Psoralen Plus UVA Therapy Research Articles

605 Phototherapy-induced IFNκ drives type I IFN induced anticancer responses in CTCL

Study of Stage I-II mycosis fungoides (MF) skin lesions from 14 patients by gene expression profiling demonstrated reduced expression of six type I IFNs compared to healthy human skin. Psoralen plus UVA therapy (PUVA) induced increased levels of type I IFNs that were associated with CD8 T cell recruitment into tumors, expression of antigen specific T cell activation genes and depletion of malignant T cells. MF skin lesions expressed significantly higher levels of two negative regulators of IFN production, IRF2 and IFI35; IRF2 levels correlated with the number of malignant T cells in skin. IRF2 is known to antagonize epithelial production of type I IFNs. Indeed, we found reduced expression of ULBP2, a marker of epithelial type I interferon production. Immunostaining confirmed reduced epidermal production of type I alpha IFNs that was reversed by PUVA therapy. IFNκ is an epithelial type I interferon induced by UVB that triggers production of other type I IFNs and is responsible for the flaring of cutaneous lupus after sun exposure. We studied human keratinocytes treated with UVA with or without psoralen. IFNκ enhanced keratinocyte production of type I IFNs and downstream interferon genes in response to UVA. IFNκ knockout keratinocytes had markedly reduced type I IFNs induction after UVA, illustrating the key role of epithelial IFNκ in boosting type I interferon production. In summary, we find that type I IFNs are markedly reduced in MF lesions, that phototherapy induces epithelial type I interferon production via INFκ and that this increase is associated with effective tumor clearance. Our results suggest other medications that induce epithelial type I IFNs, including MEK or EGFR inhibitors, may be effective therapies for CTCL.

Bath Psoralen Plus UVA Therapy Suppresses Keratinocyte-Derived Chemokines in Pathogenetically Relevant Cells

Psoriasis is a chronic inflammatory proliferative skin disease involving various types of chemokines regulating immune cell migration, localization, and activation. Bath psoralen plus UVA (PUVA) treatment is an established phototherapy for psoriasis, but its effects on chemokine levels remain unknown. We investigated the levels of 22 serum chemokines in 20 patients with psoriasis first treated with bath PUVA therapy between 2007 and 2011 in a single center and analyzed the associations between the chemokines and disease severity (PASI) before and after therapy to investigate the mechanisms of action of bath PUVA therapy. Before bath PUVA therapy, the PASI scores correlated with the serum levels of CCL17 (r = 0.581), CCL18 (r = 0.462), CCL19 (r = 0.477), and CXCL16 (r = 0.524). After bath PUVA, the serum levels of CCL17, CCL22, CXCL1, and CXCL9 were significantly decreased. Heatmap clustering and network analysis based on statistically significant Spearman correlations among the chemokines showed distinctive changes in the chemokine signature. Our findings revealed that the levels of several chemokines correlated with the disease state of psoriasis. Furthermore, bath PUVA therapy reduced the secretion of keratinocyte-derived chemokines that induce the migration of immune cells important for psoriasis pathogenesis, partly revealing the mechanism of the therapeutic activity.

Phototherapy in Atopic Dermatitis: A Systematic Review of the Literature

BackgroundPhototherapy is a treatment option for atopic dermatitis recommended by several guidelines. ObjectiveTo perform a systematic review of the efficacy of different modalities of phototherapy and photochemotherapy in moderate to severe atopic dermatitis. Material and methodsWe considered all randomized clinical trials (RCTs) performed in patients with atopic dermatitis, and accepted all outcome measures. Articles were identified via an online search of the MEDLINE (via Ovid) and Embase databases and the Cochrane Central Register of Controlled Trials. We also searched for clinical trials registered in Current Controlled Trials and in the World Health Organization's International Clinical Trials Registry Platform. ResultsTwenty-one RCTs (961 patients) were included in the qualitative analysis. Two of the trials included children and adolescents (32 patients). The efficacy of narrow-band UV-B and UV-A1 phototherapy was similar for the different outcome measures contemplated. Two RCTs assessed the efficacy of psoralen plus UV-A therapy (PUVA). No serious adverse events were described. In general, the publications reviewed were characterized by a high risk of bias and poor reporting of methodology and results. ConclusionsThere is evidence for the use of narrow-band UV-B and UV-A1 phototherapy in moderate to severe atopic dermatitis. Evidence supporting the use of PUVA in atopic dermatitis is scarce and there is little information on the use of phototherapy in childhood. For the purpose of future studies, it would be advisable to use comparable criteria and scales for the evaluation of disease severity and patients, to standardize radiation methods, and to establish a minimum follow-up time.

