Q:

8/20/2013
I have a 6 month old male with a history of chronic urticaria (CU) on a daily basis for the past two months. He was seen by dermatology initially with a biopsy that confirmed urticaria and ruled out urticaria pigmentosa. Patient was started on Zyrtec 2.5 mg po qd and Zantac po bid with significant improvement with his hives and itching. Lab work up from Quest included CBC, LFT's, BUN/CR, TSH, ANA, Tryptase, Histamine Release were all normal except the Histamine Release was significantly elevated. I suspect this patient has autoimmune chronic urticaria. For adults and older kids with CU, I have used between 2-4x recommended dose of antihistamines. Are there any recommendations or guidelines about using higher than recommended doses for kids between 6 months to 2 years with CU? Are there any studies looking at really young children with autoimmune chronic urticaria? Thank you.

A:

Thank you for your inquiry.

The patient you presented is one which all allergists see, and one which is quite difficult. There are reports in the literature of children with autoimmune urticaria that discuss therapeutic strategies, and there are reviews of urticaria in children which you might also find helpful. I have copied the abstracts and references to a number of these below.

In my opinion, in a child this age, one would be limited to the use of antihistamines (both H1 and H2 antagonists) and perhaps an antileukotriene.

Usually standard dosages are all that one would administer, but some children can certainly tolerate higher doses, and this can be considered especially if one is using a nonsedating antihistamine.

The "good news,” as is noted in some of the references below, is that such urticaria is almost universally transient and subsides spontaneously in most infants within weeks to months.

Thank you again for your inquiry and we hope this response is helpful to you.

Acta Dermatovenerol Croat. 2008;16(2):65-71.
Chronic autoimmune urticaria in children.
Dodig S, Richter D.
Source
Srebrnjak Children's Hospital, Reference Center for Pediatric Allergology of the Ministry of Health and Social Welfare, Srebrnjak 100, HR-10000 Zagreb, Croatia.
Abstract
Results of determination of circulating histamine releasing autoantibodies using histamine release urticaria test in 12 children (aged 3 to 18 years, mean age 8.5 years; 7 female and 5 male) with chronic urticaria are presented. Standard work-up including detailed history, allergy testing and routine laboratory findings did not disclose any plausible cause of chronic/recurrent urticarial eruption in these children. All children underwent serum-induced basophil histamine release urticaria test. At serum dilution of 12.5%, the mean percent of histamine liberation was 40.8% (range 18%-77%; normal <16.5%), which indicated the presence of autoantibodies to Fc epsilon RI and/or to the IgE-Fc epsilon RI complex. The percent of histamine release did not correlate with patient age or duration and severity of symptoms. Thus the autoimmune basis of chronic urticaria was established. Associated antithyroid autoantibodies were found in two patients. Complete or partial remission was obtained with treatment that included antihistamines, low salicylate-low preservative diet in all, and high dose intravenous immunoglobulin in 3 children.

Eur Ann Allergy Clin Immunol. 2008 May;40(1):5-13.
Urticaria and urticaria related skin condition/disease in children.
Novembre E, Cianferoni A, Mori F, Barni S, Calogero C, Bernardini R, Di Grande L, Pucci N, Azzari C, Vierucci A.
Source
Department of Pediatrics, University of Florence, Italy.
Abstract
Urticaria is a rash, that typically involves skin and mucosa, and is characterized by lesions known as hives or wheals. In some cases there is an involvement of deep dermis and subcutaneous tissue that causes a skin/mucosa manifestation called angioedema. Urticaria and angioedema are very often associated: urticaria-angioedema syndrome. The acute episodic form is the most prevalent in the pediatric population, and it is often a recurrent phenomenon (recurrent urticaria). Acute episodic urticaria it is usually triggered by viruses, allergic reactions to foods and drugs, contact with chemicals and irritants, or physical stimuli. In many instances it is not possible to identify a specific cause (idiopathic urticaria). Chronic urticaria is a condition that can be very disambling when severe. In children is caused by physical factors in 5-10% of cases. Other trigger factors are infections, foods, additives, aeroallergens and drugs. The causative factor for chronic urticaria is identified in about 20% of cases. About one-third of children with chronic urticaria have circulating functional autoantibodies against the high affinity IgE receptor or against IgE. (chronic urticaria with autoantibodies or "autoimmune" urticaria). It is not known why such antibodies are produced, or if the presence of these antibodies alter the course of the disease or influence the response to treatment. Urticaria and angioedema can be symptoms of systemic diseases (collagenopathies, endocrinopathies, tumors, hemolytic diseases, celiachia) or can be congenital (cold induced familiar urticaria, hereditary angioedema). The diagnosis is based on patient personal history and it is very important to spend time documenting this in detail. Different urticaria clinical features must guide the diagnostic work-up and there is no need to use the same blood tests for all cases of urticaria. The urticaria treatment includes identification of the triggering agent and its removal, reduction of aspecific factors that may contribute to the urticaria or can increase the itch, and use of anti-H1 antihistamines (and/or steroids for short periods if antihistamines are not effective). In some instances an anti-H2 antihistamine can be added to the anti-H1 antihistamines, even if the benefits of such practice are not clear. The antileucotriens can be beneficial in a small subgroup of patients with chronic urticaria. In case of chronic urticaria resistant to all the aforementioned treatments, cyclosporine and tacrolimus have been used with good success. When urticaria is associated to anaphylaxis, i.m epinephrine needs to be used, together with antihistamines and steroids (in addition to fluids and bronchodilatators if required).

