Recurrent abdominal pain due to hereditary angioedema
http://www.100md.com
《美国医学杂志》
Department of Pediatrics, Amrita Institute of Medical Sciences, Elamakkara (P.O.), Kochi, Kerala, India
Recurrent abdominal pain is a common problem in children that may need invasive procedures for diagnosis. Hereditary angioedema (HAE) is rarely considered in the differential diagnosis. Here it is reported a girl with HAE, who presented initially as recurrent abdominal pain without cutaneous manifestations. Each episode was managed elsewhere as an acute surgical emergency and an exploratory laparotomy was planned. Diagnosis was confirmed by quantitative assay of C1 inhibitor. On detailed evaluation, many members of her family were affected.
Keywords: Hereditary angioedema; C1 inhibitor deficiency; Recurrent abdominal pain
Hereditary angioedema (HAE) is an autosomal dominant disorder with an estimated prevalence of 1/150,000 population.[1],[2] Although this condition is rare one should be aware of its consequences, as it can be life threatening at times.[3] The disorder is characterized by non-pruritic angioedema of face, extremities or larynx and can be associated with abdominal pain.[2],[4] There are no documented reports in children of HAE manifesting initially as isolated recurrent abdominal pain. We report a 10-year-old girl with HAE, who suffered from recurrent abdominal pain without cutaneous manifestations for 5 years before a diagnosis of HAE was made.
Case Report
A 10-year-old girl was referred with history of recurrent attacks of abdominal pain since the age of 5 years. She was hospitalized several times a year for the same. A surgical cause was suspected and an exploratory laparotomy was planned elsewhere. Cutaneous manifestations were absent during the initial 5 years of illness. Abdominal radiographs showed nonspecific bowel gas patterns. There was no relation of these episodes to food intake or drugs.
During the past 1 year, she also developed 3 episodes of non-pruritic, non-erythematous swelling of the face and neck. There was no history of swelling in any other part of the body, hoarseness of voice or breathing difficulty. Each episode lasted for 3-4 days and subsided spontaneously with symptomatic treatment.
At admission she had non-tender, non-erythematous ill-defined edema of face and neck. Lips were edematous and she had difficulty in opening the mouth. Vitals were stable. There was no cyanosis, stridor or rhonchi on examination. Abdomen was soft and nontender. Laryngeal edema was ruled out by indirect laryngoscopy after admission to ICU.
On probing further, the parents revealed that many members of the family including the father had recurrent attacks of abdominal pain, non-pruritic skin rashes and occasional episodes of breathing difficulty. Two siblings of the father died during the third decade due to acute respiratory distress [Figure - 1].
A clinical diagnosis of HAE was made. Investigations revealed normal blood counts, urinalysis, serum amylase, hepatic and renal function tests. Ultrasound scanning of the abdomen was normal. Antinuclear antibody and urine for porphobilinogen were negative. Serum C4 estimation done as a screening test for common pathway, was found to be reduced to 7.5 mg/dl (Normal: 22.6-59 mg/dl). C1 inhibitor protein (C1 INH) level was reduced to 64 mg/dl (Normal: 275-400 mg/dl). After the patient's diagnosis was confirmed, her family was investigated. Serum C4 levels of her father (8.6 mg/dl) and two symptomatic cousins (5.6 mg/dl and 6.9 mg/dl respectively) were also decreased.
The girl improved with good supportive care. Later she was started on danazol at a dose of 2 mg/Kg/day. The child is asymptomatic during the 6 months follow up period. The affected family members are also remaining symptom free on prophylactic medication.
Discussion
HAE is a rare inherited disorder that results in dysregulation of complement and kallikrein- kinin system due to deficiency or dysfunction of C1 esterase inhibitor.[2] C1 INH deficiency allows unopposed activation of C1 and thereby activation of C4 and C2.[3] Histamine and other inflammatory mediators do not seem to have any causative role in this type of angioedema.
Traditionally HAE has been classified into 2 types. Type I which is the most common form, is characterized by low quantitative levels of C1 INH. Type II that affects 15% is characterized by a dysfunctional protein, which has abnormal function.[4] The clinical symptoms include non-pruritic angioedema, abdominal pain and life threatening episodes of laryngeal obstruction.[5] Although attacks occur spontaneously, anxiety, stress, minor trauma and surgery have been cited as triggers. Gastrointestinal manifestations like nausea, vomiting, abdominal pain or diarrhoea results from bowel wall edema and partial gut obstruction.[1],[2] The patient presented initially with recurrent abdominal pain without cutaneous, oropharyngeal and respiratory involvement. These attacks can mimic a surgical emergency and the diagnosis of HAE may be delayed.
The evaluation of recurrent abdominal pain in children is problematic and invasive procedures may be required for diagnosis. In this scenario, a detailed family history as in our case may provide a useful clue to diagnosis of HAE.
