The activation of mast cells by extra domain A of fibronectin (FN-EDA), an endogenous ligand of TLR4, and its contribution to the pathogenesis of rheumatoid arthritis (RA) in vivo were examined. FN-EDA, but no other domain of the fibronectin fragment, III(11) (FN-III(11)) and III(12) (FN-III(12)), stimulated bone marrow-derived murine mast cells (BMMCs) dose-dependently to secret cytokines (TNF-alpha, IL-6, and IL-1beta), similar to the pattern produced by LPS. FN-EDA-induced cytokine production was mediated by TLR4, as cytokine production by FN-EDA was absent in TLR4-deficient (TLR4-/-) BMMCs. We examined the roles of TLR4-mediated mast cell activation by this form of fibronectin fragment in the pathogenesis of RA in vivo. The injection of FN-EDA, but not FN-III(11)and FN-III(12), to joints resulted in joint swelling of mice in vivo. Genetically mast cell-deficient WBB6F(1)-W/W(v) mice exhibited significantly less swelling and cytokine production compared with mast cell-sufficient +/+ mice, suggesting that swelling and inflammatory cytokine production were partially dependent on tissue mast cells. Reduced swelling and cytokine production were recovered by the reconstitution of tissue mast cells by the injection of BMMCs from wild-type mice but not from TLR4-/- mice. Altogether, these results suggest that the TLR4-mediated activation of mast cells by endogenous ligand FN-EDA might contribute to the pathogenesis of RA through proinflammatory cytokine production.
BackgroundAtopic dermatitis (AD) is a common skin condition among Asians. Recent studies have shown that Asian AD has a unique clinical and immunologic phenotype compared with European/American AD.ObjectiveThe Asian Academy of Dermatology and Venereology Expert Panel on Atopic Dermatitis developed this reference guide to provide a holistic and evidence-based approach in managing AD among Asians.MethodsElectronic searches were performed to retrieve relevant systematic reviews and guidelines on AD. Recommendations were appraised for level of evidence and strength of recommendation based on the U.K. National Institute for Health and Care Excellence and Scottish Intercollegiate Guidelines Network guidelines. These practice points were based on the consensus recommendations discussed during the Asia Pacific Meeting of Experts in Dermatology held in Bali, Indonesia in October 2016 and April 2017.ResultsThe Expert Panel recommends an approach to treatment based on disease severity. The use of moisturizers is recommended across all levels of AD severity, while topical steroids are recommended only for flares not controlled by conventional skin care and moisturizers. Causes of waning efficacy must be explored before using topical corticosteroids of higher potency. Topical calcineurin inhibitors are recommended for patients who have become recalcitrant to steroid, in chronic uninterrupted use, and when there is steroid atrophy, or when there is a need to treat sensitive areas and pediatric patients. Systemic steroids have a limited role in AD treatment and should be avoided if possible. Educational programs that allow a patient-centered approach in AD management are recommended as an adjunct to conventional therapies. Recommendations on the use of phototherapy, systemic drugs, and emerging treatments are also included.ConclusionThe management of AD among Asians requires a holistic approach, integrating evidence-based treatments while considering accessibility and cultural acceptability.
Epidermal nevus syndromes are a group of rare multiorgan disorders. Schimmelpenning syndrome is a clinical variant of epidermal nevus syndromes. This congenital syndrome is characterized by the existence of nevus sebaceous and usually accompanied by abnormalities of the eyes, skeletal, cardiovascular, and central nervous systems. A 2-year-old girl presented with large, hairless, yellowish-brown plaques on the scalp and face along with multiple brownish-black verrucose plaques and brownish-black macules on almost all parts of the body. The skin-colored verrucose tumors were also found on the lips and around the mouth. Histopathological examination of the lesion on the forehead revealed hyperkeratosis, acanthosis, and sebaceous gland hyperplasia supporting the diagnosis of nevus sebaceous, while histopathological examination of the lesions on the lips and abdomen demonstrated hyperkeratosis, acanthosis, and papillomatosis consistent with verrucous epidermal nevus. The pediatrician suspected that the patient had mental retardation; however, there were no neurological, cardiac, skeletal, nor ophthalmologic abnormalities. The lesions on the lips and around the mouth were excised, and it demonstrated a good result. To conclude, epidermal nevus syndrome (e.g., Schimmelpenning syndrome) should be considered in children born with nevus sebaceous.
Dialkylcarbamoylchloride (DACC)‐coated cotton acetate dressing works directly through hydrophobic interaction to reduce the number of bacteria without the risk of resistance. It is easy to use and therefore expected to improve patient's compliance. This study aimed to assess the clinical efficacy of DACC‐coated cotton acetate dressing compared to a combination of normal saline dressing and 2% mupirocin ointment. A single‐blind controlled trial was conducted and included 14 infected epidermolysis bullosa (EB) wounds which were divided into two groups. Group I received DACC‐coated cotton acetate dressing, and Group II received the combination of normal saline dressing and 2% mupirocin ointment. Study results showed that the average time required for complete wound closure was 8.6 and 11.1 days in Groups I and II, respectively (p = .014), which was statistically significant. Both groups showed complete bacterial elimination on Day 3 based on negative Gram stain results and on Day 6 based on clearance of clinical manifestations (p = 1.000). This is a novel study in EB‐infected wounds, which shows that DACC‐coated cotton acetate dressing promotes faster wound closure and is as effective as the combination of normal saline dressing and 2% mupirocin ointment in eliminating bacterial infection.
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