Imagine this clinical scenario: you are presented with a three-year-old neutered male Labrador Retriever, who was previously diagnosed with atopic dermatitis, with a history of non-seasonal pruritus affecting the feet, face, axillae and groin.
The pruritus has recently increased to a moderate level, so you want to prescribe a systemic medication to help manage it in the short term. The owner’s financial restrictions limit you to either glucocorticoids or antihistamines. While glucocorticoids are known to be effective in managing atopic dermatitis, adverse effects are common, including polydipsia, polyuria and polyphagia. Antihistamines are a very diverse group of drugs typically used to treat allergic disease through a variety of pathways, ultimately reducing histamine release from mast cells. They can also be used to inhibit the action of histamine on other receptors, and so may cause sedative, anti-emetic and anti-psychotic activity.
Does the evidence suggest that antihistamines are as effective as glucocorticoids in managing atopic dermatitis?
Three studies were critically appraised: two randomised control trials and one crossover placebo-controlled trial.
In the first study (Plevnik et al., 2009), 30 client-owned dogs of different breeds, age and sex with a clinical diagnosis of atopic dermatitis were studied. Dogs were randomly allocated to two treatment groups; one group was given methylprednisolone orally at 0.5mg/kg q24h for five days, then 0.5mg/kg q48h. The second group was given fexofenadine orally at 18mg/kg q24h.
Canine atopic dermatitis extent severity index (CADESI-02) scores and pruritus visual analogue scale (PVAS) scores were measured. For both the methylprednisolone and fexofenadine groups, mean CADESI-02 and PVAS scores were significantly lower on days 21 and 42 compared to day 0. For the fexofenadine group, mean PVAS scores were not significantly different between days 0 and 21 but were significantly lower by day 42. Both medications showed significant improvements in clinical assessment and pruritus at the end of the trial. Fexofenadine demonstrated a greater effect than methylprednisolone with longer-term use but was less effective at controlling pruritus during the first three weeks of treatment. Limitations include that the statistical analyses were poorly reported.
A second study by Plevnik et al. (2006) investigated eight dogs, four of which were treated with 18mg/kg q24h fexofenadine orally, and four with 0.5mg/kg q24h methylprednisolone orally for five days then 0.5mg/kg every other day. Treatment was continued for six weeks, with assessments made at days 0, 21 and 42. Both medications reduced mean CADESI and PVAS scores by at least 50 percent at day 42 compared to day 0, but only fexofenadine produced a statistically significant reduction in lesion scores and methylprednisolone only produced a statistically significant reduction in pruritus, although this may have been affected by the small group sizes.
The final study (Paradis et al., 1991) was a double-blinded crossover placebo-controlled trial, in which 30 dogs were treated with each drug individually for one week, followed by a two-day wash-out period. The drugs used were astemizole, clemastine, doxepin, trimeprazine, trimeprazine with prednisone, prednisone and a placebo. The owners recorded daily drug administration and observations. Prednisone was the most effective drug, with a satisfactory response in 17/30 dogs, but showed a greater satisfactory response when used in combination with trimeprazine in 23/30 dogs. Clemastine was the most effective antihistamine with a satisfactory response in 9/30 dogs, and all other medications showed very low levels of satisfactory responses. It is unknown whether the order of medication given was randomised, and the sequence of administration could have potentially impacted the findings, alongside the short two-day wash-out period. More objective measurement of improvements would be beneficial alongside the owners’ assessment.
Overall, there is relatively little evidence available comparing the efficacy of antihistamines against glucocorticoids in dogs with atopic dermatitis. Paradis et al. (1991) reported the greatest owner satisfaction with oral prednisone, either alone or in combination with trimeprazine. This conflicts with the results from Plevnik et al. (2009) and Plevnik et al. (2006), which both demonstrated some effect of antihistamines on pruritus and CADESI scores. A limitation is that these two studies were conducted by the same lead researcher who was employed by the manufacturer of fexofenadine, which introduces the potential for bias.
The International Task Force on Canine Atopic Dermatitis treatment guidelines (Olivry et al., 2010) advises that type-1 histamine receptor antagonists or inverse agonists are unlikely to be beneficial in acute and chronic atopic dermatitis based on the evidence available. Antihistamines may be best suited for use as preventatives, allowing the drug to block the histamine receptors before histamine is released. Even if a particular antihistamine has been shown to be ineffective or effective in managing a particular condition, this is not necessarily applicable to other antihistamines.
Overall, additional studies comparing the short- and long-term efficacy of commonly used antihistamines with glucocorticoids would be beneficial, particularly as atopic dermatitis is a chronic condition that requires long-term medical therapy.