# Angioedema due to acquired C1-inhibitor deficiency: spectrum and treatment with C1-inhibitor concentrate.

- **DOI:** [10.1186/s13023-019-1043-3](https://doi.org/10.1186/s13023-019-1043-3)
- **Rating:** Limited (2.7 out of 5)
- **Verdict:** A clinically valuable rare-disease series supplies substantial real-world treatment evidence, but uncontrolled historical comparisons prevent firm causal efficacy conclusions.
- **Framework version:** v5.9
- **Pipeline version:** v0.4
- **Evaluation date:** 2026-09-18
- **Evaluation page:** https://www.nabu.science/paper/10.1186%2Fs13023-019-1043-3

## Key claims

1. Treatment with pdC1-INH shortened attacks by an average (SD) 54.4 (± 32.8) hours (P < 0.0001).
   - Support: Tentative
   - Type: Primary finding
   - Basis: historical within-patient comparison with severity-based treatment selection and patient-reported durations
   - Location: Abstract, Results
2. pdC1-INH is highly effective in treating AAE-C1-INH patients and is also effective in the vast majority of attacks in patients with anti-C1-INH autoantibodies.
   - Support: Tentative
   - Type: Secondary
   - Basis: subjective response assessments from an uncontrolled series with incomplete antibody testing
   - Location: Abstract, Conclusions
3. In 9 (75.0%) of 12 patients, the associated malignant lymphoma was detected following diagnosis of AAE-C1-INH.
   - Support: Well-supported
   - Type: Secondary
   - Basis: directly documented chronology in all twelve lymphoma cases
   - Location: Results, Associated Disorders

## Strengths

- **Substantial rare-disease treatment experience documented** The study follows 44 patients and reports treatment experience in 32 patients across 3,636 stated attacks, providing an unusually extensive dataset for AAE-C1-INH.
  - Dimension: contribution
  - Location: Results, Patient Characteristics and Plasma-derived C1-inhibitor concentrate treatment
- **Detailed within-patient efficacy analyses reported** Attack duration, time to relief, time to resolution, dose, and patient-assessed response are reported on per-patient and per-attack bases, with a sensitivity analysis for injection timing.
  - Dimension: methodological rigour
  - Location: Results, Efficacy, Effect of Time to Injection, and Tables 3–5
- **Prior resistance evidence directly engaged** The Discussion contrasts the observed antibody-positive response rate with earlier reports of partial or complete resistance and identifies higher dose requirements in some patients.
  - Dimension: positioning
  - Location: Discussion, autoantibody treatment paragraphs

## Limitations

- **Historical comparison cannot isolate treatment effects** Untreated attacks occurred before pdC1-INH use, while mild attacks were specifically not treated and other therapies continued during the treatment period. These features leave severity selection, temporal change, and concomitant treatment as alternative explanations for part of the observed difference.
  - Dimension: methodological rigour
  - Location: Methods, Study Design and Treatment; Results, Prior and Concomitant Treatment
- **Patient-reported outcomes limit causal certainty** Attack duration and effectiveness were obtained through questionnaires, interviews, or diaries without blinded or objective outcome confirmation. The Discussion acknowledges possible bias but the Conclusions retain definitive efficacy wording.
  - Dimension: reporting
  - Location: Methods, Study Design; Discussion, final paragraph; Conclusions
- **Attack counts contain material discrepancies** Table 2 location counts total 4,493 while the paper states that 3,636 attacks were treated, without explaining overlapping categories. The efficacy narrative also reports 88 non-effective attacks where the reported totals and Tables 4–5 imply 83.
  - Dimension: methodological rigour
  - Location: Results, Table 2 and Efficacy of pdC1-INH concentrate treatment; Tables 4–5

## Reliability checks

Concerns (4 of 4 checks).

- **Internal coherence:** Concern. Several tabulated or narrative counts are internally inconsistent. The most material discrepancy concerns the attack-location denominator in Table 2, while other errors appear to be isolated reporting or formatting problems.
- **Research conduct:** Noted. Ethics approval, informed consent, and a reasonable-request data statement are reported. No funding or conflict-of-interest disclosure appears in the supplied article despite repeated identification of a single commercial product.
- **Reference integrity:** Clean. 27 of 27 checkable references verified
  - 27 references in manuscript
  - References not verified automatically are resolved manually within 24 hours.

## Post-publication record

- **Status:** Clean
- **Summary:** No retraction or expression of concern found in Crossref (includes Retraction Watch).
- **Last checked:** 2026-10-17