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.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. OBJECTIVE: There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. METHODS: All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. RESULTS: A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). CONCLUSIONS: Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

A review on PUVA pricks-A debilitating adverse event.

PURPOSE: PUVA phototherapy is indicated for various dermatological conditions. Adverse events due to PUVA phototherapy are seen in a sizable number of patients and can result in therapy cessation. This review will focus on PUVA pricks, an adverse event first reported by Tegner in 1979. METHODS: Articles were retrieved from PubMed starting from January 1979 until February 2021 yielding 1228 unique articles. Articles were included when they described individual patient characteristics, and patients were treated with PUVA therapy. RESULTS: After screening, 33 patients were extracted from 9 articles, published between 1979 and 2005. CONCLUSION: PUVA pricks are paroxysmal episodes of burning or prickling pain, akin to peripheral neuropathy of the unmyelinated C-fibers. Increased excitability of TRPV1 and TRPA1 channels while under PUVA therapy might be a contributing factor. Effective topical treatment options for PUVA pricks are capsaicin 8% cream, urea 4%, or petrolatum emollients. Antiepileptics such as phenytoin, clonazepam, and gabapentin are acceptable oral treatment options. A possible role of N-acetylcysteine in the prevention of PUVA pricks is discussed, though further research is required.

Risk of cutaneous carcinogenesis with phototherapy in Indian subpopulation: A 10-year analysis and a review of literature.

Phototherapy is an extremely effective and established therapeutic modality in a variety of dermatological disorders. However, there has been a constant concern with respect to its long-term usage as some of the studies have identified the risk of cutaneous malignancy associated with phototherapy. The carcinogenic potential of PUVA has been demonstrated in most US studies; however, the studies done on Asian and Arabian-African population have not corroborated similar findings, thus suggesting that the darker skin may confer protection against the development of cutaneous malignancy following phototherapy. The main aim of the present study was to assess the safety of phototherapy (bath PUVA and NBUVB) in Indian population (Fitzpatrick skin types IV and V) with respect to its carcinogenic potential and to determine the maximum cumulative dose that our patients could tolerate without developing any untoward complications such as cutaneous malignancy. All patients who received phototherapy between January 2006 and October 2016 were enrolled in the study. Details such as cumulative dose, number of phototherapy sessions received, indication for phototherapy, adverse effects such as pigmentary changes, new growths on the skin surface following the therapeutic sessions were entered in a predesigned proforma. This ambispective study had 1300 patients who had received phototherapy over a period of 10 years. A total of 929 patients had received PUVA, and the remaining 371 patients had received NBUVB for various dermatological indications. The average follow-up period for PUVA was 3 years and 6.5 years for NBUVB. The maximum cumulative dose of UVA and UVB that could be safely administered in our patients was 2085 J/cm2 and 1985 mJ/cm2, respectively. None of our patients developed any features of cutaneous malignancy during their follow-up. Both bath-PUVA and NBUVB are safe and efficacious in treating patients of darker skin types (IV and V). The risk of developing cutaneous malignancy is negligible in this subset of patients. However, more studies need to be done on the Asian population to substantiate the same.

Clinical Trial of High-Dose Pegylated-Interferon-Alfa-2b Combined With Phototherapy in Advanced Stage Mycosis Fungoides.

The combination of Interferon-α-2b (IFN-α-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.

Use of psoralen therapies obtained abroad in two children with Vitiligo.

We describe two American-born children with vitiligo, each of whom travelled to their family's ancestral home (India and Ethiopia), where their skin conditions were treated with PUVAsol, which involves the use of topical or oral psoralens followed by exposure to natural sunlight. Both children experienced modest repigmentation and were subsequently seen in our dermatology clinics. PUVAsol may be an attractive treatment option for some families, but there are potentially serious side effects including phototoxicity and cutaneous malignancy. Dermatologists should be aware of the existence of this treatment modality as well as its complications.

