INTRODUCTION: Acquired angioedema with C1 inhibitor deficiency (AAE-C1-INH) is rare but a potentially life-threatening disease. There are no official prevalence data, nor approved therapies for this condition. OBJECTIVE: In this study, we aimed to collect and analyze clinical data on patients with AAE-C1-INH in the Czech Republic. METHODS: We have conducted a retrospective analysis of AAE-C1-INH patients from Czech referral centers for the treatment of hereditary angioedema with C1 inhibitor deficiency. The inclusion criteria involved recurrent episodes of angioedema with the first manifestation at or after the age of 40, negative family history of angioedema, and C1 inhibitor function 50% or less. RESULTS: A total of 14 patients (7 males and 7 females) met the inclusion criteria for AAE-C1-INH. The median age of the symptom onset was 59.5 years, and the median diagnosis delay was 1 year. The most common clinical manifestation was facial edema (100%) and upper airway swelling (85.7%). All patients responded to the acute attack treatment with icatibant and plasma-derived or recombinant C1 inhibitor concentrate. Lymphoid malignancy was identified in 9 patients (64%), monoclonal gammopathy of uncertain significance in 3 (21%), and in 1 patient autoimmune disease (ulcerative colitis) was considered causative (7%). We were not able to identify any underlying disease only in 1 patient (7%). In 6 of 7 patients (86%) treated for lymphoma, either a reduction in the frequency of angioedema attacks or both angioedema symptoms' disappearance and complement parameter normalization was observed. CONCLUSIONS: The prevalence of AAE-C1-INH in the Czech Republic is about 1:760,000. This rare condition occurs in approximately 8% of the patients with angioedema with C1 inhibitor deficiency. AAE-C1-INH is strongly associated with lymphoproliferative disorders, and treating these conditions may improve the control of angioedema symptoms.
The prevalence of AAE-C1-INH in the Czech Republic is about 1:760,000.
transparent national case count and population denominator, with possible underdiagnosis limiting completeness
This rare condition occurs in approximately 8% of the patients with angioedema with C1 inhibitor deficiency.
reported national counts directly yield 8%, subject to referral-based ascertainment
AAE-C1-INH is strongly associated with lymphoproliferative disorders, and treating these conditions may improve the control of angioedema symptoms.
association is directionally consistent, but treatment improvement rests on seven uncontrolled heterogeneous cases
All patients responded to the acute attack treatment with icatibant and plasma-derived or recombinant C1 inhibitor concentrate.
all recorded treated cases met the response definition, without controlled comparative evidence
Derived from the full evaluation — not a separate score.
Strengths
All four Czech referral centres searched their databases using common inclusion criteria, supporting comprehensive capture of symptomatic treated patients within the national specialist system.
↳ Materials and Methods, p. 643
Tables 2–4 report diagnostic features, laboratory values, treatments, associated conditions, and response classifications for individual patients rather than only aggregate summaries.
↳ Tables 2–4, pp. 644–646
The Discussion compares prevalence, AAE-to-HAE ratio, diagnostic delay, manifestations, and treatment observations with the closest French, Danish, and Italian cohorts.
↳ Discussion, pp. 647–648
Limitations
Treatment observations derive from heterogeneous, concurrent interventions in 14 patients, including only seven lymphoma-treated cases. The article appropriately states that it cannot determine treatment superiority.
↳ Results, pp. 645–647; Discussion, p. 648
The 6-of-7 lymphoma-response statement combines biological, complete, and partial responses, including one outcome explicitly affected by tranexamic acid and one case too early for assessment.
↳ Abstract; Results, p. 647; Table 4
The prevalence estimate depends on Czech referral-centre capture, while laboratory methods, insurance coverage, underlying diseases, and concomitant treatments varied. These features constrain direct transfer to other health systems.
↳ Materials and Methods, pp. 643–644; Table 1; Discussion, pp. 647–648
The nationwide search across all four referral centres and the patient-level data in Tables 2–4 support a competent descriptive study of a very rare condition. The principal epidemiological estimates are transparent, and the Discussion places them alongside the nearest European cohorts. Management inference is less secure because treatment exposures were uncontrolled and heterogeneous, and the lymphoma-response summary includes concurrent prophylaxis and differing response categories. The article’s explicit refusal to claim treatment superiority and its cautious conclusion keep these limitations from undermining the descriptive findings.
Nabu’s assessment, alongside the field’s view.
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Sound3.6
Confidence highThe study adds the first Czech nationwide estimate of identified AAE-C1-INH prevalence and a national clinical series to a sparse European evidence base. Its contribution remains incremental because the cohort contains 14 patients and largely confirms previously reported disease associations.
“This is the first study in the Czech Republic evaluating patients with AAE-C1-INH.”
All four national referral centres were searched using explicit inclusion criteria, and Tables 2–4 provide patient-level diagnostic, treatment, and associated-disease data with defined response categories. Treatment trajectories and pre/post attack counts remain compressed, while assays differed across centres and anti-C1-INH antibody testing was unavailable.
“diverse laboratory methods were used”
The paper follows a coherent progression from national ascertainment through clinical features, management, and comparison with prior cohorts. The Abstract compresses the acute-treatment denominator and the heterogeneous 6-of-7 lymphoma outcomes, although the Results and Conclusion provide sufficient qualification to preserve the main interpretation.
“lymphoma treatment may improve the control of AAE manifestation”
The Discussion compares prevalence, diagnostic delay, manifestations, and treatment observations with French, Danish, and Italian cohorts. It connects sample heterogeneity and concurrent treatments to the inability to determine treatment superiority rather than presenting those limitations generically.
“we were not able to evaluate the superiority of one particular treatment over the other”
Lower confidence on Methodological Rigour, Reporting — domain match limited.
Caveats4 of 4 checks
The numerical results are internally consistent overall, including the prevalence calculation and disease-category totals. Two Abstract statements compress denominators or heterogeneous outcomes relative to the Results and Table 4, but they do not directly contradict the reported data.
Ethics approval, written consent, lack of study funding, and author conflicts are explicitly declared. The disclosed relationships include manufacturers whose angioedema treatments are discussed, making them relevant context without indicating concealment or misconduct.
Flags: 2 declared / 5 total
12 of 12 checkable references verified
15 references in manuscript 3 are books, websites or datasets — counted, but not index-checkable
References not verified automatically are resolved manually within 24 hours.
No retraction or expression of concern found in Crossref (includes Retraction Watch).
Sources: Crossref (incl. Retraction Watch) ✓
Where this paper’s evidence sits on the path from initial observation to real-world use.
The study reports experience from routine national referral-centre practice, giving the findings real-world descriptive relevance. Its retrospective uncontrolled design does not validate comparative management or establish the effect of treating underlying disease.
“our group is rather small and quite heterogenic”
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