Bath psoralen plus ultraviolet-A photochemotherapy for chronic graft-versus-host disease: a retrospective cohort study.

BACKGROUND: Chronic graft-versus-host disease is a severe complication of allogeneic stem cell and bone marrow transplantation. First-line immunosuppressive agents, such as steroids, are used to prevent this disease; however, they have multiple side effects. Therefore, bath psoralen plus ultraviolet-A (PUVA) is an alternative second-line treatment. This study aimed to evaluate the clinical efficacy of bath PUVA for managing chronic graft-versus-host disease. METHODS: This retrospective, case-control study included 14 patients with extensive cutaneous chronic graft-versus-host disease, resistant to systemic corticosteroid, treated with bath PUVA. Major and partial responses were defined as clinical improvements of >70% and 50-70%, respectively. We analyzed the graft-versus-host disease clinical presentation and timing after allogeneic stem cell and bone marrow transplantation, bath PUVA doses, background diseases, additional treatments, and adverse effects. RESULTS: We observed eight major (three lichenoid and five sclerodermatoid) and six partial (three lichenoid and three sclerodermatoid) responses after a mean of 28 treatment sessions. After 6 to 25 months, four of the eight patients with sclerodermatoid lesions and all those with lichenoid lesions experienced relapse but responded to additional treatment cycles. CONCLUSIONS: Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.

Psoralen induces liver injury and affects hepatic bile acids metabolism in female and male C57BL/6J mice.

Psoralen is a major component of Fructus Psoraleae that could induce liver injury. In this study, C57BL/6J mice were administered with psoralen at doses of 80 mg/kg for 3, 7 and 14 days. Blood and liver samples were collected for serum biochemistry and histopathology examinations, respectively. Psoralen led to liver injury with significantly increased liver weight and liver coefficient and up regulated serum ALT, AST and TG but down regulated serum TC and TP. The expression of bile acid-associated transporters and enzymes was detected by western blot, and the results showed that psoralen significantly down-regulates the expressions of CYP7A1, CYP27A1, BSEP and OSTα protein while up-regulates the expressions of HMGCR and FASN, resulting in the obstacles of bile acid efflux in the liver. The contents of 24 kinds of bile acids in the liver were measured by LC-MS/MS, and the results showed that psoralen led to the accumulation of unconjugated bile acids in the liver, such as ALCA and CA, which were more severe in male mice than female mice. It was indicated that psoralen may disrupt the balance of bile acid metabolism by inhibiting the expression of the efflux transporter, which then leads to liver damage.

Anaphylaxis following administration of extracorporeal photopheresis for cutaneous T cell lymphoma.

Extracorporeal photopheresis is a non-invasive therapy used for the treatment of a range of T cell disorders, including cutaneous T cell lymphoma. During extracorporeal photopheresis, peripheral blood is removed from the patient and the white blood cells are separated from whole blood via centrifugation. The white blood cells are exposed to psoralen (a photosensitizing agent) and ultraviolet A radiation, causing cell apoptosis. The apoptotic leukocytes are subsequently re-infused into the patient, resulting in the production of tumor suppressor cells and clinical improvement. Extracorporeal photopheresis is generally regarded as safe with few side effects. We report a dermatology patient who developed anaphylaxis after receiving extracorporeal photopheresis for the treatment of leukemic mycosis fungoides. We suspect that our patient's anaphylaxis resulted from exposure to an agent used in extracorporeal photopheresis.

Drug and chemical induced photosensitivity from a clinical perspective.

Drug photosensitivity is a relatively common occurrence and a range of mechanisms may be involved. Some of these mechanisms will be discussed, including the most common, that of drug phototoxicity. Different types of photosensitivity are addressed with respect to clinical presentation, mechanisms and additionally the contribution to our understanding through clinically directed investigations and regulatory requirements. Repeated controlled therapeutic use of drug phototoxicity, with psoralen-UVA (PUVA) photochemotherapy and photodynamic therapy (PDT) will also be discussed. Finally, the potential for drug-induced photocarcinogenesis will also be covered.

An observer-blinded randomized controlled pilot trial comparing localized immersion psoralen-ultraviolet A with localized narrowband ultraviolet B for the treatment of palmar hand eczema.

BACKGROUND: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen-ultraviolet A (PUVA) with narrowband ultraviolet B (NB-UVB) have been small, nonrandomized and retrospective. OBJECTIVES: To conduct an observer-blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB-UVB for the treatment of chronic hand eczema unresponsive to topical steroids. METHODS: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB-UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). RESULTS: In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention-to-treat (ITT) response rate 43%]. In the NB-UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB-UVB 9) and at 12 weeks (PUVA 3, NB-UVB 4). Changes in DLQI were similar, with improvements in both groups. CONCLUSIONS: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems - PGA, mTLSS and DLQI - as measures of treatment response, the trial demonstrated that both PUVA and NB-UVB reduced the severity of chronic palmar hand eczema.

Treatments for Cutaneous Lichen Planus: A Systematic Review and Meta-Analysis.

