Cornell Feline Health Center Veterinary News Spring 1983

Autonomic Polyganglionopathy: A New Clinical Entity of Cats Jeffrey E. Barlough, D.V.M. and Fredric W. Scott, D.V.M., Ph.D.

Since February 1982 numerous reports of an have developed dryness and reddening of unusual, new disease entity of cats have the oral mucosa and dry crusting of the appeared in the British veterinary litera­ external nares. Mucopurulent ocular ture.1-11 xhe basic underlying lesion and nasal discharges may develop fol­ produces a functional disturbance of the lowing secondary bacterial infection. autonomic nervous system, with associated clinical signs. No specific etiology has 3. Megaesophagus. In some cases, gagging yet been demonstrated, nor has any and swallowing reflex deficits have specific treatment regimen been uniformly been noticed initially. These are successful. The purpose of this brief overshadowed in many animals by chronic report is to acquaint practitioners in the regurgitation which can be shown by United States and in other countries with contrast radiography to be associated what has come to be known over the past with either a localized or generalized year as the "Key-Gaskell Syndrome," or megaesophagus. autonomic polyganglionopathy (APG). 4. Bradycardia. The heart rate in cats Most cases of APG have occurred in with APG frequently ranges from 90 to young adult, domestic shorthair cats. 120 beat s/mi nut e. ^ This sign is prob­ Onset of signs can be variable, from a few ably reflective of sympathetic nervous hours to gradual development of signs over system involvement. a period of weeks. In some cases, the syndrome commences as a mild upper respi­ Associated generalized signs of APG ratory condition, with transient fever and include anorexia, depression, weight loss, diarrhea. The major clinical signs which and constipation. In some cats there may have been widely observed include: be additional neurologic abnormalities, including fecal or urinary incontinence, 1. Persistent pupillary dilatation. This bladder atony, mild hindlimb ataxia, or sign may not be noticed initially due placing reflex deficits. In most cases to bilateral elevation of the nictita­ hematologic examination, clinical chem­ ting membranes. Dilatation is usually istry profiles, and urinalysis are bilateral and nonresponsive to light, normal. Virus isolation attempts have but sight does not appear to be been unsuccessful to date. impaired. In a small number of cases, dilatation has been unilateral and in Most reports of APG have occurred as at least two cases has been absent. single isolated cases, although in a few instances more than one cat in a household 2. Decreased tear production and dryness has been affected. There is one report of of mucous membranes. Most affected APG in which 2 kittens from the same cats have demonstrated a decrease in litter were affected.10 There have been tear production (Schirmer test), and (Continued on page 8.) 2

Feline Chronic Progressive Polyarthritis: A Brief Review James W. Crissman, D.V.M.

Feline chronic progressive polyarthritis gene products. Third, the HLA-B27 type (FCPP) is an uncommon disease which has may have a different distribution of been diagnosed exclusively in castrated or tissue receptors for infectious agents. intact adult, male cats. The syndrome has been recently well defined by Pedersen^ as FCPP has the same sex predilection and a specific, though dimorphic, clinical a strong association with FeSFV and FeLV. entity. Though the etiology is complex, The pathologic similarities in the disease the disease is considered to be immunolog- are also striking, tempting one to draw ically mediated. Its t'wo forms resemble conclusions; however nothing is known two diseases of man: rheumatoid and about feline histocompatibility types. Reiter's arthritises. Additionally, the viral agents associated with FCPP should be contrasted with the Pathogenes is bacterial or ureaplasmal agents associated with Reiter's disease, and it should be Pedersen found evidence of feline syncy­ noted that the temporal association in tial forming virus (FeSFV) infection in FCPP between viral infection and onset of 18/18 cats, either by serology or by disease is unknown. direct viral isolation. Sixty percent of the cats were also positive for feline Clinical Features leukemia virus (FeLV). Both of these values represent significant deviations Male cats generally present with painful, from the infection rates expected in this group of cats; however several efforts to reproduce the disease were unsuccessful. Cornell Feline Health Center The pathogenesis of FCPP may be similar to Reiter's arthritis in its multifactor­ Veterinary News ial nature. In this latter disease there is a marked preponderence of males A publication for veterinary professionals involved, a disproportionate share of whom carry the HLA-B27 histocompatability type. While the joints are sterile, their The ultimate purpose of the Cornell Feline Health Center is to improve the health of cats everywhere, by developing methods to disease is preceded by one of several prevent or cure feline diseases, and by providing continuing educa­ infectious diseases; thus the designation tion to veterinarians and cat owners. All contributions are tax- deductible. of Reiter's disease as "reactive arthri­ tis." Director: Fredric W. Scott, D.V.M., Ph.D. Asst. Director-Public Affairs: Edna H. Federer Editor: Joyce Tumbelston There are several hypotheses concerning Secretary: Sheryl A. Bronger Special Consultant: Leo A. Wuori, D.V.M. the mechanism of interaction of these factors. First, HLA-B27 genes are linked ®1983 by the Cornell Feline Health Center, Cornell University, College of Veterinary to immune response genes, which may Medicine, Ithaca, NY 14853. All rights express an aberrant response to the infec­ reserved. Permission to reprint selected portions must be obtained in writing. Cornell tion. Second, there may be immunologic University is an equal opportunity, affirma­ cross-reaction by antibodies directed at tive action educator and employer. exogenous infectious agents with HLA-B27 3

symmetrical polyarthritis, with the sever­ form of the disease has been reported est lesions found in the most distal limb primarily in older cats and is differenti­ joints. The frequency and severity of ated by the very severe, marginal subchon­ lesions lessen in the more proximal joints dral joint erosions, which result in joint of affected limbs. Lameness, soft tissue instability and eventual deformation. swelling and hyperesthesia of the limbs This latter "rheumatoid form" is slower in are found. Lymph nodes are generally onset and clinical course than the more markedly enlarged. In the initial stage common form. In either syndrome, lymph of the disease, fever and malaise occur. node hyperplasia may be so exuberant that In addition, there is intermittent anorex­ a mistaken diagnosis of neoplasia may be ia and often cachexia. made.

Radiology Treatment

The skeletal abnormalities are usually Various regimens of immunosuppressive very evident in radiographs. Periartic­ agents have been attempted with only poor ular erosions, coarse trabecular patterns to fair results. Glucocorticoids may in portions of the long bones adjacent to alleviate some clinical signs and slow the affected joints, and periosteal new bone progression of the disease. Temporary formation are seen in the more common form remissions have been gained with combina­ of the disease. In the rheumatoid form, tion therapy using prednisolone, azathio- subchondral cysts may be seen, as well as prine and cyclophosphamide; however, the very severe erosions and the luxation severe, unwanted side effects are very of joints. common.

Clinical Pathology Summary

A leukocytosis with mature neutrophilia is FCPP is a severe inflammatory disease of the common hemogram. However, this find­ male cats warranting a poor long-term ing has been inconsistent, as several of prognosis. It should be differentiated the cats in Pedersen's study show absolute from degenerative joint disease and other lymphocytosis or, conversely, leukocyte causes of lameness in the cat including counts in the low normal range. The degenerative joint disease, infectious acute-phase reactant proteins, gamma-2- arthritis due to bacte'rial or mycoplasmal globulin and plasma fibrinogen, were agents, trauma, and "transient febrile generally elevated. In a case^ presented limping syndrome of kittens" caused by to us and in most of Pedersen's cats, calicivirus, as recently reported by joint fluid was hypercellular with most of Pedersen et al.3 the cells being neutrophils.

