Case Presentation June 25, 2004

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Case PresentationJune 25, 2004

• H. Henry Li, MD, PhD
• Institute for Asthma and Allergy

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Patient History

• 52 Y/O, F
• Frequent Abdominal pain since early childhood
• No vomiting, diarrhea, or skin rash
• Evaluation for food allergies, parasite
  infections, etc. all negative

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Patient History

• In her 20s, appendectomy
• In her 30s, ectopic pregnancy
• In her 40s, cholycystectomy
• Six exploratory abdominal procedures in 30 year
  period of time
• 2 month before the OV, started to have lip and
  tongue swelling

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Laboratory Examination

• C1 esterase inhibitor None detected
• C1 esterase inhibitor, functional None
• C4 lt 6 mg/dl
• Hgb 9.6,
• Iron 32 mg/dl
• Ferritin 10 ng/dl

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Family History
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Major Features of Hereditary Angioedema

• Onset generally in youth
• Autosomal dominant inheritance, Incomplete
  penetrance, de novo mutation
• Abdominal pain common
• Laryngeal edema relatively common
• Urticaria and pruritus absent
• C1 inhibitor deficiency

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Contact activation pathway leading to bradykinin
formation.
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C1 Inhibitor Functions

• Inhibits C1r and C1s of the complement system
• Inhibits activated factor XIIa and kallikrein
• An inhibitor of factor XIa and plasmin
• Inhibits activation of C1

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Role of C1 inhibitor
Trace Factor XIIa
Prekallikrein
HK
Factor XII
Factor XIIa
Surface
Surface
Kallikrein
Bradykinin
Plasminogen
Factor XIIf
Plasmin
C4, C2 digestion
C1
C1
Inhibited By C1 INH
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Further Data Regarding C1 INH

• Complete acid sequence known heavily
  glycosylated
• Generation of cDNA clones accomplished,
  localization to chromosome 11
• Deficiency heterogeneous by DNA restriction
  fragment length polymorphisms
• Deficiency frequently associated with autoimmune
  phenomena
• Mechanisms of acquired C1 inhibitor deficiency
• Depletion by complement activation
• Contact system activation
• Anti-C1 inhibitor antibodies
• Anti-idiotypic antibodies

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Lab Tests for C1 INH Deficiency

• C4 low C4d/C4 ratio always elevated
• C1 inhibitor protein low in about 85 of cases
• C1 inhibitor only functionally deficient in about
  15
• C1q antigen low in acquired deficiency
• Abnormal C1 inhibitor mobility (lower molecular
  weight) on SDS gel electrophoresis

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Treatment of HAE

• Patient education very important test family
• No regular medication needed in many cases
• Long term prophylactic anabolic androgens and
  antifibrinolytics
• Short term prophylaxis
• Symptomatic treatment during attacks

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Long Term Prophylaxis

• Stanozolol (1-4 mg/day) (more virilizing, less
  expensive)
• Danozol (50 mg qod 200 mg tid)
• Epsilon aminocaproic acid (EACA, Amicar) an
  option

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Short Term Prophylaxis

• Fresh frozen plasma, 2 units, 7 hour before
  procedure
• High dose of Danazol/Stanozolol, 7 10 days
  before procedure

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Treatment of Acute Attacks

• Antihistamine, Epinephrine, corticosteroids,
  limited value
• Pain relieve with narcotics
• C1 INH infusion
• EACA IV
• FFP use with care
• New medications

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Future Treatment Options

• C1 esterase inhibitor infusion
• Human Concentrates
• Transgenic rh C1 INH
• Kallikrein inhibitor
• Bradykinin receptor blocker