Management of atopic dermatitis using photo(chemo)therapy

The conclusions that may be drawn by interpreting the current literature on the efficacy of photo(chemo)therapy in the treatment of atopic dermatitis (AD) are limited by several factors including publication bias, small sample sizes, high variability of parameters used in different studies, and in particular the lack of randomized controlled trials comparing different photo(chemo)therapeutic modalities. The newer ultraviolet (UV) modalities, such as medium-dose UVA1 and narrowband (NB) UVB, with a high output and a narrow emission spectrum may be considered the probably most efficacious regimens for treating acute and chronic AD, respectively, in particular when compared to conventional broadband UV regimens. There are no prospective trials on AD patients comparing NB UVB and UVA1 with more complex regimens such as heliotherapy, balneophototherapy, psoralen plus UVA (PUVA), and extracorporeal photophoresis. Support for the role of the aforementioned regimens in the treatment of AD is generally weaker than for the newer modalities including medium-dose UVA1 and NB UVB. When photo(chemo)therapy is considered for AD patients, its use is very much dedicated by the cost-effectiveness, availability, and the practicality of attending the clinic several times a week.     

A large scale analytical study on efficacy of different photo(chemo)therapeutic modalities in the treatment of psoriasis,vitiligo and mycosis fungoides

Psoriasis, vitiligo, and mycosis fungoides (MF) are among the most frequently treated dermatological diseases by photo(chemo)therapy. The objectives are to determine which photo (chemo) therapeutic modality could achieve the best response in the treatment of psoriasis, vitiligo, and MF. The design used in this study is retrospective analytical study. The study included 745 patients' records; 293 with psoriasis, 309 with vitiligo, and 143 with early MF, treated in the Phototherapy Unit, Dermatology Department, Kasr El‐Aini Hospital, Cairo University by either psoralen and ultraviolet A (PUVA), narrow band ultraviolet B (NB‐UVB), psoralen and narrow band UVB (P‐NBUVB), broad band UVB (BB‐UVB), or broad band UVA (ΒΒ‐UVA). Data were retrieved from the computer database of the unit and statistically analyzed. In psoriasis, oral and topical PUVA and NB‐UVB were found to be equally effective, whereas oral PUVA had significantly better results than both UVA and BB‐UVB at the end of therapy. In generalized vitiligo, PUVA and P‐NBUVB had significantly better results than NB‐UVB alone. In early MF, there was no statistically significant difference between the response to oral PUVA and NB‐UVB. PUVA and NB‐UVB are good choices in patients with psoriasis and early stage MF, whereas PUVA appears the best choice in the treatment of vitiligo.     

Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. In 14 patients, an area of psoriasis and adjacent uninvolved skin were exposed to a series of UVA doses (350 ± 30 nm, 1–16 J/cm²), using an irradiation monochromator. Six other patients were similarly phototested with a series of UVB doses (300 ± 5 nm, 20–112 mJ/cm²) to both uninvolved and lesional skin. Erythema was judged visually at 72 h for psoralen–UVA, and at 24 h for UVB, and measured using a scanning laser–Doppler velocimeter. In 10 patients, PUVA therapy using high-dose UVA was subsequently given to lesional skin (8–16 J/cm² twice weekly) in addition to conventional whole-body PUVA. For psoralen–UVA, the minimal phototoxic dose within psoriasis was increased by a factor of 4 compared with non-lesional skin (P < 0.01, Wilcoxon signed-rank test). For UVB, the minimal erythema dose within psoriasis was higher than that for non-lesional skin (medians > 112 and 28 respectively, P < 0.05). Laser–Doppler measurements confirmed that the reduced erythemal sensitivity was not due to masking of response by pre-existing increased blood flux within psoriasis. In six patients, the sites subsequently treated twice weekly with PUVA, using high-dose UVA, cleared faster (median number of treatments 3), but with a similar cumulative UVA dose, compared with adjacent lesional skin treated with conventional PUVA (median number of treatments 12). This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease.     

