URTICARIA/ HIVES/ ANGIOEDEMA
Urticaria are raised, discrete erythematous dermal lesions which may be an isolated symptom or may occur with other symptoms of anaphylaxis. Allergen contact results in mast cell activation with degranulation of histamine, prostaglandins, leukotrienes, and cytokines. These mediators cause vasodilation, increased vascular permeability, and the local recruitment of inflammatory cells (neutrophils and eosinophils) and T cells. Urticaria usually last several hours and then resolve but may recur at other locations at a later time. It is always prudent to try to determine the inciting allergen or antigen and counsel patients to avoid further contact; however, in many cases, the inciting substance can not be identified. When the subcutaneous or submucosal tissues are involved, angioedema is the resulting clinical manifestation. Angioedema may affect the face, lips, tongue, extremities, respiratory tract, or gastrointestinal tract. When symptoms last less than 6 weeks they are termed acute urticaria. When symptoms are recurrent for greater than 6 weeks, they are termed chronic urticaria.
The differential diagnosis of lesions which may mimic urticaria includes bullous pemphigoid, vasculitides, systemic lupus erythematosus, dermatitis herpetiformis, erythema multiforme, urticaria pigmentosa, angioedema (hereditary, acquired, chronic idiopathic, and ACEI induced) and morbiliform drug eruptions. Causes of secondary urticaria include viral infections particularly hepatitis, bacterial infections, fungal infections, parasitic infections, connective tissue disorders (SLE, Sjogren's syndrome, rheumatoid arthritis), malignancies, physical stimuli, medication reaction, and food additives. Specific urticarial syndromes include autoimmune mast cell disease, urticarial vasculitis, physical urticaria, and exercise-induced urticaria.
Autoimmune mast cell disease results when patients possess an IgG autoantibody that causes histamine release form peripheral blood basophils and tissue mast cells. Urticarial vasculitis is diagnosed by biopsy in patients with chronic outbreaks of urticaria. The lesions of urticarial vasculitis are often painful, have central clearing with a dusky discoloration, last greater than 24 hours, and leave a residual pigmentation upon clearing. Physical urticarias can be brought on by contact with environmental factors (cold, heat, water, or light) while exercise-induced urticaria becomes symptomatic minutes after initiation of exercise.
Hereditary angioedema and acquired angioedema are recurrent forms of angioedema that results from a decrease in the function or level of C1-inhibitor and thus result in activation of the first component of the complement system. Clinically, these disorders are very similar. Symptoms depend on which organ system is involved. When the skin is the major site of involvement, nonpitting edema without associated pruritis can affect the face, extremities, and genitalia. Urticarial lesions are not associated with these disorders, and their presence eliminates these diagnostic possibilities.
Acute urticaria resolves spontaneously before 6 weeks. Chronic urticaria however may need further evaluation with a CBC, ESR, TSH, complement values, and serum chemistry. Punch biopsy should be consider in refractory cases or cases where urticarial vasculitis is suspected. Allergen testing may also be useful to identify the underlying cause. It is unfortunate that in the majority of cases of chronic urticaria the inciting allergen, antigen, or etiology is never discovered despite an evaluation.
Therapy for urticaria is with H1 and H2 receptor blocking agents and avoidance of any known inciting allergens or antigens. Second generation H1 receptor blockers have the advantage of a lower side effect profile; however, excessive doses 3-4 times the normal dose may be required for the treatment of chronic urticaria. Tricyclic antidepressants (doxepin HCl or amitriptyline HCl) or leukotriene receptor antagonists may prove effective in cases of refractory chronic urticaria. Since approximately 15% of cutaneous histamine receptors are H2 receptors, the addition of an H2 receptor antagonist augments the action of H1 blocker therapy. Doxepin offers both H1 and H2 receptor antagonism and is often an effective therapeutic choice; however, sedation is a limiting side effect. When the above mentioned therapies fail, a brief course of corticosteroid therapy may be required to control the disease. When symptoms are severe (anaphylaxis) at presentation, airway management should be secured, fluid boluses may be required for hypotension, and therapy with epinephrine or steroids may be required. If patients with autoimmune mast cell disease are refractory to the above therapy, treatment with plasmapheresis, cyclosporine or intravenous immune globulin may be required. Therapy for urticarial vasculitis may require steroids, however, other options include indomethacin, hydroxychloroquine sulfate, colchicine (0.6 mg BID), or dapsone (50-150 mg/day). Refractory cases of urticarial vasculitis may require azathioprine or cyclophosphamide to help lessen the amount of steroid needed to control symptoms.