Pawinee Rerknimitr

The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus and recurrent eczematous lesions that are accompanied by T‐helper (Th)2‐dominated inflammation. AD Etiology is not yet completely understood, but it is multifactorial. Moreover, the disease is characterized by complex interactions between genetic and environmental factors, such as skin barrier dysfunctions, allergy/immunity, and pruritus. For example, filaggrin is a key protein involved in skin barrier function. Th2 cells produce interleukin (IL)‐31, which provokes pruritus, and other Th2 cytokines decrease filaggrin expression by keratinocytes. Dupilumab has recently been developed for AD treatment; its mechanism of action is to bind to IL‐4 receptor α and inhibit downstream signaling induced by IL‐4 and IL‐13. This review summarizes the etiopathogenesis of AD and provides the rationale for selecting a novel targeted therapy.

In Vitro Test to Confirm Diagnosis of Allopurinol‐Induced Severe Cutaneous Adverse Reactions

Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs), such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The reactions can potentially be fatal. As drug rechallenge in patients with a history of drug‐induced SCARs is contraindicated, in vitro testing may have a diagnostic role as a confirmation test.

The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus

Atopic dermatitis (AD) is a common chronic skin inflammatory disorder characterized by recurrent eczema accompanied by an intractable itch that leads to an impaired quality of life. Extensive recent studies have shed light on the multifaceted pathogenesis of the disease. The complex interplay among skin barrier deficiency, immunological derangement, and pruritus contributes to the development, progression, and chronicity of the disease. Abnormalities in filaggrin, other stratum corneum constituents, and tight junctions induce and/or promote skin inflammation. This inflammation, in turn, can further deteriorate the barrier function by downregulating a myriad of essential barrier-maintaining molecules. Pruritus in AD, which may be due to hyperinnervation of the epidermis, increases pruritogens, and central sensitization compromises the skin integrity and promotes inflammation. There are unmet needs in the treatment of AD. Based on the detailed evidence available to date, certain disease mechanisms can be chosen as treatment targets. Numerous clinical trials of biological agents are currently being conducted and are expected to provide treatments for patients suffering from AD in the future. This review summarizes the etiopathogenesis of the disease and provides a rationale for choosing the novel targeted therapy that will be available in the future.

Non-ablative fractional photothermolysis in treatment of idiopathic guttate hypomelanosis.

Idiopathic guttate hypomelanosis (IGH) is a common pigmentary disorder affecting a large number of individuals. Many patients seek medical attention due to aesthetic concern. However, no standard treatment is available.

Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with : 01 allele in the Thai population hla-b : 01 allele in the Thai population*13: 01 allele in the Thai population

Objectives A previous publication in Chinese leprosy patients showed that the HLA-B*13:01 allele is a strong genetic marker for dapsone-induced drug hypersensitivity reactions, however there are no data describing whether HLA-B*13:01 is a valid marker for prediction of dapsone-induced drug hypersensitivity reactions in other ethnicities or nonleprosy patients. The aim of this study is to investigate whether there is an association between HLA genotypes and dapsone-induced severe cutaneous adverse reactions (SCARs) in Thai nonleprosy patients. Patients and methods HLA-B genotypes of 15 patients with dapsone-induced SCARs (11 drug reaction with eosinophilia and systemic symptoms, 4 Stevens–Johnson syndrome/toxic epidermal necrolysis), 29 control patients, and 986 subjects from the general Thai population were determined by the reverse PCR sequence-specific oligonucleotides probe. Results The HLA-B*13:01 allele was significantly associated with dapsone-induced SCARs compared with dapsone-tolerant controls (odds ratio: 54.00, 95% confidence interval: 7.96–366.16, P=0.0001) and the general population (odds ratio: 26.11, 95% confidence interval: 7.27–93.75, P=0.0001). In addition, HLA-B*13:01 associated with dapsone-induced SJS-TEN (OR: 40.50, 95% confidence interval: 2.78-591.01, P=0.0070) and DRESS (OR: 60.75, 95% confidence interval: 7.44-496.18, P=0.0001). Conclusion This study demonstrated an association between HLA-B*13:01 and dapsone-induced SCARs including Stevens–Johnson syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms in nonleprosy patients. Moreover, these results suggest that the HLA-B*13:01 allele may be a useful genetic marker for prediction of dapsone-induced SCARs in Thai and Han-Chinese populations.

A Frameshift Mutation in PEN-2 Causes Familial Comedones Syndrome

Background: Familial comedones without dyskeratosis are a rare autosomal dominant skin disorder, characterized by the occurrence of comedones that are distributed all over the body with specific features. We have previously reported two Thai families with familial comedones with expanded phenotypic spectrum. However, its genetic defect and pathogenesis remain unknown. Objective: To explore the molecular defect causing familial comedones. Methods: Whole-genome linkage analysis and whole-exome sequencing in family I were performed. Results: We identified a heterozygous one-base pair insertion, c.84_85insT (p. L28FfsX93) in PEN-2, located within the linked region on chromosome 19. PCR-Sanger sequencing confirmed the identified mutation. The mutation segregated with the disease phenotype in family I and was fully penetrant. This similar mutation was also present in the unrelated affected individual from family II. Quantitative PCR revealed increased mRNA expression of PEN-2 in leukocytes of affected individuals. Conclusion: We for the first time identify PEN-2 as the causative gene of familial comedones.

