Evaluation
First and foremost, in establishing a diagnosis the primary care clinician knows the importance of a complete history and physical examination of the patient. The patient with urticaria or angioedema typically is assigned the correct diagnostic classification following the history and physical examination. This information establishes whether the disease process is acute or chronic. Hives or swelling persisting beyond 6 wk will be assigned to the chronic designation. Questioning will reveal whether those cases with a duration of more than 6 wk represent recurrent episodes of acute urticaria following inadvertent ingestion or exposure to allergens. A history will reveal whether a child has had an acute viral prodrome and/or is taking antibiotics for a presumed bacterial infection. Furthermore, a careful history will reveal medications or over-the-counter preparations that can result in urticaria. Review of the patient’s dietary history is paramount in determining whether foods in the diet or food additives are the culprit. Finally, a discussion with the patient regarding activities and any relationship of hives or swelling with exposure to physical stimuli or exercise might reveal physical urticaria as the diagnosis. Mild dermatographism or pressure-induced urticaria can be present in patients with chronic urticaria; other physically induced hives are always separate. If the urticariahas persisted beyond 6 wk and does not appear to be recurrent episodes of acute urticaria, the primary care clinician must pursue other issues in the patient’s history. The patient needs to be questioned about traveling to areas that could have endemic parasitic disease (eosinophilia is a clue to this). The review of systems also must pursue complaints that reflect the possibility of underlying systemic disease. Symptoms of importance include fevers, night sweats, unintentional weight loss, changes in vision, mouth sores, swollen lymph nodes, nausea, vomiting, abdominal pain, genitourinary discomfort, or joint discomfort. A careful and complete physical examination should be performed. Specific attention should be focused on mucosal lesions, adenopathy, thyromegaly, abnormal chest findings on auscultation, hepatosplenomegaly, synovitis, and joint effusions.
Commonly, an episode of acute urticaria in a child or an adult is secondary to the ingestion of a specific food or medication. The history will reveal this connection, and treatment will be empiric for symptom relief. The evaluation should be expanded to confirm or refute any food and medication allergy. Skin tests often confirm the suspicion that a dietary component is responsible for the allergic reaction. In equivocal cases, the gold standard for establishing a food allergy is a double-blind, placebo-controlled food challenge. However, this should be recommended and performed only by an individual who is trained in this procedure. Life-threatening allergic reactions can be induced on challenging individuals with foods or medications to which they have an immunoglobulin E-mediated process. Penicillin and other p -lactams frequently are responsible for acute immunoglobulin E-mediated eruptions. This diagnosis can be confirmed through skin testing to investigate immunoglobulin E-mediated processes to both the major and minor determinants of penicillin. Skin testing to cephalosporins can be done as well. Skin testing is especially helpful for the patient in whom it is unclear whether the infectious process or the antibiotic is responsible for the urticarial eruption. Again, this procedure does carry significant risk for side effects and should be performed only in a controlled setting by individuals who are trained and experienced in the diagnosis and treatment of allergic reactions. Further laboratory workup might not be indicated in the patient in whom a diagnosis of urticaria has been established following the history and physical examination.
Evaluation and Workup of Urticaria and Angioedema
Acute Urticaria Angioedema
• History and physical
• Consider skin testing or double-blind, placebo-controlled food challenge for possible food allergy.
• Consider penicillin skin testing with major and minor determinants for possible p-lactam allergy.
• Skin biopsy not recommended (will show only dermal edema) Chronic Urticaria!Angioedema
• History and physical examination
• Laboratory studies to be considered (CBC, UA, ESR, thyroid function tests, ANA, serum chemistries, antiperoxidase antibody, antithyroglobulin anti body)
• Skin biopsy if lesion is atypical or if there is suspicion of underlying systemic disease
The evaluation of chronic urticaria and angioedema is fundamentally different from that of acute urticarial disease. Other coincident disease must be considered in the patient who discloses a history of more than 6 wk of urticaria and angioedema. Generally, the history and physical will have excluded the possibility of a clear relationship between a specific food or medication and the development of hives or swelling. The history should reveal whether the individual has hypertension or heart disease and is presently taking an angiotensin-converting enzyme inhibitor that might be resulting in chronic angioedema. Historical evidence of musculoskeletal disease and the possible need for nonsteroidal anti-inflammatory drugs might suggest a nonspecific mast cell degranulation following the alteration of arachidonic acid metabolism in mast cells. Travel to underdeveloped countries and gastrointestinal complaints might provide evidence of an underlying parasitic infection. Similarly, a history of blood transfusion, intravenous drug abuse, or jaundice might establish the possibility of viral hepatitis causing an urticarial eruption. Any atypical aspects to the gross appearance of the lesions described by the patient might indicate other systemic disease. Following a careful history and physical examination, laboratory studies might be helpful in the patient with protracted disease. Laboratory studies that can be considered include a complete blood count with differential, urine analysis, and determination of the erythrocyte sedimentation rate. Underlying hepatic or renal disease might be reflected in abnormalities found in serum chemistries. If petechiae or purpura are present, antinuclear antibody and cryo-globulin determinations might be helpful. Thyroid function tests, including serum thyroxine (T4) and thyroid-stimulating hormone, as well as antiperoxidase and antithyroglobulin antibody, should be performed. Approximately 25% of individuals with chronic idiopathic urticaria have abnormal thyroid laboratory results. Other autoimmune serological findings might be useful for the individual in whom there is suspicion of an underlying autoimmune disease. Finally, IgG anti-immunoglobulin E receptor antibodies have been described in approx 35-45% of patients with chronic idiopathic urticaria. This antibody crosslinks the immunoglobulin E receptor and activates complement, which together lead to mast cell degranulation. However, at this time anti-immunoglobulin E receptor antibodies are exclusively used in research efforts and are not clinically available.
Skin biopsy can be a helpful tool in patients with atypical skin lesions that have a questionable appearance and are suggestive of vasculitis. Histopathological study of an acute urticarial lesion reveals dermal edema with a minimal cellular infiltrate. Physically induced hives (except delayed-pressure urticaria) have no infiltrate at all. This results primarily from the release of histamine, which causes vasodilatation and increased vascular permeability. However, chronic urticaria does reveal a prominent perivascular mononuclear cell infiltrate (CD4+ lymphocytes and monocytes) with increased numbers of mast cells and variable numbers of neutrophils and eosinophils. Although this is similarly nonspecific as compared with the dermal edema seen with acute urticaria, the cellular infiltrate does reflect chronicity of the process and release of chemotactic substances in sufficient concentration and of sufficient duration to attract blood cells. The vessel wall is, however, intact. There is no necrosis of cells or deposition of immune complexes. Thus, it is clearly distinguishable from true vasculitis.
The most important reason for performing a skin biopsy is to eliminate the possibility of any coincident systemic disease that would have a different prognosis or require a different therapeutic approach. Invasion of the dermal blood vessels with neutrophils in combination with leukocytoclasis, nuclear debris, and deposition of either complement or immunoglobulins suggests vasculitis. This finding should prompt further investigation to differentiate the possibility of cutaneous vasculitis from a systemic disorder in which there is a cutaneous vasculitis component.
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