Article The lesions of toe tip necrosis in southern Alberta feedlot cattle provide insight into the pathogenesis of the disease Lana A. Gyan, Chad D. Paetsch, Murray D. Jelinski, Andrew L. Allen Abstract — Gross and histologic postmortem studies were performed on the hind feet of feedlot cattle that had, or were free from, lesions of toe tip necrosis. The hind feet of feedlot cattle were collected by 3 veterinary feedlot practices in southern Alberta, Canada. Three studies of these feet were conducted: i) prediction of disease based on the presence or absence of apical white line separation, ii) gross assessment of the distribution and severity of lesions within affected claws, and iii) microscopic evaluation of the distal phalanx and surrounding soft tissues of affected claws. Prediction of toe tip necrosis based on the presence of apical white line separation was statistically significant (P , 0.0001). This, combined with a pattern of lesions indicative of an ascending infection of the distal phalanx and the absence of other lesions, suggests that the pathogenesis involves bacterial infection originating from the most distal aspect of the toe, at the apical white line. Résumé — Les lésions de la nécrose du bout des orteils chez le bétail des parcs d’engraissement du sud de l’Alberta fournissent des renseignements sur la pathogénèse de la maladie. Des études post-mortem macroscopiques et histologiques ont été réalisées sur les pieds arrière du bétail d’engraissement qui avait ou n’avait pas des lésions de nécrose du bout des orteils. Les pieds arrière du bétail d’engraissement ont été recueillis par trois pratiques vétérinaires de parcs d’engraissement du sud de l’Alberta, au Canada. Trois études de ces pieds ont été réalisées : i) prédiction de la maladie en fonction de la présence ou de l’absence d’une séparation de la ligne blanche apicale, ii) une évaluation macroscopique de la répartition et de la gravité des lésions dans les onglons affectés et iii) une évaluation microscopique des phalanges distales et des tissus mous entourant les onglons affectés. La prédiction de la nécrose du bout des orteils basée sur la présence d’une séparation de la ligne blanche apicale était significative du point de vue statistique (P , 0,0001). Ce fait, combiné à une tendance de lésions indiquant une infection ascendante des phalanges distales et l’absence d’autres lésions, suggère que la pathogénèse comporte une infection bactérienne provenant de l’aspect le plus distal de l’orteil, à la ligne blanche apicale. (Traduit par Isabelle Vallières) Can Vet J 2015;56:1134–1139
L
Introduction
ameness is the alteration of the gait of an animal and can be associated with painful conditions of the limbs. Pain, including pain in the feet of cattle, can manifest in signs that are difficult to recognize, such as decreased physical activity, and a reduction in food and water consumption. While lameness in dairy cattle has received far more attention than lameness in feedlot cattle, much of what is known regarding the impact of lameness in dairy cattle can be extrapolated to feedlot cattle. So,
for a variety of reasons, including reduced feed conversion and weight gain, costs of treating lame animals, humane euthanasia of animals before reaching slaughter, lameness is associated with financial losses. Therefore, lameness is an issue of great importance to cattle feedlot operators and veterinarians for both welfare and economic concerns (1–6). There are several causes of lameness in cattle attributable to lesions in the foot. One such cause in feedlot cattle that has been previously reported in the scientific veterinary literature
Department of Veterinary Pathology (Gyan, Allen) and the Department of Large Animal Clinical Sciences (Paetsch, Jelinski), Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4. Address all correspondence to Dr. Andrew Allen; e-mail: [email protected] Dr. Gyan’s current address is the Veterinary Diagnostic Laboratory, Ministry of Food Production, Eric Williams Medical Sciences Complex, Building 49, Uriah Butler Highway, Champs Fleurs, Trinidad and Tobago. Dr. Paetsch’s current address is Paetsch Veterinary Services, Box 264, Muenster, Saskatchewan S0K 2Y0. Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere.
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or being free of, TTN and, in doing so, ii) further characterize the lesions of TTN and provide insights into the pathogenesis of the disease.
Materials and methods The animals used in this study came from feedlots located in southern Alberta, during October and November of 2012. Generally, the animals were commercial mixed-breed beef cattle that would have arrived at the feedlot, on different dates, from either an auction mart or a beef cattle ranch. During the time when samples were collected, these animals, both males and females, would have ranged from 7 to 9 mo of age and weighed between 175 and 320 kg. Shortly after arrival, and following a period for acclimation and processing, cattle received a total mixed ration consisting of alfalfa hay, barley silage, and a vitamin and mineral supplement. During the collection period, animals would have been on this feed for an average of 23 d. Typically, the animals were kept in groups of about 300, in open feeding pens measuring about 50 3 80 m, with a base of dirt or dirt and gravel that was sloped away from the feed bunk to promote drainage, and covered with straw. The feed bunk in each pen was constructed of concrete or wood which would have included a 1 to 2 m wide concrete apron for the animals to stand upon while eating. Handling alleys had a gravel base and processing facilities had a concrete base, sometimes augmented with metal. Environmental temperatures during October and November of 2012 ranged from a low of about 210°C to a high of about 110°C. As a result, damp portions of a pen may have been frozen (i.e., contained ice). The hind feet of some of these cattle were collected by 3 veterinary feedlot practices during October and November of 2012. The veterinarians collected either 1 or both hind feet from cattle they had euthanized following a clinical diagnosis of TTN or TTNS. In some instances, TTN was confirmed at the feedlot by removing the apex of at least 1 claw and observing the appropriate lesions. Claws from which the apex had been removed were not used in any of the studies described here. During the same time period, intact hind feet were collected from other cattle in the same feedlots that had died or been euthanized for causes unrelated to TTNS. At least 1 foot was submitted from 67 animals affected with TTNS (i.e., CASES), and 68 animals that died or were euthanized with other diseases (i.e., CONTROLS). All feet submitted from the 135 animals were examined and 3 separate studies were conducted using different subsets of the submitted feet. For the purposes of these studies, TTN was defined as a lesion of the foot involving inflammation or necrosis of the corium with or without any combination of inflammation, necrosis, or lysis of P3. However, TTN did not include other known causes of lameness including, but not limited to, septic arthritis, fractures, and interdigital dermatitis.
