✅ Model Answer:
• Diagnosis: Hereditary angioedema (HAE type 1) – recurrent non-pitting, non-pruritic swelling of extremities, lips, abdominal pain without urticaria. Low C4, low C1-INH protein and function, normal C1q (excludes acquired angioedema). Positive family history.
• Any other test: low C1-INH Protein(normal 22-45), low C1-INH Functionnormal (>50%), Genetic testing (SERPING1 gene mutation), family screening (C4, C1-INH levels in first-degree relatives), rule out acquired angioedema (C1q low in acquired).
• What to do next: Acute attack: C1-INH concentrate (Berinert) IV, or icatibant (SC bradykinin antagonist), or ecallantide (SC kallikrein inhibitor). Avoid ACE inhibitors (precipitate attacks).
• Follow-up plan: Long-term prophylaxis: SC C1-INH (Haegarda), lanadelumab (anti-kallikrein), or berotralstat (oral). Danazol (attenuated androgen) second-line in adolescents. Patient education: medical ID, home therapy for acute attacks.

✅ Model Answer:
• Swelling (angioedema):
- Non-pitting, non-pruritic (not itchy like urticaria)
- Affects extremities (hands, feet), face (lips, eyelids, tongue), genitals
- May involve the airway (laryngeal edema – life-threatening)
- Usually asymmetric
- Lasts 2-5 days and resolves spontaneously
• Abdominal attacks:
- Severe colicky abdominal pain, nausea, vomiting, diarrhea
- May mimic surgical abdomen (but no peritoneal signs)
- Caused by bowel wall edema
• No urticaria (key distinguishing feature from allergic angioedema)
• Triggers: Trauma, stress, infection, menstruation, ACE inhibitors, dental procedures

✅ Model Answer:
• Pathophysiology: Deficiency or dysfunction of C1 esterase inhibitor (C1-INH) – a serine protease inhibitor.
• Normally: C1-INH regulates the complement, kinin, and coagulation systems.
• In HAE: ↓ C1-INH → uncontrolled activation of the kallikrein-kinin system → increased bradykinin production.
• Bradykinin causes increased vascular permeability → fluid extravasation → edema.
• Types:
- Type 1: Low C1-INH protein and function (85% of cases)
- Type 2: Normal C1-INH protein but low function (15%)
- Type 3: Normal C1-INH, estrogen-associated (rare, often in females)

✅ Model Answer:
• Clinical criteria:
- Recurrent non-pitting, non-pruritic swelling (skin, GI tract, upper airway)
- No urticaria
- Recurrent abdominal pain without peritoneal signs
- Family history of HAE
• Laboratory criteria (for Type 1 and 2):
- C4: Low (most sensitive screening test)
- C1-INH protein: Low (Type 1) or normal (Type 2)
- C1-INH function: <50% of normal
- C1q: Normal (differentiates from acquired angioedema)
• Confirmatory: Genetic testing (SERPING1 gene mutations)

✅ Model Answer:
• First-line agents (for acute attacks):
- C1-INH concentrate (Berinert, Cinryze): IV, 20 U/kg – most effective, rapid onset
- Icatibant (Firazyr): SC bradykinin B2 receptor antagonist – given as 30 mg SC injection
- Ecallantide (Kalbitor): SC kallikrein inhibitor (for HAE type 1/2)
- Recombinant C1-INH (Ruconest): IV (not available everywhere)
• Supportive care:
- Airway monitoring: Laryngeal edema is life-threatening; intubation may be needed
- IV fluids: For abdominal attacks (hydration)
- Pain relief: Analgesics for abdominal pain
- Avoid: Corticosteroids, antihistamines, epinephrine (ineffective in HAE)

✅ Model Answer:
• Long-term prophylaxis (for frequent attacks):
- Lanadelumab (Takhzyro): SC monoclonal antibody against kallikrein – first-line (300 mg every 2 weeks)
- Berotralstat (Orladeyo): Oral kallikrein inhibitor – daily (150 mg)
- SC C1-INH (Haegarda): Subcutaneous C1-INH – 60 IU/kg twice weekly
- IV C1-INH (Cinryze): 1000 U every 3-4 days
• Short-term prophylaxis (for procedures/triggers):
- C1-INH concentrate given before dental/surgical procedures
- Androgens (Danazol): Increases C1-INH levels – used in adolescents (virilization, HPA axis suppression)
- Antifibrinolytics (Tranexamic acid): Less effective, used in children

✅ Model Answer:
• Complications:
- Laryngeal edema: Most feared complication – can cause airway obstruction, asphyxiation, death (if not treated urgently)
- Abdominal complications: Severe pain → unnecessary abdominal surgery (laparotomy) if misdiagnosed
- Psychological impact: Anxiety, depression due to unpredictable attacks
- School/Work absenteeism: Frequent attacks affect daily life
- Swelling complications: Disfigurement, functional impairment (if hands/feet affected)
- Mortality: 25-40% lifetime risk of asphyxiation if untreated (reduced to <1% with modern therapy)
- Medication side effects: Androgen therapy → virilization, growth suppression, hepatotoxicity

✅ Model Answer:
• Prognosis:
- Excellent with proper diagnosis and treatment (mortality <1% with modern therapy)
- Lifelong disease – requires chronic management
- Onset: Usually begins in childhood/adolescence; attacks become more frequent during puberty
- Pregnancy: Attacks may worsen (estrogen effect)
• Long-term management:
- Regular follow-up with allergist/immunologist
- Patient education: Self-administration of acute therapy, recognition of laryngeal edema
- Medical ID: Alert bracelet/necklace
- Avoid triggers: ACE inhibitors, trauma, stress
- Genetic counseling for families (autosomal dominant inheritance)
- Normal life expectancy with appropriate treatment