recorded weekly. Turbo-PUVA allowed higher UV-A exposures with minimal burns, showed faster clearing, and required fewer treatments for 90% clearing ( P Conclusions Protection of uninvolved skin by DHA during PUVA treatment allows higher UV-A exposures to be tolerated, demonstrates faster clearing, and requires fewer treatments to clear psoriasis. By reducing the total body dose received, Turbo-PUVA may also reduce long-term risks.

Objective To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen–UV-A [PUVA]) in patients with chronic plaque-type psoriasis. Design Open, nonrandomized, intraindividually controlled paired comparison study. Setting Phototherapeutic unit in a university hospital. Patients Twenty-five patients with chronic plaque-type psoriasis. Interventions Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. Main Outcome Measures Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. Results The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance ( P =.17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B ( P =.03). Conclusions Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.

Objective To assess the risk of squamous cell carcinoma (SCC) and the relation of dose to risk among groups of patients with psoriasis exposed to psoralen–UV-A (PUVA). Data Sources Four electronic databases were searched from 1984 to 1998. Study Selection In addition to the PUVA Follow-up Study, we included all English-language studies from the United States and Europe with at least 150 patients enrolled, who were followed up for at least 5 years as identified from our bibliographic search. Data Extraction A custom-designed questionnaire was used to extract data from each of the articles. For each study, if possible, we determined the incidence of basal cell carcinomas and SCCs and the incidence rate ratio of SCC among patients exposed to low-dose (we defined as 2 ) compared with high-dose PUVA (>200 treatments or 2000 J/cm 2 ). Exact methods were used to calculate the incidence rate ratios. Data Synthesis In addition to our study, we identified and reviewed 8 other studies. Overall, the incidence among patients exposed to high-dose PUVA was 14-fold higher than among patients with low-dose exposure (95% confidence interval, 8.3-24.1); a greater dose-dependent increase in risk than that observed in the PUVA Follow-up Study. Conclusion Although the incidence of SCC reported among groups of PUVA-treated patients followed up for at least 5 years varies greatly, compared with the risk in low-dose patients, long-term high-dose exposure to PUVA was consistently observed to significantly increase the risk of SCC in all studies reviewed.

Background Psoriasis vulgaris can be effectively treated with trimethylpsoralen (TMP) bath PUVA therapy (psoralen plus UVA), but no data exist on the extent to which psoriatic pathology is affected by this treatment, or on its cellular mechanism of action. Observations Eleven patients with recalcitrant psoriasis vulgaris were treated with TMP bath PUVA therapy and observed through clinical and histological measures. Clinical resolution of psoriasis was achieved in 10 of 11 patients. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 90% of individuals treated with TMP bath PUVA. Epidermal acanthosis was reduced by 40% at 2 weeks and 66% by the end of treatment. Epidermal improvement correlated best with reduction in intraepidermal T lymphocytes, which were reduced by 76% at 2 weeks of treatment and 93% at the end of treatment. Furthermore, following TMP bath PUVA therapy, the numbers of epidermal CD1a + Langerhans cells were markedly reduced, and CD86 + cells were eliminated. Through in vitro assays, TMP was found to be about 10000-fold more active as a lymphotoxic agent compared with 8-methoxypsoralen (8-MOP). Additionally, at physiologic concentrations, lymphocytes were killed more readily by TMP PUVA (TMP plus UVA) than were keratinocytes. Conclusions Treatment with TMP bath PUVA was effective in treating moderate to severe psoriasis, even in darker pigmented individuals. It is likely that this treatment ameliorates psoriasis through direct effects on activated leukocytes in lesional skin.

The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects Of PUVA therapy.