Modalidades de fototerapia para el tratamiento de la dermatitis atópica: revisión sistemática de la literatura

BackgroundPhototherapy is a treatment option for atopic dermatitis recommended by several guidelines. ObjectiveTo perform a systematic review of the efficacy of different modalities of phototherapy and photochemotherapy in moderate to severe atopic dermatitis. Material and methodsWe considered all randomized clinical trials (RCTs) performed in patients with atopic dermatitis, and accepted all outcome measures. Articles were identified via an online search of the MEDLINE (via Ovid) and Embase databases and the Cochrane Central Register of Controlled Trials. We also searched for clinical trials registered in Current Controlled Trials and in the World Health Organization's International Clinical Trials Registry Platform. ResultsTwenty-one RCTs (961 patients) were included in the qualitative analysis. Two of the trials included children and adolescents (32 patients). The efficacy of narrow-band UV-B and UV-A1 phototherapy was similar for the different outcome measures contemplated. Two RCTs assessed the efficacy of psoralen plus UV-A therapy (PUVA). No serious adverse events were described. In general, the publications reviewed were characterized by a high risk of bias and poor reporting of methodology and results. ConclusionsThere is evidence for the use of narrow-band UV-B and UV-A1 phototherapy in moderate to severe atopic dermatitis. Evidence supporting the use of PUVA in atopic dermatitis is scarce and there is little information on the use of phototherapy in childhood. For the purpose of future studies, it would be advisable to use comparable criteria and scales for the evaluation of disease severity and patients, to standardize radiation methods, and to establish a minimum follow-up time.

Biochemical Changes Observed After PUVA Versus PUVA Plus Methotrexate Therapy in Mycosis Fungoides Using Synchrotron Infrared Microspectroscopy

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma in which the distinction between early stage MF and other inflammatory dermatosis remains difficult. Twenty patients of early stage MF and nine patients with psoriasis and lichen planus were included in this study. Ten MF patients were treated with psoralen plus UVA (PUVA) and the other 10 MF patients were treated with PUVA plus methotrexate (MTX) until complete clinical remission. Synchrotron infrared microspectroscopy (SIRM) found that MF lesions were biochemically different compared to inflammatory diseases. After treating MF with either therapeutic modality, the lymphocytic count decreased significantly in both the epidermis and dermis (P < 0.001) but no biochemical changes were observed in the remaining lymphocytes after treatment, indicating the disease process was slowed by treatment but not eradicated. In conclusion SIRM is a promising method for distinguishing MF from other inflammatory diseases such as psoriasis and lichen planus. A significant reduction in lymphocyte count indicated that PUVA therapy is an effective treatment for early stage MF, and MTX could be reserved for more advanced cases that are not PUVA responsive. However, SIRM evidence of persistent disease suggests that maintenance therapy is recommended after clinical remission.

Principal Determinants of the Length of Remission of Psoriasis Vulgaris After Topical, NB-UVB, and PUVA Therapy

