What is the likely cause and appropriate management for a 16‑year‑old female with daily, short‑lasting non‑pitting swelling of the hands and legs that resolves within hours and was provoked by minor trauma (venipuncture) with localized itching and swelling?

Hereditary Angioedema (HAE) Type I or II

This 16-year-old female most likely has hereditary angioedema (HAE), a potentially life-threatening condition characterized by recurrent, non-pruritic, non-pitting swelling episodes lasting hours to days that can be triggered by minor trauma such as venipuncture. 1

Key Diagnostic Features Present

Your patient demonstrates the classic presentation of HAE:

• Age and onset pattern: Symptoms typically begin in childhood, with 50% of HAE patients experiencing first swelling before age 10, and symptoms frequently worsen around puberty 1. At 16 years old, she fits this pattern perfectly.

• Swelling characteristics: HAE attacks are characterized by non-pruritic, non-pitting angioedema of the extremities (hands and legs in this case) 1, 2. The swelling lasts "a couple of hours" in your patient, which aligns with HAE attacks that typically progress over 24 hours and resolve over 48-72 hours 1.

• Trauma-induced provocation: The venipuncture triggering localized swelling with itching is highly characteristic—minor trauma is a well-recognized precipitant of HAE attacks 1, 3.

• Daily frequency: While attack frequency varies greatly (from every few days to years apart), daily attacks indicate severe, poorly controlled disease 4.

Critical Distinction from Urticaria

The absence of wheals (hives) is crucial. HAE presents with angioedema unaccompanied by urticaria 2. The localized itching at the venipuncture site may represent early swelling discomfort rather than true allergic pruritus. Ordinary urticaria produces wheals lasting 2-24 hours 5, which is not described here.

Immediate Diagnostic Workup Required

Order these tests urgently to confirm HAE and determine the subtype:

1. Serum C4 level (screening test): Will be low in >95% of HAE cases during and between attacks 1, 5
2. C1-inhibitor antigenic level (quantitative)
3. C1-inhibitor functional level (activity assay)

1, 5

Interpretation:

• Type I HAE (85% of cases): Low C1-inhibitor antigen AND low functional activity 1
• Type II HAE (15% of cases): Normal or elevated C1-inhibitor antigen BUT low functional activity 1

Pathophysiology Explaining Her Symptoms

HAE results from deficient C1-inhibitor activity, leading to uncontrolled bradykinin generation—the primary mediator causing vascular permeability and tissue swelling 1. The venipuncture activated the contact system (Hageman factor pathway), generating excess bradykinin locally 1.

Immediate Management Actions

For Current Episode

• Do NOT use antihistamines, corticosteroids, or epinephrine—they are ineffective in HAE because the mechanism is bradykinin-mediated, not histamine or IgE-mediated 1, 2
• Provide supportive care and monitor for progression
• If available, treat acute attack with C1-inhibitor concentrate (plasma-derived), icatibant (bradykinin receptor antagonist), or ecallantide (kallikrein inhibitor) 1, 6

Airway Emergency Protocol

This is critical: HAE can cause fatal laryngeal edema 1, 7. If she develops:

• Throat tightness
• Hoarseness
• Difficulty swallowing or breathing
• Tongue or facial swelling

Immediately:

• Call emergency services
• Administer C1-inhibitor concentrate if available (20 U/kg) 1
• Prepare for emergency airway management—intubation may be required 1
• Do NOT rely on epinephrine—it does not work for HAE 1

Family History Assessment

Ask specifically about:

• Family members with recurrent unexplained swelling
• Deaths from "asphyxiation" or "throat swelling"
• Unexplained abdominal pain episodes requiring hospitalization

HAE follows autosomal dominant inheritance—each child of an affected parent has 50% risk 1. However, 25% of cases represent de novo mutations with no family history 1, so negative family history does not exclude HAE.

Long-Term Management After Diagnosis

Once HAE is confirmed:

1. Long-term prophylaxis to prevent attacks: Attenuated androgens (danazol, stanozolol) or plasma-derived C1-inhibitor concentrate 1, 7, 3

2. Short-term prophylaxis before procedures (dental work, surgery): C1-inhibitor concentrate or tranexamic acid 1, 3

3. On-demand treatment for acute attacks: C1-inhibitor concentrate, icatibant, or ecallantide 1, 6

4. Patient education: Avoid estrogen-containing contraceptives (worsen attacks), recognize early attack symptoms, carry medical alert identification 7, 3

Common Pitfalls to Avoid

• Do not dismiss this as "allergic reaction"—the daily pattern, trauma provocation, and lack of wheals argue strongly against IgE-mediated allergy 1, 2
• Do not delay testing—mortality from undiagnosed HAE historically reached 30% due to airway obstruction 3
• Do not prescribe antihistamines or steroids—they provide false reassurance while the patient remains at risk for fatal laryngeal edema 1, 2
• Do not assume negative family history excludes HAE—25% are de novo mutations 1

Referral

Refer urgently to an allergist/immunologist experienced in HAE management for confirmation of diagnosis, treatment planning, and family screening 1.