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What are the usual causes of angioedema?
G Model
EURGER-850; No. of Pages 2 European Geriatric Medicine xxx (2017) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Letter to the editor What are the usual causes of angioedema?
A R T I C L E I N F O
Keywords: Angioedema Angiotensin-converting enzyme inhibitors Elderly Adverse drug event
Angioedema is rare but potentially life-threatening [1]. It is characterized by a localized, non-pruritic and non-pitting edema of the hypodermis. The areas usually involved are the face, lips, tongue, oropharynx, upper respiratory tract [2]. Here, we report the case of a 71-year-old man who was admitted in a geriatric unit for rehabilitation after a functional decline related to lower limb erysipelas and gout crisis. His relevant comorbidities were a chronic obstructive pulmonary disease, an ischemic heart disease treated by lisinopril (5 mg/ d) and rosuvastatin (10 mg/d) for more than 1 year, recurrent gout attacks, depression and a morbid obesity. His usual medications were clopidogrel, budesonide, pantoprazole, mirtazapine, zopiclone. Several treatments were added during his stay: oral morphine, transdermal fentanyl patch, furosemide, allopurinol, colchicine and tamsulosin. Six weeks after his hospitalization, he suddenly suffered from cervical edema associated with dysphonia. Geriatricians suspected an allergic reaction due to the recent introduction of allopurinol. They stopped this medication, performed an intravenous infusion of methylprednisolone (1 mg/kg) and introduced amoxicillin clavulanate as empiric antiobiotherapy after otorhinolaryngology advice. A computed tomography scan showed a cellulitis aspect associated with a neck fasciitis. After 6 hours of improvement, the patient suddenly presented an acute and severe respiratory distress and was transferred to an intensive care unit and tracheotomised. The therapeutic management was a high dosage of corticosteroid (2 mg/kg), invasive mechanical ventilation and broad-spectrum antibiotics. A second computed tomography scan confirmed the diagnosis and an excision of cellulitis was performed. No germ or inflammation was observed in sample exams. Then, the patient’s health status progressively improved. The final diagnosis was a drug-induced angioedema related to ACE inhibitors, and revealed by opioids and tamsulosin. ACE inhibitors and sartans were definitively contra-indicated. Allopurinol and colchicine were re-introduced without problem. ACE-inhibitor induced angioedema is a well-known adverse effect described for about 0.1 to 2.2% of patients [1,3]. The
mechanism involves the bradykinin’s accumulation, due to inhibition of its degradation. It leads to release vasodilators factors causing vascular permeability, vasodilatation and then swelling [4]. In most cases, it happens during the first week of treatment. However, angioedema can occur until 10 years of therapy [5]. Crossreaction with sartans is frequently observed. The addition of other medications known to cause angioedema (non-steroidal antiinflammatory drugs, antibiotics and iodinated contrast products) appears to be relevant in patients treated by ACE inhibitor [6]. For our patient, the addition of morphine and tamsulosin probably potentiated the effect and led to the crisis. Opioids might indeed induce angioedema by direct action on mast-cells, with releasing of histamine [6,7]. Concerning tamsulosin, the mechanism remains unclear, but this adverse drug reaction seems to be a rare side effect. Moreover, with increasing age, integrity and function of the endothelial barrier decline, increasing the risk of microvascular dysfunction and hyperpermeability [8]. Swelling location, age over 65 years old, cardiopulmonary disease and smoking history are predictive of severe angioedema [4,9]. The first step in managing induced angioedema is the discontinuation of drugs potentially involved. The symptoms usually resolve within 24 to 48 hrs after [3]. Supportive medications such as steroids and antihistamines are often used without real evidence of their effectiveness. Ventilatory support is uncommon (less than 1% of cases for tracheotomy and 16% for intubation) [10]. Side effects to medications must be systematically questioned especially in polymedicated older patients. This case shows that even if a patient was stable on ACE-inhibitor, the risk of induced angioedema must not be forgotten.
Disclosure of interest The authors declare that they have no competing interest. References [1] Lerch M. Drug-induced angioedema Adverse Cutan Drug Erupt, 97. Karger Publishers; 2012. p. 98–105. [2] Kulthanan K, Jiamton S, Boochangkool K, Jongjarearnprasert K. Angioedema: clinical and etiological aspects. Clin Dev Immunol 2007;2007:1–6. http:// dx.doi.org/10.1155/2007/26438. [3] Vasekar M, Craig TJ. ACE inhibitor–induced angioedema. Curr Allergy Asthma Rep 2012;12:72–8. http://dx.doi.org/10.1007/s11882-011-0238-z. [4] Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P. Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy 2009. http://dx.doi.org/10.1111/ j.1365-2222.2009.03323.x. [5] Malde B, Regalado J, Greenberger PA. Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Ann Allergy Asthma Immunol 2007;98:57–63.