References Pathology ^Pedersen NC, Pool RR, O'Brien T: Feline chronic pro­ gressive polyarthritis. Am J Vet Res 41:522-535, 1980. The most common form of the disease, seen ^Moise NS, Crissman JW: Chronic progressive polyarthri­ in 17 of 20 of Pedersen's cases and the tis in a cat. J Am An Hosp Assoc 18:965-969, 1982. case we reported, resembles Reiter's ■^Pedersen NC, Laliberte L, Ekman S: A Transient Febrile arthritis. This form is characterized by "Limping" Syndrome of Kittens Caused by Two Different periosteal reactive bone formation and 8trains of Feline Calicivirus. Fel Prac 13:26-35, 1983. osteopenia surrounding the inflamed joints. This may progress, producing James W. Crissman (MSU '77) is working moderate periarticular bone erosion, toward a Ph.D. in Veterinary Pathology at pannus formation, collapse of the joint Cornell. The subject of his research is space and, finally, fibrous amylosis of "Arthritis in the Cat due to Mycoplasma the joint. The second, or rheumatoid, gatae." Cornell Feline Health Center Veterinary News 4

Recommendations for Prevention and Treatment of Kitten Mortality Complex Cheryl A. Stoddart, B.S.

Yearly surveys conducted by the Cornell atresia ani, umbilical hernias, kittens Feline Health Center in conjunction with with flat chests, and so-called "swimmer" the Research Committee of the Cat Fanciers kittens. Association (CFA) from 1975 to 1980 revealed that kitten mortality was a seri­ Kitten mortality is usually exhibited ous problem in many catteries throughout by the "fading kitten syndrome." The kit­ the United States. Over the 6-year tens either are born weak and die within a period, a total of 9,517 kittens born in few hours or seem healthy and live for 2,309 litters from 28 breeds was surveyed, days, weeks, or even months but then 9.3% of which were stillborn. Of the become depressed and anorectic, eventually 8,630 kittens born alive, 5.8% died within dying of starvation or secondary bacterial 24 hours of birth, 2.8% died the second infections. Perhaps the most dramatic day, 13.2% had died by the first week, and expression of kitten mortality is in acute 24.2% failed to reach one year of age. congestive cardiomyopathy. These kittens Stillbirths and deaths by one year of age suddenly are unable to breathe, become considered together resulted in a total cyanotic, and die within a few hours. mortality rate of 31.1% for those kittens Postmortem and histologic examinations surveyed over the 6-year period. reveal hugely dilated and thin-walled hearts with acute muscle fiber degenera­ During 1977 and 1978, many cat breeders tion, usually accompanied by fluid-filled and their veterinarians consulted the thoracic cavities and lungs. A small Cornell Feline Health Center, reporting percentage of kitten mortality is due to alarming reproductive failure and high feline infectious peritonitis (FIP), kitten mortality. These and other second­ usually the granulomatous (dry) form as hand reports were strikingly similar. opposed to the more typical effusive (wet) Everyone's story was the same: convincing form. evidence that a specific disease complex, termed kitten mortality complex (KMC), was In the adult cats, endometritis and occurring throughout the country. Kitten pyometritis are both common and highly mortality rates in certain extensively consistent findings in the catteries studied catteries ranged from 40-80% experiencing KMC. The respiratory disease during peak periods of kitten loss. It is usually chronic and mild, involving the was apparently a new disease whose etiol­ upper respiratory tract with sneezing as ogy was and still is unknown. its most common symptom. Watery ocular and nasal discharges may also occur, but KMC is characterized by 3 main prob­ the cat seldom becomes seriously ill. lems: reproductive failure, kitten Many queens (up to 40% in some catteries) mortality, and various diseases in the have vaginal discharges; further examina­ adult. Reproductive failures include tion usually reveals endometritis or pyo­ repeat breeders, fetal resorptions between metra. Other reported problems include 4 and 6 weeks of gestation, abortion (usu­ adults and older kittens with intermittent ally during the last 2 weeks), still­ and usually low grade fevers, acute births, and congenital malformations congestive cardiomyopathy, and other These malformations have included skull cardiovascular diseases. defects, open-top fontanelles, cleft palates, "open stomachs," heart defects, Although the exact causes of KMC are 5

