Page 615 - Clinical Immunology_ Principles and Practice ( PDFDrive )

592 ParT fivE Allergic Diseases

Drug-induced. Angioedema develops in 0.1–2% of patients DIFFERENTIAL DIAGNOSIS
on ACEIs. Of these, up to 40% of patients present with life-
threatening angioedema of the upper airway. It is thought to Several dermatoses may present with urticarial lesions, including
result from inhibition of kininase II, which breaks down bra- erythema multiforme minor, bullous pemphigoid, and dermatitis
dykinin, as well as converting angiotensin I to angiotensin II in herpetiformis. These dermatoses can nearly always be distin-
the renin–aldosterone pathway. It usually presents with episodic guished clinically from urticaria on the basis of their polymorphic
and unpredictable swellings of the head and neck, especially of pattern, prolonged duration of individual lesions, lack of daily
the tongue and oropharynx. Although, in most cases, angioedema fluctuation, development of vesicles or blisters, and resistance
develops within the first week of treatment with ACEIs, symptom to conventional therapy for urticaria. Very occasionally, skin
onset may occur after several years on treatment. Management biopsy, with or without indirect immunofluorescence, may be
involves discontinuation of ACEI therapy. Angioedema often required to make the distinction.
recurs on reexposure to ACEIs. ACEIs may also precipitate Papular urticaria is an urticarial reaction to insect bites in
angioedema in patients with angioedema from other causes, sensitized individuals. The lesions are fixed rather than fluctuating,
including C1-INH deficiency. Rare instances of angioedema have may take days or weeks to resolve fully, and may leave pigmenta-
been reported with angiotensin II receptor antagonists. tion or scars. Bites often occur asymmetrically in groups or lines.
Although histamine is involved in the initial pruritic lesions,
Autoinflammatory Syndromes Presenting With oral antihistamines are usually unhelpful, and potent topical
Urticarial Rash steroids may be required to speed up natural resolution.
Acquired
Schnitzler syndrome. Schnitzler syndrome is a rare form of WORKUP IN PATIENTS WITH URTICARIA
CU with intermittent fever, bone pain, high ESR, and monoclonal
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IgM, or, very rarely, IgG gammopathy. Clinically, patients present Evaluation of patients with urticaria requires a detailed history
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with nonpruritic or mildly pruritic CU, mainly affecting the and a physical examination. The history is particularly important
trunk and limbs. The wheals are resistant to antihistamines, and in patients with urticaria and should include a thorough inquiry
angioedema is rare. Fever bouts may exceed 40°C, sometimes for all potential causes of the disorders, possible precipitating
with chills and nocturnal sweating. Patients often suffer from and aggravating factors, the timing of onset and duration of
bone pains, mainly in the pelvis or tibias, arthralgia, and some- individual wheals, associated symptoms as well as travel history,
times full-blown arthritis. Lymphadenopathy, hepatomegaly, and recent infection, occupational exposure, food and drug intake,
splenomegaly may be present. and comorbidity. Patients may be asked to keep a diary of attacks
1
Kappa light-chain monoclonal IgM and, less commonly, IgG and complete weekly urticarial activity scores for CSU. The
paraproteins are found on serum electrophoresis. The ESR is duration of individual lesions can be very helpful in distinguishing
persistently elevated at 60–100 mm/hour, with leukocytosis, the different clinical patterns of urticaria.
elevated platelet count, and anemia. Skin histology shows
neutrophilic urticaria with a tendency to localize around append-
ages in most cases; monoclonal IgM is deposited in the epidermis CLiNiCaL PEarLS
around the keratinocytes and along basement membranes on Diagnosis of Clinical Patterns of Urticaria
direct immunofluorescence. Bone examination may demonstrate
hyperostosis on radiography and hyperfixation on bone tech- • The duration of individual wheals can help define the pattern of
netium scanning. Bone marrow examination shows normal results urticaria.
in most patients, but nonspecific lymphocytic, plasmocytic, or • Wheals lasting ≤1 hour are usually triggered by a physical stimulus.
• Localized wheals lasting up to 2 hours may be caused by skin or
polyclonal infiltration is present in about 20%. mucosal contact with an allergen or a nonimmunological exposure.
The pathophysiology of Schnitzler syndrome is still unclear, • Wheals that take 1–24 hours to fade are usually a presentation of
and the severity of urticarial rash does not depend on the chronic spontaneous urticaria.
paraprotein level. Evidence of activation of interleukin-1 (IL-1), • Wheals lasting >24 hours may be caused by delayed pressure urticaria
increased IL-6, and granulocyte macrophage–colony-stimulating or urticarial vasculitis.
factor (GM-CSF) and anecdotal reports of complete clinical
responses to the IL-1 receptor antagonist anakinra suggest that
cytokines play a leading role in its pathogenesis. The prognosis Physical examination should focus on skin lesion morphology
is generally good. However, long-term follow-up is recommended and careful systemic evaluation for underlying disease or comor-
because patients may develop B-cell lymphomas 10–20 years bidities. If the patient is symptom-free at the time of evaluation,
after its onset. photographs taken when the symptoms occur are helpful. The
approximate duration of individual lesions can be assessed by
Hereditary (Cryopyrin-Associated) Periodic Syndromes outlining a particular lesion with a pen and observing it for a
Several hereditary autoinflammatory urticarial syndromes show day. The appearance and distribution of skin lesions may suggest
mutations of the NLRP-3 gene on chromosome 1q44. NLRP-3 a diagnosis (e.g., the pinpoint lesions with a large flare in cho-
encodes a protein called cryopyrin, which is involved in apoptosis linergic urticaria or lesions on sun-exposed areas in solar
and inflammation. These rare autosomal dominant disorders urticaria).
include familial cold autoinflammatory syndrome (FCAS), Further evaluation of patients with urticaria is guided by the
Muckle-Wells syndrome (MWS), and chronic infantile neurologi- patient history and clinical pattern of disease. However, it must
cal, cutaneous and articular (CINCA) syndrome, now grouped be remembered that there can be more than one cause for urticaria
under the inclusive term cryopyrin-associated autoinflammatory and that different clinical subtypes of urticaria can coexist in
syndrome (CAPS). 20 one patient.