Andreas Recke’s research while affiliated with Universitätsklinikum Schleswig - Holstein and other places

Prurigo nodularis (PN) is a chronic skin disorder. Emerging, though limited, evidence suggests an association between PN and psychiatric comorbidities. Furthermore, the temporal relationship between PN and the onset of psychiatric conditions remains unclear. To address these unresolved, clinically relevant questions, retrospective cohort studies were conducted. Here, PN patients exhibited significantly higher risks of suicidal ideations, depressive disorders, and schizophrenia compared to matched controls. The findings underscore the importance of integrating mental health screening and support into PN patient care.

Background Symptoms of hereditary angioedema (HAE) typically first present during childhood, but the frequency/severity of attacks often increases at puberty. Real‐world data on long‐term HAE prophylaxis in adolescents are limited. We report pooled data from adolescent patients enrolled in two Phase 4 studies (EMPOWER, ENABLE) evaluating the effectiveness/safety of lanadelumab (monoclonal antibody directed against plasma kallikrein) for the prevention of HAE attacks. Methods Adolescent patients (aged 12 to <18 years) with HAE‐C1INH enrolled in EMPOWER and ENABLE received open‐label lanadelumab 300 mg once every 2 weeks. Effectiveness outcomes were based on patient‐reported assessments of on‐treatment HAE attacks. Safety was assessed through the recording of treatment‐emergent adverse events (TEAEs) and serious adverse events. This analysis categorized patients as “new” or “established” lanadelumab patients. Results Thirteen new and seven established patients on lanadelumab were included. The observed monthly attack rate in new patients fell from 3.8 (mean) and 2.8 (median) during the pre‐enrollment period to 0.65 (mean) and 0.21 (median) during the cumulative study period after lanadelumab initiation (84.2% and 92.9% reductions, respectively). In established patients, mean (SD) HAE attack rate (as treated) during the overall study period was 0.04 (0.03) attacks/month. Most HAE attacks were of mild/moderate severity. Nine new patients reported 42 TEAEs, mostly mild/moderate in severity, with 3 TEAEs reported as serious. Seven established patients reported 12 TEAEs (all mild/moderate and non‐serious). No TEAEs were related to lanadelumab. Conclusion These data support lanadelumab's effectiveness/safety in adolescents with HAE, consistent with results from Phase 3 lanadelumab studies in mixed adult/adolescent populations. Clinical Trial Identifiers NCT03845400 (EMPOWER) and NCT04130191 (ENABLE).

Background Type 2 chronic inflammatory diseases (T2IDs) are highly prevalent among women of reproductive age. Dupilumab, a monoclonal antibody, is increasingly used to treat T2IDs. While dupilumab is not approved during pregnancy, smaller studies suggest no increased risk of pregnancy complications (adverse pregnancy outcomes (APOs)). Additional data are required to better assess the drug's safety during pregnancy. Objectives To retrospectively assess the risk of APOs in dupilumab‐treated pregnant women in a large real‐world database. Methods Pregnant women with T2ID and dupilumab treatment during pregnancy were retrieved from the US Collaborative Network of TriNetX. Pregnant women with T2ID and without dupilumab treatment served as controls. Propensity score matching (PSM) for demographics, diagnoses, medications and putative APO risk factors was employed. Outcomes analysed included various maternal pregnancy complications, including premature obstetric labour, pregnancy‐induced hypertension, gestational diabetes, puerperal infections and spontaneous abortion. Survival analyses were assessed using the Kaplan–Meier method, outcome differences the log‐rank test and hazard ratios (HR) the Cox regression model. Results During pregnancy, 293 women were exposed to dupilumab. Following PSM, no increased risks for APOs were noted. Of note, reduced risks for premature obstetric labour (HR: 0.11, confidence interval (CI): 0.03–0.45, p = 0.0002 ) and ‘any APO’ (HR: 0.53, CI: 0.33–0.84, p = 0.0067) in the dupilumab‐treated group were found. Furthermore, no difference in risks for any APO was noted between dupilumab‐treated and untreated women up to 6 months before pregnancy or during the postpartum period. Conclusions This large‐scale propensity‐matched retrospective cohort study suggests a favourable safety profile of dupilumab during pregnancy. Given the difficulties of prospective studies during pregnancy, it provides valuable insights, though further studies are needed to confirm these findings and explore causal relationships.

