AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 88:389-400 (1992) Erosive Arthritis and Spondyloarthropathy in Old World Primates BRUCE M. ROTHSCHILD AND ROBERT J. WOODS Arthritis Center of Northeast Ohio, (B.M.R., R.J. W.) Youngstown, Ohio 44512; Northeast Ohio Universities College of Medicine, (B.M.R.) Rootstown, Ohio 44272; University of Akron, (B.M.R.)Akron, Ohio 44242; The Carnegie Museum, (B.M.R.) Pittsburgh, Pennsylvania 15213; Ohio State University, (R.J.W.) Columbus, Ohio 43210 KEY WORDS Skeletal pathology; Primate, Theropithecus, Papio, Cercopithecus, Macaca, Hylobates, Colobus, Presbytis ABSTRACT Presence of spine and sacroiliac involvement and the nature and distribution of the erosive lesions allow definitive diagnosis of spondyloarthropathy. Thus, spondyloarthropathy was identified in Theropithecus, Papio, Cercopithecus, Macaca, Colobus, Presbytis, and Hylobates. Only monarticular erosive disease was present in prosimians, precluding a diagnosis of spondyloarthropathy for that group. The distribution of erosive disease and axial joint involvement in 1,349 non-prosimian Old World primates is quite characteristic of that noted in human psoriatic arthritis. While Reiter’s syndrome must also be considered, the histologic appearance of skin lesions in Macaca is characteristic of psoriasis. Evidence of spondyloarthropathy abounds in the literature of primate skeletal disease. Environmentally based contagions may be important in the pathophysiology of spondyloarthropathy. The wide geographic distribution of the phenomena in monkeys suggests a “panendemic,”with limited individual susceptibility (compared to that noted in gorillas and chimpanzees). Identical occurrence of erosive arthritis/spondyloarthropathyin free-ranging and artificially restrained animals suggests that spondyloarthropathy can validly be studied in artificially restrained populations. This perspective should allow application of human therapeutic approaches to and perhaps improve the quality of life for artificially restrained, afflicted individuals. 0 1992 Wiley-Liss, Inc. Spondyloarthropathy classifies a variety of arthritis. It is characterized by specific patterns of erosive joint disease and a tendency to spine and sacroiliac fusion (McEwen et al., 1971; Resnick and Niwayama, 1988; Rothschild, 1982; Woodrow, 1985). The nomenclature for this classification might suggest that all individuals have axial joint (spine and sacroiliac) disease. However, axial joints are unaffected in more than half of all individuals with spondyloarthropathy (McEwen et al., 1971; Resnick and Niwayama, 1988; Rothschild, 1982; Rothschild and Woods, 1989). The category spondyloarthropathy actually is composed of several disorders which typically, but not invariably, affect the axial joints. These in0 1992 WILEY-LISS. INC. clude ankylosing spondylitis, Reiter’s syndrome, psoriatic arthritis, the arthritis of inflammatory bowel disease, and “undifferentiated spondyloarthropathy” (McEwen et al., 1971; Mielants et al., 1989; Resnick and Niwayama, 1988; Rothschild, 1982). The above perspectives were applied to analysis of the published literature on arthritis in monkeys. “Articular changes” and “arthritis deformans” have been reported in Dynastic Egyptian and contemporary Received April 12,1990; accepted December 31,1991. Address reprint requests to Bruce M. Rothschild, Arthritis Center of Northeast Ohio, 5701 Market Street, Youngstown, OH 44512. B.M. ROTHSCHILD AND R.J. WOODS 390 monkeys (Bramblett, 1968; Bywaters, 1981; Driesch, 1985; Ford et al., 1986; Fox, 1939). Did these animals actually have spondyloarthropathy? “Arthritic changes” were reported in two elbows, one wrist, two hips, and two knees of a Papio cynocephalus (Bramlett, 1968). This distribution pattern, sparing the small joints of the hands, occurs in spondyloarthropathy (Resnick and Niwayama, 1988; Rothschild, 1982; Rothschild and Woods, 1989). Asymmetrical erosive arthritis and proximal interphalangeal and metacarpal phalangeal joint marginal erosions with ankylosis have been reported in Macaca mulatta (Bywaters, 1981; Obeck et al., 1976). These patterns are also highly suggestive