Major histocompatibility complex diversity is positively associated with stream water temperatures in proximate populations of sockeye salmon.

Local adaptation to heterogeneous environments generates population diversity within species, significantly increasing ecosystem stability and flows of ecosystem services. However, few studies have isolated the specific mechanisms that create and maintain this diversity. Here, we examined the relationship between water temperature in streams used for spawning and genetic diversity at a gene involved in immune function [the major histocompatibility complex (MHC)] in 14 populations of sockeye salmon (Oncorhynchus nerka) sampled across the Wood River basin in south-western Alaska. The largest influence on MHC diversity was lake basin, but we also found a significant positive correlation between average water temperature and MHC diversity. This positive relationship between temperature and MHC diversity appears to have been produced by natural selection at very local scales rather than neutral processes, as no correlation was observed between temperature and genetic diversity at 90 neutral markers. Additionally, no significant relationship was observed between temperature variability and MHC diversity. Although lake basin was the largest driver of differences in MHC diversity, our results also demonstrate that fine-scale differences in water temperature may generate variable selection regimes in populations that spawn in habitats separated by as little as 1 km. Additionally, our results indicated that some populations may be reaching a maximum level of MHC diversity. We postulate that salmon from populations in warm streams may delay spawning until late summer to avoid thermal stress as well as the elevated levels of pathogen prevalence and virulence associated with warm temperatures earlier in the summer.

Histopathologic features of erythematous papulopustular eruption to epidermal growth factor receptor inhibitors in cancer patients.

BACKGROUND: Erythematous papulopustular eruption (EPPE) is the most frequent skin adverse event to epidermal growth factor receptor (EGFR) inhibitors but its histopathologic features have been poorly studied. As EPPE is a strong predictor of patient's treatment response, the EPPE histopathologic features and their correlations with skin eruption severity and involved drug were investigated. METHOD: An involved skin biopsy was carried out in 39 informed patients treated with EGFR inhibitors (mainly cetuximab and erlotinib). The cutaneous changes in hematoxylin-eosin stained sections were evaluated. RESULTS: The EPPE to EGFR inhibitors is histopathologically characterized by neutrophilic subcorneal or intraepidermal pustules and polymorphous infiltrate of the superficial dermis during the earliest phases and by lymphocytic perifolliculitis and/or suppurative folliculitis at a later phase. The widespread dermis inflammation was more frequent in severe EPPEs and in patients treated with cetuximab, while the hair follicle inflammation was observed only in mild/moderate EPPEs. CONCLUSION: Our study shows the histopathologic signs of EPPE and their correlation with clinical severity and the offending drug.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Clinical epidemiology of hand eczema in patients accessing dermatological reference centres: results from Italy.

BACKGROUND: Data on the epidemiological impact and clinical characteristics of chronic hand eczema in Southern Europe are lacking. OBJECTIVES: To estimate the prevalence of chronic hand eczema in its different stages of severity and refractoriness to standard therapy in patients accessing Italian dermatological reference centres, and to evaluate sociodemographic and clinical factors associated with each stage. METHODS: A cross-sectional multicentre study was conducted. Adult patients with hand eczema, consecutively accessing 14 centres over a 6-month period, were enrolled. Patients were classified according to disease duration, severity and response to standard therapy with potent topical corticosteroids. Logistical regression was performed to investigate the relationship between sociodemographic and clinical data with different stages of eczema. RESULTS: The total number of participants was 981. Hand eczema was chronic in 83·5% of patients; 21·3% had severe eczema, with 62·0% of these patients refractory to standard therapy. Food processing and related work, the health professions, craft and related trade works (building, plumbing, electrical), hairdressing/beauty and handicraft work were most frequently associated with chronic hand eczema. Severe chronic hand eczema was more likely to be seen in men, older patients and those with less education. Severe and refractory hand eczema was also more likely among the unemployed and patients with allergic rhinitis and/or atopic dermatitis. CONCLUSIONS: Chronic hand eczema is frequent among patients with hand eczema accessing dermatology centres. Many patients were severe and refractory to standard therapy. The appropriate identification of hand eczema is the first step in implementing effective and efficient treatments.

Histopathological and immunohistochemical features of drug-induced exanthems.

