Reduced IL-1Ra/IL-1 ratio in ultraviolet B-exposed skin of patients with polymorphic light eruption.

Polymorphic light eruption (PLE) is a putative delayed-type allergic reaction to (solar) ultraviolet (UV) exposure. Inadequate immune suppression after UVB-induced sunburn appears to be associated with reduced trafficking of Langerhans cells (LCs) out of and neutrophils into the epidermis of patients sensitive to UVB provocation of PLE. Therefore, we investigated whether pro-inflammatory and chemotactic cytokines are differentially expressed in UVB-irradiated skin of UVB-provocable PLE patients (n = 6) and age- and gender-matched healthy controls (n = 6). Interstitial interleukin-1alpha (IL-1alpha), IL-1beta, IL-1Ra, IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein 1-alpha (MIP-1alpha), MIP-1beta and monocyte chemotactic protein-1 (MCP-1) were measured in suction blister fluid raised 16 h after exposure to 0, three and six minimal erythemal UVB doses. In unirradiated skin, the IL-1Ra levels were significantly lower in the PLE patients than in controls (P < 0.05). IL-8 and TNF-alpha levels increased strongly upon UVB irradiation in both groups. No differential shifts in cytokine profiles were found that could explain a reduced trafficking of Langerhans cells and neutrophils in PLE patients. Dose-trend analyses showed that UVB irradiation caused significant increases in IL-1alpha in both groups, and that the levels of IL-1alpha and IL-1beta were on average twofold higher in the PLE group (P = 0.03 and P = 0.004, respectively.). Accordingly, the ratios of IL-1Ra over IL-1alpha and over IL-1beta were overall lower in the skin of PLE patients (P = 0.015 and P < 0.001, respectively.). This shift in cytokines in UVB-irradiated skin of PLE patients reveals an amplified early pro-inflammatory cytokine response, which may contribute to the allergic reaction to UVB radiation.

Normalized ultraviolet (UV) induction of Langerhans cell depletion and neutrophil infiltrates after artificial UVB hardening of patients with polymorphic light eruption.

BACKGROUND: Ultraviolet (UV) B hardening has been widely used as a prophylactic treatment in patients with polymorphic light eruption (PLE). Recent investigations have shown that in patients with PLE Langerhans cells (LCs) and neutrophils display less migration from and to the epidermis after an intense UVB irradiation compared with controls. OBJECTIVES: To investigate the effect of UVB hardening of patients with PLE on their cell migratory responses after intense UVB exposure. METHODS: Thirteen patients with PLE were recruited and UVB provocation testing was performed before entering the study. Among these patients, seven developed PLE rash upon UVB provocation ('UVB-P') and the other six did not respond ('UVB-NP'). Eleven age/sex-matched controls were included. Buttock skin of all included individuals was exposed to 6 minimal erythema doses (MED) of UVB (TL-12 lamps). Biopsies were taken after 24 h and 48 h, together with one control biopsy of unirradiated skin. Patients received total-body UVB hardening therapy consisting of 12 irradiations, on average rising from 10% to 140% of the initial MED in 6 weeks. Subsequently, MEDs were reassessed and biopsies were taken from newly irradiated (6 MED UVB) and unirradiated buttock skin. Skin sections were stained for the presence of LCs, macrophages and neutrophils. The cross-sectional area (in percentage) of positively stained cells within the epidermis was assessed from patients before and after hardening and compared with controls. RESULTS: Before therapy, epidermal LC depletion and neutrophil influx at 48 h after 6 MED were most significantly reduced in 'UVB-P' patients (P = 0.025 and P =0.006, respectively) when compared with controls. 'UVB-NP' patients did not differ significantly from controls. After therapy, there were no longer any significant differences in the cell numbers among these three groups. CONCLUSIONS: UVB hardening significantly improves UV-induced cell migratory responses in patients with PLE. UVB provokability of PLE appears to be most strongly linked to reduced UVB-induced trafficking of LCs and neutrophils, and 'UVB-P' patients show normalization of these responses after UVB hardening.

Mast cell distribution in normal adult skin.

AIMS: To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. METHODS: Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. RESULTS: There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. CONCLUSIONS: MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.