Acute Erythroderma in a Patient Receiving TNF-α-Blocking Therapy for Hidradenitis Suppurativa

Tumor necrosis factor-α (TNF-α) normally binds to TNF-α receptors, leading to the inflammatory response of autoimmune diseases. Adalimumab is a TNF-inhibiting, anti-inflammatory, biological medication which binds to TNF-α, thus reducing this inflammatory response. The use of TNF-α-inhibiting medication, such as adalimumab, being the first FDA-approved treatment for hidradenitis suppurativa, has drastically changed the management of dermatological diseases. One rarely reported manifestation that occurs as a side effect associated with the use of TNF-α-blocking agents is erythroderma. This study, for the first time, reports the case of a patient suffering from hidradenitis suppurativa with concomitant psoriasis, who developed a severe and acute erythrodermic rash after the start of adalimumab therapy

Overview and comparison of the clinical scores in hidradenitis suppurativa: A real-life clinical data

IntroductionPartly due to its clinical heterogeneity, hidradenitis suppurativa (HS) is difficult to score accurately; illustrated by the large number of disease scores. In 2016, a systematic review by Ingram et al. reported the use of about thirty scores, and since then, this number has increased further. Our aim is twofold: to provide a succinct but detailed narrative review of the scores used to date, and to compare these scores with each other for individual patients.Materials and methodsThe review of the literature was done among articles in English and French, on Google, Google scholar, Pubmed, ScienceDirect and Cochrane. To illustrate the differences between scores, data from some Belgian patients included in the European Registry for HS were selected. A first series of patients compares the severity of the following scores: Hurley, Hurley Staging refined, three versions of Sartorius score (2003, 2007, 2009), Hidradenitis Suppurativa Physician Global Assessment (HS-PGA), International Hidradenitis Suppurativa Severity Scoring System (IHS4), Severity Assessment of Hidradenitis Suppurativa (SAHS), Hidradenitis Suppurativa Severity Index (HSSI), Acne Inversa Severity Index (AISI), the Static Metascore, and one score that is not specific to HS: Dermatology Life Quality Index (DLQI). A second set of patients illustrates how some scores change over time and with treatment: Hurley, Hurley Staging refined, Sartorius 2003, Sartorius 2007, HS-PGA, IHS4, SAHS, AISI, Hidradenitis Suppurativa Clinical Response (HiSCR), the very new iHS4-55, the Dynamic Metascore, and DLQI.ResultsNineteen scores are detailed in this overview. We illustrate that for some patients, the scores do not predictably and consistently correlate with each other, either in an evaluation of the severity at a time-point t, or in the evaluation of the response to a treatment. Some patients in this cohort may be considered responders according to some scores, but non-responders according to others. The clinical heterogeneity of the disease, represented by its many phenotypes, seems partly to explain this difference.ConclusionThese examples illustrate how the choice of a score can lead to different interpretations of the response to a treatment, or even potentially change the results of a randomized clinical trial

A Belgian consensus on the definition of a treat‐to‐target outcome set in psoriasis management

Objective: Treat-to-target (T2T) is an algorithm to reach a predefined outcome. Here, we define a T2T outcome for moderate-to-severe psoriasis vulgaris. Methods: Briefly, the study included a literature review, discussions with key opinion leaders, recruitment of additional dermatologists with experience in managing moderate-to-severe psoriasis, 3 eDelphi survey rounds and a patient focus group. Relevant topics were selected during discussions prior to the survey for the statements. Surveys were based on the eDelphi methodology for consensus-building using a series of statements. Consensus was defined as at least 80% of participants agreeing. A psoriasis patient focus group provided feedback on topic selection and outcome. Results: A total of 5 discussions were held, and 3 eDelphi rounds were conducted with an average of 19 participants per round. The T2T outcome was set assuming shared decision between patient and dermatologist, awareness and referral for comorbidities by the dermatologist and appropriate treatment adherence by the patient. We defined 'ideal' and 'acceptable' targets; the latter referring to conditions restricting certain drugs. The T2T outcome was multidimensional, including >= Delta PASI90/75 or PGA <= 1, itch VAS score <= 1, absence of disturbing lesions, DLQI <= 1/3, incapacity daily functioning VAS score <= 1, safety <= mild side-effects and full/mild tolerability of treatment for the ideal and acceptable target, respectively. Finally, time to achieve the T2T outcome was set at 12 weeks after initiation for all treatments. At all times, safety should not exceed the presence of mild side-effects. Conclusion: With this novel T2T composite outcome for psoriasis, clinicians and patients can make shared decisions on the treatment goals they envisage, as a guidance for future treatment steps - leading to a tight control management of the disease

What causes hidradenitis suppurativa? - 15 years after

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30?April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as ?the only inflammatory skin disease than can be healed?. This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future

The Global Hidradenitis Suppurativa Atlas (GHiSA) methodology: Combining global proportions in a pooled analysis

Introduction: Data concerning the global burden of Hidradenitis Suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalence rates have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. Methods: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). Conclusion: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation, and synthesized using a random-effects model. The novel standardization of the Global Prevalence studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies

Outcome measures for the evaluation of treatment response in hidradenitis suppurativa for clinical practice

Importance Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting

What causes hidradenitis suppurativa ?—15 years after

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30–April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote “Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.” (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, th

Quantitative infrared thermography in hidradenitis suppurativa

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Epidermal autonomous VEGFA/Flt1/Nrp1 functions mediate psoriasis-like disease