Efficacy and safety of bexarotene combined with photo(chemo)therapy for cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. International treatment guidelines for CTCL are widely followed in Europe and the USA. Combination therapy with therapeutic agents for CTCL and phototherapy is effective on the basis of European data. The efficacy and safety of combination therapy for Japanese CTCL patients are not established. We investigated the efficacy and safety of combination therapy with photo(chemo)therapy and bexarotene in Japanese CTCL patients. Twenty-five patients received daily oral bexarotene (300 mg/m2 body surface), followed by bath-psoralen plus ultraviolet (UV)-A (PUVA) or narrowband UV-B. Treatment results were evaluated using the modified Severity-Weighted Assessment Tool (mSWAT) and the Physician Global Assessment of Clinical Condition (PGA) up to week 24. Safety was also assessed. Twenty-four weeks after initiating treatment, the total response rate was 80.0% (mSWAT) and 84.0% (PGA). Response rates did not differ when stratified by disease stage. Number of days (mean ± standard deviation) for time to response, duration of response and time to progression determined by the mSWAT were 20.7 ± 9.62, 117.0 ± 43.0 and 163.6 ± 28.8, respectively. T-helper 2 chemokine levels in patients at stage IIA or more decreased significantly at weeks 12 and 24. All patients experienced adverse events and adverse drug reactions. Serious adverse drug reactions included sepsis, anemia and congestive cardiac insufficiency (n = 1 each). Other adverse drug reactions were of mild to moderate severity. Combination therapy with bexarotene and PUVA was safe and effective in Japanese CTCL patients.

Adverse Events Leading to Discontinuation of Phototherapy: An Observational Study.

The aim of this prospective study in a phototherapy unit was to describe adverse events (AEs) associated with discontinuation of phototherapy in a clinical setting. A total of 872 included patients received 1,256 courses of phototherapy treatment: 76.9% narrow-band UVB (NBUVB); 9.6% systemic psoralen plus UVA (PUVA); 11.4% topical PUVA; and 2.1% UVA. Approximately a fifth of the treatments (n = 240, 19.1%) were associated with AEs, the most frequent of which was erythema (8.8%). Systemic PUVA had the highest rate of AEs (32.5%). Mycosis fungoides was the dermatosis with the highest rate of AE (36.9%). A total of 216 (17.2%) patients stopped treatment: 23.6% because of AEs (4.1% of all treatments). Treatment suspension due to AEs was associated with PUVA, both topical and systemic (p < 0.001), and diagnoses of mycosis fungoides (p <0.001), palmoplantar psoriasis (p = 0.002), hand eczema (p = 0.002) and pityriasis lichenoides (p = 0.01). In conclusion, one in every 5 patients receiving phototherapy had an AE, but few stopped treatment for this reason.

[Phototoxic reaction due to solar radiation exposure in a psoriatic patient treated with PUVA therapy]. / Reakcja fototoksyczna po ekspozycji na promieniowanie sloneczne u pacjentki leczonej metoda PUVA z powodu luszczycy.

A phototoxic reaction may be induced by additional exposure to solar radiation during photochemotherapy (psoralen, ultra-violet A - PUVA treatment). A woman was admitted to Dermatology and Venereology Clinic in Lódz as an emergency case due to extensive erythematous-vesicular lesions on the skin of the lower limbs, accompanied by pain, itching and burning of the skin. The interview found that the patient was undergoing PUVA phototherapy for psoriatic lesions, with hypertension and nicotine dependence. Physical examination revealed large blisters, filled with serum and congestive erythematous lesions located on the lateral surfaces of the thighs and backs of the feet, as well as marked swelling of the lower limbs. Also, discs coated with thin scales were found on the upper and lower limbs and on the trunk. The entire body was intensely tanned. The patient was diagnosed with acute phototoxic reaction and general corticosteroids, antihistamine drugs, an antibiotic, antihypertensive drugs and topical treatment were introduced. Immunological tests were performed during the first days of hospitalization following the emergence of new blisters. Negative results ruled out bullous pemphigoid and pemphigus. Gradual clinical improvement was observed. To avoid the occurrence of acute phototoxicity during phototherapy, patients require education about the need to avoid UV exposure and to use photoprotection, when receiving UV-sensitizing treatment. Med Pr. 2019;70(6):763-8.

PUVA-induced pityriasis lichenoides chronica-like papular lesions in patients with mycosis fungoides: a clinical, histopathological and immunohistochemical study.

Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma (CTCL) with many clinical variants including papular and pityriasis lichenoides chronica (PLC)-like variants. During psoralen and ultraviolet A (PUVA) treatment of MF, PLC-like papular lesions were observed to appear. The exact nature of these lesions is not fully understood. This work aimed to study PLC-like papular lesions arising in MF patients receiving PUVA therapy clinically, histopathologically and immunohistochemically (using monoclonal antibodies against CD4 and CD8) and to compare them with lesions in classic PLC patients. Fifteen MF patients with PLC-like papular lesions arising during PUVA treatment were included and 15 patients with classic PLC served as controls. While the extent of these lesions significantly correlated with their duration (p < 0.05), it showed no significant correlation with the TNMB stage of MF, number of phototherapy sessions or cumulative UVA dose at which they started to appear. The response status of MF to PUVA did not affect their development. Compared to classic PLC, these lesions showed significantly more acute onset (p = 0.003). None of these lesions showed histopathological features essential to diagnose papular/PLC-like MF and no significant difference existed with regard to their histopathological and CD4/CD8 phenotypic features compared to classic PLC. Papular lesions mimicking PLC in MF patients receiving PUVA mostly represent an upgrading reaction with possible good prognostic implication.