Combination of non-ablative fractional photothermolysis and 0.1% tacrolimus ointment is efficacious for treating idiopathic guttate hypomelanosis

Abstract Background: The efficacy of fractional photothermolysis and topical use of calcineurin inhibitors as treatments of idiopathic guttate hypomelanosis (IGH) have been reported. Data on combination treatments are lacking. Objectives: To evaluate the efficacy and safety of 1550-nm ytterbium/erbium fiber laser combined with 0.1% tacrolimus ointment as a treatment of IGH. Methods: In each patient with IGH, two lesions were assigned as a treatment group, whilst two lesions on another side were chosen as control. Four treatments by fractional 1550-nm ytterbium/erbium fiber laser were delivered every four weeks combined with a twice daily topical application of 0.1% tacrolimus ointment. Lesional skin color was measured by colorimeter. Digital and dermoscopic digital photographs were taken and evaluated by three dermatologists. Results: A total of 120 lesions were treated. Combination treatment normalized the relative lightness index of IGH which reached statistical significant compared with the control at week 12, after three sessions of laser treatment (p = 0.026). Physicians’ assessment score revealed that 91.67% of the lesions on treatment side showed an improvement. Swelling and redness were the most common side effects which spontaneously resolved. Conclusion: Fractional 1550-nm ytterbium/erbium fiber laser combined with topical 0.1% tacrolimus ointment was effective for IGH.

Expanding Phenotypic Spectrum of Familial Comedones

Familial comedones is a rare autosomal dominant disorder characterized by thousands of comedones developing in teens. Some pits or inflammatory lesions may coexist. Only 32 patients from three families have previously been reported. We report herein 12 cases in two unrelated families with familial comedones. Clinical manifestations among members in the same family vastly vary from scattered comedones on the face, trunk, upper and lower extremities to generalized thousands of open comedones, a large number of skin pits and acneiform inflammatory lesions over the entire body. Additionally, multiple severe purulent nodules and abscesses that leave unsightly scars similar to those of hidradenitis suppurativa are observed. Lesions of long-standing inflammation in two patients had developed into squamous cell carcinoma with a poor prognosis. The phenotypic spectrum of familial comedones varies to a large degree. Most importantly, there is potential for some long-standing inflammatory lesions to develop into squamous cell carcinoma. Extra vigilance in surveillance and prompt treatment for such lesions are recommended.

Anterior Tragal Crease Is Associated With Atherosclerosis: A Study Evaluating Carotid Artery Intima–Media Thickness:

The utility of the ear crease sign, anterior tragal crease (ATC), as a marker of atherosclerosis is yet to be established. The intima–media thickness of the common carotid artery (IMT-CCA) has been used as a noninvasive surrogate marker for atherosclerosis. History of traditional risk factors for atherosclerosis was obtained from 147 volunteers; ear examination was also performed and venous blood was drawn for laboratory analysis. The volunteers then underwent an ultrasonography measurement of the IMT-CCA. In univariate analysis, presence of ATC, age, underlying hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular disease, cigarette smoking, low-density lipoprotein, and high-sensitivity C-reactive protein were significantly associated with the IMT-CCA. Further multivariate analysis confirmed a significant association between the presence of ATC and IMT-CCA, when adjusted for other factors (adjusted βATC = .010, 95% confidence interval: 0.0021-0.019). Anterior tragal crease is a potential clinical sign that can predict atherosclerosis. The sign is easily recognizable and may help health-care professionals to identify those at risk of atherosclerosis, especially in people with no clinical signs of the disease.

Pulsed-dye laser as an adjuvant treatment for discoid lupus erythematosus: a randomized, controlled trial

Abstract Purpose: To evaluate the efficacy and safety of pulsed-dye laser (PDL) for discoid lupus erythematosus (DLE) in a double blinded, randomized, controlled fashion. Method: Forty-eight DLE lesions from nine patients were recruited. The lesions on one side of the body were randomized into the treatment group and the other side served as a control. Treatments with the PDL (595 nm) were delivered every four weeks for four consecutive months. The patients were evaluated at weeks 0, 4, 8, 12, 16 and 24. Erythema index (EI) and Texture index (TI) were obtained by Antera3D®. Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) and physician global assessment (PGA) scores were assessed in every visit. Lesional skin biopsies before and after the PDL treatment were taken from four patients. Results: The lesions treated with the PDL demonstrated significantly more decreases in EI, TI and improvement in PGA scores compared to the control. Though there was improvement of mCLASI in the laser group, the significance difference was not observed. Interestingly, real-time polymerase chain reaction showed a reduction in CXCL-9, 10, IFN-γ, IL-1β, TNF-α and TGF-β. Additionally, post-treatment DLE lesions demonstrated decreased CD3, CD4, CD8 and CXCR3-positive cells. Conclusions: Improvements of DLE can be achieved with PDL.