Oral psoralen plus UV-A (PUVA) therapy was originally developed for the treatment of vitiligo. 1,2 With the introduction of potent UV-A irradiation sources between 1972 and 1974, UV-A irradiation following psoralen application was found to be a highly efficient therapy for proriasis. 3-5 The acronym PUVA was created and the potential use of PUVA was investigated in a large spectrum of different inflammatory and neoplastic skin diseases. 6-8 Psoralen plus UV-A has profoundly influenced the therapeutic concepts of dermatology, as demonstrated in the recent review by Honig et al. 8 An alternative approach, psoralen bath plus UV-A therapy (PUVA bath therapy) that avoids the adverse effects associated with oral PUVA therapy has increasingly been used during recent years. Psoralen bath plus UV-A therapy is not simply a technical variant of photochemotherapy; it is obviously superior to oral PUVA, at least for some indications, and it has considerably enlarged the spectrum of diseases responsive to photochemotherapy.

To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar.Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist.General clinical research center of a university hospital inpatient unit.Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study.Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression).Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment.Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.

The mechanism by which oral psoralen with UV-A (PUVA) stimulates melanocyte proliferation in vitiligo is unknown. This study was conducted to examine the hypothesis that it does so by stimulating the release of growth factors that stimulate melanocyte proliferation.We examined the effect of serum samples obtained from patients with vitiligo before and following 2 and 4 months of PUVA therapy, and from non-PUVA-treated patients with vitiligo and normal individuals on the growth of melanocytes in vitro.Outpatient clinic in referral center.The study was conducted on serum samples obtained from 18 patients with vitiligo, 8 of whom were treated with PUVA, and from 10 normal individuals.Treatment with PUVA.Ability of serum samples to stimulate the growth of melanocytes in culture.Proliferation of melanocytes in serum collected after 4 months of PUVA therapy was on the average 3-fold greater than that in serum samples collected from the same patients prior to therapy with PUVA. This circulating growth factor was absent in serum samples of non-PUVA-treated patients with vitiligo and normal individuals. The effect was nonspecific, as it also stimulated the proliferation of fibroblasts.These findings suggest that PUVA treatment results in the release into the circulation of growth factor(s) that can stimulate a proliferation of melanocytes and of other cells. This could account for the repigmentation of vitiligo by PUVA treatment. As the growth factor(s) also stimulated the growth of other cells, it could also explain the thickening of the epidermis that occurs following exposure to UV light.

REPORT OF A CASE A 4-month-old female infant presented with 1 month of blisters on her chin and temple that progressed to diffuse blistering. Blisters formed if the infant was scratched or rubbed (Figure 1). She had numerous bullae and erosions on her trunk and extremities and her skin had a diffuse doughy texture. The patient had no wheezing or gastrointestinal symptoms and was otherwise healthy. The family history was negative for any dermatologic, gastrointestinal, or hematologic diseases. One month of antibiotic therapy resulted in no change and bacterial blister culture results were negative. Biopsy samples showed a dense dermal infiltrate of mast cells consistent with mastocytosis. A Leder stain accentuated the mast cell granules. Evaluation for systemic involvement, including bone marrow biopsy and aspiration, computed tomography of the abdomen, a bone scan, and an upper gastrointestinal tract series with small-bowel follow-through, produced normal results. Initial treatment consisted of topical

Oral psoralen with UV-A (PUVA) photochemotherapy is known to cause cutaneous malignancies and has been associated with cutaneous immunosuppression. Human papillomavirus infection has also been associated with cutaneous malignancies and with immunosuppressed individuals. We therefore sought evidence of human papillomavirus infection in a patient with a long history of PUVA therapy and multiple cutaneous malignancies.During a 15-year period, an otherwise healthy patient with psoriasis who had undergone a 10-year course of PUVA photochemotherapy developed 13 squamous cell carcinomas, eight lesions diagnosed as "squamous cell carcinoma vs keratoacanthoma," 14 other keratoacanthomas, six basal cell carcinomas, one melanoma in situ, and 18 other keratinocytic dysplasias. Twenty-two of the 30 lesions tested for human papillomavirus DNA by polymerase chain reaction were positive for type 16/18, including six of the seven basal or squamous cell carcinomas tested.We hypothesize that PUVA therapy-induced immunosuppression may play an important role in PUVA-related carcinogenesis by affecting the extent and pathogenicity of human papillomavirus infection.

Objective To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients. Design A registry inception cohort was used. Setting Thirteen dermatology departments in Spain participated. Patients A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included. Exposure Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease. Main Outcome Measures Serious adverse events as defined by the International Conference on Harmonization were evaluated. Results In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs. Conclusions Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.

