PUVA therapy in persistent cutaneous histiocytosis: Case report and literature review.

BACKGROUND: Cutaneous and mucocutaneous histiocytosis (group C) comprise a wide variety of entities affecting skin and/or mucosae. Although they are considered as reactive proliferations, their exact pathophysiology remains unknown and, therefore, they lack a specific treatment. AIMS: The aim of this study is to review the evidence on cases of histiocytosis treated with UVB and/or UVA and to report a new case of relapsing group C histiocytosis that has been successfully treated with PUVA therapy. MATERIALS & METHODS: We have conducted a review of the literature published over the last 40 years on the treatment of histiocytosis with phototherapy in the online PubMed database. We also describe a new case of successful treatment of histiocytosis with PUVA therapy. RESULTS: Our patient was a 27-year-old man with persistent outbreaks of cutaneous histiocytosis over the previous 8 years. He responded successfully to PUVA therapy, and no relapse has been detected after one year of follow-up. DISCUSSION: Self-involution is usual in group C histiocytosis, so conservative management is usually the first approach. Relapsing cases pose a therapeutic challenge. Reported treatment options for these patients include isotretinoin, cryotherapy, immunosuppressants, low-dose chemotherapy, CO2 laser, radiotherapy, and surgery. Phototherapy and photochemotherapy have been used in a small number of patients with considerable success. The main limitation to provide firm recommendations on histiocytosis therapy is the absence of solid evidence, as the articles published are mainly case reports with a short follow-up. In our patient, despite the short follow-up we have considered photochemotherapy to be effective since no spontaneous remission had been achieved in the previous 8 years. CONCLUSION: PUVA therapy could be a safe and effective option to treat persistent cutaneous manifestations in patients with histiocytosis, although more evidence is required to support this statement.

A novel mouse model of cutaneous T-cell lymphoma revealed the combined effect of mogamulizumab with psoralen and ultraviolet a therapy.

Mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Topical or systemic treatment with psoralen, such as 8-methoxypsoralen (8-MOP), followed by ultraviolet A (UVA) irradiation (PUVA therapy) is an effective phototherapy for early-stage MF. However, the efficacy of PUVA therapy for advanced-stage MF is not satisfactory, and the ideal combination partner for PUVA therapy has not yet been found. In this study, we developed a new mouse model of CTCL in which efficacy of PUVA was detected and further evaluated the efficacy of combination treatment of PUVA and mogamulizumab, an anti-CCR4 monoclonal antibody. Cytotoxicity of PUVA therapy against HH cells, a CTCL cell line, was observed in vitro. The cytotoxicity was dependent on both 8-MOP and UVA. Using HH cells, we developed a mouse model in which HH cells were subcutaneously inoculated in the ear. In this model, PUVA therapy suppressed tumour growth with statistical significance, while 8-MOP or UVA alone did not. Combination therapy of PUVA and mogamulizumab showed greater antitumor activity than either monotherapy with statistical significance. In the histological analysis of the tumour tissue, PUVA accelerated tumour necrosis and then induced the infiltration inflammatory cells in the necrotic area, suggesting that these cells served as effector cells for mogamulizumab. This combination therapy is expected to be a beneficial option for CTCL therapy.

In situ monitoring PUVA therapy by using a cell-array chip-based SERS platform.

Psoralen ultraviolet A (PUVA) therapy has thrived as a promising treatment for psoriasis. However, overdose of PUVA treatment will cause side-effects, such as melanoma formation. And these side-effects are often ignored during PUVA therapy. Hence, in situ monitoring therapeutic response of PUVA therapy is important to minimize side-effects. Aberrant expression of tyrosinase (TYR) has been proved to be associated with melanoma, indicating that TYR is a potential target for evaluation of PUVA therapy. Herein, we reported a strategy for in situ monitoring TYR activity during PUVA therapy by using a cell-array chip-based SERS platform. The cell-array chip was used to simulate cell survival environment for cell culture. Capture of single cells and living cell analysis were realized in the isolated microchambers. An enzyme-induced core-shell self-assembly substrate was used to evaluate TYR activity in living cells during PUVA therapy. The gold nanoparticle modified with a SERS reporter, 4-mercaptobenzonitrile (4-MBN), was used as the core. In the presence of oxygen and TYR, hydroxylation of l-tyrosine occurred, leading to the reduction of silver ion on the surface of gold cores. The growth of silver shells was accompanied by the increased SERS intensity of the reporter, which is related directly to TYR activity. The detection limit for TYR activity is 0.45 U/mL. Upregulation of TYR activity was successfully monitored after PUVA therapy. Notably, real-time and in situ information of therapeutic response can be obtained through monitoring PUVA therapy by using a cell-array chip-based SERS platform, which has great potential to guide the clinical application of PUVA therapy.

