Introduction
Methods
Search Strategies
Search |
(Angioedema OR ‘angio edema’ OR angioedemas) AND (treatment OR therapy OR antihistamines OR (ciclosporine OR CsA OR cyclosporine) OR (omalizumab OR (anti IgE)) OR (danazol OR ‘attenuated androgen’ OR androgen) OR C1 inhibitor concentrate OR (tranexamic acid OR TTA OR cyklokapron OR AMCA OR ‘trans aminomethyl cyclohexane carboxylic acid’) OR biological OR antileukotrienes OR (‘H2 antagonist’ OR ‘histamine antagonist’) OR (TCA OR antidepressant) OR (icatibant OR ‘bradykinin receptor antagonist’) OR (MTX OR methotrexate) OR (AZA OR azathioprine OR Imuran) OR (corticosteroids OR prednisone OR glucocorticosteroids) OR Adrenaline OR sulphasalazine OR (dapson OR dapsone) OR hydroxychloroquine OR Plasmapheresis OR (‘intravenous immunoglobulin’ OR IVIG)) OR (‘Fresh Frozen Plasma’ OR FFP)) |
Inclusion and Exclusion Criteria
Selection of Studies
Risk of Bias
Data Extraction and Synthesis
Results
Search Results and Quality Assessment
Acute setting | Selection bias | Performance bias | Detection bias | Attrition bias | Reporting bias | Remarks | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Study | Design | AE subtype | Usable sample size | Randomization | Allocation concealment | Case description | Blinding patient and personnel | Intervention | Blinding outcome | Assessment outcome | Adverse events | Incomplete outcome data | Selective reporting | |
Lewis [4] | RCT | ACEi-induced | 58 + 18 | + | + | na | + | na | + | na | na | + | + | |
Bas [5] | RCT | ACEi-induced | 13 + 14 | + | + | na | + | na | + | na | na | + | + | |
Bernstein [7] | RCT | ACEi-induced | 26 + 24 | + | + | na | + | na | + | na | na | + | + | |
Mansi [19] | Cohort | Idiopathic | 26 | na | na | + | na | + | na | +/− | − | + | + |
a
|
Bouillet [20] | Cohort | Idiopathic | 48 | na | na | +/- | na | +/− | na | +/− | − | + | + | |
Bova [21] | CS | ACEi-induced | 13 | na | na | + | na | + | na | + | + | na | na | |
Greve [22] | CS | ACEi-induced | 10 | na | na | + | na | + | na | + | + | na | na | |
Bas [6] | CS | ACEi-induced | 8 | na | na | + | na | + | na | + | + | na | na | |
Hassen [23] | CS | ACEi-induced | 7 | na | na | + | na | + | na | + | − | na | na | |
Bartal [24] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Lipski [25] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Charmillon [26] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Crooks [27] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | + | na | na | |
Rasmussen [28] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Yates [29] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Bledsoe [30] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Volans [31] | CR | ACEi-induced | 2 | na | na | + | na | + | na | + | − | na | na | |
Bolton [32] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Gallitelli [33] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Millot [34] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Stewart [35] | CR | ACEi-induced | 2 | na | na | + | na | + | na | + | − | na | na | |
Bas [36] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Schmidt [37] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Dehne [38] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Nielsen [39] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Karim [40] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | |
Bertazzoni [41] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | − | na | na | |
Nanda [42] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | + | na | na | |
Stahl [43] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | − | na | na |
a
|
Montinaro [44] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | − | na | na | |
O’Keefe [45] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | − | na | na | |
Lleonart [46] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | + | na | na | |
Sridhara [47] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | − | na | na | |
Vela Vizcaino [48] | CR | Idiopathic | 1 | na | na | + | na | + | na | +/− | − | na | na |
a
|
Colas [49] | CR | Idiopathic | 1 | na | na | + | na | + | na | − | − | na | na | |
Seoane [50] | CR | Idiopathic | 1 | na | na | +/− | na | +/- | na | − | − | na | na | |
Illing [51] | CR | ACEi-induced | 1 | na | na | + | na | + | na | + | − | na | na | Ineff. |
Tran [52] | CR | Idiopathic | 1 | na | na | +/− | na | + | na | + | +/− | na | na | Ineff. |
Prophylactic setting | Selection bias | Performance bias | Detection bias | Attrition bias | Reporting bias | Remarks | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Study | Design | AE subtype | Usable sample size | Randomization | Allocation concealment | Case description | Blinding patient and personnel | Intervention | Blinding outcome | Assessment outcome | Adverse events | Incomplete outcome data | Selective reporting | |
Zazzali [53] | RCT | AE with wheals | 208 | +a
| +a
| na | +a
| na | +a
| na | na | + | + |
a
|
Rijo Calderón [54] | Cohort | AE with wheals | 10 | na | na | +/− | na | +/− | na | +/− | + | na | na | |
Cohort | Idiopathic | 4 | na | na | +/− | na | +/− | na | +/− | + | na | na | ||
Mansi [19] | Cohort | Idiopathic | 44 | na | na | + | na | + | na | + | + | + | + |
b
|
Wintenberger [55] | Cohort | Idiopathic | 25 | na | na | + | na | + | na | + | + | + | + | |
Firinu [56] | Cohort | Idiopathic | 16 | na | na | + | na | + | na | + | +/− | + | + | |
Saule [57] | Cohort | Idiopathic | 20 | na | na | + | na | +/− | na | + | + | na | na | |
Du-Thanh [58] | CS | Idiopathic | 25 | na | na | + | na | + | na | + | + | na | na | |
Cicardi [59] | CS | Idiopathic | 15 | na | na | + | na | + | na | + | + | na | na | |
Azofra [60] | CS | Idiopathic | 8 | na | na | + | na | + | na | + | + | na | na | |
Sands [61] | CS | Idiopathic | 3 | na | na | + | na | + | na | + | − | na | na | |
vd Elzen [62] | CS | AE with wheals | 3 | na | na | + | na | + | na | + | +/− | na | na | |
Groffik [63] | CS | AE with wheals | 2 | na | na | + | na | + | na | + | +/− | na | na | |
Büyüköztürk [64] | CS | AE with wheals | 1 | na | na | + | na | + | na | + | + | na | na | |
CS | Idiopathic | 2 | na | na | + | na | + | na | + | + | na | na | ||
Perez [65] | CS | Idiopathic | 2 | na | na | + | na | + | na | + | + | na | na | |
Ghazanfar [66] | CR | AE with wheals | 1 | na | na | + | na | + | na | + | + | na | na | |
Wieder [67] | CR | AE with wheals | 1 | na | na | + | na | + | na | + | − | na | na | |
