Role of antimicrobial peptides in atopic dermatitis

Host defense peptides (HDPs) or antimicrobial peptides (AMPs) are short cationic amphipathic peptides of divergent sequences, which are part of the innate immune system and produced by various types of cells and tissues. The predominant role of HDPs is to respond to and protect humans against infection and inflammation. Common human HDPs include defensins, cathelicidin, psoriasin, dermcidin, and ribonucleases, but these peptides may be dysregulated in the skin of patients with atopic dermatitis (AD). Current evidence suggests that the antimicrobial properties and immunomodulatory effects of HDPs are involved in AD pathogenesis, making HDPs research a promising area for predicting disease severity and developing novel treatments for AD. In this review, we describe a potential role for human HDPs in the development, exacerbation, and progression of AD and propose their potential therapeutic benefits

Genetic Association of Co‐Trimoxazole‐Induced Severe Cutaneous Adverse Reactions Is Phenotype‐Specific: HLA Class I Genotypes and Haplotypes

Co‐trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case‐control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX‐induced SCARs, including Stevens‐Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX‐induced SCARs were enrolled and compared with 91 CTX‐tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX‐induced SCARs was phenotype‐specific. HLA‐B*15:02 and HLA‐C*08:01 alleles were significantly associated with CTX‐induced SJS/TEN, whereas the HLA‐B*13:01 allele was significantly associated with CTX‐induced DRESS. In addition, a significant higher frequency of HLA‐A*11:01‐B*15:02 and HLA‐B*13:01‐C*03:04 haplotypes were detected in the group of CTX‐induced Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX‐induced SCARs is phenotype‐specific. Interestingly, these association was observed only in HIV‐infected patients but not in non‐HIV‐infected patients

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

Abstract 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

Gefitinib-associated lichen planus pigmentosus-like eruption

The epidermal growth factor receptor (EGFR) signaling pathway is one of the oncogenic pathways in non-small cell lung cancer. Gefitinib is classified as a first-generation EGFR-tyrosine kinase inhibitor (TKI). A variety of cutaneous adverse effects related to the drug has been reported. Cutaneous hyperpigmentation is a rare side effect of EGFR inhibitor (EGFRi). Herein, we report a 62-year-old woman with non-small cell lung carcinoma who presented with symmetrical, slate-gray-to-brownish-black macular pigmentation on sun-exposed and non-sun-exposed areas after eight months of gefitinib administration. The clinical features were consistent with lichen planus pigmentosus. This case highlights the unusual hyperpigmented condition occurring in patients taking EGFR-TKIs

Gefitinib-associated lichen planus pigmentosus-like eruption

The epidermal growth factor receptor (EGFR) signaling pathway is one of the oncogenic pathways in non-small cell lung cancer. Gefitinib is classified as a first-generation EGFR-tyrosine kinase inhibitor (TKI). A variety of cutaneous adverse effects related to the drug has been reported. Cutaneous hyperpigmentation is a rare side effect of EGFR inhibitor (EGFRi). Herein, we report a 62-year-old woman with non-small cell lung carcinoma who presented with symmetrical, slate-gray-to-brownish-black macular pigmentation on sun-exposed and non-sun-exposed areas after eight months of gefitinib administration. The clinical features were consistent with lichen planus pigmentosus. This case highlights the unusual hyperpigmented condition occurring in patients taking EGFR-TKIs

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS): 11 years retrospective study in Thailand

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but life-threatening adverse drug reaction. Several criteria have been established to aid the diagnosis. However, patients with DRESS remained underdiagnosis and undertreatment. Methods: Medical records of hospitalized patients at the King Chulalongkorn Memorial Hospital from January 2004–December 2014 due to DRESS were enrolled retrospectively using RegiSCAR diagnostic criteria. Results: A total of 52 patients were included. Thirty-seven patients (71.2%) were female. The four most common causative agents were phenytoin (23.1%), nevirapine (17.3%), allopurinol (15.4%), and cotrimoxazole (13.5%). The overall prevalence was 9.63 cases per 100,000 inpatients. Median onset time (IQR) was 16 (9–27) days. Allopurinol was associated with longer onset time than others (p = 0.014). Clinical presentation: skin rash 100%, fever 78.8%, and lymphadenopathy 50%. The majority (84.6%) had single internal organ involvement. The most common internal organ involvement was liver (94.2%). Allopurinol was associated with higher incidence of renal involvement (p = 0.01). Up to 60% of patients had eosinophilia. Allopurinol was associated with higher eosinophilia (p = 0.003). A half of patients received systemic corticosteroids. Two mortality cases were reported (omeprazole-fulminant hepatitis and phenytoin-nosocomial infection). Conclusions: DRESS is associated with severe morbidity and mortality. Phenytoin, nevirapine, allopurinol, and cotrimoxazole were the major causes. Allopurinol-induced DRESS had the longest onset time, and was associated with higher eosinophilia and incidence of renal involvement. Raising awareness among both health care providers and public for early detection and withdrawal of the causative agent is critical to save life and reduce morbidity

Red light emitting diode as an adjuvant treatment for epidermal growth factor receptor inhibitors-induced paronychia

We evaluated the efficacy and safety of red light LED as an adjuvant treatment for epidermal growth factor receptor inhibitor-induced paronychia. Eight patients were recruited in this randomized, single-blinded controlled trial. They were randomized to receive red-light on one hand or foot 2–3 times/week for 6 weeks while the contralateral side served as controls. The standard treatments were continued. Erythema and lesion elevation observed by Anthera® 3D, severity and pain scores were obtained at weeks 0, 2, 4, 6, and 8. The red light group showed significantly lower erythema, severity, and pain scores at weeks 4, 6, and 8. The elevation was significantly lower in the red light group at every follow-up visit. No adverse events occurred. Red light therapy may be an option as adjunctive treatment for EGFRi-induced paronychia

Skin Manifestations in Patients with Adult-onset Immunodeficiency due to Anti-interferon-gamma Autoantibody: A Relationship with Systemic Infections

Adult-onset immunodeficiency due to anti-interferon-γ autoantibody is an emerging acquired immunodeficiency with frequent skin manifestations. A retrospective chart review was conducted and identified 41 patients with the syndrome. Skin involvement was detected in 33 (80%) patients, 15 (45%) with infective skin diseases and 27 (82%) with reactive skin disorders. Reactive lesions were mostly neutrophilic dermatoses, e.g. Sweet syndrome. Of note, the presence of neutrophilic dermatoses was highly associated with infections of other sites. An adjusted odds ratio for the existence of infections in patients with neutrophilic dermatoses was 14.79 (95% CI: 5.13, 42.70; p < 0.001). Moreover, neutrophilic dermatoses were significantly correlated with opportunistic infections observed in those with defects in cell-mediated immunity including non-tuberculous mycobacterium and disseminated fungal infection. The odds ratio for opportunistic infections in the presence of neutrophilic dermatoses was 12.35 (95% CI: 5.00, 30.55; p < 0.001). Thus, the presence of neutrophilic dermatoses in patients with the syndrome can signal opportunistic infections that warrant physician attention

Correlations between histopathologic findings, serum biomarker levels, and clinical outcomes in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Abstract Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease