Perspectives in Biology and Medicine

CANINE PAIN SYNDROME IS A MODEL FOR THE STUDY OF KAWASAKI DISEASE JANE C. BURNS* PETERJ. FELSBURG,t HARRY WILSONj FRED S. ROSEN,§ and LAWRENCE T. GLICKMANt Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown cause that affects infants and young children [I]. It is characterized by intense inflammation of predominantly medium-sized muscular arteries [2]. The principal complication of the vasculitis is coronary artery damage , which can be detected in approximately 20 percent of patients [3]. Intravenous administration of large doses of gamma globulin reduces the signs of systemic inflammation and the prevalence of coronary artery abnormalities, although its mechanism of action is unknown [4]. Study of the pathogenesis of this disease and of its therapy has been hampered by (1) difficulty in obtaining affected arteries for study during the acute phase, (2) failure to elucidate the causative agent of KD, and (3) the absence of a suitable animal model. A recently described spontaneous vasculitis of young dogs, designated canine pain syndrome (CPS) [5, 6], shares many clinical, immunological, and pathological features with KD. We present here a comparison of the two syndromes and suggest ways in which CPS may be an appropriate model for the etiology, immunopathology, and effect of therapy in KD. Comparison ofEpidemiological and Clinical Features Both KD and CPS affect their respective hosts at a similarly young age. The peak incidence of KD is in the second year of life with a slight Supported in part by USPHS grants HL-01855, the Canine Research Fund of Purdue University School of Veterinary Medicine, and a gift from Smith Kline Laboratories. *Department of Pediatrics, University of California—San Diego School of Medicine, LaJoIIa, California 92093. !Department of Pathology, Purdue University School of Veterinary Medicine, West Lafayette, Indiana 47907. ^Department of Pathology, Children's Hospital, Denver, Colorado.§Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115.© 1991 by The University of Chicago. All rights reserved. 003 1 -5982/92/350 1-0745$0 1 .00 68 Jane C. Burns et al. ¦ Kawasaki Disease predominance of male patients [7]. Canine pain syndrome is observed between 3 months and 2 years of age (equivalent to 5-24 years in humans [8]), and both sexes are affected equally [5]. Kawasaki disease was first described in 1967 inJapanese children [9]. Although sporadic cases may have occurred in previous years [10, 11], the prevalence of the disorder dramatically increased during the 1960s and 1970s [7]; CPS also appears to be a disease with recently increased prevalence. In a survey of the spontaneous occurrence of CPS in the largest commercial beagle kennel in the United States (approximately 18,000 pups/year in 1989), we identified the syndrome in 96 dogs less than 18 months of age over a 10-year period (unpublished observations). Males and females were equally represented, and the coefficients of inbreeding and relatedness were not significantly different for CPS dogs compared to unaffected dogs in the same kennel. The true incidence of CPS is likely to be much higher since most dogs are sold by 6 months of age. The syndrome is often first diagnosed by veterinarians at pharmaceutical companies where the dogs are used for biomedical research. The incidence of CPS in other breeds and in the pet dog population is unknown, although many sporadic cases have been described [12—17]. Other epidemiological features shared by CPS and KD include the occurrence of epidemics and the lack of evidence to support individual-to-individual, germ-line, or vector-borne transmission. The clinical and laboratory similarities between the canine and human disease are striking (table 1). Both diseases begin with the sudden onset of fever in previously healthy individuals. In KD, the systemic inflammation is also manifested by rash, mucositis, swelling and erythema of the extremities, and cervical lymphadenopathy. Meningeal signs may be present, and evidence of inflammation is often found if the cerebrospinal fluid is sampled [18]. The coronary arteritis and myocarditis are usually clinically silent during the acute illness, although mycardial infarction , arrhythmia, and congestive heart failure may occur. In CPS, coronary artery vasculitis may also occur and is usually asymptomatic . The major clinical features are fever and pain with guarding and a characteristic hunched...