BACKGROUND: Cutaneous lichen planus (CLP) is an inflammatory dermatosis. Its chronic relapsing course and frequently spontaneous regression hamper the assessment of treatment effectiveness. OBJECTIVE: To evaluate the efficacy of available treatment modalities for CLP. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov registry. METHODS: We performed a systematic review of the current literature. All randomized controlled trials, nonrandomized case-control studies, and cohort studies with more than one treatment arm were included. The primary outcomes were complete response and time to complete response. The secondary outcomes were partial response, relapse, time to relapse, reduction of itch, the adverse event rate, and withdrawal due to adverse events. DATA SYNTHESIS: Sixteen studies met the inclusion criteria, of which 11 were randomized controlled trials. Most trials had a small sample size. In the rare studies in which variants other than generalized or classic lichen planus were included, they could not be analyzed separately. Body-of-evidence quality ranged from very low to moderate. Acitretin, sulfasalazine, and griseofulvin were associated with increased overall response rates in comparison with placebo. Narrow-band ultraviolet B radiation (NBUVB) was more effective than 6 weeks' low-dose prednisolone in achieving a complete response, and prednisolone was more effective than enoxaparin. Hydroxychloroquine was more effective than griseofulvin in achieving an overall response. Betamethasone valerate 0.1% ointment had comparable efficacy to calcipotriol ointment. Methotrexate was effective, with a nonsignificant difference in the complete response rate in comparison with oral betamethasone. In nonrandomized controlled trials, oral psoralen plus ultraviolet A photochemotherapy (PUVA) had comparable efficacy to a PUVA bath and NBUVB. Psoralen plus sunlight exposure (PUVASOL) and betamethasone dipropionate 0.05% cream were effective relative to a short course of oral metronidazole. CONCLUSIONS: Several effective treatment options are available for CLP. Further well-designed studies are warranted to investigate the efficacy of topical glucocorticoids-the current first-line therapy-as well as other treatment modalities, and the treatment of different variants of CLP.

The role of phototherapy in cutaneous chronic graft-vs-host disease: a retrospective study and review of the literature.

INTRODUCTION AND OBJECTIVES: Cutaneous chronic graft-vs-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Phototherapy is a therapeutic option for patients with skin involvement and for those who require high doses of corticosteroids. We analyze the cases treated in our department and review the literature. MATERIAL AND METHODS: All patients with GVHD treated with phototherapy in the dermatology department of Hospital Universitario y Politécnico la Fe in Valencia, Spain between March 2011 and October 2014 were identified. Data were gathered retrospectively. RESULTS: There were 16 patients: 10 treated with psoralen-UV-A and 6 with narrowband-UV-B. Complete response was achieved in 9 patients and partial response in 7; 2 patients with partial responses relapsed after treatment. Ten patients were able to decrease their dose of corticosteroids during treatment, and a further 3 decreased the number of other immunosuppressant drugs. No serious adverse effects occurred. CONCLUSIONS: Phototherapy is a good therapeutic option for patients with chronic GVHD with extensive cutaneous involvement, as well as for those who fail to respond to topical treatment or who have become steroid-dependent. The main benefits are that, as the treatment targets the skin, it reduces corticosteroid requirements and has a good safety profile. Treatment must be individualized and, in our experience, both the initial dose and the maximum dose per session can be lower than for other diseases.

Blue vitiligo following intralesional injection of psoralen combined with ultraviolet B radiation therapy.

A 23-year-old Chinese man presented with a 16-month history of white patches on his abdomen and neck. He had previously received an intralesional injection of psoralen along with narrowband psoralen ultraviolet B radiation (PUVB) therapy. Blue macules had appeared in and around the injection sites 1 week later. Dermoscopy revealed blue spots and reticular telangiectasia within the white patches. Histological examination revealed an absence of epidermal melanocytes and pigment in the basal layer, as well as deposition of melanophages between collagen bundles or surrounding blood vessels and appendages in the middle and lower parts of the dermis. A diagnosis of blue vitiligo was made. The blue colour faded gradually over time. Our case provides direct evidence to support the previous surmise that PUVB can contribute to blue vitiligo. To our knowledge, this is only the fourth reported case of blue vitiligo in the English literature.

Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis therapy.

Recent reports have indicated that psoriasis may be caused by malfunctioning dermal immune cells, and psoralen ultraviolet A (PUVA) is an effective treatment for this chronic disease. However, conventional topical formulations achieve poor drug delivery across patches of psoriasis to their target sites. The present study describes the development of a novel psoralen transdermal delivery system employing ethosomes, flexible vesicles that can penetrate the stratum corneum and target deep skin layers. An in vitro skin permeation study showed that the permeability of psoralen-loaded ethosomes was superior to that of liposomes. Using ethosomes, psoralen transdermal flux and skin deposition were 38.89±0.32 µg/cm(2)/h and 3.87±1.74 µg/cm(2), respectively, 3.50 and 2.15 times those achieved using liposomes, respectively. The ethosomes and liposomes were found to be safe following daily application to rat skin in vivo, for 7 days. The ethosomes showed better biocompatibility with human embryonic skin fibroblasts than did an equivalent ethanol solution, indicating that the phosphatidylcholine present in ethosome vesicles improved their biocompatibility. These findings indicated that ethosomes could potentially improve the dermal and transdermal delivery of psoralen and possibly of other drugs requiring deep skin delivery.

Severe burn on 81% of body surface after sun tanning.

We report herein the case of a 42-year-old woman who presented to the Burns Unit with 81% of her body surface severely burned following sun bathing, after applying fig leaf tea as a tanning agent. The patient was hospitalized for 13 days in a Burns Intensive Care Unit, and was discharged for an ambulatory follow-up. The treatment of such burns does not differ from any conventional treatment for heat- induced second-degree burns. The physiopathology of the phytophotodermatitis induced by such homemade tanning solutions rich in psoralen is discussed in detail.

Comparative study of systemic psoralen and ultraviolet A and narrowband ultraviolet B in treatment of chronic urticaria.

BACKGROUND: Previous success rates of psoralen and ultraviolet A (PUVA) and narrowband UVB (NB-UVB) in the treatment of chronic urticaria are reported in few studies with no previous reports on the comparable efficacy of both modalities in the disease. AIM: We aimed to compare the efficacy of PUVA versus NB-UVB in the treatment of chronic urticaria. METHODS: Twenty-four patients with chronic urticaria were included and divided into two groups: 12 patients subjected to PUVA and 12 subjected to NB-UVB. They were compared according to the urticaria Total Severity Score (TSS) before and after treatment, cumulative dose, and side effects. RESULTS: There was a statistically significant decrease in urticaria TSS in both the NB-UVB- and PUVA-treated groups after than before treatment (P < 0.05), with no significant difference between both groups regarding the percentage of improved patients and the mean decrease of urticaria TSS (P > 0.05). Gastrointestinal upset was reported at a significantly higher percentage in the PUVA-treated group than in the NB-UVB-treated group. CONCLUSION: Both NB-UVB and PUVA show comparable efficacy in the treatment of chronic urticaria with minimal reversible side effects.

DNA interstrand crosslinks induce a potent replication block followed by formation and repair of double strand breaks in intact mammalian cells.

DNA interstrand crosslinks (ICLs) are highly toxic lesions that covalently link both strands of DNA and distort the DNA helix. Crosslinking agents have been shown to stall DNA replication and failure to repair ICL lesions before encountered by replication forks may induce severe DNA damage. Most knowledge of the ICL repair process has been revealed from studies in bacteria and cell extracts. However, for mammalian cells the process of ICL repair is still unclear and conflicting data exist. In this study we have explored the fate of psoralen-induced ICLs during replication, by employing intact mammalian cells and novel techniques. By comparative studies distinguishing between effects by monoadducts versus ICLs, we have been able to link the block of replication to the ICLs induction. We found that the replication fork was equally blocked by ICLs in wild-type cells as in cells deficient in ERCC1/XPF and XRCC3. The formation of ICL induced double strand breaks (DSBs), detected by formation of 53PB1 foci, was equally induced in the three cell lines suggesting that these proteins are involved at a later step of the repair process. Furthermore, we found that forks blocked by ICLs were neither bypassed, restarted nor restored for several hours. We propose that this process is different from that taking place following monoadduct induction by UV-light treatment where replication bypass is taking place as an early step. Altogether our findings suggest that restoration of an ICL blocked replication fork, likely initiated by a DSB occurs relatively rapidly at a stalled fork, is followed by restoration, which seems to be a rather slow process in intact mammalian cells.

Efficacy and safety of non-laser, targeted UVB phototherapy alone and in combination with psoralen gel or calcipotriol ointment in the treatment of localized, chronic, plaque-type psoriasis.

BACKGROUND: Topical drugs enhance the therapeutic effects of ultraviolet (UV)-based therapy for psoriasis. However, their efficacy has yet to be established in a clinical trial. OBJECTIVES: This study aimed to compare the efficacy of targeted microphototherapy alone and in combination with psoralen or calcipotriol in the treatment of plaque-type psoriasis. METHODS: Thirty individuals, affected by plaque-type psoriasis, were treated with targeted narrowband UVB phototherapy alone (Group 1), in combination with psoralen gel (Group 2), or in combination with calcipotriol ointment (Group 3) three times per week based on predetermined minimal erythema doses for 10 weeks. RESULTS: All patients in each group completed the study. The percentages of improvement in Psoriasis Area and Severity Index (PASI) and Psoriasis Severity Index (PSI) scores were 33.9% and 38.3% in Group 1, 29.9% and 29.8% in Group 2, and 67.2% and 59% in Group 3, respectively. There was no statistically significant difference in improvement between Groups 1 and 2 (P > 0.05). Outcomes in Group 3 were found to be superior compared with those in the other groups. CONCLUSIONS: The addition of calcipotriol ointment in targeted phototherapy enhances the therapeutic effects of phototherapy in the treatment of plaque-type psoriasis.