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Respiratory Medicine CME 4 (2011) 15e16

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Respiratory Medicine CME

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Case Report

Hereditary angio-oedema: Long-term prophylaxis with danazol

S. Hammami a,*, K. Harrathi b, S. Hadded a, L. Ghédira Besbès a, A. Elkorbi b, S. Chouchane a,Ch. B. Meriem a, A. Gassab b, M.N. Guediche a

a Paediatric Department, Fattouma Bourguiba Hospital, Monastir, TunisiabORL Department, Fattouma Bourguiba Hospital, Monastir, Tunisia

a r t i c l e i n f o

Article history:Received 15 January 2010Accepted 18 January 2010

Keywords:Hereditary angio-oedemaChildrenLaryngeal oedemaDanazol

* Corresponding author. Tel.: þ216 73 460 819; faxE-mail address: hamami_sabeur@yahoo.fr (S. Ham

1755-0017/$36.00 � 2010 Elsevier Ltd. All rights resedoi:10.1016/j.rmedc.2010.01.006

a b s t r a c t

Hereditary angio-oedema is a rare autosomal dominant disease characterized by recurrent attacks ofsubcutaneous oedema and caused by a deficiency of the plasma protein C1 inhibitor. Hereditary angio-oedema attacks carry a high risk of morbidity or even mortality. In literature, there are only a fewpublications on the treatment and follow-up of paediatric patients. We report the case of a 14-year-oldmale with known hereditary angio-oedema since the age of six years, revealed by a recurrent acuteabdominal pain and oedema in subcutaneous tissues of extremities and face, and he was admitted oncefor sub mucosal oedema of larynx with suffocation, treated by fresh-frozen plasma with favourableoutcome. Danazol was used for long-term prophylaxis. Clinical course improved over a follow-up of12 months.

� 2010 Elsevier Ltd. All rights reserved.

1. Introduction

Hereditary angio-oedema (HAE) results from the deficiency ofC1-esterase inhibitor (C1-INH). It is caused by the mutation of theC1 inhibitor gene, located in the 1, 2-q13 subregion of humanchromosome 11. Two major phenotypes of HAE have beendescribed. The classic type or type I is found in 85% of the patientswith HAE and it is characterized by low C1-INH antigenic andfunctional levels. The other 15% of the patients have type II andhave normal serum levels of C1-INH, but the C1-INH protein is non-functional. Even today, HAE remains a severe disease. In fact, if nottreated adequately the acute attacks of HAE can be life threatening,especially in case of involvement of the upper airways.

2. Case report

A 14 year-old-male with known HAE type I since the age of sixyears presented to our paediatric unit on the 13th January 2009 fortachypnea and face swelling. On examination, her temperaturewas 37 �C, pulse rate was 120 beats per minute, respiratory ratewas 30 cycles per minute, blood pressure was 110/60 mmHg, andarterial oxygen saturation was 85% on ambient air and 98% on 30%inspired oxygen. His facial examination was remarkable for facialswelling. His pulmonary examination showed only tachypnea. Afiberoptic examination showed important laryngeal oedema. The

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remaining physical examination was normal. Laboratory studiesshowed a C1-INH level of 85 mg/L. His chest radiographic wasunremarkable. He was treated with corticosteroids, epinephrinenebulized and fresh-frozen plasma with improvement ofsymptoms. He had no other episodes of respiratory distress. Hewas discharged on the fourth day without complications. Lookingfor severity of acute oedematous attack and history of recurrentabdominal pain, our patient received a long-term drug prophylaxiswith danazol 200 mg/day. Clinical course improved withoutrecurrence of oedematous attacks over 12-month follow-up. C1-INH level at 12-month follow-up was 250 mg/L. In order to taperthe cumulative dose, the dosage interval was increased to 2 daysafter 6 months of clinical remission. No adverse effect waspotentially related to long-term prophylaxis with danazol. Thebone age, skeletal growth, and weight development were normal.

3. Discussion

HAE is a raredisease in childhood. C1 inhibitordeficiency leads torecurrent angio-oedemathat canbe life threateningespeciallywhenthe larynx is involved.1,2 In undiagnosed cases, themortality of acuteoedematous attacks is still high. Then, it is imperative that diagnosisof HAE be established early and correctly. The prevalence of HAE isnot well known. It has been estimated to range from 1:10,000 to1:150,000. According to literature, 85% of HAE patients suffer fromtype I disease. In general, initial clinical manifestations of HAEappear before 6 years of age.3 In our case report, onset of diseasewasat 6 years of age. Severity of HAE manifestations shows substantial

S. Hammami et al. / Respiratory Medicine CME 4 (2011) 15e1616

inter-individual variation. In paediatric population, Farkas4 foundthat eleven out of the 26 children followed up had frequent andsevere attacks. Most precipitation factors of HAE attacks aremechanical trauma and upper airways infection. In children,oedema of the extremities is the dominant manifestation. Abdom-inal attacks and laryngeal oedema are the most frequent severemanifestation of HAE, witch should be considered as realemergencies.5,6 The treatment of HAE consists of long-termprophylaxis, short-term prophylaxis, and management of acuteattacks.7,8 In life-threatening HAE attacks, the most adequatetherapy is the intravenous administration of C1-INH concentrate.9,10

Nevertheless, in our case report, therapy with fresh-frozen plasmawas also effective. In paediatric population, anti-fibrinolytic agentsare the first choice for long-term prophylaxis.7,11 In adult's patients,danazol has demonstrated its efficacy by increasing serumcomplement parameters significantly and reducing the frequencyand severity of clinical manifestations.12 Because of the mechanismof action of danazol has not yet been elucidated and regarding for itspotential adverse effects, experience use in paediatric populationhas been limited in patients with idiopathic thrombocytopenicpurpura.13 Long-term prophylaxis with danazol has been started inour casewith both improvement of clinical and biological course. Nodrug- adverse effect has been recorded. Undesirable adverse effectscan be avoided by using the lowest effective drug dose and anintermittent dosage regimen.

4. Conclusion

The main purpose of the management of HAE remains makingthe correct diagnosis. Laryngeal oedema is the most common causeof death related to HAE. It must be suspected and correctlymanaged in any child presenting with severe respiratory distress.

Long-term prophylaxis with danazol in childhood may reduce bothfrequency and severity of HAE acute attacks.

Conflict of interest statementNone of the authors have a conflict of interest to declare in

relation to this work.

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