Hidradenitis Suppurativa Area and Severity Index Revised (HASI-R): psychometric property assessment.

BACKGROUND: Validated, reliable, globally accepted outcome measurement instruments for hidradenitis suppurativa (HS) are needed. Current tools to measure the physical signs domain for HS rely on lesion counts, which are time-consuming and unreliable. OBJECTIVES: To assess the reliability and validity of the Hidradenitis suppurativa Area and Severity Index Revised (HASI-R) tool, a novel method for assessing HS severity, incorporating signs of inflammation and body surface area involved. METHODS: The measurement properties of the HASI-R tool were evaluated. The tool was created by combining the previously published HASI and Severity and Area Score for Hidradenitis instruments. Twenty raters evaluated 15 patients with HS in a hospital-based ambulatory dermatology clinic. The objectives of the study were to assess inter- and intra-rater reliability of the HASI-R and its components, as well as its construct and known-groups validity. Existing lesion count-based clinician-reported measures of HS and their components were also assessed. Raters were also asked their preferences regarding the various HS severity assessment tools. RESULTS: The HASI-R had moderate inter-rater reliability [intra-class correlation coefficients (ICC) 0·60]. This was better than all other HS physical sign outcome measures evaluated, which had poor inter-rater reliability (ICC < 0·5). HASI-R had the highest intra-rater reliability (ICC 0·91). The HASI-R had good construct validity and demonstrated known-groups validity. The HASI-R was also the most preferred tool by all raters. CONCLUSIONS: Results from the clinometric assessment of the HASI-R are encouraging, and support continued evaluation of this clinician-reported outcome measure.

Identifying key components and therapeutic targets of the immune system in hidradenitis suppurativa with an emphasis on neutrophils.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent and debilitating skin disease of the hair follicle unit that typically develops after puberty. The disorder is characterized by comedones, painful inflammatory nodules, abscesses, dermal tunnels and scarring, with a predilection for intertriginous areas of the body (axillae, inguinal and anogenital regions). Recruitment of neutrophils to HS lesion sites may play an essential role in the development of the painful inflammatory nodules and abscesses that characterize the disease. This is a review of the major mediators involved in the recruitment of neutrophils to sites of active inflammation, including bacterial components (endotoxins, exotoxins, capsule fragments, etc.), the complement pathway anaphylatoxins C3a and C5a, tumour necrosis factor-alpha, interleukin (IL)-17, IL-8 (CXCL8), IL-36, IL-1, lipocalin-2, leukotriene B4, platelet-activating factor, kallikreins, matrix metalloproteinases, and myeloperoxidase inhibitors. Pharmacological manipulation of the various pathways involved in the process of neutrophil recruitment and activation could allow for successful control and stabilization of HS lesions and the remission of active, severe flares.

The mechanistic basis for psoriasis immunopathogenesis: translating genotype to phenotype. Report of a workshop, Venice, 2012.

The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the pathogenic mechanisms that constitute psoriasis. In September 2012, a workshop was held at the 42nd Annual European Society for Dermatological Research in Venice, Italy. By assembling a panel of global dermatology and immunology experts, the objective was to evaluate the current status of the science explaining the mechanism of disease in psoriasis, e.g. dysregulation of the skin immune system and perturbations of epidermal homeostasis. The workshop consisted of four oral presentations, which addressed key topics in psoriasis, delivered by Hervé Bachelez (Paris, France), Antonio Costanzo (Rome, Italy), Michelle Lowes (New York, NY, U.S.A.) and Frank Nestle (London, U.K.). A global expert panel was assembled to stimulate dialogue and debate: Kevin Cooper (Cleveland, OH, U.S.A.), Michel Gilliet (Lausanne, Switzerland), Joerg Prinz (Munich, Germany), Martin Röcken (Tubingen, Germany), Jens Schroeder (Kiel, Germany), Manuelle Viguier (Paris, France), Mayte Suárez-Fariñas (New York, NY, U.S.A.) and Cristina Zielinski (Berlin, Germany). Collectively, the presentations demonstrated the significant advances in understanding immune regulation that have occurred over the past decade by virtue of the study of psoriasis subtypes, phenotypic manifestations and genetic associations. Elucidating the pathogenic and genetic basis of psoriasis holds the promise of a complete understanding of disease mechanisms, predictors of treatment response, novel drug development strategies and customized therapeutic regimens for the individual patient.

