Chronic Urticaria in children: Italian multidisciplinary management guideline
Chronic urticaria (CU) is characterized by recurrent migrating skin lesions, called wheals or hives, angioedema (AE) or both lasting over 6 weeks. Wheals consist of a swelling area of different size and shape with a larger erythema, often pruritic. Lesions usually disappear in 24 h. In vasculitis and pressure urticaria lesions persist longer.
AE is a submucosal or subcutaneous swelling and involves areas such as lips, eyelids, back of the hands and feet, scrotum. AE resolves in 1–3 days and causes pain, tingling, burning sensation or tension, but not itching. Prognosis quoad vitam and quoad valetudinem of CU is generally good. However, comorbidities can occur. Overall, it is a condition of mostly unknown etiopathogenesis, and a frequent cause of specialist consultation and inappropriate diagnostic investigation, aimed at identifying a causal factor which is often not evident by history alone.
Question 1. What is the definition of CU, in the paediatric age?
Answer. CU in paediatric age is defined by the daily presence of wheals, that is not always associated with angioedema, for over 6 weeks or with brief periods of well-being due to therapy.
Question 2. What is the classification of CU?
Answer. CU in the child must be classified in “spontaneous” or “inducible”, in relation to the evidence of a triggering factor (Table 1).
Question 3. What is the prevalence and incidence of CU in the paediatric population?
Answer. Few data exist on the epidemiology of urticaria in children, however, it is reasonable to think that prevalence and incidence of CU in developmental age are both below 1% (Level of evidence IV).
Question 4. What is the natural history of CU in paediatric age?
Answer. Remission at 3 years from the onset of CSU in children happens in 30% to 50% of cases. Anaphylaxis is reported only in CIU (Level of evidence IV).
Question 5. What is the etiopathogenesis of CU in children?
Answer. In most cases, CU in children is spontaneous and no external cause is found. However, in half of the cases of CSU, an autoimmune mechanism is possible. In a minority of patients, CU is associated with inducing factors, often physical (Level of evidence V).
Question 6. Is CU in children associated to other organ diseases or systemic diseases more frequently than in non-selected population?
Answer. There is no evidence of an association of CU in children and other organ or systemic diseases (Level of evidence V)
Question 7. Can psychological factors determine CU or exacerbate it?
Answer. Studies performed on adults might suggest a role of psychological factors in the development or exacerbation of CU. In small populations of children, weak data seem to support this hypothesis (Level of evidence IV).
Question 8: Can clothes or temperature changes worsen CU?
Answer. There are no studies that document the role of clothes and temperature on the course of CU in children, excluding subjects with cold-urticaria, heat-urticaria, cholinergic urticaria (Level of evidence VI).
Question 9. Which are the criteria that allow diagnosing CU in children?
Recommendation. The diagnosis of childhood CU is based on the appearance of itchy wheals, not always associated with AE, persisting daily or on most days for at least 6 weeks. No laboratory test is needed to diagnose CU (Level of evidence VI. Strength of the recommendation A)
Question 10. Which conditions should be considered in the differential diagnosis of CU and what are the clinical or laboratory criteria that help in the differential diagnosis? Are vasculitic urticaria, monogenic syndrome associated urticaria and bradykinin mediated AE different clinical entities from common CU?
Recommendation. Differential diagnosis is necessary in any case of CU as wheals can be found in many acquired or hereditary conditions, with different pathogenic mechanisms, such as papular urticaria, mastocytosis, some vasculitis and genetic syndromes. Wheals must also be differentiated from other elementary lesions, as papulae. Recurrent isolated AE should be distinguished from bradykinin mediated angioedema, hypoproteinemic oedema and some cancers. Evaluation of the morphology of lesions, duration and associated signs and symptoms leads toward a diagnostic hypothesis that must be confirmed or not by diagnostic tests listed in Table 2 (Level of evidence VI. Strength of recommendation A).
Question 11. What is the role of history and physical examination in identifying the aetiology of CU in children?
Recommendation. History and physical examination are the guides to identify a possible underlying cause of CU and decide whether other diagnostic tests are needed (Level of evidence V. Strength of recommendation A).
Question 12. In the case of suspected CIU, is it necessary to perform diagnostic tests for inducible urticaria?
Recommendation. Specific tests should be used to confirm the suspect of inducible CU (Level of evidence V. Strength of recommendation B).
Question 13. When clinical history does not indicate an underlying cause, is it recommended to perform laboratory tests to identify allergic or infective triggers, in a child?
Recommendation. When clinical history does not suggest a temporal relationship between exposure to an allergen and onset of symptoms, it is not recommended to perform allergy tests to foods, additives, inhaled particles or medications (Level of evidence VI. Strength of recommendation D).