Periods of remission and of exacerbation of psoriatic lesions are common in psoriasis. We recently reported C-reactive protein (CRP) as a marker of psoriasis severity and that some patients still presented with a residual inflammation after treatment. We wondered if this residual inflammation could underlie an earlier exacerbation of psoriasis. The purpose of our study was to evaluate if there is a relationship between CRP levels, Psoriasis Area and Severity Index (PASI), and body mass index (BMI), at the end of psoriasis treatment, with the length of psoriasis remission. We followed 46 patients studied at the end of treatment, to record the length of remission; 9 of the patients were treated with topical agents, 17 with narrow-band UVB (NB-UVB), and 20 with psoralen plus UVA (PUVA). We found that the length of remission correlated with the values for PASI and CRP at the end of therapy. By performing a multiple linear regression analysis, CRP, PASI, and BMI were each significantly associated with length of remission. Patients with residual inflammation at the end of treatment presented with a significantly shorter length of remission. When considering patients grouped according to the used therapies, CRP and PASI also emerged as potential determinants of length of remission, especially in the case of patients treated with NB-UVB and topical therapy. Our data suggest that CRP and PASI are important determinants of length of psoriasis remission for patients treated with phototherapy or topical therapy. Further studies with larger groups of patients are warranted to test this hypothesis. Moreover, we propose that, by the end of the treatment, the evaluation of CRP and PASI could be important to decide, when possible, if the treatment should be continued to achieve lower CRP values and longer periods of remission.

Narrowband UVB as an effective substitute for psoralen plus UVA: lessons from a psoralen shortage

From March to August 2010, there was a shortage of encapsulated liquid 8-methoxypsoralen (8-MOP), the psoralen used for bath psoralen plus UVA (PUVA) in Toronto, Canada. Patients were forced to discontinue bath PUVA treatment and were transitioned to other therapeutic modalities, including narrowband UVB (nbUVB). A retrospective chart review was conducted of all patients who discontinued bath PUVA due to the unavailability of 8-MOP, with a focus on those who were switched to nbUVB. Sixty-three patients discontinued PUVA, 39 of whom were switched to nbUVB. Fifteen of 17 patients with mycosis fungoides (MF) who were switched to nbUVB improved, and patients with earlier-stage disease were more likely to improve. Ten of 13 (77%) psoriasis patients improved with nbUVB, including two patients whose psoriasis cleared completely. All three small-plaque parapsoriasis patients who switched to nbUVB had complete clearance of their lesions. In conclusion, nbUVB may be a suitable alternative for patients with MF, small-plaque parapsoriasis and psoriasis who cannot access PUVA therapy.

Topical steroids versus PUVA therapy in moderate plaque psoriasis: A clinical trial along with cost analysis

Background: Psoriasis is a common chronic disease. It is estimated that between US$1.6 billion and US$3.2 billion is spent per year to treat psoriasis. Objective: To compare psoralen plus UV-A (PUVA) therapy with topical steroids in moderate plaque psoriasis. Methods: In this randomized, clinical trial with cost analysis, 88 patients with moderate plaque psoriasis were recruited in two equal groups to receive either PUVA therapy or topical steroids. The induction phase was applied for 4 months and the patients were followed-up for another 3 months, while the maintenance therapy continued. Outcome, direct cost (related to medications, phototherapy, laboratory tests, and medical consultation), indirect cost (related to transportation and other extra expenditures) and total cost (direct plus indirect costs) were compared between the two groups. Results: The outcome was equally satisfactory in both groups. The indirect cost was significantly higher in the PUVA group, while the direct and total costs as well as the patients' satisfaction rate were comparable. Recurrence was significantly more frequent in the topical group. Conclusion: Although both PUVA therapy and topical steroids are equally efficient and cost-effective in moderate plaque psoriasis, the recurrence rate is higher in the latter group.

5-Methoxypsoralen plus ultraviolet (UV) A is superior to medium-dose UVA1 in the treatment of severe atopic dermatitis: a randomized crossover trial