not known, many feline viruses can cause be given earlier, perhaps at 4 or 6 reproductive failure, fetal malformations, weeks of age. Another possibility is neonatal kitten death, and various other to vaccinate the queen before breeding diseases in the adult. These include to boost her immune response. feline viral rhinotracheitis (FVR), feline Modified-live vaccines should never be calicivirus (FCV), feline panleukopenia given to pregnant queens. Vaccination (FPL), and feline leukemia virus (FeLV). against pneumonitis, a chlamydial Many catteries experiencing KMC have cats infection, should also be considered which are FIP antibody-positive, and for cats with respiratory problems. therefore FIP virus (FIPV) has been incriminated as an etiologic agent of KMC. 2. FeLV: Any cattery having KMC problems At the present time, however, we do not should be tested for FeLV. If cats completely understand the relationship are found to be positive, a proper between FIPV and kitten mortality and course of action must quickly be there is no conclusive evidence that FIPV implemented to either isolate or is a main- cause of KMC. It is important eliminate those positive cats. to note that the great majority of catter­ ies have FIP antibody-positive cats, both 3. Uterine/Vaginal Bacterial Infections. those which are experiencing KMC and those which have had no problems whatsoever. 4. Toxoplasmosis.

Since the causes of KMC are not pres­ 5. Fleas and Gastrointestinal Parasites. ently known, there are no definitive methods of treatment. In many catteries, Exposure to Infectious Agents the problems have disappeared as fast as they appeared, so this may be the only 6. Cat Shows: Breeders must understand consolation for cat breeders with affected the risks involved in showing their catteries. For the veterinarian confront­ cats. Cats are particularly suscepti­ ing KMC and seeking some advice, there are ble to infectious agents when grouped three main areas to explore: 1) diagnosis together in large numbers, especially and treatment of infections, 2) restric­ when there is much stress involved. tion of cattery cats from exposure to Infectious agents can easily be trans­ infectious agents, and 3) alleviation of mitted from to cat to cat via aerosols stress. The following items might be and contaminated show cages. A cat seriously considered in attempting to just returning to the cattery from a treat KMC. show is very Likely to spread these agents to the rest of the cats and Infect ions should be quarantined for 1 to 2 weeks, perhaps longer if feasible. 1. Proper vaccination regimen: Kittens should be vaccinated against FVR, FCV, 7. Introducing New Cats: New cats coming and FPL twice, preferably at 8 and into the cattery either as acquisi­ 12-16 weeks of age to provide full tions or for stud service are another protective immunity. The respiratory potential source of infectious agents viruses can still be shed by a fully and should be restricted from full run vaccinated asymptomatic queen, which of the cattery. These cats should can then infect susceptible kittens. definitely be healthy, free of respir­ If the queen has little antibody atory disease, and tested for FeLV against these viruses, the kittens' before admission into the cattery. maternal immunity will wane sooner and they may be unprotected before 8 8. Outdoor Animals: Animals which have weeks. If respiratory disease is a free run of the outdoors should not be problem, the first vaccination should allowed to mingle with cattery cats. 6

