Macrolides in Chronic Inflammatory Skin Disorders

Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents

Candida albicans and Napkin Dermatitis: Relationship and Lesion Severity Correlation

Introduction: Napkin Dermatitis (ND) is a common problem in infancy that affects almost every child during the early months and years of their lifetime. It is a skin disease that becomes a challenge for both parents and physicians because of its frequency and difficulty in eliminating all of the causative factors in diapered infants. Usually Napkin dermatitis is self-limiting but when associated with Candida albicans (C. albicans) seems to be moderate to severe.Aim: The aim of the present study was to determine the colonization of C. albicans in children with Napkin dermatitis and to correlate between intensity of C. albicans colonization and the severity of napkin rash.Patients and Methods: This case-controlled study was conducted at Qassim University pediatric outpatient clinics, during the period from August 2014 to July 2015. Sixty patients with diaper dermatitis and 33 healthy controls were enrolled to this study. Sociodemographic and clinical data were obtained from the parents of each participant using questionnaires Paired (stool and skin) samples were collected from all cases and healthy control children. The samples were cultured on differential and selective chromogenic medium for isolation and initial identification of candida species. Identification confirmation of the isolates was determined by the Vitek 2 compact automated system.Results: Diaper dermatitis shows significant outcome to washing diaper area (per day) (P=0.001), History of diarrhea last 7 Days (P˂0.001), skin lab results (+/-) for Candida albicans, (P˂0.001), skin colony count, (P˂0.001), However, there is no correlation to age (P=0.828), gender (P=0.368) and feeding style (P=0.401).Conclusion: The severity score of napkin dermatitis was significantly observed among cases with diaper dermatitis (p-value<0.001) and control children (p-value<0.001) respectively.Keywords: Candida albicans; Napkin dermatitis; Diaper dermatitis; Vitek 2 compact system; Qassim

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Genetic prediction of male pattern baldness

Male pattern baldness can have substantial psychosocial effects, and it has been phenotypically linked to adverse health outcomes such as prostate cancer and cardiovascular disease. We explored the genetic architecture of the trait using data from over 52,000 male participants of UK Biobank, aged 40-69 years. We identified over 250 independent genetic loci associated with severe hair loss (P<5x10-8). By splitting the cohort into a discovery sample of 40,000 and target sample of 12,000, we developed a prediction algorithm based entirely on common genetic variants that discriminated (AUC = 0.78, sensitivity = 0.74, specificity = 0.69, PPV = 59%, NPV = 82%) those with no hair loss from those with severe hair loss. The results of this study might help identify those at greatest risk of hair loss, and also potential genetic targets for intervention

Autoimmune response against tyrosinase induces depigmentation in C57BL/6 black mice

Regulation of melanogenesis by tyrosinase has now become an attractive approach for treatment of vitiligo but still the role of tyrosinase in the induction of depigmentation remains largely unexplored. This study was explored the role of tyrosinase in the induction of autoimmune depigmentation in C57BL/6 mice. Depigmentation was induced in C57BL/6 mice by tyrosinase immunization. Induced depigmentation was characterized by visual detection and was verified by histopathological analysis of lesional and non-lesinal skin biopsies. Moreover, induced depigmentation was re-validated by gene expression analysis of vitiligo-relevant genes by Taqman assays. Immunization of C57BL/6 mice by tyrosinase induces depigmentation on hairs as well as on skin. Immunoassays with Protein A-purified immune IgGs showed high titre antibodies against tyrosinase. Histopathological analysis showed that the total melanocytes were depleted from the basal layer of the epidermis and also from the dermis of depigmented lesions. The gene expression of vitiligo-relevant genes TYRP1, DCT, MLANA, MCIR, POMC, FOXJ2, CSNK1G3, SOX10, PMEL and KIT was significantly low in lesional skin as compared with non-lesional skin (p < .05). In contrast, the mRNA expression of CASP3 and NFκB1 was significantly high in lesional skin of depigmented mice as compared with non-lesional skin (p < .05). Furthermore, involvement of cellular immunity in depigmentation was confirmed by the reduction of CD4+:CD8+ lymphocytes ratio. In conclusion, this study shows that the autoimmune response against tyrosinase induces depigmentation in black C57BL/6 mice. The data obtained from the lesional and non-lesional skin biopsies showed the same features as were reported in human vitiligo patients