Exanthematic eruptions, together with urticaria-angioedema syndrome and fixed drug eruption, are the most frequent cutaneous adverse drug reactions. Among the drug-induced exanthems (DIEs), erythematous maculopapular eruptions are the most common. Their management, especially when retrospective, is often not easy, and it is based on the use of clinical criteria, history, results of some laboratory tests, drug elimination test, skin tests, and oral challenge test. The superficial perivascular and spongiotic dermatitis, which is the prevalent histopathological features of DIEs, is not very useful in the differential diagnosis with virus- and bacteria-induced exanthems (VBIEs). On the contrary, some immune-histochemical findings (interleukin-5 overexpression, concomitant enhancement of perforin, interleukin-5, and granzyme B production, positivity for fatty acid synthase-ligand-L in amoxicillin-induced exanthems) seem to be more important. These data justifie the inclusion of DIEs in the subtypes IVb and IVc of delayed hypersensitivity reactions.

Investigation of new vehicles to patch test corticosteroids: our experience with ethoxydiglycol to detect contact allergy to hydrocortisone butyrate.

Topical corticosteroids (CS) are widely used in dermatology because of their anti-inflammatory, anti-proliferative and immuno-suppressive properties. On the other hand, the prolonged application of corticosteroids may induce adverse reactions such as allergic contact dermatitis (ACD). Patch testing CS often poses methodological issues correlated to their drug properties that may hide the manifestations of a positive reaction. Furthermore, the ideal concentration to patch test corticosteroid is still a matter of study and some vehicles have some well-known limitations. This article is divided into two parts: the first one investigated vehicles that may efficiently dissolve the corticosteroids, according to the polarity of the latter; the second part compared the results of the patch tests with hydrocortistone-17-butyrate using two different vehicles: ethanol, which is the standard one, and another vehicle selected as suitable from our CS solubility test.

Allergic and photoallergic contact dermatitis from ketoprofen: evaluation of cross-reactivities by a combination of photopatch testing and computerized conformational analysis.

Allergic contact dermatitis (ACD) and photo-ACD are cell-mediated delayed hypersensitivity reactions of the skin caused by a wide range of substances. Topical ketoprofen (KP), a nonsteroidal anti-inflammatory drug (NSAID), can induce ACD and photo-ACD. Patients with ACD and/or photo-ACD to KP frequently show concomitant sensitization to other substances. The aim of this study was to identify the substances most frequently associated with sensitization to KP, and to evaluate, by means of computerized conformational analysis, whether this association could be due to cross-allergy. 15 subjects with ACD and photo-ACD to KP were tested with the SIDAPA (Società Italiana di Dermatologia Allergologica Professionale ed Ambientale) patch test standard series, including fragrance mix and its components (eugenol, isoeugenol, oak moss, geraniol, hydroxycitronellal, amylcinnamaldehyde, cinnamyl alcohol and cinnamaldehyde) and with the SIDAPA photopatch test series. Allergic reactions to cinnamyl alcohol were noted in all patients, whereas some patients also showed positive reactions to fenticlor, octocrylene and benzophenone-10. Computerized conformational analysis demonstrated that the structure of cinnamyl alcohol is similar to that of KP, whereas the structures of benzophenone-10, octocrylene and fenticlor are completely different. These results suggest that in patients with contact allergy to KP, concomitant positive reactions to cinnamyl alcohol are due to cross-sensitization, whereas simultaneous allergic reactions to fenticlor, octocrylene and benzophenone-10 should be regarded as co-sensitizations.

Differential diagnosis of psoriasis.

The clinical diagnosis of psoriasis is relatively easy, especially when the lesions consist of erythematous, silvery white scaly, sharply demarcated, indurated plaques, distributed symmetrically on the extensor surfaces of limbs, the lower back and the scalp. These clinical features reflect the histopathological findings observed in active lesions, characterized by parakeratosis, acanthosis of the epidermal ridges, tortuous and dilated blood vessels, and perivascular leukocytic infiltrate; the Munro microabscess and the spongiform pustule of Kogoj are diagnostic. Diagnostic doubts, however, may arise in several clinical variants and atypical cases (guttate psoriasis, follicular or spinulosic psoriasis, erythrodermic psoriasis, pustular psoriasis) or when the psoriatic lesions are localized in particular sites (palms, soles, scalp, body folds, penis, nails). The value of erythemato-papulosquamous psoriasiform eruptions occurring during or after the administration of a diagnostic or therapeutic agent especially in psoriatic subjects is discussed.

Reactivity to euro coins and sensitization thresholds in nickel-sensitive subjects.

