Q:

11/4/2015  
I have a 40 yo male patient who recently moved from Canada and was told he is a "carrier" for hereditary angioedema. He has never had an attack. However, he has a very strong family h/o hereditary angioedema on the maternal side (mom, maternal uncle, maternal grandfather and great grandfather, and one maternal 1st cousin). I am currently checking his labs. He was told at the age of 10 to "never take aspirin or NSAIDs." To your knowledge, is there any contraindication to taking ASA or NSAIDs in patients who have hereditary angioedema?

A:


Your patient’s comment about being a “carrier” for hereditary angioedema is interesting since it is autosomal dominant with variable clinical presentations, even within the same family and presumably with the same mutation. He may develop angioedema episodes in the future but the majority present by the age of 15 years (1-4), so I would recheck his laboratory tests to confirm the diagnosis.

Assuming he has hereditary angioedema, I am not aware of any contraindication of using aspirin or other NSAIDs unless there is a separate intolerance to these drugs. Certainly idiopathic urticaria and angioedema can be aggravated by NSAIDs and occasionally this is limited to select NSAIDs and not the entire class. In general, aspirin and ibuprofen are the most likely to cause exacerbation of idiopathic urticaria and/or angioedema. However, none of the NSAIDs are associated with exacerbation of hereditary angioedema. Rather stress, surgery, menstrual cycles, hormone therapy, and possibly ACE inhibitor therapy are associated with HAE swelling.

In summary, there is no contraindication with ASA or NSAID therapy in individuals with HAE. In light of the absence of symptoms, I would measure a C1 esterase function/antigen and C4 to confirm that your patient has HAE since there is no carrier status to my knowledge.

1. Hereditary angioedema: new findings concerning symptoms, affected organs, and course.
Bork K, Meng G, Staubach P, Hardt J
Am J Med. 2006;119(3):267.
Purpose: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Our aim was to examine a temporal and spatial pattern of the edema episodes by evaluating the long-term course of hereditary angioedema in order to establish a specific swelling pattern.
Subjects and Methods: Data were generated from 221 patients with C1 inhibitor deficiency by asking them about symptoms they experienced during their edema episodes. Documentation was accomplished through the use of standardized questionnaires.
Results: A total of 131110 edema episodes were observed. Clinical symptoms started at a mean age of 11.2 (SD 7.7) years. During the following cumulative 5736 years, only 370 (6.5%) symptom-free years occurred. Skin swellings, including extremity, facial, genital, and trunk swellings, and abdominal attacks occurred in 97.4% of all edema episodes of the disease. The other episodes were laryngeal edema (0.9%); edema of the soft palate (0.6%); tongue swellings (0.3%); headache episodes (0.7%); episodes affecting urinary bladder (0.3%), chest (0.2%), muscles (0.4%), joints (0.1%), kidneys (0.1%), and esophagus (0.05%), and were partly combined with other edema episodes. The per-patient analysis and the per-episode analysis revealed markedly discrepant results. On average, women had a more severe course of the disease than men. Patients with early onset of clinical symptoms were affected more severely than those with late onset.
Conclusion: The described swelling pattern is specific for HAE and allows a tentative diagnosis based on clinical symptoms and the course of the disease.

2. Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients.
Agostoni A, Cicardi M
Medicine (Baltimore). 1992;71(4):206.
Two hundred and twenty-six patients with inherited C1 inhibitor (C1-INH) deficiency, also known as hereditary angioedema (HAE), have been studied. They belonged to 80 unrelated families, and in 11 of them C1-INH was functionally deficient but antigenically normal (type II HAE). Genetic analysis of type 1 families demonstrated restriction fragment length polymorphisms in 11% and abnormal mRNAs in 25%. In type II families, the site of the mutation appeared to determine the rate of catabolism of the dysfunctional C1-INH and its antigenic plasma levels. Clinical symptoms (subcutaneous and mucous swellings) generally first appeared within the second decade of life. The frequency of symptoms was highly variable from patient to patient, but a few patients remained asymptomatic throughout their lives. Prophylactic treatment with attenuated androgens was administered to 59 patients and was totally effective in 57, without significant side effects. Sixty-seven laryngeal and 15 abdominal attacks were treated with C1-INH plasma concentrate, yielding initial regression of symptoms in 30 to 90 minutes. The acquired deficiency of C1-INH, also known as acquired angioedema, was diagnosed in 9 patients. Eight of them had an autoantibody against C1-INH; the only patient without the autoantibody had associated chronic lymphocytic leukemia. Prophylactic treatment with attenuated androgens was effective in this last patient, while those withthe autoantibody against C1-INH benefited from prophylaxis with antifibrinolytic agents. Replacement therapy with C1-INH concentrate was necessary only for patients with autoantibodies and required doses 3 or 4 times higher than those used in HAE.

3. Hereditary angioneurotic edema: a clinical survey.
Donaldson VH, Rosen FS
Pediatrics. 1966;37(6):1017.

4. Hereditary angioedema: an appraisal of 104 cases.
Cicardi M, Bergamaschini L, Marasini B, Boccassini G, Tucci A, Agostoni A
Am J Med Sci. 1982;284(1):2.
One hundred and four patients affected by hereditary angioedema belonging to 31 families have been studied. Twenty-two percent had the variant form related to the deficiency of the functional activity of serum C1 esterase inhibitor. The remaining 78% of patients had the predominant form, characterized by low antigenic levels and low functional activity of serum C1 esterase inhibitor. Attacks of swelling affected the subcutaneous tissue in 86% of patients; the upper airways in 76% of patients, and the bowel mucose in 75% of patients. Before treatment was available the mortality rate was 56%. One or more attacks a month were present in 46% of cases. The infusion of C1 inhibitor concentrate promptly reversed 14 severe attacks without any side effect. Twenty-nine patients were given long term prophylactic treatment with androgen derivatives with full success. Tranexamic acid reduced the frequency of swelling of 70% of the patients.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

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