SummaryBackgroundData on the prevalence and clinical features of Austrian patients with hereditary angioedema (HAE) with C1‐inhibitor (C1‐INH) deficiency (HAE‐1) or dysfunction (HAE‐2) are lacking.MethodsCurrent baseline data were collected in a national survey. The records of HAE patients at the Medical University of Graz were analyzed with regard to clinical characteristics.ResultsA total of 137 patients were identified, yielding a prevalence of 1 : 64,396. The median age at the onset of symptoms was 6.5 years, and the median age at the time of correct diagnosis 21.0 years. The median delay in diagnosis was 15.0 years for newly diagnosed patients without a family history of HAE. Patients with a family history of HAE received an immediate diagnosis. HAE patients without a family history of HAE and born before 1960 had to wait a median of 16.0 years until they were diagnosed correctly. Patients born after 1980 still experienced a median diagnostic delay of 6.5 years.ConclusionPatients with this condition still face an excessive diagnostic delay in some parts of Austria, or their disorder may even remain unrecognized by specialists. This underlines the need for better awareness of the disease.

Treatment recommendations for pityriasis rubra pilaris (PRP) are based solely on case reports and small case series, as to-date no randomized controlled trials are available. We present here a case series of 3 patients and a literature review of 28 studies treating a total of 116 patients, with the aim of providing data regarding efficacy and safety of methotrexate in the treatment of PRP. Methotrexate was effective in our patients; the review showed an overall response rate of 65.5% with complete clearing in 23.3% and excellent improvement in 17.2%, respectively. After excluding studies with other concurrent systemic therapies or low reliability, the overall response rate increased to 90.9%, with complete clearing in 40.9% and excellent improvement in 31.8%, respectively. Sixteen adverse reactions, of which 11 were mild, were observed in 15 patients (12.9%). In conclusion, the available literature supports good response rates and safety of methotrexate in PRP.

Zusammenfassung Hintergrund Zur Prävalenz und zu den klinischen Merkmalen österreichischer Patienten mit hereditärem Angioödem (HAE) mit C1‐Esterase‐Inhibitor (C1‐INH)‐Defizienz (HAE‐1) oder ‐Dysfunktion (HAE‐2) liegen keine Daten vor. Methodik In einer landesweiten Befragung wurden aktuelle Basisdaten erfasst. Krankenakten der HAE‐Patienten der medizinischen Universität Graz wurden im Hinblick auf klinische Merkmale ausgewertet. Ergebnisse Insgesamt wurden 137 Patienten identifiziert, was einer Prävalenz von 1 : 64 396 entspricht. Das mediane Alter bei Einsetzen der Symptome betrug 6,5 Jahre, das mediane Alter zum Zeitpunkt der korrekten Diagnose 21,0 Jahre. Die mediane diagnostische Verzögerung lag bei 15,0 Jahren bei neu diagnostizierten Patienten ohne HAE in der Familienanamnese. Patienten mit HAE in der Familienanamnese erhielten ihre Diagnose unmittelbar. HAE‐Patienten ohne HAE in der Familienanamnese, die vor 1960 geboren wurden, mussten bis zur korrekten Diagnose im Median 16,0 Jahre warten. Bei Patienten, die nach 1980 geboren wurden, betrug die mediane Zeit bis zur Diagnose immer noch 6,5 Jahre. Schlussfolgerungen Patienten mit hereditärem Angioödem müssen in einigen Teilen Österreichs nach wie vor mit einer unverhältnismäßig langen diagnostischen Verzögerung rechnen, oder ihre Erkrankung wird unter Umständen selbst von Spezialisten nicht erkannt. Die vorliegenden Ergebnisse unterstreichen die Notwendigkeit, das Bewusstsein für HAE zu stärken.

Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.