In vivo imaging of patients with chronic pruritus of unknown origin reveals partial sweat duct obstruction with partial itch resolution upon retinoid treatment.

Background: Chronic pruritus of unknown origin (CPUO) is poorly understood and lacks effective treatment options. Objectives: We aimed to elucidate abnormalities in the sweat apparatus of patients with CPUO, and to assess efficacy and safety of treatment with systemic retinoids. Methods: An initial case-control study included 20 affected patients and five healthy controls, for whom heat and sweating were induced, either through a standardized exercise protocol or ingestion of hot water. In vivo high-definition optical coherence tomography, whole-body starch-iodine testing, and skin biopsy for immunofluorescence staining were done to evaluate for sweat duct obstruction. A subsequent retrospective cohort analysis included 56 patients with CPUO, seen at an Itch subspecialty clinic of a single tertiary referral centre, who failed conventional treatments and were treated with isotretinoin and/or acitretin from May 2014 to November 2020. Treatment response to retinoids was defined as a sustained reduction in itch score of ≥2/10. Safety was assessed by proportion stopping treatment due to side effects. Results: In vivo imaging in 19 (95%) patients revealed features of partial keratinaceous sweat duct obstruction with statistically significant luminal dilatation compared to controls. Immunofluorescence studies of three patients' paired lesional/non-lesional biopsies revealed dermcidin accumulation within sweat glands coupled with dermcidin leakage in itchy skin. Fifty-six patients (mean [SD] age 55.2 [17.5] years, 69.6% male) were treated with systemic retinoids. Mean (SD) duration of itch was 116.3 (140.4) months and mean (SD) itch score was 8.2 (1.8). Forty-one (73.2%) initially received isotretinoin, and 15 (26.8%) acitretin. At three months, mean itch score reduced by 2.38 (95% CI -3.2 to -1.6, p < 0.0001). Thirty-eight (67.9%) had a sustained response. Eight (14.81%) achieved an itch score of 0 or 1, with four stopping treatment for a mean (SD) of 318.5 (291.2) days without relapse. Eight (14.3%) stopped or switched retinoid due to adverse effects, with similar incidences between both retinoids, the commonest being dryness. Conclusion: Based on novel findings from physiological imaging studies identifying partial keratinaceous sweat duct obstruction in CPUO, we instituted systemic retinoid treatment to address the underlying pathology. In patients who failed conventional therapies, the treatment appears effective and safe.

Photopatch testing in Singapore: A 10-year retrospective study.

BACKGROUND: Photopatch testing represents the gold standard for the diagnosis of photoallergic contact dermatitis (PACD). We aimed to identify common photoallergens in our tertiary dermatological referral centre from 2012 to 2021, to compare this to the preceding period studied, and data from other communities. METHODS: We conducted a retrospective review of all 90 patients who underwent photopatch testing at the National Skin Centre, Singapore, between 2012 and 2021. RESULTS: Of 90 patients, 19 (21.1%) were male, and the mean age was 41.6 years. Eighty-four (93.3%) underwent testing to our standard sunscreen series, 10 (11.1%) to our extended series, and 73 (81.1%) to their own items. Seventeen (18.9%) were diagnosed with PACD (i.e., photocontact allergy with present or past relevance), 12 (13.3%) with ACD, and 4 (4.4%) with photoaugmented ACD. Relevant reactions were commonest to oxybenzone (8, 9.5%) and mexenone (3, 3.6%). Eleven (15.1%) had PACD to their own items, with 3 of 4 (75%) tested to ketoprofen diagnosed with PACD and the remaining 1 (25%) with photoaugmented ACD. Age, race, sex, atopy, and site of involvement were not associated with photocontact allergy. Compared to the preceding time period, the overall frequency of photocontact allergy and PACD decreased, but rates of photoallergic reactions to individual photoallergens were not significantly different. CONCLUSION: Organic ultraviolet absorbers such as oxybenzone and mexenone remained the most relevant photoallergens. Personal item testing was valuable, and testing to ketoprofen should be considered.

