Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare disease with no prevalence data or approved therapies.
To report data on patients with C1-INH-AAE followed at Angioedema ...Center, Milan (from 1976 to 2015).
Diagnostic criteria included history of recurrent angioedema without wheals; decreased C1-INH antigen levels and/or functional activity of C1-INH and C4 antigen less than 50% of normal; late symptom onset (>40 years); no family history of angioedema and C1-INH deficiency.
In total, 77 patients (58% females; median age, 70 years) were diagnosed with C1-INH-AAE and 675 patients with hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) (1 patient with C1-INH-AAE/8.8 patients with C1-INH-HAE). Median age at diagnosis was 64 years. Median time between symptom onset and diagnosis was 2 years. Sixteen patients (21%) died since diagnosis, including 1 because of laryngeal edema. Angioedema of the face was most common (N = 63 82%), followed by abdomen (N = 51 66%), peripheries (N = 50 65%), and oral mucosa and/or glottis (N = 42 55%). Forty-eight of 71 patients (68%) had autoantibodies to C1-INH. In total, 56 patients (70%) used on-demand treatment for angioedema including intravenous pdC1-INH 2000 U (Berinert, CSL Behring, Marburg, Germany) (N = 49) and/or subcutaneous icatibant 30 mg (Firazyr, Shire; Milano, Italy) (N = 27). Eventually, 8 of 49 patients receiving pdC1-INH became nonresponsive; all had autoantibodies. Thirty-four patients received long-term prophylaxis with tranexamic acid (effective in 29) and 20 with androgens (effective in 8).
The incidence of C1-INH-AAE was 1 for every 8.8 patients with C1-INH-HAE. Thirty percent of the deaths were related to the disease. Treatments approved for C1-INH-HAE are effective in C1-INH-AAE, although with minimal differences.
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently ...misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.
To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).
The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE.
In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 41.7% vs 38 of 58 65.5%, respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001).
From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment.
ClinicalTrials.gov: NCT01034969.
To the Editor: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling attacks mediated by bradykinin, which is released on activation of the contact ...system in patients lacking the C1 inhibitor (C1-INH).1 Replacement therapy with intravenous plasma-derived C1-INH (pdC1-INH) aims at restoring control of bradykinin release by maintaining protective C1-INH activity trough levels.2 Approved doses of pdC1-INH, 1000 IU twice weekly for prophylaxis,3 are generally effective but can fail in some patients with severe C1-INH-HAE.4 This prospective, single-center, open-label study was designed to assess whether catabolism of C1-INH influences the response to pdC1-INH therapy in poor-response patients with severe C1-INH-HAE. Seventeen patients with C1-INH-HAE with normal responses to pdC1-INH served as retrospective controls, providing blood samples obtained before and after 20 attacks that were treated with pdC1-INH (Berinert, CSL Behring). For the poor-response patient, the elimination half-life was derived from estimated PK parameters (T1/2 = 0.693 x apparent volume of distributionVD/apparent total plasma clearance CL). Other physiologic pathways of C1-INH catabolism include interaction with target proteases or binding to hepatic asialoglycoprotein receptors.8 In our poor-response patient, high doses of pdC1-INH apparently normalized PD parameters and controlled clinical symptoms without changing the PK, suggesting that clearance of C1-INH was not dependent on the catabolic pathways provided by protease-inhibitor interaction. ...changes in the expression of hepatic asialoglycoprotein receptors, related to still undefined circumstances, could explain increased C1-INH clearance in our poor-response patient. Concentration Mean concentration in % (SD; CV) Preinfusion Postinfusion, 10 min after end of infusion Functional...
The Icatibant Outcome Survey (IOS; NCT01034969) is an international observational study monitoring the safety and effectiveness of icatibant in a real-world setting.
While icatibant is licensed in numerous countries for hereditary angioedema (HAE) attacks in adults with C1-INH deficiency, we report IOS data for off-label use in angioedema due to acquired C1-INH ...deficiency.
Diagnosing angioedema Cicardi, Marco; Zanichelli, Andrea
Immunology and allergy clinics of North America,
11/2013, Letnik:
33, Številka:
4
Journal Article
Recenzirano
Angioedema usually occurs within the setting of allergic diseases or urticaria, but situations occur in which angioedema itself represents a disease, such as in hereditary angioedema. Evaluation of ...patients for recurrent angioedema without wheals must take into account both specific clinical signs and symptoms and specialized laboratory testing.
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