Twenty-eight subjects were phototested to determine their erythemal responses to oral methoxsalen with UV-A and UV-B irradiation. Skin pigmentation was measured by skin reflectance at 550 and 660 nm before irradiation. The smallest UV radiation dose to produce erythema (minimal phototoxic dose and minimal erythema dose, respectively) was determined. The serum concentration of methoxsalen was measured at the time of UV-A irradiation.There was a positive correlation between skin pigmentation and both 72-hour minimal phototoxic dose and 24-hour minimal erythema dose. No correlation was demonstrated between methoxsalen serum concentration and minimal phototoxic dose. The combination of skin pigmentation and methoxsalen level did not give a better prediction of minimal phototoxic dose than skin pigmentation alone.Skin pigmentation measurements can be used to predict the minimal phototoxic and erythema doses. Skin pigmentation measurements are easy to perform and should be included in both phototherapy and photochemotherapy to improve the efficiency and reliability of the treatment.

BACKGROUND AND DESIGN--The optimal therapy for the mycosis fungoides type of cutaneous T-cell lymphoma has yet to be determined. Based on recent reports on the efficacy of high-dose interferon alfa in cutaneous T-cell lymphoma, we chose to test the hypothesis that systemic adjunctive therapy with low-dose interferon alfa along with psoralen and long-wave UV-A radiation (PUVA) could decrease the amount of PUVA necessary to achieve the best response, as well as improve the therapeutic effect of PUVA. Five patients with cutaneous T-cell lymphoma (mycosis fungoides type) were initially treated unsuccessfully with PUVA alone (three times a week for at least 3 months); PUVA was stopped, patients' diseases were re-staged, then interferon alfa (3 x 10(6) U/d for 1 week, then 6 x 10(6) U/d for 1 week) was initiated 2 weeks prior to restarting PUVA. Responses to treatment were graded as complete remission (skin clear, or negative biopsy specimens of remaining dermatitic lesions), partial remission (50% improvement), progression (25% worsening), or no change (failure to qualify for other categories) at 4, 8, 12, and 16 weeks. OBSERVATIONS--After 3 to 5 months of treatment with PUVA thrice weekly, none of the patients treated with PUVA alone had achieved complete remission. By contrast, systemic adjunctive therapy with low-dose interferon alfa along with PUVA resulted in complete remissions in all five (100%) patients in an average of 3.2 months (in three patients, lesions were cleared by 3 months). Average of 107 additional joules (68% more) and 1.6 additional months of PUVA administered thrice weekly was required to achieve the best response attainable with PUVA alone compared with complete remissions achieved with combined interferon alfa and PUVA therapy.--These data indicate that patients with disease refractory to PUVA alone can achieve a complete remission if they restart treatment with PUVA in combination with well-tolerated low doses of interferon alfa. In addition, the duration of PUVA exposure can be reduced with the addition of low-dose interferon alfa to the conventional PUVA treatment of cutaneous T-cell lymphoma of the mycosis fungoides type in such patients.

• Background and Design.— There is an increasing concern about the long-term carcinogenic effect of oral psoralen with long-wave UV radiation in the A range (PUVA). Most follow-up investigations indicate a definite risk of squamous cell carcinoma of the skin with long-term PUVA treatment. In a recently published study of 4799 Swedish patients who had received PUVA, it was noted that 833 patients who had received trioxsalen bath or oral trioxsalen did not show any increased risk of skin cancer in contrast to oral methoxsalen. This finding has been further investigated in this study. We compared four dermatologic university clinics in Sweden with regard to the carcinogenic potential of the PUVA regimen used. One clinic used trioxsalen bath PUVA exclusively and the other three used oral methoxsalen. Information on their PUVA-treated patients was collected and linked with information from the Swedish Cancer Registry to identify individuals with squamous cell carcinoma of the skin. Results.— A total of 18 squamous cell carcinomas of the skin were reported in 2975 PUVA-treated patients until 1987. The expected number was 3.1. The center using bath PUVA only had no increased risk of squamous cell carcinoma of the skin in contrast to the three centers using oral methoxsalen-PUVA. The increased risk for male subjects from those centers varied from six to 13 times that in the general population, but for female subjects a significant increased relative risk was found only at one center. Conclusion.— In this preliminary report, PUVA treatment with trioxsalen bath seems to be less carcinogenic than the oral dosage. However, differences in the patient populations might also have affected the outcome of the study. More information on this field is needed. (Arch Dermatol.1992;128:1341-1344)