Specimen Collection for Translational Studies in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.

Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.

BACKGROUND: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-gamma, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. OBJECTIVES: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. METHODS: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. RESULTS: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-gamma, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-gamma, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. CONCLUSIONS: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.

Quality of life and sexual health in patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating follicular disease. The effect of HS on physical and psychological aspects of sexual function is not well understood. OBJECTIVE: The objective of this study is to investigate the contribution of sexual dysfunction to the quality of life (QoL) of patients with HS and to investigate the extent to which sexual health predicts the QoL in these patients. METHODS: This is an observational cross-sectional study of 50 patients with HS and 50 healthy volunteers who completed questionnaires to measure QoL and sexual functioning using four validated tools. RESULTS: Male patients experienced higher sexual dysfunction and a reduced quality of sexual life, while female patients reported higher sexual distress, compared with control groups. In male patients, sexual QoL and erectile dysfunction predicted a 72% decline in QoL. In female patients, sexual distress and sexual dysfunction predicted 46% variability in QoL index scores, beyond the effects of disease severity. CONCLUSION: Disruptions to sexual functioning greatly contribute to QoL impairments in patients with HS regardless of genital lesions. Health care professionals should inquire about and pay close attention to sexual health concerns in patients with HS.

T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas.

Spontaneous tumor regression, which is observed clinically and histologically in some primary melanomas, occurs in the absence of any effective therapy. It is probably immunologically mediated, because regressing melanomas are infiltrated with larger numbers of activated T cells, primarily CD4+, than nonregressing melanomas. To investigate the hypothesis that spontaneous regression of melanomas is caused by T-cell cytokine production, cytokine mRNA expression in 20 primary melanomas was examined using a noncompetitive, quantitative reverse-transcriptase polymerase chain reaction method. DNA standards were used to generate known numbers of molecules in each sample. Results were standardized to the internal control, glyceraldehyde-3-phosphate dehydrogenase. mRNA for CD35, lymphotoxin (TNF-beta), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-gamma mRNA was also elevated in regressing melanomas but failed to reach statistical significance. The Th2 cytokines IL-10 and IL-13 did not show differences in the regressing melanomas compared to nonregressing melanomas; neither did the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha, nor the growth factors, bFGF and TGF-beta or GM-CSF. This study shows an association between Th1 cytokines and spontaneously regressing melanomas. Although we have not shown that these cytokines cause regression, these findings support our hypothesis that activated CD4+ T cells may mediate melanoma regression by secretion of Th1 cytokines.

Regression of melanoma, but not keratoacanthoma, is associated with increased HLA-B22 and decreased HLA-B27 and HLA-DR1.

Sixty three Caucasian patients with either melanoma, keratoacanthoma or squamous cell carcinoma were human leucocyte antigen (HLA) typed. The regressing tumour groups were compared with their non-regressing counterparts, and the patient groups were compared with a control Caucasian population. Melanoma patients showing histological regression were more likely to be HLA-B22 positive, and HLA-B27 and -DR1 negative, than those without features of regression. When compared with a control population, the group of melanoma patients were more likely to be HLA-B22 positive. Comparison of the group of keratoacanthomas, a self-regressing tumour, and the group of squamous cell carcinomas, a non-regressing tumour, did not show any significant differences in HLA typing.

Retinal detachment after cataract extraction in myopic eyes.

