Urticaria and Angioedema • Urticaria • Angioedema
Etiology of Urticarial Reactions:Allergic Triggers • Acute Urticaria • Drugs • Foods • Food additives • Viral infections • hepatitis A, B, C • Epstein-Barr virus • Insect bites and stings • Contactants and inhalants (includes animal dander and latex) • Chronic Urticaria • Physical factors • cold • heat • dermatographic • pressure • solar • Idiopathic
Role of Mast Cells in Chronic Urticaria:Lower Threshold for Histamine Release • Release threshold decreased by: • Cytokines & chemokines in the cutaneous microenvironment • Antigen exposure • Histamine-releasing factor • Autoantibody • Psychological factors Cutaneous mass cell • Release threshold increased by: • Corticosteroids • Antihistamines • Cromolyn (in vitro)
An Autoimmune Basis for Chronic Idiopathic Urticaria: Antibodies to IgE
Initial Workup of Urticaria • Patient history • Sinusitis • Arthritis • Thyroid disease • Cutaneous fungal infections • Urinary tract symptoms • Upper respiratory tract infection (particularly important in children) • Travel history (parasitic infection) • Sore throat • Epstein-Barr virus, infectious mononucleosis • Insect stings • Foods • Recent transfusions with blood products (hepatitis) • Recent initiation of drugs • Physical exam • Skin • Eyes • Ears • Throat • Lymph nodes • Feet • Lungs • Joints • Abdomen
Laboratory Assessment for Chronic Urticaria • Possible tests for selected patients • Stool examination for ova and parasites • Blood chemistry profile • Antinuclear antibody titer (ANA) • Hepatitis B and C • Skin tests for IgE-mediated reactions • Initial tests • CBC with differential • Erythrocyte sedimentation rate • Urinalysis • RAST for specific IgE • Complement studies: CH50 • Cryoproteins • Thyroid microsomal antibody • Antithyroglobulin • Thyroid stimulating hormone (TSH)
Histopathology • Polymorphous perivascular infiltrate • Neutrophils • Eosinophils • Mononuclear cells • Sparse perivascular lymphocytes
Urticaria/Angioedema • Definition • affects more than 20% of the population at some time in their lives • smooth, evanescent, edematous lesion (wheals) • heat, drugs, infections, and emotional stress are the most frequent triggers • Classification • acute if duration < 6 wks, otherwise chronic • 3 major groups: (a) immunologic urticaria; (b) non-immunologic urticaria; c: idiopathic urticaria
Allergic reactions: Angioedema • Usually localised (to head & neck) but may be more generalised (especially GI) +/- urticaria. Presents as swelling of the face, neck and oropharynx. Represents mast cell degranulation in skin deep to dermis vs. superficial dermis in urticaria. • Inherited - C1 esterase inhibitor deficiency due to mutation (autosomal dominant) of the C1-INH gene. • Acquired - usually autoantibodies to C1-INH in the context of autoimmune disease or lymphoproliferative disorders. Rarer reports of hypercatabolism of C1-INH in infection. • Drug-induced - commonest culprit ACE inhibitors.
ACE inhibitors & Angioedema • Mechanism probably related to massive elevation of BK but unclear why it can appear days to years after 1st dosing. • Incidence probably <0.1% - Afro-Caribbean and renal/cardiac transplant patients may be at increased risk. • Treatment is usually with standard therapy for an anaphylactic reaction +/- inhaled Epi but not mast cell dependent! If airway threatened, intubation or tracheostomy needed. • Under recognised especially in milder forms. ACE inhibitors should be stopped and an AT2 receptor antagonist substituted if necessary (e.g. Losartan) BUT isolated reports have appeared of angioedema with these agents! • New combined ACE/NEP inhibitors suffer same problem.
Common Causes of Acute Urticaria • Idiopathic • Immune-mediated (IgE) • foods (shellfish, nuts) • drugs • Noimmune-mediated • opiates • Nonspecific • viral infections (influenza) • bacterial infections (occult abscess, mycoplasma)
Urticaria Associated With Other Conditions • Collagen vascular disease (eg, systemic lupus erythematosus) • Complement deficiency, viral infections (including hepatitis B and C), serum sickness, and allergic drug eruptions • Chronic tinea pedis • Pruritic urticarial papules and plaques of pregnancy (PUPPP) • Schnitzler’s syndrome
Therapy for Urticaria • Abbreviated search for triggers • treat the treatable causes • Anti-histamines • Short-acting (Benadryl, Atarax) • Long-acting (Claritin, Reactine) • Corticosteroids • start around 1 mg/kg/day (single or divided doses)
Treatment of Urticaria: Pharmacologic Options • Antihistamines, others • First-generation H1 • Second-generation H1 • Antihistamine/decongestant combinations • Tricyclic antidepressants (eg, doxepin) • Combined H1 and H2 agents • Beta-adrenergic agonists • Epinephrine for acute urticaria (rapid but short-lived response) • Terbutaline • Corticosteroids • Severe acute urticaria • avoid long-term use • use alternate-day regimen when possible • Avoid in chronic urticaria (lowest dose plus antihistamines might be necessary) • Miscellaneous • PUVA • Hydroxychloroquine • Thyroxine
H1-Receptor Antagonists: Pros and Cons for Urticaria and Angioedema • First-generation antihistamines (diphenhydramine and hydroxyzine) • Advantages: Rapid onset of action, relatively inexpensive • Disadvantages: Sedating, anticholinergic • Second-generation antihistamines (astemizole, cetirizine, fexofenadine, loratadine) • Advantages: No sedation (except cetirizine); no adverse anticholinergic effects; bid and qd dosing • Disadvantages: Prolongation of QT interval; ventricular tachycardia (astemizole only) in a patient subgroup
Four-week Treatment Period:Fexofenadine HCl Mean Pruritus Scores/Mean Number of Wheals/Mean Total Symptom Scores