95 results on '"Diercks GFH"'
Search Results
2. Blisters in disguise
- Author
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Dowlatshahi, EA, primary, Diercks, GFH, additional, and van Doorn, MBA, additional
- Published
- 2018
- Full Text
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3. Orf-induced pemphigoid with antilaminin-332 antibodies
- Author
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van den Bos, Renate, Middelburg, Tom, van Biezen, p, Baltissen - van der Eijk, Annemiek, Pas, HH, Diercks, GFH, Dermatology, Internal Medicine, and Virology
- Published
- 2012
4. Effects of fosinopril and pravastatin on cardiovascular events in microalbuminuric subjects without hypertension and hypercholesterolemia: A single-center, double-blind, randomized, placebo-controlled trial with 2 x 2 factorial design (PREVEND IT)
- Author
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Asselbergs, FW, Diercks, GFH, Hillege, HL, van Boven, AJ, Janssen, WMT, Voors, AA, de Zeeuw, D, de Jong, PE, van Veldhuisen, DJ, van Gilst, WH, Cardiovascular Centre (CVC), and Groningen Kidney Center (GKC)
- Published
- 2003
5. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity
- Author
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Hillege, HL, Janssen, WMT, Bak, AAA, Diercks, GFH, Grobbee, DE, Crijns, HJGM, van Gilst, WH, de Zeeuw, D, de Jong, PE, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), and Translational Immunology Groningen (TRIGR)
- Subjects
PREDICTOR ,PEOPLE ,MORTALITY ,population ,risk factors ,cardiovascular diseases diagnosis ,CONSUMPTION ,URINARY ALBUMIN EXCRETION ,HEART-DISEASE ,ESSENTIAL-HYPERTENSION ,SMOKING ,albuminuria epidemiology ,cross sectional studies - Abstract
Objectives. To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. Design. Cross-sectional cohort study. Setting. Inhabitants of the city of Groningen, the Netherlands. Subjects. All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. Main outcome measures. Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. Results. Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. Conclusions. Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.
- Published
- 2001
6. Relation between albumin in the urine and electrocardiographic markers of myocardial ischemia in patients without diabetes mellitus
- Author
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Diercks, GFH, Hillege, HL, van Boven, AJ, Kors, JA, Janssen, WMT, Grobbee, DE, Crijns, HJGM, van Gilst, WH, Medical Informatics, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), and Translational Immunology Groningen (TRIGR)
- Subjects
PREDICTOR ,SDG 3 - Good Health and Well-being ,MORTALITY ,MICROALBUMINURIA ,ESSENTIAL-HYPERTENSION ,REFLECTS ,ELDERLY PEOPLE ,DISEASE ,POPULATION - Abstract
We demonstrated that in a large nondiabetic population, a graded continuous relation was present between the level of urinary albumin excretion and ischemic electrocardiographic abnormalities, without an apparent threshold. These data suggest that the level of urinary albumin excretion can be used to establish cardiovascular risk in the population at large.
- Published
- 2001
7. High tasting glucose and QTc duration in a large healthy cohort
- Author
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Lefrandt, JD, Diercks, GFH, van Boven, AJ, Crijns, HJGM, van Gilst, WH, Gans, ROB, Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), and Translational Immunology Groningen (TRIGR)
- Subjects
INTERVAL PROLONGATION - Published
- 2000
8. Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with Fosinopril and Pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the Prevention of REnal and Vascular ENdstage Disease Intervention Trial [PREVEND IT])
- Author
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Diercks, GFH, Janssen, WMT, van Boven, AJ, Bak, AAA, de Jong, PE, Crijns, HJGM, van Gilst, WH, Cardiovascular Centre (CVC), and Translational Immunology Groningen (TRIGR)
- Subjects
PREDICTOR ,MORBIDITY ,ALBUMINURIA ,MORTALITY ,ENDOTHELIAL DYSFUNCTION ,ANTIHYPERTENSIVE DRUGS ,PROTEINURIA ,DIABETES-MELLITUS ,ESSENTIAL-HYPERTENSION ,CONVERTING-ENZYME-INHIBITION - Abstract
This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/day will prevent cardiovascular and renal disease in nonhypertensive (RR 10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease. (C) 2000 by Excerpta Medica, Inc.
- Published
- 2000
9. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria.
- Author
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Asselbergs FW, Diercks GFH, Hillege HL, van Boven AJ, Janssen WMT, Voors AA, de Zeeuw D, de Jong PE, van Veldhuisen DJ, van Gilst WH, and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators
- Published
- 2004
10. Blisters in disguise
- Author
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Dowlatshahi, EA, Diercks, GFH, and van Doorn, MBA
11. Relation of electrocardiographic abnormalities to levels of serum C-reactive protein.
- Author
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Asselbergs FW, van Boven AJ, Stuveling EM, Diercks GFH, Hillege HL, Kors JA, de Jong PE, van Gilst WH, Prevention of REnal and Vascular ENdstage Disease (PREVEND) Study Group, Asselbergs, Folkert W, van Boven, Ad J, Stuveling, Erik M, Diercks, Gilles F H, Hillege, Hans L, Kors, Jan A, de Jong, Paul E, van Gilst, Wiek H, and PREVEND Study Group
- Published
- 2003
- Full Text
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12. An Unexpected Finding of a PTPN11 Germline Mutation in a Patient With a Melanocytic Lesion With a Somatic MAP2K1 Mutation. Coincidence or Not?
- Author
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van der Woude S, Klein Wassink-Ruiter JS, Kluiver J, de Jonge M, and Diercks GFH
- Abstract
Melanocytic tumors are a diverse group of lesions and are traditionally classified based on a combination of clinical presentation as well as histological examination. More recently, molecular diagnostics has become an increasingly important part of differentiating different melanocytic lesions in the current WHO standards. This molecular testing, however, can result in unexpected findings. In this report, we describe that molecular testing of a clinical atypical melanocytic lesion showed a mutation in the MAP2K1 gene as well as an unexpected germline mutation in PTPN11, indicative of Noonan syndrome. Based on these findings we concluded that the patient had a MAP2K1 associated melanocytic lesion with Noonan syndrome as an incidental finding. Melanomas are classically not associated with Noonan syndrome. However, we hypothesized that the germline mutations of PTPN11 and the somatic second hit mutation in the MAP2K1 genes might be involved in the formation of the aforementioned lesion. As they are both part of the RAS-MAPK pathway. Furthermore, with the expansion of molecular diagnostics in melanomas, we expect to find an increase in unexpected (germline) mutations., (© 2024 The Author(s). Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)
- Published
- 2024
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13. Variants in the L12 linker domain of KRT10 are causal to atypical epidermolytic ichthyosis.
