In silico allergen identification: Proposal for a revision of FAO/WHO guidelines

Allergy is a widespread, often severe health problem. In vivo or in vitro identification of new allergenic proteins (natural or bioengineered) is time- and resource-consuming, and in vivo testing can be dangerous. Thus, allergenicity prediction through computation (in silico) was proposed to narrow down the number of potential allergens to be tested with traditional methods. In 2001, the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) officially defined guidelines for in silico allergenicity prediction, based on amino acid sequence similarity to known allergens; these guidelines, however, have been criticized because of frequent false positives. In the present work, the BLAST (Basic Local Alignment Search Tool) software was used to compare known and potential allergens, and select only statistically significant homologies (i.e. homologies whose E value, calculated by BLAST, was 1); FAO/WHO rules were then applied to these homologies. With this method, correct recognition of all known allergens, with only 10 false positives (1.26% of all predicted allergens) was achieved when using an upper limit of 0.1 for E values; complete suppression of wrong predictions, while maintaining 100% sensitivity, was obtained with little modifications of the minimum requirements contained in the FAO/WHO guidelines

Homology between TSH-R/Tg/TPO and Hashimoto's encephalopathy autoantigens.

Hashimoto's encephalopathy (HE) is a syndrome occurring in some patients with Hashimoto's thyroiditis or, less frequently, Graves' disease. Three known autoantigens are involved in HE: alpha-enolase, dimethylargininase-I (DDAHI) and aldehyde reductase-I (AKRIAI). We searched for amino acid sequence homologies between these proteins and the three classical thyroid autoantigens (thyroperoxidase (TPO), thyroglobulin (Tg), TSH-receptor (TSH-R)), which are also expressed in the central nervous system (CNS). TSH-R shows homologies with alpha-enolase (n=4), DDAHI (n=2) and AKRIAI (n=5); of these segments, two, two and four, respectively, overlap totally or partially with epitope-containing TSH-R segments. Tg has 10 homologies with alpha-enolase, five with DDAHI, and eight with AKRIAI; epitope-containing segments of Tg overlap four, three and four segments, respectively. TPO has six segments homologous to alpha-enolase, three to DDAHI and seven to AKRIAI; of these segments, five, one and four, respectively, are located in epitope-containing parts. These data suggest that cross-reactivity between CNS autoantigens and thyroid autoantigens might contribute to the HE pathogenesis, together with other proposed mechanisms, including autoimmunity involving autoantigens common to CNS and thyroid

Perioral Dermatitis after Dental Filling in a 12-Year-Old Girl: Involvement of Cholinergic System in Skin Neuroinflammation?

The etiopathogenesis of perioral dermatitis (PD) is still unknown and, consequently, medical treatment is difficult, not precisely defined, and often unsatisfactory. On the basis of a peculiar case that appeared soon after multiple dental fillings with a mercury-containing amalgam, we proposed that neurogenic inflammation could play a role in the pathogenesis of PD. According to the new findings provided by clinical and basic research, neurogenic inflammation has a relevant part in the pathogenesis of many cutaneous diseases. We report a similar case of PD, taking into account, more specifically, the possible involvement of the cholinergic system. Also in this case, PD seems to be mainly related to the mercury contained in dental fillings and/or its organic compounds formed by oral/gut bacteria. We examined the possible role of these substances as causes of PD, providing new information on the possible cross-talk between neuroimmunodermatology and potential triggers of PD

Airborne contact dermatitis and asthma in a nail art operator

AbstractNail art (creation and decoration of artificial nails) is a growing fashion trend. Proportionally to its popularity, the number of allergic reactions to the materials used has recently increased. We report the case of a nail art operator who developed occupational allergy to acrylates, manifested with the unusual simultaneous presence of asthma and dermatitis. Cutaneous lesions only affected areas not covered by individual protection devices or clothes, even if such areas were not in direct contact with acrylates, suggesting airborne allergic contact dermatitis. While respiratory problems were solved with the correct use of a mask at the workplace, facial dermatitis proved impossible to avoid or control and, for this reason, the patient had to change her work

Results from an extended study on the reliability of a questionnaire for the diagnosis of sensitive skin: Confirmations and improvements

