File(s) not publicly available
Photosensitivity in cutaneous lupus erythematosus clinical and experimental studies
Lupus erythematosus (LE) is an autoimmune disease in which the skin is one of the main target organs. Photosensitivity is a common feature for the different subtypes of cutaneous LE, but photosensitivity has not been well defined. Polymorphous light eruption (PLE) is a common form of photosensitivity in otherwise healthy individuals, and the differential diagnosis can be difficult. The keratinocytes and dermoepidermal junction have been extensively studied in LE, contrary to the cells in the dermis, especially fibroblasts and endothelial cells. We studied different aspects of UV-induced cutaneous reactions in LE patients, with emphasis on early cellular events in evolving lesions. We also investigated the roles of endothelial cells and fibroblasts.
Methods: A mailed questionnaire with questions about worsening by sunlight and about history of PLE was sent to 387 consecutive patients from dermatological university clinics in Finland and Sweden. Sixty- seven of the responders were interviewed about their photosensitivity, and went through phototesting and photoprovocations with UVB and UVA. Consecutive biopsies from UV-induced, evolving cutaneous reactions were obtained from LE and PLE patients until the reactions subsided, and from healthy, photoprovoked individuals. The biopsies were analysed with direct immunofluorescence using antibodies against IgG, IgM, C3 and C1q, with immunohistochemistry for expression of ICAM-1, VCAM-1 and E-selectin and with routine histopathology. Levels of soluble CAMs were analysed with ELISA kits in a retrospective study on frozen sera from LE patients and controls. Fibroblasts were cultured from scarring and non-scarring LE lesions and healthy controls. The cells were counted every third day during nine days. Cytokines and soluble CAMs in supernatants were analysed before and after irradiation of the cells with UVA.
Results: LE patients reported worsening by sunlight in 242 (72%) of 337 responders to the questionnaire. A history consistent with PLE was reported by 165 (49%). PLE had started before LE in the majority of patients with both diagnoses. UVA and UVB induced reactions with clinical and micromorphological features of LE or PLE. A specific, granular epidermal staining pattern ("dust-like particles"), was found in immunofluorescence biopsies from the first two weeks after irradiation in LE patients and within 3 days at the earliest. Complement (C1q) was often present. Specific patterns of CAM expression were seen in different diagnostic groups and as an early event in lesions of different duration. UVA but not UVB possibly had a direct influence on endothelial VCAM-1 and E-selectin expression. Soluble (s)E-selectin was elevated in serum from DLE patients with active, widespread lesions compared to controls and patients with limited disease. sICAM-1 and sVCAM-1 were elevated in patients with SLE and SCLE, and correlated to systemic but not to cutaneous symptoms. Cultured fibroblasts from scarring LE lesions, showed markedly impaired proliferation compared to fibroblasts from non-scarring LE lesions and controls. UVA irradiation did not significantly influence levels of cytokines and CAMs in supernatants from cultured fibroblasts.
Conclusions: The photosensitivity in LE patients displays a clinical spectrum from transient, PLE-like reactions to persistent, clinically typical LE lesions. CAM expression patterns are influenced by the patient's disease. Complement, endothelial cells and fibroblasts seem to play roles in the pathogenesis of UV-induced LE lesions. Hypothetically, an altered expression of CAMs, induced by an unbalanced cytokine network brought about by an altered T-cell/B-cell repertoire in genetically susceptible individuals, could be a unifying concept for the findings in our studies.
History
Defence date
1999-01-22Department
- Department of Clinical Neuroscience
Publication year
1999Thesis type
- Doctoral thesis
ISBN-10
91-628-3344-8Language
- eng