- Author
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van der Velden JJAJ, van Gisbergen MW, Kamps MAF, Janssen R, Diercks GFH, Steijlen PM, van Geel M, and Bolling MC
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- Adult, Child, Preschool, Female, Humans, Male, HaCaT Cells, Heterozygote, Keratin-1 genetics, Mutation, Missense, Protein Domains genetics, Skin pathology, Infant, Newborn, Hyperkeratosis, Epidermolytic genetics, Hyperkeratosis, Epidermolytic pathology, Hyperkeratosis, Epidermolytic diagnosis, Keratin-10 genetics, Pedigree
- Abstract
Epidermolytic ichthyosis (EI) is a type of congenital ichthyosis, characterized by erythema and blistering at birth followed by hyperkeratosis. EI is caused by pathogenic variants in the genes KRT1 and KRT10, encoding the proteins keratin 1 (KRT1) and keratin 10 (KRT10), respectively, and is primarily transmitted by autosomal-dominant inheritance, although recessive inheritance caused by nonsense variants in KRT10 is also described. The keratins form a network of intermediate filaments and are a structural component of the cytoskeleton, giving strength and resilience to the skin. We present three cases of mild EI caused by pathogenic KRT10 variations in the L12 linker domain. To our knowledge, this is the first time L12 linker domain pathogenic variants are identified in KRT10 for EI. The aim of this study was to identify gene variants for patients with EI in KRT1 or KRT10. To establish the pathogenicity of the found variations in KRT10, we evaluated all patients and available family members clinically. Genetic analyses were performed using Sanger sequencing. Vectors containing wild-type or mutated forms of KRT10 were transfected into HaCaT cells and analyzed by high-resolution confocal microscopy. Genetic analysis of KRT10 identified a heterozygous de novo variant c.910G>A p.(Val304Met) in family 1, a familial heterozygous variant c.911T>C p.(Val304Ala) in family 2, and a familial heterozygous variant c.917T>C p.(Met306Thr) in family 3. All identified missense variants were located in the L12 linker domain of KRT10. In vitro study of aggregate formation of the missense variants in KRT10 only showed a very mild and not quantifiable aggregate formation in the KRT10 network, compared with the wild-type sequence. We report three different novel missense variants in the L12 linker domain of KRT10 in patients with an atypical, milder form of EI resembling peeling skin syndrome., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)
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- 2024
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14. Utility and Micro-Costing Framework for TERT Promoter Mutation Analysis in Melanocytic Lesions of Uncertain Malignant Potential: A Retrospective Study in Dutch Local Clinical Practice.
- Author
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Barrutia L, Schuuring E, Rácz E, Diercks GFH, and van Kempen LC
- Abstract
The 2018 WHO edition on the classification of cutaneous melanocytic tumors recognizes eight evolutionary pathways of melanoma and describes tumors of uncertain malignant potential for each. When histology and immunohistochemistry do not support a confident conclusion about its malignant potential, a window of diagnostic uncertainty is created. Mutations in the telomerase reverse transcriptase gene promoter ( TERT p) are highly specific for melanoma and can be used as an ancillary technique to acquire a higher level of confidence in the diagnosis. However, little is known about the cost-effectiveness of testing for TERT p mutations. The aims of this study were to determine how often knowledge of the TERT p mutation status contributed to the final diagnosis and to develop a micro-costing framework to calculate cost-effectiveness. A retrospective analysis of all cutaneous melanocytic lesions that were discussed in the Noord-Nederland Melanoma Panel from January 2021 to October 2022 was performed to identify the cases in which the preliminary histopathological diagnosis was uncertain regarding malignancy (ambiguous, likely benign, or likely malignant). For cases in which a TERTp mutation analysis was performed, the final diagnoses were collected, and it was determined whether this impacted the overall conclusion. A micro-costing framework was established to model the financial impact of introducing TERTp mutation analyses and subsequent clinical procedures. The study included 367 cases, of which 175 diagnoses of uncertain malignant potential were initially reported. TERTp mutation analysis was performed for 151/175 (86%). In 38% of these cases, a higher level of confidence regarding malignant potential was obtained. The implementation of TERT p mutation analyses for cutaneous melanocytic proliferations with uncertain malignant potential can narrow the window of diagnostic uncertainty. For the patient group with an initial uncertain diagnosis, the increased cost for molecular testing (86.145 €) was compensated by a reduced overall treatment cost (-122.304 €). A microsimulation model to determine the cost-effectiveness of TERT p mutation analysis projected an overall saving for the healthcare system.
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- 2024
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15. Beyond the skin: B cells in pemphigus vulgaris, tolerance and treatment.
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Strandmoe AL, Bremer J, Diercks GFH, Gostyński A, Ammatuna E, Pas HH, Wouthuyzen-Bakker M, Huls GA, Heeringa P, Laman JD, and Horváth B
- Subjects
- Humans, Autoantibodies immunology, Immune Tolerance immunology, Pemphigus immunology, Pemphigus drug therapy, Pemphigus therapy, B-Lymphocytes immunology, Rituximab therapeutic use
- Abstract
Pemphigus vulgaris (PV) is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted. However, the exact pathomechanism, mechanisms of onset, disease course and relapse remain unclear. In this narrative review, we provide an overview of the fundamental research progress that has unfolded over the past few centuries to give rise to current and emerging therapies. Furthermore, we summarize the multifaceted roles of B cells in PV, including their development, maturation and antibody activity. Finally, we explored how these various aspects of B-cell function contribute to disease pathogenesis and pave the way for innovative therapeutic interventions., Competing Interests: Conflicts of interest A.G. reports fees from AbbVie, Sanofi and UCB (advisory boards, shares, speaker); Eli Lilly, Janssen and Pfizer (advisory boards, shares); Leo Pharma and Regeneron (advisory boards); and GSK (shares). B.H. reports fees from AbbVie and Janssen-Cilag (advisory boards, consultations, educational grants, investigator initiative studies); Novartis Pharma (advisory boards, consultations, investigator initiative studies); Argenx, Boehringer-Ingelheim and UCB Pharma (advisory boards, consultations); Akari Therapeutics and Celgene (consultations, investigator initiative studies); Leo Pharma, Philips, Regeneron, Roche and Sanofi (consultations); and Solenne B.V. (investigator initiative studies); which fees were paid to the institution. A.-L.S., J.B., G.F.H.D., E.A., H.H.P., M.W.-B., G.A.H., P.H., and J.D.L. declare that they have no conflicts of interest regarding the scope of this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)
- Published
- 2024
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16. Increased Interferon Signaling in Vaginal Tissue of Patients With Primary Sjögren Syndrome.
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Visser A, van Nimwegen JF, Wilbrink R, Liefers SC, van der Tuuk K, Mourits MJE, Diercks GFH, Bart J, van der Vegt B, van Kempen LC, Bootsma H, Kroese FGM, and Verstappen GM
- Subjects
- Humans, Female, Adult, Middle Aged, Myxovirus Resistance Proteins genetics, Myxovirus Resistance Proteins metabolism, Biopsy, Vaginal Diseases metabolism, Vaginal Diseases pathology, Vaginal Diseases immunology, Sjogren's Syndrome metabolism, Sjogren's Syndrome immunology, Sjogren's Syndrome pathology, Vagina pathology, Vagina immunology, Vagina metabolism, Signal Transduction, Interferons metabolism
- Abstract
Objective: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in the vaginal tissue of patients with pSS., Methods: Vaginal biopsies of 8 premenopausal patients with pSS experiencing vaginal dryness and 7 age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using NanoString technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells [pDCs])., Results: The most enriched pathway in vaginal biopsies from patients with pSS compared to non-pSS controls was the interferon (IFN) signaling pathway ( P < 0.01). Pathway scores for Janus kinase and signal transducer and activator of transcription (JAK-STAT) and Notch signaling were also higher ( P < 0.01 for both pathways). Conversely, transforming growth factor-β signaling and angiogenesis pathway scores were lower in pSS ( P = 0.02 and P = 0.04, respectively). Differences in IFN signaling between patients with pSS and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. IFN-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity., Conclusion: Upregulation of IFN signaling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology (ie, vaginal dryness)., (Copyright © 2024 by the Journal of Rheumatology.)
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- 2024
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17. Expression of myxovirus resistance protein A in lupus nephritis and other glomerular nephropathies.
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Liu L, de Leeuw K, der Meer BD, van Goor H, Stegeman CA, van den Heuvel MC, Diercks GFH, and Westra J
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- 2024
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18. Absence of Epidermal Antibodies in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Patients but Beware of Single Positive Results.
