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Effectiveness of Medium-Dose Ultraviolet A1 Phototherapy in Localized Scleroderma

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Effectiveness of Medium-Dose Ultraviolet A1 Phototherapy in Localized Scleroderma Pharmacology and therapeutics Effectiveness of medium-dose ultraviolet A1 phototherapy in localized scleroderma Ozlem Su1, MD, Nahide Onsun1, MD, Hulya Kapran Onay2, MD, Yeliz Erdemoglu1, MD, Dilek Biyik Ozkaya1, MD, Filiz Cebeci1, MD, and Adnan Somay3, MD 1Department of Dermatology, Abstract Bezmialem Vakif University, Faculty of Background Recently, ultraviolet (UV) A1 phototherapy has been suggested as an effec- 2 Medicine, Neoson Imaging Center, tive treatment for localized scleroderma (LS); however, the optimal dose of UVA1 still has Radiology, and 3Department of not been determined. Pathology, Vakif Gureba Teaching and 2 Research Hospital, Istanbul, Turkey Objective We aimed to evaluate the therapeutic effectiveness of medium-dose (30 J/cm ) UVA1 phototherapy and to show that 13 MHz ultrasound is a valuable tool for assessing Correspondence the results of UVA1 phototherapy in LS. Ozlem Su, MD Methods Thirty-five patients with LS were treated with medium-dose (30 J/cm2) UVA1. Sıgırtmac Sok. No. 21 B blok d. 7 In total, 30–45 treatments and 900–1350 J/cm2 cumulative UVA1 doses were evaluated by Osmaniye Bakirkoy clinical scoring in all patients. In 14 patients, skin thickness was also determined by Istanbul 13 MHz ultrasound examination. Turkey Results In all patients, medium-dose UVA1 therapy softened sclerotic plaques, and E-mail: [email protected] marked clinical improvement was observed in 29 of 35 (82. 85%) patients. Ultrasound mea- surements showed that skin thickness was significantly reduced. No side effects were Conflicts of interest: None. observed during or after treatment. Conclusion Medium-dose UVA1 phototherapy is a highly effective, safe, and well-tolerated therapeutic modality for treatment of all types of LS. A 13 MHz ultrasound probe may be used for evaluating UVA1 phototherapy results. developed lesions, the inflammatory cell infiltrate largely Introduction disappears, and dermal collagen bundles appear thick and Localized scleroderma, or morphea, is a connective tissue coarse and replace areas of subcutaneous fat.5 Rarely, disorder characterized by thickening and sclerosis of the morphea and lichen sclerosis et atrophicus (LSA) occur skin. A recent classification has grouped localized sclero- simultaneously in the same patient.6 derma into five subtypes: circumscribed morphea, linear Although the disease has a benign course, the lesions scleroderma (LS), generalized morphea, pansclerotic are cosmetically disfiguring and may cause psychological morphea, and a mixed subtype, when a combination of distress. Moreover, it sometimes progresses and may two or more of the previous subtypes is present.1 When involve underlying tissues of the skin (fat, fascia, and LS involves the face, it is called ‘‘en coup de sabre’’ muscle). This may lead to muscle atrophy, flexion con- (ECDS). A particularly rare subtype of localized sclero- tractures if localized over the joints, and poorly healing derma is bullous morphea.2 The most common circum- ulcerations that can cause significant morbidities.7,8 scribed morphea (plaque type) is characterized by single The pathogenesis of scleroderma has not been com- or multiple, circumscribed, ivory-white, indurated, some- pletely delineated, but three processes have been demon- times confluent plaques, which may be up to 20 cm in strated: disturbance of collagen metabolism,9 vascular diameter.3 During the active stages, lesions frequently alteration,10 and autoimmune activity.11 Fibrosis in sclero- expand with a violaceous border, the so-called lilac ring derma is preceded by a T-helper lymphocytic infiltrate (inflammatory halo).4 Histopathological examination of with subsequent collagen deposition and an increased syn- morphea during the active inflammatory stages in a thesis of type I and type III collagen. In fibroblasts from peripheral violaceous border shows a rather marked sclerotic skin lesions, increased collagen expression was inflammatory cell infiltrate, particularly in the reticular associated with decreased collagenase I expression, which 10 1006 dermis. In late sclerotic stages, as seen in the central well- may be important in collagen accumulation. International Journal of Dermatology 2011, 50, 1006–1013 ª 2011 The International Society of Dermatology Su et al. UVA1 phototherapy in localized scleroderma Pharmacology and therapeutics 1007 Numerous therapeutic agents have been used, with morphea, seven had late-stage sclerotic and 11 had active limited success, including topical, intralesional, and inflammatory lesions. One patient with linear morphea had systemic glucocorticoids, penicillin G, D-penicillamine, upper limb involvement associated contractures. Four