Considering the high plasticity of FoxP3+ regulatory T (Treg) cells and Interleukin (IL)-17-producing Th17 cells, we hypothesized that a Th17 inflammatory milieu may impair the functional properties of Treg cells in chronic inflammatory arthritides. Therefore, a cross-sectional explorative analysis was set up in patients with psoriatic arthritis (PsoA), rheumatoid arthritis, or spondyloarthritis to investigate the features of Th17 and Treg cells. T cell subpopulation counts, FOXP3 mRNA expression, CpG methylation of the FOXP3 gene, and the suppressive capacity of isolated Treg cells were determined. Ex vivo analysis of PsoA-derived peripheral blood lymphocytes showed a Th17-mediated inflammation. It was accompanied by demethylation of the FOXP3 promotor and Treg-specific demethylated region (TSDR) in Treg cells which, however, resulted neither in elevated FOXP3 mRNA expression nor in increased suppressive Treg cell capacity. To clarify this conundrum, in vitro stimulation of isolated Treg cells with Th17-inducing cytokines (IL-1β, IL-6, IL-23, TGFβ), recombinant IL-17, or the anti-IL-17A antibody secukinumab was performed, demonstrating that cell culture conditions polarizing towards Th17, but not IL-17 itself, impair the suppressive function of Treg cells, accompanied by diminished FOXP3 mRNA expression due to hypermethylation of the FOXP3 promotor and TSDR. This potential causal relationship between Th17 inflammation and impaired Treg cell function requires attention regarding the development of immunomodulatory therapies.

Abstract is missing (Short communication)

Bullous pemphigoid is the most common autoimmune blistering disease in industrialized countries and particularly affects the elderly. In this patient population, comorbid diseases are frequent and may complicate management and treatment of bullous pemphigoid. A better understanding why distinct diseases are more frequent in bullous pemphigoid patients may lead to new pathophysiological insights and - as a consequence - result in better patient care. The association of bullous pemphigoid with neurological and psychiatric diseases is well known and confirmed by several case-control studies. Association with further diseases such as malignancy and metabolic diseases are still discussed controversially. In recent years new relationships between bullous pemphigoid and autoimmune as well as inflammatory skin diseases have been reported. This review provides a systematic overview on studies addressing comorbidity in bullous pemphigoid patients. Increasing the awareness of both, common and rare comorbid diseases, may enable clinicians to optimize patient support and individualized treatment of bullous pemphigoid.

This paper presents an overview of the group of blistering autoimmune dermatoses, focusing on their most important forms: bullous pemphigoid, pemphigus vulgaris and pemphigus foliaceus. The most common form of blistering autoimmune dermatosis - a rare disease overall - is bullous pemphigoid (BP), which mainly affects patients over the age of 60. Its characteristic symptom is the appearance of tense blisters accompanied by severe itching. A longer stage without blistering, also known as premonitory stage, is not uncommon. There are also variants with a different appearance, such as localised BP. The gold standard in diagnosis is direct immunofluorescencemicroscopy of a perilesional skin biopsy, which shows linear deposits of IgG and C3 along the basement membrane. Indirect immunofluorescencemicroscopy and further ELISA examinations, which help to detect circulating autoantibodies in the patient's serum, complete the diagnosis. The most important target antigen is BP180, a hemidesmosomal protein expressed by keratinocytes. In addition, a histopathological examination can be performed. However, this only provides information on the cleavage plane and the infiltrate pattern (mostly dominated by eosinophils) and is not sufficient on its own for establishing the diagnosis. The pathogenesis of BP is the subject of scientific debate. Drugs such as dipeptidyl peptidase-4 inhibitors may be triggers; associations with neurological diseases are common. According to current guidelines, BP is treated with topical or systemic glucocorticoids, possibly in combination with doxycycline, dapsone or an immunosuppressant. In case of therapy resistance, intravenous immunoglobulins or the anti-CD-20 antibody Rituximab are used. As mortality is relatively high due to patient age and iatrogenic immunosuppression, new therapeutic approaches are being sought. Case series, cohort analyses and phase 1/2 studies with anti-IgE antibodies and inhibitors of eosinophil granulocytes as well as the complement system show promising effects in some cases. The most important forms of the pemphigus diseases are pemphigus vulgaris (PV), pemphigus foliaceus (PF) and the very rare paraneoplastic pemphigus (PNP). Clinically, PV presents with mucosal erosions, mostly enoral, and sometimes additional erosions on the free skin. PF manifests only on free skin. As in BP, the diagnosis is made by direct immunofluorescencemicroscopy, which in PV and PF shows reticular deposits of IgG and C3 within the epidermis. The most common target antigens are desmogleins 1 and 3. It is known that there are genetic predispositions for PV and PF, and these are the reason why the frequency varies globally. PNP is always associated with malignant disease and is characterised by a progressive course with high mortality. Therapeutically, pemphigus often requires more aggressive approaches than BP. In addition to systemic glucocorticoids and immunosuppressants, the anti-CD-20 antibody rituximab is recommended for PV and PF. New therapeutic approaches include the inhibition of Bruton's tyrosine kinase as well as the neonatal Fc receptor (FcRN). In a phase 2 trial, efgartigimod, an antagonist of FcRN, has shown high treatment efficacy for patients with PV and PF.

Zusammenfassung Diese Arbeit gibt eine Übersicht über die Gruppe blasenbildender Autoimmundermatosen und stellt deren wichtigste Vertreter, das bullöse Pemphigoid, den Pemphigus vulgaris sowie den Pemphigus foliaceus, vor. Die häufigste der insgesamt seltenen blasenbildenden Autoimmundermatosen ist das bullöse Pemphigoid (BP). Es betrifft v.a. Patienten jenseits des 60. Lebensjahrs. Charakterisiert ist es typischerweise durch das Auftreten praller Blasen, die mit einem heftigen Juckreiz einhergehen. Ein längeres, sogenanntes prämonitorisches Stadium ohne Blasenbildung ist nicht ungewöhnlich. Es gibt außerdem Varianten mit anderem Erscheinungsbild wie das lokalisierte BP. Der diagnostische Goldstandard ist die direkte Immunfluoreszenzmikroskopie einer periläsional entnommenen Hautbiopsie, welche lineare Ablagerungen von IgG und C3 an der Basalmembran zeigt. Vervollständigt wird die Diagnostik durch die indirekte Immunfluoreszenzmikroskopie sowie weiterführende ELISA-Untersuchungen, mittels derer zirkulierende Autoantikörper im Patientenserum nachgewiesen werden können. Das wichtigste Zielantigen ist BP180, ein hemidesmosomales, von Keratinozyten exprimiertes Protein. Ergänzend kann eine histopathologische Untersuchung erfolgen, die allerdings nur Hinweise zur Spaltebene und zum (meist Eosinophilen-dominierten) Infiltratmuster geben kann und alleine nicht zur Diagnosestellung ausreicht. Die Pathogenese des BP ist Gegenstand der wissenschaftlichen Diskussion. Medikamente wie Dipeptidylpeptidase-4-Inhibitoren können Auslöser sein; Assoziationen zu neurologischen Erkrankungen finden sich häufig. Entsprechend aktueller Leitlinien wird das BP mit topischen bzw. systemischen Glukokortikoiden ggf. in Kombination mit Doxyzyklin, Dapson oder einem Immunsuppressivum behandelt. Bei Therapieresistenz werden intravenöse Immunglobuline oder der anti-CD-20-Antikörper Rituximab eingesetzt. Aufgrund einer vergleichsweise hohen Mortalität bedingt durch Patientenalter und iatrogener Immunsuppression werden neue Therapieansätze gesucht. Fallserien, Kohortenanalysen und Phase 1-/2-Studien mit anti-IgE-Antikörpern und Inhibitoren der eosinophilen Granulozyten sowie des Komplementsystems zeigen teils vielversprechende Effekte. Die wichtigsten Vertreter der Pemphiguserkrankungen sind der Pemphigus vulgaris (PV), der Pemphigus foliaceus (PF) und der sehr seltene paraneoplastische Pemphigus (PNP). Klinisch präsentiert sich der PV mit meist enoralen Schleimhauterosionen und teilweise zusätzlichen Erosionen an der freien Haut. Der PF manifestiert sich nur an der freien Haut. Wie beim BP wird die Diagnose mittels direkter Immunfluoreszenzmikroskopie gestellt, welche beim PV und PF netzförmige Ablagerungen von IgG und C3 innerhalb der Epidermis zeigt. Die häufigsten Zielantigene sind die Desmogleine 1 und 3. Genetische Prädispositionen für den PV und PF sind bekannt und Grund für eine global unterschiedliche Häufigkeit. Der PNP ist immer mit einer malignen Erkrankung assoziiert und von einem progredienten Verlauf mit hoher Mortalität geprägt. Therapeutisch erfordern die Pemphiguserkrankungen oft aggressivere Ansätze als das BP. Neben systemischen Glukokortikoiden und Immunsuppressiva wird für den PV und PF der anti-CD-20-Antikörper Rituximab empfohlen. Neue Therapieansätze sind die Hemmung der Bruton-Tyrosinkinase sowie des neonatalen Fc-Rezeptors (FcRN). In einer Phase 2-Studie zeigte Efgartigimod, ein Antagonist des FcRN, eine hohe Therapieeffektivität für Patienten mit PV und PF.

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 21, Issue 6 p. 655-658 CLINICAL LETTEROpen Access Transformation eines Pemphigus foliaceus in einen Pemphigus herpetiformis Judith Kühn, Corresponding Author Judith Kühn [email protected] Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany Korrespondenzanschrift Judith Kühn, Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. Email: [email protected]Search for more papers by this authorTina Giner, Tina Giner Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorSandrine Benoit, Sandrine Benoit Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorMatthias Goebeler, Matthias Goebeler Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorMarion Wobser, Marion Wobser Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this author Judith Kühn, Corresponding Author Judith Kühn [email protected] Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany Korrespondenzanschrift Judith Kühn, Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. Email: [email protected]Search for more papers by this authorTina Giner, Tina Giner Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorSandrine Benoit, Sandrine Benoit Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorMatthias Goebeler, Matthias Goebeler Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorMarion Wobser, Marion Wobser Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this author First published: 20 June 2023 https://doi.org/10.1111/ddg.15037_gAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume21, Issue6June 2023Pages 655-658 RelatedInformation

Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option.Objectives To assess the clinical efficacy of IA in addition to best medical treatment (BMT).Methods We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods.Results The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index >= 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients).Conclusions In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits. Immunoadsorption (IA) has been proposed as a fast and effective adjuvant treatment option for pemphigus vulgaris and pemphigus foliaceus in case series. In this randomized controlled trial, IA combined with the best medical treatment, comprising oral prednisolone and azathioprine or mycophenolate, was compared with best medical treatment alone. The primary endpoint, i.e. time to clinical remission, was not significantly different between the two treatment groups. In contrast, the cumulative prednisolone dose was significantly lower in the IA group and in patients with extensive disease, and a tendency towards faster remission was observed in the IA arm. We conclude that adjuvant IA may be valuable in the initial treatment phase of patients with severe pemphigus.

BACKGROUND:Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed.OBJECTIVE:To determine associations of autoantibody reactivities with comorbidities and concomitant medication.METHODS:In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed.RESULTS:An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine.CONCLUSION:Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Background and objectives: Bullous pemphigoid (BP) is associated with neuropsychiatric disorders. Other comorbid diseases are discussed controversially. We evaluated the prevalence of comorbidity in BP patients in a representative area of Germany. Patients and methods: Medical files of all BP patients treated at the Department of Dermatology, University Hospital Wurzburg, Germany, between June 2002 and May 2013 were retrospectively reviewed. Bullous pemphigoid was diagnosed based on established criteria. For each patient, two controls were individually matched. Records were evaluated for age, sex, laboratory values, concomitant medication and comorbidity. Conditional logistic regression, multivariable regression analysis and complex regression models were performed to compare results. Results: 300 BP patients were identified and compared to 583 controls. Bullous pemphigoid was associated with neuropsychiatric disorders as well as laboratory abnormalities including leukocytosis and eosinophilia. Importantly, a highly significant association of BP with anemia (OR 2.127; 95 % CI 1.532-2.953) and renal impairment (OR 2.218; 95 % CI 1.643-2.993) was identified. No association was found with malignancy and arterial hypertension. Conclusions: Our data revealed an increased frequency of anemia and renal impairment in BP patients. In accordance with previous studies the strong association for neuropsychiatric disorders was confirmed (p < 0.0005).

INTRODUCTION:Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk.OBJECTIVES:The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP.METHODS:The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status.RESULTS:We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, Staphylococcus aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters.CONCLUSION:The present study suggests Staphylococcus aureus may be a key taxon associated with BP disease status. Importantly, we however find contrasting patterns in the relative abundances of Staphylococcus hominis and Staphylococcus aureus reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting.

ZusammenfassungHintergrund und ZielePatienten mit bullösem Pemphigoid (BP) leiden gehäuft an neuropsychiatrischen Krankheiten. Im Gegensatz dazu werden Assoziationen mit anderen Krankheiten kontrovers diskutiert. Daher haben wir in dieser großen Fall‐Kontroll‐Studie einer repräsentativen Region Deutschlands das Spektrum komorbider Erkrankungen von BP‐Patienten untersucht.Patienten und MethodikDie Krankenakten aller zwischen Juni 2002 und Mai 2013 an der Klinik für Dermatologie des Universitätsklinikums Würzburg behandelten BP‐Patienten wurden retrospektiv ausgewertet. Die Diagnose BP wurde anhand definierter Kriterien gestellt. Jedem Patienten wurden zwei Kontrollen zugeordnet. Erhoben wurden Daten wie Alter, Geschlecht, Medikation, Begleiterkrankungen und Laborparameter. Die Ergebnisse wurden mittels bedingt logistischer Regression, multivariabler Regressionsanalyse sowie eines komplexen Regressionsmodells ausgewertet.Ergebnisse300 BP‐Patienten wurden ermittelt und mit 583 Kontrollpersonen verglichen. Bei Patienten mit BP zeigte sich eine Assoziation mit neuropsychiatrischen Erkrankungen. Zudem wiesen BP‐Patienten häufiger eine Leukozytose und Eosinophilie auf. Bemerkenswert war die hochsignifikante Assoziation zwischen BP und Anämie (OR 2,127; 95 % KI 1,532–2,953) beziehungsweise Nierenfunktionsstörungen (OR 2,218; 95 % KI 1,643–2,993). Keine signifikanten Zusammenhänge konnten zwischen BP und Tumorerkrankungen sowie arterieller Hypertonie ermittelt werden.SchlussfolgerungenUnsere Untersuchungen weisen auf ein vermehrtes Auftreten von Anämien und Nierenfunktionsbeeinträchtigungen bei BP‐Patienten hin. Die starke Assoziation mit neuropsychiatrischen Erkrankungen (p < 0,0005) bestätigt Ergebnisse vorangegangener Studien.

Additional file 4. Dataset 3. HLA sequencing “conditional” analysis data list.

Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HLA loci, HLA-DQA1*05:05 and HLA-DRB1*07:01. Further studies with increased sample sizes and complex studies integrating multiple pathogenic drivers will be conducted.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 18, Issue 10 p. 1162-1164 Clinical LetterOpen Access Rituximab-mediated late onset neutropenia in autoimmune blistering diseases: negligible or under-estimated threat? Christine Hosp, Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorMatthias Goebeler, Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorSandrine Benoit, Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorJohanna Stoevesandt, Corresponding Author stoevesandt_j@ukw.de orcid.org/0000-0001-6681-3192 Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, Germany Correspondence to Johanna Stoevesandt, MD Department of Dermatology, Venereology and Allergology University Hospital Würzburg Josef-Schneider-Strasse 2 97080 Würzburg, Germany E-mail: stoevesandt_j@ukw.deSearch for more papers by this author Christine Hosp, Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorMatthias Goebeler, Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorSandrine Benoit, Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, GermanySearch for more papers by this authorJohanna Stoevesandt, Corresponding Author stoevesandt_j@ukw.de orcid.org/0000-0001-6681-3192 Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, Germany Correspondence to Johanna Stoevesandt, MD Department of Dermatology, Venereology and Allergology University Hospital Würzburg Josef-Schneider-Strasse 2 97080 Würzburg, Germany E-mail: stoevesandt_j@ukw.deSearch for more papers by this author First published: 12 July 2020 https://doi.org/10.1111/ddg.14159Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume18, Issue10October 2020Pages 1162-1164 RelatedInformation

SummaryBackground and objectivesCurrent guidelines recommend high‐dose intravenous immunoglobulin (IVIG) as a rescue therapy to treat severe cutaneous autoimmune disorders. Data on IVIG‐induced hematological adverse events are limited in dermatological patients. We assessed the incidence and clinical implications of IVIG‐induced neutropenia.Patients and methodsPatients who received one or several cycles of IVIG between 2014 and 2019 were retrospectively evaluated. IVIG was given according to standardized infusion protocols. Daily differential blood counts were performed. Information on clinical baseline data, dermatological diagnosis, immunosuppressive pre‐treatment, and IVIG‐related adverse events was retrieved from patient files.ResultsSeventeen patients received 106 IVIG treatment cycles. Neutrophil counts below 1,500/μL were documented during 36 (34.0 %) cycles, and neutrophils fell below 1,000/μL in 14 (13.2 %) cases. The average drop of neutrophils from day one (pre‐dose) to days 2 and 3 of IVIG therapy was statistically significant (p = 0.006, and p = 0.002, respectively) despite correction for hemodilution, and so was a slight decrease of thrombocytes (p = 0.029, and p = 0.011, respectively). Four patients developed seven episodes of bacterial infections during or immediately after IVIG therapy.ConclusionsIVIG‐induced neutropenia is frequent in dermatological patients. A risk of secondary bacterial infections cannot be excluded.

ZusammenfassungHintergrund und Ziele:Leitlinien empfehlen hochdosierte intravenöse Immunglobuline (IVIG) zur Behandlung therapierefraktärer kutaner Autoimmunerkrankungen. Für dermatologische Patienten liegen nur wenige Daten zu hämatologischen Nebenwirkungen dieser Therapie vor. In der vorliegenden Arbeit werden Inzidenz und klinische Folgen der IVIG‐induzierten Neutropenie untersucht.Patienten und Methodik:Alle Datensätze von Patienten unserer Klinik, die zwischen 2014 und 2019 mindestens einen Zyklus einer IVIG‐Therapie erhalten haben, wurden retrospektiv ausgewertet. Die Infusionen erfolgten anhand standardisierter Protokolle, die tägliche Kontrollen des Differenzialblutbildes beinhalteten. Informationen zu klinischen Basisdaten, dermatologischer Hauptdiagnose, immunsuppressiver Vortherapie und IVIG‐assoziierten Nebenwirkungen wurden den Patientenakten entnommen.Ergebnisse:Siebzehn Patienten erhielten 106 Behandlungen mit IVIG. Während 36 (34,0 %) Zyklen wurden Neutrophilenzahlen < 1500/μl dokumentiert, in 14 (13,2 %) Fällen sanken diese unter 1000/μl. Der durchschnittliche Abfall der Neutrophilen von Tag 1 (vor Therapiebeginn) zu den Tagen 2 und 3 war trotz Korrektur des volumenbedingten Verdünnungseffektes statisch signifikant (p = 0,006 beziehungsweise p = 0,002). Dieses galt auch für einen leichten Abfall der Thrombozyten (p = 0,029 von Tag 1 zu 2, p = 0,011 von Tag 1 zu 3). Vier Patienten entwickelten sieben Episoden bakterieller Infekte während oder unmittelbar nach IVIG‐Therapie.Schlussfolgerungen:Neutropenien während einer IVIG‐Therapie dermatologischer Patienten sind häufig. Ein dadurch erhöhtes Risiko bakterieller Infektionen kann nicht ausgeschlossen werden.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 18, Issue 10 p. 1162-1164 Clinical LetterOpen Access Rituximab-induzierte, verzögert auftretende Neutropenie bei blasenbildenden Autoimmunerkrankungen: harmlos oder unterschätzte Gefahr? Christine Hosp, Christine Hosp Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum WürzburgSearch for more papers by this authorMatthias Goebeler, Matthias Goebeler Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum WürzburgSearch for more papers by this authorSandrine Benoit, Sandrine Benoit Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum WürzburgSearch for more papers by this authorJohanna Stoevesandt, Corresponding Author Johanna Stoevesandt stoevesandt_j@ukw.de Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg Korrespondenzanschrift Dr. med. Johanna Stoevesandt Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg Josef-Schneider-Straße 2 97080 Würzburg E-Mail: stoevesandt_j@ukw.deSearch for more papers by this author Christine Hosp, Christine Hosp Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum WürzburgSearch for more papers by this authorMatthias Goebeler, Matthias Goebeler Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum WürzburgSearch for more papers by this authorSandrine Benoit, Sandrine Benoit Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum WürzburgSearch for more papers by this authorJohanna Stoevesandt, Corresponding Author Johanna Stoevesandt stoevesandt_j@ukw.de Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg Korrespondenzanschrift Dr. med. Johanna Stoevesandt Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Würzburg Josef-Schneider-Straße 2 97080 Würzburg E-Mail: stoevesandt_j@ukw.deSearch for more papers by this author First published: 28 October 2020 https://doi.org/10.1111/ddg.14159_gAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue10October 2020Pages 1162-1164 RelatedInformation