Dermatology MCQ - Inflammatory Dermatoses - Recurrent angio-oedema without weals

A 45-year-old man presents with a 2-year history of recurrent, self-limiting episodes of non-pitting swelling of the lips, face, and occasionally the hands. Each episode lasts for 48-72 hours and is not associated with pruritus or urticarial wheals. He reports no history of atopy. His current medication list includes lisinopril for hypertension, started approximately 3 years ago. The most critical initial investigation is:

A. Serum tryptase level during an acute attack
B. C4 level and C1 esterase inhibitor (C1-INH) level/function
C. ANA and dsDNA to rule out lupus
D. Thyroid function tests and thyroid autoantibodies
E. Allergy skin prick testing to common aeroallergens

Correct Answer: B. C4 level and C1 esterase inhibitor (C1-INH) level/function

Answer & Explanation

Explanation:

The presentation of recurrent angioedema without urticaria, especially when episodes are prolonged (>24 hours) and involve the face, should immediately raise suspicion for C1 esterase inhibitor deficiency (C1-INH). This can be hereditary (HAE) or acquired (AAE). Key clues in this case are:

• Absence of Urticaria: Urticaria is not a feature of C1-INH deficiency.

• Prolonged Duration: Swelling in HAE/AAE typically lasts 2-5 days, unlike the shorter duration of histaminergic angioedema.

• Common Precipitating Triggers: Minor trauma, stress, or infections can provoke attacks.

• Critical Medication History: The patient is on an ACE inhibitor (lisinopril). ACE inhibitors are a leading cause of drug-induced angioedema, which is also bradykinin-mediated and can present identically to HAE. Therefore, the two most critical and life-threatening diagnoses to rule out are ACE-inhibitor induced angioedema and hereditary angioedema (HAE).

Measuring C4 and C1-INH is the cornerstone of the initial laboratory workup. A low C4 is a sensitive screening test, even between attacks. Confirmation involves measuring C1-INH protein level and, crucially, its functional activity.

The other options are incorrect as first-line investigations:

• A. Serum tryptase: This is a marker of mast cell degranulation and is elevated in anaphylaxis and systemic mastocytosis. It is not elevated in bradykinin-mediated angioedema (C1-INH deficiency or ACE-inhibitor induced).

• C. ANA and dsDNA: While SLE can be associated with angioedema, it is rarely the sole presenting feature and is usually accompanied by other systemic symptoms and urticarial vasculitis.

• D. Thyroid function tests: Thyroid autoimmunity is linked with chronic spontaneous urticaria and angioedema, but not typically with isolated, recurrent angioedema without wheals.

• E. Allergy skin prick testing: This is for identifying IgE-mediated triggers (e.g., to foods, pollen), which would typically cause acute urticaria and angioedema together, not isolated, prolonged angioedema.

Key Associations for Recurrent Angioedema Without Weals

• Pathophysiology: This condition is divided into two main mechanistic pathways:

  1. Bradykinin-Mediated: This is the mechanism for C1-INH deficiency (HAE Types I & II, AAE) and ACE-inhibitor angioedema. Bradykinin causes profound vasodilation and vascular leakage. This type does not respond to antihistamines, corticosteroids, or epinephrine.

  2. Idiopathic/Histaminergic: Some patients have isolated angioedema with the same mechanism as urticaria (mast cell mediators). This type typically responds to high-dose antihistamines.

• Differential Diagnosis: The key is to distinguish bradykinin-mediated from histaminergic causes. The main differentials are: Hereditary Angioedema (HAE), Acquired Angioedema (AAE), ACE-inhibitor induced angioedema, and idiopathic non-histaminergic angioedema.

• Prognosis: HAE is a lifelong condition with a risk of fatal laryngeal edema. ACE-inhibitor angioedema resolves upon discontinuation of the drug, but this can take days to weeks.

• Management:

  • First Step: IMMEDIATELY DISCONTINUE THE ACE INHIBITOR. This is both diagnostic and therapeutic.

  • For Acute HAE Attacks: Specific treatments include C1-INH concentrate (plasma-derived or recombinant), the bradykinin B2 receptor antagonist icatibant, and the kallikrein inhibitor ecallantide.

  • Prophylaxis for HAE: Attenuated androgens (danazol), tranexamic acid, and prophylactic C1-INH are used.

  • For Idiopathic Histaminergic Angioedema: High-dose second-generation H1-antihistamines are the mainstay, similar to CSU management.