Comparison of the relative therapeutic efficacy of 7-methyl pyridopsoralen and 8-methoxypsoralen in photochemotherapy in psoriasis treatment

A newly-synthesized, monofunctional psoralen derivative, 7-methyl pyrido (3,4-C) psoralen (MPP) was compared with 8-methoxypsoralen (8MOP) with respect to their therapeutic efficacy in photochemotherapy of psoriasis. Psoriatic lesions of six patients were treated with topical application of MPP plus UVA (MPP PUVA) or with 8MOP plus UVA (8MOP PUVA). The UVA doses used in each treatment were 7.5 or 10 J/cm² with MPP and from 1.2 to 3.6 J/cm² with 8MOP. In every patient, marked improvement was observed after 2 to 6 treatments with MPP PUVA or 8MOP PUVA. Three patients showed clearance of each psoriatic lesion treated 9 to 17 times with MPP or 8MOP PUVA. Althought MPP required much higher UVA doses than 8MOP, MPP PUVA was as effective as 8MOP PUVA in treating psoriasis. When irradiating with identical doses of UVA, MPP PUVA appeared to be less active than 8MOP PUVA. None of the patients developed any severe dermatitis reactions during 20 exposures to MPP PUVA, indicating that the probability of inducing allergic contact and photocontact dermatitis may be extremely low. Erythemogenic and pigmentogenic activities of MPP and 8MOP were also compared. The data demonstrated that 8MOP is more than 8 times as effective as MPP for both activities. With the UV doses used in this study, however, every patient produced marked pigmentation after MPP PUVA therapy. Finally, the UVA dose-dependency of MPP PUVA was studied with an additional patient. Both therapeutic and pigmentogenic effects increased as a function of the UVA dose; it appeared impossible to clear psoriasis without producing pigmentation.     

New aspects in uv and photochemotherapy

Recent data show that from a pharmacological point of view topical (cream or bath) PUVA therapy is superior to systemic PUVA. Due to a significant reduction of side effects compared to systemic PUVA, bath PUVA has now started to replace oral PUVA therapy. Narrowband UVB has proved to be superior to broadband UVB in the treatment of psoriasis and is effective for a number of dermatoses such as vitilgo, atopic dermatitis and polymorphic light eruption. UVA1 phototherapy is highly effective in the treatment of moderate to severe atopic dermatitis and sclerosing diseases of the skin. Data dealing with UVA1 phototherapy for other indications are still preliminary. High-dose UVA1 is has been widely replaced by medium-dose UVA1, as a number of studies have shown similar therapeutic efficacy of both dose regimens.     

Phototherapy: Theory and practice

Despite the development of highly effective biologics for skin diseases such as psoriasis or atopic dermatitis, UVA and UVB therapy, alone or in combination, are still essential components of various guidelines. Phototherapy is not only a first-line treatment and highly effective for a number of skin diseases, but is also economical and has few side effects. The targeted use of UVA and UVB, if necessary, in combination with the photosensitizer psoralen in the context of PUVA therapy, enables the dermatologist to effectively treat a wide variety of skin diseases. Indications for phototherapy include epidermal diseases such as atopic dermatitis, psoriasis and vitiligo, as well as photodermatoses, mycosis fungoides, graft-versus-host disease and deep dermal diseases such as scleroderma. This article reviews the physical principles, molecular mechanisms, current treatment regimens, and individual indications for phototherapy and photochemotherapy.     

Management of polymorphous light eruption : clinical course,pathogenesis, diagnosis and intervention

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.     

Treatment of persistent severe atopic dermatitis in 113 Japanese patients with oral psoralen photo-chemotherapy

Oral administration of psoralen and whole body exposure to UVA (oral PUVA) has been used for the treatment of 113 patients with severe atopic dermatitis (AD). 8-Methoxypsoralen (8-MOP) was given at a dose of 0.5-0.6 mg/kg two hours prior to UVA (3-8 J/cm2) irradiation. Patients were treated three times a week while hospitalized. Other medications which had been given before PUVA therapy were permitted. At four and eight weeks after PUVA therapy, the severity score of AD had decreased by 51% and 80%, and the cumulative doses of UVA were 51.2 J/cm2 and 115.3 J/cm2, respectively. The amounts and strength of topical cortico-steroids were decreased during PUVA therapy. No adverse effects that required discontinuation of the PUVA therapy were observed. After discharge, maintenance therapy with UVB phototherapy and/or conventional treatment of AD kept the patients in remission in the outpatient clinic. The QOL of patients was greatly improved. Photochemotherapy with oral 8-MOP can be indicated in patients with severe, widespread AD, especially if standard therapy fails. This is the first report of oral PUVA therapy in a large series of Japanese patients with AD.     

[开放获取] 长波紫外线1皮肤科临床应用专家共识（2022）

【摘要】 长波紫外线1（UVA1）在皮肤疾病治疗中已有较广泛的应用,与传统的UVA加补骨脂素（PUVA）以及中波紫外线光疗法相比,UVA1不仅穿透较深,而且无PUVA相关光毒反应等不良反应,为局限性硬皮病、特应性皮炎及蕈样肉芽肿等提供了新的治疗方法。为保障UVA1光疗的有效性及安全性,相关领域专家基于国内外临床研究数据及临床经验,在充分讨论后拟定本共识,从UVA1光谱特性及作用机制、适应证及禁忌证、治疗方案、常见不良反应与处理等方面阐述,为皮肤科临床医师提供指导意见。     

Antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro

Summary We investigated the antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro. First, Staphylococcus aureus samples were obtained using stamp agar medium from inflammatory lesions of 29 adult patients with atopic dermatitis before and after a single photochemotherapy. Therapy was oral PUVA (30 mg 8-methoxypsoralen, 8MOP plus 5 J/cm²UVA), topical PUVA (0·3% 8MOP plus 200mJ/cm²UVA) or UVB (80mJ/cm²) irradiation. The number of S. aureus on the lesions was significantly reduced, even after a single treatment with all therapies. Reductions (mean± SD) were 69·3 ± 26.9%, 76·3 ± 31·3% and 83·8 ± 18·5%. respectively. Secondly, we investigated the effect of PUVA (0·001% 8MOP plus 10, 20, 30, 40, or 50 mJ/cm²UVA) and UVB (10, 30, 50, or 100 mJ/cm²) irradiation on the proliferation of S. aureus in vitro. PUVA and UVB treatment markedly inhibited the proliferation in a dose-dependent manner. These results seem to indicate the possibility that the antimicrobial effect of UV radiation contributes to successful photochemotherapy in patients with atopic dermatitis.     

Cutaneous carcinoma and PUVA lentigines in Thai patients treated with oral PUVA

A total of 113 Thai patients who were treated with oral PUVA from 1979 to 1992 were examined for long-term cutaneous side effects of PUVA. Two psoriatic patients developed PUVA keratosis on non-sun-exposed areas. Both were skin type IV and had had phototherapy with UVB and sunlight previously. The total doses of UVA were 909 J/cm² and 242 J/cm² respectively. One psoriatic patient developed Bowen's disease. He had had a cumulative dose of UVA 2207 J/cm². He also had a past history of arsenic intake and phototherapy with UVB and sunlight. PUVA lentigines were seen in 58 patients (51.4%). It was associated with older age at starting PUVA, higher cumulative UVA dose and greater number of PUVA treatment. This study suggests that previous exposure to other risk factors is important for inducing skin cancer in populations with skin phototype III, IV and V treated with oral PUVA.     

Chronic actinic dermatitis developed during phototherapy for psoriasis

A patient with psoriasis vulgaris had been successfully treated with PUVA and UVB therapy. During maintenance phototherapy, he suddenly became photosensitive and developed eczematous eruption. Minimal response doses to UVB and UVA were extremely low--1.09 mJ/cm2 and 0.3 J/cm2, respectively. No chemical substances were identified as the responsible photosensitizer. The condition was diagnosed as chronic actinic dermatitis (CAD). PUVA therapy was unsatisfactory because it was not possible to administer an adequate dose of UVA. Oral cyclosporine, topical corticosteroid and sunscreen were used with beneficial therapeutic effects on psoriasis and CAD. As far as we know, the development of CAD during phototherapy has not been previously reported.     

