Pemphigus Complex (Wildfire): Epidemiology and Clinics
World Small Animal Veterinary Association World Congress Proceedings, 2009
Carlos Eduardo Larsson, DVM, MSc, PhD
Full Professor of the Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, Dermatology Service Av. Prof. Dr. Orlando Marques de Paiva, São Paulo

The Pemphigus complex (PC) belongs to a group of autoimmune illnesses, with increasing worldwide prevalence but in the last decades it has been particularly true in Brazil as well as in the bordering countries. It is recognized in dogs, cats and horses and the pathogenic specter is similar in both animal and human cases. In domestic carnivores at least five forms of clinical presentation are recognized, whereas in domestic herbivores three forms are described. The PC lesions are characterized by vesicles, bullae and pustules which formation are a consequence of acantholytic phenomenon represented by the dissociation of the epidermic cells, through the action of autoantibodies targeting the desmosomal antigens (desmogleins--DsG), composed of inter or transmembranae glycoproteins from the caderine's family. The antigen-antibody reaction destroys the linkage among epithelial cells, leading to a loss of superficial tension and a modification of the cell architecture--from polyhedral to round shape (acantholytic or Tzanck cell). When the cleavage process is high, with the involvement of the granular or the sub-corneal layer, it is classified as superficial pemphigus (foliaceus or erythematosus). Pemphigus foliaceous (PF) is undeniably the most common pemphigus variety worldwide. In human medicine, PF has two distinct forms: the classic or European described by Cazenave in 1844 (Cazenave Pemphigus) and the endemic (also called Brazilian Pemphigus, South American Pemphigus, endemic Pemphigus, wildfire, "fuego salvaje", "fogo selvagem") reported by Vieira in 1940. The latter is considered such an intriguing condition frequently mentioned in classical veterinary dermatology textbooks and considered a very serious illness during BC period (BC = before corticosteroids).

PF is a disease of familial occurrence and it has been reported in young adults and children living nearby water courses or rural areas as well as in individuals from aboriginal tribes localized in various Brazilian federative units (e.g., GO, DF, MT, MS, TO, MG, PR, SP, AM, RO, AC). It is probably triggered by environmental factors such as ultraviolet radiation and thiol, although it has never been described in domestic and wild animals from Brazilian fauna. The endemic form of Pemphigus stimulates the curiosity of Brazilian dermatologists mainly because of its possible occurrence in animals raised up in Brazilian conditions as well as in susceptible individuals, exposed to a huge number of arthropods, such as aboriginal individuals, farmers and workers living in miserable social, unhygienic conditions and in close contact with insects. The argument favouring the role of mosquitoes (e.g., "pium", "borrachudo", black fly), particularly from Simuliidae family (Simulium nigrimanun), has not been ruled out and the current hypothesis refers to an antigenic mimicry. According to it, Simulides and any other arthropods can prick a genetically predisposed susceptible individual and through its saliva, the antigens are inoculated and are responsible for the formation of antibodies that cross react with DsG (España, Mascaró, 2004; Sampaio & Rivitti, 2007).

It is important to mention a recent study (Sampaio & Rivitti, 2008) in which blood samples of human patients with infectious dermatoses (Hansen´s disease, paracoccidioidomycosis) who lived in endemic areas of PF were searched for serum antibodies anti-DsG. The same investigation was performed in patients affected by certain diseases transmitted by phlebotomidae (leishmaniasis), simullidae (onchocercosis), and triatomidae (Chagas disease) vectors. Positive reactions (i.e., presence of anti-DsG) was significantly higher in the patients affected by arthropod vector diseases (onchocercosis: 83%, leishmaniasis: 43%, Chagas disease: 58%) compared to patients in which the diseases was not depended of insects for the transmission chain (Hansen´s disease: 17%, paracoccidioidomycosis: 25%). These findings are found in a classic human dermatology textbook (Azulay et al., 2008; Sampaio & Rivitti, 2008) and stimulate further research regarding to the participation of some vectors (Simulinae, Phlebotominae, ticks) also in aethiopathogenesis of canine, feline and equine pemphigus. SCOTT et al. (2001) considered the existence of three forms of canine PF, the first being spontaneous (Chow-Chow and Akita). The second one would be mediated by drugs (e.g., potentiated sulfa, phenylbutazone) or immunogens (excessive use of several vaccines). Finally, the third form would be seen in animals with chronic dermatitis (allergic or bacterial) as a consequence of continuous exposure to either medication or bacterial superantigens (Werner, 1999). Wherever animal cases of PF are diagnosed, it is considered that such form shares great similarities with the classic variety.