of spondyloarthropathy (Resnick and Niwayama, 1988; Rothschild, 1982; Rothschild and Woods, 1989). That diagnostic suspicion is supported by observation of “spondylitis” in “sacred monkeys of the ancient temples near Thebes” (Ruffer, 1921) and in contemporary Macaca by Sokoloff et al. (1968). Observation of 10 cases of inflammatory arthritis each year in a 2,000 monkeys Macaca mulatta breeding colony suggests that this phenomena may not be uncommon (Ford et al., 1986). Among humans, the frequent association of spine and sacroiliac pathology with peripheral joint disease characterizes spondyloarthropathy (Resnick and Niwayama, 1988; Rothschild, 1982; Rothschild and Woods, 1989). This is sometimes also called reactive arthritis (Ah0 et al., 1985; Woodrow, 1985). This association has been clearly demonstrated in the great African apes, Gorilla and Pan (Rothschild and Woods, 1989, 1991b). Recognition of a n erosive disease of the spondyloarthropathy variety, indistinguishable in gorillas from human psoriatic arthritis, stimulated this systemic review of Old World primates. METHODS The articular skeletons of adult Old World primates were examined from the following collections: American Museum of Natural History (AMNH) (New York City), Carnegie Museum (CM) (Pittsburgh, PA), Cleveland Museum of Natural History (CMNH) (Ohio), Field Museum of Natural History (FMNH) (Chicago, IL), Florida State Museum (UF TABLE 1. Erosive DatholoPv in Drosimians Isolated’ lesions Genera Galago Euoticus Lemur Propithecus Microcebus Daubentonia Tamandua Hapalemur Tarsius Varecia Lepilemur Cheirogaleus Indri Nycticebus Periodicticus Avahi Pot0 Tupaia Arctocebus Loris Joint affected % # 1.1 0 2.9 0 0 0 0 0 0 0 5.0 20.0 12.5 3.3 0 0 0 0 0 1 MCP2 2 MCP, knee Total examined 94 1 70 14 26 4 1 1 1 1 MTP3 Carpus MTP Elbow n 1 10 19 8 20 5 8 33 19 3 1 5 3 i_n” ’Isolated indicates monoarticular disease. ‘MCP = metacarpal phalangeal joint. “MTP = metatarsal phalangeal joint. and FSM) (Gainesville, FL), Museum of Comparative Zoology (MCZ) (Harvard University, Cambridge, MA), National Museum of Natural History (NMNH) (Washington, D.C.), University of Washington (PHY) (Seattle, WA), and Wake Forest University (WFU) (Winston-Salem, NC). Closure of peripheral epiphyses was accepted as evidence of maturity. All animals were either freeranging or had been raised in colonies or zoos. The macerated primate skeletons were surveyed for visible evidence of articular and periarticular joint and spine pathology. Most of the macerated specimens had been treated with lye to remove the soft tissues. Examined post-cranial skeletons were, with rare exception (representing less than 1% of examined specimens), completely preserved. Each skeletal element of all sampled individuals was carefully observed by both authors (Tables 1, 2). Concurrence was obtained to a specific observation representing an erosion and ruling out artifact, such a s post-mortem trauma (e.g., drawer damage). For purposes of this study, articular surfaces were treated a s missing if artifactual damage precluded demonstration of joint disease. The latter was a very infrequent SPONDYLOARTHROPATHY IN OLD WORLD MONKEYS 391 TABLE 3. Bone pathology in Old World monkeys and prosimians * c .- ~ 0 0 0 0q ,o 4 q 0 0 0 c9 0 0 c m ..- In mC 6 m c d m 3 Condition Erosions Isolated Oligo/Polyarticular Fusion Peripheral joint or symphysis pubis Axial joint Diffuse Idiopathic Skeletal hyperostosis Prosimian Old World monkev 7 (2.0%) 0 27 (2.1%) 16 (1.2%) 1 (0.3%) 13 (1.0%) 0 14 (1.1%) 0 9 (0.7%) occurrence. The spine and sacroiliac joints were also assessed in a n additional 17 Colobus and 42 Presbytis. All pathologic specimens were subjected to radiologic examination in the anatomical position, in which they would be viewed during in vivo radiology. RESULTS Isolated erosions Isolated erosions or holes were noted in 2.0% of prosimians (Table 3). These were predominantly localized to metacarpal phalangeal and metatarsal phalangeal joints (Table 1). Such isolated erosions or holes were present in 2.1% of bon-prosimian Old World primates (Table 2). These were localized predominantly to carpals and