Nico Mousdicas

Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor

Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor-positive and -negative (PAF-R-positive and -negative) cells and PAF-R-deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R-positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R-deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R-expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis.

Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid.

BACKGROUND Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown. OBJECTIVE We sought to characterize the amounts of the biologically active bacterial lipoprotein lipoteichoic acid (LTA) in infected AD lesions. METHODS Eighty-nine children with clinically impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically by using the Eczema Area and Severity Index (EASI), wash fluid obtained from the lesion for quantitative bacterial culture, and measurement of LTA and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities. The patients were treated with a regimen that included topical corticosteroids and systemic antibiotics, and the lesion was reanalyzed after 2 weeks. RESULTS S aureus was identified in 79 of 89 children enrolled in the study. The bacterial colony-forming unit (CFU) counts correlated with the EASI lesional score (P = .04). LTA levels as high as 9.8 mug/mL were measured in the wash fluid samples, and the amounts correlated with the lesional EASI scores (P = .01) and S aureus CFU (P < .001). Approximately 30% of clinically impetiginized AD lesions contained greater than 1 mug/mL LTA, amounts that exert effects on various cell types in vitro. Moreover, injection of skin tissue ex vivo with amounts of LTA found in AD lesions resulted in epidermal cytokine gene expression. CONCLUSION Pharmacologic levels of LTA are found in many infected atopic dermatitis lesions.

Pediatric Contact Dermatitis Registry Inaugural Case Data

BackgroundLittle is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. ObjectiveThe aim was to quantify patch test results from providers evaluating US children. MethodsThe study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015–2016). ResultsOne thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). ConclusionsThis US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products.

Pediatric Contact Dermatitis Registry Data on Contact Allergy in Children With Atopic Dermatitis

Importance Atopic dermatitis (AD) and allergic contact dermatitis (ACD) have a dynamic relationship not yet fully understood. Investigation has been limited thus far by a paucity of data on the overlap of these disorders in pediatric patients. Objective To use data from the Pediatric Contact Dermatitis Registry to elucidate the associations and sensitizations among patients with concomitant AD and ACD. Design, Setting, and Participants This retrospective case review examined 1142 patch test cases of children younger than 18 years, who were registered between January 1, 2015, and December 31, 2015, by 84 health care providers (physicians, nurse practitioners, physician assistants) from across the United States. Data were gathered electronically from multidisciplinary providers within outpatient clinics throughout the United States on pediatric patients (ages 0-18 years). Exposures All participants were patch-tested to assess sensitizations to various allergens; history of AD was noted by the patch-testing providers. Main Outcomes and Measures Primary outcomes were sensitization rates to various patch-tested allergens. Results A total of 1142 patients were evaluated: 189 boys (34.2%) and 363 girls (65.8%) in the AD group and 198 boys (36.1%) and 350 girls (63.9%) in the non-AD group (data on gender identification were missing for 17 patients). Compared with those without AD, patch-tested patients with AD were 1.3 years younger (10.5 vs 11.8 years; P < .001) and had longer history of dermatitis (3.5 vs 1.8 years; P < .001). Patch-tested patients designated as Asian or African American were more likely to have concurrent AD (odds ratio [OR], 1.92; 95% CI, 1.20-3.10; P = .008; and OR, 4.09; 95% CI, 2.70-6.20; P <.001, respectively). Patients with AD with generalized distribution were the most likely to be patch tested (OR, 4.68; 95% CI, 3.50-6.30; P < .001). Patients with AD had different reaction profiles than those without AD, with increased frequency of reactions to cocamidopropyl betaine, wool alcohol, lanolin, tixocortol pivalate, and parthenolide. Patients with AD were also noted to have lower frequency of reaction to methylisothiazolinone, cobalt, and potassium dichromate. Conclusions and Relevance Children with AD showed significant reaction patterns to allergens notable for their use in skin care preparations. This study adds to the current understanding of AD in ACD, and the continued need to investigate the interplay between these disease processes to optimize care for pediatric patients with these conditions.

Fibroblast Senescence and Squamous Cell Carcinoma: How Wounding Therapies Could Be Protective

BACKGROUND Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age‐dependent disease, with the majority of these cancers diagnosed in people age 70 and older. Recent findings have led to a new hypothesis on the pathogenesis of SCC. OBJECTIVES To evaluate the potential of preventive therapies to reduce the incidence of SCC in at‐risk geriatric patients. MATERIALS AND METHODS Survey of current literature on wounding therapies to prevent SCCs. RESULTS This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in the dermis, resulting in a reduction in dermal insulin‐like growth factor‐1 (IGF‐1) expression. This lack of IGF‐1 expression sensitizes epidermal keratinocytes to fail to suppress ultraviolet light B (UVB)‐induced mutations, leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF‐1 expression, and correct the inappropriate UVB response found in geriatric skin, protecting geriatric keratinocytes from UVB‐induced SCC initiation. CONCLUSIONS In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC.