patients antimalarials, sulfasalazine, vitamin D analogs, vitamin E, with generalized morphea presented with late-stage lesions. imiquimod, topical tacrolimus, etretinate, potassium The remaining three patients with generalized morphea p-aminobenzate, griseofulvin, interferon gamma, metho- presented with active inflammatory lesions. The disease trexate, cyclosporine, phototherapy, and extracorporeal duration varied between three months and 55 years. Before photopheresis.4,7,12,13 treatment, skin biopsies were taken from lesional skin. Recently, different types of phototherapy, such as psor- Unfortunately, post-treatment histopathological examination was alen and ultraviolet (UV) A,14 broadband UVA (320– done on only four of these patients. Fourteen of 35 patients 400 nm),15 and UVA1 (340–400 nm)4,10,11 have been were evaluated by clinical score as well as by 13 MHz advocated as a new line of therapy, based on the finding ultrasound. that synthesis of collagenase can be directly stimulated in human skin fibroblasts by UVA radiation. Very promising Ultraviolet A1 equipment results have notably been achieved with UVA1 photother- The UVA1 irradiation equipment consisted of a Waldmann apy thus far, with low-dose (LD) and medium-dose (MD) 7001 K cabin with Waldmann TL10R low-pressure lamps UVA1 seeming to be as effective as high-dose (HD) (Waldmann Gmblt, Schvenningen, Germany). These lamps UVA1, with a possible better risk–benefit ratio.4,10,11,16 generate UVA1 wavelengths in the 340–400 nm range. In The optimal dose regarding therapeutic efficacy vs. possi- addition, infrared irradiation is emitted, but this is filtered out by ble side effects remains to be evaluated. an acrylic glass screen. The UVA1 irradiation levels are We aimed to evaluate the therapeutic effectiveness of approximately 35 mW/cm2. A dose of 30 J/cm2 is achieved in MD (30 J/cm2) UVA1 phototherapy and to show that approximately 30 minutes. 13 MHz ultrasound is a valuable tool for the assessment of diagnosis and treatment results in LS. Treatment In all patients, total body UVA1 phototherapy (340–400 nm) was administered 3–5 times a week for 10–15 weeks, resulting Materials and methods in a total of 30–45 treatment sessions. Each treatment session Patients consisted of an exposure of 30 J/cm2 UVA1 per body half, Thirty-five patients with localized scleroderma were selected for resulting in a cumulative UVA1 dose of 900–1350 J/cm2. During MD UVA1 phototherapy and were treated after informed therapy, patients wore eye goggle protection against UVA consent at our dermatology clinic between April 2005 and June radiation. Emollients had been applied once daily in the 2009. For each patient, a complete disease history was evening. Emollients were not applied shortly before or after obtained before starting irradiation therapy. Laboratory UVA1 phototherapy. examinations included complete blood cell count, liver and kidney parameters, rheumatoid factor, antinuclear antibodies, Assessment and serology for Borrelia burgdorferi. In all patients (27 female and 8 male; age 3.5–75 years), the diagnosis of LS was made Clinical evaluation on clinical and histopathological features. None of the patients All patients were assessed before, during, and after UVA1 had any evidence of systemic sclerosis or pseudoscleroderma. phototherapy by palpation for tethering and thickening of the All patients had at least two clinically identical scleroderma skin. Clinical severity of LS was assessed by a scoring system lesions (mostly contralateral). All patients included in the study created by Rook et al.17 Briefly, the method consists of scoring were Caucasian; 15 patients had skin type II, 15 had skin type sclerosis of different topographic sites. The most severely III, and five had skin type IV according to Fitzpatrick’s affected site selected for assessment of clinical severity was classification. Exclusion criteria were as follows: pregnancy or examined in each patient by the same investigator (OS). The lactation, any internal immunomodulation or immunosuppressive severity of sclerosis was scored from 0 (like normal skin) to 10 therapy within the last four weeks, any topical therapy within the (extremely sclerotic, wooden hard). last two weeks other than the use of emollients, current use of potentially photosensitizing drugs, history of relevant cardiac/ Ultrasound analysis (13 MHz) cardiovascular events, and a history of an autoimmune disease Ultrasound imaging was performed with a high-resolution or neoplasm. Patients were classified to have plaque (n = 18), B-mode ultrasound system (Sanoline Antares; Siemens Medical linear (n = 4), ECDS (n = 3), generalized morphea (n = 7), deep System, Erlangen, Germany) with a 13 MHz CVFX 13-5 linear or pansclerotic (n = 1), and generalized associated with probe by a second investigator (HK). The usable depth of signal overlying LSA (n = 2) subtypes.
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