Dermatologic examination
Figure 2. In the dog in Case #2, matted crusts were found over the shoulder region; the hair was clipped in this area. The
arrangement of these skin lesions, in a saddle-like pattern possibly related to the dissemination of the preventive over the
dog's body, is unique. In addition to these lesions, grouped intact pustules with peripheral erythema (arrowheads) were seen
between the digits in this patient (inset). These pustules were rich in acantholytic keratinocytes.
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At presentation, the dog was found to be in good general health with a temperature of 101.5 F (38.6 C). Large pustules and
severe crusting extended from the product application site down to the lateral thorax (Figure 2) and both front legs but also spread to areas distant from the application site. Lesions were seen bilaterally on the pinnae,
interdigital spaces of all four paws, the ventral abdomen, and flanks. Pustules and crusts were surrounded by moderate erythema
(Figure 2).
Microscopic examination of the content of a superficial pustule revealed neutrophils, eosinophils, and acantholytic keratinocytes
and was suggestive of pemphigus foliaceus. Skin biopsy samples were obtained for histologic examination and direct immunofluorescence
testing. Serum was collected for circulating antikeratinocyte autoantibody detection by indirect immunofluorescence testing.
Diagnosis and treatment
Pending biopsy results, and because of the strong clinical suspicion of ProMeris-triggered pemphigus foliaceus, prednisolone
(0.8 mg/kg orally twice daily) was administered.
Figure 3. Histologic changes of ProMeris-triggered pemphigus foliaceus mirror those of naturally occurring pemphigus foliaceus.
The stratum corneum (arrows) lifts away from the hyperplastic epidermis (asterisk) during formation of a subcorneal pustule
that contains neutrophils and acantholytic keratinocytes (box inset) (hematoxylin-eosin stain; bar = 50 µm).
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Histologic examination results showed intraepidermal pustules with large numbers of acantholytic cells and neutrophils typical
of canine pemphigus foliaceus (Figure 3). Superficial epidermal fungal or bacterial organisms were not identified by using special stains (periodic acid-Schiff and
Gram's, respectively). Direct immunofluorescence testing revealed intercellular deposits of IgG (Figure 4) and IgM in the superficial layers of lesional epidermis.
Figure 4. Direct immunofluorescence revealed the presence of IgG (green) deposited in an intercellular pattern between epidermal
keratinocytes (blue nuclei) (IgG-fluorescein, DAPI nuclear counterstain).
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Serum antikeratinocyte IgG autoantibodies were not detectable by indirect immunofluorescence testing.
In this case, the historical use of ProMeris and the subsequent development of an acantholytic pustular dermatitis originating
from the application site in the absence of microorganisms were consistent with a diagnosis of generalized ProMeris-triggered
pemphigus foliaceus.
Follow-up
The patient returned for reevaluation 11 days after the initial presentation to NCSU. The dog was still receiving 0.8 mg/kg
prednisolone twice daily, and the dermatologic examination revealed only minor dry and peeling crusts with no new pustules
or erythema surrounding them. The patient was in good general health, and the prednisolone was tapered.
Over the next two weeks, the patient's ProMeris-triggered pemphigus foliaceus went into complete remission, its lameness resolved,
and the prednisolone was discontinued. The patient began to receive monthly topical flea and tick prevention, using either
Frontline Plus (Merial), Advantage (Bayer Animal Health), or, most recently, Vectra 3D (Summit VetPharm) on an alternate basis.
A recurrence of the skin lesions was not reported by the owner, and this dog's disease has remained in remission for more
than 27 months.
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