Chronic Spontaneous Urticaria (CSU)
Work-Up
History, physical, basic tests, assess disease activity/impact/control, labs [1] - 7Cs:
confirm (rule out other disorders), cause (look for markers of autoimmunity), co-factors
(identify triggers), consequences (other autoimmune disorders, QOL), components (predictors of treatment/biomarkers), course (monitoring CSU control) [3]
Recommended laboratory work-up
- CBC w/ diff (look for eosinophilia, which may indicate underlying disease; may see
basopenia and eosinopenia in 10-15% CSU [2, 3])
o Baso-/eosinopenia, low IgE may predict poor response to H1 anti-histamines and/or
omalizumab [3]
o May be inaccurate if patient recently received systemic glucocorticoids - anti-TPO
Ab: anti-TPO IgG more commonly measured vs anti-TPO IgE [3] o Serologic testing for anti-TSH receptor and anti-thyroglobulin antibodies can be considered, although data on their association with CSU is less robust than for anti TPO
o Intact omalizumab responsiveness in patients with anti-TPO IgE antibodies in one
study (dosing was based on total IgE) [11]
- Total IgE: conflicting evidence - some studies show no difference in total IgE in autoimmune vs non-autoimmune CSU [2], but other studies have demonstrated low total IgE in autoimmune CSU [13]
o High levels may indicate alternative etiology
- Obtain TSH, free T4 if history supports thyroid dysfunction and/or if anti-thyroid antibodies present
- CU index: in vitro basophil histamine release assay; indicates anti-IgE/-FcεR antibodies (RI
or II) or presence of histamine-releasing serum factor) [18]
o May indicate more difficult-to-treat disease – some studies have demonstrated higher values in refractory CSU cases (symptomatic despite anti-histamines +/- leukotriene receptor antagonist) [19, 20]
- CRP, ESR
- C4 if isolated angioedema
- Some guidelines recommend CRP and ESR in all, with anti-TPO IgG and total IgE for those receiving specialist care [1, 3]
- 80-90% of patients have no identifiable cause [21]
Secondary work-up to consider (based on history, exam, other labs [1])
- H. pylori stool antigen test- Toxacara canis antibody test
- Stool ova and parasites
- GI referral (if concern for inflammatory bowel disease)
- ANA, other rheumatologic labs
- IgE antibody (anti-IgE IgG), CU index
- Tryptase if suspected mastocytosis and/or hereditary alpha-tryptasemia (HaT) o May be
elevated in CSU, including into abnormal range, and may correlate with disease
activity [22, 23]
- Specialist care: consider based on history, exam, other labs [1]
o Food, drug or other trigger testing
o Paraproteinemia
o Gene mutation analysis for hereditary periodic fever syndromes (especially if
pediatric patient and episodic symptoms; rash, ulcers, lymphadenopathy,
abdominal pain, pharyngitis, conjunctivitis)
o C4, C1-INH level and function, C1q, C1-INH antibodies if suspecting bradykinin
mediated angioedema
- Autologous serum skin testing: plasma or serum obtained during a period of active
disease injected intradermally (IDT; 0.05 mL) in area of uninvolved skin; wheal ≥ 1.5
mm larger than saline control is suggestive of autoimmune etiology [2]
- IL-6 may correlate with CRP and disease activity, although is not regularly utilized in
clinical practice [24]