Ultraviolet (UV) A1 and psoralen plus UVA (PUVA) are effective treatment options for severe atopic dermatitis (AD); however, their relative efficacy has not yet been determined in a head-to-head study. To compare UVA1 and oral 5-methoxypsoralen (5-MOP) plus UVA with respect to efficacy, tolerability and duration of response in patients with severe generalized AD. Forty patients were included in this randomized observer-blinded crossover trial. The patients received either 15 exposures to medium-dose UVA1 as the first treatment and, in cases of relapse, another 15 exposures to 5-MOP plus UVA as the second treatment, or vice versa. All patients were followed until 12 months after discontinuation of the last treatment. The SCORAD score was determined by a blinded investigator at baseline, after 10 and 15 treatments each and during the follow-up period. In addition, all adverse events were recorded during the whole study period. Twenty-three patients completed the crossover treatment. Both phototherapies resulted in clinical improvement; however, PUVA reduced the baseline SCORAD score to a significantly greater extent than UVA1 (mean +/- SD 54.3 +/- 25.7% vs. 37.7 +/- 22.8%; P = 0.041). The median length of remission was 4 weeks (interquartile range 4-12) after UVA1 and 12 weeks (interquartile range 4-26) after PUVA therapy (P = 0.012). PUVA provides a better short- and long-term response than medium-dose UVA1 in patients with severe AD.

Ultravioletttherapie des chronischen Handekzems

Treatment of hand eczema is dominated by the administration of topical glucocorticosteriods. If topical treatment fails, the best second-line option is ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen plus UVA) therapy is effective and has relatively few side effects. Due to the localized nature of the disease, topical PUVA therapy is preferable to systemic PUVA treatment. Among the topical methods, cream PUVA therapy is simple, safe and highly effective. Recent clinical studies have demonstrated the therapeutic efficacy of a new retinoid called alitretinoin, a 9-cis-retinoic acid. However, even this form of treatment does not lead to a complete cure in all patients. Under the primacy of multimodal treatment, UV therapy should be administered as combination therapy if oral retinoids are not sufficiently effective.

Bullous pemphigoid in a patient with psoriasis during the course of PUVA therapy: study by ELISA test

A 65-year-old woman had a history of deep vein thrombosis and depression. Psoriasis was diagnosed in 1986 and various topical and systemic therapies, singly or in combination, were prescribed: tar, topical corticosteroids, cyclosporine, etretinate, and methotrexate. Two courses of oral and one course of bath psoralen plus UVA (PUVA) therapy (cumulative dose, 467 J/cm(2)) and UVB (2.96 J/cm(2)) had been given. In January 1999, she developed a flare of generalized psoriasis. In May 1999, therapy with PUVA (8-methoxypsoralen) plus topical acetonide triamcinolone 0.1% was initiated. At the time, she was taking acenocoumarol, lorazepam, and hydroxyzine chlorhydrate. In August 1999, at session 30, when the dose of UVA was 9 J/cm(2), and the total dose was 205 J/cm(2), a bulla appeared on the dorsum of the toe and was controlled with topical antibiotics. Five further sessions of PUVA were given and a generalized itching bullous eruption appeared all over the body. PUVA was stopped and the patient was hospitalized. On physical examination, extensive psoriatic plaques plus vesicles and bullae on the normal skin and on psoriatic lesions were observed all over the body (Fig. 1). Histopathologic study of a lesion showed a subepidermal vesicle containing fibrin, neutrophils, and a few eosinophils. No sunburn cells were observed (Fig. 2). The direct immunofluorescence (DIF) test of perilesional uninvolved skin revealed immunoglobulin G (IgG) (Fig. 3) and C3 at the dermal-epidermal junction. The DIF study using the patient's skin, previously treated with 1 m NaCl, localized the IgG at both the epidermal and dermal sides of the basement membrane zone (Fig. 4). Bullous pemphigoid (BP) was diagnosed and therapy with prednisone (60 mg/day) was started. The disease was well controlled in 3 weeks. The dose of prednisone was tapered and stopped 20 months later, without any recurrence. Study of the antibodies by the indirect immunofluorescence (IIF) test, using monkey esophagus and guinea pig as substrate, was positive at a titer of 1/160 in September 1999. The titer decreased to 1/10 in January 2000, and was negative in July 2000. An enzyme-linked immunosorbent assay (ELISA) test, performed using the commercial kit MBL, which identifies antibodies directed against epitopes of the extracellular fragment NC16 of antigen 2 of BP, was positive at 15 U/mL (normal value, < 9 U/mL) in September 1999, and negative in July 2000 (Table 1).

UVA1 phototherapy for treatment of necrobiosis lipoidica

The primary cause of collagen degeneration in necrobiosis lipoidica (NL) is proposed to be immunologically mediated vascular disease. Ultraviolet (UV)A1 has been used successfully to treat scleroderma in which both vascular damage and collagen dysregulation also occur. We treated six patients with NL [(five women; mean age of 32 years (range 22-70) and mean disease duration of 2.9 years (range 6 months to 5 years)] with a high-output ultraviolet (UV)A1 2-kW filtered metal halide source (Dr Hönle; Dermalight ultrA 1) having an emission spectrum of 340-440 nm. All patients had NL on the shins, which had been unresponsive to potent topical corticosteroid therapy (n = 6) and had responded minimally or not at all to TL-01 UVB (n = 2), topical psoralen plus UVA (PUVA) soaking (n = 2) or oral PUVA (n = 1) therapy. Patients received a variable number of total exposures (15-51), given 3-5 times weekly. NL resolved completely in one patient; this patient had minimal improvement after the first course of 16 exposures, but after a further 13 exposures, resolution occurred 6 months later. Two subjects obtained moderate improvement in their overall disease severity after 15 and 24 exposures, while two had only minimal improvement after 15 and 51 exposures. The remaining patient had no improvement after 16 treatments. Patients with the shortest disease duration had the greatest response. UVA1 therapy may be of benefit for the treatment of NL as an adjuvant therapy to topical corticosteroids or as a second-line alternative to other phototherapies, and may have a superior outcome in a proportion of patients.

Successful management of a case of diffuse cutaneous mastocytosis with recurrent anaphylactoid episodes and hypertension

Rationale Diffuse cutaneous mastocytosis (DCM) is a rare form of mastocytosis characterized by a diffuse mast cell infiltration of the skin frequently associated with complications due to mast cell (MC) degranulation, which include bleeding, severe diarrhea, hypotension, and shock. Methods A 4-month-old male was diagnosed of DCM at birth. At 6-months he was admitted to the Intensive Care Unit (ICU) due to recurrent anaphylactoid episodes with hypotension, generalized erytrodermia, bullae, blistering formation, occasional bronchospasm and bleeding. Increased blood pressure, requiring antihypertensive therapy, was noted between episodes. Bone marrow study showed MC with the aberrant immunophenotype (CD2+/CD25++). Baseline total serum tryptase levels were 30.9 ng/ml and higher than 1,000 ng/ml during anaphylactoid episodes. Despite treatment with sedating and non-sedating H1 and H2 blockers, disodium cromoglycate and prednisone (for three weeks), life-threatening hypotensive episodes recurred, requiring epinephrine, mechanical ventilation and continued sedation. Twice weekly oral psoralen plus UV-A therapy (PUVA) was begun and a total dose of 40 J were delivered. Results A dramatic response was obtained after PUVA therapy with progressive decrease of hypotensive episodes and bullae formation. At 25 months, he is growing and developing well without anaphylactoid episodes, and his blood pressure is normal without therapy. The skin has markedly improved and tryptase levels are normal. Conclusions The combined use of H1 and H2 blockers, sodium cromoglycate, and PUVA was remarkably effective in this case and should be considered in cases of DCM suffering from life-threatening anaphylactoid episodes.

Oral Retinoids Reduce Risk for PUVA-Associated SCC

Patients with psoriasis often receive long-term oral psoralen plus UVA therapy (PUVA), but such therapy increases the risk for skin cancer. To assess whether oral retinoids reduce such risk, these authors studied the development of skin cancers in 135 patients, each of whom underwent PUVA therapy while taking and while not taking retinoids. Use …

