Hives (Urticaria) and Angioedema
Patients with urticaria experience itchy welts of varying size on any part of their skin. This condition affects 15-20% of general population and is accompanied by angioedema (body swelling) up to half of the patients. Angioedema is not itchy but gives burning sensation deep under the skin and involves the tissues where blood supply is ample such as lips, tongue, eye socket, hands, feet, and scrotum. Angioedema occurring alone without hives deserves special consideration.
Urticaria may be of a short duration resolving after only a few days spontaneously or in response to the elimination of the causative agents or to the administration of anti-histamines. However, the symptoms may last much longer sometimes for months or even years. When symptoms persist longer than six weeks, the condition is defined as chronic (versus acute).
Most common causes of an acute disease are drug or food hyper-sensitivities and viral diseases (see the list below). In chronic disease, the causes cannot be found in the majority of the cases. In less than 10% of the cases, one may find causes such as physical stress (pressure, vibration, cold or warmth), hepatitis, or vasculitis (disease of small blood vessels) as in systemic lupus. In vasculitis, the hives tend to stay in one place, often involve hand and feet, and do not blanch when pressed.
Current thinking is that majority of these “idiopathic” (cause unknown) hives are due to an autoimmune phenomenon. In other words, these patients develop antibodies which attack their own skin! This may be one reason why in 20-30% of patients, thyroid autoantibodies are found and even thyroid function may be abnormal. This can be tested by doing a skin test using patient’s own serum (Ask the lab technician to draw 0.5 ccs of extra serum and put in a test tube and bring it to Dr. Song’s office).
Although more than 2/3 of patients recover in one year, chronic urticaria is one of the most annoying and frustrating diseases for patients and doctors alike. So patients need patience and tincture of time!
Major causes of urticaria and diagnoses
- Drug reaction:
- Food or food additives:
- Inhalation, ingestion, or contact with antigen
- Infections; virus, bacteria, mycoplasma, parasite; LAB test
- Insect bites
- Collagen vasculitis: Lupus, serum sickness, erythema multiforme, etc: LAB tesy
- Physical urticarias: cold, cholinergic, dermographism, pressure, vibratory, solar, aquatic
- Malignancy; very rarely: LAB test
- Urticaria pigmentosa: systemic mastocytosis: LAB, SKIN BIOPSY
- Chronic idiopathic: more than half are auto-immune: Skin Test wit patient's serum
Major causes of angiodema
- Hereditary angioedema (C1 inhibitor deficiency): LAB TEST
- Acquired angioedema (associated malignancy): LAB TEST
- Drug-induced (ACE inhibitors)
- Antihistamines are the backbone of the treatment
- Long-acting; Allegra, Claritin, Clarinex, Zyrtec (combination of the these can be used in higher doses)
- Short-acting: Atarax is a favored one. The dose can be gradually increased up to 50 mg, 4 x/day, to control the symptoms. Initially, patients may feel drowsy, but most get used to them.
- For nocturnal itching, Doxepen can be used.
- Steroid: When antihistamines alone do not control symptoms, oral steroid may be employed. Minimal effective dose needs to be used, since long-term use of steroid is associated with many side effects such weight gain, cataract, bone loss, GI bleeding, depression, adrenal suppression, etc. Once the control of symptoms is obtained, prednisone needs to be tapered gradually. However, if this is not possible, other drugs need to be added
- Dapsone: This anti-leprosy drug can be a useful adjunctive drug.
- Immune-suppressing drugs: If steroid does not reduce the symptoms or cannot be tapered, these agents need to be used. Most of these drugs are used as anti-cancer drugs and are associated with side effects. Literature reports the successful use of Cytotoxan, Cyclosporin, Methotrexate, and Cellcept. Of this Cellcept probably has the least side effects.
- IVIG (intravenous immunoglobulin G): There are reports of successful use of this product. Although the use of drug is tightly guarded acquiring review process by the insurance companies because of its limited availability and expense, it is associated with very little side effects. The product may be given by a home health nurse at patient’s home (Crescent Home Health Care is a leading agent in our area).
- Omalizumab (Xolair): Improves the symptoms and signs in patients with chronic idiopathic urticaria who failed to antihistamine treatment (New England J. of medicine 2/24/2013).
CBC with ESR
Eosinophilia: allergy and parasites.
Urobilinogen in hepatitis, blood and/or protein in some vasculitis
in viral hepatitis
(TFT, thyroid antibodies)
TFT or ¯ in autoimmune thyroid diseases, anti-thyroglobulin and /or anti-microsomal antibodies in thyroiditis and some euthyroid patients
Temporal relationship to drugs, foods, and contacts
Adverse reactions to, e.g, penicillin, fish, latex, etc
History of physical exposure
Physical urticaria (Cold, heat, pressure, vibratory, aquagenic, solar, etc)
Induced by exercise
Cholinergic, exercise-induced urticaria, and anaphylaxis
History of trauma
Viral/bacterial/mycoplasma infections, vasculitis including systemic lupus erythematosus and serum sickness, Henoch-Schonlein purpura
Hereditary angioedema, amyloidosis with deafness and urticaria, C3b inactivator deficiency
By Physical Exam
Size of urticaria
Cholinergic, cold-cholinergic, aquagenic, insect bites, scabies
Physical urticaria (cold, dermatographism, solar, pressure, vibratory, aquagenic)
Hereditary angioedema, acquired angioedema associated with malignancy, drug or contact-induced angioedema
Involves palms and soles
Specific antigen sensitivity
Temporal relationship to ingestants or
IgE mediated in some.
Temporal relationship to application of physical stimuli
Demonstrable lesions from application of physical stimuli
Demonstrated after skin is stroked.
Demonstrated after sun light.
Demonsrated after water is applied.
Exercise and heat
Application of heat
Methacholine challenge is positive in 1/3
Wheezing, angioedma, shock
Exercise challenge test
Confined to the exposed parts of the body
Ice cube test
History of exposure to contactants
Confined to the the exposed parts of the body
Hx not helpful
IgG ab to IgE or IgE R
History of systemic illness
¯CH50, ¯C3, ¯C4
Angioedma without urticaria
¯CH50, ¯C3, ¯C4
Hx of transfusion
May evolve into erythema multiforme
Direct MC degranulating
In the area where physical force is applied such as belted area.
Arachdonic acid metabolism altering
Hx of drug ingestion
When the initial history/exam(1) yields a specific diagnosis, such as cholingeric urticaria or food allergy, manage accordingly. When it yields no result, do screening lab tests(2) and start symptomatic treatment. If the screening lab tests indicate a specific diagnosis such as thyroiditis or hepatitis, manage accordingly. If no etiology is found, repeat the evaluation in 6 weeks (3). If still no diagnosis is obtained, manage it as idiopathic urticaria.