Study 1: Prediction of TTN based on the presence of apical white line separation Thirty-nine, arbitrarily selected, intact hind claws, both medial and lateral, and excluding those claws where the apex had been 1135
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is a so-called toe abscess (3,7–11). However, Kofler (12), in a paper describing the same or similar condition in dairy cattle, argued that the term “abscess” was inappropriate, and that a toe ulcer complicated by necrosis of the apex of the distal phalanx (P3) was a more accurate description. Recently, the terms “toe necrosis” (1) or “toe-tip necrosis syndrome” (TTNS) (13) have been introduced into the lexicon of those working on lameness in ruminants. The latter term incorporates the lesions in the foot, or toe tip necrosis (TTN), and the sequelae, TTNS, which may include interphalangeal arthritis, osteomyelitis of the middle and proximal phalanges, flexor tendonitis, cellulitis, and embolic spread of bacteria to the lungs, liver, and kidneys (8,11,13). Greenough (3) has provided a summary of the limited literature concerning TTN, and Blowey (1) has published some useful images of the lesions. Toe tip necrosis is a disorder most commonly affecting the lateral claw of the hind feet of 10- to 12-month-old beef cattle that develops within several days to a few weeks after processing, weaning, and transportation to a feedlot. The epidemiology and pathogenesis of TTN has never been critically studied (3,13); however, several hypotheses have been suggested. One hypothesis is that trauma, in the form of excessive wear of the sole associated with abrasive surfaces such as concrete, metal, and ice, allows bacteria to enter the white line at the apex of the claw (3). Another suggests that hypostasis — the settling of blood in the distal limbs — associated with lack of mobility while being transported for long periods of time results in ischemic necrosis of the apex of the P3, which is followed by rupture of the white line (3). Three other hypotheses have not been clearly articulated in the literature. However, it has been speculated that the rapid shift to a high grain ration upon arrival at the feedlot leads to a metabolic disturbance and laminitis, which then allows for the displacement or rotation of P3 relative to the claw capsule and penetration of the apex of P3 through the sole (3–5). At the same time, cattle infected with bovine viral diarrhea virus (BVDV) are typically present within populations of western Canadian feedlots (14,15) and morbid feedlot cattle often have vascular lesions in the heart and lungs (7,16). So, it has been speculated that BVDV might cause vascular lesions and ischemic necrosis in the claws and predispose some animals to TTNS (13). Finally, because some animals with TTNS have evidence of embolic bacterial disease, consideration should be given to the possibility that TTN is the result of bacteria arriving in the claw hematogenously. Historically, TTNS is believed to affect approximately 2 per 10 000 feedlot cattle. The incidence of TTNS can vary between feedlots, but this variability appears to be related to lots, i.e., financial entities of large groups of animals, typically more than 100 and less than 1000. Most lots of feedlot cattle will have no animals affected with TTNS, while a few lots could have between 0.01% to 1.3% of animals affected (17). The studies reported here were part of a larger epidemiologic study of TTNS in western Canadian feedlot cattle and were performed with the following goals: i) to conduct gross and histologic postmortem examinations on a subset of the feet of feedlot cattle diagnosed ante-mortem as either suffering with,
A R T I C LE
A
B
C
D
E
F
Figure 1. A — The hind foot of a feedlot animal showing apical white line separation in 1 of the claws. B — A sagittal section of a hind claw of a feedlot animal with lesions of toe tip necrosis. Superimposed on the image are lines which divide the claw into subdivisions 1 through 5 that were used to evaluate the distribution of lesions. C — A sagittal section of a hind claw of feedlot animal Y6616 with subtle apical white line separation and small, focal lesions of toe tip necrosis involving subdivision 1. D — A sagittal section of a hind claw of feedlot animal G7443 with apical white line separation and extensive lesions of toe tip necrosis involving subdivisions 1, 2, and 3. E — A sagittal section of a hind claw, different from that in C, of feedlot animal Y6616. There is apical white line separation and lesions of toe tip necrosis involving all subdivisions (1 through 5) of the claw. Note the extension of lesions into the distal interphalangeal joint, joint capsule and distal sesamoid bone. F — A sagittal section of a hind claw different from that in E, of feedlot animal G7743. There is apical white line separation and lesions of toe tip necrosis involving all subdivisions (1 through 5) of the claw. Note the absence or loss of subdivision 1. There is also extension of lesions into the distal interphalangeal joint, joint capsule and distal sesamoid bone.
removed by the practitioner, from 28 animals underwent an external gross inspection by LAG and ALA, who were “blind” as to disease status, i.e., whether the feet were from CASES or CONTROLS as diagnosed by the submitting practitioner, to identify the presence or absence of apical white line separation (AWLS) (Figure 1A). Each claw was then serial sectioned in the sagittal plane using a band saw and the internal structures examined by a third person (CDP) to identify the presence or absence of gross lesions of TTN. CDP was “blind” to the presumptive clinical disease status as diagnosed by the submitting practitioner and “blind” to the presence or absence of AWLS. The results of these 2 examinations were plotted in a 2 3 2 contingency 1136
table (Table 1) and, using Fisher’s exact test, the probability of the distribution, predictive values, and sensitivity and specificity calculated using an analytical software program (Prism 6 for Windows; GraphPad Software, La Jolla, California, USA).