- Author
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Diercks GFH, Meijer JM, Bolling MC, Scholtens-Jaegers SMHJ, Bremer J, and Horvath B
- Abstract
Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and potentially life-threatening mucocutaneous blistering diseases that clinically can resemble autoimmune bullous diseases. Moreover, it has been shown that autoantibodies against epidermal proteins are present in SJS/TEN., Objectives: To establish the presence of antibodies against desmosomal and hemidesmosomal proteins in confirmed SJS/TEN patients., Methods: Serum of SJS/TEN patients diagnosed based on clinical criteria, e.g., epidermal detachment with erosions and severe mucosal lesions, (suspicion of) a culprit drug, and matching histologic results was evaluated by various techniques, e.g., indirect immunofluorescence on monkey esophagus, salt split skin and rat bladder, immunoblotting (IB) and immunoprecipitation (IP), ELISAs against desmogleins and BP180, keratinocyte footprint assay, and keratinocyte binding assay., Results: A total of 28 patients were included in this study, 15 men and 13 women with a mean age of 56 years. In most patients, none of the serological tests were positive. In two patients, an elevated DSG3 titer was found suspicious for pemphigus vulgaris. Three patients had elevated NC16a titers, suggesting bullous pemphigoid. However, in all these patients, no other tests were positive and in these patients, the biopsy for direct immunofluorescence showed no evidence for an autoimmune bullous disease. Three patients showed reactivity against rat bladder rat bladder; these were, however, completely negative for A2ML1, envoplakin, and periplakin in the IB as well as the IP., Conclusions: Serological analysis for desmosomal and hemidesmosomal antibodies is reliable to rule an autoimmune bullous disease in patients with suspected SJS/TEN. However, one should not rely on one single test method since false positive results can occur. Moreover, this study also makes it less plausible that antibodies against desmosomal and/or hemidesmosomal components are involved in the pathogenesis of SJS/TEN., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Gilles F. H. Diercks et al.)
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- 2024
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19. Evolution of genome diagnostics in epidermolysis bullosa: Unveiling the power of next-generation sequencing.
- Author
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Baardman R, Lemmink HH, Yenamandra VK, Commandeur-Jan SZ, Viel M, Kooi KA, Diercks GFH, Meijer R, van Geel M, Scheffer H, Sinke RJ, Sikkema-Raddatz B, Bolling MC, and van den Akker PC
- Abstract
Background: Genome diagnostics is considered gold standard diagnostics for epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous group of rare disorders characterized by blistering and wounding of mucocutaneous tissues. EB is caused by pathogenic variants in genes encoding proteins of the dermo-epidermal junction. Accurate genetic diagnosis of EB is crucial for prognostication, counselling and precision-medicine. Genome diagnostics for EB started in 1991 with the introduction of Sanger sequencing (SS), analysing one gene at a time. In 2013, SS was superseded by next-generation sequencing (NGS), that allow for high-throughput sequencing of multiple genes in parallel. Several studies have shown a beneficial role for NGS in EB diagnostics, but its true benefit has not been quantified., Objectives: To determine the benefit of NGS in EB by systematically evaluating the performance of different genome diagnostics used over time based on robust data from the Dutch EB Registry., Methods: The diagnostic performances of SS and NGS were systematically evaluated in a retrospective observational study including all index cases with a clinical diagnosis of EB in whom genome diagnostics was performed between 01 January 1994 and 01 January 2022 (n = 308), registered at the Dutch EB Expertise Centre., Results: Over time, a genetic diagnosis was made in 289/308 (94%) EB cases. The diagnostic yield increased from 89% (SS) to 95% (NGS). Most importantly, NGS significantly reduced diagnostic turnaround time (39 days vs. 211 days, p < 0.001). The likelihood of detecting variants of uncertain significance and additional findings increased from 5% and 1% (SS) to 22% and 13% (NGS) respectively., Conclusions: Our study quantifies the benefit of NGS-based methods and demonstrate they have had a major impact on EB diagnostics through an increased diagnostic yield and a dramatically decreased turnaround time (39 days). Although our diagnostic yield is high (95%), further improvement of genome diagnostics is urgently needed to provide a genetic diagnosis in all EB patients., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2024
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20. Epidermal growth factor receptor inhibition leads to cellular phenotype correction of DSP-mutated keratinocytes.
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Andrei D, Bremer J, Kramer D, Nijenhuis AM, van der Molen M, Diercks GFH, van den Akker PC, Vermeer MCSC, van der Meer P, and Bolling MC
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- Humans, Epidermis metabolism, Keratinocytes metabolism, Phenotype, Skin metabolism, Desmoplakins genetics, Desmoplakins metabolism, ErbB Receptors genetics, ErbB Receptors metabolism, Hair Diseases genetics, Keratoderma, Palmoplantar genetics
- Abstract
Desmoplakin (DSP) is a desmosomal component expressed in skin and heart, essential for desmosome stability and intermediate filament connection. Pathogenic variants in the DSP gene encoding DSP, lead to heterogeneous skin, adnexa and heart-related phenotypes, including skin fragility, woolly hair (WH), palmoplantar keratoderma (PPK) and arrhythmogenic/dilated cardiomyopathy (ACM/DCM). The ambiguity of computer-based prediction analysis of pathogenicity and effect of DSP variants, indicates a necessity for functional analysis. Here, we report a heterozygous DSP variant that was not previously described, NM_004415.4:c.3337C>T (NM_004415.4(NP_004406.2):p.(Arg1113*)) in a patient with PPK, WH and ACM. RNA and protein analysis revealed ~50% reduction of DSP mRNA and protein expression. Patient's keratinocytes showed fragile cell-cell connections and perinuclear retracted intermediate filaments. Epidermal growth factor receptor (EGFR) is a transmembrane protein expressed in the basal epidermal layer involved in proliferation and differentiation, processes that are disrupted in the development of PPK, and in the regulation of the desmosome. In skin of the abovementioned patient, evident EGFR upregulation was observed. EGFR inhibition in patient's keratinocytes strongly increased DSP expression at the plasma membrane, improved intermediate filament connection with the membrane edges and reduced the cell-cell fragility. This cell phenotypic recovery was due to a translocation of DSP to the plasma membrane together with an increased number of desmosomes. These results indicate a therapeutic potential of EGFR inhibitors for disorders caused by DSP haploinsufficiency., (© 2024 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
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- 2024
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21. Infiltration analysis of eosinophils and basophils and co-expression of CD69, CD63, IL-31 and IgE in patients with bullous and non-bullous pemphigoid.
- Author
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Kotnik N, Langner A, Meyer NH, Pas HH, Gibbs BF, Meijer JM, Diercks GFH, Horváth B, and Raap U
- Subjects
- Humans, Basophils, Immunoglobulin E, Collagen Type XVII, Autoantibodies, Tetraspanin 30, Eosinophils, Pemphigoid, Bullous
- Published
- 2024
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22. Patients suffering from dystrophic epidermolysis bullosa are prone to developing autoantibodies against skin proteins: A longitudinal confirmational study.
- Author
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Bremer J, Pas HH, Diercks GFH, Meijer HJ, van der Molen SM, Nijenhuis AM, van Nijen-Vos LL, Morandé P, Yubero MJ, Palisson F, Fuentes I, and Pasmooij AMG
- Subjects
- Humans, Autoantibodies, Skin metabolism, Epidermolysis Bullosa Dystrophica genetics, Epidermolysis Bullosa metabolism, Epidermolysis Bullosa, Junctional genetics, Autoimmune Diseases
- Abstract
Epidermolysis bullosa (EB) is a heritable skin blistering disease caused by variants in genes coding for proteins that secure cell-cell adhesion and attachment of the epidermis to the dermis. Interestingly, several proteins involved in inherited EB are also associated with autoimmune blistering diseases (AIBD). In this study, we present a long-term follow-up of 15 patients suffering from recessive dystrophic or junctional EB. From these patients, 62 sera were analysed for the presence of autoantibodies associated with AIBD. We show that patients suffering from recessive dystrophic EB (RDEB) are more susceptible to developing autoantibodies against skin proteins than patients suffering from junctional EB (70% vs. 20%, respectively). Interestingly, no correlation with age was observed. Most patients showed reactivity to Type XVII collagen/linear IgA bullous dermatosis autoantigen (n = 5; 33%), followed by BP230 (n = 4; 27%), Type VII collagen (n = 4; 27%) and laminin-332 (n = 1; 7%). The pathogenicity of these autoantibodies remains a subject for future experiments., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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23. Disruption of TUFT1, a Desmosome-Associated Protein, Causes Skin Fragility, Woolly Hair, and Palmoplantar Keratoderma.