Expression of Staphylococcus aureus Virulence Factors in Atopic Dermatitis.

Atopic dermatitis (AD) is a skin inflammatory disease in which the opportunistic pathogen Staphylococcus aureus is prevalent and abundant. S. aureus harbors several secreted virulence factors that have well-studied functions in infection models, but it is unclear whether these extracellular microbial factors are relevant in the context of AD. To address this question, we designed a culture-independent method to detect and quantify S. aureus virulence factors expressed at the skin sites. We utilized RNase-H‒dependent multiplex PCR for preamplification of reverse-transcribed RNA extracted from tape strips of patients with AD sampled at skin sites with differing severity and assessed the expression of a panel of S. aureus virulence factors using qPCR. We observed an increase in viable S. aureus abundance on sites with increased severity of disease, and many virulence factors were expressed at the AD skin sites. Surprisingly, we did not observe any significant upregulation of the virulence factors at the lesional sites compared with those at the nonlesional control. Overall, we utilized a robust assay to directly detect and quantify viable S. aureus and its associated virulence factors at the site of AD skin lesions. This method can be extended to study the expression of skin microbial genes at the sites of various dermatological conditions.

Older Age Is Not Associated with Worse Outcomes Following Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Decompressive hemicraniectomy (DHC) is commonly offered after large spontaneous intracerebral hemorrhage (ICH) as a life-saving measure. Based on limited available evidence, surgery is sometimes avoided in the elderly. The association between age and outcomes following DHC in spontaneous ICH remains largely understudied. OBJECTIVE: The goal of this study is to investigate the influence of older age on outcomes of patients who undergo DHC for spontaneous ICH. METHODS: In this retrospective cohort study, inpatient data were obtained from the United States Nationwide Inpatient Sample from 2000 to 2011. Using International Classification of Diseases, ninth revision designations, patients with a primary diagnosis of nontraumatic ICH who underwent DHC were identified. The primary outcome of interest was the association of age to inpatient mortality and poor outcome. Subjects were grouped by age: 18-50, 51-60, 61-70, and more than 70 years. Sample characteristics were compared across age groups using χ2 testing, and univariate and multivariate Poisson Regression was performed using a generalized equation to estimate rate ratios for primary and secondary outcomes. RESULTS: One thousand one hundred and forty four patient cases were isolated. Death occurred in an estimated 28.9% and poor outcome in 86.4%. In multivariate Poisson regression models, there was no difference in hospital mortality or poor outcome by age group. Although younger patients were more likely to be diagnosed with herniation, total complication rate was similar between age groups. CONCLUSIONS: Our study results do not provide evidence that age independently predicts in-hospital mortality or poor outcomes. The true influence of age on outcomes is unclear, and further study is needed to determine which factors may be best in selecting candidates for DHC following spontaneous ICH.

Systematic review of immunomodulatory therapies for hidradenitis suppurativa.

Background: Greater understanding of the roles of tumor necrosis factor-α, IL-1ß, IL-10, and the IL-23/T-helper (Th) 17 and IL-12/Th1 pathways in immune dysregulation in moderate/severe hidradenitis suppurativa (HS) has helped in developing new regimens. We aim to review the use of different immunomodulatory therapies used to manage HS. Methods: A comprehensive literature search was conducted on the PubMed and Clinicaltrials.gov databases from 1 January 1947 to 31 December 2018. Only clinical trials, case reports, case series and retrospective analyses published in the English language were included. Results: Our search yielded 107 articles and 35 clinical trials, of which 15 are still ongoing. The tumor necrosis factor-α inhibitors adalimumab and infliximab were the most comprehensively studied agents. Published data from clinical trials support the efficacy of adalimumab, infliximab, anakinra, ustekinumab, bermekimab and apremilast but not etanercept and MEDI8968. Clinical trials for CJM112 have been completed, with results awaiting publication. Trials are underway for secukinumab, IFX-1, INCB054707 and bimekizumab. Biologics used in smaller cohorts include canakinumab, golimumab and rituximab. Most agents are well tolerated and demonstrate a good safety profile, with the most commonly reported adverse event being infections. Discussion and conclusions: To date, adalimumab is the only biologic which has been approved by the United States Food and Drug Administration for HS. However, other agents also show promise, with further trials underway to evaluate their efficacy, tolerability and safety profiles. Different clinical measurement scores and endpoints used to make direct comparison difficult. Longitudinal surveillance and pooled registry data are paramount to evaluate the long-term safety profile and efficacy of therapy.

Management of severe hidradenitis suppurativa with biologic therapy and wide excision.

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular occlusive disease that involves the intertriginous areas. Treatment methods include conventional topical and systemic medication, radiotherapy, biologic agents, and surgical excision. Of late, there has been an increased focus on the use of biologic agents in patients with moderate to severe HS. Here, we present the case of a 46-year-old man with Hurley stage III HS for whom wide excision was ultimately curative, after aggressive medical therapy with the use of infliximab and adalimumab had succeeded in limiting the body surface area affected by the disease. This case demonstrates the effective treatment of severe HS with a combination of biologic therapy and surgery.

Management of severe hidradenitis suppurativa with biologic therapy and wide excision

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular occlusive disease that involves the intertriginous areas. Treatment methods include conventional topical and systemic medication, radiotherapy, biologic agents, and surgical excision. Of late, there has been an increased focus on the use of biologic agents in patients with moderate to severe HS. Here, we present the case of a 46-year-old man with Hurley stage III HS for whom wide excision was ultimately curative, after aggressive medical therapy with the use of infliximab and adalimumab had succeeded in limiting the body surface area affected by the disease. This case demonstrates the effective treatment of severe HS with a combination of biologic therapy and surgery.

Aesthetic assessment in periciliary "v-incision" versus conventional external dacryocystorhinostomy in Asians.

PURPOSE: To determine the functional and aesthetic outcomes of periciliary "v-incision" external dacryocystorhinostomy (DCR) and to compare with conventional approach. METHOD: Charts review of consecutive cases of "v-incision" (VDCR) or conventional DCR performed in a single institute, between January 2007 and March 2014. All procedures were performed or supervised by a single surgeon. Two periciliary incisions were made near the skin-mucosal junction at the upper and lower eyelid margins medial to the punctum joining at the medial canthal angle to form a "v" shape. Subcutaneous dissection was carried out inferomedially to reach the anterior lacrimal crest. DCR was then performed in the usual manner. Functional success was defined as no persistent or recurrent epiphora and patency on irrigation of the lacrimal drainage system at least 6 months post-surgery. A cross-sectional aesthetic survey was conducted by asking the patients to rate their scar appearance satisfaction on a visual analogue scale (VAS). External photographs were graded by two independent, masked physicians using VAS as well as the Stony Brook scar evaluation scale (SBSES). RESULTS: Sixty-one patients with median age of 64 years met the inclusion criteria, with median follow-up duration of 28 months. Thirty-eight eyes underwent VDCR, and 23 had conventional DCR. The functional success rate for VDCR was 83.3, 95 % confidence intervals (95%CI) [lower 0.68, upper 0.92] and for conventional DCR was 73.9 %, 95%CI [lower 0.54, upper 0.87]; without statistically significant difference (p = 0.38). VDCR patients rated higher aesthetic outcome on VAS (mean scores 95.5 ± 16.8 vs 82.9 ± 25.1, p = 0.03). On the SBSES, both observers gave higher aesthetic scores to the VDCR group (observer #1 4.6 ± 1.1 and #2 4.7 ± 1.2, p < 0.01) than conventional DCR (observer #1 3.1 ± 2.8 and #2 2.8 ± 2.1, p < 0.01). More patients reported that they could wear spectacles within 1 week post-VDCR (44.7 vs 4.3 %, p < 0.01). CONCLUSION: "V-incision" external DCR has a similar functional success rate to that of the conventional approach and has superior aesthetic outcomes as reported by surgeons and patients. However, a higher proportion of trainees under supervision performed conventional DCR, and it is uncertain whether the outcomes were also influenced by the level of surgeon's expertise.