Objectives Proteinuria, amyloidosis, and kidney failure are the main long-term renal complications of familial Mediterranean fever (FMF). This study assesses their risk factors, independent of ethnicity or residence. Material and methods Patients’ data were drawn from the International AIDA Network registry for monogenic autoinflammatory diseases. Results A total of 598 FMF patients were enrolled, with 80 having proteinuria, 61 amyloidosis, and 25 kidney failure. At multivariate regression analysis, proteinuria was associated with out-of-flares thrombocytosis (OR: 4.78, 95%CI 1.54-14.8, p=0.007), increased out-of-flares erythrocyte sedimentation rate (ESR) (OR: 2.7, 95%CI 1.3-5.6, p=0.008), homozygous M694V mutation (OR: 2.27, 95%CI 1.1-4.66, p=0.025), and heterozygous M694V mutation (OR: 0.29, 95%CI 0.09-0.86, p=0.026); amyloidosis was associated with the disease duration (OR: 1.034, 95% CI1.004-1.065, p=0.027), during-flares anemia (OR: 2.9, 95%CI 1.18-7.19, p=0.021), out-of-flares leukocytosis (OR: 7.47, 95%CI 1.6-34.7, p=0.01), increased out-of-flares ESR (OR: 3.6, 95%CI 1.48-8.81, p=0.005), and heterozygous M694V mutation (OR: 0.18, 95%CI 0.035-0.9, p=0.04); kidney failure was associated with the age at diagnosis (1.04, 1.0003-1.19, p=0.048), the disease duration in years (OR: 1.07, 95%CI 1.02-1.12, p=0.005), attack frequency per year (OR: 1.04, 95%CI 1.007-1.076, p=0.019), anemia out-of-flares (OR: 4.7, 95% CI: 1.004-22.1, p=0.049), and out-of-flares leukocytosis (OR: 25.8, 95%CI 2.75-242, p=0.004). The intraclass correlation coefficient related to ethnicity and country of residence was 6.7% and 6.8% for amyloidosis, respectively, and 0% for proteinuria and kidney failure. Conclusions FMF patients with older age at diagnosis, longer disease duration, anemia, leukocytosis, thrombocytosis, elevated ESR, and homozygous M694V mutation are at higher risk of kidney complications.

β-lactam antibiotics (BLAs) are still the antibiotics of first choice for the treatment of many bacterial infections. Treatment with a BLA is often hindered by a suspected allergy, up to 10% of the population report an allergy to penicillin. After allergological evaluation of the suspected allergic reaction to a BLA, most patients show a low probability of a BLA allergy; only in a minority of cases an allergic reaction to the repeated administration of a BLA appear likely in view of the previous history. In > 90% of cases, the suspected BLA allergy can be ruled out by allergy diagnostics. We recommend a risk-stratified approach in the context of an urgent need for BLA, which should enable most patients to receive a BLA therapy. After acute therapy, allergy diagnostics have to be done to clearly prove or reliably rule out a BLA allergy.

Purpose: Short-read genome sequencing (GS) is a comprehensive genetic testing method capable of detecting multiple variant types. Despite its technical advantages, systemic comparisons of singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) in real-world diagnostics remain limited. Methods: We systematically compared sGS, tGS, and SoC genetic testing in 448 patients with rare diseases in a blinded, prospective study. Three independent teams evaluated the diagnostic yield, variant detection capabilities, and clinical feasibility of GS as a first-tier test. Diagnostic yield was assessed through both prospective and retrospective analyses. Results: In prospective analyses, tGS achieved the highest diagnostic yield for likely pathogenic/pathogenic variants (36.8%) in a newly trained team, outperforming the experienced SoC team (36.0%) and the sGS team (30.4%). Retrospective analyses, accounting for technical variant detection and team experience differences, reported diagnostic yields of 38.6% for SoC, 41.3% for sGS, and 42.2% for tGS. GS excelled in identifying deep intronic, non-coding, and small copy-number variants missed by SoC. Notably, tGS additionally identified three de novo variants classified as likely pathogenic based on recent GeneMatcher collaborations and newly published gene-disease association studies. Conclusion: GS, particularly tGS, demonstrated superior diagnostic performance, supporting its use as a first-tier genetic test. sGS offers a cost-effective alternative, enabling faster, more efficient diagnoses for rare disease patients.

Background and objectives: Patients with rare diseases like hereditary angioedema (HAE) are usually referred to an angioedema center to ensure guideline-compliant and experience-based therapy. Even though there are established guidelines and several approved therapeutics, there are still open questions and situations in the daily care of HAE patients, where an exchange between centers is needed. Materials and methods: A survey was conducted among physicians from German angioedema centers regarding challenges and issues in everyday HAE treatment. The main focus was on the topic of long-term prophylaxis (LTP). For rarer subcategories of angioedema, the centers conducted a literature review to discuss open questions. Results: The responses of 12 physicians from 8 angioedema centers were analyzed in the survey. The attack frequency was the most important criterion for deciding to initiate LTP in HAE patients (100%). Two centers no longer generally recommend the initiation of pre-interventional prophylaxis in HAE patients under LTP. The therapeutic concepts of acquired angioedema due to C1 inhibitor deficiency and HAE in children were two associated specialized areas that were discussed in more detail. Conclusion: The current guideline serves as the foundation for daily practice in treating HAE at specialized centers. Thus, for rare conditions like HAE, an exchange among the treating centers is essential to adequately address specific issues and rare subgroups.