9. Isolation of Queens: Pregnant queens growth and maintenance are far better and queens with nursing kittens should balanced nutritionally than most home­ be completely isolated from other made diets. Some foods can certainly cattery cats. It is also wise for the be added to the diet, but the mainstay breeder to wash hands and don a clean (80-85%) should be a good commercial coat or apron before coming into product. contact with the queen and kittens. 16. Inbreeding: The effects of inbreeding 10. Separation of Kittens: The breeder can be devastating to cats and must be may try taking kittens away from the discontinued if problems such as KMC queen shortly after nursing and hand appear in litters from very close rearing them in isolation to prevent matings. Even though the breeder is them from contracting an infection inbreeding in order to produce that from the queen. This is particularly certain "look" that will be successful helpful in the case of respiratory in the show ring, they must understand problems. the dire consequences of extensive inbreeding. 11. Cattery Cleanliness: The general cleanliness of the cattery must be Although some of these items may be kept optimal. Litter should be unpalatable to the breeder, impossible to changed frequently and animal pens, implement, or simply ineffective, they floors, litter pans, food dishes, should be examined and discussed. Many of etc., should be regularly disinfected the results will depend on the willingness (Clorox diluted at 1:32 is ideal). of the breeder to confront and deal with this frustrating disease. All dead kit­ Stress tens should be refrigerated and autopsied as soon as possible. Tissues should be 12. Rest Queens Between Litters: Queens submitted for histopathology, particularly should not give birth more than twice if lesions are present. Particular atten­ a year. tion should be paid to the size and appearance of the heart since cardiomyo­ 13. Cat Shows: Cats are particularly pathy is often easily overlooked in very sensitive to stress and catteries in young kittens. the throes of KMC should definitely avoid the stress implicit in shows. The Cornell Feline Health Center is interested in working with veterinarians 14. Toxic Agents: Cats are also very and their clients who are confronting KMC sensitive to chemicals and can be and wish to have more extensive work per­ adversely affected by toxic agents in formed. Various isolations for infectious their environment. Disinfectants agents can be done free of charge on an containing phenol should not be used individual basis if there is sufficient and cats should not be allowed to eat interest on the part of the veterinarian house plants. Although there is no and client. Please do not hesitate to evidence that they can be harmful to contact us for more information, to give cats, airborne agents like cigarette your additional suggestions, or to report smoke and formaldehyde-based blown on the results of these suggestions. insulation should be considered since they have been implicated in human Cheryl Stoddart has been studying feline health problems. Griseofulvin is a coronaviruses and their possible relation­ proven teratogen in cats. ship to kitten mortality complex since 1979. She is currently completing her 15. Nutrition: Commercial cat foods M.S. and plans to continue at Cornell for formulated along NRC guidelines for her Ph.D. in Veterinary Virology. 7

CATS Performance Boosts Camuti Fund

The Cornell Feline Health Center thanks every renowned photographer Claudio Edinger. Mr. person who joined us for the special benefit and Mrs. Ellice McDonald, Jr., of Montchanin, performance of Broadway's "CATS" on March 5. Delaware, are to be commended for their very Proceeds have been added to the fund for the generous contribution, although they were not Feline Consultation and Diagnostic Service in able to attend. memory of Dr. Louis J. Camuti, a charter We are also grateful for the many veteri­ member of our Feline Advisory Council and a narians who came out, showing they stand with renowned New York City feline practitioner for us in the effort to establish the Feline 60 years. It was a fantastic show, made all Consultation and Diagnostic Service. This has the more special by the presence of Mrs. Alex­ really boosted our determination to obtain the andra Camuti, several of Dr. Camuti's family remaining funds needed to provide the first members and dearest friends, and a sizable full-time service to benefit cats, veterinar­ contingent of veterinarians from the New York- ians, and cat owners nationwide. Thanks to New Jersey-Connect icut area and beyond. ail of you for your support. The evening began with a pre-theater dinner at Gallagher's Restaurant graciously hosted by Dr. and Mrs. Lewis Berman of New York City. Feline Health Seminar in June We are indebted to Lew and Amanda not only for Our third annual feline health seminar, their hospitality but also for the immense June 22-24, is designed for serious cat help they provided in planning and publicizing owners and shelter personnel, but will the entire theater event. also be informative for veterinarians. The show itself was a lively, out-of-this- Topics include feline reproductive physi­ world experience. Dancers dressed in leotards ology and disorders, embryology, neonatal and fur, made up to look like so many differ­ care, genetics, neurological diseases, ent cats, leaped and roamed throughout the infectious diseases, zoonoses, FIP, newer audience. Twice during the show, a large, diseases, and design of animal shelters orange cat came down and bestowed a big kiss and catteries. Faculty participants will on the guest of honor, Mrs. Camuti. Ruth include Drs. Fredric Scott, Robert Kirk, McCarthy (wife of John B. McCarthy, the newly Alexander de Lahunta, Howard Evans, Drew inducted AAHA president) appeared absolutely Noden, Dorothy Holmes, Jeffrey Barlough, delighted when one of the hairy creatures led and Donald Lein, among others. her onto the stage, whirled her around, and Of particular interest to veterinarians gallantly escorted her back to her seat. will be a section on Computerized Diagnos­ Several CFHC staff members were especially tic Techniques in Small Animal Medicine, privileged to attend a reunion of the Camuti the trend of the future. Dr. Roy Pollock family afterwards at Luchow's Restaurant. The will show how computers can not only genuine warmth and friendliness of those down- modernize your practice, but deliver to-earth people made the evening even more perpetual continuing education as well. memorable. Twenty hours (2 units) of continuing Several individuals gave personal assist­ education credit will be awarded. The fee ance without which the benefit would not have for the 3-day program is only $150. For been nearly as successful. In addition to the more information or registration, contact Bermans, we would like to acknowledge the Linda A. Ritzier at the Office of Continu­ valuable contribution of time and effort made ing Education, N.Y.S. College of Veteri­ by Ms. Sina Essary, vdio not only brought a nary Medicine, Cornell University, Ithaca, large group of guests, but also helped with New York 14853, telephone (607) 256-5454, publicity and arranged for the services of the ext. 2200. Cornell Feline Health Center