BACKGROUND: The 1- and the 2-euro coins consist of nickel alloys, which release nickel. The nickel released by far exceeds the amount allowed by the European Union Nickel Directive referring to products intended to come into direct and prolonged contact with the skin. As there is only temporary contact with the skin, the clinical relevance of nickel-containing coins with regard to nickel dermatitis is a matter of debate, although there is evidence that the nickel released from the coins affects some nickel-sensitive subjects through occupational exposure. OBJECTIVES: Our aim was to study skin reactivity to euro coins, and to correlate the frequency and intensity of coin patch test responses to sensitization thresholds to nickel. PATIENTS AND METHODS: Sixty-four nickel-sensitized and 30 non-nickel-sensitized subjects were patch tested with serial dilutions of nickel sulfate (5, 1, 0.5, 0.1, 0.05, 0.01 and 0.005% in distilled water) and with coins. Italian coins (500, 200, 100 and 50 lira) and euro coins (2 and 1 euros, 20 and 5 euro cents) were used for patch testing and compared. RESULTS: The application of 1- and 2-euro coins to the skin induced eczematous reactions, being more frequent and intense in comparison with those provoked by other coins. A correlation between intensity of responses to coin patch tests and sensitization threshold to nickel was observed. Patients with the strongest reactions to 1- and 2-euro coins showed positive responses to the lowest nickel concentrations. CONCLUSIONS: The nickel content in euro coins represents a possible health hazard, especially for highly nickel-sensitive subjects. We recommend that nickel sulfate patch tests should be performed at different concentrations to determine sensitization thresholds at least in individuals with occupational exposure to coins.

T-lymphocyte cytokine profiles in compositae airborne dermatitis.

Compositae airborne dermatitis is a well-recognized disorder characterized by erythematosquamous lesions and papules on light-exposed areas. The presence of positive patch test reactions and the absence of specific serum IgE suggest delayed-type hypersensitivity, the murine model of which is characterized by a Th1 cytokine production profile [high amounts of interferon (IFN)-gamma and interleukin (IL)-2; little or no IL-4 and IL-5]. The aim of this study was to evaluate the cytokine profile of T-cell lines and T-cell clones from peripheral blood in a 38-year-old non-atopic male woodcutter affected by seasonal airborne contact dermatitis. The patient showed positive patch test reactions to several Compositae extracts (Achillea millefolium, Chamomilla recutita, Tanacetum parthenium, T. vulgare) and sesquiterpene lactone mix. On prick testing with Compositae and other plants, serum-specific IgE levels and phototesting were negative or normal. Allergen-specific T-cell lines produced with Compositae extracts showed a good in vitro cell proliferation only to C. recutita extract. Serial cloning performed using the C. recutita-specific T-cell lines revealed an alphabeta+CD4+ phenotype with high amounts of IFN-gamma and IL-4 in T-cell clones. Thus, these cells expressed a preferential Th0 phenotype. These data suggest that in addition to IFN-gamma, other T-cell derived cytokines, such as IL-4, may play a part in the immunopathogenesis of contact dermatitis.

Is benzoquinone the prohapten in cross-sensitivity among aminobenzene compounds?

Cross-sensitivity in allergic contact dermatitis is a simultaneous allergy to 2 or more contact substances which have in common an antigenic determinant or a metabolic derivative. One of the most notable examples is the cross-sensitivity among aromatic compounds which may be oxidized in vivo to benzoquinone (BQ). However, it has also been hypothesized that the allergenicity and cross-sensitization are modulated by the chemical reactivity of the substituents in the para position. A serial dilution of BQ (from 1% to 0.1% in pet.) and three 1,4-substituted benzene derivatives (p-aminophenol, hydroquinone, metol), theoretically capable of conversion to BQ by oxidation, were patch tested in 22 p-phenylenediamine (PPD) positive patients and in 20 controls. The patients and a further 116 subjects with a positive history of sensitivity to 1 or more aminoaromatic compounds were also tested with some haptens of the para group (PPD, p-aminobenzoic acid, p-aminodiphenylamine, benzocaine, procaine chloride, p-toluenediamine sulfate). The results show that (i) the optimal patch test concentration for BQ was 0.2%, (ii) only 4 of the 22 patients allergic to PPD gave a clearly positive allergic reaction to BQ, and (iii) the number of positive reactions to the aromatic compounds was correlated with the presence of activating (-NH2, -OH, -CH3) and deactivating (-COOH) groups in the para position or, perhaps, with their effect on percutaneous penetration. The data suggest that BQ is not the only intermediate in the cross-sensitization of para group haptens. This is probably conditioned by other oxidation products and/or the chemical structure of the substituents in position 4 of the benzene ring.