Large-Bowel Obstruction Induced by Hereditary Angioedema: A Case-Based Scientific Review

Keywords: hereditary angioedema, large-bowel obstruction, C1 esterase inhibitor deficiency, abdominal angioedema, gastrointestinal edema, complement system disorder, bowel ischemia, bowel wall thickening

Abstract

Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by episodes of severe swelling due to C1 esterase inhibitor (C1-INH) deficiency. While common manifestations include cutaneous and oropharyngeal edema, gastrointestinal involvement is frequently underrecognized. This article presents a case of large-bowel obstruction due to bowel wall edema secondary to HAE and discusses the underlying etiology, clinical presentation, imaging findings, and management strategies, with emphasis on the need for early recognition and appropriate long-term prophylaxis.

Introduction

Large-bowel obstruction (LBO) represents a surgical emergency with multiple potential etiologies. Among them, angioedema-induced LBO remains an exceptionally rare but important cause, especially in patients with undiagnosed hereditary angioedema (HAE). This case illustrates a classic, yet often overlooked, manifestation of HAE and highlights diagnostic and therapeutic considerations that are critical for clinicians across disciplines.

Case Presentation

A 37-year-old male presented to the emergency department with severe abdominal pain and vomiting of 8 hours' duration. Physical examination revealed diffuse abdominal distension and hypoactive bowel sounds. He had no prior history of abdominal surgery.

Radiologic Evaluation

Plain abdominal radiograph (Fig. 1) showed markedly dilated loops of small bowel and proximal colon.
Barium enema study revealed an abrupt transition point at the splenic flexure, indicating high-grade large-bowel obstruction.

[Figure 1]: Plain abdominal X-ray showing dilated small bowel loops and large bowel distension consistent with mechanical obstruction.

Surgical Intervention

Emergent laparotomy demonstrated severe mucosal edema and massive distension of the transverse colon extending to the ascending colon. A segmental colectomy was performed.

Postoperative history revealed multiple episodes of unexplained abdominal pain, swelling in hands, feet, and scrotum, beginning at age 18, without accompanying urticaria. The patient had no history of ACE inhibitor use but reported similar episodes in his father and relatives.

Laboratory Findings

C4 complement: Low
C1-INH level: 6 mg/dL (reference: 19–37 mg/dL)

A diagnosis of hereditary angioedema type I was confirmed.

Etiology and Pathophysiology

Hereditary angioedema is an autosomal dominant disorder caused by a quantitative or functional deficiency of C1 esterase inhibitor, leading to uncontrolled activation of the complement and contact systems. The resultant bradykinin excess increases vascular permeability, resulting in episodic localized edema.

Gastrointestinal tract involvement is common in HAE but often misdiagnosed as functional bowel disorders or a surgical abdomen. Severe cases can result in bowel wall edema, impaired peristalsis, and even mechanical obstruction, as in this case.

Epidemiology

HAE prevalence: ~1 in 50,000 individuals
No racial or gender predilection
~80–85% cases are Type I (C1-INH deficiency)
GI symptoms occur in up to 93% of patients during attacks, but are frequently overlooked

Clinical Presentation

Symptoms vary depending on the affected site:

Cutaneous edema: face, limbs, genitalia
Respiratory: laryngeal edema (life-threatening)
Abdominal: pain, nausea, vomiting, diarrhea, or obstruction

The absence of pruritus or urticaria is key in distinguishing HAE from allergic angioedema.

Imaging Features

Plain films: non-specific bowel distension
CT: bowel wall thickening, mucosal edema, ascites, and "target sign"
Barium enema: transition point without intrinsic lesion

In this case, radiologic signs mimicked mechanical obstruction, leading to unnecessary surgery. Early suspicion could have prevented operative intervention.

Treatment and Management

Acute Attacks

C1-INH concentrate (e.g., Berinert)
Bradykinin receptor antagonist (e.g., Icatibant)
Kallikrein inhibitor (e.g., Ecallantide)

Long-Term Prophylaxis

Attenuated androgens (e.g., Danazol)
C1-INH replacement (e.g., Cinryze)
Lanadelumab (kallikrein mAb)

In this case, the patient was started on Danazol and prophylactic C1-INH therapy.

Genetic Counseling

Given the autosomal dominant inheritance, first-degree relatives should be screened for C1-INH deficiency, especially in cases of unexplained swelling or abdominal pain.

Prognosis

Without treatment, HAE can lead to fatal airway obstruction or unnecessary surgeries due to misdiagnosis. With proper prophylaxis and patient education, most individuals can live normal lives.

Discussion

This case underscores the importance of considering hereditary angioedema in patients with recurrent abdominal symptoms or unexplained bowel obstruction without an identifiable cause. Radiologists, surgeons, and internists should maintain a high index of suspicion, especially in patients with:

No prior abdominal surgery
Family history of similar symptoms
No urticaria
Low C4 and C1-INH levels

Quiz

1. Which of the following laboratory findings is most consistent with hereditary angioedema?

A. Elevated IgE levels
B. Normal C1-INH level
C. Low C4 and low C1-INH
D. High C-reactive protein

2. What is the most appropriate treatment for acute abdominal HAE attacks?

A. Antihistamines and corticosteroids
B. Surgical resection
C. C1-INH concentrate and bradykinin antagonist
D. Broad-spectrum antibiotics

Answer & Explanation

1. Answer: C. Low C4 and low C1-INH
Explanation: HAE is characterized by complement consumption (low C4) and deficient or dysfunctional C1 esterase inhibitor levels. Elevated IgE and CRP are more indicative of allergic or inflammatory processes.

2. Answer: C. C1-INH concentrate and bradykinin antagonist
Explanation: Unlike allergic angioedema, HAE is bradykinin-mediated and unresponsive to steroids or antihistamines. C1-INH and agents like Icatibant are the first-line treatments.

Conclusion

Hereditary angioedema is an underdiagnosed cause of gastrointestinal symptoms and large-bowel obstruction. Accurate diagnosis hinges on clinical suspicion and laboratory confirmation. Preventing unnecessary surgery and providing targeted therapy can significantly improve outcomes. Physicians should consider HAE in the differential diagnosis of abdominal pain and obstruction, particularly in patients with a personal or family history of unexplained swelling.

References

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