Adjunctive topical corticosteroids are often administered with UV-B phototherapy or oral psoralen plus UV-A (PUVA) photochemotherapy for the treatment of psoriasis. Five studies comparing PUVA alone with PUVA and topical corticosteroid preparations showed more rapid rates of clearing and a smaller total UV-A exposure with the latter regimen. However, one study demonstrated a higher relapse rate in association with corticosteroid use. Further studies to better define these risks are recommended. Six of seven reports evaluating the use of topical corticosteroid preparations with UV-B phototherapy failed to demonstrate an advantage to this regimen when compared with UV-B phototherapy alone. Therefore, the use of a topical corticosteroid preparation with UV-B phototherapy for the treatment of psoriasis is not recommended.

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.

Because oral methoxsalen and UV-A radiation (PUVA) therapy is mutagenic, concern exists about the potential for teratogenic effects resulting from the use of this therapy at the time of conception and during pregnancy. After 12.8 years of prospective study, we documented the pregnancy outcomes among 1380 patients (892 men and 488 women) who received PUVA treatments. Ninety-four men reported 167 pregnancies in their partners, and 93 women reported 159 pregnancies. For 34% of pregnancies among partners of male patients, the man received PUVA therapy near the time of conception. Nineteen percent of female patients reported exposure to PUVA at the time of conception or during pregnancy. Induced and spontaneous abortions were reported as the outcome of pregnancy more often by female than by male patients (12% vs 30%). Two congenital malformations and two stillbirths occurred, an incidence not significantly different from that expected for the general population. Although the power of our study to detect an increase in the risk of specific defects is limited, our data show no evidence to suggest that PUVA is a potent teratogen. Still, because PUVA is mutagenic, we believe it prudent for patients to avoid PUVA treatment during pregnancy whenever practical.

Various forms of treatment for generalized granuloma annulare have been employed with little success. The results of treatment with topical and intralesional corticosteroids, as well as systemic therapy with corticosteroids, salicylates, aspirin, niacinamide, and chloroquine, have been generally disappointing. We describe five patients with generalized granuloma annulare of several years' duration who were treated with oral psoralen plus ultraviolet A irradiation. Lesions were present on the extremities, buttocks, and trunk in the form of macules, papules, and plaques. One patient also had perforating lesions on her thighs. Flattening of the lesions with decreased erythema and pigmentation was noted as early as 1 month after initiation of treatment. Complete clearance was achieved in all patients. Maintenance therapy has been required, resulting in prolonged disease-free intervals. Although the mechanism of action of oral psoralen plus ultraviolet A irradiation in granuloma annulare is unclear, one possibility is selective elimination of the cells that are responsible for initiating the disease.

Several therapeutic regimens combining topical agents with UV light have been developed and widely used in the treatment of psoriasis. In this study, we compared the clinical efficacy and safety of the combined therapy of oral psoralen plus UV-A (PUVA) with calcipotriol vs PUVA therapy alone. Materials and Methods. Twenty-eight outpatients (11 women and 17 men), with mean age of 45 years (age range, 20-69 years), with moderate, chronic, stable plaque psoriasis (Psoriasis Area and Severity Index range, 8-15) were enrolled in this study. Patients had not used systemic antipsoriatic drugs or UV radiation therapy for at least 2 months and topical treatment for at least 2 weeks prior to the study. Women were included only if they were not pregnant or breast-feeding. We excluded patients receiving treatment with vitamin D or calcium, phosphate, or other drugs that might influence calcium or phosphate metabolism (eg, steroids or biphosphonate); patients needing