http://dx.doi.org/10.1016/j.eurger.2017.02.001 C 2017 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. 1878-7649/
Please cite this article in press as: Duplin EM, et al. What are the usual causes of angioedema?. Eur Geriatr Med (2017), http://dx.doi.org/ 10.1016/j.eurger.2017.02.001
G Model
EURGER-850; No. of Pages 2 2
Letter to the editor / European Geriatric Medicine xxx (2017) xxx–xxx
[6] Banerji A, Oren E, Hesterberg P, Hsu Y, Camargo CA, Wong JT. Ten-year study of causes of moderate to severe angioedema seen by an inpatient allergy/immunology consult service. Allergy Asthma Proc 2008;29: 88692. [7] Wang H. Agents that induce pseudo-allergic reaction. Drug Discov Ther 2011;5. http://dx.doi.org/10.5582/ddt.2011.v5.5.211. [8] Vascular hyperpermeability and aging. Aging Dis 2014;5. http://dx.doi.org/ 10.14336/AD.2014.0500114. [9] Loftus PA, Tan M, Patel G, Lin J, Helman S, Badhey A, et al. Risk factors associated with severe and recurrent angioedema: an epidemic linked to ACE-inhibitors: risk factors associated with severe and recurrent AE. Laryngoscope 2014;124:2502–7. http://dx.doi.org/10.1002/ lary.24777. [10] Kieu MCQ, Bangiyev JN, Thottam PJ, Levy PD. Predictors of airway intervention in angiotensin-converting enzyme inhibitor-induced angioedema. Otolaryngol Head Neck Surg 2015;153:544–50. http://dx.doi.org/10.1177/ 0194599815588909.
E.M. Duplina, A.S. Mange´a, C. McCambridgea,*, S. Ge´rardb, P. Cestaca, A. Didierc, Y. Rollandb a Department of pharmacy, CHU de Toulouse, 330, avenue de GrandeBretagne, 31059 Toulouse cedex 9, France b Department of geriatric medicine, CHU de Toulouse, 224, avenue de Casselardit, 31059 Toulouse cedex 9, France c Department of pneumology and allergology, CHU de Toulouse, 24, chemin de Pouvourville, 31059 Toulouse cedex 9, France *Corresponding author. E-mail address: [email protected] (C. McCambridge). Available online xxx
Please cite this article in press as: Duplin EM, et al. What are the usual causes of angioedema?. Eur Geriatr Med (2017), http://dx.doi.org/ 10.1016/j.eurger.2017.02.001
EURGER-850; No. of Pages 2 European Geriatric Medicine xxx (2017) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Letter to the editor What are the usual causes of angioedema?
A R T I C L E I N F O
Keywords: Angioedema Angiotensin-converting enzyme inhibitors Elderly Adverse drug event
Angioedema is rare but potentially life-threatening [1]. It is characterized by a localized, non-pruritic and non-pitting edema of the hypodermis. The areas usually involved are the face, lips, tongue, oropharynx, upper respiratory tract [2]. Here, we report the case of a 71-year-old man who was admitted in a geriatric unit for rehabilitation after a functional decline related to lower limb erysipelas and gout crisis. His relevant comorbidities were a chronic obstructive pulmonary disease, an ischemic heart disease treated by lisinopril (5 mg/ d) and rosuvastatin (10 mg/d) for more than 1 year, recurrent gout attacks, depression and a morbid obesity. His usual medications were clopidogrel, budesonide, pantoprazole, mirtazapine, zopiclone. Several treatments were added during his stay: oral morphine, transdermal fentanyl patch, furosemide, allopurinol, colchicine and tamsulosin. Six weeks after his hospitalization, he suddenly suffered from cervical edema associated with dysphonia. Geriatricians suspected an allergic reaction due to the recent introduction of allopurinol. They stopped this medication, performed an intravenous infusion of methylprednisolone (1 mg/kg) and introduced amoxicillin clavulanate as empiric antiobiotherapy after otorhinolaryngology advice. A computed tomography scan showed a cellulitis aspect associated with a neck fasciitis. After 6 hours of improvement, the patient suddenly presented an acute and severe respiratory distress and was transferred to an intensive care unit and tracheotomised. The therapeutic management was a high dosage of corticosteroid (2 mg/kg), invasive mechanical ventilation and broad-spectrum antibiotics. A second computed tomography scan confirmed the diagnosis and an excision of cellulitis was performed. No germ or inflammation was observed in sample exams. Then, the patient’s health status progressively improved. The final diagnosis was a drug-induced angioedema related to ACE inhibitors, and revealed by opioids and tamsulosin. ACE inhibitors and sartans were definitively contra-indicated. Allopurinol and colchicine were re-introduced without problem. ACE-inhibitor induced angioedema is a well-known adverse effect described for about 0.1 to 2.2% of patients [1,3]. The
mechanism involves the bradykinin’s accumulation, due to inhibition of its degradation. It leads to release vasodilators factors causing vascular permeability, vasodilatation and then swelling [4]. In most cases, it happens during the first week of treatment. However, angioedema can occur until 10 years of therapy [5]. Crossreaction with sartans is frequently observed. The addition of other medications known to cause angioedema (non-steroidal antiinflammatory drugs, antibiotics and iodinated contrast products) appears to be relevant in patients treated by ACE inhibitor [6]. For our patient, the addition of morphine and tamsulosin probably potentiated the effect and led to the crisis. Opioids might indeed induce angioedema by direct action on mast-cells, with releasing of histamine [6,7]. Concerning tamsulosin, the mechanism remains unclear, but this adverse drug reaction seems to be a rare side effect. Moreover, with increasing age, integrity and function of the endothelial barrier decline, increasing the risk of microvascular dysfunction and hyperpermeability [8]. Swelling location, age over 65 years old, cardiopulmonary disease and smoking history are predictive of severe angioedema [4,9]. The first step in managing induced angioedema is the discontinuation of drugs potentially involved. The symptoms usually resolve within 24 to 48 hrs after [3]. Supportive medications such as steroids and antihistamines are often used without real evidence of their effectiveness. Ventilatory support is uncommon (less than 1% of cases for tracheotomy and 16% for intubation) [10]. Side effects to medications must be systematically questioned especially in polymedicated older patients. This case shows that even if a patient was stable on ACE-inhibitor, the risk of induced angioedema must not be forgotten.
Disclosure of interest The authors declare that they have no competing interest. References [1] Lerch M. Drug-induced angioedema Adverse Cutan Drug Erupt, 97. Karger Publishers; 2012. p. 98–105. [2] Kulthanan K, Jiamton S, Boochangkool K, Jongjarearnprasert K. Angioedema: clinical and etiological aspects. Clin Dev Immunol 2007;2007:1–6. http:// dx.doi.org/10.1155/2007/26438. [3] Vasekar M, Craig TJ. ACE inhibitor–induced angioedema. Curr Allergy Asthma Rep 2012;12:72–8. http://dx.doi.org/10.1007/s11882-011-0238-z. [4] Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P. Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy 2009. http://dx.doi.org/10.1111/ j.1365-2222.2009.03323.x. [5] Malde B, Regalado J, Greenberger PA. Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Ann Allergy Asthma Immunol 2007;98:57–63.
http://dx.doi.org/10.1016/j.eurger.2017.02.001 C 2017 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. 1878-7649/
Please cite this article in press as: Duplin EM, et al. What are the usual causes of angioedema?. Eur Geriatr Med (2017), http://dx.doi.org/ 10.1016/j.eurger.2017.02.001
G Model
EURGER-850; No. of Pages 2 2
Letter to the editor / European Geriatric Medicine xxx (2017) xxx–xxx
[6] Banerji A, Oren E, Hesterberg P, Hsu Y, Camargo CA, Wong JT. Ten-year study of causes of moderate to severe angioedema seen by an inpatient allergy/immunology consult service. Allergy Asthma Proc 2008;29: 88692. [7] Wang H. Agents that induce pseudo-allergic reaction. Drug Discov Ther 2011;5. http://dx.doi.org/10.5582/ddt.2011.v5.5.211. [8] Vascular hyperpermeability and aging. Aging Dis 2014;5. http://dx.doi.org/ 10.14336/AD.2014.0500114. [9] Loftus PA, Tan M, Patel G, Lin J, Helman S, Badhey A, et al. Risk factors associated with severe and recurrent angioedema: an epidemic linked to ACE-inhibitors: risk factors associated with severe and recurrent AE. Laryngoscope 2014;124:2502–7. http://dx.doi.org/10.1002/ lary.24777. [10] Kieu MCQ, Bangiyev JN, Thottam PJ, Levy PD. Predictors of airway intervention in angiotensin-converting enzyme inhibitor-induced angioedema. Otolaryngol Head Neck Surg 2015;153:544–50. http://dx.doi.org/10.1177/ 0194599815588909.
E.M. Duplina, A.S. Mange´a, C. McCambridgea,*, S. Ge´rardb, P. Cestaca, A. Didierc, Y. Rollandb a Department of pharmacy, CHU de Toulouse, 330, avenue de GrandeBretagne, 31059 Toulouse cedex 9, France b Department of geriatric medicine, CHU de Toulouse, 224, avenue de Casselardit, 31059 Toulouse cedex 9, France c Department of pneumology and allergology, CHU de Toulouse, 24, chemin de Pouvourville, 31059 Toulouse cedex 9, France *Corresponding author. E-mail address: [email protected] (C. McCambridge). Available online xxx
Please cite this article in press as: Duplin EM, et al. What are the usual causes of angioedema?. Eur Geriatr Med (2017), http://dx.doi.org/ 10.1016/j.eurger.2017.02.001