Diagnosis of PF is not difficult to establish. The identification (e.g., age, breed) and anamnestic data (e.g., lesions distribution, types and distribution of primitive lesions and poor response to therapy with antibiotics), clinical findings from both physical and dermatological examination as well as a positive Nikolsky´s sign are the key elements for a correct diagnosis. The clinician should utilize complementary exams such as cytology (Tzanck smear) in which content of pustular lesions are searched for the presence of either isolated or grouped acantholytic cells (resembling dentated wheels or clock gear). The histopathological evaluation is essential and it should be performed from samples obtained by biopsy of the entire hemispheric lesion. Hematoxylin and eosin stained samples characteristically show cleavage and sub-corneal cracks (intramalpighian or intragranulous) containing acanthocytes (in 77% of the cases), neutrophils and eosinophils (16%), exocytosis and sometimes compromising the hair follicle (sterile follicle disease). In order to complement the diagnosis, one can perform immunohistopathology or serology (indirect immunofluorescence) using bovine esophagus or pads as substrate.

Treatment of PF involves the usage of steroids (mainly prednisone or prednisolone at the oral dose of 2-8mg/kg PO q 24 hs) which can be used solely (orthodox therapy) or in association with cytotoxic agents (azathioprine at the oral dose of 2mg/kg PO q 24 h) as an alternative therapy. Prognosis is reserved, with lethality ranging from 30 to 50% of the treated patients. Epidemiologically the PF does not show an evident sexual predisposition. However, an age predisposition seems to occur, with affected animals generally being 4 years or older. The PF is more frequent in pure breed animals. Clinical manifestations are predominantly seen in the integument and skin appendages (claws, nails or hooves) rarely involving mucosa or mucocutaneous junctions. Besides the severe pruritus (seem in 30% of the cases), pain, pyrexia, edematous areas, depression, lymphadenopathy and sanguineous dyscrasia are rare. In a retrospective study of dermatological casuistry from the HOVET/USP (Veterinary Teaching Hospital of the University of São Paulo), the analysis of two time periods (1986-1999 and 2000-2005) revealed an increase in the number of diagnosed PF cases on monthly basis, respectively from 0.23 to 0.7 cases/month. Aiming to characterize the disease in Brazil (São Paulo) we utilized resumed data collected from the period from 2000 to 2005, in which 43 cases of canine PF were diagnosed. Among those animals, 24 (56%) were female, 33 (76.7%) were pure breed (Cocker: 27%, Dachshund: 12.1%, Poodle: 12.1% and Akita: 9.1%). About 53% of the dogs were ranged 4 and 9 years of age (average age: 50 months) and the disease was generalized in 91% of the patients. The pruritus was present in 77% of the cases (intense: 42.4%, moderate: 36.3%, mild: 21.2%). Once suspicious diagnosis was established (based on clinical and lesion findings) and confirmed by histopathology in these 43 animals, therapy with prednisone was started and a successful response was seen in 23 (53.5%) dogs. The 20 dogs that did not show a significant response to steroid therapy alone received both prednisone/azathioprine (alternative protocol). Two (4.6%) animals showed a transient thrombocytopenia. From the 43 treated animals 38 were closely monitored during a period of 3-5 months and 37 (97.3%) had significant improvement (70 to 100%) with both protocols (Balda et al., 2008).


References are available upon request.

Speaker Information
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Carlos Eduardo Larsson, DVM, MSc, PhD
Faculdade de Medicina Veterinária e Zootecnia
Universidade de São Paulo
São Paulo, Brazil

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