Management of Polymorphous Light Eruption

Optimal management of patients with polymorphous light eruption (PLE), the most frequent photodermatosis, requires knowledge of the individual clinical course of the disease and pathogenic factors. As PLE often causes problems during leisure-time activities and holidays, resulting in a substantial loss of quality of life, prophylaxis is the most important therapeutic approach. Management of PLE must, therefore, focus on basic preventative measures and additional therapeutic approaches, depending on the clinical condition. PLE can be classified into four severity groups (mild, moderate-to-severe, severe and therapy-resistant), which are useful for determining appropriate prophylactic measurements. No specific laboratory tests are available for the diagnosis of PLE, therefore, a clinician must rely on the clinical appearance of the disorder (e.g. clinical symptoms, the location of the lesions, the relationship of the occurrence of the lesions with sun exposure and the time course of the lesions) as well as a patient's medical history in order to make a diagnosis. Basic preventative management of PLE consists of adequate sun protection comprising avoidance of sun exposure, the use of textile sun protection and the application of broadband sunscreens with high UVA protection potential. Other supportive measurements have to be managed individually and are dependent on the patient's medical history and the severity of the disease. Topical antioxidants, systemic immunomodulation, photo(chemo)therapy and systemic immunosuppression may be required in some cases of PLE. Topical antioxidants represent a new treatment approach for moderate-to-severe PLE and are an effective and well tolerated option for this patient population. Severe PLE also requires photo(chemo)therapy. Phototherapy can be in the form of 311 nm UVB or UVA1 irradiation. In cases where 311 nm UVB or UVA1 are ineffective, psoralen plus UVA (PUVA) bath therapy may be used. However, PUVA bath therapy must be used with caution because it is associated with acute and long-term adverse effects. In rare exceptions we would consider using oral PUVA therapy. However, in our outpatient department, quality of life of most patients is improved with the treatment regimens that are recommended for patients with moderate-to-severe PLE, without the need for photo(chemo)therapy.

Medical therapies for vitiligo

: There are many options available for the treatment of vitiligo, the majority of which have as their goal to restore pigment. Sunscreens not only help prevent sunburn (thus preventing the resulting Koebnerization), but they also lessen the contrast between normal skin and the vitiliginous lesions. There are two major types of sunscreens: chemical sunscreens which function by absorbing the ultraviolet B (UVB) and/or UVA and physical sunscreens which block or scatter the ultraviolet rays. Cosmetics can be used for patients with limited lesions, especially those on the face and neck. An advantage to cosmetics is their limited number of side effects and ease of application. Topical corticosteroids are another option available for treating vitiligo. Lesions on the face, neck and extremities (with the exception of the fingers and toes) appear to repigment better with corticosteroids than other parts of the body. Repigmentation may take 4 months or longer; however, it should be noted that recurrence can occur upon discontinuation. Psoralen plus UVA (PUVA) therapy, both topical and oral, is the most common medical treatment for vitiligo. PUVA therapy is usually administered once or twice a week, but not on two consecutive days. Narrow-band UVB radiation is an alternative to standard PUVA therapy, but without many of its side effects. The frequency of narrow-band UVB treatments is similar to that for PUVA therapy.

Management of vitiligo. Results of a questionnaire among dermatologists in The Netherlands.

Several therapeutic options are available for the treatment of vitiligo. Concern exists that there is no uniform approach towards the management of vitiligo among Dutch dermatologists. A written survey concerning the management of vitiligo was sent to 332 dermatologists in The Netherlands. The response rate was 86%. "Giving information and reassurance concerning the nature of disease" was regarded by most dermatologists (68%) as being the most important goal in the management of vitiligo. Only 16% of the dermatologists aimed for active treatment in vitiligo. The reported therapy choices in children resembled those of adults, except that slightly more dermatologists did not prescribe active therapy in children. Nine different therapeutic modalities were mentioned as first choice therapies. Topical corticosteroids were indicated by most dermatologists as first choice therapy (241 out of 266, i.e. 91%); however, only 2% indicated that 50% or more of the patients achieved a successful treatment; 66% found that less than 25% of the patients were successfully treated with topical corticosteroids. Only 15% of the respondents reported that 50% or more of the patients were treated successfully with narrow-band UVB. The observed response profile to broad-band UVB therapy was found to be comparable with that of narrow-band UVB. The classical therapy with oral psoralen plus UVA (PUVA) was prescribed as first choice therapy by only 12% (32 out of 266) of the dermatologists. Only 6% of these respondents observed that 50% or more of the patients achieved successful therapy using oral PUVA. The recommended maximum treatment duration for topical corticosteroids, oral PUVA, and UVB therapy was found to vary from 3 to 12 months. Most dermatologists in The Netherlands do not offer active treatment in vitiligo, probably because the estimated effectiveness of (nonsurgical) repigmentation therapy is low. In cases where treatment is prescribed, there appears to be no consensus on the choice of therapies and treatment strategies. The development of practice guidelines may be helpful in reducing inappropriate care and improving treatment outcome.