Kutlu [68] | CR | AE with wheals | 1 | na | na | + | na | + | na | + | − | na | na | |
Ozturk [69] | CR | AE with wheals | 1 | na | na | + | na | + | na | + | − | na | na | |
Sánchez-Machín [70] | CR | AE with wheals | 1 | na | na | + | na | + | na | + | + | na | na | |
Korkmaz [71] | CR | AE with wheals | 1 | na | na | + | na | + | na | + | − | na | na | |
Stahl [43] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | − | na | na |
b
|
von Websky [72] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | + | na | na | |
Suna [73] | CR | Idiopathic | 1 | na | na | + | na | + | na | + | + | na | na | |
Bayer [74] | CR | Idiopathic | 1 | na | na | + | na | +/− | na | − | − | na | na | |
Vela Vizcaino [48] | CR | Idiopathic | 1 | na | na | + | na | + | na | +/− | − | na | na |
b
|
Maggadottir [75] | CS | AE with wheals | 2 | na | na | +/− | na | +/− | na | +/− | − | na | na | Ineff. |
Treatment of Acute Attacks of AE
Author | Year | Study design | Size | Previous therapy | Therapy | Dosage | Effect |
---|---|---|---|---|---|---|---|
Lewis [4] | 2015 | RCT | 58 + 18 | AH + C + E + H2 | Ecallantide | 10–60 mg | Predefined criteria ≤6 h met in 88 vs. 72 % for PLC (difference = 16 %; 95%CI = 11–41) |
Bernstein [7] | 2015 | RCT | 26 + 24 | AH + C + E | Ecallantide | 30 mg | Discharge criteria ≤4 h in 31 vs. 21 % for PLC (difference = 10 %; 95 %CI = 14–34 %) |
Bas [5] | 2015 | RCT | 13 + 14 | None | Icatibant | 30 mg | Median IR = 120 min (95%CI = 60–480) vs. 702 min (480–1080); CR = 8.0 vs. 27.1 h (3.0–16.0) |
Bova [21] | 2015 | CS | 13 | AH + C + E | Icatibant | 30 mg | IR = 30 min (IQR = 27.5–70); CR = 5 h (IQR = 4–7) |
Bas [6] | 2010 | CS | 8 | None | Icatibant | 30 mg | IR = 50.6 min (SD = 21); CR = 4.4 h (SD = 0.8) |
Volans [31] | 2013 | CS | 2 | AH + C + E + TA | Icatibant | 30 mg | IR = 20 min; CR = 4 h |
Bartal [24] | 2015 | CR | 1 | AH + C + E + H2 | Icatibant | 30 mg | IR within minutes; CR = 0.5 h |
Charmillon [26] | 2014 | CR | 1 | n.r. | Icatibant | 30 mg | CR = 1 h |
Crooks [27] | 2014 | CR | 1 | AH + C + E | Icatibant | 30 mg | IR = 30 min; CR = 24 h |
Gallitelli [33] | 2012 | CR | 1 | None | Icatibant | 30 mg | CR = 10 h |
Bas [36] | 2011 | CR | 1 | C | Icatibant | 30 mg | IR = 55 min; CR = 4 h |
Schmidt [37] | 2010 | CR | 1 | AH + C + E + C1INH | Icatibant | 30 mg | IR = 15 min |
Greve [22] | 2014 | CS | 10 | None | C1INH (B) | 1000 U | IR = 88 min (SD = 38); CR = 10.1 h (SD = 3) |
Lipski [25] | 2015 | CR | 1 | C + E + FFP | C1INH (B) | 20 U/kg | CR < 1 h |
Rasmussen [28] | 2014 | CR | 1 | None | C1INH | 15 U/kg | IR = 40 min; CR < 24 h |
Dehne [38] | 2007 | CR | 1 | AH + C + E + P + FFP | C1INH (B) | 1000 IE | IR = 2 days after initial worsening in the first 24 h |
Nielsen [39] | 2006 | CR | 1 | AH + C | C1INH (B) | 1500 U | IR = 20 min |
Hassen [23] | 2013 | CS | 7 | AH + C + E + H2 | FFP | 1-3 U | IR = 2 h; CR = 48 h |
Stewart [35] | 2012 | CR | 2 | C | FFP | 2 U | IR = 2.5 h in 1 patient; CR = 4.75 in the other |
Yates [29] | 2014 | CR | 1 | None | FFP | 2 U | CR = 4 h |
Bledsoe [30] | 2013 | CR | 1 | AH + C + E + H2 | FFP | 2 U | IR within a few hours. CR < 48 h |
Bolton [32] | 2012 | CR | 1 | Not known | FFP | 2 U | CR = 2 h |
