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Three Part Question

In [a child with varicella zoster infection] can [calamine lotion or antihistamines] reduce [pruritus]?

Clinical Scenario

A 2-year-old girl presents with chickenpox. The girl has typical vesicular lesions but has no evidence of complications on examination. Her mother reports that she is scratching continuously and has had very little sleep over the past few days as a result of the pruritus. Considering the therapeutic options, we wonder whether there is any evidence to support the use of either calamine lotion or antihistamines to alleviate pruritus in varicella zoster infection.

Search Strategy

Cochrane Library using "varicella and calamine", "varicella and antihistamine", "chickenpox and anitihistamine" and "chickenpox and calamine": no relevant results.
PubMed (no limits set) using the search terms given above. The search produced the same results irrespective of whether "chickenpox" or "varicella" was used. Three publications related to "varicella and calamine": none were relevant (one case report and two cross-sectional surveys).
In addition, PubMed was searched for "varicella" or "chickenpox", respectively, in combination with (and) the proprietary names of all antihistamines currently licensed for use in the UK (based on British National Formulary 51, March 2006 and British NationalFormulary for Children 2005). For topical antihistamines: antazoline, diphenhydramine and mepyramine. For systemic antihistamines: acrivastine, alimemazine (trimeprazine), brompheniramine, chlorpheniramine (chlorphenamine), cetirizine, cinnarizine, clemastine, cyclizine, cyproheptadine, desloratidine, diphenhydramine, diphenylpyraline, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratidine, mizolastine, promethazine, terfenadine and triproledene. Fourteen studies were found: one each related to cetirizine, doxylamine, and promethazine, and 11 related to diphenhydramine—none were relevant (search date 14 April 2006).

Search Outcome

Twenty two publications related to "varicella and antihistamines": only one study was relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Englisch and Bauer,	128 paediatric patients (age 1–6 years) with chickenpox randomised to DMM 0.1 mg/kg/day or 0.05 mg/kg/day or placebo (1/3 of the dose given at am 2/3 given at pm) Duration of treatment: 7 days	Double-blind randomised controlled trial, multicentre study (level 1b)	Change in ISS from baseline ISS composed of severity of itching during daytime rated on 4-point scale by parents ("no itching" to "itching is dominant") and disturbance of sleep during the first 8 days of the illness	DMM groups showed significant reduction of ISS compared with placebo group No significant difference between the two different DMM dosages Secondary outcome measures: better appetite and less sleep disturbance in DMM groups (significance not calculated), no difference regarding skin superinfection	All patients additionally received topical treatment (astringent lotion—active ingredient: tannin) Process of randomisation not described Methods of blinding not described Only minor adverse events (tiredness in 2 cases), no serious adverse events

Comment(s)

No studies were found that evaluated the effect of calamine lotion on pruritus associated with varicella zoster infection. Nevertheless, the drug—a basic zinc silicate—has a good safety profile and in our personal experience, many patients (or their parents) report symptomatic relief. A study investigating the effectiveness of calamine lotion in varicella zoster infection is desirable. Only one trial has examined the use of one particular systemic antihistamine in this context—dimethindene maleate (DMM), a non-sedating H1 blocker,(Schaffler) which is not available in the UK. Two different regimens were used in this trial—a dose of 0.1 mg/kg/day, which is the standard recommended dose and a "low-dose" treatment with 0.05 mg/kg/day. The study showed considerable improvement in severity of itching in both treatment groups, as well as some improvement in appetite and sleep disturbance. However, neither the method of randomisation nor the blinding process is described. The blinding process seems particularly relevant, as the primary outcome measure—the itching severity score—is composed of subjective measures rated by the patient's parents. Although other systemic antihistamines would probably produce a similar effect, there is currently no definite evidence to support their use. Given that antihistamines are a heterogenic group of drugs—with the shared property of H1 receptor binding but variable antiadrenergic, anticholinergic and antiserotoninergic properties—it is uncertain whether the results of this study can be extrapolated to the use of other antihistamines (Welch). Despite the fact that no serious adverse events were observed in this study, there are several publications reporting adverse effects in children with varicella zoster infection treated with diphenhydramine, including ataxia, (McGann) urinary retention, (McGann) clouding of consciousness,(Bernhardt). behavioural abnormalities and hallucinations. ,(Bernhardt, Chan, Reilly). The side effects are thought to be related to the anticholinergic properties, are usually short lived and have been reported in association with systemic, (McGann, Chan, Woodward). as well as topical use (Chan, Reilly) of diphenhydramine. The decision to use systemic antihistamines should therefore be based on the potential benefit of symptomatic relief weighed against possible side effects on an individual basis.

Clinical Bottom Line

No published evidence is available to support the use of calamine to alleviate pruritus in varicella infection (grade D). Only limited evidence is found to support the use of systemic antihistamines in this context and benefits have to be weighed against potential risks (grade B).

References

1. Englisch W, Bauer CP. Dimethindene maleate in the treatment of pruritus caused by varizella zoster virus infection in children. Arzneimittelforschung/Drug Res 1997;47:1233–5.
2. Schaffler K, Wauschkuhn CH. Martinelli M. et al. Influences of dimethindene maleate in a new formulation on oculo and psychomotor performance using the oculodynamic test (ODT) in volunteers. Agents Actions 1994;41:C136–7.
3. Welch MJ. Meltzer EO, Simons FE. H1-antihistamines and the central nervous system. Clin Allergy Immunol 2002;17:337–88.
4. McGann KP. Pribanich S. Graham JA. et al. Diphenhydramine toxicity in a child with varicella. A case report. J Fam Pract 1992;35:210, 213-14.
5. Bernhardt DT. Topical diphenhydramine toxicity. Wis Med J 1991;90:469–71.
6. Chan CY, Wallander KA. Diphenhydramine toxicity in three children with varicella-zoster infection. DICP 1991;25:130–2.
7. Reilly JF Jr. Weisse ME. Topically induced diphenhydramine toxicity. J Emerg Med 1990;8:59–61.
8. Woodward GA, Baldassano RN. Topical diphenhydramine toxicity in a five year old with varicella. Pediatr Emerg Care 1988;4:18–20.