Ultraviolet radiation and skin mast cells: Effects, mechanisms and relevance for skin diseases.

Mast cells (MCs) are well known as versatile effector cells in allergic reactions and several other immune responses. Skin MCs and cutaneous MC responses are subject to the effects of environmental factors including ultraviolet radiation (UVR). Numerous studies have assessed the effects of UVR on MCs, in vitro and in vivo. Interestingly, UVR seems to have variable effects on non-activated and activated mast cells. In general, UV therapy is beneficial in the treatment of urticaria and mastocytosis, but the effects are variable depending on treatment regimen and type of UVR. Here, we review and summarise key reports from the older and current literature on the crosstalk of UVR and skin MCs. Specifically, we present the literature and discuss published reports on the effects of UVR on skin MCs in rodents and humans. In addition, we review the role of MCs in UVR-driven skin diseases and the influence of UV light on MC-mediated skin diseases. This summary of our current understanding of the interplay of skin MCs and UVR may help to improve the management of patients with urticaria and other MC disorders, to identify current gaps of knowledge, and to guide further research.

Pediatric cutaneous lupus erythematosus treated with pulsed dye laser.

Pulsed dye laser (PDL) has been used in adults to treat refractory cutaneous lupus erythematosus (CLE). We report the first case of CLE in a child successfully treated with PDL.

The efficacy of pulsed dye laser treatment for inflammatory skin diseases: a systematic review.

BACKGROUND: The position of the pulsed dye laser (PDL) in the treatment of inflammatory skin diseases is still unclear. Evidence-based recommendations are lacking. OBJECTIVES: We sought to systematically review all available literature concerning PDL treatment for inflammatory skin diseases and to propose a recommendation. METHODS: We searched for publications dated between January 1992 and August 2011 in the database PubMed. All studies reporting on PDL treatment for an inflammatory skin disease were obtained and a level of evidence was determined. RESULTS: Literature search revealed 52 articles that could be included in this study. The inflammatory skin diseases treated with PDL consisted of: psoriasis, acne vulgaris, lupus erythematodes, granuloma faciale, sarcoidosis, eczematous lesions, papulopustular rosacea, lichen sclerosis, granuloma annulare, Jessner lymphocytic infiltration of the skin, and reticular erythematous mucinosis. The efficacy of PDL laser treatment for these inflammatory skin diseases was described and evaluated. LIMITATIONS: Most conclusions formulated are not based on randomized controlled trials. CONCLUSIONS: PDL treatment can be recommended as an effective and safe treatment for localized plaque psoriasis and acne vulgaris (recommendation grade B). For all other described inflammatory skin diseases, PDL seems to be promising, although the level of recommendation did not exceed level C.

Increased expression of guanylate binding protein-1 in lesional skin of patients with cutaneous lupus erythematosus.

The large GTPase human guanylate binding protein-1 (GBP-1) is a key mediator of angiostatic effects of inflammation and is induced by interferon (IFN)-α and IFN-γ in endothelial cells (ECs). The aim of this study was to investigate whether GBP-1 is a marker of skin lesions in patients with cutaneous lupus erythematosus (CLE). Western blotting revealed that GBP-1 was in vitro induced by IFN-α and -γ in primary keratinocytes obtained from healthy controls. Moreover, we found that this protein was expressed by keratinocytes and ECs in primary and ultraviolet (UV)-induced skin lesions from patients with various subtypes of CLE, when compared to non-lesional skin. No GBP-1 expression was noted in skin biopsy specimens 24 or 72 h after UV irradiation prior to lesion formation in patients with CLE or in healthy control specimens with or without UV irradiation. Initial findings suggest that GBP-1 is not expressed in other skin diseases with different inflammatory aetiology, such as atopic dermatitis. We conclude that GBP-1 expression is closely associated with skin lesions in patients with CLE, suggesting a contribution of GBP-1 in the pathogenesis of this disease.

[Four cases of photopheresis treatment for cutaneous lupus erythematosus refractory to standard therapy]. / Traitement par photochimiothérapie extracorporelle de quatre cas de lupus érythémateux cutané réfractaires aux traitements conventionnels.

BACKGROUND: Photopheresis is a leucopheresis procedure in which cells are photoactivated by psoralen and then irradiated by ultraviolet A. We report four cases of women with refractory cutaneous lupus erythematosus (LE) who responded to this treatment. PATIENTS AND METHODS: We treated one patient with subacute LE having a contraindication to antimalarials and to thalidomide and three patients with chronic LE (lupus panniculitis, lupus tumidus and disseminated discoid LE) refractory to treatment with hydroxychloroquine, chloroquine, thalidomide and dapsone, and also, in some cases, to oral and intravenous corticosteroids, methotrexate, colchicine, acitretine, sulfasalazine, mycophenolate mofetil and intravenous immunoglobulin. Treatment consisted of two 4-hour sessions fortnightly. Only antimalarials were continued during photopheresis. RESULTS: Photopheresis had a positive effect on all four patients. We noticed complete remission in two patients and interruption of progression followed by partial remission in the other two after a mean delay of two to three months of treatment. All treatments other than antimalarials were stopped. DISCUSSION: Photopheresis appears to be an effective treatment option in patients with cutaneous LE. Due to its high cost, it should nevertheless remain an exceptional therapeutic option restricted to patients with cutaneous LE resistant to standard therapy.

Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation.

OBJECTIVE: To examine whether apoptosis contributes to the pathogenesis of skin lesions in patients with cutaneous lupus erythematosus (CLE) after ultraviolet (UV) irradiation. METHODS: In situ nick translation and TUNEL were performed to detect apoptosis in 85 skin biopsy specimens from patients with various subtypes of CLE. Specimens from normal healthy donors and patients with polymorphous light eruption were used as controls. In addition to assessment of primary lesions, provocative phototesting was carried out to investigate events occurring secondary to UV irradiation during a very early stage of lesion formation. RESULTS: A significant increase in apoptotic nuclei was found in the upper epidermal layer of primary and UV light-induced skin lesions of CLE patients compared with controls. In tissue sections obtained from control subjects at 24 hours after a single exposure to UV light, a slight increase in the count of epidermal apoptotic nuclei was present as compared with skin tissue from CLE patients obtained under the same conditions before lesion formation. In sections obtained from controls at 72 hours after irradiation, a significant decrease in the apoptotic nuclei count was observed, consistent with a proper clearance of apoptotic cells in the period between 24 and 72 hours after irradiation. In striking contrast, the number of apoptotic nuclei increased significantly within this period in tissue sections from patients with CLE. CONCLUSION: These data support the hypothesis that apoptotic cells accumulate in the skin of patients with CLE after UV irradiation, as a result of impaired or delayed clearance. The nonengulfed cells may undergo secondary necrosis and release proinflammatory compounds and potential autoantigens, which may contribute to the inflammatory micromilieu that leads to formation of skin lesions in this disease.

UV hardening therapy: a novel intervention in patients with photosensitive cutaneous lupus erythematosus.

BACKGROUND: Patients with cutaneous lupus erythematosus (LE) and a history of disease- related photoaggravation, confirmed by phototesting, may not respond to photoprotection and/or medical intervention. Ultraviolet B-hardening therapy may improve tolerance for environmental ultraviolet radiation (UVR) in photosensitive disorders. OBJECTIVE: We studied the effect of UVB hardening on the cutaneous manifestations of patients with LE and their tolerance for UVR. PATIENTS AND METHODS: A retrospective study of continuous, home-based, UVB-hardening therapy in 44 patients with cutaneous LE (systemic LE: 9 patients; chronic LE: 21 patients; subacute cutaneous LE: 10 patients; cutaneous LE not specified: 4 patients) who had confirmed photosensitivity. Exposure to the UVB source was performed year-round, 3 times weekly, with increasing doses to a maximum of 10 minutes per session. Tolerance for environmental UVR was established through questionnaires, phototesting, and assessment of disease activity by physician and patient. RESULTS: Of 44 patients, 35 were able to gradually increase their monthly UVB doses. Nine patients dropped out because of insufficient efficacy or skin irritation, or were unable to adhere to the hardening regimen. Of the 35 patients who succeeded in hardening their skin with UVB, 28 patients reported an improved tolerance for environmental UVR. This outcome was confirmed by repeat phototesting in a subgroup. In only 5 patients, an improvement of cutaneous LE symptoms was noted by either physician or patient. No serious adverse events were encountered. LIMITATIONS: This was a retrospective study and no control group was used. CONCLUSION: This is the first report that describes UVB hardening as a potential therapy in patients with cutaneous LE and confirmed photosensitivity. This intervention may lead to improved tolerance for environmental UVR and, in a minority of patients, even to decreased cutaneous activity of LE.

Treatment of lupus erythematosus with pulsed dye laser.

BACKGROUND AND OBJECTIVES: The treatment of cutaneous lupus erythematosus (CLE) with dye and argon laser has been evaluated in a number of articles in recent years. The improvement of telangiectasias and chronic erythema of the cutaneous lesions was based on the selective photothermolysis ablation of the dilated capillaries and venules. STUDY DESIGN/MATERIALS AND METHODS: We describe the results of the treatment of cutaneous lesions of 14 patients; eight with discoid lupus erythematosus (DLE) and six with systemic lupus erythematosus (SLE). Three patients received a treatment with flashlamp pulsed dye laser (FPDL) (585 nm, 450 microseconds) with fluences in the range from 5 to 7.75 J/cm(2); the other 11 patients were treated with long pulsed dye laser (LPDL) (595 nm, 1.5-10 milliseconds) with fluences in the range from 6 to 13 J/cm(2) depending on the pulse duration. RESULTS: During a median follow-up of 10 months, we observed an average improvement in over 60% of the lesions. A few side effects were observed in all patients: four had transient hyperpigmentation and one patient had light scarring. Three patients had a relapse after more than 1 year; they were then offered conventional treatment. CONCLUSIONS: We confirm that pulsed dye laser is a good alternative treatment for the erythema in active cutaneous lesions of lupus erythematosus (LE).

Ultraviolet therapy in lupus.

This review examines the use of ultraviolet (UV) therapy in lupus erythematosus (LE), a disorder usually associated with abnormally increased photosensitivity. In addition to the abnormal cutaneous response to ultraviolet radiation (UVR) exposure, photo-aggravation of systemic disease activity in systemic LE (SLE) may also occur. However, courses of UVR exposure may also be used in the treatment or prophylaxis of various photodermatoses, and LE now appears to be included in that group. Thus, several studies have reported apparent benefits of phototherapy in both cutaneous and systemic LE, although the underlying mechanisms remain obscure and final confirmation of such efficacy is still awaited in continuing studies.

Cutaneous lupus erythematosus-treatment with pulsed dye laser.

Because of its vascular selectivity, the flashlamp-pumped pulsed dye laser (585 nm) is efficacious in the treatment of vascular lesions and is successfully used for the treatment of port-wine stains and haemangiomas in children. Based on the encouraging results with these cutaneous vascular disorders, the cutaneous lesions of patients with lupus erythematosus (LE) have now also been treated with the pulsed dye laser. Cutaneous lesions in lupus erythematosus are often difficult to treat with readily available local therapeutic methods. We report here on a group of 12 patients whose LE lesions were treated with the pulsed dye laser. In 10 patients, the LE was limited to the skin, while two patients had systemic LE (SLE). Even in the two patients with SLE, a significant improvement of skin lesions was achieved. After a mean number of 51 laser sessions, a median clearance rate of 70% was attained for nine patients. In one case, the laser treatment failed to clear the lesions. Two patients did not show any visible improvement of the lesions, but pain and itching were significantly reduced. There were few side-effects. No prolonged laser-induced scarring occurred and in only two patients was hyperpigmentation seen, which had resolved completely after 4 and 5 months, respectively. During a median follow-up of 7 months (range: 3-32 months), only one patient (after a complete clearance of the skin lesions) had a small relapse. In summary, the pulsed dye laser is an effective therapy for the treatment of superficial skin lesions in LE.

[UV-A-1 therapy of subacute cutaneous lupus erythematosus]. / UV-A-1-Therapie bei subakut-kutanem Lupus erythematodes.

Because of relative contraindications to corticosteroid or immunosuppressive treatment, a 71-year-old female patient with subacute cutaneous lupus erythematosus underwent serial whole-body irradiation with extremely long-wave ultraviolet light (UVA-1). The cumulative dosage was 186.1 J/cm2 within 9 weeks. Impressive improvement was achieved with some delay.