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Harrison’s Manual of Medicine



Urticaria and Angioedema
Allergic Rhinitis
Systemic Mastocytosis

DEFINITION   These diseases result from IgE-dependent release of mediators from sensitized basophils and mast cells on contact with appropriate antigen (allergen). Associated disorders include anaphylaxis, allergic rhinitis, urticaria, asthma, and eczematous (atopic) dermatitis. Atopic allergy implies a familial tendency to the development of these disorders singly or in combination.
PATHOPHYSIOLOGY   IgE binds to surface of mast cells and basophils through a high-affinity receptor. Cross-linking of this IgE by antigen causes cellular activation with the subsequent release of preformed and newly synthesized mediators. These include histamine, prostaglandins, leukotrienes (including C4, D4, and E4, collectively known as slow-reacting substance of anaphylaxis—SRS-A), acid hydrolases, neutral proteases, proteoglycans, and cytokines (Fig. 310-2, p. 1914, HPIM-15). The mediators have been implicated in many pathophysiologic events associated with immediate type hypersensitivity, such as vasodilatation, increased vasopermeability, smooth-muscle contraction, and chemotactic attraction of neutrophils and other inflammatory cells. The clinical manifestations of each allergic reaction depend largely on the anatomic site(s) and time course of mediator release.
DEFINITION   May occur together or separately. Urticaria involves superficial dermis and presents as circumscribed wheals with raised serpiginous borders and blanched centers; wheals may coalesce. Angioedema involves deeper layers of skin and may include subcutaneous tissue. These disorders may be classified as (1) IgE-dependent, including atopic, secondary to specific allergens, and physical stimuli, especially cold; (2) complement-mediated (including hereditary angioedema and hives related to serum sickness or vasculitis); (3) nonimmunologic due to direct mast cell–releasing agents or drugs that influence mediator release; and (4) idiopathic.
PATHOPHYSIOLOGY   Characterized by massive edema formation in the dermis (and subcutaneous tissue in angioedema). Presumably the edema is due to increased vasopermeability caused by mediator release from mast cells or other cell populations.
DIAGNOSIS   History, with special attention to possible offending exposures and/or ingestion as well as the duration of lesions. Vasculitic urticaria typically persists >72 h, whereas conventional urticaria often has a duration <48 h.

Skin testing to food and/or inhalant antigens.

Physical provocation, e.g., challenge with vibratory or cold stimuli

Laboratory exam: complement levels, ESR (neither an elevated ESR nor hypocomplementemia is observed in IgE-mediated urticaria or angioedema); C1-esterase inhibitor levels if history suggests hereditary angioedema; cryoglobulins, hepatitis B antigen, and antibody studies; autoantibody screen.

Skin biopsy may be necessary.
DIFFERENTIAL DIAGNOSIS   Atopic dermatitis, cutaneous mastocytosis (urticaria pigmentosa), systemic mastocytosis.
PREVENTION   Identification and avoidance of offending agent(s), if possible.


H1 and H2 antihistamines may be helpful: e.g., ranitidine 150 mg PO bid; diphenhydramine 25–50 mg PO qid; hydroxyzine 25–50 mg PO qid.

Cyproheptadine 4 mg PO tid may be helpful.

Sympathomimetic agents occasionally are useful.

Topical glucocorticoids are of no value in the management of urticaria and/or angioedema. Because of their long-term toxicity, systemic glucocorticoids should not be used in the treatment of idiopathic, allergen-induced, or physical urticaria.

DEFINITION   An inflammatory condition of the nose characterized by sneezing, rhinorrhea, and obstruction of nasal passages; may be associated with conjunctival and pharyngeal itching, lacrimation, and sinusitis. Seasonal allergic rhinitis is commonly caused by exposure to pollens, especially from grasses, trees, weeds, and molds. Perennial allergic rhinitis is frequently due to contact with house dust (containing dust mite antigens) and animal danders.
PATHOPHYSIOLOGY   Impingement of pollens and other allergens on nasal mucosa of sensitized individuals results in IgE-dependent triggering of mast cells with subsequent release of mediators that cause development of mucosal hyperemia, swelling, and fluid transudation. Inflammation of nasal mucosal surface probably allows penetration of allergens deeper into tissue, where they contact perivenular mast cells. Obstruction of sinus ostia may result in development of secondary sinusitis, with or without bacterial infection.
DIAGNOSIS   Accurate history of symptoms correlated with time of pollenation of plants in a given locale; special attention must be paid to other potentially sensitizing antigens such as pets.

