Persistent pruritic rash in an 8-year-old boy

Figure

THE CASE

An 8-year-old boy is brought to the office for evaluation of a persistent itchy rash on his extremities, trunk, and face. Although the rash has been present for longer than 3 months, individual skin lesions change from hour to hour and occasionally the rash clears completely only to recur several hours later. He is otherwise healthy with no known allergies, changes in diet, medication use, or recent illness.

Dermcase Diagnosis: Chronic urticaria

Background

Urticaria or hives is a common skin condition characterized by development of raised wheals or welts, with or without angioedema. Urticaria is classified based on duration and is considered to be chronic when lesions are present for longer than than 6 weeks.¹

Chronic urticaria (CU) is further subclassified into spontaneous or inducible CU. The majority of CU is spontaneous, in which no specific cause can be identified (50% to 80% of cases). For inducible CU in children, the most frequent triggers include physical stimuli (eg, cold urticarial, exercise-induced urticaria, nonsteroidal anti-inflammatory drugs, and antibiotics).¹ Viral infectious also have been shown to exacerbate symptoms of CU.²

The pathogenesis of CU has not been definitively established, although multiple lines of evidence suggest that an autoimmune component is implicated. Some patients with CU are positive for an immunoglobulin (Ig) G autoantibody directed against the IgE receptor, which leads to mast cell activation and degranulation. Other autoimmune conditions, such as rheumatoid arthritis, lupus erythematous, thyroid disease, and dermatomyositis, are also associated with CU.³ Although CU is not considered to be a manifestation of IgE-mediated food allergy, 7% of CU patients have a confirmed food allergy.

The prevalence of CU is estimated to be 1.8%.⁴ One study reports that 18% of children who present to the emergency department (ED) with urticaria are diagnosed with CU.⁴ Although CU is not life threatening, the condition is distressing for patients and frequently impairs their quality of life. 

Clinical findings

Urticarial lesions present as erythematous plaques that may be annular, round, and serpiginous with variable size. Although CU is defined by the presence of lesions for longer than 6 weeks, individual lesions are transient and resolve within 24 hours with no residual discoloration. Angioedema may coexist with urticarial lesions.⁵ Whereas systemic symptoms such as fever, joint pain, and headache are often present in adult patients, no clinical studies have examined the prevalence of these symptoms in childhood CU.

Diagnosis

Clinical history and physical exam are essential for the diagnosis of CU. Laboratory tests are rarely abnormal in children with CU. However, a limited set of tests may be needed to rule out other underlying systemic diseases that may present with similar cutaneous findings. These include complete blood count with differential, erythrocyte sedimentation rate, C-reactive protein, and liver function tests. Antinuclear antibody, thyroid function tests, and complement also may be considered if an autoimmune condition is suspected.⁶

Management

The cornerstone of therapy involves avoidance of exacerbating triggers, if they are identified. A symptom diary can be helpful for documenting possible factors that may precipitate urticaria. A stepwise approach is used for medical management of CU in adults involving antihistamines followed by immunomodulatory therapy in refractory cases.⁶ It appears that a similar management approach may be appropriate for children, although there are few clinical studies that focus on pediatric CU. 

In both pediatric and adult patients, the mainstay of pharmacologic management involves the use of selective (nonsedating) H1 antihistamines.^1,6 Desloratadine has been shown to be safe and effective for the treatment of CU in children aged older than 2 years in randomized control trials.⁷ Cetirizine and levocetirizine also have been found to effectively decrease the recurrence of urticaria in infants.⁸ Nonselective (classical) H1 antihistamines should be avoided in children because of significant anticholinergic adverse effects (such as disruption of sleep cycle).⁹ Cyclosporine has been shown to be effective in some children with CU, and the Royal College of Pediatrics and Child Health currently recommends cyclosporine as a second-line treatment for childhood CU.^1,10 Although omalizumab has shown promising results for the management of refractory CU in adults and children aged older than 12 years, its use in younger pediatric patients is currently limited and requires further investigation.¹¹

Other immunomodulating therapy may be considered on a case-by-case basis. The role of dietary modification for the treatment of CU is controversial and is not currently recommended.¹

Patient outcome

The patient was treated symptomatically with cetirizine. At his 4-week follow-up visit, urticarial lesions had regressed. After 1 year, his symptoms had resolved. 

Approximately 17% of children with CU have similar outcomes and can achieve remission within 1 year. In general, spontaneous remission occurs in 39% and 50% of children with CU at ages 3 and 5 years, respectively.¹²

References:

1. Tsakok T, Du Toit G, Flohr C. Pediatric urticaria. Immunol Allergy Clin North Am. 2014;34(1):117-139.

2. Wedi B, Raap U, Wieczorek D, Kapp A. Urticaria and infections. Allergy Asthma Clin Immunol. 2009;5(1):10.

3. Kasumagic-Halilovic E, Beslic N, Ovcina-Kurtovic N. Thyroid autoimmunity in patients with chronic urticaria. Med Arch. 2017;71(1):29-31.

4. Lee SJ, Ha EK, Jee HM, et al. Prevalence and risk factors of urticaria with a focus on chronic urticaria in children. Allergy Asthma Immunol Res. 2017;9(3):212-219.

5. Zuberbier T, Bindslev-Jensen C, Canonica W, et al; EAACI/GA2LEN/EDF. EAACI/GA2LEN/EDF guideline: definition, classification, and diagnosis of urticaria. Allergy. 2006;61(3):316-320.

6. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133(5):1270-1277.

7. Augustin M, Ehrle S. Safety and efficacy of desloratadine in chronic idiopathic urticaria in clinical practice: an observational study of 9246 patients. J Eur Acad Dermatol Venereol. 2009;23(3):292-299. Erratum in: J Eur Acad Dermatol Venereol. 2009;23(3):498.

8. Simons FE. H1-antihistamine treatment in young atopic children: effect on urticaria. Ann Allergy Asthma Immunol. 2007;99(3):261-266.

9. Pampura AN, Papadopoulos NG, Spicak V, Kurzawa R. Evidence for clinical safety, efficacy, and parent and physician perceptions of levocetirizine for the treatment of children with allergic disease. Int Arch Allergy Immunol. 2011;155(4):367-378.

10. Neverman L, Weinberger M. Treatment of chronic urticaria in children with antihistamines and cyclosporine. J Allergy Clin Immunol Pract. 2014;2(4):434-438.

11. Saini S, Rosen KE, Hsieh HJ, et al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011;128(3):567e1-573.e1.

12. Sahiner UM, Civelek E, Tuncer A, et al. Chronic urticaria: etiology and natural course in children. Int Arch Allergy Immunol. 2011;156(2):224-230.