Phototherapy in pediatric patients

The treatment of children with psoriasis, atopic dermatitis (AD), pityriasis lichenoides, and scleroderma poses a therapeutic problem because all therapeutic options are associated with numerous side effects. Therefore ultraviolet A and B (UVA and UVB) phototherapy is presented as a possible alternative to some of these therapies, primarily topical and systemic corticosteroids, in children. Our results in treating children with phototherapy and psoralen plus UVA (PUVA) bath phototherapy over the past 5 years are reported. UVB therapy (TL01) was used in 20 psoriatic children (6 boys, 14 girls; ages 6-14 years) during the stage of disease exacerbation and in 9 children (3 boys, 6 girls; ages 8-16 years) with pityriasis lichenoides. Combined UVA/UVB phototherapy was applied in 21 AD children (7 boys, 14 girls; ages 4-15 years). Photochemotherapy with local application of a PUVA bath was used in six children (2 boys, 4 girls; ages 9-16 years) with circumscribed scleroderma and in one girl with systemic scleroderma. All children received short courses of phototherapy with either no maintenance or short maintenance. All three therapeutic protocols resulted in a certain degree of improvement in most of the study patients. None of the patients exhibited any early phototherapy side effects. We conclude that phototherapy and PUVA bath are valuable and safe therapeutic options for selected children who do not respond to other treatments.     

The effect of antibiotics on the production of superantigen from Staphylococcus aureus isolated from atopic dermatitis

Staphylococcus aureus (S. aureus) often colonizes on the skin of patients with atopic dermatitis. It is known that superantigens which are staphylococcal enterotoxins can activate T cells without processing by antigen presenting cells. It has been suggested that activated T cells release various cytokines which may exacerbate or prolong the cutaneous inflammation associated with atopic dermatitis. Reduction of bacterial colonization from skin lesions has been reported to be effective in the treatment of atopic dermatitis. Therefore, antimicrobial therapy using antibiotics may be a treatment option for atopic dermatitis in selected patients. We examined the effect of antibiotics on the production of superantigen from S. aureus in vitro to determine the action mechanism of antibiotics in the treatment of atopic dermatitis. It was found that antibiotics with inhibitory effect on protein synthesis can suppress the production of superantigen. On the other hand, the superantigen production was not suppressed by antibiotics having either the inhibitory effect on cell wall synthesis or on nucleic acid synthesis. Levels of the suppressive effect on superantigen production by S. aureus varied with strains tested in this study. Moreover, we demonstrated that replication of DNA coding of superantigen produced by S. aureus was suppressed only by roxithromycin (ROX), which is a new macrolide. This finding suggests that ROX may have an effect at the gene level. These results suggested that the suppressive effects of antimicrobial agents that act as inhibitors of protein synthesis on superantigen production from S. aureus may be useful in the treatment of atopic dermatitis.     

Encoding a superantigen by Staphylococcus aureus does not affect clinical characteristics of infected atopic dermatitis lesions

Background Bacterial infection with Staphylococcus aureus is a known trigger for the worsening of atopic dermatitis (AD). Staphylococcal superantigens have been theorized to make a potential contribution to this worsening of AD seen with infection. Objectives We sought to assess whether encoding a superantigen by S. aureus affects the inflammatory characteristics of impetiginized AD skin lesions. Methods Fifty‐two children with clinically impetiginized lesions of AD which were positive for S. aureus were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index (EASI), and then wash fluid was obtained from the lesion for quantitative bacterial culture, and measurement of bacterial products lipoteichoic acid and staphylococcal protein A and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities and the presence of a superantigen. Results Fifty‐four per cent (28 of 52) of the staphylococcal isolates encoded a superantigen. The presence of a superantigen had no significant effect on EASI score, amounts of bacterial products or inflammatory cytokines in the AD lesion. Conclusions These studies suggest that the expression of a superantigen by S. aureus alone does not play an important role in the increased skin inflammation associated with staphylococcal infection in childhood AD.     

特应性皮炎和湿疹皮肤金黄色葡萄球菌肠毒素及中毒休克综合征毒素-1的检测

目的 探讨皮肤金黄色葡萄球菌(金葡菌)肠毒素及中毒休克综合征毒素-1(TSST-1)在特应性皮炎及湿疹中的致病作用。方法 反向被动乳胶凝集法测定来自117例特应性皮炎和199例湿疹患者皮肤共140株金葡菌的肠毒素/TSST-1。结果 140株金葡菌中60株产生超抗原,阳性率为42.9%,其中43株只产生一种超抗原,17株产生至少两种超抗原。特应性皮炎组超抗原总阳性率为51.5%,皮损与非皮损处无差别。湿疹组超抗原总阳性率为34.7%,阳性株均为皮损处菌。特应性皮炎组超抗原总阳性率、皮损处超抗原总阳性率及中毒休克综合征毒素-1阳性率均高于湿疹组。结论 与湿疹相比,特应性皮炎与金葡菌超抗原的关系较为密切。     

A randomised controlled trial on photo(chemo)therapy of subacute prurigo

BACKGROUND: Psoralen ultraviolet A (PUVA) is the standard photo(chemo)therapeutic regimen for patients suffering from subacute prurigo (SP). HYPOTHESIS: Regarding efficacy, bath PUVA is not superior to medium-dose ultraviolet-A1 (MD-UVA1) and narrowband ultraviolet-B (NB-UVB), which may be considered the new photo(chemo)therapeutic options for SP. METHODS: We performed a prospective randomised, controlled, three-arm photo(chemo)therapeutic study. Patients suffering from histopathologically proven SP with a clinical score (PIP score; papules, infiltration and pruritus) of at least 5 points were enrolled into the study. Treatment with bath PUVA was performed 4 times weekly and MD-UVA1 and NB-UVB 5 times weekly. Photo(chemo)therapy was administered over a 4-week period. Outcome measure was the severity of SP investigated by means of the PIP score after 4 weeks of therapy. RESULTS: In total, 33 patients with SP were randomly allocated to photo(chemo)therapy. Bath PUVA (n = 9), MD-UVA1 (n = 11) and NB-UVB (n = 13) resulted in a significant reduction of the baseline PIP score as assessed on the basis of intention-to-treat (ITT) analysis (P = 0.003). However, ITT analysis revealed significantly higher PIP score reduction in patients who were treated with bath PUVA and MD-UVA1 compared with NB-UVB (P < 0.01, 95% CI 1.1-3.63 and P < 0.05, 95% CI 0.42-2.70, respectively). CONCLUSIONS: Photo(chemo)therapy, including bath PUVA, MD-UVA1 and NB-UVB, appears to be an effective and safe treatment option for patients suffering from SP. UVA1 and particularly PUVA seem superior to NB-UVB in the management of SP.     

Oral psoralen photochemotherapy in severe childhood atopic eczema: an update

Over a 6-year period, oral psoralen photochemotherapy (oral PUVA) has been used to treat 53 children (mean age 11. 2 years) with severe atopic eczema unresponsive to other therapy. Twiceweekly treatment resulted in clearance or near-clearance of disease in 39 (74%) after a mean of 9 weeks. Thirty-two (82%) of these 39 children were subsequently able to achieve remission of disease following gradual withdrawal of treatment: the mean duration of treatment to remission was 37 weeks; the mean cumulative UVA dose was 1118 J/cm² and the mean number of treatments was 59. Twenty-two remain in remission a year after discontinuing treatment. Short- and medium-term adverse effects, other than occasional intolerance of treatment, have not been prominent. Despite anxieties about possible long-term hazards, it is our view that oral PUVA Is justified in a small proportion of older children with disabling atopic eczema. We believe that it has substantial advantages over other therapeutic options in selected cases, particularly in providing improved growth and an opportunity for sustained remission. riately     

Interaction of ultraviolet-B-rich and ultraviolet-A-rich radiation in ketoprofen-induced photohemolysis

Interactions between different wavelengths can cause inhibition or enhancement of various biological reactions. We evaluated in vitro the effect of UVB-rich irradiation on UVA-induced phototoxicity. Suspensions of human erythrocytes were incubated with ketoprofen, a phototoxic nonsteroidal anti-inflammatory drug. These samples were exposed to 0, 20, 40, 80, 160 or 320 mJ/cm² UVB followed by irradiation with 0 or 6 J/cm² UVA. Photo-induced hemolysis was calculated as a percentage of complete hemolysis. Ketoprofen-dependent hemolysis due to UVA alone was 63% (median). UVB did not induce ketoprofen-dependent photohemolysis at doses <80 mJ/cm². Exposure to UVB at all doses enhanced significantly (P<0.01) UVA-induced ketoprofen-dependent hemolysis in samples from 9 of 15 donors. However, with erythrocytes from the other 6 donors, 20 or 40 mJ/cm² UVB reduced the median of UVA-induced photohemolysis by 69% (P<0.05) or 47% (not significant), respectively. Co-incubation of samples with ascorbic acid resulted in a profound inhibition of ketoprofen-dependent photohemolysis. These results indicate that the effect of low UVB doses on UVA-induced phototoxicity depends on individual, yet unknown characteristics of the target cells.