Psoriasin: A Novel Marker Linked Obesity with Psoriasis

To evaluate the role of psoriasin, koebnerisin, interleukn (IL)-12 and IL-23 in the pathogenesis of psoriasis and their relations to Psoriasis Area Severity Index (PASI) and obesity. Thirty patients had chronic plaque psoriasis and 30 healthy subjects matched in age and sex were enrolled in this study. Serum from all subjects were used for determination of psoriasin, koebnerisin, IL-12 and IL-23 by ELISA kits. IL-23 and psoriasin were significantly higher in skin psoriasis compared to controls and psoriatic arthritis (PsA). There was a correlation between psoriasin and both PASI and obesity. On the other hand, IL-12 was significantly increased in PsA compared to skin psoriasis (p = 0.000) and controls. Its sensitivity and specificity were 87%, 93%; respectively. To our knowledge, psoriasin is the first biomarker confirm the link between obesity and psoriasis. The risk of developing psoriasis is directly related to higher BMI

Prevalence of Leishmania species among patients with cutaneous leishmaniasis in Qassim province of Saudi Arabia

Abstract Background Leishmaniasis is a parasitic infection endemic in more than ninety countries of the world. The cutaneous leishmaniasis (CL) is a most common form of leishmaniasis and it remains to be a major public health issue in Saudi Arabia. This study was undertaken to investigate the Leishmania species responsible for CL infection in different provinces of Qassim, Saudi Arabia. Methods Skin biopsies were obtained from CL patients and DNA was extracted using the Magna pure system. Leishmania species were identified by highly specific/sensitive quantitative and qualitative PCR. Results Out of total 206 CL biopsies, 49.5% biopsies were found to be positive for Leishmania major (L. major), 28.6% biopsies were positive for Leishmania tropica (L. tropica), 3.9% were found to be positive for Leishmania infantum/donovani (L. infantum/donovani). Not only have these, all tested CL biopsies showed negative test for Leishmania mexicana (L. mexicana) and Leishmania viannia (L. viannia). Conclusions This is the first comprehensive study that shows the majority of CL in Qassim was caused by L. major and L. tropica. To the best of our knowledge, this is the very first report that shows the occurrence of L. infantum/donovani in Saudi Arabia. This requires higher alert to the Ministry of Health of Saudi Arabia to take proactive actions in preventing the onset of L. major, L. tropica, L. infantum and L. donovani infections

Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata

AbstractBackgroundToll-like receptors (TLRs) are pattern-recognition-receptors that sense a variety of pathogens and initiation of innate and adaptive immune responses. This study was undertaken to investigate the expression of TLRs in peripheral blood-mononuclear cells (PBMCs) of AA patients and to determine whether TLR-mediated inflammatory signals are important for the perspective of AA management.MethodsGene expression of TLRs and T-helper (Th) type-1, Th-2, Th-17 and regulatory T-cell cytokines in PBMCs was quantified by TaqMan Assays. Production of these cytokines in serum samples was determined by sandwich ELISAs.ResultsAll TLRs (TLRs 1–10) were expressed in PBMCs of AA patients. Importantly intracellular TLRs (TLRs 3, 7, 8 and 9) were significantly up-regulated in AA patients as compared with controls (p<0.05). Interleukin (IL)-2, TNF-α, and IL-17A gene expression in patients' PBMCs and their secretion in patients' sera were significantly higher as compared with their respective controls (p<0.05). Whereas, TGF-β gene expression in patients' PBMCs and TGF-β protein level in patients' sera were significantly lower as compared with their controls (p<0.05).ConclusionThis is the first report that shows the comprehensive expression profile of TLRs in AA patients. We conclude that up-regulated expression of intracellular TLRs in PBMCs of AA patients may play an active role in abnormal regulation of Th-1, Th-17 and regulatory T-cell cytokines in alopecia areata.General significanceTargeting of TLRs and their associated inflammatory signaling will open new areas of research; this may lead to the development of novel therapeutic targets for the treatment of AA or other skin disorders