The polymorphous light eruption-severity assessment score does not reliably predict the results of phototesting.

BACKGROUND: Polymorphous light eruption (PLE) is a very common photodermatosis in which patient history is highly specific. Phototesting is used to confirm the diagnosis and to determine the action spectrum and the severity of this disease. In daily practice and in research studies, it would be convenient to assess disease severity by patient history only. OBJECTIVES: This study aims to assess PLE disease severity via patient history and compares this with severity assessment via phototesting. PATIENTS AND METHODS: Sixty-one patients with PLE were asked 10 standard questions and all were phototested. The answers to the standard questions were coded with linear scores ranging from 0 to 10. The score of each question was plotted as independent variable in a multiple linear regression model against the score of the phototest (minimal number of irradiations necessary to elicit a positive skin lesion, with a maximum of 6 irradiations) as dependent variable using an enter approach. Furthermore, the scores of the separate questions were added to form a total score, the PLE-severity assessment score (PLE-SAS). The medians of these PLE-SASs were compared with the result scores obtained by phototesting. Phototesting was done with ultraviolet A and ultraviolet B irradiation. RESULTS: Fifty-seven of the 61 patients had a positive test result (93%). Using the multiple linear regression model, the severity assessment by patient history (PLE-SAS) compared with the result of phototesting showed two significant contributing questions (adjusted PLE-SAS) (P < 0.05) but with a regression coefficient of 0.2. A significant difference in median scores with the severity assessment (PLE-SAS and adjusted PLE-SAS) between patients testing positive after 1-3 irradiations compared with those testing positive after 4-6 irradiations was present (P < 0.05). However, the overlap quartile range between both groups was such that the PLE-SAS and the adjusted PLE-SAS have little predictive value in individual patients. CONCLUSIONS: We showed that in PLE, disease severity as determined using the PLE-SAS or adjusted PLE-SAS did not reliably predict severity as assessed by phototesting. Two significant contributing questions were not discriminating enough to be used as predicting questions to assess severity. Accurate patient history proved to be a reliable method to diagnose PLE. Phototesting is useful to determine the responsible ultraviolet action spectrum and to exclude differential diagnoses like photosensitive eczema, lupus erythematosus or chronic actinic dermatitis. PLE-SAS cannot replace phototesting for determining the severity of PLE.

Cow's milk allergy in adults is rare but severe: both casein and whey proteins are involved.

BACKGROUND: Studies on cow's milk allergy (CMA) in adults are scarce. Little is known about the clinical symptoms, eliciting doses (ED), and allergens involved. OBJECTIVE: The aim of this study was to analyse the clinical symptoms, ED and allergen recognition in adult CMA patients, compared with cow's milk (CM)-sensitized, but tolerant controls. METHODS: Adult CMA patients were evaluated by standardized questionnaires (n=30), skin prick tests (SPTs) and specific IgE for CM allergens (n=18), and a double-blind placebo-controlled food challenge (DBPCFC, n=10). A control group (n=25) of CM-sensitized, but tolerant adults was included. RESULTS: The majority of CMA patients (20/30, 67%) reported severe symptoms. In all patients participating in DBPCFC, CMA was confirmed. ED for subjective symptoms (0.3-300 mg CM protein) were significantly lower than that for objective symptoms (300-9000 mg CM protein). The severity of CMA by history and ED was not correlated with SPT or IgE. Patients had higher SPT reactivity than controls for CM, alpha-lactalbumin and beta-lactoglobulin (P=0.002, P=0.014 and P=0.004) but not for casein. Specific IgE to CM tended to be higher (P=0.068) and IgE to casein was higher in patients than that in controls (P=0.016). No difference was observed for IgE to alpha-lactalbumin and beta-lactoglobulin. CONCLUSION: Adult CMA is severe in nature. ED are low, starting from 0.3 mg CM protein. Patients with CMA recognize the same major allergens (casein and whey proteins) as controls, but display a stronger SPT and IgE reactivity.

CD11b+ cells and ultraviolet-B-resistant CD1a+ cells in skin of patients with polymorphous light eruption.

After ultraviolet exposure Langerhans cells (epidermal CD1a+ cells) disappear from the healthy skin, and CD11b+ macrophage-like cells, which are reported to produce interleukin-10, appear in a matter of days. These phenomena are related to the ultraviolet-induced local suppression of contact hypersensitivity reactions. A defect in this suppression might allow inadvertent immune reactions to develop after ultraviolet (over)exposure; i.e., it could cause ultraviolet-B-induced polymorphous light eruption. In order to test this we first exposed buttock skin of eight healthy volunteers to six minimal erythema doses from Philips TL12 lamps, and indeed observed a dramatic disappearance of CD1a+ cells 48 and 72 h later, at which time the number of CD11b+ cells increased in the dermis, and some occurred in the epidermis. The epidermis thickened and showed large defects, filled by CD11b+ cells, just below the stratum corneum. In 10 patients with polymorphous light eruption (five with a normal minimal erythema dose and five with a low minimal erythema dose) CD1a+ cells were present in the epidermis as well as in the dermis before exposure. Strikingly, these cells were still present in considerable number at 48 and 72 h after exposure to six minimal erythema doses. CD11b+ cells already present in the dermis before ultraviolet exposure, increased after ultraviolet exposure, and subsequently also invaded the epidermis. Despite the six minimal erythema doses, there were no apparent defects in the epidermis of the polymorphous light eruption patients. This deviant early response to ultraviolet radiation is likely to be of direct relevance to the polymorphous light eruption and is perhaps useful as a diagnostic criterion.

Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.

Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis.

Induction and disappearance of thymine dimers in human skin exposed to UVB radiation: flow cytometric measurements in replicating and nonreplicating epidermal cells.

We have earlier reported on determining UV-induced DNA damage in murine epidermal cell suspensions by flow cytometric analysis of the fluorescence from a fluorescein isothiocyanate-labeled antibody (H3) directed against thymine dimers (T < > T). Here we present an optimization of the technique for analysis of epidermal cell suspensions from 4 mm biopsies from human skin. Cells with different DNA contents can easily be distinguished in flow cytometry by the intensity of DNA-specific 7-amino-actinomycin D fluorescence. Genuine G2-M-phase cells can further be distinguished from cell doublets by pulse-shape discrimination. Thus, T < > T levels in individual cells with different DNA contents (i.e. G0-G1, S or G2-M phases) can be determined after in vivo exposure of human skin to environmentally relevant UVB (280-315 nm) doses. The method was applied to measure the decrease of T < > T in nonreplicating cells (G0-G1 phase) and replicating cells (S phase or G2-M phase) from seven volunteers exposed to twice their minimal erythema dose. The reduction in the average T < > T-specific fluorescence at 24 h after exposure was 46% (ranging between 16% and 66%) for the G0-G1 cells and 70% (ranging between 37% and 100%) for the S + G2-M cells. The difference was statistically highly significant. Determination of individual DNA repair capacities with this method can become a convenient diagnostic tool for patients with DNA repair disorders, or it may even be used to identify individuals with low repair proficiencies and increased risk of developing skin cancers.

Detection of photorepair of UV-induced thymine dimers in human epidermis by immunofluorescence microscopy.

To investigate the effect of visible light on the level of UV-induced thymine dimers in human epidermal cells in vivo, we exposed volunteers to UV-B alone, or to a serial combination of UV-B and visible light. Dimers were assayed in skin sections by immunofluorescence microscopy with a monoclonal antibody against the cyclobutyl thymine dimer. The dimer-specific fluorescence from epidermal cell nuclei, identified by counterstaining with propidium iodide, was quantified through computer-mediated image processing and analysis. After a single UV exposure (2-3 MED), significant dimer-specific fluorescence was measured, but no difference could be detected between skin kept in the dark after UV-irradiation and that exposed to visible light. In three other experiments, the UV dose was split into 3 parts (1 MED each), given at 2.5-h intervals. Half of the skin area was exposed to visible light following each dose fraction. After the second and third dose fractions, skin areas treated with visible light clearly showed lower levels of dimers (i.e., about 40% reduced) than skin kept in the dark. The results provide evidence that photorepair of dimers does occur in human skin, but not immediately after a first UV exposure of naive skin.