Karim [40] | 2002 | CR | 1 | AH + C | FFP | 4 U | IR < 2 h |
Millot [34] | 2012 | CR | 1 | AH + C + E | Kanokad | 1500 U | IR = 20 min; CR = 8 h |
Author | Year | Study design | Size | Previous therapy | Therapy | Dosage | Effect |
---|---|---|---|---|---|---|---|
Bouillet [20] | 2014 | Cohort | 48 | Unknown | Icatibant | n.r. | Median time to CR = 26.6 h (IQR = 8.3–46) |
Bertazzoni [41] | 2015 | CR | 1 | AH + C + E | Icatibant | 30 mg | IR = 20 min |
Seoane [50] | 2014 | CR | 1 | AH + C | Icatibant | n.r. | “Rapid response” |
Vela Vizcaino [48] | 2014 | CR | 1 | AH + C + E | Icatibant | n.r. | CR = 45 min |
Montinaro [44] | 2013 | CR | 1 | AH + C | Icatibant | 30 mg | IR = 45 min; CR = 9 h |
Colás [49] | 2012 | CR | 1 | AH + C + E + H2 + C1INH | Icatibant | 30 mg | IR = 25 min |
Lleonart [46] | 2012 | CR | 1 | AH + C + E | Icatibant | 30 mg | IR = 30 min; CR = 6 h |
Sridhara [47] | 2012 | CR | 1 | AH + C + E + H2 + H + LTRA | Icatibant | 30 mg | IR = 20 min |
Mansi [19] | 2014 | Cohort | 1 | None | Icatibant | 30 mg | CR = 4 h |
2014 | Cohort | 24 | None | TA | ≤6 g/day | Decreased severity and duration of symptoms in 13 (54 %) | |
2014 | Cohort | 1 | None | C1INH | 1000 U | CR = 1 h | |
Stahl [43] | 2014 | CR | 1 | AH + C + E + H2 + TA + H + AB + LTRA + FFP + Icatibant | C1INH | 20 U/kg | IR = 2 h |
O’Keefe [45] | 2013 | CR | 1 | C + E | C1INH | 500 U | IR = 20 min |
Nanda [42] | 2014 | CR | 1 | AH + C + E | Ecallantide | 30 mg | CR < 1 h |
Prophylactic Treatment of AE
Author | Year | Study design | Size | Disease duration (years) | Previous therapy | Therapy | Dosage scheme | Effect | Follow-up (months) |
---|---|---|---|---|---|---|---|---|---|
Zazzali [53] | 2014 | RCT | 208 | n.r. | AH | OMA | 75–300/4 | Mean proportion AE-free days = 90.1–95.8 % vs. 88.7 % | 3 |
Rijo Calderón [54] | 2013 | Cohort | 10 | n.r. | AH + C + dapsone | OMA | 150–300/2–4 | No further attacks in 5, mild symptoms in 7a
| n.r. |
vd Elzen [62] | 2014 | CS | 3 | 2,4,9 | AH + C + LTRA + H2 + AB + I + MTX + HC | OMA | 150–300/2–4 | CR < 9 days | 24 |
Groffik [63] | 2010 | CS-1 | 1 | 1 | AH + C + LTRA | OMA | 300/2 | IR < 2 months | 4 |
CS-2 | 1 | 19 | AH + C + LTRA | OMA | 150/2 | CR < 2 months | 4 | ||
Büyüköztürk [64] | 2012 | CS | 1 | 7 | AH | OMA | 225/4 | IR <1 week | 8 |
Ghazanfar [66] | 2015 | CR | 1 | n.r. | AH + C + I | OMA | 150/2 → 300/4 | CR < 1 day | 48 |
Wieder [67] | 2015 | CR | 1 | n.r. | AH + C + LTRA + I + O | OMA | 300/4 | IR after first dose | 29 |
Kutlu [68] | 2014 | CR | 1 | n.r. | AH + C + E | OMA | 300/4 | IR = 2 months; CR = 3 months | 3 |
Ozturk [69] | 2014 | CR | 1 | n.r. | AH + C + O | OMA | 300/4 | No further attacks | 3 |
Sánchez-Machín [70] | 2011 | CR | 1 | 9 | AH + C + I + O | OMA | 300/2 → 300/6 | IR = <3 days; CR = 14 days | 36 |
Korkmaz [71] | 2010 | CR | 1 | n.r. | AH + C + LTRA + H2 + AB + I | OMA | 300/2 | IR = 2 days; CR = 14 days | n.r. |
Author | Year | Study design | Size | Disease duration (years) | Previous therapy | Therapy | Dosage scheme | Effect | Follow-up (months) |
---|---|---|---|---|---|---|---|---|---|
Mansi [19] | 2014 | Cohort | 44 | n.r | n.r. | TA | 3 g/day → 0.5–3 mg/day | Reduction recurrences in 43 (98 %) | n.r. |
