Transcript Angioedema of the GI Tract Howard Weiner, MD

Angioedema of the GI Tract
Howard Weiner, MD
June 21, 2006
C.K. 41 YO WHITE FEMALE
11.01.05 – Admitted via Internist’s Office
HPI:
1 day history of abdominal pain, fever, nausea, vomiting;
several days of minimal diarrhea
PMH:
Heartburn, hypercholesterolemia, asthma, hypertension, breast biopsy
SH:
ENT Office Worker; FMH: None
MEDS:
Lipitor, Protonix, Advair, Singulair, Dyazyde, Tri-norinyl; NKA
PE:
152/100
P116
T100.2
ASD: obese, soft, bowel sounds normal, mild epigastric tenderness
LAB:
WBC 21,200; HGB 14; LFTS, Amylase, Lipase WNL
CT SCAN:
Markedly thickened duodenum and proximal jejunum, some free fluid
in the pelvis, fatty liver.
C.K.
11.03.05
Endoscopy:
acute duodenitis, with edema and erosions, extending into
jejunum, erosive gastritis
Biopsy:
Bulb: mild increase in chronic inflammatory cells
11.04.05
Discharged
C.K.
01.29.06 – Admitted via ER
HPI:
1 week of increased bowel frequency, followed by cramps, nausea,
vomiting 1 day PTA
MEDS:
Lisinopril, Singulair, Lipitor, Prevacid, Trinorinyl
PE:
137/96
P100
T98.6 R18
ABD: obese, mild mid and lower abdominal tenderness.
LAB:
WBC 20,100; HgB 14.4; AST 43, GLU 131, stool Heme  stool WBC Ө
CT:
Markedly thickened 3rd, 4th duodenum and proximal jejunum, free fluid,
fatty liver
C.K.
01.30.06
Enteroscopy to 190 cm: copious secretions, slightly edematous with focal
submucosal erythema in small bowel
Biopsy: increased intramucosal chronic inflammatory cells
Post procedure: sore throat; 1½ hour post procedure uvula, face, tongue, lips are
swollen
Subsequent history of regarding lisindpril
C1 Esterase inhibitor 28 (21 – 29 mg/dL)
Angioedema (AE)
Non-inflammatory disease
Increased capillary permeability
in various organs/areas
1st described in 1882
1st report of hereditary AE in 1888 (Osler)
Classification
Hereditary
Non-Hereditary
Classification of Recurrent Angioedema
1.
Hereditary angioedema due to defiC1ency of C1 inhibitor protein and activity
(hereditary angioedema type I)
2.
Hereditary angioedema due to defiC1ency of C1 inhibitor activity (hereditary
angioedema type II)
3.
Hereditary angioedema with normal C1 inhibitor activity in women (hereditary
angioedema type III)
4.
Acquired angioedema due to increased consumption of C1 inhibitor or
autoantibody formation (acquired angioedema types I and II)
5.
Recurrent angioedema due to angiotensin-converting enzyme inhibitors or
angiotensin II-receptor antagonists
6.
Urticaria-related angioedema
7.
Idiopathic angioedema
Angioedema
Clinical characteristics
Episodes last 1-3 days
Face, airway, GI tract, skin, brain, muscle, urogenital tract
Provocative Factors
Infection, diagnostic tests, drugs, hormones
Hereditary AE
Defect of C1 esterase inhibitor
Dominant trait, variable penetrance 20-25% do not have FMH
Incidence
1:50,000 to 1:150,000
Onset early adolescence
Variable Presentation
Skin
Abdominal
Laryngeal
91%
73%
48%
Hereditary AE
Mechanism
C1 INH prevents conversion of inactive C1 to active form
C1 INH blocks plasma proteases, kallikrein, factor XII
If C1 INH is not present or functional, vasoactive mediators
are released
Lab Studies
Treatment
C4, C2, C1 inhibitor levels
Antihistamine
C1 inhibitor activity
Epinephrine
C3
Steroids
SPEP
Androgen (Danazol)
C1 INH concentrate
Plasminogen inhibitor
Acquired AE (C1 INH deficiency)
Paraneoplastic syndrome
•
Lymphomas
•
Multiple myeloma
•
Waldenstrom’s
•
CLL
•
Other neoplasms
Autoimmune disease
Caused by various mechanisms involving paraproteins and immune complexes
leading to activation of the C1 complex and depletion of C1 inhibitor
Angioedema Due to ACE Inhibitors
•
1st reported with enalapril - 06.1988
•
Incidence 0.1-0.2%
Octave trial 0.68%
•
Usually apparent within 7 days of initiating Rx; risk levels off by 9 weeks
•
Less severe than hereditary AE
•
Isolated tongue swelling more common
•
Hereditary and idiopathic AE may predispose as may prior drug reactions/seasonal
allergies
•
Black
•
Female
•
Small percentage get it with ARB’s also
•
Proposed Mechanisms
•
ACE (Kininase II) degrades bradykinin; when this doesn’t occur vasoactive
compounds produce vasodilatation
•
Genetic defects in Kininase I may predispose
•
Induction of tissue or drug specific antibodies
•
Induction of C1 inhibitor deficiency
ACE Inhibitors
Benazepril
Lotensin
Captopril
Calan
Enalapril
Vasotec
Lexxel
Fosinopril
Monopril
Lisinopril
Prinivil
Zestril
Moexipril
Unirotic
Ramipril
Altace
Trandolapril
Mavik
Tarka
Visceral Angioedema Due to ACE Inhibitors
Case Reports ’88, ’93, ’94, ’97, ’00
1st case report of lisinoril causing isolated
visceral AE in
04.97
Female predominance
Areas of involvement
Symptoms
•
Jejunum
•
Abdominal pain
•
Ileum
•
Nausea, vomiting
•
Duodenum
•
Diarrhea
•
Stomach
•
Ascites
•
Colon
•
No fever
•
Pancreas/Biliary tree
•
Ascites
Visceral Angioedema Due to ACE Inhibitors
Differential Diagnosis
• Inflammatory bowel disease
• Hemorrhage
• Ischemic bowel
• Neoplasm
• Vasculitis
• Bowel obstruction
• Pseudo obstruction
Findings
• Leukocytosis
• Ascites
• Imaging of bowel wall edema
• All stool studies negative
Lab Evaluations
• C1 inhibitor level normal
• No other complement components depleted
Treatment of ACE Inhibitor AE
•
Stop ACE Inhibitor
•
Probably don’t use ARB
•
Antihistamines
•
Epinephrine
•
Coricosteroids
Miscellaneous
•
Multiple presentations
•
IBD therapy
•
surgery/cholecystectomy
Angioedema and Gastroenterology
•
Report associating AE with midazolam
•
Report associating AE with Bezocaine
•
Study showing increased incidence of AE with H. pylori