Acta Derm Venereol. 2013 Apr 2. doi: 10.2340/00015555-1573. [Epub ahead of print]
Management of Childhood Urticaria: Current Knowledge and Practical Recommendations.
Pite H, Wedi B, Borrego LM, Kapp A, Raap U.
Source
Department of Immunoallergy, Hospital Dona Estefania, Centro Hospitalar Lisboa Central Rua Jacinta Marto, 1169-045 Lisbon, Portugal.
Abstract
Urticaria, defined by the presence of wheals and/or angio-edema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for pae-diatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.

Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):485-90. doi: 10.1097/ACI.0b013e3283574cb3.
Childhood urticaria.
Marrouche N, Grattan C.
Source
Norfolk and Norwich University Hospital, Norwich, UK.
Abstract
Purpose of Review: The present article reviews childhood urticaria. It provides an update on the current understanding of its pathophysiology and highlights the current practice in the management of this condition.
Recent Findings: Progress has been made in understanding the pathophysiology of urticaria with the elucidation of an autoimmune basis in a significant proportion of children with chronic spontaneous urticaria. H1-antihistamines remain the mainstay of therapy, but there is increasing awareness on the risks of sedating first-generation antihistamines. Omalizumab is increasingly being used off-license in the most refractory cases.
Summary: Urticaria is a common disease that affects children and adults. However, paediatric urticaria has specific features and remains poorly understood. Acute spontaneous urticaria is the most common clinical presentation in childhood. It is caused by viral infection in most cases with an identifiable trigger. By contrast, chronic spontaneous urticaria in children may be autoimmune, but more studies are needed to understand the clinical significance of functional autoantibodies in this subgroup of patients. Investigations should always be guided by history. Treatment remains largely symptomatic. H1-antihistamines are the mainstay of therapy but are insufficient to control symptoms in all patients. There is an urgent need for more efficacious therapies.

Eur J Pediatr. 2013 Apr;172(4):569. doi: 10.1007/s00431-013-1936-4. Epub 2013 Jan 20.
Autoimmune chronic urticaria: transferability of autologous serum skin test.
Pastore S, Berti I, Longo G.
Source
University of Trieste, Trieste, Italy.
Abstract
At least 30 % of children with chronic urticaria have an autoimmune aetiology with a positive autologous serum skin test (ASST). ASST is cheap, easy to perform and has good sensibility and specificity in detecting autoantibodies. In case of concern about reliability of ASST because of antihistamine medications, test transferability seems to be feasible.

Pediatr Dermatol. 2011 Nov-Dec;28(6):629-39. doi: 10.1111/j.1525-1470.2011.01518.x. Epub 2011 Oct 4.
Evidence-based evaluation and management of chronic urticaria in children.
Zitelli KB, Cordoro KM.
Source
Psoriasis Treatment Center, University of California at San Francisco, San Francisco, California 94143, USA.
Abstract
Urticaria affects nearly 25% of the population at some time in their lives. In a subset of children, urticaria will develop into a chronic condition that can greatly affect quality of life. Although numerous causes and triggers are proposed for chronic urticaria (CU) in children, ranging from infections, allergens, and medications to physical factors and autoimmune disease, the exact etiology is not always identifiable. Accordingly, a large subset of cases are designated "chronic idiopathic urticaria." Because of the clinical complexities of CU, as well as the confusing literature on this topic, we have developed a conceptual framework based on the cumulative evidence to assist with the categorization, clinical evaluation, and treatment of CU in children.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology