Metaflumizone-amitraz (Promeris)-associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug-triggered pemphigus foliaceus : Promeris-associated pemphigus foliaceus

The mode of action of amitraz is thought to be its toxic effects on a receptor for a neuromodulator, octopamine. Resistance could arise from modifications of this receptor so that it would not be affected by amitraz. A putative octopamine receptor cDNA was cloned and sequenced from a cattle tick in Australia. However, when the sequence was compared between Australian strains of amitraz-susceptible and resistant ticks, no differences were detected. We have sequenced this putative octopamine receptor gene in tick strains from America. The American ticks have a sequence almost identical to that of the Australian ticks with no deletions or additions in the open reading frame. In a Brazilian strain and a Mexican strain that are very resistant to amitraz, there are two nucleotide substitutions that result in amino acids different from all the susceptible strains. Discovery of these mutations only in amitraz-resistant ticks provides the first evidence for the possibility of an altered pesticide target site as a mechanism of amitraz resistance in ticks.

Pemphigus is a severe autoimmune blistering skin disease. The two main forms of pemphigus, pemphigus vulgaris and pemphigus foliaceus, are primarily caused by autoantibodies against the desmosomal cadherins desmoglein 1 and desmoglein 3. The histopathological hallmark is the loss of cell adhesion between neighbouring keratinocytes, a phenomenon called acantholysis. Various underlying mechanisms of acantholysis have been described including apoptosis. The role of apoptosis in pemphigus pathogenesis is unclear at present and the focus of this review. While characteristic signs of apoptosis can be found in lesional patient skin these can be missing in very early lesions of macroscopically perilesional skin where acantholysis is detected by light microscopy. Under experimental conditions, activation of apoptotic signalling can be induced by pemphigus IgG as well as by pemphigus serum which contains large amounts of Fas ligand. Studies using caspase inhibitors which were effective to block acantholysis indicate that the apoptotic machinery contributes to cell dissociation. However, acantholysis can occur in the absence of apoptosis which demonstrates that apoptosis is not strictly required for skin blistering in pemphigus. Taken together, signalling events leading to apoptosis including activation of executioner caspases are not required but may participate in the cellular response to pemphigus autoantibodies leading to acantholysis.

In humans, the pemphigus denomination encompasses a group of autoimmune blistering skin diseases with intraepidermal separation resulting from cell-cell detachment by acantholysis. Entities are classified based on the level of blistering in the epidermis, and both superficial (pemphigus foliaceus, IgA pemphigus) and deep (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) variants are recognized. In domestic animals, subsets of pemphigus have been recognized since the mid-1970s, and the disease classification resembles that used for human patients. This article reviews up-to-date knowledge on the epidemiology, clinical signs, histopathology, immunopathology and treatment outcome of superficial pemphigus in domestic animals. Detailed information on canine, feline, equine and caprine pemphigus foliaceus, canine and feline pemphigus erythematosus and canine panepidermal pustular pemphigus is provided.