Study 2: Distribution and severity of lesions based on gross evaluation Thirteen, arbitrarily selected, intact claws from 1 or both hind feet of 6 CASES, different from those used in Study 1, were serially sectioned in the sagittal plane using a band saw and the internal structures examined to identify any lesions present. Claws with lesions of TTN were studied further. Color images CVJ / VOL 56 / NOVEMBER 2015
Table 1. The 2 3 2 contingency table showing the distribution of apical white line separation and the presence of toe tip necrosis in hind claws collected from southern Alberta feedlot cattle during October and November of 2012
TTN TTN present absent Total
AWLS present AWLS absent Total
4 0 4 1 34 35 5 34 39
TTN — toe tip necrosis; AWLS — apical white line separation.
Study 2: Distribution and severity of lesions based on gross evaluation Evaluation of Table 2 reveals that grossly visible lesions of TTN were present in every claw examined and in 36 of the 65 subdivisions of the claws, or 55.4%. Toe tip necrosis always involved the distal tip of the claw (subdivision 1) and never appeared at the proximal aspect of P3 (subdivisions 4 and 5) without also being present in the intervening area (subdivisions 2 and 3).
Study 3: Distribution and characterization of lesions based on microscopic evaluation
Study 3: Distribution and characterization of lesions based on microscopic evaluation
An approximately 4-mm sagittal section, containing the most extensive lesions, of a claw from each of the affected animals (CASES) represented in Study 2, was fixed in 10% neutral buffered formalin. Following fixation, each sagittal section was further cut into the 5 previously described subdivisions using a band saw. The hoof, or keratin capsule, was removed from the underlying tissue with a scalpel with an effort to include as much corium as possible. Each subdivision was then decalcified in 20% formic acid and routinely processed, i.e., embedded in paraffin, cut at 4 mm, mounted on glass slides, stained with hematoxylin and eosin, and cover slipped, for routine microscopic examination. Selected subdivisions were also stained with the periodic acid-Schiff reaction and Gram’s stain to help identify the basement membrane of the epidermal lamellae, and for bacteria, respectively. Each subdivision of P3 and the surrounding soft tissue was then microscopically evaluated for the presence of inflammation, including laminitis and vasculitis; thrombi; necrosis of bone, soft tissues, or both; the presence of bacteria; and changes to the epidermal lamellae suggestive of laminitis (3). A summary of the lesions present in each subdivision is found in Table 3.
Sixty-four slides, 1 of each subdivision of each of the 13 claws, were evaluated. One section, from subdivision 1 of animal G7443 could not be made because of the absence of tissues (Figure 1F). The results, summarized in Table 3, reveal that microscopic lesions were present in 57 of the 64 subdivisions of affected claws. If subdivision 1 of animal G7443 is added to these totals, then lesions would have been present in 58 of 65 subdivisions, or 89.2%.
Results Study 1: Prediction of TTN based on the presence of apical white line separation The hind feet examined came from 10 CASES and 18 CONTROLS as diagnosed by the submitting practitioner. During the “blind” examination of the 39 claws, the presence of AWLS correctly predicted the presence of TTN in 4 of 4 instances (100%); and the absence of AWLS correctly predicted the absence of TTN in 34 of 35 instances (97%) (Table 1), representing a sensitivity of 80% and a specificity of 100%. The probability of obtaining this distribution by chance is remote (P , 0.0001). An interesting finding was the presence of TTN in the feet of 2 animals that were diagnosed as CONTROLS by the submitting practitioner. CVJ / VOL 56 / NOVEMBER 2015
Discussion Under the conditions of Study 1, the positive predictive value of AWLS for the diagnosis of TTN was 100% and the negative predictive value of the absence of AWLS for the absence of TTN was 97%. However, given the relatively small number of claws examined, it remains uncertain if AWLS is necessary for TTN to develop, or if the development of TTN leads to AWLS. The fact that 1 claw was diagnosed as having TTN in the absence of AWLS might provide some insight into this question. However, the 2 pathologists participating in this study (LAG and ALA) believed the diagnosis of TTN in that claw may have been the result of interpreting changes associated with postmortem freezing, i.e., interpreting the redness within the corium associated with postmortem lysis of erythrocytes, as redness associated with inflammation. Regardless, examination of the distribution and severity of lesions, as summarized in Tables 2 and 3, support 2 ideas. First, that microscopic evaluation is a more sensitive means of identifying and characterizing the presence of lesions than is gross evaluation and, second, that it was never the case that lesions were present in the more proximal aspects of the claw without being present in the distal aspects. The latter observation suggests that TTN is the result of an ascending infection that starts at the distal tip of the claw and progresses proximally. This finding supports the hypothesis that AWLS is the primary lesion that allows for the development of TTN. 1137
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of the sagittal sections of each claw were made and divided into 5 subdivisions as illustrated in Figure 1B. The subdivisions were created by drawing a line through P3 that extended from the distal tip to the center of the proximal articular surface. This line was then measured and subsequently divided into approximately equal thirds by drawing 2 lines, perpendicular to the first line, which extended between the dorsal and plantar surfaces. Lesions included any changes in color, texture, or both; interpreted to be any combination of inflammation, necrosis, or lysis. An estimate of the proportion of the subdivision affected was made and categorized as “no visible lesions,” “, 25% of the subdivision affected,” “26% to 50% of the subdivision affected,” “51% to 75% of the subdivision affected,” or “. 76% of the subdivision affected” and entered into a summary table (Table 2). An example of small, focal lesions, restricted to subdivision 1 is presented in Figure 1C. An example of extensive lesions, involving subdivisions 1, 2, and 3 is presented in Figure 1D. An example of nearly diffuse lesions, involving subdivisions 1 through 5 is presented in Figure 1E.
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Table 2. Distribution and severity of lesions within subdivisions of a sagittal section of a hind claw diagnosed with toe tip necrosis. The claws were collected from southern Alberta feedlot cattle during October and November of 2012
Table 3. The presence or absence of histologic lesions within subdivisions of a sagittal section of a hind claw diagnosed with toe tip necrosis. The claws were collected from southern Alberta feedlot cattle during October and November of 2012
Subdivision number
Subdivision number
Animal Claw 1 2 3 4 5
Animal Claw 1 2 3 4 5
7565
**** **** **** **** **** **** **** **** — —
7565 1 1 2 1
1 1
1 1 1 1 — 1
E9516 1 2
** — — — — **** — — — —
E9516 1 1 2 1
1 1
1 1
1 1
— 1
G7443a 1 2 3
**** * * *** ** ** — — — — **** ** ** — —
G7443a 1 n/a 1 2 1 1 3 1 1
1 1 1
1 1 1
1 — 1
K2084 1 2
**** * * — — * ** ** — —
K2084 1 1 2 1
1 1
1 1
1 1
1 1
P0384a 1
**** ** ** — —
P0384a 1
1
1
1
1
* * — — — * — — — — **** **** **** **** ****
Y6616a 1
1 — 1
1 1 1
— — 1
— 1 1
1 2
Y6616a 1
2 3
1
1 2 1 3 1
a These
animals had an odd number of claws examined because the apical portion of the remaining claw had been removed by the practitioner at the feedlot. — = no visible lesions; * = , 25% of the subdivision affected; ** = 26% to 50% of the subdivision affected; *** = 51% to 75% of the subdivision affected; **** = . 76% of the subdivision affected.
a These
The finding that AWLS likely precedes, and may be necessary for, the development of TTN supports the hypothesis that TTNS is the result of excessive wear in the region of the apical white line. In fact, in other studies of the feet submitted, Paetsch (17) found that the thickness of the apical sole at the white line of affected claws from CASES was statistically significantly (P , 0.001) thinner than was the sole of CONTROLS at the same location. In the affected claws examined grossly and histologically there was no evidence of necrosis in the absence of inflammation suggesting that aseptic necrosis, as would be seen in ischemic necrosis associated with hypostasis or thrombosis associated with vasculitis, does not occur in TTN. Further to this, vasculitis was not seen and changes to blood vessels were not present without evidence of inflammation of the surrounding tissues. In none of the claws examined was there evidence of displacement of P3 relative to the hoof capsule and neither were there any histologic lesions consistent with laminitis (18) without there also being evidence of inflammation due to the presence of bacteria. Finally, there was no evidence of embolic spread of bacteria to the claw such as isolated foci of inflammation surrounded by normal tissue. Instead, what was present were different forms of evidence that TTN starts as a defect at the white line at the apex of the claw and that the presence of this defect allows for the entry of bacteria into the corium that can then spread, by extension, proximally to P3. Bacteria within the claw may then serve as a nidus for the local or more distant spread of bacteria and the lesions of TTNS. The white line is a structure susceptible to injury because it represents the junction between the horn of the walls and the horn of the sole and is, therefore, unstable. The horn of the white line is also very soft, being only 20% as hard as the horn of the wall (3). Finally, the white line terminates at the sole and
is subject to various environmental factors combined with the wear and tear of ambulating (3,5). The fact that lesions of TTN were identified in the feet of 2 animals that were diagnosed as CONTROLS by the submitting practitioner, and in both claws in the same foot and, in some cases, all 4 hind claws, suggests that TTN and TTNS may go unrecognized in some feedlot cattle. If these lesions are associated with stress or pain, or are otherwise associated with poor performance, TTNS may be a much larger welfare and financial issue than is currently believed. An important shortcoming of these studies is the relatively small numbers of claws that were examined from few animals. Nevertheless, we believe these studies have heuristic value that provides insights into the pathogenesis of TTN and TTNS; suggest further methods of inquiry; and contribute to future lines of investigation. Future postmortem studies of TTN will almost certainly benefit from the examination of apparently unaffected claws from animals diagnosed with TTNS, as well as the examination of claws from feedlot cattle thought to be free of TTN. Given the results of these studies, feedlot operators, veterinarians, and researchers would be justified in directing future studies of TTN in areas such as determining risk factors for development of disease and the introduction of preventative measures.
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animals had an odd number of claws examined because the apical portion of the remaining claw had been removed by the practitioner at the feedlot. 1 = lesions present; — = no visible lesions; n/a = not applicable as there were no tissues to evaluate.
Acknowledgments These studies were supported by grants from the Beef Cattle Research Council and the Saskatchewan Ministry of Agriculture’s Agriculture Development Fund. CVJ
References 1. Blowey RW, Weaver AD. Color Atlas of Diseases and Disorders of Cattle. 3rd ed. New York, New York: Mosby Elsevier, 2011:99–146.
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12. Kofler J. Clinical study of toe ulcer and necrosis of the apex of the distal phalanx in 53 cattle. Vet J 1999;157:139–147. 13. Paetsch CD, Jelinski MD. Toe-tip necrosis syndrome in feedlot cattle in Western Canada. Proc 17th Int Symp & 9th Conf Lameness in Ruminants, Bristol, UK 2013:152–153. 14. Haines DH, Matin KM, Clark EG, Jim GK, Janzen ED. The immunohistochemical detection of Mycoplasma bovis and bovine viral diarrhea virus in tissues of feedlot cattle with chronic, unresponsive respiratory disease and/or arthritis. Can Vet J 2001;42:857–860. 15. Taylor LF, Van Donkersgoed J, Dubovi EJ, et al. The prevalence of bovine viral diarrhea virus infection in a population of feedlot calves in Western Canada. Can J Vet Res 1995;59:87–93. 16. Shahriar FM, Clark EG, Janzen E, West K, Wobeser G. Coinfection with bovine viral diarrhea virus and Mycoplasma bovis in feedlot cattle with chronic pneumonia. Can Vet J 2002;43:863–868. 17. Paetsch CD. Epidemiology of toe tip necrosis syndrome in Western Canadian feedlot cattle [MSc thesis]. Saskatoon, Saskatchewan: University of Saskatchewan, 2014. 18. Thoefner MB, Wattle O, Pollitt CC, French KR, Nielsen SS. Histopa thology of the oligofructose-induced acute laminitis in heifers. J Dairy Sci 2005;88:2774–2782.
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2. Chenoweth PJ. Cow/calf welfare considerations. In: Chenoweth PJ, Sanderson MW, eds. Beef Practice: Cow-Calf Production Medicine. Ames, Iowa: Blackwell, 2005:251–264. 3. Greenough PR. Bovine Laminitis and Lameness: A Hands-on Approach. New York, New York: Saunders Elsevier, 2007:1–7, 8–28, 36–54, 84–106. 4. Stokka GL, Lechtenberg K, Edwards T, et al. Lameness in feedlot cattle. Vet Clin North Am Food Anim Pract 2001;17:189–207. 5. van Amstel SR, Shearer J. Manual for Treatment and Control of Lameness in Cattle. Ames, Iowa: Blackwell, 2006:1–15, 16–30, 31–41. 6. Vermunt JJ, Malmo J, Parkinson TJ. Diseases of Cattle in Australasia: A Comprehensive Textbook. Wellington, New Zealand: VetLearn, 2010: 660–719. 7. Griffin D. Feedlot diseases. Vet Clin North Am Food Anim Pract 1998;14:199–230. 8. Miskimins DW. Bovine toe abscesses. Proc 8th Int Symp Disorders of the Ruminant Digit and Int Conf on Bovine Lameness, Banff, Alberta 1994:54–57. 9. Miskimins DW. Predominant causes of lameness in feedlot and stocker cattle. Proc 12th Int Symp Lameness in Ruminants, Orlando, Florida, USA 2002:147–151. 10. Miskimins DW. Update on toe abscesses in feedlot cattle. Proc 12th Int Symp Lameness in Ruminants, Orlando, Florida 2002:448–449. 11. Sick FL, Bleeker CM, Mouw JK, Thompson WS. Toe abscesses in recently shipped feeder cattle. Vet Med Small Anim Clin 1982;77: 1385–1387.
L
Introduction
ameness is the alteration of the gait of an animal and can be associated with painful conditions of the limbs. Pain, including pain in the feet of cattle, can manifest in signs that are difficult to recognize, such as decreased physical activity, and a reduction in food and water consumption. While lameness in dairy cattle has received far more attention than lameness in feedlot cattle, much of what is known regarding the impact of lameness in dairy cattle can be extrapolated to feedlot cattle. So,
for a variety of reasons, including reduced feed conversion and weight gain, costs of treating lame animals, humane euthanasia of animals before reaching slaughter, lameness is associated with financial losses. Therefore, lameness is an issue of great importance to cattle feedlot operators and veterinarians for both welfare and economic concerns (1–6). There are several causes of lameness in cattle attributable to lesions in the foot. One such cause in feedlot cattle that has been previously reported in the scientific veterinary literature
Department of Veterinary Pathology (Gyan, Allen) and the Department of Large Animal Clinical Sciences (Paetsch, Jelinski), Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4. Address all correspondence to Dr. Andrew Allen; e-mail: [email protected] Dr. Gyan’s current address is the Veterinary Diagnostic Laboratory, Ministry of Food Production, Eric Williams Medical Sciences Complex, Building 49, Uriah Butler Highway, Champs Fleurs, Trinidad and Tobago. Dr. Paetsch’s current address is Paetsch Veterinary Services, Box 264, Muenster, Saskatchewan S0K 2Y0. Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere.
1134
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or being free of, TTN and, in doing so, ii) further characterize the lesions of TTN and provide insights into the pathogenesis of the disease.