When there is a history of cause-effect relationship between exposure to an allergen and occurrence of urticaria and IgE tests are positive to the relevant allergen, diagnosis can be ascertained by the effectiveness of allergen avoidance and positive provocation test to the same allergen (Level of evidence V. Strength of recommendation A).
Diagnostic tests for an infectious disease should be performed only when there is a suspicion based on clinical history or laboratory tests (Level of evidence V. Strength of recommendation B).
Question 14. Is it useful to perform Autologous Serum Skin Test (ASST) in the diagnostic workup of CU?
Recommendation. ASST should be considered a screening test for autoantibodies (Level of evidence IV. Strength of recommendation B). ASST should not be routinely performed in children with CU (Level of evidence IV. Strength of recommendation D)
Question 15. Is it useful to perform tests to rule out coeliac disease, thyroiditis, other autoimmune or neoplastic disorders in children with negative history and physical examination?
Recommendation. Children with CU should be screened for coeliac disease and thyroid diseases (Level of evidence V. Strength of recommendation B) but not for other autoimmune diseases or malignancies (Level of evidence V. Strength of recommendation D).
Question 16. Which diagnostic workup is appropriate for children with CSU?
Recommendation. In children with CSU with negative history and physical examination, it could be considered to perform blood tests for inflammatory diseases (blood cell count, CRP, ESR (Level of evidence V. Strength of recommendation B), and to test for autoimmune diseases (coeliac disease, thyroiditis) (Level of evidence V. Strength of recommendation B.)
Question 17. Is it advisable to use severity scores in children with CSU?
Recommendation. Currently, there are no validated severity scores for CSU in paediatric age. However, in clinical practice, it is possible to use adult scores (Urticaria Activity Score 7-UAS 7) to rate the severity of disease and to assess the response to treatment (Level of evidence V. Strength of recommendation B).
Question 18. Can treatment of autoimmune thyroiditis or coeliac disease cure CU?
Recommendation. There is no clear evidence that treatment of autoimmune thyroid disease or coeliac disease associated with CU can have an impact on the natural course of CU. However, in clinical practice the treatment is advisable (Level of evidence V. Strength of recommendation B).
Question 19. Is it advisable to start an additive and/or pseudo-allergen-free diet in the child with CU?
Recommendation. When history is negative, children should not go on an additive and/or pseudo-allergen-free diet (Level of evidence V. Strength of recommendation E).
Question 20. What is the drug of choice for CU?
Recommendation. Second-generation H1-antihistamines are the first-choice treatment for CU (Level of evidence I. Strength of recommendation B).
Question 21. Is there any evidence of greater efficacy of an H1-antihistamine compared to the others? In case of failure of H1-antihistamine at standard dosing, should a different H1-antihistamine be used?
Answer: There is no evidence that any H1-antihistamine is more effective than the others in the treatment of CU, therefore no specific H1-antihistamine is recommended as a first option. (Level of evidence I. Strength of recommendation D.)
Question 22. In case of failure of second-generation H1-antihistamine at standard dosing, what are the options? Should the dosage of H1-antistamines be increased? If there is no control of symptoms, should a different H1-antihistamine be prescribed?
Recommendation. In children over 12 years of age, if standard dosing of second-generation H1-antihistamine does not adequately control CU, after evaluation of the risk-benefit ratio, an increase in the daily dosage (by increasing frequency of administration) up to fourfold may be recommended (off-label) (Level of evidence I. Strength of recommendation B)
Question 23. When second-generation H1-antihistamines are not adequate to control CU, should a combination of second-generation H1-antistamine and first-generation H1-antihistamine or H2-antihistamine be given?
Recommendation. A combination of second-generation H1-antistamine and first-generation H1-antihistamine, or of H1-and H2-antagonists should not be given in CU. (Level of evidence I. Strength of recommendation D).
Question 24. When second-generation H1-antihistamine do not adequately control CU, could other treatments be recommended in children?
Recommendation. In patients 12 years of age and older with CSU, omalizumab should be added to second-generation H1-antistamines as a second-line therapy when second-generation H1-antistamines alone do not give adequate relief.
Question 26. Does CU have an impact on patient's quality of life, and which is the burden of the disease on psychological aspects? How should psychological distress be addressed?
Recommendation. CU affects children's quality of life and their families. The most effective instrument to evaluate quality of life is the care relationship. When necessary, however, the CU-Q2oL can be useful. (Level of evidence V. Strength of recommendation B.)
For more details click on the link: https://doi.org/10.1186/s13052-019-0695-x