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Year : 2016  |  Volume : 30  |  Issue : 2  |  Page : 109-111

Clinical profile of patients with C1-inhibitor deficiency from Eastern India

Department of Allergy and Immunology, Apollo Gleneagles Hospital, Kolkata, West Bengal, India

Date of Web Publication5-Dec-2016

Correspondence Address:
Sujoy Khan
Department of Allergy and Immunology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata - 700 054, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-6691.195271

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C1-inhibtor deficiency or hereditary angioedema is a rare, autosomal dominant disorder that is characterized by severe episodic attacks of angioedema that can affect any part of the body. It is caused by mutations in the C1-inhibitor gene (C1-INH or SERPING 1 gene) that is mapped to chromosome 11 (11q12-q13.1). The majority of patients have a family history although 25% of cases can be de novo mutations (i.e., no family history). Distinguishing the angioedema due to C1-inhibitor deficiency from allergic or idiopathic angioedema requires clinical acumen, and this delay in diagnosis leads to unnecessary surgical interventions, and in unfortunate cases, mortality that is now possible to prevent with easy access to screening tests and proper management.

Keywords: Angioedema, C1-inhibitor deficiency, complement C4, hereditary angioedema

How to cite this article:
Khan S. Clinical profile of patients with C1-inhibitor deficiency from Eastern India. Indian J Allergy Asthma Immunol 2016;30:109-11

How to cite this URL:
Khan S. Clinical profile of patients with C1-inhibitor deficiency from Eastern India. Indian J Allergy Asthma Immunol [serial online] 2016 [cited 2023 Feb 5];30:109-11. Available from: https://www.ijaai.in/text.asp?2016/30/2/109/195271

  Introduction Top

C1-inhibitor deficiency (hereditary angioedema [HAE]) is a rare autosomal dominant, potentially life-threatening disorder (estimated prevalence 1/10,000-1/150,000 worldwide) that manifests with swelling attacks of lips, tongue, airways, and abdomen. [1] The previous nationwide surveys from six countries in Europe published in 2013 had shown that the median delay in the diagnosis of C1-inhibitor deficiency from onset of symptoms was 8.5 years that ranged from 2.0 years (0.0-62.0) (Germany) to 15.0 years (0.0-57.0) (Italy), [2] which is a significant improvement from a diagnostic delay of 21 years in the year 1976. [3] Data on clinical profile and diagnostic delay of HAE from the Indian subcontinent remain unknown.

  Case Report Top

This case series of eight patients from five families with Type I HAE is presented that aims to highlight the causes of diagnostic delay and the morbidity faced by such patients. Participants gave written informed consent, and patient anonymity was preserved using methods approved by the Ethics Committee.

P1 is a 25-year-old male who had >100 swelling episodes since 12 years of age. He had been admitted several times with severe peripheral angioedema affecting his fingers, toes, as well as facial attacks of angioedema [Figure 1]. He was on intermittent steroids for 2-3 months at a time and daily antihistamines with no effect. Clinical examination revealed angioedema affecting his right thumb and forefingers. He was avoiding several "allergenic" foods as serum IgE was raised at 684 IU/ml. Undetectable C4 and low C1-inhibitor antigenic level confirmed Type I HAE [Table 1]. Regular treatment with danazol 200mg and tranexamic acid 500 mg twice daily controlled the attacks and remains on danazol 100 mg once daily.
Figure 1: Peripheral attack of angioedema in a patient with Type I hereditary angioedema

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Table 1: Profile of patients with Type I C1 - inhibitor deficiency

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P2 is a 56-year-old woman (mother of P1) who also had a similar history of recurrent angioedema but more abdominal attacks (at least 2/month) for over 40 years. She avoided solid foods for 7-10 days/month due to unbearable pains leading to severe weight loss. Diagnosis remained elusive and had undergone probable unnecessary appendicectomy including extensive investigations to exclude gastrointestinal malignancy. Interestingly, several tooth extractions and hysterectomy had not triggered angioedema episodes. At the time of consultation, she was on a very restricted diet of boiled vegetables and rice as they were probably the only "nonallergenic" foods according to the treating physicians. Treatment with danazol 100 mg and intermittent tranexamic acid was successful with no reported facial or abdominal attacks for the past 12 months.

P3 is a 45-year-old man with no family history of angioedema attacks, but he had several attacks of peripheral and mucosal angioedema (antihistamine unresponsive) for 10 years. On clinical examination, there was significant lip and mild testicular swelling. Tests confirmed Type I HAE [Table 1]. He has a 15-year-old daughter with no angioedema episodes (C4 level - 36 mg/dl). Treatment with danazol 200 mg and tranexamic acid 500 mg twice daily controlled the episodes. Ultrasound liver after 6 months on danazol revealed a hemangioma with normal liver function tests; alpha-fetoprotein level and remains on regular follow-up.

P4 is a 12-year-old female who complained of episodic severe facial angioedema for 3 years. An ELISA-based allergy test was positive for multiple foods that she was constantly avoiding, but the severity of the attacks prompted self-referral. Tests confirmed Type I HAE. Her father had died following a severe typhoidal illness in his mid-40s; however, the family had noted severe facial angioedema at the time (possible abdominal attack). She remains well only on as-required tranexamic acid 500 mg just during her menstrual periods.

P5 is a 41-year-old male who had >100 attacks of angioedema for 22 years affecting face, lips [Figure 2], feet, legs, genitalia, and a traumatic episode to the hand that followed with edema lasting for almost 2 weeks. C4 level tested elsewhere 1 year ago was <5 mg/dl but was not started on treatment. His mother also had peripheral attacks of angioedema during her life and had developed extensive facial edema after a fall that had resulted in severe tongue edema and could not be resuscitated. His sister also has episodic mild peripheral angioedema and never had facial or abdominal attacks. He has remained asymptomatic on stanozolol 4 mg once daily for the past 2 years.
Figure 2: Facial attack of angioedema

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P6 is a 34-year-old female who had severe lip and throat angioedema after eating prawns at a restaurant in the USA where during routine investigations, she was found to have C1-inhibitor deficiency. On follow-up, the C4 level was 3 mg/dl and since she was largely asymptomatic, chose to be treated on as-required basis.

P7 is her 65-year-old father who had attacks for 28 years and was diagnosed with C1-inhibitor deficiency 3 years before the incident with P6 but was not offered family screening. He was on regular danazol 100 mg on alternate days. Interestingly, on routine coagulation tests before a surgical intervention, he was found to have low activated partial thromboplastin time (aPTT) (that remained low on several occasions) with negative Factor V Leiden mutation. In spite of the low C4 level, he has only episodic mild peripheral attacks and continues on danazol 100 mg alternate days, storvas 20 mg (hyperlipidemia), and bisoprolol 2.5 mg (for hypertension).

P8 is the 28-year-old brother of P6 who also had several attacks of peripheral and lip angioedema since 16 years of age. He was on treatment for anxiety, obsessive-compulsive disorder, and the angioedema episodes were attributed to adverse drug reactions to psychotropic medications. He was confirmed to have Type I HAE and remains asymptomatic on danazol 100 mg alternate days.

  Discussion Top

This case series reveals that the median diagnostic delay in diagnosis of C1-inhibitor deficiency in India is higher at 12 years (mean, 16.1 years) when compared to the UK. [2] The spontaneous mutation rate noted was 20% while the reasons behind low aPTT in HAE remain unknown. [4] While unawareness among nonspecialist physicians may still be the primary reason behind the diagnostic delay, confusing terminologies such as "angioneurotic edema" in textbooks downplay the seriousness of this disorder. This is compounded by the prevalent myth that in the absence of availability of expensive medications such as C1-inhibitor concentrate or bradykinin antagonists in India, there are no treatment options left to patients even after diagnosis. Some patients, therefore, do not seek further specialist help that leads to higher morbidity and mortality, adverse side effects of unnecessary medications and surgical interventions. [5],[6]

There is, therefore, an urgent need to reduce diagnostic delay and ensure patients with C1-inhibitor deficiency is appropriately managed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med 2008;359:1027-36.  Back to cited text no. 1
Zanichelli A, Magerl M, Longhurst H, Fabien V, Maurer M. Hereditary angioedema with C1-inhibitor deficiency: Delay in diagnosis in Europe. Allergy Asthma Clin Immunol 2013;9:29.  Back to cited text no. 2
Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: The clinical syndrome and its management. Ann Intern Med 1976;84:580-93.  Back to cited text no. 3
Khan S, Adhya Z, Karim Y, Griffiths H, Deacock S, Bright P, et al. Low APTT in C1-inhibitor deficiency: An audit of two immunology centres in the UK. Immunology 2010;131 Suppl 1:118.  Back to cited text no. 4
Zanichelli A, Vacchini R, Badini M, Penna V, Cicardi M. Standard care impact on angioedema because of hereditary C1-inhibitor deficiency: A 21-month prospective 2 study in a cohort of 103 patients. Allergy 2011;66:192-6.  Back to cited text no. 5
Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol 2012;130:692-7.  Back to cited text no. 6


  [Figure 1], [Figure 2]

  [Table 1]


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