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Chronic Spontaneous Urticaria (CSU)

Evaluation

- Careful history required, starting with duration of symptoms and duration of each lesion -

Search for identifiable triggers

- Detailed review of systems to evaluate diagnostic mimickers or comorbid rheumatologic

disease (some studies have noted increased risk of autoimmunity, including thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, DM I, celiac disease) [2, 3, 17] - Identifyimpact on QOL

- Take careful medication history (ex. ACEI, NSAIDs, new medications or OTC vitamins,

minerals, supplements)

- Biopsy if there are concerning or atypical features (prolonged lesion duration, abnormal skin findings with lesion resolution, significant pain, signs of end-organ dysfunction, very high CRP/ESR)

o 4 mm punch biopsy of newly formed lesion (placed in formalin for standard tissue

processing) +/- perilesional skin if suspicion for autoimmune blistering disease

(placed in Michel’s media for direct immunofluorescence [DIF])

o CSU: interstitial edema with perivascular mixed infiltrate comprised typically of

eosinophils, neutrophils and lymphocytes

o Leukocytoclasis, small vessel damage, perivascular and interstitial fibrinoid deposits

support urticarial vasculitis (small vessel vasculitis) [1]

- Monitoring:

o Disease activity: Urticaria Activity Score-7 (UAS7) and/or Angioedema Activity

Score (AAS7); Itch Severity Score (ISS7) – data from previous 7 days

o Disease control: Urticaria Control Test (UCT), Angioedema Control Test (AECT) –

data from previous 4 weeks

o Quality of life: Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL),

Angioedema Quality of Life Questionnaire (AE-QOL)

- Differential diagnosis:

o Wheals and angioedema:

▪ Urticarial vasculitis (lesions lasting > 24 hours and/or are painful with residual

dyspigmentation or presence of systemic symptoms)

▪ Anaphylaxis

▪ Serum sickness-like reaction

▪ Mast cell disorder: mast cell activation syndrome (MCAS), systemic mastocytosis

▪ Hypereosinophilic syndrome

▪ Eosinophilic granulomatosis with polyangiitis (EGPA; end-organ

involvement, eosinophils ≥ 1500)

o Urticaria-predominant:

▪ Urticarial vasculitis

▪ Urticarial bullous pemphigoid

▪ Neutrophilic urticarial dermatosis

▪ Arthropod assault

▪ Adult-onset Still’s disease

▪ Urticarial dermatitis

▪ Cryopyrin-associated periodic syndromes (familial cold autoinflammatory

syndrome, Muckle-Wells syndrome, neonatal-onset multisystem

inflammatory disorder)

▪ Cryoglobulinemia (cold-induced lesions especially on buttocks and lower

extremities, hepatitis B or C)▪ Schnitzler’s syndrome (monoclonal IgM or IgG, fever, bone pain,

lymphadenopathy, weight loss)

▪ Well’s syndrome

▪ Systemic or maculopapular cutaneous mastocytosis

o Angioedema-predominant:

▪ Bradykinin-mediated angioedema (ACEI-induced, hereditary, acquired –

especially if episodic abdominal pain)

▪ Drug reaction

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