With Can f 5—a protein expressed in the prostate of male dogs—as one of the several allergenic molecules making up dog dander, the theory arose that dog-allergic patients mono-sensitized to Can f 5 could tolerate female dogs, explains Ann-Marie Malby Schoos, MD, PhD. With confirmation of this theory in practice lacking, Dr. Schoos and colleagues conducted a double-blind, randomized clinical trial to investigate whether children monosensitized to Can f 5 show different reactions to provocation tests with male versus female dog dander.

Testing Male- & Female-Specific Dog Dander

For the study, published in The Journal of Allergy and Clinical Immunology: In Practice, Dr. Schoos and colleagues enrolled patients aged 15-18 years with a history of dog sensitization in the first-of-its-kind study. Following assessment of skin-prick tests (SPTs), specific immunoglobulin E levels to dog dander (e5), and dog components Can f 1 (lipocalin), 2 (lipocalin), 3 (albumin), and 5 (arginine esterase, prostatic kallikrein), the study team performed SPT and conjunctival allergen provocation tests (CAPs) using dog dander collected separately from male and female golden retrievers according to standard extraction procedures for dander.

A dilution of the extracts was made to perform the SPTs with a concentration of 25 mg/mL. Histamine dihydrochloride (10 mg/mL) and physiological sodium chloride (9 mg/mL) were used as positive and negative controls, respectively. Double SPTs were performed on both volar forearms, including application of the positive and negative controls and the three extracts (dog, male dog, female dog), with the latter two blinded to both the investigator and patient through use of identical-looking bottles marked with a number on them. Final results used for analysis were an average of the two corresponding tests, with positive responses defined as greater than or equal to 2 mm than the negative control.

To perform the CAPs using the male and female dog extracts, Dr. Schoos and colleagues applied a droplet of extract with a concentration of 0.25 mg/mL, and every 15 minutes increased the concentration until a final concentration of 25 mg/mL or a positive response. During visits a minimum of 1 week apart, one eye was used as a control and installed with a drop of physiological sodium chloride (9 mg/mL). Positive responses were assessed with the Total Ocular Symptom Score, with evaluations of itchiness (0-4), redness (0-3), and tearing (0-3) and a total score of 4 considered a positive response.

Dog Allergy Isn’t So Simple

Among Can f 5 monosensitized participants, 100% had a positive SPT result to male dog extract, with an average wheal diameter to the male dog extract of 3.6 mm (Figure). Conversely, “none of the patients who were monsensitized to Can f 5 had a reaction to the female extract using the SPT,” explains Dr. Schoos, with an average wheal diameter to the female dog extract of 1.3 mm among these patients. One patient in this group who reacted to both extracts was found upon further testing to not be Can f 5 monosensitized. Among children with a mixed sensitization pattern, 62.5% responded positively to the male extract and 87.5% responded positively to the female extract. Respective average wheal diameters were 2.7 and 3.0 mm.

While none of the Can f 5 monosensitized participants had positive CAP test result to the female dog extract, most, but not all (71.4%) reacted to the male extract, “as we would expect,” says Dr. Schoos. “We found that the eye provocation test was a bit difficult to interpret.” No difference was observed between reactions to male and female dog extract provocation in children sensitized to a mix of the dog components.

“Dog allergy isn’t so simple after all,” notes Dr. Schoos. “Many patients can actually tolerate female dogs, or neutered male dogs, which can often be verified in the patient’s history if physicians ask questions regarding whether reactions are to only male dogs. If the patient also reacts around female dogs, there is no need to explore this any further.” With larger studies needed to confirm their results, blood tests being difficult to interpret, and the SPTs used in the study not available commercially, Dr. Schoos says the patient history is a good place to start.


Children Monosensitized to Can f 5 Show Different Reactions to Male and Female Dog Allergen Extract Provocation: A Randomized Controlled Trial