Volume 53 | Issue 1 Article 4 1991 Pemphigus: An Autoimmune Complex in Dogs and Cats A. K. Takayama Iowa State University D. S. Busch Follow this and additional works at: https://lib.dr.iastate.edu/iowastate_veterinarian Part of the Immune System Diseases Commons, and the Small or Companion Animal Medicine Commons Recommended Citation Takayama, A. K. and Busch, D. S. (1991) "Pemphigus: An Autoimmune Complex in Dogs and Cats," Iowa State University Veterinarian: Vol. 53 : Iss. 1 , Article 4. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol53/iss1/4 This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Pemphigus: An Autoimmune Complex in Dogs and Cats A. K. Takayama, BBA, BS, DVM* D.S. Busch, DVM** Introduction sponse to the host cell antigen by T helper cells, (5) autoantigen modification -- modification of a The nan1e Pemphigus, derived 'from the Greek host cell antigen that renders it autoantigenic, (6) word for blister, describes a group of vesiculobull­ cross-reacting antigens -- sharing of determi­ ous diseases of the skin of dogs, cats, and hu­ nants between exogenous antigens and host cell n1ans. The pemphigus complex is an autoim­ antigens."5 In addition to these, Muller et al mune disease of the skin characterized by lesions proposes an inappropriate interleukin 2 produc­ ranging from vesiculobullous/pustular to erosive/ tion and an idiotype-anti-idiotype imbalance as ulcerative. Lesions of pemphigus are due to the well as sexual dimorphism ("with female sex binding of autoantibody to an antigen in the epi­ hormones tending to accelerate immune re­ dermal cell membrane or the glycocalyx causing sponses and male sex hormones tending to sup­ a release of an enzyme(s) resulting in disruption press responses") as mechanisms of autoim­ of intercellular attachn1ents and acantholysis. 1 mune diseases.2 The pemphigus complex is a Pemphigus produces lesions that are restricted group of disorders characterized by an inappro­ to the epidermis. More speci"fically, these lesions priate immune response. are suprabasilar, each variant being character­ Although the exact mechanism of lesions ized by location within the epidermal layer and by produced in pemphigus is not fully understood, location of lesions on the body. Muller et al have proposed a pathomechanism for lesion production which includes: "(1) the binding Pathogenesis of pemphigus antibody at the glycocalyx of ker­ atinocytes, (2) internalization of the pemphigus There are several mechanisms proposed for antibody and fusion of the antibody with intracel­ the breakdown or loss of control in self-tolerance. lular Iysosomes, and (3) resultant activation and Gorman and Werner have proposed the following release of a keratinocyte proteolytic enzyme mechanisms of autoimmune disease: "(1) poly­ ("pempbigus acantholytic factor"), which diffuses clonal B cell activation -- B cell clones are stimu­ into extracellular space and hydrolyzes the glyco­ lated by a pathogen as well as autoreactive B cell calyx" resulting in "acantholysis and blister forma­ clones resulting in the production of autoantibod­ tion within the epidermis."2 The acantholysis in ies, (2) T suppressor cell bypass -- effective T cell pemphigus has been likened to a Type II hy­ suppression is bypassed when the presence of an persensitivity reaction. There seems to be a exogenous agent on a cell surface induces a controversy remaining over whether or not com­ response to the exogenous antigen and the cell plen1ent is involved in lesion production in pem­ surface antigen, (3) T suppressor cell dysfunc­ phigus. Muller et al2 believe that "pemphigus tion-- allows expansion of autoreactive B cell and antibody-induced acantholysis is not dependent T cell clones, (4) increased T helper cell function­ on complement or inflammatory cells." However, - increases recognition and induction of a re- Jordan et al state that "complement activation by pemphigus antibodies provides an additional *Dr. Takayama is a 1990 graduate of the College mechanism for loss of epidermal cell cohesion in of Veterinary Medicine. addition to the plasminogen-plasmin system."3 It **Dr. Busch, formerly a resident in Internal Medi­ has long been known that complement (espe­ cine in the College of Veterinary Medicine at Iowa cially C3) deposits are present in pemphigus State University, is in private practice in Baltimore, lesions as has been shown through immunofluo­ Maryland. rescence staining, but their role in lesion produc- Vol 53, No.1 15 lesion production is still not clear. Medleau et al ciency, diabetes, heavy metal poisonings, viral seemed to clear up the discrepancy best. She diseases (FeLV, feline rhinotracheitis, feline cal­ states that "complement does not appear to have icivirus), neoplasia, granuloma, pemphigus, and a primary role (in lesion production) because IgG lupus erythematosus. from C3-depleted serum can induce acantholysis in epidermal cell cultures, hO\NeVer, complement Pemphigus Vegetans may have a secondary role in that extracellular proteases released subsequent to pemphigus Pernphigus vegetans is believed to be a be­ binding may generate chemotactic fragments of nign variant of pemphigus vulgaris and has been 2 C3 or C5 which in turn could recruit polymor­ rarely reported in the dog. ,9 In humans, pem­ phonuclear granulocytes into the area."4 phigus vegetans is classified as either the Neu­ mann or the Hallopeau type. Clinically, the Neu­ Pemphigus Vulgaris mann type forms vesicles and bullae as in pem­ phigus vulgaris, but during the healing process Of the pernphigus complex, pemphigus vul­ the affected areas form verrucous vegetations. garis was first reported in 1975 and has been The Hallopeau type form pustules initially and recognized in dogs and cats. The disease does also have a papillomatous, proliferative healing not seem to have any age, breed, or sex predilec- response. 9 There are apparently no age, breed, tions. It is a vesiculobullous disease that quickly or sex predilections. Differentials for pernphigus develops into erosive/ulcerative lesions of the vegetans include: bacterial and fungal granulo­ skin, oral cavity, and mucocutaneous junctions. mas, Iymphoreticular neoplasia, mastocytoma, Muller et al2 report that "ninety percent of dogs and papilloma and fibropapilloma.2 cats with pemphigus vulgaris have oral lesions." Pemphigus vulgaris lesions, strictly limited to the Pemphigus Foliaceus skin, are rare.? In dogs, the cutaneous lesions are commonly found in the axillary and groin areas. Pemphigus foliaceus is considered the most Although this is a vesiculobullous disorder, ves­ cornmon form of pemphigus in the dog and cat. icles are very transient and fragile, thus the clinical There seems to be no sex predilection. The lesions appear as erosions and ulcers bordered disease seems to affect rrliddle-aged dogs and 2 by epidermal collarettes. ,6 The Nikolsky sign is according to a study done by Ihrke et ai, four characteristic of pemphigus and can be elicited by breeds of dogs were at a higher risk: Bearded applying finger pressure at the lateral aspect of an Collie, Akita, Newfoundland, and Schipperke. 10 erosion or to normal-appearing skin, which would Muller2adds Chow Chows, Doberman Pinschers, dislodge the epidermis from the dern1is thus cre­ and Dachshunds to the above list of breeds that ating a new erosion. This sign mayor may not be are apparently predisposed to pemphigus foli­ present and is not diagnostic fOr"pemphigus. The aceus. They often have footpad lesions charac­ disease may also have systemic effects in which terized by erythematous swelling at the pad mar­ anorexia, depression, and fever may be present. gins, cracking, and villous hypertrophy (villous In the dog, the list of differential diagnoses for hyperkeratosis or "hard pad").2,1o These footpad pemphigus vulgaris include: bullous pemphigoid, lesions often cause pain with resulting lameness. systemic lupus erythematosus, erythema rnulti­ Vesicles and bullae are transient and the animals forme, toxic epidermal necrolysis, drug eruption, are usually presented with pustules and erosions mycosis fungoides, Iymphoreticular neoplasia, bordered by epidermal collarettes. The epidermal candidiasis, and numerous causes of ulcerative collarettes with accompanying alopecia, scaling, stomatitis.2 and crusting usually start on the face, bridge of the In the cat, lesions of pemphigus vulgaris nose, and pinnae then gradually spread to the .con1monly affect the gums, !"ips, hard palate, and ventrum. As with the other variants of pemphigus nasal philtrum. 6 Vesicles and bullae are rarely (i.e. -- pemphigus vulgaris), pain and pruritus are seen, thus erosions and ulcers are the usual variable and anorexia, depression, and fever are clinical presentations. The list of differential diag­ seen in severely affected animals.2 noses for ulcerative stomatitis in the cat is quite Scaling and crusting are the most common extensive. According to Manning et al 8 the differ­ clinical signs in cases of pemphigus foliaceus entials include: recurrent necrotizing stomatitis, hence the origin of the name, "foliaceus", mean­ Vincent's stomatitis, renal disease, vitamin defi- ing leafy.10 Noxon and Myers reported a case of 16 Iowa State University Veterinarian 2 pemphigus foliaceus in two