elbows. Occurrence of isolated erosions was independent of geographic distribution (Table 4). The carpus and elbow are most commonly affected (76%) in Old World primates (Tables 1, 2). Eighteen percent of isolated lesions were localized to the knee, metacarpal phalangeal, or metatarsal phalangeal joints. Six percent of isolated lesions were localized to the shoulder or ulnar styloid. Isolated lesions were typically small and therefore below the threshold for radiologic detection. Those lesions observed on x-ray were “punched out” articular margin or surface lesions, without associated peri-articular osteopenia. New bone formation was occasionally noted, but the bone immediately surrounding the areas of “bone accretionn revealed no other evidence of architectural distortion. B.M. ROTHSCHILD AND R.J. WOODS 392 TABLE 4. Occurrence of isolated erosions on a function of Old World primate geographic distribution Primate Erosions Africa + + Arabia Prosimians Galago Propithecus Daubentonia Tarsius Cheirogaleus Indri Nycticebus Periodicticus Tupaia Loris Old World monkeys Papio Theropithecw Colobus Nasalis Cercopithecus Macaca Erythrocebus Pygathrix Rhinopithecus Cercoceb us Hylobates Asia + + + Borneo Madagascar i + + + + + +c + + + + + + + + + + + t + + + tion in Table 2, and species susceptibility in Table 5. Peripheral joint fusion was found only in non-prosimian Old World primates. Carpal, metacarpal, and metatarsal fusion were each noted a s isolated findings in D X PIP Macaca. Osteoarthritis and calcium pyroDIP phosphate deposition disease occurred once * a . ma mo* a . * as a secondary phenomenon (Fig. 3). . o shaldr The distribution of erosions among Old m * * ON World primates was shoulders (26%), elI(nr Mde bows (44%),wrists (62%), metacarpal phax * * YTP langeal joints (12%), proximal interphaSI langeal joints (7%), hips (O%), knees (34%), ankles (31%), and metatarsal phalangeal joints (27%). Most lesions were below the threshold of x-ray resolution. The density of the surrounding bone was maintained in those erosions that were visualized radiologically. No periarticular osteopenia was present. A sclerotic margin (to the erosion) Oligo- and polyarticular erosive disease was present in approximately 50% of eroErosive disease, not limited in distribu- sions visible on x-ray. tion to a single joint, was not found in prosCalcification of the anulus fibrosus formimians (Tables 2,3; Figs. 1-3). Such erosive ing syndesmophytes and sacroiliac erosions disease was found in 1.2% of free-ranging or fusion were not found in any of the prosnon-prosimian primates, compared to 1.1% imians examined (Figs. 4, 5). Such axial leof primates from zoos or colonies (Chi square sions were found in sixteen (1.2%)non-pros= 0.14, non-significant). Distribution of imian Old World primates (Figs. 4,5; Tables joint involvement in each individual skele- 2, 5). As not all individuals with axial diston is illustrated in Figure 1, sex distribu- ease had erosions and not all individuals b 0 0 b 0 * I 0 0 0 . 0 . # I D 0 ) , .* I . . SPONDYLOARTHROPATHY IN OLD WORLD MONKEYS 393 Fig. 2. Erosive arthritis. a: Pupio distal radius erosion with minimal reactive new bone formation. b: Macucu distal humeral erosion with reactive new bone formation. TABLE 5. Frequency of oligo- and polyarticular erosive arthritis and axial lesions among speciated Cercopithecus and Macaca Percent affected Erosive Axial Cercopithecus neglectus mitis kolbi aethiops nictitanus pygery thrus albogularis Macaca nemestrinus fuscutus arctoides mulatta maurus fascicularis Fig. 3. Distribution of erosive arthritis in Pupio FMNH 123072, with notation of distribution of secondary osteoarthritis and calcium pyrophosphate deposition disease. with erosions had axial disease, these groups overlap in Table 2. Examination of the spine and sacroiliac joints of an addi- Number examined 10.0 7.7 0 0 0 0 0 20.0 7.7 25.0 0 0 0 0 10 14 4 135 14 9.4 14.3 2.0 2.9 0 6.3 0 0 2.9 50.0 32 n n 14 12 7 50 34 2 118 tional42 Presbytis and 17 Colobus revealed sacroiliac erosions in one Presbytis (AMNH 43078) and one Colobus (AMNH 52334). The sacroiliac joint erosions in Colobus AMNH 52334 were associated with elbow and carpal erosions. The axial lesions were frequently associated with zygoapophyseal joint fusion (Fig. 4). Occasional fusion of costovertebral joints (Fig. 4) or of the symphysis pubis was noted (Table 2). Ossification of longitudinal ligaments of the spine is referred to as diffuse idiopathic skeletal hyperostosis, or DISH (Resnick and Niwayama, 1988; Rothschild, 1982,1985).It was found in only 10 (0.74%)non-prosimian 394 B.M. ROTHSCHILD AND R.J. WOODS in a single individual is quite remote (McCarty, 1989; Rothschild, 1982). Too many of the Old World primates studied had involvement of both peripheral and axial joints to suggest co-occurrence of two diseases. The nature and distribution of the erosions in Old World primates were identical, independent of spine or sacroiliac (axial joint) involvement. This again suggests that all were manifestations of a single disease. The term oligo-articular implies involvement of less than 5 peripheral joints, while polyarticular is used when 5 or more peripheral joints are affected. The oligo-articular distribution of arthritis in Macaca, Cercopithecus, Colobus, Presbytis, and Hylobates is actually the most common appearance of spondyloarthropathy in humans (McCarty, 1989; Rothschild, 1982). The radiologic picture of erosions with sclerotic margins and no peri-articular osteopenia is also characteristic of spondyloarthropathy (Resnick and Niwayama, 1988; Rothschild, 1982; Rothschild and Woods, 1989, 1991a). Both Fig. 4. Macaca spine with classic syndesmophytes oligo-articular and polyarticular disease producing fusion through the anulus fibrosus. Zygoapo- were noted, similar to patterns noted in the physeal and costovertebral joint fusion are also promispectrum of human disease (Fig. 1) (Mcnent. Carty, 1989; Rothschild, 1982). The nature and distribution of the lesions and the occurrence and frequency of spine Old World primates (Fig. 6; Table 2). All afand sacroiliac involvement allow definitive fected individuals of determinate sex were diagnosis of spondyloarthropathy in Theromale and all but two were from artificial pithecus, Papio, Cercopithecus, Macaca, Coloenvironments. bus, Presbytis, and Hylobates. The presence of anulus fibrosus calcification, sacroiliac DISCUSSION fusion, or erosions is sufficient and diagnosDiagnosis tic (Resnick and Niwayama, 1989; RothsErosive disease, not limited in distribu- child, 1982; Rothschild and Woods, 1988). Fusion of the symphysis pubis was tion to a single joint, was found in 1.2% of non-prosimian Old World primates (Figs. 2, present only in genera of Old World pri3). Attribution of a single diagnosis to this mates susceptible to spondyloarthropathy phenomenon is predicated upon a major (Papio, Cercopithecus, Macaca, and Hyloassumption. An anthropomorphizing ap- bates). As one-fifth of symphysis pubis fuproach is utilized. “Human” characteristics sions were associated with sacroiliac fusion are extended to non-human primates from or anulus fibrosus syndesmophyte formahuman disease. Relatively few erosive disor- tion, such fusion may represent part of the ders (that are not predominantly monoartic- spectrum of spondyloarthropathy or at least ular) occur with any frequency within hu- a tendency to fusion in susceptible groups man populations. Rheumatoid arthritis and (Table 2). Similarly, the peripheral joint fuspondyloarthropathy are the prime diagnos- sion noted in Macaca may represent part of tic candidates (McCarty, 1989; Resnick and the spectrum of spondyloarthropathy, as it Niwayama, 1988; Rothschild, 1982). The does in humans (Rothschild and Woods, likelihood of co-occurrence of both diseases 1991a). SPONDYLOARTHROPATHYIN OLD WORLD MONKEYS 395 Fig. 5. Sacroiliac joint fusion. A: Anterior view of Mucacu sacroiliac joint fusion. B: Radiograph of Hylobutes pelvis revealing fusion of the right sacroiliac joint. Isolated erosions were statistically analyzed as to their genus frequency and geographic distribution (Table 6). They were uniformly distributed among genera of spondyloarthropathy-afflicted Old World primates, with the exception of Macaca (Tables 1, 2, 4). The significance of sparing of