Phototherapy

Abstract Of all the therapeutic options available in Dermatology, few of them have the history, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1 are currently the most common types of phototherapy used. Although psoriasis is the most frequent indication, it is used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma, and cutaneous sclerosis, among others. Before indicating phototherapy, a complete patient assessment should be performed. Possible contraindications should be actively searched for and it is essential to assess whether the patient can come to the treatment center at least twice a week. One of the main method limitations is the difficulty that patients have to attend the sessions. This therapy usually occurs in association with other treatments: topical or systemic medications. Maintaining the regular monitoring of the patient is essential to identify and treat possible adverse effects. Phototherapy is recognized for its benefits and should be considered whenever possible.

Phototherapy.

Of all the therapeutic options available in Dermatology, few of them have the history, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1 are currently the most common types of phototherapy used. Although psoriasis is the most frequent indication, it is used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma, and cutaneous sclerosis, among others. Before indicating phototherapy, a complete patient assessment should be performed. Possible contraindications should be actively searched for and it is essential to assess whether the patient can come to the treatment center at least twice a week. One of the main method limitations is the difficulty that patients have to attend the sessions. This therapy usually occurs in association with other treatments: topical or systemic medications. Maintaining the regular monitoring of the patient is essential to identify and treat possible adverse effects. Phototherapy is recognized for its benefits and should be considered whenever possible.

[UV phototherapy : UV phototherapy and photodiagnostics-a practical overview]. / UV-Phototherapie : UV-Phototherapie und Photodiagnostik ­ eine praktische Übersicht.

UV phototherapy is an essential and efficient therapeutic option in the treatment of dermatological diseases. It is an integral part of multiple guidelines and maintains its high clinical significance despite the development of new therapeutic options for systemic treatment. Due to the difficult revenue situation, the market for ready-to-use products of psoralen and UV therapy devices is constantly changing.

Maintenance Phototherapy for the Treatment of Early-stage Mycosis Fungoides.

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. Phototherapy is a first-line treatment option of early stages MF. The present study aimed at assessing the efficacy of phototherapy in Tunisian patients with MF treated with phototherapy and evaluate the efficacy of maintenance phase.

[Apremilast in the treatment of palmoplantar pustulosis : A case series]. / Apremilast in der Therapie der palmoplantaren Pustulose : Eine Fallserie.

This is a case series of 8 patients with palmoplantar pustulosis. These patients were treated with the phosphodiesterase­4 inhibitor apremilast at our psoriasis outpatient clinic at the dermatological department of the University Hospital Innsbruck and we compared and documented the clinical response using an Investigator's Global Assessment (IGA) score over several months. This disease is characterized by its strong negative impact on the quality of life in affected patients, and by its resistance to therapy and its high relapse rate. Therapy options are relatively rare or off label. Apremilast is a safe and effective therapeutic approach in palmoplantar pustulosis.

Methoxsalen-induced advanced bull's eye maculopathy.

A number of systemic medications are known to cause macular toxicity, and bull's eye maculopathy is caused by some of them like hydroxychloroquine and clofazimine. A 55-year-old female, known case of vitiligo with history of undergoing methoxsalen-ultraviolet A therapy, presented with painless defective vision in both eyes. Fundus examination and autofluorescence showed macular degeneration with bull's eye configuration. Optical coherence tomography showed perifoveal loss of photoreceptors and outer retinal thinning with foveal sparing appearing as 'flying saucer'. Multifocal electroretinogram showed pan-macular suppression of waveforms. Patient was diagnosed as case of methoxsalen-induced advanced macular toxicity. This is the first reported case of methoxsalen-induced advanced bull's eye maculopathy.

Fototerapia con Lámpara de Diodos Emisores de Luz (LED) versus Lámpara Fluorescente Estudio Clínico Cuasi-aleatorizado / Light-Emitting Diode (LED) Lamp Phototherapy versus Fluorescent Lamp Quasi-randomized Clinical Study

Introducción: Se ha establecido que la fototerapia con tecnología LED es más efectiva que la fototerapia convencional para el tratamiento de hiperbilirrubinemia neonatal al reducir el número de horas de tratamiento requerido en los recién nacidos a término y pretérmino. El objetivo del presente estudio fue realizar un estudio clínico aleatorizado con tres tipos de lámparas incluida una de prototipo. Métodos: En el presente estudio clínico con un diseño paralelo de tres grupos, participaron recién nacidos con necesidad de tratamiento por hiperbilirrubinemia, ingresados en la Unidad de Neonatología del Hospital Homero Castanier Crespo en Azogues-Ecuador. Fueron distribuidos en 3 grupos: Grupo 1 (G1) Fototerapia con lámpara fluorescente, Grupo 2 (G2) fototerapia LED comercializada (Medix®, Mediled®), Grupo 3 (G3) con Fototerapia LED de prototipo. Se mide la concentración de bilirrubinas y la diferencia de medias de su reducción en cada grupo para demostrar no inferioridad. Resultados: El peso en G1 (n=30) fue 3050 ±134 gr, en G2 (n=30): 3200 ±186; G3 (n=30): 3034 ±234 (P=0.70). La edad gestacional en G1: 39 ±1 semanas, en G2 39.1±1.1, en G3 39 ±1.1 (P=0.80). Bilirrubina en G1: 15.8 ±6.2, en G2: 14. 93 ±5.9 y en G3: 15.62 ±5.9 mg/dl. (P=0.60). Las diferencias de bilirrubina (Delta 1) pre-tratamiento y a las 24 horas de tratamiento fueron -2.4 en G1, -2.4 en G2 y -2.25 mg/dl en G3 (P=0.60). Delta 2 a las 48 horas: -4.5 en G1, -4.26 en G2 y -4.42 mg/dl en G3 (P=0.62). Conclusión: los tres tratamientos demostraron No inferioridad en el tratamiento de hiperbilirrubinemia neonatal

Introduction: It has been established that phototherapy with LED technology is more effective than conventional phototherapy for the treatment of neonatal hyperbilirubinemia by reducing the number of hours of treatment required in term and preterm newborns. The objective of the present study was to carry out a randomized clinical study with three types of lamps, including a prototype. Methods: In the present clinical study with a parallel design of three groups, newborns with need of treatment for hyperbilirubinemia, admitted to the Neonatology Unit of the Homero Castanier Crespo Hospital in Azogues-Ecuador, participated. They were divided into 3 groups: Group 1 (G1) Phototherapy with fluorescent lamp, Group 2 (G2) commercialized LED phototherapy (Medix®, Mediled®), Group 3 (G3) with prototype LED phototherapy. The bilirubin concentration and the mean difference of its reduction in each group are measured to demonstrate non-inferiority. Results: The weight in G1 (n = 30) was 3050 ± 134 gr, in G2 (n = 30): 3200 ± 186; G3 (n = 30): 3034 ± 234 (P = 0.70). Gestational age in G1: 39 ± 1 weeks, in G2 39.1 ± 1.1, in G3 39 ± 1.1 (P = 0.80). Bilirubin in G1: 15.8 ± 6.2, in G2: 14. 93 ± 5.9 and in G3: 15.62 ± 5.9 mg / dl. (P = 0.60). The differences in bilirubin (Delta 1) pre-treatment and at 24 hours of treatment were -2.4 in G1, -2.4 in G2 and -2.25 mg / dl in G3 (P = 0.60). Delta 2 at 48 hours: -4.5 in G1, -4.26 in G2 and -4.42 mg / dl in G3 (P = 0.62). Conclusion: the three treatments demonstrated non-inferiority in the treatment of neonatal hyperbilirubinemia

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.