Materials and methods The animals used in this study came from feedlots located in southern Alberta, during October and November of 2012. Generally, the animals were commercial mixed-breed beef cattle that would have arrived at the feedlot, on different dates, from either an auction mart or a beef cattle ranch. During the time when samples were collected, these animals, both males and females, would have ranged from 7 to 9 mo of age and weighed between 175 and 320 kg. Shortly after arrival, and following a period for acclimation and processing, cattle received a total mixed ration consisting of alfalfa hay, barley silage, and a vitamin and mineral supplement. During the collection period, animals would have been on this feed for an average of 23 d. Typically, the animals were kept in groups of about 300, in open feeding pens measuring about 50 3 80 m, with a base of dirt or dirt and gravel that was sloped away from the feed bunk to promote drainage, and covered with straw. The feed bunk in each pen was constructed of concrete or wood which would have included a 1 to 2 m wide concrete apron for the animals to stand upon while eating. Handling alleys had a gravel base and processing facilities had a concrete base, sometimes augmented with metal. Environmental temperatures during October and November of 2012 ranged from a low of about 210°C to a high of about 110°C. As a result, damp portions of a pen may have been frozen (i.e., contained ice). The hind feet of some of these cattle were collected by 3 veterinary feedlot practices during October and November of 2012. The veterinarians collected either 1 or both hind feet from cattle they had euthanized following a clinical diagnosis of TTN or TTNS. In some instances, TTN was confirmed at the feedlot by removing the apex of at least 1 claw and observing the appropriate lesions. Claws from which the apex had been removed were not used in any of the studies described here. During the same time period, intact hind feet were collected from other cattle in the same feedlots that had died or been euthanized for causes unrelated to TTNS. At least 1 foot was submitted from 67 animals affected with TTNS (i.e., CASES), and 68 animals that died or were euthanized with other diseases (i.e., CONTROLS). All feet submitted from the 135 animals were examined and 3 separate studies were conducted using different subsets of the submitted feet. For the purposes of these studies, TTN was defined as a lesion of the foot involving inflammation or necrosis of the corium with or without any combination of inflammation, necrosis, or lysis of P3. However, TTN did not include other known causes of lameness including, but not limited to, septic arthritis, fractures, and interdigital dermatitis.
Study 1: Prediction of TTN based on the presence of apical white line separation Thirty-nine, arbitrarily selected, intact hind claws, both medial and lateral, and excluding those claws where the apex had been 1135
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is a so-called toe abscess (3,7–11). However, Kofler (12), in a paper describing the same or similar condition in dairy cattle, argued that the term “abscess” was inappropriate, and that a toe ulcer complicated by necrosis of the apex of the distal phalanx (P3) was a more accurate description. Recently, the terms “toe necrosis” (1) or “toe-tip necrosis syndrome” (TTNS) (13) have been introduced into the lexicon of those working on lameness in ruminants. The latter term incorporates the lesions in the foot, or toe tip necrosis (TTN), and the sequelae, TTNS, which may include interphalangeal arthritis, osteomyelitis of the middle and proximal phalanges, flexor tendonitis, cellulitis, and embolic spread of bacteria to the lungs, liver, and kidneys (8,11,13). Greenough (3) has provided a summary of the limited literature concerning TTN, and Blowey (1) has published some useful images of the lesions. Toe tip necrosis is a disorder most commonly affecting the lateral claw of the hind feet of 10- to 12-month-old beef cattle that develops within several days to a few weeks after processing, weaning, and transportation to a feedlot. The epidemiology and pathogenesis of TTN has never been critically studied (3,13); however, several hypotheses have been suggested. One hypothesis is that trauma, in the form of excessive wear of the sole associated with abrasive surfaces such as concrete, metal, and ice, allows bacteria to enter the white line at the apex of the claw (3). Another suggests that hypostasis — the settling of blood in the distal limbs — associated with lack of mobility while being transported for long periods of time results in ischemic necrosis of the apex of the P3, which is followed by rupture of the white line (3). Three other hypotheses have not been clearly articulated in the literature. However, it has been speculated that the rapid shift to a high grain ration upon arrival at the feedlot leads to a metabolic disturbance and laminitis, which then allows for the displacement or rotation of P3 relative to the claw capsule and penetration of the apex of P3 through the sole (3–5). At the same time, cattle infected with bovine viral diarrhea virus (BVDV) are typically present within populations of western Canadian feedlots (14,15) and morbid feedlot cattle often have vascular lesions in the heart and lungs (7,16). So, it has been speculated that BVDV might cause vascular lesions and ischemic necrosis in the claws and predispose some animals to TTNS (13). Finally, because some animals with TTNS have evidence of embolic bacterial disease, consideration should be given to the possibility that TTN is the result of bacteria arriving in the claw hematogenously. Historically, TTNS is believed to affect approximately 2 per 10 000 feedlot cattle. The incidence of TTNS can vary between feedlots, but this variability appears to be related to lots, i.e., financial entities of large groups of animals, typically more than 100 and less than 1000. Most lots of feedlot cattle will have no animals affected with TTNS, while a few lots could have between 0.01% to 1.3% of animals affected (17). The studies reported here were part of a larger epidemiologic study of TTNS in western Canadian feedlot cattle and were performed with the following goals: i) to conduct gross and histologic postmortem examinations on a subset of the feet of feedlot cattle diagnosed ante-mortem as either suffering with,
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A
B
C
D
E
F
Figure 1. A — The hind foot of a feedlot animal showing apical white line separation in 1 of the claws. B — A sagittal section of a hind claw of a feedlot animal with lesions of toe tip necrosis. Superimposed on the image are lines which divide the claw into subdivisions 1 through 5 that were used to evaluate the distribution of lesions. C — A sagittal section of a hind claw of feedlot animal Y6616 with subtle apical white line separation and small, focal lesions of toe tip necrosis involving subdivision 1. D — A sagittal section of a hind claw of feedlot animal G7443 with apical white line separation and extensive lesions of toe tip necrosis involving subdivisions 1, 2, and 3. E — A sagittal section of a hind claw, different from that in C, of feedlot animal Y6616. There is apical white line separation and lesions of toe tip necrosis involving all subdivisions (1 through 5) of the claw. Note the extension of lesions into the distal interphalangeal joint, joint capsule and distal sesamoid bone. F — A sagittal section of a hind claw different from that in E, of feedlot animal G7743. There is apical white line separation and lesions of toe tip necrosis involving all subdivisions (1 through 5) of the claw. Note the absence or loss of subdivision 1. There is also extension of lesions into the distal interphalangeal joint, joint capsule and distal sesamoid bone.
removed by the practitioner, from 28 animals underwent an external gross inspection by LAG and ALA, who were “blind” as to disease status, i.e., whether the feet were from CASES or CONTROLS as diagnosed by the submitting practitioner, to identify the presence or absence of apical white line separation (AWLS) (Figure 1A). Each claw was then serial sectioned in the sagittal plane using a band saw and the internal structures examined by a third person (CDP) to identify the presence or absence of gross lesions of TTN. CDP was “blind” to the presumptive clinical disease status as diagnosed by the submitting practitioner and “blind” to the presence or absence of AWLS. The results of these 2 examinations were plotted in a 2 3 2 contingency 1136
table (Table 1) and, using Fisher’s exact test, the probability of the distribution, predictive values, and sensitivity and specificity calculated using an analytical software program (Prism 6 for Windows; GraphPad Software, La Jolla, California, USA).