Psoriasis is a common long-lasting skin disorder characterized by erythematous plaquescovered with white scales. Microscopic examination of psoriatic skin demonstrates three main hallmarks: an epidermal hyperplasia resulting from an abnormal proliferation and differentiation of the keratinocytes, an immune infiltration mainly located in the upper dermis, and an increasednumber of blood vessels associated with enhanced permeability. It remains unclear whether theinitiation of psoriasis occurs in keratinocytes or in immune cells. Various evidence supports the role of vascular endothelial growth factor A (VEGFA), a potent pro-angiogenic factor, in the pathogenesis of psoriasis. Mainly released by activated keratinocytes and immune cells, VEGFA is associated with the development of psoriasis. Using a psoriasis mouse model mediated by Vegfa overexpression in the epidermis, weshowed that conditional deletion in epidermal cells of Flt1 (Vegfr1) or Neuropilin1 (Nrp1), Vegfa receptor and co-receptor respectively, completely blocked Vegfa-induced psoriasis by regulating the three main hallmarks of the psoriatic skin (epidermal hyperplasia, immuneinfiltrate and neoangiogenesis process). These data clearly show that the main effects of Vegfa are mediated through Nrp1 and Flt1. The epidermal deletion of Flt1 in another mouse model of psoriasis induced by epidermal deletion of c-Jun/JunB was also associated with a decrease of epidermal thickness, neoangiogenesis process and immune infiltration.To identify the downstream signaling of Vegfa in keratinocytes we used transcriptional and chromatin profiling of keratinocytes following Vegfa gain of function together with and without Flt1 or Nrp1 deletion. We showed that the majority of the genes regulated by Vegfa overexpression in keratinocytes depends on the cellular autonomous signaling of Vegfa in keratinocytes that are dependent on Flt1 and/or Nrp1 expression. Analysis of the chromatin remodeling by ATAC-sequencing showed that the chromatin regions that are remodelled presented a significant enrichment in transcription factors binding sites associated with Vegfa overexpression, such as AP-1, p63 and Krüppel Like Factor, thatplay important roles in the skin homeostasis.Using shRNA KO of Fosl1, a transcription factor upregulated under Vegfa overexpression, demonstrated the key role of Fosl1 in promoting chromatin remodeling and change in gene expression following Vegfa overexpression. In conclusion, our study identifies, for the first time to our knowledge, a cellular autonomous Vegfa signaling involving Nrp1 and Flt1 in keratinocytes that mediates psoriaticlike disease and demonstrates the potential clinical relevance of blocking Nrp1/Flt1 for the treatment of psoriasis.Le psoriasis est une maladie chronique de la peau caractérisée par le développement de plaques érythémateuses recouvertes de squames blanches. L'examen microscopique d'une peau psoriasique met évidence 3 modifications importantes: une hyperplasie de l'épiderme résultant d'une prolifération et différentiation anormale des kératinocytes, un infiltrat inflammatoire localisé dans le derme superficiel et une augmentation du nombre de vaisseaux sanguins et de leur perméabilité. Cependant, il n'est pas encore clairement établi si la cellule initiatrice est le kératinocyte ou les cellules immunitaires. De nombreux travaux supportent le rôle du VEGFA ( Vascular endothelial growth factor), qui est un facteur pro-angiogenique, dans le développement du psoriasis. En utilisant un modèle murin de psoriasis résultant d'une surexpression du VEGFA par les cellules kératinocytaires, nous avons démontré que la délétion simultanée au sein des kératinocytes de Flt1 et Nrp1, respectivement récepteur et co-récepteur au VEGFA était associée à une résolution du psoriasis en régulant la prolifération des kératinocytes, l'infiltrat inflammatoire et la néo-angiogénèse. Par ailleurs, nous avons également démontré que la délétion de Flt1 au niveau des kératinocytes dans un autre modèle de psoriasis résultant d'une délétion épidermique de c-Jun/JunB, était également associé à une diminution de la prolifération des kératinocytes, une diminution de l'infiltrat inflammatoire et une diminution de la néo-angiogenèse. Afin d'identifier la cascade résultant de l'activation du Vegfa, nous avons étudié le profil transcriptionnel et chromatinien des kératinocytes en l'absence de Nrp1 ou Flt1. Nous avons observé que la plupart des gènes dérégulés par la surexpression au niveau des kératinocytes du Vegfa normalisaient leur expression quand Nrp1 ou Flt1 n'étaient plus exprimés par les kératinocytes. L'étude du profil chromatinien de ces gènes par ATAC-sequencing a permi de mettre en évidence des potentiels régulateurs comme AP-1, p63 ou Klf qui sont des facteurs de transcription jouant un rôle crucial dans le développement de l'épiderme. En bloquant l'expression de Fosl1, une membre de la famille AP-1 et qui était surexprimé après surexpression épidermique du Vegfa et qui voyait son expression se normalisé quand Flt1 n'était pas exprimé par les kératinocytes, nous avons pu mettre en évidence son implication dans la régulation du profil chromatinien et du profil transcriptionnel des gènes dérégulés par la surexpression du Vegfa. En conclusion, notre travail a démontré pour la première fois le rôle de l'axe VEGFA/Flt1/Nrp1 dans le psoriasis et nous avons également démontré la relevance du blocage de Flt1 et Nrp1 dans le psoriasis.Doctorat en Sciences médicales (Médecine)info:eu-repo/semantics/nonPublishe

Hidradenitis Suppurativa in General Practice: A Pilot Study

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