Estimation of C4 level during an attack is a good screening test for HAE.[3],[4] If C4 level is low during an episode, C1 INH level and function should be assessed to confirm the diagnosis of HAE.[4]
The management of HAE involves treatment of acute episodes, short-term prophylaxis and long-term prophylaxis. Prophylactic treatment is indicated if the patient develops a life threatening attack, or has 3 or more attacks in a year.[1] Attenuated androgens like danazol, oxandrolone, stanazolol and antifibrinolytic agents are used for prophylaxis.[6] Treatment of choice for established acute attack is purified C1 inhibitor concentrate when available.[7] Fresh frozen plasma helps to tide over the crisis in an emergency if synthetic inhibitor is not available. New inhibitors of fibrinolytic system such as kallikrein inhibitor DX88 and bradykinin receptor blocker Icatibant hold promise for use in HAE and trials are commencing.[4]
Our patient was started on Danazol in a dose of 2 mg/Kg/day. She is remaining symptom free and without complications during the follow up period. The affected symptomatic family members were also started on prophylaxis and are remaining symptom free.
HAE should be considered in children with unexplained recurrent abdominal symptoms suggestive of intestinal pseudo obstruction, so that unnecessary invasive procedures can be avoided. A detailed family history may provide a useful clue to diagnosis. Serum C4 estimation may be a simple screening test during an acute attack. Early diagnosis and prophylactic therapy when indicated are life saving.
Contributors: DJ reviewed the literature and drafted the initial manuscript. SN was involved in the management of the patient, designing the article, revision of manuscript and will act as a guarantor for the paper. STS was involved in the management of the patient and in critical revision of the manuscript.
Funding none.
Competing interest-none
References
1.Avnish KS, Velu N, Jasjith S, Ved PD. Hereditary angioedema with recurrent abdominal pain. Indian Gastroenterol 2002; 21: 82-83.
2.Weinstock LB, Kothari T, Sharma SN. Recurrent abdominal pain as the sole manifestation of hereditary angioedema in multiple family members. Gastroenterology 1987; 93 : 1116-1118.
3.Arun KB, Surjit Singh, Latha Kumar. Hereditary Angioedema. Indian Pediatrics 1999; 36 : 187-189.
4.Gompels MM, Lock RJ, Abinun M et al. C1 inhibitor deficiency: consensus document. Clinical and experimental Immunology 2005; 139 : 379-394.
5.Bork K, Barnstedt SE. Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with HAE. Arch Intern Med 2001; 161 : 714-718. [PUBMED] [FULLTEXT]
6.Gelfand JA, Sherins RJ, Alling DW et al. Treatment of hereditary angioedema with danazol: reversal of clinical and biochemical abnormalities. N Engl J Med 1976; 295 : 1444.
7.Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor treated C1 inhibitor concentrate. N Engl J Med 1996; 334 : 1630-1634. [PUBMED] [FULLTEXT](Janardhanan Deepa, Nair Sajitha, Subrama)
Recurrent abdominal pain is a common problem in children that may need invasive procedures for diagnosis. Hereditary angioedema (HAE) is rarely considered in the differential diagnosis. Here it is reported a girl with HAE, who presented initially as recurrent abdominal pain without cutaneous manifestations. Each episode was managed elsewhere as an acute surgical emergency and an exploratory laparotomy was planned. Diagnosis was confirmed by quantitative assay of C1 inhibitor. On detailed evaluation, many members of her family were affected.
Keywords: Hereditary angioedema; C1 inhibitor deficiency; Recurrent abdominal pain
Hereditary angioedema (HAE) is an autosomal dominant disorder with an estimated prevalence of 1/150,000 population.[1],[2] Although this condition is rare one should be aware of its consequences, as it can be life threatening at times.[3] The disorder is characterized by non-pruritic angioedema of face, extremities or larynx and can be associated with abdominal pain.[2],[4] There are no documented reports in children of HAE manifesting initially as isolated recurrent abdominal pain. We report a 10-year-old girl with HAE, who suffered from recurrent abdominal pain without cutaneous manifestations for 5 years before a diagnosis of HAE was made.
Case Report
A 10-year-old girl was referred with history of recurrent attacks of abdominal pain since the age of 5 years. She was hospitalized several times a year for the same. A surgical cause was suspected and an exploratory laparotomy was planned elsewhere. Cutaneous manifestations were absent during the initial 5 years of illness. Abdominal radiographs showed nonspecific bowel gas patterns. There was no relation of these episodes to food intake or drugs.
During the past 1 year, she also developed 3 episodes of non-pruritic, non-erythematous swelling of the face and neck. There was no history of swelling in any other part of the body, hoarseness of voice or breathing difficulty. Each episode lasted for 3-4 days and subsided spontaneously with symptomatic treatment.
At admission she had non-tender, non-erythematous ill-defined edema of face and neck. Lips were edematous and she had difficulty in opening the mouth. Vitals were stable. There was no cyanosis, stridor or rhonchi on examination. Abdomen was soft and nontender. Laryngeal edema was ruled out by indirect laryngoscopy after admission to ICU.
On probing further, the parents revealed that many members of the family including the father had recurrent attacks of abdominal pain, non-pruritic skin rashes and occasional episodes of breathing difficulty. Two siblings of the father died during the third decade due to acute respiratory distress [Figure - 1].
A clinical diagnosis of HAE was made. Investigations revealed normal blood counts, urinalysis, serum amylase, hepatic and renal function tests. Ultrasound scanning of the abdomen was normal. Antinuclear antibody and urine for porphobilinogen were negative. Serum C4 estimation done as a screening test for common pathway, was found to be reduced to 7.5 mg/dl (Normal: 22.6-59 mg/dl). C1 inhibitor protein (C1 INH) level was reduced to 64 mg/dl (Normal: 275-400 mg/dl). After the patient's diagnosis was confirmed, her family was investigated. Serum C4 levels of her father (8.6 mg/dl) and two symptomatic cousins (5.6 mg/dl and 6.9 mg/dl respectively) were also decreased.
The girl improved with good supportive care. Later she was started on danazol at a dose of 2 mg/Kg/day. The child is asymptomatic during the 6 months follow up period. The affected family members are also remaining symptom free on prophylactic medication.
Discussion
HAE is a rare inherited disorder that results in dysregulation of complement and kallikrein- kinin system due to deficiency or dysfunction of C1 esterase inhibitor.[2] C1 INH deficiency allows unopposed activation of C1 and thereby activation of C4 and C2.[3] Histamine and other inflammatory mediators do not seem to have any causative role in this type of angioedema.
Traditionally HAE has been classified into 2 types. Type I which is the most common form, is characterized by low quantitative levels of C1 INH. Type II that affects 15% is characterized by a dysfunctional protein, which has abnormal function.[4] The clinical symptoms include non-pruritic angioedema, abdominal pain and life threatening episodes of laryngeal obstruction.[5] Although attacks occur spontaneously, anxiety, stress, minor trauma and surgery have been cited as triggers. Gastrointestinal manifestations like nausea, vomiting, abdominal pain or diarrhoea results from bowel wall edema and partial gut obstruction.[1],[2] The patient presented initially with recurrent abdominal pain without cutaneous, oropharyngeal and respiratory involvement. These attacks can mimic a surgical emergency and the diagnosis of HAE may be delayed.
The evaluation of recurrent abdominal pain in children is problematic and invasive procedures may be required for diagnosis. In this scenario, a detailed family history as in our case may provide a useful clue to diagnosis of HAE.
Estimation of C4 level during an attack is a good screening test for HAE.[3],[4] If C4 level is low during an episode, C1 INH level and function should be assessed to confirm the diagnosis of HAE.[4]
The management of HAE involves treatment of acute episodes, short-term prophylaxis and long-term prophylaxis. Prophylactic treatment is indicated if the patient develops a life threatening attack, or has 3 or more attacks in a year.[1] Attenuated androgens like danazol, oxandrolone, stanazolol and antifibrinolytic agents are used for prophylaxis.[6] Treatment of choice for established acute attack is purified C1 inhibitor concentrate when available.[7] Fresh frozen plasma helps to tide over the crisis in an emergency if synthetic inhibitor is not available. New inhibitors of fibrinolytic system such as kallikrein inhibitor DX88 and bradykinin receptor blocker Icatibant hold promise for use in HAE and trials are commencing.[4]
Our patient was started on Danazol in a dose of 2 mg/Kg/day. She is remaining symptom free and without complications during the follow up period. The affected symptomatic family members were also started on prophylaxis and are remaining symptom free.
HAE should be considered in children with unexplained recurrent abdominal symptoms suggestive of intestinal pseudo obstruction, so that unnecessary invasive procedures can be avoided. A detailed family history may provide a useful clue to diagnosis. Serum C4 estimation may be a simple screening test during an acute attack. Early diagnosis and prophylactic therapy when indicated are life saving.
Contributors: DJ reviewed the literature and drafted the initial manuscript. SN was involved in the management of the patient, designing the article, revision of manuscript and will act as a guarantor for the paper. STS was involved in the management of the patient and in critical revision of the manuscript.
Funding none.
Competing interest-none
References
1.Avnish KS, Velu N, Jasjith S, Ved PD. Hereditary angioedema with recurrent abdominal pain. Indian Gastroenterol 2002; 21: 82-83.
2.Weinstock LB, Kothari T, Sharma SN. Recurrent abdominal pain as the sole manifestation of hereditary angioedema in multiple family members. Gastroenterology 1987; 93 : 1116-1118.
3.Arun KB, Surjit Singh, Latha Kumar. Hereditary Angioedema. Indian Pediatrics 1999; 36 : 187-189.
4.Gompels MM, Lock RJ, Abinun M et al. C1 inhibitor deficiency: consensus document. Clinical and experimental Immunology 2005; 139 : 379-394.
5.Bork K, Barnstedt SE. Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with HAE. Arch Intern Med 2001; 161 : 714-718. [PUBMED] [FULLTEXT]
6.Gelfand JA, Sherins RJ, Alling DW et al. Treatment of hereditary angioedema with danazol: reversal of clinical and biochemical abnormalities. N Engl J Med 1976; 295 : 1444.
7.Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor treated C1 inhibitor concentrate. N Engl J Med 1996; 334 : 1630-1634. [PUBMED] [FULLTEXT](Janardhanan Deepa, Nair Sajitha, Subrama)