ObjectiveA recently proposed self-assessment questionnaire aimed at diagnosing sensitive skin provided promising results in a relatively small population. The main objectives were: (i) to assess the reliability of the aforementioned questionnaire in a larger population and verify the cut-off score previously found to predict skin sensitivity (defined as positivity to LAST, lactic acid stinging test) and (ii) to define a formula that yields the probability of a positive LAST result. MethodsAdult volunteers were included in this observational, cross-sectional, extended study. Both LAST-positive subjects, who were considered as having sensitive skin ('patients') and negative ones ('controls') completed the questionnaire, which concerned sensitivity to possible triggers of unpleasant skin sensations in real life. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items. ResultsThree hundred and sixty-four subjects were enrolled, 214 patients and 150 controls. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls. Using two different methods, cut-off values of 4 and 5 were defined for the identification of LAST-positive subjects, with 76.6% and 72.8% accuracy, respectively. Scores below 4 or above 5 showed a high (80% or better) negative or positive predictive value, respectively. The coefficients found that in multivariate analysis for each questionnaire item, gender and age allowed us to calculate the probability of LAST positivity with higher precision taking into account the 'relative weight' of each factor. ConclusionWith small variations in the results, the self-assessment questionnaire confirmed its reliability for diagnosing sensitive skin in clinical practice

Urticaria and hyposideremia: a case report

The authors report the case of an 86-year-old man with a six-month history of chronic idiopathic urticaria, refractory to standard treatments. The patient did not report concomitant diseases and all clinical tests performed were normal. Laboratory tests showed only mild anemia and low serum iron (31 mcg/dl, normal value 59-158). After oral iron supplementation (105 mg/day of elemental iron, taken as ferrous sulphate) for two months, normal serum iron levels and complete remission of urticaria were observed. No further episodes of urticaria were reported at follow-up visits, six and twelve months later. The possible link between hyposideremia and urticaria is also discussed. In vitro experimental data suggest that transferrin inhibits histamine release from mast cells, and a direct correlation exists between the level of transferrin saturation and the degree of inhibition of histamine release. Reduced transferrin saturation due to hyposideremia could lower the threshold of stimulation required for mast cell degranulation, thus increasing the risk of urticaria in response to endogenous and/or exogenous pathogenic stimuli, even minimal. Further studies are necessary to better understand frequency and pathogenic mechanism(s) of “sideropenic urticaria” (chronic urticaria associated with hyposideremia and favourably responding to iron supplementation). From a clinical point of view, evaluation of serum iron levels in selected patients appears advisable, in the light of the relatively low cost and possible significant benefit

correlation between endocrinological parameters and acne severity in adult women

Many studies demonstrate increased androgen levels and high prevalence of polycystic ovaries in women affected by acne. We evaluated the relationship between clinical features, ultrasonographic data on polycystic ovaries and hormonal parameters in 129 women w17 years of age with acne. Serum levels of androgens of ovarian and adrenal origin were measured. Menstrual cycle regularity, hirsutism, body mass index and ultrasonographic evaluation of ovaries were recorded. Raised levels of at least one androgen were evident in a majority of our patients. Only 19% of them had polycystic ovary syndrome. Hirsutism and acne severity correlated negatively with serum sex hormone-binding globulin (SHBG) levels ( pv0.05). No correlation between acne severity and hirsutism was found. In post-pubertal women, severity of acne seems to depend on peripheral hyperandrogenism, with a negative relationship between the acne severity and serum SHBG levels. We strongly recommend the evaluation of serum SHBG levels in women with acne in order to select patients who can have a better response to appropriate hormonal regimes. Key words: acne; polycystic ovary; ultrasound examination; sex hormone-binding globulin; sebocyte

Rheumatoid Arthritis and Erythema Multiforme: A Possible Pathogenetic Link for T-Cell-Mediated Autoimmune and Reactive Skin Diseases?

We present the case of a woman, with a 14 years’ history of rheumatoid arthrtitis, who showed simultaneously gradually appearing, annular, erythematous, itchy patches and exacerbation of the joint symptoms, of one month duration, after a pregnancy. Clinical and histologic features led us to the diagnosis of erythema multiforme. While it is not possible to exclude that the co-occurrence of the two conditions is coincidental, our case suggests the possibility that erythema multiforme is a sign of an ample alteration of the immune system, that may occur in patients with systemic immunologic diseases as a consequence of the action of various triggering factors, such as molecular mimicry between endogenous and exogenous antigens or pregnancy, which is notoriously a period of complex and still largely unexplored alterations of the reactivity of the immune syste

Photodistributed telangiectasia following use of escitalopram.

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Clinical and dermoscopic characteristics of congenital and non-congenital nevus-associated melanomas

No specific features of nevus-associated melanoma (NAM) are currently defined