Oxyradical-mediated clastogenic plasma factors in psoriasis: increase in clastogenic activity after PUVA.

Psoriasis is a common skin disorder characterized by hyperproliferation and incomplete differentiation of epidermal keratinocytes. Psoralen plus UVA (PUVA) is one of the treatments proposed for this disease. We had reported previously that exposure of regular blood cultures from healthy donors to PUVA leads to chromosomal breakage via the formation of transferable clastogenic materials, a phenomenon inhibitable by superoxide dismutase. In the present paper we show that these clastogenic factors (CF) are also formed in vivo. The CF were found in about 50% of the psoriasis patients studied (14 out of 31). In PUVA-treated psoriasis patients, the clastogenic activity of the plasma increased significantly between the first and the last (16th) exposure to PUVA. We hypothesize that CF formation in psoriasis is similar to that in other diseases accompanied by oxidative stress, in particular chronic inflammatory diseases with autoimmune reactions such as lupus erythematosus, progressive systemic sclerosis, rheumatoid arthritis and others. Increased superoxide production by phagocytes, formation of lipid peroxidation products and release of cytokines are considered to be responsible for the superoxide-stimulating and chromosome-damaging properties of patients' plasma. During PUVA therapy, superoxide generated via the interaction of psoralen with UVA may contribute to CF formation in addition to superoxide from inflammatory cells. An increased risk of cancer and leukemia is observed in diseases accompanied by CF formation. Therefore CF may contribute to the well-known risk of photocarcinogenesis by PUVA therapy. This additional risk may be preventable by antioxidants and superoxide scavengers.

Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes: a possible mechanism of action of PUVA therapy.

The mechanism of action of psoralen plus UVA (PUVA) and photopheresis is not entirely understood. These therapies are assumed to be immunomodulating partly by gradually decreasing leukocyte viability. We investigated whether this delayed form of cell death was due to apoptosis. Untreated and treated (PUVA exposed) leukocytes obtained from six patients with systemic sclerosis and (untreated) leukocytes from healthy control individuals were studied. Qualitative gel electrophoresis and quantitative in situ nick translation analysis of DNA fragmentation was performed. Apoptosis of the treated cells did occur (gel electrophoresis) after 24 h. At t = 0 h, immediately after exposure to PUVA, there was no evidence of DNA fragmentation in the treated cells. The percentage of treated cells undergoing apoptosis was 20-55% at t = 24 h (in situ nick translation). The untreated leukocytes of the patients and the healthy individuals showed no distinctive rise in apoptotic cells. Apoptosis of the leukocytes after PUVA or photopheresis treatment might be a mechanism of action and might explain the therapeutic response.

Psoralen plus UVA protocol for compositae photosensitivity

Background: Patients allergic to sesquiterpene lactones found in Compositae plants may develop severe photosensitivity, which can result in persistent light reaction. Treatment of these exquisitely photosensitive individuals can be very difficult, often requiring hospitalization. Although some treatment regimens have used psoralen plus UVA (PUVA) therapy, no specific outpatient protocol has been established. Objective: The purpose of this study was to develop an effective PUVA outpatient regimen to treat Compositae photosensitivity. Methods: A prednisone-assisted PUVA protocol was established in which the prednisone dose was decreased weekly, and the PUVA dose was increased during the same time interval. Results: Both patients enrolled in the study experienced dramatic improvement in their previously unresponsive eruptions. Conclusions: Two men aged 66 and 80 years were subjected to this protocol. Both men had chronic photodistributed dermatitis that resolved with this treatment and in one instance has remained clear for 18 months without needing further PUVA therapy.