- Author
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Verkerk AJMH, Andrei D, Vermeer MCSC, Kramer D, Schouten M, Arp P, Verlouw JAM, Pas HH, Meijer HJ, van der Molen M, Oberdorf-Maass S, Nijenhuis M, Romero-Herrera PH, Hoes MF, Bremer J, Slotman JA, van den Akker PC, Diercks GFH, Giepmans BNG, Stoop H, Saris JJ, van den Ouweland AMW, Willemsen R, Hublin JJ, Dean MC, Hoogeboom AJM, Silljé HHW, Uitterlinden AG, van der Meer P, and Bolling MC
- Subjects
- Animals, Humans, Mice, Desmoplakins genetics, Desmoplakins metabolism, Desmosomes metabolism, Hair metabolism, Skin metabolism, Hair Diseases genetics, Hair Diseases metabolism, Keratoderma, Palmoplantar genetics, Keratoderma, Palmoplantar metabolism, Skin Abnormalities metabolism
- Abstract
Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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24. Cutaneous Lesions of Mastocytosis: Mast Cell Count, Morphology, and Immunomolecular Phenotype.
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Damman J, Diercks GFH, van Doorn MB, Pasmans SG, and Hermans MAW
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- Adult, Child, Humans, Prospective Studies, Mast Cells pathology, Phenotype, Cell Count, Proto-Oncogene Proteins c-kit analysis, Mastocytosis diagnosis, Mastocytosis pathology, Mastocytosis, Cutaneous pathology, Dermatitis pathology
- Abstract
Abstract: Mastocytosis is a condition characterized by accumulation of clonal mast cells (MCs) that often involves the skin. Pathologists are often challenged with skin biopsies with a question of cutaneous lesions of mastocytosis (CLM) including cutaneous mastocytosis, mastocytosis in the skin, or systemic mastocytosis. The histopathological criteria for CLM remain poorly defined due to heterogeneity of the published literature and the lack of comparative prospective studies. MC count is greatly influenced by detection and counting techniques, criteria for viable MCs used, anatomical location biopsied, and the dermal level that is analyzed. Although MC numbers in CLM can be significantly higher compared with healthy controls and a patient with other inflammatory skin diseases, in some instances, considerable overlap exists. Based on the largest studies published, it is suggested that a number of MCs between 75 and 250 MCs/mm 2 are a range in which CLM should be considered and, above 250 MC/mm 2 , a diagnosis of CLM can be made. A recent study showed a high specificity of >95% of a MC count >139 MC/mm 2 compared with patients with other inflammatory skin diseases. Noteworthy, the total number and percentage of MCs is significantly higher in children compared with adults, particularly in polymorphic maculopapular cutaneous mastocytosis. In difficult cases, ancillary techniques such as D816V mutation analysis on formalin-fixed paraffin-embedded tissue have a high sensitivity and specificity. There is no enough evidence that immunohistochemistry of CD25, CD2, or CD30 has any additional value in the diagnosis, subtyping, or clinical course of mastocytosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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25. Histological evidence of a connection between true and false lumen in spontaneous coronary artery dissection.
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Houck CA, Diercks GFH, Adlam D, Sheppard MN, and Vink A
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- Humans, Coronary Vessels diagnostic imaging, Coronary Vessels pathology, Heart, Aortic Dissection diagnostic imaging, Vascular Diseases pathology
- Abstract
The pathophysiological mechanism underlying spontaneous coronary artery dissection remains unclear. Although an endothelial-intimal disruption is assumed to be involved as either a primary or secondary event, the presence of a tear in the coronary intima has not been histologically presented, to our knowledge. We present three autopsy cases of spontaneous coronary artery dissection in which histopathological examination revealed an intimal tear and connection between true and false lumen in the area of the dissection., Competing Interests: Declaration of Competing Interest D.A. has received funding to support a clinical research fellow from Abbott vascular. He has also received funding from Astra Zeneca, Inc. for unrelated research and has conducted unrelated consultancy for GE, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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26. Gene Expression Profiling Suggests that Complement Activation Is Important for Blister Formation in Bullous Pemphigoid.
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Lamberts A, Kotnik N, Meijer JM, van Kempen LC, Diercks GFH, and Horváth B
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- Humans, Blister genetics, Blister metabolism, Complement Activation genetics, Gene Expression Profiling, Pemphigoid, Bullous genetics, Pemphigoid, Bullous metabolism, Skin Diseases
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- 2023
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27. Successful pharmacological intervention at different levels of the complement system in an in vitro complement fixation model for bullous pemphigoid.
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Giang J, van Doorn MBA, Diercks GFH, de Cordoba SR, van den Bosch TPP, Schreurs MWJ, Poppelaars F, and Damman J
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- Humans, Retrospective Studies, Complement System Proteins, Antibodies, Dexamethasone, Pemphigoid, Bullous
- Abstract
Bullous pemphigoid (BP) is characterized by deposition of immunoglobulins and complement along the epidermal basement membrane (BM). In humans, there is a lack of functional studies targeting the complement system (CS). This study investigates activation of all complement pathways in BP skin biopsies. Moreover, pharmacological inhibition at different levels of the CS was investigated using anti-complement compounds in a complement fixation BP assay. In this retrospective study, 21 frozen biopsies from BP patients were stained by direct immunofluorescence for C1q, MBL, ficolin-2, C4d, properdin, C3c and C5b-9. Sera from 10 patients were analysed in a complement fixation assay in the presence of C1 inhibitor, anti-factor B monoclonal antibody (mAb), anti-C3 mAb and anti-C5 mAb and compared with dexamethasone. The two readouts were the quantity of complement deposited along the BM and the release of sC5b-9 in the supernatant. Our results show classical and alternative complement pathway activation in BP skin biopsies, but could not demonstrate significant lectin pathway activation. In contrast to dexamethasone, complement deposition along the BM could be selectively inhibited by anti-C1 and anti- factor B. More downstream, selective intervention at the level of C3 and C5 could effectively reduce complement deposition along the BM and the release of sC5b-9 in the supernatant. This study shows that selective intervention in either the classical, alternative or terminal pathway prevented deposition of complement along the BM in an in vitro BP model. The results of our study greatly encourage the clinical development of complement inhibitors for the treatment of BP., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
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- 2023
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28. PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis.
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van de Beek I, Glykofridis IE, Oosterwijk JC, van den Akker PC, Diercks GFH, Bolling MC, Waisfisz Q, Mensenkamp AR, Balk JA, Zwart R, Postma AV, Meijers-Heijboer HEJ, van Moorselaar RJA, Wolthuis RMF, and Houweling AC
- Subjects
- Humans, Genes, Tumor Suppressor, DNA-Binding Proteins genetics, Transcription Factors genetics, Proto-Oncogene Proteins genetics, Tumor Suppressor Proteins genetics, Birt-Hogg-Dube Syndrome genetics, Birt-Hogg-Dube Syndrome pathology, Carcinoma, Renal Cell genetics, Skin Neoplasms genetics, Lipomatosis genetics, Kidney Neoplasms genetics
- Abstract
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder characterized by fibrofolliculomas, pulmonary cysts, pneumothoraces and renal cell carcinomas. Here, we reveal a novel hereditary disorder in a family with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with BHD based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. By whole exome sequencing we identified a heterozygous missense variant (p.(Cys677Tyr)) in a zinc-finger encoding domain of the PRDM10 gene which co-segregated with the phenotype in the family. We show that PRDM10Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN. We propose that PRDM10 controls an extensive gene program and acts as a critical regulator of FLCN gene transcription in human cells. The germline variant PRDM10Cys677Tyr curtails cellular folliculin expression and underlies a distinguishable syndrome characterized by extensive lipomatosis, fibrofolliculomas and renal cell carcinomas., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2023
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29. Paraneoplastic pemphigus: A detailed case series from the Netherlands revealing atypical cases.
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Zaheri F, Pas HH, Bremer J, Meijer JM, Bolling MC, Horvath B, and Diercks GFH
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- Humans, Retrospective Studies, Netherlands, Pemphigus, Paraneoplastic Syndromes diagnosis, Paraneoplastic Syndromes etiology, Stomatitis complications
- Abstract
Background: Paraneoplastic pemphigus (PNP) is an extremely rare life-threatening blistering autoimmune disease that is associated with an underlying neoplasm. There is a set diagnostic criterion for PNP, which is primarily based on a severe stomatitis and the detection of specific antibodies against envoplakin, periplakin and alpha-2-macroglobulin-like protein 1. However, it has become increasingly evident that there are patients with PNP that do not meet all the diagnostic criteria requirements., Objectives: The aim of this study was to analyse our cohort of Dutch patients and to define the atypical cases that did not meet the diagnostic criteria., Methods: A retrospective case study of all known Dutch PNP patients of the past 25 years. Patients' clinical and immunological variables were thoroughly analysed and described., Results: Twenty-four patients were included in this study. The results revealed several atypical patient cases that did not completely meet the set diagnostic criteria. Of the 24 patients, two patients presented without stomatitis, in three patients an underlying neoplasm could not be detected, and in two patients the presence of specific autoantibodies could not be demonstrated, although all other criteria for PNP were met. Finally, three of the 24 patients survived the disease., Conclusion: Although our findings showed similarities to previous studies and most of the patients met the criteria, there were a few atypical patient cases; highlighting the importance of not strictly adhering to the set criteria when making a diagnosis, as this can lead to a missed or late diagnosis. Thus, it is of crucial importance to combine clinical and elaborate laboratory results to confirm the diagnosis of PNP in suspected patients. Although PNP harbours an unfavourable prognosis in most cases, it might be resolved by timely treatment of the underlying cause., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2023
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30. [Eosinophilic dermatoses].
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Papakonstantinou E, Fischer J, Limberg MM, Diercks GFH, Horvath B, and Raap U
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- Humans, Eosinophils pathology, Eosinophilia diagnosis, Fasciitis pathology, Dermatitis, Atopic diagnosis, Prurigo pathology
- Abstract
Eosinophilic dermatoses are a heterogeneous group of rare diseases that histopathologically display the defining pattern of an eosinophil-rich dermal infiltrate. In these eosinophilic dermatoses, a histopathologic pattern called flame figures, which result from degranulation of eosinophils in the tissue, can be observed. Although eosinophil granulocytes can also be detected in other dermatoses such as atopic dermatitis, urticaria, prurigo and bullous pemphigoid, the eosinophil-rich infiltrate is decisive for classic eosinophilic dermatoses. Accordingly, eosinophilic dermatoses include hypereosinophilic syndrome, eosinophilic fasciitis, granuloma faciale, pustular sterile eosinophilia, and angiolymphoid hyperplasia with eosinophilia. These eosinophilic dermatoses display clinical different patterns and are discussed in this article, as well as the interesting eosinophils and novel therapeutic options., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
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- 2022
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31. Fluorescence molecular imaging using cetuximab-800CW in cutaneous squamous cell carcinoma surgery: a proof-of-concept study.
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Vonk J, de Wit JG, Voskuil FJ, Koldijk M, Rácz E, Hooghiemstra WTR, Doff JJ, Diercks GFH, van Dam GM, Witjes MJH, and de Visscher SAHJ
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- Humans, Cetuximab, Optical Imaging, Molecular Imaging, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell surgery, Carcinoma, Squamous Cell pathology, Skin Neoplasms diagnostic imaging, Skin Neoplasms surgery, Head and Neck Neoplasms
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- 2022
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32. The aggressive behaviour of squamous cell carcinoma in epidermolysis bullosa: analysis of clinical outcomes and tumour characteristics in the Dutch EB Registry.
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Harrs C, van den Akker PC, Baardman R, Duipmans JC, Horváth B, van Kester MS, Lemmink HH, Rácz E, Bolling MC, and Diercks GFH
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- Humans, Registries, Epidermolysis Bullosa pathology, Carcinoma, Squamous Cell etiology, Epidermolysis Bullosa Dystrophica, Epidermolysis Bullosa, Junctional
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- 2022
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33. Prediction of Poor Outcome for Cutaneous Squamous Cell Carcinoma of the Head and Neck Comparing Classification Systems: A Competing Risk Analysis.
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Leus AJG, van Dijk BAC, Postmus D, Plaat BEC, Halmos GB, Diercks GFH, Rácz E, and van Kester MS
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- Humans, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Assessment, Squamous Cell Carcinoma of Head and Neck pathology, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell therapy, Head and Neck Neoplasms pathology, Head and Neck Neoplasms therapy, Skin Neoplasms pathology
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- 2022
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34. Natural Occurrence of Autoantibodies against Basement Membrane Proteins in Epidermolysis Bullosa.
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Gostyński A, Diercks GFH, Escamez MJ, Chandran NS, de Lucas R, Garcia-Martin A, Del Rio M, Bremer J, Bolling MC, Meana A, Llames SG, Schmidt E, Ludwig R, Jonkman MF, Pas HH, and Pasmooij AMG
- Subjects
- Autoantibodies, Basement Membrane, Humans, Membrane Proteins, Epidermolysis Bullosa, Epidermolysis Bullosa Acquisita
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- 2022
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35. Insights into clinical and diagnostic findings as well as treatment responses in patients with mucous membrane pemphigoid: A retrospective cohort study.
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Rashid H, Meijer JM, Bolling MC, Diercks GFH, Pas HH, and Horváth B
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- Autoantibodies, Humans, Laminin, Mouth Mucosa pathology, Mucous Membrane pathology, Retrospective Studies, Pemphigoid, Benign Mucous Membrane diagnosis, Pemphigoid, Benign Mucous Membrane drug therapy, Pemphigoid, Bullous
- Abstract
Background: The variable clinical severity of mucous membrane pemphigoid (MMP) often leads to diagnostic and therapeutic delays., Objective: To describe the characteristics of a large cohort of patients with MMP., Methods: A retrospective review of clinical and diagnostic characteristics as well as treatment responses in 145 patients with MMP., Results: Monosite involvement was seen in 41.4% and multisite involvement in 58.6% of the patients. The oral mucosa was affected in 86.9% of the patients, followed by the ocular mucosa (30.3%), skin (26.2%), genital mucosa (25.5%), nasal mucosa (23.4%), and pharyngeal and/or laryngeal mucosa (17.2%). Ocular disease developed during the disease course in 41.7% of patients with initially other mucosal site involvement. The malignancy rate was significantly higher in patients with autoantibodies against laminin-332 than in patients with MMP without laminin-332 autoantibodies (35.3% vs 10.9%, respectively; P = .007). Systemic immunosuppressive or immunomodulatory therapy was administered to 77.1% of the patients, mainly to patients with multisite (P < .001), ocular (P < .001), and pharyngeal and laryngeal involvement (P = .002). The remaining patients (22.9%) received topical therapy. Adverse events were frequently reported., Limitations: Retrospective design., Conclusion: Patients with MMP present with a heterogeneous clinical presentation, and new symptoms may develop during the disease course. Cancer screening should be considered for patients with MMP and, in particular, for those with autoantibodies against laminin-332., Competing Interests: Conflicts of interest Dr Horváth reports fees from Janssen-Cilag (advisory boards, educational grants, consultations, investigator initiative studies), AbbVie (advisory boards, educational grants, consultations, investigator initiative studies), Novartis Pharma (advisory boards, consultations, investigator initiative studies), UCB Pharma (advisory boards, consultations), Leo Pharma (consultations), Solenne B.V. (investigator initiative studies), Celgene (consultations, investigator initiative studies), Akari Therapeutics (consultations, investigator initiative studies), Philips (consultation), Roche (consultation), Regeneron (consultation), and Sanofi (consultation). Drs Rashid, Meijer, Bolling, Diercks, and Pas have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2022
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36. Evaluation of Nomacopan for Treatment of Bullous Pemphigoid: A Phase 2a Nonrandomized Controlled Trial.
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Sadik CD, Rashid H, Hammers CM, Diercks GFH, Weidinger A, Beissert S, Schauer F, Fettiplace J, Thaçi D, Ngai Y, Nunn MA, Zillikens D, and Horváth B
- Subjects
- Aged, Female, Germany, Humans, Male, Neoplasm Recurrence, Local, Pruritus, Quality of Life, Autoimmune Diseases, Pemphigoid, Bullous drug therapy
- Abstract
Importance: Bullous pemphigoid is a difficult-to-treat autoimmune blistering skin disease that predominantly affects older adults and is associated with an increased mortality rate., Objective: To examine the safety and therapeutic potential of nomacopan, an inhibitor of leukotriene B4 and complement C5, in patients with bullous pemphigoid., Design, Setting, and Participants: This multicenter, single-group, phase 2a nonrandomized controlled trial was conducted in the dermatology departments of universities in the Netherlands and Germany. Participants were enrolled between September 2018 and April 2020. Older adult patients (aged ≥55 years) with mild to moderate, new-onset or relapsing bullous pemphigoid were recruited into the study., Interventions: Patients received nomacopan, 90 mg, subcutaneously on day 1 and 30 mg subcutaneously daily until day 42., Main Outcomes and Measures: The primary end point was the proportion of patients with grade 3 to 5 (severe) adverse events associated or possibly associated with nomacopan. Secondary end points included mean absolute and percentage changes in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score, the BPDAI pruritus score, and the patient-reported outcome measures Dermatology Life Quality Index (DLQI) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL)., Results: A total of 9 patients (median [range] age, 75 [55-85] years) with bullous pemphigoid were included in the trial, of whom 5 were women (55.6%). No serious adverse events associated with nomacopan were found. The mean (90% CI) BPDAI activity score decreased from 32.0 (8.7) points on day 1 to 19.6 (9.0) points on day 42. Seven of 9 patients (77.8%) responded to nomacopan with a reduction in the BPDAI activity score of at least 8 points between days 1 and 42; in 3 responders, the reduction was 80% or greater. On day 42, the mean (90% CI) BPDAI pruritus score had decreased by 6.8 (4.6) points from 17.6 (4.0) points on day 1. The mean (90% CI) DLQI score decreased from 11.3 (4.2) points at baseline to 6.4 (3.8) points by day 42, and the mean (90% CI) TABQOL score decreased from 14.6 (5.4) points at baseline to 10.3 (5.0) points on day 42., Conclusions and Relevance: Results of this nonrandomized controlled trial suggest that nomacopan can be well tolerated in older patients with bullous pemphigoid and may have therapeutic benefits for suppressing acute flares of this disease. A larger, placebo-controlled randomized clinical trial is warranted to confirm this safety profile and to establish nomacopan as a new therapeutic option for bullous pemphigoid., Trial Registration: ClinicalTrials.gov Identifier: NCT04035733.
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- 2022
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37. The Effect of Tumor Characteristics and Location on the Extent of Lymph Node Metastases of Head and Neck Cutaneous Squamous Cell Carcinoma.
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van Leer B, Leus AJG, van Dijk BAC, van Kester MS, Halmos GB, Diercks GFH, van der Vegt B, Vister J, Rácz E, and Plaat BEC
- Abstract
Background: The extent of a neck dissection for patients with metastasis of cutaneous squamous cell carcinoma of the head and neck (HNcSCC) is still subject to debate and clear guidelines are lacking. Tumor characteristics like size, differentiation and tumor location are known risk factors for lymph node metastasis (LNM). There is some evidence that, depending on tumor location, LNM follows a specific pattern. This study aims to identify which tumor characteristics can predict the pattern and extent of LNM., Method: In this cohort study 80 patients were included, who underwent a primary neck dissection for LNM of HNcSCC between 2003 and 2018 at the University Medical Center Groningen, the Netherlands. Retrospective data was collected for primary tumor characteristics and LNM and included surgical and follow-up data. Influence of tumor characteristics on the extent of LNM was analyzed using non-parametric tests. Logistic regression analysis were used to identify a metastasis pattern based on the primary tumor location., Results: Only primary tumor location was associated with the pattern of LNM. HNcSCC of the ear metastasized to level II (OR = 2.6) and the parotid gland (OR = 3.6). Cutaneous lip carcinoma metastasized to ipsilateral and contralateral level I (OR = 5.3). Posterior scalp tumors showed a metastasis pattern to level II (OR = 5.6); level III (OR = 11.2), level IV (OR = 4.7) and the parotid gland (OR = 10.8). Ear canal tumors showed a low risk of LNM for all levels. The extent of LNM was not related to age or any tumor characteristics i.e. tumor diameter, infiltration depth, differentiation grade, perineural growth and vascular invasion., Conclusion: Primary tumor location determines the LNM pattern. Whereas known unfavorable tumor characteristics did not relate to the extent of LNM. Location guided limited neck dissection combined with parotidectomy will treat most patients adequately., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Leer, Leus, van Dijk, van Kester, Halmos, Diercks, van der Vegt, Vister, Rácz and Plaat.)
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- 2022
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38. Subepidermal type VII collagen speckles as an additional clue for diagnosing epidermolysis bullosa acquisita by salt-split skin serum analysis.
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Gribaleva E, van der Molen SM, Kramer D, Horvath B, Allenova A, Diercks GFH, and Pas HH
- Subjects
- Autoantibodies, Collagen Type VII genetics, Humans, Skin, Epidermolysis Bullosa Acquisita diagnosis, Pemphigoid, Bullous diagnosis
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- 2022
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39. Autologous Lipofilling Improves Clinical Outcome in Patients With Symptomatic Dermal Scars Through Induction of a Pro-Regenerative Immune Response.
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Spiekman M, Francia DL, Mossel DM, Brouwer LA, Diercks GFH, Vermeulen KM, Folkertsma M, Ghods M, Kzhyshkowska J, Klüter H, Krenning G, van der Lei B, and Harmsen MC
- Subjects
- Adult, Humans, Immunity, Prospective Studies, Transplantation, Autologous adverse effects, Cicatrix etiology, Cicatrix therapy, Skin pathology
- Abstract
Background: Autologous lipofilling is an emerging procedure to treat and possibly reverse dermal scars and to reduce scar-related pain, but its efficacy and mechanisms are poorly understood., Objectives: The aim of this study was to test the hypothesis that repeated lipografts reverse dermal scars by reinitiation of wound healing., Methods: In a prospective, non-placebo-controlled clinical study, 27 adult patients with symptomatic scars were given 2 lipofilling treatments at 3-month intervals. As primary outcome, clinical effects were measured with the Patient and Observer Scar Assessment Scale (POSAS). Scar biopsies were taken before and after treatments to assess scar remodeling at a cellular level., Results: Twenty patients completed the study. Patients' scars improved after lipofilling. The total POSAS scores (combined patient and observer scores) decreased from 73.2 [14.7] points (mean [standard deviation]) pretreatment to 46.1 [14.0] and 32.3 [13.2] points after the first and second lipofilling treatment, respectively. Patient POSAS scores decreased from 37.3 [8.8] points to 27.2 [11.3] and 21.1 [11.4] points, whereas observer POSAS scores decreased from 35.9 [9.5] points to 18.9 [6.0] and 11.3 [4.5] points after the first and second treatment, respectively. After each lipofilling treatment, T lymphocytes, mast cells, and M2 macrophages had invaded scar tissue and were associated with increased vascularization. In addition, the scar-associated epidermis showed an increase in epidermal cell proliferation to levels similar to that normal in skin. Moreover, lipofilling treatment caused normalization of the extracellular matrix organization towards that of normal skin., Conclusions: Autologous lipofilling improves the clinical outcome of dermal scars through the induction of a pro-regenerative immune response, increased vascularization, and epidermal proliferation and remodeling of scar tissue extracellular matrix., (© 2021 The Aesthetic Society.)
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- 2022
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40. Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck.
- Author
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Leus AJG, Haisma MS, Terra JB, Diercks GFH, Van Kester MS, Halmos GB, Rácz E, Van Dijk BAC, and Plaat BEC
- Subjects
- Aged, Disease Progression, Humans, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck pathology, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell therapy, Head and Neck Neoplasms pathology, Head and Neck Neoplasms therapy, Skin Neoplasms pathology
- Abstract
Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher's exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease.
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- 2022
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41. Eligibility criteria for programmed death receptor 1 inhibitors vs. real-world advice: a retrospective analysis of 69 patients with advanced cutaneous squamous cell carcinoma of the head and neck.
- Author
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Leus AJG, Horváth B, Terra JB, Diercks GFH, Plaat BEC, Oosting SF, and Rácz E
- Subjects
- Humans, Receptors, Death Domain, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms drug therapy, Skin Neoplasms drug therapy, Skin Neoplasms pathology
- Published
- 2022
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42. A Rare Case of Epstein-Barr Virus-Positive T-Cell Lymphoma in the Skin of an Immunocompromised Patient.
- Author
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van Eijk LE, Koldijk MJ, van Kester MS, Diepstra A, and Diercks GFH
- Subjects
- Adalimumab adverse effects, Adult, Epstein-Barr Virus Infections pathology, Fatal Outcome, Female, Herpesvirus 4, Human, Humans, Immunocompromised Host drug effects, Lymphoma, T-Cell, Cutaneous virology, Skin Neoplasms virology, Tumor Necrosis Factor Inhibitors adverse effects, Epstein-Barr Virus Infections virology, Lymphoma, T-Cell, Cutaneous pathology, Skin Neoplasms pathology
- Abstract
Abstract: Immunodeficiency-associated lymphoproliferative disorders are associated with latent infection by Epstein-Barr virus (EBV). Most cases of EBV-positive immunodeficiency-associated lymphoproliferative disorders arise from B cells, although some are of T-cell or natural killer origin. Cutaneous involvement is unusual and sporadically reported in the literature. We describe a rare case of an EBV-positive T-cell lymphoma presenting in the skin of a 32-year-old woman using adalimumab for neurosarcoidosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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43. Comparison of Two Diagnostic Assays for Anti-Laminin 332 Mucous Membrane Pemphigoid.
- Author
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Goletz S, Giurdanella F, Holtsche MM, Nijenhuis M, Horvath B, Diercks GFH, Zillikens D, Hashimoto T, Schmidt E, and Pas HH
- Subjects
- Adult, Aged, Aged, 80 and over, Autoantigens genetics, Autoantigens metabolism, Biomarkers blood, Case-Control Studies, Cell Adhesion Molecules genetics, Cell Adhesion Molecules metabolism, Female, Fluorescent Antibody Technique, Indirect, Germany, HEK293 Cells, Humans, Japan, Keratinocytes immunology, Keratinocytes metabolism, Male, Middle Aged, Netherlands, Pemphigoid, Benign Mucous Membrane blood, Pemphigoid, Benign Mucous Membrane immunology, Predictive Value of Tests, Reproducibility of Results, Kalinin, Autoantibodies blood, Autoantigens immunology, Biological Assay, Cell Adhesion Molecules immunology, Pemphigoid, Benign Mucous Membrane diagnosis
- Abstract
Anti-laminin 332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by predominant mucosal lesions and autoantibodies against laminin 332. The exact diagnosis of anti-laminin 332 MMP is important since nearly 30% of patients develop solid cancers. This study compared two independently developed diagnostic indirect immunofluorescence (IF) tests based on recombinant laminin 332 expressed in HEK239 cells (biochip mosaic assay) and the migration trails of cultured keratinocytes rich in laminin 332 (footprint assay). The sera of 54 anti-laminin 332 MMP, 35 non-anti-laminin 332 MMP, and 30 pemphigus vulgaris patients as well as 20 healthy blood donors were analyzed blindly and independently. Fifty-two of 54 and 54/54 anti-laminin 332 MMP sera were positive in the biochip mosaic and the footprint assay, respectively. In the 35 non-anti-laminin 332 MMP sera, 3 were positive in both tests and 4 others showed weak reactivity in the footprint assay. In conclusion, both assays are easy to perform, highly sensitive, and specific, which will further facilitate the diagnosis of anti-laminin 332 MMP., Competing Interests: DZ and ES have obtained grants from Euroimmun, Lübeck, for research and development projects. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goletz, Giurdanella, Holtsche, Nijenhuis, Horvath, Diercks, Zillikens, Hashimoto, Schmidt and Pas.)
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- 2021
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44. Case report of a clinically indolent but morphologically high-grade cutaneous mast cell tumor in an adult: Atypical cutaneous mastocytoma or mast cell sarcoma?
- Author
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Wardle CLW, Oldhoff JM, Diepstra A, Valent P, Horny HP, Oude Elberink HNG, Kluin PM, and Diercks GFH
- Subjects
- Adult, Diagnosis, Differential, Humans, Male, Mast-Cell Sarcoma diagnosis, Mastocytoma, Skin diagnosis, Mast-Cell Sarcoma pathology, Mastocytoma, Skin pathology
- Abstract
We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within 2 years, was reexcised after 4 years and did not recur >6 years after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67-staining from the onset. No KIT mutations were identified in the tumor and bone marrow. Serum tryptase levels and a bone marrow aspirate and trephine biopsy were normal. Although the histomorphology of the skin tumor was consistent with mast cell sarcoma, the clinical behavior without systemic progression argued against this diagnosis. The tumor was finally considered as atypical mastocytoma, borderline to mast cell sarcoma. Currently, the patient is in close follow-up and still in complete remission., (© 2021 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)
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- 2021
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45. European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II.
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Schmidt E, Rashid H, Marzano AV, Lamberts A, Di Zenzo G, Diercks GFH, Alberti-Violetti S, Barry RJ, Borradori L, Caproni M, Carey B, Carrozzo M, Cianchini G, Corrà A, Dikkers FG, Feliciani C, Geerling G, Genovese G, Hertl M, Joly P, Meijer JM, Mercadante V, Murrell DF, Ormond M, Pas HH, Patsatsi A, Rauz S, van Rhijn BD, Roth M, Setterfield J, Zillikens D, C Prost, Zambruno G, Horváth B, and Caux F
- Subjects
- Autoantibodies, Autoantigens, Humans, Mucous Membrane, Dermatology, Pemphigoid, Benign Mucous Membrane diagnosis, Pemphigoid, Benign Mucous Membrane drug therapy, Pemphigoid, Bullous, Venereology
- Abstract
This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2021
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46. Diagnostic Utility of C4d by Direct Immunofluorescence in Bullous Pemphigoid.
- Author
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Damman J, Edwards G, van Doorn MB, Horvath B, and Diercks GFH
- Subjects
- Aged, Aged, 80 and over, Biomarkers metabolism, Case-Control Studies, Complement C3c metabolism, False Positive Reactions, Female, Fluorescent Antibody Technique, Direct, Humans, Immunoglobulin G metabolism, Male, Retrospective Studies, Sensitivity and Specificity, Complement C4b metabolism, Pemphigoid, Bullous diagnosis, Peptide Fragments metabolism
- Abstract
Abstract: Bullous pemphigoid (BP) is an autoimmune blistering disease that commonly affects elderly patients. Direct immunofluorescence (DIF) for immunoglobulin G (IgG) and C3c on frozen skin biopsies is the gold standard for the diagnosis of BP. In a minority of cases, IgG and/or C3c are found negative, and in these situations, there is a need for a more stable diagnostic marker of BP. C4d is biologically inactive, but has a long half-life, rendering it a long-lived marker for antibody-mediated complement activation. Previous studies already demonstrated that C4d was diagnostically useful in formalin-fixed paraffin-embedded skin biopsies of patients with BP. We hypothesized that C4d detected by DIF could also be a promising diagnostic marker for BP, particularly in IgG and/or C3c DIF-negative cases. In this single-center retrospective study, 69 cases of BP were analyzed for linear deposition of C4d; of the 69 cases, n = 26 were IgG+/C3c-, n = 10 IgG+/C3c+, and n = 33 IgG-/C3c-. Results were compared with n = 39 negative controls. Seven of the 26 (27%) IgG+/C3c- and 3 of the 33 (9%) IgG-/C3c- BP cases were positive for C4d. All 10 IgG+/C3c+ cases were also C4d positive. In the negative control group, 2 of the 39 (5%) were found positive for C4d. In conclusion, the current study shows that C4d is a more sensitive but not a 100% specific marker of BP. We conclude that C4d by DIF could be an interesting diagnostic adjunct for BP, particularly in IgG-/C3c- double negative cases., Competing Interests: B. Horvath reports fees from Janssen-Cilag (advisory boards, educational grants, consultations, and investigator initiative studies), AbbVie (advisory boards, educational grants, consultations, and investigator initiative studies), Novartis Pharma (advisory boards, consultations, and investigator initiative studies), UCB Pharma (advisory boards and consultations), Leo Pharma (consultations), Solenne B. V. (investigator initiative studies), Celgene (consultations and investigator initiative studies), Akari therapeutics (consultations and investigator initiative studies), Philips (consultation), Roche (consultation), Regeneron (consultation), and Sanofi (consultation), fees which were paid to the institution. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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47. European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.
- Author
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Rashid H, Lamberts A, Borradori L, Alberti-Violetti S, Barry RJ, Caproni M, Carey B, Carrozzo M, Caux F, Cianchini G, Corrà A, Diercks GFH, Dikkers FG, Di Zenzo G, Feliciani C, Geerling G, Genovese G, Hertl M, Joly P, Marzano AV, Meijer JM, Mercadante V, Murrell DF, Ormond M, Pas HH, Patsatsi A, Prost C, Rauz S, van Rhijn BD, Roth M, Schmidt E, Setterfield J, Zambruno G, Zillikens D, and Horváth B
- Subjects
- Autoantibodies, Autoantigens, Humans, Mucous Membrane, Quality of Life, Systematic Reviews as Topic, Dermatology, Pemphigoid, Benign Mucous Membrane diagnosis, Pemphigoid, Benign Mucous Membrane therapy, Pemphigoid, Bullous, Venereology
- Abstract
This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2021
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48. Paraneoplastic pemphigus associated with post-transplant lymphoproliferative disorder after small bowel transplantation.
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Fidder SAR, Bolling MC, Diercks GFH, Pas HH, Hooimeijer LHL, Bungener LB, Willemse BWM, Scheenstra R, Stapelbroek JM, and van der Doef HPJ
- Subjects
- Child, Fatal Outcome, Female, Humans, Immunosuppressive Agents therapeutic use, Twins, Monozygotic, Intestine, Small transplantation, Lymphoproliferative Disorders complications, Paraneoplastic Syndromes diagnosis, Pemphigus diagnosis, Protein-Losing Enteropathies surgery
- Abstract
Background: PNP is a malignancy-associated autoimmune mucocutaneous syndrome due to autoantibodies against plakins, desmogleins, and other components of the epidermis and basement membrane of epithelial tissues. PNP-causing malignancies comprise mainly lymphoproliferative and hematologic neoplasms. PNP is extremely rare, especially in children., Methods: Here, we present the first case of a child who developed PNP on a PTLD after small bowel transplantation because of a severe genetic protein-losing enteropathy., Results: The patient in this case report had a severe stomatitis, striate palmoplantar keratoderma, and lichenoid skin lesions. In addition, she had marked esophageal involvement. She had lung pathology due to recurrent pulmonary infections and ventilator injury. Although we found no evidence of BO, she died from severe pneumonia and respiratory failure at the age of 12 years., Conclusion: It is exceptional that, despite effective treatment of the PTLD, the girl survived 5 years after her diagnosis of PNP. We hypothesize that the girl survived relatively long after the PNP diagnosis due to strong T-cell suppressive treatments for her small bowel transplantation., (© 2021 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)
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- 2021
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49. Single glycine deletion in COL7A1 acting as glycine substitution in dystrophic epidermolysis bullosa.
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Baardman R, Bremer J, Diercks GFH, Jan SZ, Lemmink HH, Bolling MC, and Van den Akker PC
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- Glycine genetics, Humans, Male, Middle Aged, Mutation, Mutation, Missense, Pedigree, Collagen Type VII genetics, Epidermolysis Bullosa Dystrophica genetics
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- 2021
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50. Use of Convolutional Neural Networks for the Detection of u-Serrated Patterns in Direct Immunofluorescence Images to Facilitate the Diagnosis of Epidermolysis Bullosa Acquisita.
- Author
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Shi C, Meijer JM, Azzopardi G, Diercks GFH, Guo J, and Petkov N
- Subjects
- Epidermolysis Bullosa Acquisita pathology, Fluorescent Antibody Technique, Direct, Humans, Microscopy, Fluorescence methods, Sensitivity and Specificity, Epidermolysis Bullosa Acquisita diagnosis, Image Interpretation, Computer-Assisted methods, Neural Networks, Computer
- Abstract
The u-serrated immunodeposition pattern in direct immunofluorescence (DIF) microscopy is a recognizable feature and confirmative for the diagnosis of epidermolysis bullosa acquisita (EBA). Due to unfamiliarity with serrated patterns, serration pattern recognition is still of limited use in routine DIF microscopy. The objective of this study was to investigate the feasibility of using convolutional neural networks (CNNs) for the recognition of u-serrated patterns that can assist in the diagnosis of EBA. The nine most commonly used CNNs were trained and validated by using 220,800 manually delineated DIF image patches from 106 images of 46 different patients. The data set was split into 10 subsets: nine training subsets from 42 patients to train CNNs and the last subset from the remaining four patients for a validation data set of diagnostic accuracy. This process was repeated 10 times with a different subset used for validation. The best-performing CNN achieved a specificity of 89.3% and a corresponding sensitivity of 89.3% in the classification of u-serrated DIF image patches, an expert level of diagnostic accuracy. Experiments and results show the effectiveness of CNN approaches for u-serrated pattern recognition with a high accuracy. The proposed approach can assist clinicians and pathologists in recognition of u-serrated patterns in DIF images and facilitate the diagnosis of EBA., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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