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. 2018 Jun;54(3):412-431.
doi: 10.1007/s12016-016-8585-0.

Efficacy of Treatment of Non-hereditary Angioedema

Mignon van den Elzen  1   2 , M F C L Go  3 , A C Knulst  3 , M A Blankestijn  3 , H van Os-Medendorp  3 , H G Otten  4
Affiliations

Efficacy of Treatment of Non-hereditary Angioedema

Mignon van den Elzen et al. Clin Rev Allergy Immunol. 2018 Jun.

Abstract

Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.

Keywords: Angioedema; Angiotensin-converting enzyme inhibitor; Idiopathic; Treatment; Wheals.

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Conflict of interest statement

Conflict of Interest

M.T. van den Elzen has received speaker’s fees from Novartis. A.C. Knulst is a member of the national and international Novartis Omalizumab Advisory Council and has received speaker’s fees from Novartis and sponsoring for scientific studies from Novartis and Pharming. The rest of the authors declare that they have no relevant conflicts of interest.

Funding

None.

Figures

Fig. 1
Fig. 1
Flowchart of the included and excluded articles
Fig. 2
Fig. 2
a–d Responses to treatment. NA not available, Anti-vit K anti-vitamin K, C1INH complement 1 esterase inhibitor, MTX methotrexate, TA tranexamic acid, P progestin. Numbers on the Y-axis represent the reference number for each study; n indicates the number of patients included from each study. Not shown in (c): Mansi et al., 13 of 24 patients had partial response to tranexamic acid. Not shown in (d): Zazzali et al., in 208 patients treated with omalizumab, the mean proportion of AE-free days was 90.1–95.8 % vs. 88.7 % for placebo
Fig. 2
Fig. 2
a–d Responses to treatment. NA not available, Anti-vit K anti-vitamin K, C1INH complement 1 esterase inhibitor, MTX methotrexate, TA tranexamic acid, P progestin. Numbers on the Y-axis represent the reference number for each study; n indicates the number of patients included from each study. Not shown in (c): Mansi et al., 13 of 24 patients had partial response to tranexamic acid. Not shown in (d): Zazzali et al., in 208 patients treated with omalizumab, the mean proportion of AE-free days was 90.1–95.8 % vs. 88.7 % for placebo
Fig. 2
Fig. 2
a–d Responses to treatment. NA not available, Anti-vit K anti-vitamin K, C1INH complement 1 esterase inhibitor, MTX methotrexate, TA tranexamic acid, P progestin. Numbers on the Y-axis represent the reference number for each study; n indicates the number of patients included from each study. Not shown in (c): Mansi et al., 13 of 24 patients had partial response to tranexamic acid. Not shown in (d): Zazzali et al., in 208 patients treated with omalizumab, the mean proportion of AE-free days was 90.1–95.8 % vs. 88.7 % for placebo
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References

    1. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868–887. doi: 10.1111/all.12313. - DOI - PubMed
    1. Cicardi M, Aberer W, Banerji A, Baş M, Bernstein JA, Bork K, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69:602–616. doi: 10.1111/all.12380. - DOI - PubMed
    1. Schulkes KJG, Van den Elzen MT, Hack EC, Otten HG, FM B-KCa, Knulst AC. Clinical similarities among bradykinin-mediated and mast cell-mediated subtypes of non-hereditary angioedema: a retrospective study. Clin Transl Allergy. 2015;5:5. doi: 10.1186/s13601-015-0049-8. - DOI - PMC - PubMed
    1. Lewis LM, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, et al. Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Ann Emerg Med. 2014;65:1–10. - PubMed
    1. Baş M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015;372:418–425. doi: 10.1056/NEJMoa1312524. - DOI - PubMed

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