Veterinary News 8

A P G (Continued from page 1.) practitioners in other countries regarding no associated clinical signs in nonfeline possible cases of APG would be greatly contact animals or in the owners of appreciated in order to further investiga­ affected cats. tion into the etiology and pathogenesis of The prognosis for survival is dependent APG. upon the degree of esophageal involve­ References ment. ^ Moderate or severe impairment of lBedford PGC: A new disease in the cat. Vet Rec 111:473, 1982. esophageal motility is an unfavorable ^Gaskell CJ, Rochlitz I: Key-Gaskell syndrome. Vet Rec 111: 564, sign, and animals so affected generally do 1982. not thrive. Cats with less severe impair­ ^Griffiths IR, Nash AS, Sharp NJH: The Key-Gaskell syndrome: The ment can recover, although there may be current situation. Vet Rec 111:532-533, 1982. residual neurologic signs, such as persis­ ^Janz R: The Key-Gaskell syndrome. Vet Rec 111:401, 1982. tence of pupillary dilatation. ^Key TJA, Gaskell CJ: Puzzling syndrome in cats associated with pupillary dilatation. Vet Rec 110:160, 1982. Pathologic examination of cats with APG ^Kock R: The Key-Gaskell syndrome. Vet Rec 111:469, 1982. has failed to reveal gross anatomic 7Madeiros CA: Key-Gaskell syndrome. Vet Rec 111:540, 1982. changes.^However, histologic abnor­ ®Nash AS, Griffiths IR, Sharp NJH: The Key-Gaskell syndrome - an malities consisting of degenerative autonomic polyganglionopathy. Vet Rec 111:307-308, 1982. changes in the peripheral and central ^Nash AS, Griffiths IR, Sharp NJH: Key-Gaskell syndrome. Vet Rec 111:564, 1982. nervous systems have been found.^>8 lOpower JC, Temple JD: Key-Gaskell syndrome. Vet Rec 111:540, Lesions are most severe in the autonomic 1982. ganglia, and there may also be lesions in **Tutt JB: The Key-Gaskell syndrome. Vet Rec 111:353, 1982. many autonomic nerves. Ultrastructural studies have demonstrated an underlying Jeffrey E. Barlough. (Davis '79) has been disruption of protein synthesis within with the Cornell Feline Health Center affected neurons.^ since 1980, studying the feline immune There is currently no specific therapy response to feline infectious peritonitis for APG, and treatment is symptomatic and (FIP). He plans to complete his Ph.D. in supportive. Persistent pupillary dilata­ Veterinary Virology next year. tion has responded to ophthalmic prepara­ tions such as pilocarpine*»^>6,7,8 or Fredric W. Scott (Cornell ’62; Ph.D., physostigmine^»^ As of this writing Cornell ’68), Director of the Cornell (February 1983) cases of this unusual Feline Health Center since its inception disease entity appear to be confined to in 1974, is also a Professor of Veterinary Great Britain.^ However, information from Virology.

Cornell Feline Health Center Cornell University College of Veterinary Medicine Ithaca, New York 14853