Physical examination: nasal mucosa may be boggy or erythematous; nasal polyps may be present; sinuses may demonstrate decreased transillumination; conjunctivae may be inflamed or edematous; manifestations of other allergic conditions (e.g., asthma, eczema) may be present.

Skin tests to inhalant and/or food antigens.

Nasal smear may reveal large numbers of eosinophils; presence of neutrophils may suggest infection.

Total and specific serum IgE (as assessed by immunoassay) may be elevated.
DIFFERENTIAL DIAGNOSIS   Vasomotor rhinitis, URI, irritant exposure, pregnancy with nasal mucosal edema, rhinitis medicamentosa, nonallergic rhinitis with eosinophilia, rhinitis due to use of b-adrenergic agents.
PREVENTION   Identification and avoidance of offending antigen(s).


Antihistamines, e.g., sustained-release chlorpheniramine 12 mg PO bid, terfenadine 60 mg PO bid, astemizole 10 mg PO qd, loratidine 10 mg PO qd. Note: life-threatening cardiac arrhythmias have occurred due to inhibition of the metabolism of terfenadine or astemizole by concomitantly administered macrolide antibiotics (such as erythromycin and clarithromycin) or broad-spectrum antifungal agents such as ketoconazole or itraconazole. The use of either terfenadine or astemizole is contraindicated in combination with these drugs and in individuals with concomitant medical illnesses that impair hepatic function or predispose to cardiac arrhythmias.

Oral sympathomimetics, e.g., pseudoephedrine 30–60 mg PO qid; may aggravate hypertension; combination antihistamine/decongestant preparations may balance side effects and provide improved pt convenience.

Topical vasoconstrictors—should be used sparingly due to rebound congestion and chronic rhinitis associated with prolonged use.

Topical nasal steroids, e.g., beclomethasone 2 sprays in each nostril bid–tid.

Topical nasal cromolyn sodium 1–2 sprays in each nostril qid.

Hyposensitization therapy if more conservative therapy is unsuccessful.

DEFINITION   A systemic disorder characterized by mast cell hyperplasia; generally recognized in bone marrow, skin, GI mucosa, liver, and spleen. Classified as: (1) indolent, (2) associated with concomitant hematologic disorder, (3) aggressive, and (4) mastocytic leukemia.
PATHOPHYSIOLOGY AND CLINICAL MANIFESTATIONS   The clinical manifestations of systemic mastocytosis are due to tissue occupancy by the mast cell mass, the tissue response to that mass (fibrosis), and the release of bioactive substances acting both locally (urticaria pigmentosa, crampy abdominal pain, gastritis, peptic ulcer) and at distal sites (headache, pruritus, flushing, vascular collapse). Clinical manifestations may be aggravated by alcohol, use of narcotics (e.g., codeine), ingestion of NSAIDs.
DIAGNOSIS   May be made by measurement of urinary or blood levels of mast cell products including histamine, histamine metabolites, prostaglandin D2 (PGD2) metabolites, or mast cell tryptase, and tissue or bone marrow biopsy demonstrating increased mast cell density. Other studies including bone scan, skeletal survey, GI contrast studies may be helpful. Other flushing disorders (e.g., carcinoid syndrome, pheochromocytoma) should be excluded.


H1 and H2 antihistamines.

Proton pump inhibitor for gastric hypersecretion.

Oral cromolyn sodium for diarrhea and abdominal pain.

NSAIDs (in nonsensitive pts) may help by blocking PGD2 production.

Systemic glucocorticoids may help but frequently are associated with complications.


For a more detailed discussion, see Austen KF: Allergies, Anaphylaxis, and Systemic Mastocytosis, Chap. 310, p. 1913, in HPIM-15.


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