17 Pemphigus foliaceus in a cat
Pemphigus foliaceus is an uncommon, sterile pustular, autoimmune skin disease that is recognized in both dogs and cats. The pustules quickly rupture, resulting in the formation of extensive crusting of affected areas. The degree of crusting is one of the diagnostic features of this disease. The definitive diagnosis is confirmed by cytology and histopathological examination.
Typically, pemphigus foliaceus presents with a history of crusting skin lesions that most commonly start over the pinnae and face, with later involvement of the trunk and limbs. Paronychia is a common finding in cats. Pruritus may be absent to severe, and many cases show intermittent depression, pyrexia and anorexia. Quite frequently, when questioned, owners may have recognized a waxing and waning of the symptoms over time.
Crusting is caused by leakage of pus, serum or blood onto the skin surface. In this case the colour of the crust was not consistent with haemorrhage but suggested a purulent discharge. One possible origin of such crusts is from a pustular skin disease.
The prognosis for feline and canine pemphigus foliaceus is very variable. Mildly affected cases with localized lesions may respond to topical medications. At the other end of the spectrum, there are very severe cases that may be refractory to therapy or that may develop life-threatening side-effects to treatment. In young animals, permanent resolution may follow successful medical therapy; in other cases, ongoing therapy is required to prevent recrudescence.
Pemphigus foliaceus is currently considered a heterogeneous autoimmune skin disease, resulting from the formation of predominantly IgG1 and IgG4 autoantibodies that target the intercellular spaces of the stratum spinosum and stratum granulosum of the epidermis. The precise target(s) (autoantigens) of these antibodies remain(s) unclear. There have been no studies reporting the nature of the specific autoantigen in cats, but a considerable amount of work has been done in looking for the autoantigen in canine pemphigus foliaceus. It was originally thought that the major autoantigen was desmoglein-1, a component of the desmosomes, which are responsible for keratinocyte–keratinocyte adhesion in the epidermis of the skin and hair follicles, but recent work has shown that this is an antigen of minor importance in canine pemphigus foliaceus, highlighting the heterogeneous nature of this disease.
Pustule formation: The exact mechanism of pustule formation in association with antibody formation is complex and incompletely elucidated. However, antibody binding to desmosomal structures leads to the release of plasminogen by keratinocytes that results in activation of plasmin, a protease that destroys desmosomal structures, leading to acantholysis and the separation of keratinocytes in the stratum spinosum. The clefts thus formed are filled by neutrophils migrating into the epidermis from the circulation to form pustules. Acantholytic keratinocytes, cells that have become detached from the stratum spinosum as a result of the acantholytic process, are also present within the pustules. These cells are nucleated, as opposed to the fully differentiated cells of the stratum corneum that have lost their nuclei. They tend to have a rounded appearance and have basophilic staining characteristics. The cytological finding of acantholytic keratinocytes combined with a neutrophilic infiltrate is consistent with pemphigus foliaceus, but may also be found in cases of bacterial pyoderma and also dermatophytosis, particularly in cases of infection with Trichophyton spp.
Drug induced: Most cases of pemphigus foliaceus in both cats and dogs appear spontaneously. However, a subset of cases may be drug induced and, in these cases, the disease should resolve when the drug is discontinued. Drug-related pemphigus foliaceus has been reported following administration of cefalexin and trimethoprim-potentiated sulphonamides in dogs, and ampicillin and methimazole in cats.
Chronic skin disease: Anecdotally, dermatologists report cases of canine pemphigus foliaceus that occur in association with a history of chronic skin disease. Typically, these cases have a history of chronic inflammatory, pruritic skin disease and then suddenly develop a more severe disease associated with pustules and crusting, diagnosed as pemphigus foliaceus. Whether there is a cause and effect association with the chronic skin disease is not clear. There is the possibility that some of these cases may be a cutaneous drug reaction associated with drugs used to treat the chronic skin disease.
Sunlight: There is some evidence that sunlight exposure may be a triggering factor for pemphigus foliaceus, particularly in lesions affecting the face. Some experimental work has found that UVB exposure of non-lesional skin from a dog with facial pemphigus foliaceus led to acantholysis.