Incidence of non-melanoma skin cancer in patients treated with psoralen and ultraviolet A therapy. / Incidencia de cáncer cutáneo distinto del melanoma en pacientes tratados con PUVA oral.

INTRODUCTION: Studies reporting incidences of non-melanoma skin cancer (NMSC) are heterogeneous, depend on the geographic area of the studied population and are often short-term. The aim of this study is to determine the incidence of NMSC in patients treated with oral PUVA therapy in the Mediterranean area. MATERIAL AND METHODS: A retrospective, observational study was carried out with a sample of 234 patients treated with systemic PUVA between 1982 and 1996, carrying out a historical follow-up until May 2017. The incidencedensity rate of CCNM (crude and adjusted) was calculated by direct standardisation. The incidence of CCNM was compared with that reported in the general population in a similar geographical area. RESULTS: 50 neoplasms were diagnosed in 22 patients. The prevalence of CCNM in patients treated with phototherapy was 10.3%. The mean follow-up time was 21 years. The crude-adjusted incidence density rate of CCNM was 554.4-183.9 cases/100,000 treated patients per year. The crude-adjusted incidence density rate of basal cell carcinoma was 352.3-111.2 cases/100.000 patients and of squamous cell carcinoma was 229-77.7 cases /100,000 patients. CONCLUSION: PUVA therapy is associated with an increased risk of CCNM inthe Mediterranean population.

Photoonycholysis: new findings.

First described in 1961, photoonycholysis (PO) is a rare nail alteration that may result from drug intake, from topical aminolevulinate photodynamic therapy or from photosensitive conditions such as porphyria or pseudoporphyria. Spontaneous PO is rare. This review updates the numerous causes of PO and highlights some new ways producing this condition. Four different types of PO are clearly recognized without relationship with the responsible drug. An updated list of potential inducing drug is provided. Some practical points on PO have been raised. The inability to reproduce photoonycholysis experimentally should be emphasized, and the pathogenesis of PO still needs to be clarified.

Persistent Keratoses in Vitiligo.

The occurrence of keratoses in patients with psoriasis under treatment with psoralens and ultraviolet A (PUVA) has been described as an entity called PUVA keratosis. Similar lesions were seen later in patients with vitiligo under the same treatment. We describe the presence of distinct keratoses in the vitiligo lesions of three women patients from Rio de Janeiro, Brazil. The lesions started after PUVA treatment with total body irradiation, cabin or topical, and persisted long after the therapy was finished. All patients presented small rounded keratotic papules on achromic areas of the feet. Biopsies showed mild acanthosis, compact orthokeratotic hyperkeratosis, and hypergranulosis with increase of stratum granulosum layers or size increase of keratohyaline granules. Inflammatory infiltrate was sparse or absent. Cytologic atypia was not observed. Histologic features were compatible with reactive keratosis. None of the patients had a history of previous actinic keratosis or non-melanoma skin cancer and had been treated before with PUVA therapy either orally or topically; however, lesions occurred only in areas exposed to sunlight and persisted for long periods, even without treatment with PUVA or narrowband ultraviolet B (NB-UVB). The authors discuss whether these lesions can be considered as PUVA keratosis or if the sun exposure may have played an important role in the reported cases.

Adverse Medical Conditions Across Treatment Options in Patients With Psoriasis: A Claims-Based Analysis

Objective: To assess the real-world risk of developing adverse medical conditions (AMCs) among patients with psoriasis treated with biologic therapies or conventional systemic/topical therapies (CST/topical). Methods: Adult patients with psoriasis were identified from the Truven MarketScan US claims database (2008 Q3­2015 Q3) and classified into cohorts based on treatment initiated on the index date (adalimumab [ADA], etanercept [ETN], ustekinumab [UST], infliximab [IFX], or CST/topical). Incident AMCs were identified while on treatment from diagnoses recorded in medical claims and included abnormal test results, infections, mental disorders, cardiovascular disease, malignancies (skin and non-skin), and respiratory disease. Cox proportional hazards models were used to compare AMC risk for (1) ADA, ETN, and UST (separately) vs CST/topical, and (2) ADA vs other biologic therapies (ETN, UST, and IFX combined). Regressions were adjusted for age, gender, region, insurance plan type, year, Charlson comorbidity index, and prior AMCs; and based on stepwise selection, comorbidities, specialist encounters, and frequently prescribed treatments. Results: A total of 42,981 patients were identified (ADA: 5,197; ETN: 3,311; UST: 1,370; IFX: 187; CST/topical: 32,916). Across cohorts, median age was 46­50 years, 46.2%­53.1% were female, and median follow-up duration was 3.3­7.9 months. For all cohorts, infection was the most frequent AMC (28.7%­41.8%). Compared with CST/topical, ADA, ETN, and UST were associated with a lower risk of infections (adjusted hazard ratio [aHR]: 0.93, 0.92, and 0.86, respectively, all P<0.05). ADA was associated with a lower risk of malignancies (aHR: 0.71, P<0.05), and ETN was associated with a lower risk of respiratory disease (aHR: 0.80, P<0.05). Compared with biologic therapies, ADA was not associated with higher risk of AMCs. Conclusions: Compared to CST/topical, biologic therapies were associated with similar or lower risk of AMCs. Comparison between ADA and other biologic therapies suggests a similar safety profile with respect to the studied AMCs.

Ampollas inducidas por PUVA. Presentación de 5 casos / Blisters Induced by PUVA: A Report of 5 Cases

Las ampollas secundarias al tratamiento con PUVA son un efecto secundario de la fotoquimioterapia poco descrito en la literatura científica. Se caracteriza por la aparición espontánea de ampollas asintomáticas localizadas fundamentalmente en los miembros inferiores, que se resuelven sin necesidad de tratamiento. El diagnóstico diferencial debe plantearse con una reacción fototóxica, con la pseudoporfiria y con el penfigoide ampolloso inducido por PUVA. Presentamos 5 casos de ampollas secundarias a la terapia PUVA, con el objetivo de dar a conocer las características clínicas e histológicas de dicha entidad. Su correcto diagnóstico evitará la interrupción del tratamiento, así como la realización de procedimientos diagnósticos y terapéuticos innecesarios

Blíster associated with PUVA treatments are an adverse effect of photochemotherapy that has been reported in the literature. Asymptomatic blisters appear spontaneously mainly on the lower limbs and resolve without treatment. The differential diagnoses to consider include a phototoxic reaction, pseudoporphyria, and PUVA-induced bullous pemphigoid. We describe the clinical and histologic features in 5 cases of blistering secondary to PUVA treatment. If this adverse effect is accurately diagnosed, photochemotherapy need not be interrupted, and unnecessary diagnostic procedures and additional treatments can be avoided

Ampollas durante la fototerapia / Blistering During Phototherapy

No disponible

Blisters Induced by PUVA: A Report of 5 Cases. / Ampollas inducidas por PUVA. Presentación de 5 casos.

Blisters associated with PUVA treatments are an adverse effect of photochemotherapy that has been reported in the literature. Asymptomatic blisters appear spontaneously mainly on the lower limbs and resolve without treatment. The differential diagnoses to consider include a phototoxic reaction, pseudoporphyria, and PUVA-induced bullous pemphigoid. We describe the clinical and histologic features in 5 cases of blistering secondary to PUVA treatment. If this adverse effect is accurately diagnosed, photochemotherapy need not be interrupted, and unnecessary diagnostic procedures and additional treatments can be avoided.

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.

Malignancy Risk and Recurrence with Psoriasis and its Treatments: A Concise Update.

Psoriasis is a common inflammatory cutaneous disease that affects approximately 120 million people worldwide. Systemic treatments have significantly improved disease burden, but concerns persist regarding their association with increased risk of malignancy. Patients with psoriasis have a slightly elevated baseline risk of lymphoproliferative diseases. Studies on methotrexate and cyclosporine, as well as older biological agents such as tumor necrosis factor inhibitors, have found no increased risk of non-cutaneous solid tumors; however, positive associations between cutaneous squamous cell carcinomas and certain therapies have been found. There is conflicting evidence regarding the risk of lymphoma and melanoma. Further studies are needed to determine the long-term safety of newer psoriasis treatments (interleukin [IL]-12/23, IL-17, Janus kinase 1/3, and phosphodiesterase-4 inhibitors), specifically their safety in patients with a history of cancer. This review summarizes the most recent studies on malignancy risk from psoriasis, and its treatments in patients and cancer survivors, with the highest available level of evidence.