Erythrocebus is unclear at this time. Isolated lesions were typically small. Their significance is difficult to assess as their size was below the threshold for radiologic detection. The distortion of osseous architecture, typically noted with infectious lesions, was notably absent (Resnick and Niwayama, 1989; Rothschild, 1982). It is therefore difficult to identify the etiology of these isolated erosions. The pattern of distribution of erosive diseases in humans is a diagnostic criterium, which assists in distinguishing among them (Rothschild et al., 1988; Rothschild and Woods, 1989; Woods and Rothschild, 1988). While isolated lesions are usually not interpretable, the similarity of their distribution in non-prosimian Old World primates to the general distribution of joint disease in those with oligo- and polyarticular disease raises an interesting possibility (Fig. 2; Table 2). Could these isolated lesions represent “forme fruste” or aborted cases of spondyloarthropathy? While there did not appear to be a relationship to skeletal maturity, torrelation with age is currently under investigation in an age-verified skeletal population. Fig. 6. Lateral view of Pupio spine. Diffuse idiopathic skeletal hyperostosis is manifest as calcification of the anterior longitudinal ligament. Space is visualized between the areas of calcification and the anterior portion ofthe body, 396 B.M. ROTHSCHILD AND R.J. WOODS TABLE 6. Geographic distribution of Old World primates with spondyloarthropathy Primate Papio Theropithecus Cercopithecus Macca Colobus Pres bytis Hvlo bates Africa + + + + + Asia Arabia + t + + Frequency implications The frequency of oligo- or polyarticular erosive disease (spondyloarthropathy) in Theropithecus was significantly greater than that in Papio, Colobus, Presbytis, Cercopithecus, Macaca, and Hylobates (Chi square = 12.65, 6 d.f., P < .05). The latter combined the data from the other afflicted genera, for comparison with Theropithecus. A curious species specificity in Cercopithecus and Macaca was also noted (Table 5). It is unclear if genetic, geographic, or food gathering or intersocial habits might be implicated. Although spondyloarthropathy was unrepresented in Nasalis, Pygathrix, and Cercocebus, the small number of specimens available for assessment precludes confident exclusion of the disease in those populations. The difficulty of sample size is emphasized by Erythrocebus. Although no examples of oligo- or polyarticular erosive disease were noted among the 59 individuals studied, a disease occurring with a population frequency of 0.6 to 3.9% could easily be missed. Absence of oligo- or polyarticular erosive disease in 344 prosimians, by contrast, suggests that group is spared (Chi square = 4.53, P < .04). Differential diagnosis Differentiation of diffuse idiopathic skeletal hyperostosis (DISH) from spondyloarthropathy is important. DISH is a pain-free skeletal phenomenon, which rarely affects ability to function (McCarty, 1989; Resnick and Niwayama, 1988; Rothschild, 1985, 1987). It does not cause erosive damage to joints. Spondyloarthropathy is a frequently erosive disorder which is typically painful and often compromises function (McCarty, 1989; Resnick and Niwayama, 1988; Rothschild, 1982). DISH has been well recognized in primates (Rothschild, 1985, 1987; Rothschild and Woods, 1988; Sokoloff et al., 1968). It is clearly distinguishable in the primates examined, on the basis of calcification of longitudinal ligaments. The anulus fibrosus and zygoapophyseal and costovertebral joints are spared in DISH. Predominant occurrence of DISH in artificially restrained primates could reflect longer survival of such animals (compared to free-ranging), a hypothesis which will be testable when criteria are established for aging free-ranging primates. Limitation of DISH in Old World primates to males is not surprising, in view of the relatively small number of afflicted primates (11 individuals) and the 7:l male predominance of DISH in geriatric humans (Rothschild, 1991). Its very frequency assures co-occurrence with various forms of arthritis including spondyloarthropathy, a s was observed in this study. Rheumatoid arthritis is a symmetrical, but essentially a n axial joint sparing arthritis (Katz, 1989; McCarty, 1989; Resnick and Niwayama, 1988; Rothschild, 1982; Rothschild et al., 1990). Erosion of the odontoid process of the second cervical vertebrae is one of the few axial skeleton changes found in rheumatoid arthritis. This is clearly distinguishable from the spondyloarthropathy noted in Old World primates. The limited number of joints involved in Old World primates is clearly at variance with the involvement of almost every peripheral diarthrodial joint found in rheumatoid arthritis (Resnick and Niwayama, 1989; Rothschild, 1982; Rothschild et al., 1990). While erosions with sclerotic margins may be found in gout or infectious arthritis, epidemiologic study reveals major differences from that observed in Old World primates (Katz, 1989; McCarty, 1989; Rothschild, 1982; Rothschild and Woods, 1991a). Gout and infectious arthritis also are predominantly monoarticular disorders, in contrast to the oligo- and polyarticular erosive arthritis observed in Old World primates. Overgrowth of periosteum adjacent to gout erosions forms a highly characteristic overhanging edge (Katz, 1989; McCarty, 1989; SPONDYLOARTHROPATHY IN OLD WORLD MONKEYS 397 TABLE 7. Skeletal distribution of erosive arthritis in Old World primates and of symptomatic spondyloarthropathy (Spondylo), Reiter’s syndrome, psoriatic arthritis, and rheumatoid arthritis (RA) in Homo Sapiens’ Primates Spondylo Reiter Psoriatic RA Joint # % % % % % Shoulder Elbow Wrist MCP’ PIP2 Hip Knee Ankle 7 12 16 3 2 0 26 44 62 12 7 0 21 9 17 13 20 17 9 8 34 31 27 30 42 8 18 24-65 2-40 13-21 10-14 16-34 7-46 5-31 5-28 67-70 45-65 57 24-65 13-82 4-23 10-43 44-62 34-53 11-40 0-38 27-72 28-63 33-34 52 5-24 46 66 92 70 40 12 82 54 70 0 0 MTP’ SI2 Spine 7 8 11 8 ‘Derived from Bitar, 1980; Dryll et al., 1975; Fletcherand Rowley, 1952; Kammeret al., 1979; Kouse, 1978; Martel et al., 1965; Martioet al., 1980; McEwen et al., 1971; Moll, 1979 Peterson and Silbiger, 1967; Rothschild and Woods, 1989 Scarpa et al., 1984; Serre et al., 1970; Weissberg et al., 1978; Weldon and Scalettar, 1961. ‘MCP = metacarpal phalangeal; PIP = proximal interphalangeal; MTP = metatarsal phalangeal; SI = sacroiliac. Ortner and Putschar, 1981; Rothschild, 1982).No evidence of such a phenomena was present in Old World primates. While amyloidosis does occur as a complication of Shigella or tuberculosis infections in primates (Chapman and Crowell, 1977), amyloid only rarely produces radiologically detectable erosions (Resnick and Niwayama, 1988; Rothschild, 1982). Erosions of amyloid classically have a punched out appearance, similar to those of gout (Chapman and Crowell, 1977; Resnick and Niwayama, 1988; Rothschild, 1982). This is quite dissimilar to the erosions noted in the Old World primates studied. 7). An attempt was therefore made to identify the specific variety of spondyloarthropathy present in Old World primates. Ankylosing spondylitis and inflammatory bowel disease-associated axial (spine) disease starts in the lumbar spine and progresses cephaladly in a symmetrical, uniform manner (Katz, 1989; McCarty, 1989; Rothschild, 1982). While Reiter’s syndrome, psoriatic arthritis, and undifferentiated spondyloarthropathies may present in a similar manner, they tend to be asymmetrical and more limited in distribution. The pattern of spine involvement in Old World primates suggest Reiter’s syndrome, psoriatic arthritis, or undifferentiated spondyloarthropathy, rather than ankylosVariety of spondyloarthropathy ing spondylitis or the arthritis of inflammaSpondyloarthropathy in humans is di- tory bowel disease. vided into a number of varieties: ankylosing Reiter’s syndrome or reactive arthritis is a spondylitis, psoriatic arthritis, Reiter’s syn- reasonable consideration in Old World primates (Resnick and Niwayama, 1988; drome, inflammatory bowel disease-related arthritis, and undifferentiated spondyloar- Rothschild, 1982). Reiter’s syndrome may be thropathy (McEwen et al., 1971; Mielants of venereal or infectious agent diarrhea oriet al., 1989; Resnick and Niwayama, 1989). gin (Rothschild, 1982). Occurrence of The term undifferentiated spondyloarthrop- spondyloarthropathy in monogamous Old athy is applied when insufficient evidence is World primates (e.g., Hylobates) makes the present to diagnose one of the first four. venereal variety unlikely (Smuts et al., Failure of findings in Old World primates to 1986). Among the causes of infectious agent correlate with the “generic” spondyloar- diarrhea are Salmonella, Shigella, Yersinia, thropathy group perhaps suggests that Camplobacter, and enteropathic Escherispondyloarthropathy in Old World monkeys chia coli. These are “commonly” noted “in reflects one disease process, rather than recently imported non-human primates” several forms of spondyloarthropathy (Table (Brancker, 1985; Klumpp et al., 1986; Mc- 398 B.M. ROTHSCHILD AND R.J. WOODS Clure, 1980; Reinhardt et al., 1987). Clamydial infections are associated with human venereally transmitted reactive arthritis and have been found in Cynomolgus monkeys (Quinn e t al., 1986). Table 7 assesses the similarity of distribution of erosive lesions in Old World monkeys to the distribution in human spondyloarthropathies. Spondyloarthropathy in the table refers to frequency of involvement in a series of patients. Ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, and inflammatory bowel disease-related arthritis are grouped in Table 7 under the category of “generic” spondyloarthropathy. The distribution of erosions among Old World primates was shoulders 25%, elbows 44%, wrists 60%, metacarpal phalangeal joints 13%, proximal interphalangeal joints 7%, hips 0%, knees 34%, ankles 31%, and metatarsal phalangeal joints 27%. This falls outside the range previously reported in Reiter’s syndrome and rheumatoid arthritis (Table 7). That range has proven quite valid for comparison of skeletal and clinical distributions (Rothschild and Woods, 1989, 1991a,b; Rothschild et al., 1988, 1990). We were surprised that the findings in monkeys were so disparate from that noted for Reiter’s syndrome. As joint distribution in Reiter’s disease varies with causative organism, perhaps a different proportion of those organisms in the various affected monkeys would explain this apparent variation. Reiter’s syndrome could therefore still be responsible. The distribution of erosive disease and axial joint involvement in Old World primates is actually quite similar to that noted for human psoriatic arthritis (Table 7). The observation of Obeck et al. (1976) of a n oligoarticular arthritis associated with ankylosis in a rhesus monkey is in keeping with this diagnosis. Equal representation in male and female Papio, Presbytis, and Hylobates is in keeping with that noted in human psoriatic arthritis (Rothschild, 1982; Rothschild and Woods, 1989). Male predominance in the other afflicted genera may reflect a real difference, but is not statistically distinguishable from a 1:l ratio. Concluding that the spondyloarthropathy in Old World monkeys probably is related to psoriatic arthritis is perhaps not surprising, as skin lesions with the gross visual and histologic appearance of psoriasis have been reported in Macaca (Zanolli et al., 1988). These psoriatic lesions were described as “erythematous plaques with adherent white scale, spongiform pustules and Munro microabscesses, clinically and histologically indistinguishable from psoriasis.” One further possibility remains. While ankylosing spondylitis and inflammatory bowel disease are clearly not responsible for the primate spondyloarthropathy described in this report, Reiter’s syndrome certainly remains a possibility. Could the spondyloarthropathy in Old World primates represent a mixture of psoriatic arthritis and Reiter’s syndrome? Transition of Reiter’s syndrome to psoriatic arthritis and vice versa has clearly been recognized in humans (Katz 1989; McCarty, 1989; Rothschild, 1982). As the gross appearance of the skin and histopathology of the two diseases may at times be indistinguishable, this consideration cannot be further resolved a t this time (Katz 1989; McCarty, 1989; Rothschild, 19821. Observation of Reiter’s syndrome, as a complication of human immunodeficiency (AIDS) virus infection, requires consideration of a n analogous retrovirus phenomenon in these primates (Davis et al., 1989; Mielants and Veys, 1990; Reveille et al., 1990). This is less likely, as AIDS appears to be a relatively new phenomenon, while most of the affected animals were collected in the early part of the century. However, retroviruses have been implicated in the etiology of psoriasis and are certainly worth exploring in the pathophysiology of arthritis in monkeys (Gladman, 1990). Implications Evidence of spondyloarthropathyabounds in the literature of primate skeletal disease (Ortner and Putschar, 1981; Rothschild and Woods, 1989; Sokoloff et al., 1968; Wells, 1962). The variety observed in Old World primates is indistinguishable from human psoriatic arthritis. Other than the relationship of the articular disease to the skin condition, the etiology of psoriatic arthritis is unknown. Reiter’s syndrome must also be considered. SPONDYLOARTHROPATHY IN OLD WORLD MONKEYS 399 This analysis also provides insights for and Musculoskeletal and Skin Disease analysis of other, less studied primate grant AFt35736-03. groups. Future documentation even of peripheral joint or symphysis pubis fusion should stimulate full population skeletal LITERATURE CITED evaluation for occurrence of spondyloar- Ah0 K, Leirisalo-Repo R, and Repo H (1985) Reactive thropathy in any such populations. arthritis. Clin. Rheum. Dis. 1:25-40. As spondyloarthropathy in general and Bitar E (1980) Le rhumatisme psoriasique a u Liban. Rev. Rhum. Mal. Osteoartic, 471317-321, psoriatic arthritis in particular are indigenous in non-prosimian primates from both Bramblett CA (1968) Pathology in the Darajani baboon. Am. J. Phys. Anthropol. 26t331-340. Africa and Asia (Table 6), the possibility of a Brancker WM (1985) Primates. In J E Cooper, MF non-species specific etiology is suggested. Hutchinson, OF Jackson, and R J Maurice (eds.):ManThe limited individual susceptibility (0.1ual of Exotic Pets. Cheltenham, England: British 3.9%) in humans, lesser apes, and most Small Animal Veterinary Association, pp. 99-105. monkeys contrasts with that noted (16- Bywaters EG (1981)Observations on chronic polyarthritis in monkeys. J. R. SOC.Med. 74:794-799. 28%) in gorillas, chimpanzees, and TheroWL J r , and Crowell WA (1977)Amyloidosis in pithicus (Rothschild and Woods, 1989, Chapman Rhesus monkeys with rheumatoid arthritis and en1991b). It also contrasts with the total abterocolitis. J. Am. Vet. Med. Assoc. 1711855-858. sence of the phenomenon in prosimians. If Davis P, Stein M, Latif A, and Emmanuel J (1989)Acute environmentally based contagions are imarthritis in Zimbabwean patients: Possible relationship to human immunodeficiency virus infection. J. portant in the pathophysiology of spondyRheumatol. 161346-348. loarthropathy in primates, the wide geoDriesch A (1985)Pathologically altered skeletal remains graphic distribution of the phenomena of baboons from ancient Egypt. Tier Arztliche Praxis suggests a panendemic. Investigation of his13:367-372. tocompatibility locus antigen (HLA) and Dry11 A, Cazalis P, and Seze S (1975) Rheumatisme psoriasique. Nouv. Presse Med. 4:1408-1412. other genetic immuno-modulating systems may clarify the adaptive genetic and physio- Fletcher DE, and Rowley KA (1952) The radiologic features of rheumatoid arthritis. Br. J. Radiol. 25:282logical characteristics that define the dis295. parate disease susceptibility noted (Heise et Ford E, Hird D, Franti C, Lerche N, Lowenstein L, and al., 1987; Lawlor et al., 1988). Identical ocAnderson J . (1986)Analysis of factors associated with sixty cases of chronic arthritis in Rhesus monkeys at currence frequency of erosive arthritis/ the California Primate Research Center. Lab. h i m . spondyloarthropathyin free-ranging and arSci. 89561. tificially restrained (zoo o r colony-raised) Fox H (1939) Chronic arthritis in wild animals. Trans. animals suggests that spondyloarthropathy Am. Philos. SOC.,New Ser. 31171-149. can validly be studied in artificially re- Gladman DD (1990) Psoriatic arthritis. Curr. Opin. strained populations. 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