Study guide
15.2 Urticaria & Angioedema
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
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2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
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13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
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13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
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16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
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18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
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19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
15.2 Urticaria & Angioedema
Key Takeaways Explain This Topic AI
Hereditary angioedema, drug-induced urticaria and angioedema, other causes and contrast-related allergy are the enumerated topics.
Bradykinin-mediated angioedema lacks urticaria and pruritus and does not respond to epinephrine, antihistamines or corticosteroids.
Angiotensin-converting enzyme inhibitor angioedema may begin months to years after starting the drug and requires permanent discontinuation of the class.
Hereditary angioedema shows low C4 with low C1 inhibitor level or function, and is treated with bradykinin-targeted therapies.
Acquired C1 inhibitor deficiency additionally shows a low C1q level and is associated with lymphoproliferative disease.
Last updated: August 2026
1. Urticaria & Angioedema
Cutaneous wheals (urticaria) and deep tissue swelling (angioedema) are common clinical entities with distinct pathophysiologic pathways (histaminergic mast-cell mediated versus bradykinin-mediated) that dictate completely different therapeutic approaches.
Urticaria (Hives)
Pathophysiology: Dermal microvascular hyperpermeability driven by mast cell and basophil degranulation with local release of histamine, prostaglandin D2, and leukotrienes.
Acute Urticaria (< 6 Weeks): Usually self-limiting; commonly triggered by viral infections (upper respiratory or gastrointestinal), food/drug allergies, or insect stings.
Chronic Spontaneous Urticaria (CSU, >= 6 Weeks): Recurrent wheals with or without angioedema lasting >= 6 weeks. Etiology is autoimmune in > 40% to 50% of cases , driven by functional IgG autoantibodies directed against either IgE or the high-affinity IgE receptor alpha subunit ( FcεRIα ) on cutaneous mast cells.
Clinical Characteristics of True Urticaria:
Intensely pruritic, erythematous, raised, edematous wheals with central pallor.
Crucial Diagnostic Rule: Individual lesions are evanescent (fleeting) and resolve completely within < 24 hours without leaving bruising, scarring, or residual pigmentation , while new lesions appear elsewhere.
Urticarial Vasculitis (Critical Mimicker):
Suspect when individual lesions persist for > 24 to 48 hours in the exact same location , are described as painful, burning, or tender rather than pruritic, and leave residual purpura, ecchymosis, or hyperpigmentation upon fading.
Workup: Full-thickness punch biopsy of the skin lesion showing leukocytoclastic vasculitis (neutrophilic infiltration with nuclear debris/leukocytoclasia, fibrinoid necrosis of postcapillary venule walls, and RBC extravasation). Check serum complement levels (C3, C4, CH50) and anti-C1q antibodies; rule out systemic lupus erythematosus (SLE) and hepatitis C.
Stepwise Management Strategy for Chronic Spontaneous Urticaria (CSU):
Step 1: Standard-dose Second-Generation H1 Antihistamines (e.g., Cetirizine 10 mg, Loratadine 10 mg, Fexofenadine 180 mg, Levocetirizine 5 mg daily).
Step 2: Up-titrate the second-generation H1 antihistamine dose up to 4 times (4x) the standard licensed dose (e.g., Cetirizine 20 mg PO BID or 40 mg PO daily).
Step 3: Add Omalizumab (anti-IgE humanized monoclonal antibody, 300 mg subcutaneous injection every 4 weeks).
Step 4: Add Cyclosporine A (calcineurin inhibitor, 3–5 mg/kg/day divided BID; monitor blood pressure and renal function).
Board Pearl: Avoid long-term maintenance systemic corticosteroids for CSU due to significant cumulative toxicities and rebound flares upon steroid withdrawal.
Loading diagram... Diagnostic & Therapeutic Algorithm for Angioedema
Angioedema: Histaminergic vs. Bradykinin-Mediated
Angioedema represents localized, non-pitting edema of the deep dermis, subcutaneous tissue, or submucosal layers. Correctly distinguishing between Mast Cell / Histaminergic and Bradykinin-Mediated angioedema is a critical lifesaving skill.
