Drugs
Drugs can influence the development of pemphigus foliaceus.19 Some drugs directly induce acantholysis (drug-induced pemphigus foliaceus). Drugs can activate proteolytic enzymes in the
skin that then disrupt desmosomes and result in biochemical acantholysis. Drugs can also stimulate the development of autoantibodies
against desmosomes, resulting in immunologic acantholysis.20 Drug-triggered pemphigus foliaceus occurs in patients predisposed to pemphigus foliaceus. The combination of the drug and
other patient factors then triggers a flare-up of pemphigus foliaceus.19
Human drug-induced pemphigus foliaceus is usually associated with exposure to medications with chemical structures that can
contribute to the activation of proteolytic enzymes in the skin. These drugs include thiol compounds containing –SH, or sulfhydryl,
groups (e.g. penicillamine), medications that can undergo metabolic changes and form active –SH groups (e.g. penicillins, cephalosporins), or medications that contain active amide groups (e.g. enalapril).20 In dogs and cats, pemphigus foliaceus has been suspected to be associated with a variety of medications such as cimetidine,21 cephalexin,22 amoxicillin and clavulanic acid,23 ampicillin,24 and trimethoprim-sulfonamide combinations.25
Many patients with newly diagnosed pemphigus foliaceus have a history of exposure to multiple medications. If a patient has
either drug-induced or drug-triggered pemphigus foliaceus, discontinuing the medication could help manage the pemphigus foliaceus
or cause the pemphigus foliaceus to go into remission. It is difficult, though, to prove an association between any drug and
the pemphigus foliaceus. Drug rechallenge would definitively confirm drug-induced pemphigus foliaceus, but since this could
harm the patient, we do not recommend drug rechallenge in cutaneous drug reactions. Observing apoptotic keratinocytes histologically
cannot be used as a marker for a drug reaction since apoptotic keratinocytes may be seen in dogs with pemphigus foliaceus.26
If drug-related pemphigus foliaceus is suspected, review the patient's drug history carefully. Cutaneous drug reactions typically
develop more than seven days after the first administration of a drug. If the patient has been previously exposed to the drug,
reactions are quick and occur within 24 hours of drug re-exposure.27
More recently, we are aware of reports that administration of a topical spot-on product containing metaflumizone and amitraz
(ProMeris—Fort Dodge Animal Health) has been associated with pemphigus foliaceus in dogs. The mechanism for this reaction
is currently unknown but is an area of active research at one of our laboratories (T.O.).
Other causes
A variety of other factors are possible triggers for human pemphigus foliaceus. Fogo selvagem, a form of human pemphigus foliaceus
endemic to some rural areas of Brazil, is likely due to a combination of environmental factors and possibly the patient's
genetic susceptibility.28,29 Nutrition (thiol-containing foods such as garlic and onions30,31 ) and infection32 have also been associated with some cases of human pemphigus foliaceus. It is unknown if any of these factors, especially
diet, are triggers in canine and feline pemphigus foliaceus.
1. A pustule just caudal to the planum nasale of a dog; alopecia and erythema are also present in the dorsal nasal region.
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Canine pemphigus foliaceus can be associated with a history of chronic skin disease such as allergies,33 although no studies have definitively proved this link. Canine pemphigus foliaceus has also been reported in patients with
other conditions such as hypothyroidism,34 leishmaniasis,35 thymoma,36 and systemic lupus erythematosus.37 Pemphigus foliaceus may be present in these patients through coincidence, or pemphigus foliaceus may be occurring in these
patients through the induction of desmosome autoantibodies triggered by these systemic conditions.
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