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Angioneurotic Edema. Angioedema.
none. The authors reported no conflicts of interest regarding this report.
Introduction:
Hereditary Angioneurotic edema (Angioedema) is a rare autosomal dominant condition in which there is a deficiency of functional C1 inhibitor(1) which leads to episodic interstitial fluid accumulation in the skin, larynx or gastrointestinal tract or other region leading to various clinical presentations including life threatening hypotension and airway obstruction. The case presented demonstrates a classic presentation of angioedema of the small bowel suggested by history, CT, EGD and confirmed with C1 esterase inhibitor assay.
Endoscopic images were captured from endoscopy photographic images (Olympus) and digitized using Minolta Dimage A1 camera.
Case Report
This 21 year male presented to the emergency department in December of 2008 with a 12 hour history of cramping, mid-epigastric abdominal pain and vomiting. He denied having this pain before and had no recent illnesses or illicit drug use. His pain was not associated with eating. His emesis was bilious and without hematemesis. He also denied constipation, diarrhea, melena, hematochezia urinary symptoms, pruritis, rash, fever and weight changes.
CT scan in the emergency department suggested acute gastric outlet obstruction, as well as free abdominal fluid and bowel edema. (Figures 1-5)
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Figure 1 |
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Figure 3 |
His symptoms started improving after receiving dilaudid, ondansetron and IV fluids in the emergency department.
His past medical history was otherwise unremarkable and included depression, illicit drug use with drug-induced psychosis, and insomnia.
Current medications included venlafaxine, olanzapine and zolpidem with no recent changes. He had no allergies.
His family history was significant in that both his mother and grandfather had angioedema. His father had a myocardial infarction in his 40’s.
His physical exam included stable, normal vital signs. Patient appeared well-hydrated, healthy and in no distress. He had no swelling or hoarseness. Cardiorespiratory exam was normal. Abdomen was soft, without masses, rebound or guarding though he did have some moderate mid-epigastric tenderness to palpation.
Laboratory analysis revealed an elevated white blood count of 14.7 with 93% PMNs, CBC was otherwise normal. His BMP was remarkable for a minimally elevated bicarbonate level of 30, BUN of 29, otherwise normal. His lipase was 15 and ionized calcium was 4.1.
An upper gastrointestinal endoscopy with biopsy was performed after obtaining informed consent for the procedure. The EGD (Figures 6,7) revealed marked edema through the distal duodenum but without ulcerations or pathologic features. Biopsies of the jejunum revealed normal villus architecture with mild nonspecific chronic inflammation. The proximal duodenum was relatively normal. Gastric biopsy revealed chronic inflammation and numerous surface bacteria consistent with Helicobacter pylori infection.
Based on the rapid improvement and family history, further laboratory studies were performed which included a normal TTG but low C4 level of 9 mg/dL(normal 17-52 mg/dL), and low C1 Esterase inhibitor (C1 inh) antigen level of 5 mg/dL (normal 19-37 mg/dL). A diagnosis of Hereditary Angioedema Type I was made.
The patient’s symptoms completely resolved and he was discharged the day following admission.
This patient was seen in allergy clinic and started on danazol, an androgenic steroid also known as 17alpha-ethinyl testosterone.
Summary
Hereditary Angioedema (HAE) is an autonomic dominant condition which causes recurrent non-pitting subcutaneous or sub mucosal edema involving the arms, legs, hands, feet, genitalia, trunk, face, tongue, larynx or bowel2 though clinical symptoms may vary.1 A prodrome may be present and attacks are occasionally associated with erythematic marginatum which makes it difficult to distinguish from anaphylaxis. Common triggers of these episodes include dental work, trauma, cold, medications including ACE Inhibitors, stress and pregnancy. Helicobacter pylori has been reported as an aggravating factor in this condition.3
There are two types of hereditary angioedema, Type I and Type II. Type I leads to synthesis of C1 inh, but it is not secreted by cells. Type II leads to synthesis and secretion of a non-functional C1 inh. More than 100 genetic abnormalities have been identified leading to hereditary angioedema and the prevalence is estimated at 1/50,000.4,5 A similar type of condition, “familial angioedema,“ has been labeled angioedema Type III, though this proceeds through a different mechanism.
The C1 inhibitor protein (C1 inh) attenuates the proteolytic manufacture of bradykinin and the loss or inactivity of this protein leads to elevated bradykinin levels which has been identified as a significant factor in angioedema.6
It is important the clinician understands this condition and disease process in order to avoid unnecessary workup and intervention. CT imaging shows edema7 which resolves in a relatively short time interval. In general, endoscopy with biopsy does not add specific information regarding the diagnosis of angioedema. However, endoscopy does allow inspection of the pharynx prior to insertion of the endoscope into the esophagus to evaluate for unexpected upper airway edema. Endoscopy also allows inspection for other conditions which could lead to abnormal small bowel imaging, such as sprue. Associated conditions, such as helicobacter infections can also be identified.
Angioedema does not respond to typical therapies used in treatment of anaphylaxis though direct administration of fresh frozen plasma, epsilon-aminocaproic acid and danazol have been used.8 Cinryze, C1-esterase inhibitor product derived from human plasma, has recently been approved by FDA to prevent attacks of this condition.8,9 If there are no serious consequences of the attack (such as airway obstruction) most patients experience a resolution of their symptoms in 48-72 hours.
References:
1. Zuraw, Bruce L. Hereditary Angioedema. The New England Journal of Medicine 2008; 359: 1027-36.
2. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema as a cause of transient abdominal pain. J Clin Gastroenterol. 2002 Jan;34(1):57-61.
3. Visy B, Füst G, Bygum A, Bork K, Longhurst H, Bucher C, Bouillet L, Cicardi M, Farkas H. Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema. Helicobacter. 2007 Jun;12(3):251-7.
4. Bernstein IL. Hereditary angioedema: a current state-of-the-art review, II: historical perspective of non-histamine-induced angioedema. Ann Allergy Asthma Immunol. 2008 Jan;100(1 Suppl 2):S2-6.
5. Pappalardo E, Caccia S, Suffritti C, Tordai A, Zingale LC, Cicardi M. Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. Mol Immunol. 2008 Aug;45(13):3536-44.
6. Davis AE 3rd. The pathogenesis of hereditary angioedema. Transfus Apher Sci. 2003 Dec;29(3):195-203.
7. Wakisaka M, Shuto M, Abe H, Tajima M, Shiroshita H, Bandoh T, Arita T, Kobayashi M, Nakayama T, Okada F, Mori H, Uemura N. Computed tomography of the gastrointestinal manifestation of hereditary angioedema. Radiat Med. 2008 Dec;26(10):618-2.1.
8. Epstein TG, Bernstein JA. Current and Emerging Management Options for Hereditary Angioedema in the US Drugs. 2008;68(18):2561-73.
9. ) Lavine G. C1-Esterase Inhibitor Infusion (Cinryze) to Prevent Hereditary Angioedema Attacks FDA approves new drug to prevent hereditary angioedema attacks. Am J Health Syst Pharm. 2008 Nov 15;65(22):2080.
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