Feature Histaminergic (Mast Cell) Angioedema Bradykinin-Mediated Angioedema
Pathogenic Mediator Histamine, Leukotrienes, Prostaglandins from mast cells Bradykinin (excess production or impaired degradation)
Associated Cutaneous Signs Urticaria (hives), pruritus , erythema, flushing ABSENCE of urticaria (no hives) ; no pruritus
Gastrointestinal Symptoms Rare Frequent : Severe episodic colicky abdominal pain, nausea, vomiting, transient ascites, and bowel wall edema on CT scan
Speed of Onset Rapid (peaks in minutes to 1–2 hours) Slower, progressive swelling (peaks over 12–36 hours, resolves over 48–72 hours)
Response to Epinephrine, Antihistamines, & Steroids EXCELLENT RESPONSE (standard first-line therapy) ZERO RESPONSE (completely ineffective)
Clinical Subtypes Allergic anaphylaxis, acute viral urticaria, physical triggers ACE Inhibitor-Induced , Hereditary Angioedema (HAE) , Acquired C1-INH Deficiency
- Bradykinin-Mediated Angioedema Subtypes
- 1. ACE Inhibitor-Induced Angioedema
Mechanism: Angiotensin-Converting Enzyme (ACE / kininase II) is the primary enzyme responsible for the physiological degradation of bradykinin. Pharmacologic ACE inhibition leads to impaired bradykinin breakdown and localized accumulation, activating bradykinin B2 receptors to cause potent vasodilation and increased vascular permeability.
Epidemiology: Occurs in 0.1% to 0.7% of patients taking ACE inhibitors (up to 4- to 5-fold higher incidence in Black patients due to genetic polymorphisms in alternative bradykinin degradation enzymes like aminopeptidase P and neutral endopeptidase).
Timing: Can occur within hours/days of initiating an ACE inhibitor or after years of completely uneventful therapy .
Clinical Presentation: Asymmetric, painless, non-pruritic swelling of the tongue, lips, uvula, soft palate, and larynx. Can cause rapid life-threatening airway obstruction.
Management:
Permanently discontinue the ACE inhibitor . Mark ACE inhibitors as a severe drug allergy in the medical record.
Airway Management: Early fiberoptic nasopharyngoscopy and elective endotracheal intubation (or emergent cricothyroidotomy/tracheostomy) if laryngeal edema or stridor is present.
Antihistamines, corticosteroids, and epinephrine are ineffective but frequently given while securing the airway.
Angiotensin Receptor Blocker (ARB) Use: ARBs do not inhibit kininase II and have very low cross-reactivity (< 2% to 5%); however, in patients with prior life-threatening ACEi angioedema, ARBs should be used with extreme caution or alternative antihypertensives (e.g., CCBs) should be chosen.
2. Hereditary Angioedema (HAE)
Genetics: Autosomal dominant disorder caused by mutations in the SERPING1 gene on chromosome 11q, which encodes C1-esterase inhibitor (C1-INH). C1-INH is the primary physiological inhibitor of plasma kallikrein and activated factor XII (Hageman factor); deficiency leads to unchecked activation of the contact/kallikrein-kinin cascade and massive bradykinin generation.
Classification & Diagnostic Complement Profile:
HAE / AAE Subtype Prevalence C1-INH Protein (Antigen) Level C1-INH Functional Activity Serum C4 Level Serum C1q Level
- HAE Type 1 ~85% of HAE Markedly Low (< 50%) Markedly Low (< 50%) Persistently Low (< 50%) Normal
- HAE Type 2 ~15% of HAE Normal or Elevated Markedly Low (< 50%) Persistently Low (< 50%) Normal
Acquired C1-INH Deficiency (AAE) Rare (onset > 50y) Low or Normal Markedly Low (< 50%) Markedly Low (< 50%) UNIQUELY LOW (< 30%)
Screening Test of Choice: Serum C4 level is the premier screening test (persistently low in > 95% of patients with Type 1 and Type 2 HAE, even during asymptomatic baseline periods; drops to near undetectable during acute attacks). If C4 is low, order C1-INH antigenic level and C1-INH functional assay.
Acquired C1-INH Deficiency (AAE): Late-onset angioedema in adults aged > 50 years associated with B-cell lymphoproliferative disorders (e.g., Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, Monoclonal Gammopathy of Undetermined Significance [MGUS]) or autoantibodies directed against C1-INH. Characterized by markedly low serum C1q levels (C1q is consumed by neoplastic/autoimmune immune complexes; C1q is completely normal in hereditary forms).
Targeted Treatment of Acute HAE Attacks (On-Demand):
C1-Esterase Inhibitor Concentrates: Plasma-derived human C1-INH ( Berinert 20 U/kg IV) or recombinant human C1-INH ( Ruconest 50 U/kg IV). Restores functional C1-INH to halt bradykinin generation.
Bradykinin B2-Receptor Antagonist: Icatibant (30 mg subcutaneous injection in the abdominal wall; can be self-administered by the patient).
Plasma Kallikrein Inhibitor: Ecallantide (30 mg subcutaneous injection in 3 divided doses; risk of hypersensitivity, administer under healthcare supervision).
Long-Term HAE Prophylaxis:
Lanadelumab: Fully human monoclonal antibody against active plasma kallikrein (300 mg SC every 2 to 4 weeks; first-line prophylactic agent).
Berotralstat: Oral, once-daily plasma kallikrein inhibitor (150 mg PO daily).
Subcutaneous C1-INH Concentrate: Purified plasma-derived C1-INH ( Haegarda 60 IU/kg SC twice weekly).