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

A dermatite atopica e uma doenca cutânea inflamatoria cronica cuja prevalencia tem aumentado de forma constante, afetando 10-20% dos lactentes e 1-3% dos adultos em todo o mundo. Ela e frequentemente a primeira manifestacao clinica de doenca atopica, precedendo a asma e a rinite alergica. Provavelmente metade das criancas com dermatite atopica desenvolvem alguma outra forma de doenca atopica em outras fases da vida. A patogenia envolve uma interacao complexa entre fatores que incluem predisposicao genetica devido a uma funcao alterada da barreira cutânea ou imunologica, interacoes com o ambiente, tais como exposicao a alimentos e alergenos, e desencadeadores infecciosos de inflamacao. Nesta revisao, resumimos os avancos recentes na compreensao da contribuicao de diferentes fatores a fisiopatologia da dermatite atopica e como os novos conhecimentos proporcionam novo potencial terapeutico.

Identification of Staphylococcal Protein A in Infected Atopic Dermatitis Lesions

Staphylococcus aureus (S. aureus) infection is a known trigger for skin inflammation and can modulate immune responses. Atopic dermatitis (AD), a chronic inflammatory pruritic skin disease, affects 10–20% of children and 1–3% of adults (De Benedetto et al., 2009). Due to the loss of skin integrity by scratching, as well as decreased levels of antimicrobial peptides in comparison to normal skin or other inflammatory diseases such as psoriasis (Leung, 2003; Ong et al., 2002), patients with AD are particularly susceptible to staphylococcal skin infections, which can further worsen their skin disease (Bieber, 2008). Studies have suggested several underlying mechanisms for staphylococcus-mediated inflammation, which include production of inflammatory cytokines following either direct infection of keratinocytes or immune cells by the bacteria, or indirectly by bacterial products (Baker, 2006; Leung, 2003; Sasaki et al., 2003; Travers et al., 2001). We have demonstrated previously that lipoteichoic acid (LTA), a gram-positive bacterial lipoprotein, may be an important component of the ability of S. aureus to exacerbate AD lesions (Travers et al., 2010). In the present study, we report that staphylococcal protein A (SPA) could also contribute to this process.

The beak sign: a clinical clue to airborne contact dermatitis.

1. Warshaw E. Contact dermatitis conundrums. American Contact Dermatitis Society 24th Annual Meeting. Miami Beach, FL: American Contact Dermatitis Society; 2013. 2. Bruze M. Thoughts on standardization of multicenter patch test studies. American Contact Dermatitis Society 24th Annual Meeting. Miami Beach, FL: American Contact Dermatitis Society; 2013. 3. Bruze M, Isaksson M, Gruveberger B, et al. Recommendation of appropriate amounts of petrolatum to be applied at patch testing. Contact Dermatitis 2007;56:281Y285. 4. Jaimes JP, Liu A, Bhardwaj SS, et al. Optimizing reproducibility for clinical studies involving patch testing and application of topical preparations. Dermatitis 2006;63:284Y288. 5. Engfeldt M, Gruveberger B, Isaksson M, et al. Comparison of three different techniques for application of water solutions to Finn chambers. Contact Dermatitis 2010;63:284Y288.

Dowling–Degos disease co‐presenting with Darier disease

We present a case of a patient with long‐standing hyperpigmented macules and erythematous papules over his chest, abdomen, back and arms, suggestive of Dowling‐Degos disease (DDD). In addition, there were hyperkeratotic papules, alternating red and white nail‐bed discolouration, and V‐shaped nail notching consistent with Darier disease (DD). Histology showed findings consistent with DDD and DD on separate specimens. The lack of acantholysis in areas of filiform hyperpigmented rete ridges ruled out Galli–Galli disease (GGD). DDD results from mutations in the genes encoding keratin 5 (KRT5), protein O‐glucosyltransferase 1 (POGLUT1) or protein O‐fucosyltransferase 1 (POFUT1), while DD results from mutations in the ATP2A2 gene. Both genes are present on chromosome 12. In this case, the patient presented with features of both DDD and DD, which suggests that either a cooperating mutation or a mutation in an unrelated gene locus may underlie the findings in this patient.

Eruptive disseminated porokeratosis associated with corticosteroid-induced immunosuppression

Eruptive disseminated porokeratosis (EDP) is a disease that presents clinically with sudden onset of erythematous papules and plaques, with a ridge‐like border histologically represented by a cornoid lamella. We report a case of EDP occurring in a 39‐year‐old woman 3 days after completion of a 2‐week course of oral corticosteroid therapy for an acute asthma exacerbation. The patient was treated with emollients and sun protection. Unlike the more chronic disseminated superficial (actinic) porokeratosis, EDP secondary to immunosuppression from corticosteroid therapy has very rarely been reported in the dermatological literature.