Wintenberger [55] | 2014 | Cohort | 25 | n.r. | n.r. | TA | 2–2.5 g/day | Attack frequency from 15.2 (range = 2–50) to 3.7 (0–18) per 6 months. No response in 6 (24 %) | 6 |
Firinu [56] | 2015 | Cohort | 16 | n.r. | AH + C | TA | 1.5–3 g/day | 50 % attack frequency decrease in 8 (50 %), no response in 5 (31 %), other in 3 | n.r. |
Du-Thanh [58] | 2010 | CS | 25 | n.r. | AH + C | TA | 3 g/day | CR in 12 (48 %), PR in 11 (44 %), no response in 2 (8 %) | 20 |
Cicardi [59] | 1999 | CS | 15 | Median 6 | AH | TA | 3 g/day | No further attacks in 8 (53 %), 7 attack frequency decreased by ≥75 % | 10–282 |
Vela Vizcaino [48] | 2014 | CR | 1 | 3 | AH + C + E + C1INH | TA | 3 g/day | Attack frequency decrease from weekly to 3/8 weeks | n.r. |
Saule [57] | 2012 | Cohort | 20 | n.r. | AH | Progestin | n.r. | Improvement in 19 (95 %) | 32,4 |
Rijo Calderón [54] | 2013 | Cohort | 4 | n.r. | AH + C + dapsone | OMA | 150–300/2–4 | IR < 1 month | n.r. |
Azofra [60] | 2015 | CS | 8 | n.r. | (AH + C +) TA | OMA | 300/4 | IR = 2–14 days | 6–12 m |
Sands [61] | 2007 | CS-1 | 1 | 6 | AH + C + E + H2 | OMA | 300/3 | No further attacks | 24 |
CS-2 | 1 | 4 | AH + C + H2 | OMA | 375/2 | No further attacks | 7 | ||
CS-3 | 1 | 9 | AH + C + LTRA + H2 | OMA | 300/4 | 1 minor attack in 2 years | >12 | ||
Büyüköztürk [64] | 2012 | CS-1 | 1 | 10 | AH + C + H+ O | OMA | 300/4 | CR within 4 months | n.r. |
CS-2 | 1 | 15 | AH + C + H + IVIG + I | OMA | 300/4 | No further attacks | n.r. | ||
von Websky [72] | 2013 | CR | 1 | n.r. | AH + C + LTRA + AB | OMA | 300/4 | CR = 2 days | 18 |
Suna [73] | 2009 | CR | 1 | 19 | AH + C + H + IVIG + I | OMA | 300/2 | CR < 14 days | 4.5 |
Stahl [43] | 2014 | CR | 1 | 1 | AH + C + E + H2 + TA + H + AB + LTRA + FFP + Ica | C1INH | 1000 U/ twice weekly | Attack frequency decrease 5–7/month to 1.5/month | n.r. |
Bayer [74] | 2013 | CR | 1 | n.r. | AH + C + E + H2 + LTRA + H + I | C1INH | n.r. | Improvement after 2 doses of C1INH | n.r. |
Perez [65] | 2010 | CS-1 | 1 | 2.75 | AH + C + I | MTX | 15/1 | IR = 28 days | n.r. |
Ineffective Treatment Options
Author | Year | AE subtype | Study design | Size | Previous therapy | Ineffective therapy | Dosage |
---|---|---|---|---|---|---|---|
Articles describing ineffective and effective treatments | |||||||
Volans [31] | 2013 | ACEi-AE | CS | 2 | AH + C + E | TA | |
Schmidt [37] | 2010 | ACEi-AE | CR | 1 | AH + C + E | C1INH | |
Lipski [25] | 2015 | ACEi-AE | CR | 1 | C + E | FFP | |
Dehne [38] | 2007 | ACEi-AE | CR | 1 | AH + C + E + P | FFP | |
Colás [49] | 2012 | Idiop. (acute) | CR | 1 | AH + C + E + H2 | C1INH | |
Stahl [43] | 2014 | Idiop. (acute and proph.) | CR | 1 | AH + C + E + H2 + H + AB + LTRA | TA | |
Icatibant | |||||||
FFP | |||||||
vd Elzen [62] | 2014 | AE with wheals | CS | 1 | AH + LTRA + I | MTX | n.r. |
Vela Vizcaino [48] | 2014 | Idiopathic (acute + proph.) | CR | 1 | AH + C + E | C1INH | |
Azofra [60] | 2015 | Idiop. (proph.) | CS | 8 | AH + C, or none | TA | |
Articles describing ONLY ineffective treatments | |||||||
Illing [51] | 2012 | ACEi-AE | CR | 1 | AH + C + E | Icatibant | 30 mg |
Tran [52] | 2013 | Idiop. (acute) | CR | 1 | AH + C | FFP | n.r. |
TA | |||||||
C1INHa
| |||||||
Maggadottir [75] | 2013 | AE with wheals | CS-1 | 1 | AH + LTRA + TCA + AB + MTX | OMA | |
