Nejm 2002;346:175; 1995;332:1767; 1994;331:1272 (drug induced)

Cause & Pathophys:

Idiopathic (80%)

Direct histamine release by opiates, NSAIDs, IVP dye (steroids protect), thiamine, curare, dextrans, some antibiotics

Immunologic:

• C activation by cryoglobulins (IgG or cold agglutinins produced by tumors, multiple myeloma, SLE, arteritis, etc), or by B₁C globulin damage (snake venom, DIC). Angioneurotic edema is C mediated but is not urticaria.
• Antibodies vs mast cells; or, in chronic urticaria, their IgE receptors (Nejm 1993;328:1599)
• Mast cells as "innocent bystanders," eg, SLE, serum sickness, viral (especially coxsackie) infections or post-H. simplex with antigens in all lesions (Ann IM 1984;101:48), leukemias and other malignancies, drugs (especially sulfas, seizure meds, allopurinol, NSAIDs), parasites, hepatitis B, perhaps mononucleosis plus ampicillin; nearly all recurrent erythema multiforme and most primary episodes are due to H. simplex, but a few of the latter are due to mycoplasma and drugs (E. Ringle 1990)
• Mast cell fixed antibody (IgE), eg, to fish, bee sting, penicillin
• Type IV (DHS) immune reaction leads to vasculitis

Physical/"neurogenic":

• Cold urticaria (test with ice cube), perhaps IgE attaches to a cold-dependent skin antigen and releases platelet-activating factor (Nejm 1985;313:405; 1985;305:1074)
• Local heat urticaria
• Systemic heat urticaria, cholinergic; seen when core body temperature is elevated, starts around hair follicles; seen in runners, tennis players, etc
• Light/solar
• Stress
• Dermatographia

Associated diseases: urticaria pigmentosa occasionally (Urticaria Pigmentosa, Mastocytosis) and anaphylaxis (Anaphylaxis)

25% of adult population has had chronic urticaria × wks-mos.

Sx:Urticaria (hives), mucosal angioedema with all but physical types; abdominal pain (gi histamine release)

Si:Target skin lesions of erythema multiforme, raised urticarial lesions et al.; bilateral symmetry always suggests drug-induced first

Except in vasculitis, immunologic, and physical types, most lesions last <24 h

Epidermal detachment of mucous membranes, locally in Stevens-Johnson syndrome w 5% mortality, or extensively in toxic epidermal necrolysis (Toxic Epidermal Necrolysis (Lyell's Syndrome)) w 30% mortality (Nejm 1995;333:1660) (r/o systemic diseases like SLE, dermatomyositis, scarlet fever [Scarlet Fever])

Lab: Path:Skin bx at site of recent urticaria to r/o vasculitis

Rx:

Avoid ACE inhibitors and NSAIDs;

ephedrine 2% spray for angioedema;

H₁ receptor antagonist antihistamines like certirizine (Zyrtec) 10 mg po qd, or loratidine (Claritine) qd (Allergic Rhinitis); also cyproheptadine (Periactin); doxepin (Sinequan) 10-25 mg po bid (Nejm 1985;313:405); hydroxyzine (Atarax, Vistaril)

H₂ blockers like cimetidine sometimes also helpful

Steroids
of vasculitis: steroids
of mast cell types: ketotifen 2 mg po bid, stabilizes mast cells (Ann IM 1986;104:507); acyclovir for at least recurrent erythema multiforme