Study 2: Distribution and severity of lesions based on gross evaluation Thirteen, arbitrarily selected, intact claws from 1 or both hind feet of 6 CASES, different from those used in Study 1, were serially sectioned in the sagittal plane using a band saw and the internal structures examined to identify any lesions present. Claws with lesions of TTN were studied further. Color images CVJ / VOL 56 / NOVEMBER 2015
Table 1. The 2 3 2 contingency table showing the distribution of apical white line separation and the presence of toe tip necrosis in hind claws collected from southern Alberta feedlot cattle during October and November of 2012
TTN TTN present absent Total
AWLS present AWLS absent Total
4 0 4 1 34 35 5 34 39
TTN — toe tip necrosis; AWLS — apical white line separation.
Study 2: Distribution and severity of lesions based on gross evaluation Evaluation of Table 2 reveals that grossly visible lesions of TTN were present in every claw examined and in 36 of the 65 subdivisions of the claws, or 55.4%. Toe tip necrosis always involved the distal tip of the claw (subdivision 1) and never appeared at the proximal aspect of P3 (subdivisions 4 and 5) without also being present in the intervening area (subdivisions 2 and 3).
Study 3: Distribution and characterization of lesions based on microscopic evaluation
Study 3: Distribution and characterization of lesions based on microscopic evaluation
An approximately 4-mm sagittal section, containing the most extensive lesions, of a claw from each of the affected animals (CASES) represented in Study 2, was fixed in 10% neutral buffered formalin. Following fixation, each sagittal section was further cut into the 5 previously described subdivisions using a band saw. The hoof, or keratin capsule, was removed from the underlying tissue with a scalpel with an effort to include as much corium as possible. Each subdivision was then decalcified in 20% formic acid and routinely processed, i.e., embedded in paraffin, cut at 4 mm, mounted on glass slides, stained with hematoxylin and eosin, and cover slipped, for routine microscopic examination. Selected subdivisions were also stained with the periodic acid-Schiff reaction and Gram’s stain to help identify the basement membrane of the epidermal lamellae, and for bacteria, respectively. Each subdivision of P3 and the surrounding soft tissue was then microscopically evaluated for the presence of inflammation, including laminitis and vasculitis; thrombi; necrosis of bone, soft tissues, or both; the presence of bacteria; and changes to the epidermal lamellae suggestive of laminitis (3). A summary of the lesions present in each subdivision is found in Table 3.
Sixty-four slides, 1 of each subdivision of each of the 13 claws, were evaluated. One section, from subdivision 1 of animal G7443 could not be made because of the absence of tissues (Figure 1F). The results, summarized in Table 3, reveal that microscopic lesions were present in 57 of the 64 subdivisions of affected claws. If subdivision 1 of animal G7443 is added to these totals, then lesions would have been present in 58 of 65 subdivisions, or 89.2%.
Results Study 1: Prediction of TTN based on the presence of apical white line separation The hind feet examined came from 10 CASES and 18 CONTROLS as diagnosed by the submitting practitioner. During the “blind” examination of the 39 claws, the presence of AWLS correctly predicted the presence of TTN in 4 of 4 instances (100%); and the absence of AWLS correctly predicted the absence of TTN in 34 of 35 instances (97%) (Table 1), representing a sensitivity of 80% and a specificity of 100%. The probability of obtaining this distribution by chance is remote (P , 0.0001). An interesting finding was the presence of TTN in the feet of 2 animals that were diagnosed as CONTROLS by the submitting practitioner. CVJ / VOL 56 / NOVEMBER 2015
Discussion Under the conditions of Study 1, the positive predictive value of AWLS for the diagnosis of TTN was 100% and the negative predictive value of the absence of AWLS for the absence of TTN was 97%. However, given the relatively small number of claws examined, it remains uncertain if AWLS is necessary for TTN to develop, or if the development of TTN leads to AWLS. The fact that 1 claw was diagnosed as having TTN in the absence of AWLS might provide some insight into this question. However, the 2 pathologists participating in this study (LAG and ALA) believed the diagnosis of TTN in that claw may have been the result of interpreting changes associated with postmortem freezing, i.e., interpreting the redness within the corium associated with postmortem lysis of erythrocytes, as redness associated with inflammation. Regardless, examination of the distribution and severity of lesions, as summarized in Tables 2 and 3, support 2 ideas. First, that microscopic evaluation is a more sensitive means of identifying and characterizing the presence of lesions than is gross evaluation and, second, that it was never the case that lesions were present in the more proximal aspects of the claw without being present in the distal aspects. The latter observation suggests that TTN is the result of an ascending infection that starts at the distal tip of the claw and progresses proximally. This finding supports the hypothesis that AWLS is the primary lesion that allows for the development of TTN. 1137
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of the sagittal sections of each claw were made and divided into 5 subdivisions as illustrated in Figure 1B. The subdivisions were created by drawing a line through P3 that extended from the distal tip to the center of the proximal articular surface. This line was then measured and subsequently divided into approximately equal thirds by drawing 2 lines, perpendicular to the first line, which extended between the dorsal and plantar surfaces. Lesions included any changes in color, texture, or both; interpreted to be any combination of inflammation, necrosis, or lysis. An estimate of the proportion of the subdivision affected was made and categorized as “no visible lesions,” “, 25% of the subdivision affected,” “26% to 50% of the subdivision affected,” “51% to 75% of the subdivision affected,” or “. 76% of the subdivision affected” and entered into a summary table (Table 2). An example of small, focal lesions, restricted to subdivision 1 is presented in Figure 1C. An example of extensive lesions, involving subdivisions 1, 2, and 3 is presented in Figure 1D. An example of nearly diffuse lesions, involving subdivisions 1 through 5 is presented in Figure 1E.
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Table 2. Distribution and severity of lesions within subdivisions of a sagittal section of a hind claw diagnosed with toe tip necrosis. The claws were collected from southern Alberta feedlot cattle during October and November of 2012
Table 3. The presence or absence of histologic lesions within subdivisions of a sagittal section of a hind claw diagnosed with toe tip necrosis. The claws were collected from southern Alberta feedlot cattle during October and November of 2012
Subdivision number
Subdivision number
Animal Claw 1 2 3 4 5
Animal Claw 1 2 3 4 5
7565
**** **** **** **** **** **** **** **** — —
7565 1 1 2 1
1 1
1 1 1 1 — 1
E9516 1 2
** — — — — **** — — — —
E9516 1 1 2 1
1 1
1 1
1 1
— 1
G7443a 1 2 3
**** * * *** ** ** — — — — **** ** ** — —
G7443a 1 n/a 1 2 1 1 3 1 1
1 1 1
1 1 1
1 — 1
K2084 1 2
**** * * — — * ** ** — —
K2084 1 1 2 1
1 1
1 1
1 1
1 1
P0384a 1
**** ** ** — —
P0384a 1
1
1
1
1
* * — — — * — — — — **** **** **** **** ****
Y6616a 1
1 — 1
1 1 1
— — 1
— 1 1
1 2
Y6616a 1
2 3
1
1 2 1 3 1
a These
animals had an odd number of claws examined because the apical portion of the remaining claw had been removed by the practitioner at the feedlot. — = no visible lesions; * = , 25% of the subdivision affected; ** = 26% to 50% of the subdivision affected; *** = 51% to 75% of the subdivision affected; **** = . 76% of the subdivision affected.
a These
The finding that AWLS likely precedes, and may be necessary for, the development of TTN supports the hypothesis that TTNS is the result of excessive wear in the region of the apical white line. In fact, in other studies of the feet submitted, Paetsch (17) found that the thickness of the apical sole at the white line of affected claws from CASES was statistically significantly (P , 0.001) thinner than was the sole of CONTROLS at the same location. In the affected claws examined grossly and histologically there was no evidence of necrosis in the absence of inflammation suggesting that aseptic necrosis, as would be seen in ischemic necrosis associated with hypostasis or thrombosis associated with vasculitis, does not occur in TTN. Further to this, vasculitis was not seen and changes to blood vessels were not present without evidence of inflammation of the surrounding tissues. In none of the claws examined was there evidence of displacement of P3 relative to the hoof capsule and neither were there any histologic lesions consistent with laminitis (18) without there also being evidence of inflammation due to the presence of bacteria. Finally, there was no evidence of embolic spread of bacteria to the claw such as isolated foci of inflammation surrounded by normal tissue. Instead, what was present were different forms of evidence that TTN starts as a defect at the white line at the apex of the claw and that the presence of this defect allows for the entry of bacteria into the corium that can then spread, by extension, proximally to P3. Bacteria within the claw may then serve as a nidus for the local or more distant spread of bacteria and the lesions of TTNS. The white line is a structure susceptible to injury because it represents the junction between the horn of the walls and the horn of the sole and is, therefore, unstable. The horn of the white line is also very soft, being only 20% as hard as the horn of the wall (3). Finally, the white line terminates at the sole and
is subject to various environmental factors combined with the wear and tear of ambulating (3,5). The fact that lesions of TTN were identified in the feet of 2 animals that were diagnosed as CONTROLS by the submitting practitioner, and in both claws in the same foot and, in some cases, all 4 hind claws, suggests that TTN and TTNS may go unrecognized in some feedlot cattle. If these lesions are associated with stress or pain, or are otherwise associated with poor performance, TTNS may be a much larger welfare and financial issue than is currently believed. An important shortcoming of these studies is the relatively small numbers of claws that were examined from few animals. Nevertheless, we believe these studies have heuristic value that provides insights into the pathogenesis of TTN and TTNS; suggest further methods of inquiry; and contribute to future lines of investigation. Future postmortem studies of TTN will almost certainly benefit from the examination of apparently unaffected claws from animals diagnosed with TTNS, as well as the examination of claws from feedlot cattle thought to be free of TTN. Given the results of these studies, feedlot operators, veterinarians, and researchers would be justified in directing future studies of TTN in areas such as determining risk factors for development of disease and the introduction of preventative measures.
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animals had an odd number of claws examined because the apical portion of the remaining claw had been removed by the practitioner at the feedlot. 1 = lesions present; — = no visible lesions; n/a = not applicable as there were no tissues to evaluate.
Acknowledgments These studies were supported by grants from the Beef Cattle Research Council and the Saskatchewan Ministry of Agriculture’s Agriculture Development Fund. CVJ
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CVJ / VOL 56 / NOVEMBER 2015
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