Page 608 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Urticaria, Angioedema, and Anaphylaxis

Clive E.H. Grattan, Elena Borzova

Urticaria is a common skin disorder that can lead to severe GENETICS
impairment in quality of life. Recently, there has been substantial
progress in our knowledge and understanding of the pathophysiol- Although there is no indication of mendelian inheritance, the
ogy of the condition, offering new diagnostic and treatment frequency of chronic spontaneous urticaria (CSU) is higher in
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approaches for many patients. first-degree relatives of patients. A link between CU and human
leukocyte antigen (HLA)-DRB1*04 (DR4) and its associated
DEFINITION allele, -DQB1*0302 (DQ8), was found in British patients with
CSU with evidence of functional autoantibodies compared with
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Urticaria is characterized by itchy wheals, angioedema, or both. a control population. Strong associations with HLA-DRB1*1302
Urticarial lesions resulting from localized edema of the upper and DQB1*0609 alleles were found in aspirin-induced urticaria
dermis are called wheals (Fig. 42.1), whereas pronounced swelling in Korean patients. 6
of deeper dermal layers and subcutaneous and submucosal tissues
is known as angioedema (Fig. 42.2). CLINICAL PATTERNS
Urticaria is classified by the duration of continuous activity into
KEY CONCEPTS acute (<6 weeks), chronic (≥6 weeks), or episodic, where short
episodes occur repeatedly over a period, with short or long
Definition of Urticaria intervals. It may be spontaneous, inducible, or both. Inducible
urticarias may be triggered by mechanical, thermal, or other
• Urticaria is an illness characterized by wheals, angioedema, or both.
• Wheals are superficial swellings of the dermis of skin: they are pale stimuli. The differential diagnosis of urticaria includes urticarial
and itchy with surrounding redness when they appear and then become vasculitis, hereditary angioedema (HAE), and autoinflammatory
pink before fading. syndromes presenting with urticarial rash.
• Angioedema is a deep swelling below the skin or mucosa that usually
lasts longer than wheals and may be painful rather than itchy. ETIOPATHOGENESIS AND ETIOLOGICAL
• Wheals may occur with or without angioedema in urticaria.
• Acute urticaria lasts <6 weeks. It is common and often caused by CLASSIFICATION
viral infections. Urticaria caused by drugs and foods falls in this category,
but the diagnosis is usually clear from the history. Although many aspects of the pathophysiology of urticaria remain
• Chronic urticaria lasts ≥6 weeks with continuous disease activity. A unclear, our understanding has advanced considerably over
cause may not be found. Urticaria occurring intermittently over a the last two decades, allowing for an etiological classification
period of >6 weeks can be defined as episodic. (Table 42.1).
• When angioedema occurs without wheals, C1 esterase inhibitor
deficiency should be excluded. Mast Cell–Dependent Mechanisms
Skin mast cells are key players in the pathogenesis of urticaria.
They are predominantly located around the small blood vessels
EPIDEMIOLOGY and lymphatic vessels as well as around or within peripheral
nerves. The population density of mast cells is greatest at distal
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Urticaria is common, and up to 25% of the general population body areas, including the face, hands, and feet. There is con-
experience some form of urticaria at least once over their lifetime, flicting evidence as to whether the number of cutaneous mast
whereas the lifetime prevalence of chronic urticaria (CU) is cells is increased in patients with urticaria, but it is accepted
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0.1–3% of the general population. Acute urticaria mainly affects that these cells release mediators more readily compared with
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young adults and has an obvious female preponderance, whereas normal cells.
CU is more common in adults, affecting mainly middle-aged Human skin mast cells contain preformed mediators in their
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women, and is uncommon in children and adolescents. By granules, including histamine, proteases (tryptase, chymase), and
definition, acute urticaria resolves within 6 weeks, whereas CU heparin. They express many membrane receptors, including
may last for years. Rarely, CU may last >10 years. However, CU high-affinity immunoglobulin E (IgE) and low-affinity IgG
is almost always a self-limiting disorder, resolving spontaneously receptors. Unlike mast cells elsewhere (e.g., lung and gastro-
within 6 months of onset in 50% of patients. 3 intestinal [GI] tract), skin mast cells possess complement C5a
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