MTXb
| |||||||
2013 | AE with wheals | CS-2 | 1 | AH + C + LTRA + IVIG + I | FFP | ||
OMA | |||||||
C1INH |
Safety
Study | Angioedema subtype | Sample size | Therapy | SAEs | No. of patients with >1 TEAE | TEAEs |
---|---|---|---|---|---|---|
Lewis [4] | ACEi-induced | 58 + 18 | Ecallantide | 5 related SAEs (AE). One death in placebo group (respiratory compromise) | 30 (51.7 %) vs. 8 (44.4 %); 13/30 related | AE (20 cases); headache and hypoesthesia (2 cases each); abdominal pain, diarrhea, hematuria, injection site pain/swelling, muscle spasms, oropharyngeal pain, oral candidiasis, pain in extremity, and pruritic rash (1 each). |
Bernstein [7] | ACEi-induced | 26 + 24 | Ecallantide | 2 (7.7 %) vs. 6 (25 %), none related | 18 (75 %) vs. 17 (65.4 %); none related | n.a. |
Nanda [42] | Idiopathic | 1 | Ecallantide | 0 | 0 | n.a. |
Bas [5] | ACEi-induced | 13 + 14 | Icatibant | 0 v.s. 1 (7 %) | 1 (7 %) vs. 4 (27 %); 1/1 related | Patient-reported injection site pain; additional investigator-assessed injection site reactions in >12 (80 %) |
Bova [21] | ACEi-induced | 13 | Icatibant | n.r. | 1 | Injection site pain |
Bas [6] | ACEi-induced | 8 | Icatibant | 0 | 8 | Injection site erythema and/or itching |
Crooks [27] | ACEi-induced | 1 | Icatibant | 0 | 1 | Injection site erythema |
Lleonart [46] | Idiopathic | 1 | Icatibant | 0 | 1 | Injection site pain |
Mansi [19] | Idiopathic | 44 | TA | n.r. | 5 | Migraine, menstrual irregularities, dyspepsia, diarrhea |
Wintenberger [55] | Idiopathic | 25 | TA | 0 | 11 | Abdominal pain, dizziness, weakness, pain in lower limbs, migraine |
Du-Thanh [58] | Idiopathic | 25 | TA | n.r. | 1 | Digestive intolerance |
Firinu [56] | Idiopathic | 16 | TA | n.r. | Uncleara
| Abdominal discomfort and migraine (1 case), abdominal discomfort (unclear) |
Cicardi [59] | Idiopathic | 15 | TA | 1 (myocardial infarction) | 2 | Laryngeal/pharyngeal dryness, self-limiting in months |
Rijo Calderon [54] | AE with wheals | 10 | OMA | n.r. | 7a
| Drowsiness (n = 7), digestive, cutaneous symptoms, and weight loss (5) |
Azofra [60] | Idiopathic | 8 | OMA | 0 | 0 | n.a. |
Rijo Calderon [54] | Idiopathic | 4 | OMA | n.r. | 7a
| Drowsiness (n = 7), digestive, cutaneous symptoms, and weight loss (5) |
vd Elzen [62] | AE with wheals | 3 | OMA | 0 | 2 | Headache in patient co-treated with cyclosporine, malaise (1 case each) |
Buyukozturk [64] | Idiopathic | 2 | OMA | 0 | 0 | n.a. |
Groffik [63] | AE with wheals | 2 | OMA | 0 | 3/9a
| Headache, blood pressure decrease, fatigue; self-limiting 3–4 days after first 3 injections |
Buyukozturk [64] | AE with wheals | 1 | OMA | 0 | 0 | n.a. |
Ghazanfar [66] | AE with wheals | 1 | OMA | 0 | 0 | n.a. |
Sanchez-Machin [70] | AE with wheals | 1 | OMA | 0 | 0 | n.a. |
von Websky [72] | Idiopathic | 1 | OMA | 0 | 0 | n.a. |
Suna [73] | Idiopathic | 1 | OMA | 0 | 0 | n.a. |
Saule [57] | Idiopathic | 20 | Progestin | 0 | 17/55a
| Weight gain (5 cases), oestrogenic deficiency (4), breakthrough bleeding (2), hyperandrogenia (2), n.r. (4) |
Greve [22] | ACEi-induced | 10 | C1INH (B) | 0 | 0 | n.a. |
Perez [65] | Idiopathic | 2 | MTX | 1, unrelated | Uncleara
| Hair thinning and fatigue |