A Perspective on the Use of NB-UVB Phototherapy vs. PUVA Photochemotherapy.

Narrowband UVB (NB-UVB) phototherapy and psoralen-UVA (PUVA) photochemotherapy are widely used phototherapeutic modalities for a range of skin diseases. The main indication for NB-UVB and PUVA therapies is psoriasis, and other key diagnoses include atopic eczema, vitiligo, cutaneous T-cell lymphoma (CTCL), and the photodermatoses. The decision on choice of phototherapy is important and NB-UVB is usually the primary choice. NB-UVB phototherapy is a safe and effective therapy which is usually considered when topical agents have failed. PUVA requires prior psoralen sensitization but remains a highly effective mainstay therapy, often used when NB-UVB fails, there is rapid relapse following NB-UVB or in specific indications, such as pustular or erythrodermic psoriasis. This review will provide a perspective on the main indications for use of NB-UVB and PUVA therapies and provide comparative information on these important dermatological treatments.

[Physical therapy of psoriasis. The modern methodological approaches].

This article describes the modern approaches to the application of physical factors for the treatment of various forms of psoriasis taking into consideration the severity of clinical manifestations and the phase of the disease, the extent of disturbances of the functional state of different organs. The principles of prescription of physiotherapeutictreatmnt are formulated taking account of the stages and forms of the disease. Special attention is paid to the high therapeutic effectiveness of ultraviolet irradiation of the skin including narrow-band UVВ (311 nm) as well as to photodynamic therapy (PUVA), intravenous laser irradiation of blood, and ozone therapy. Also considered is the spa and health resort-based treatment and peloid therapy at various stages of the pathological process. The application of the combined techniques is described with special reference to radon and hydrogen sulfide baths and microwave therapy in the patients presenting with psoriatic arthritis. Much attention is given to the effectiveness of the prescription of the spa and health resort-based treatment at the stationary and regressive stages of psoriasis. The pathogenetic mechanisms underlying the therapeutic action of the physical factors used for the treatment of patients suffering from psoriasis are discussed.

Blocking or enhancing effects of some basic emollients in UVA penetration

Abstract: 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.

Phototherapy in Atopic Dermatitis.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Currently management of AD includes avoidance of triggering factors, skin care aiming to compensate the skin barrier defects, anti-inflammatory therapy (mostly topical corticosteroids and topical calcineurin inhibitors). When these first-line approaches are unsuccessful, systemic treatment or phototherapy ought to be carried out as next line of defence. Current phototherapy modalities for AD include broadband UVB (290-320 nm), narrowband UVB (311-313 nm), UVA-1 therapy (340-400 nm), UVA therapy plus 8-methoxypsoralens (PUVA), 308 nm excimer laser (EL) and Full spectrum light (FSL).

Secondary Cutaneous Amyloidosis in a Patient with Mycosis Fungoides.

Secondary cutaneous amyloidosis refers to clinically unapparent amyloid deposits within the skin in association with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease, and mycosis fungoides. A 70-year-old woman presented with a 6-month history of asymptomatic multiple yellowish plaques on both legs. She had been diagnosed with mycosis fungoides 7 years ago and was treated with psoralen and ultraviolet A radiation (PUVA) therapy, narrow-band ultraviolet B (UVB) therapy, and acitretin for 5 years. Finally, she reached complete remission of mycosis fungoides. However, new yellowish lesions started to appear 1 year after discontinuing the phototherapy. A physical examination revealed multiple yellowish plaques on both extremities. The plaques were well circumscribed and slightly elevated. All laboratory tests were normal. A biopsy specimen showed multiple nodular deposits of eosinophilic amorphous material in papillary dermis and upper reticular dermis. The deposits represented apple green birefringence on Congo red stain viewed under polarized light. Acellular small nodules in the upper dermis consisted of randomly oriented, non-branching, 6.67~12.7 nm thick amyloid fibrils on electron microscopy. We report an interesting and rare case of secondary cutaneous amyloidosis after narrow-band UVB therapy and PUVA therapy in a patient with mycosis fungoides.

Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis.

BACKGROUND: Bath-psoralen plus ultraviolet light A (PUVA) therapy is an effective, safe, and inexpensive treatment for psoriasis. Psoriasis might be due to an unbalanced ratio of Th17 cells and regulatory T cells (Treg). The Treg functional ratio is significantly lower in patients with psoriasis compared with controls and is inversely correlated with the Psoriasis Area and Severity Index score. We previously reported that bath-PUVA therapy significantly increases the number of Treg and restores Treg function to almost normal in most patients with psoriasis. OBJECTIVES: We examined the effects of bath-PUVA therapy on three distinct Foxp3+ subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive T cells. METHODS: We enrolled 15 patients with psoriasis and 11 healthy controls. We examined aTreg, rTreg, and cytokine-secreting non-suppressive T cells in peripheral blood obtained from the psoriasis patients before and after every fifth bath-PUVA therapy session. RESULTS: Levels of aTreg, which are considered to have the strongest suppressive activity in patients with psoriasis, were significantly increased in the early bath-PUVA therapy sessions, and then diminished. Levels of rTreg were lower in psoriasis patients than in healthy controls, and increased during bath-PUVA therapy. CONCLUSIONS: Bath-PUVA therapy induced aTreg and rTreg concomitantly with an improvement in the psoriatic lesions, suggesting a mechanism for the effectiveness of bath-PUVA therapy for psoriasis patients.

Secondary Cutaneous Amyloidosis in a Patient with Mycosis Fungoides

Secondary cutaneous amyloidosis refers to clinically unapparent amyloid deposits within the skin in association with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease, and mycosis fungoides. A 70-year-old woman presented with a 6-month history of asymptomatic multiple yellowish plaques on both legs. She had been diagnosed with mycosis fungoides 7 years ago and was treated with psoralen and ultraviolet A radiation (PUVA) therapy, narrow-band ultraviolet B (UVB) therapy, and acitretin for 5 years. Finally, she reached complete remission of mycosis fungoides. However, new yellowish lesions started to appear 1 year after discontinuing the phototherapy. A physical examination revealed multiple yellowish plaques on both extremities. The plaques were well circumscribed and slightly elevated. All laboratory tests were normal. A biopsy specimen showed multiple nodular deposits of eosinophilic amorphous material in papillary dermis and upper reticular dermis. The deposits represented apple green birefringence on Congo red stain viewed under polarized light. Acellular small nodules in the upper dermis consisted of randomly oriented, non-branching, 6.67~12.7 nm thick amyloid fibrils on electron microscopy. We report an interesting and rare case of secondary cutaneous amyloidosis after narrow-band UVB therapy and PUVA therapy in a patient with mycosis fungoides.

Secondary Cutaneous Amyloidosis in a Patient with Mycosis Fungoides

Secondary cutaneous amyloidosis refers to clinically unapparent amyloid deposits within the skin in association with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease, and mycosis fungoides. A 70-year-old woman presented with a 6-month history of asymptomatic multiple yellowish plaques on both legs. She had been diagnosed with mycosis fungoides 7 years ago and was treated with psoralen and ultraviolet A radiation (PUVA) therapy, narrow-band ultraviolet B (UVB) therapy, and acitretin for 5 years. Finally, she reached complete remission of mycosis fungoides. However, new yellowish lesions started to appear 1 year after discontinuing the phototherapy. A physical examination revealed multiple yellowish plaques on both extremities. The plaques were well circumscribed and slightly elevated. All laboratory tests were normal. A biopsy specimen showed multiple nodular deposits of eosinophilic amorphous material in papillary dermis and upper reticular dermis. The deposits represented apple green birefringence on Congo red stain viewed under polarized light. Acellular small nodules in the upper dermis consisted of randomly oriented, non-branching, 6.67~12.7 nm thick amyloid fibrils on electron microscopy. We report an interesting and rare case of secondary cutaneous amyloidosis after narrow-band UVB therapy and PUVA therapy in a patient with mycosis fungoides.