PURPOSE: To determine the incidence of retinal detachment (RD) after cataract extraction in people 40 years of age or older with axial myopia (i.e., axial length > or = 25.5 mm). SETTING: Fifteen Danish eye clinics. METHODS: Two hundred forty-five eyes had cataract extraction performed at 15 eye clinics; 237 eyes had extracapsular cataract extraction (ECCE) and 8 eyes, intracapsular cataract extraction (ICCE). Postoperative data were reported by the practicing ophthalmologists. Mean follow-up was 27 months (range 14 to 32 months). RESULTS: Five RDs occurred in the 245 eyes (2.0%). Excluding the ICCE cases and the two cases of combined cornea transplantation and ECCE, RD occurred in 4 of the 235 eyes that had ECCE (1.7%). The incidence after ECCE with posterior chamber lens implantation was 1.4%. Complete postoperative status was reported on 158 eyes. Forty-eight eyes (30.4%) had a neodymium:YAG capsulotomy and 3 (6.0%) developed an RD 1, 3.5, and 21 months after the capsulotomy. CONCLUSION: The RD incidence after ECCE with posterior chamber lens implantation was low but higher than that in unselected populations. The incidence increased after laser capsulotomy.

Physicochemical properties and X-ray structural studies of the trigonal polymorph of carbamazepine.

The trigonal polymorph of carbamazepine (alpha-carbamazepine) was obtained by crystallization from a number of solvents. It was characterized by means of differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, X-ray power diffraction, thermal microscopy, and powder and intrinsic dissolution rates. The crystal and molecular structures were determined by single-crystal, three-dimensional X-ray analysis. A comparison is drawn between the physicochemical properties of the monoclinic (beta) and trigonal (alpha) forms. Structural features of carbamazepine occurring in these forms and in the acetone solvate are compared. Substantial differences were detected between the two polymorphic forms with regard to infrared and differential scanning calorimetry data, thermomicroscopical behavior, morphology, and molecular conformation.

Technical hints for high dose rate interstitial tongue brachytherapy.

High dose rate (HDR) interstitial tongue brachytherapy is a new treatment modality. This study describes important technical details required for its successful use. Thirteen patients with carcinoma of the oral tongue were treated solely with interstitial brachytherapy using HDR remote afterloading techniques during the years 1994-1997. The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Custom-made mandibular lead shields were inserted prior to treatment. Special reusable Tuen Mun Hospital (TMH) lead buttons were made for improved radiation protection. The median dose given was 55 Gy in ten fractions over 6 days. The interfraction interval was 7 hours for the first seven patients treated and was extended to 8 hours for the other six. Shrinking field techniques were employed and the treatment length of the last fraction was reduced by 5 mm. Commencing with the second patient treated with double planar implants, the medial plane was treated with eight fractions while the lateral plane received ten fractions. To reduce further the potential risk of tract seeding, additional coverage to the implantation tracts was given for the last four patients, with the resultant isodose curves resembling a 'comb rake/brush'. The mean and median measured doses on the inner face of the mandibular shields were 113% and 93% of the reference dose respectively (range 77-247). The dose to the corresponding sites on the gingival surface can be reduced by 75% if the 3 mm thick lead shield is placed successfully. With the use of the TMH button, the transmitted dose to the tissue in direct contact can be reduced by one-third. With the 'comb rake/brush' dose distribution, the high dose volume of the single planar implants could be reduced by 44%, compared with the low dose rate technique, if loading to just 5 mm short of the submandibular skin was required. The mean doses for the combination of eight double planar plus two single planar implants, and ten double planar implants, are on average 29% and 37% greater than the reference dose respectively. An 8% reduction in absolute dose in the region between the planes of the catheters would lead to an even greater magnitude of reduction in morbidity to late responding tissue. The prerequisite for the success of HDR interstitial implants is to develop a good technique in positioning the afterloading catheters and protection of the normal tissue. Its importance merits special attention if HDR remote afterloading interstitial tongue brachytherapy is to realize its full potential.

Chronic progressive external ophthalmoplegia, pigmentary retinopathy, and heart block (Kearns-Sayre syndrome). Report of a case.

Chronic progressive external ophthalmoplegia associated with a pigmentary retinopathy and heart block was described by Kearns & Sayre in 1958. They suggested that the triad represented a syndrome. The cases recorded since then are reviewed and summarised, and several common features are noted. Little attention has previously been paid to the retinopathy. A similar case is presented, and the pigment changes, retinal function, annd fluorescein angiography are examined. There is no clinical evidence for the diagnosis of classical retinitis pigmentosa. The prognosis and aetiology of the condition are discussed.