A 4-week-old Thoroughbred filly foal with a history of sepsis was evaluated for right hindlimb lameness. Bilateral femoropatellar and femorotibial joint effusions were detected. Ultrasonography and radiography of the right stifle revealed signs of joint collapse and periarticular swelling. Computed tomography revealed abnormalities in the bone density of the medial femoral condyle of the right hindlimb and lateral femoral condyle of the left hindlimb. Euthanasia was recommended based on the severity of the lesions. Gross and microscopic examinations revealed extensive separation of the articular-epiphyseal cartilage complex from the subchondral bone of the femoral condyles. The histological features suggest an ischaemic aetiology; comparisons are made with lesions of osteochondrosis and avascular necrosis of bone.
Ischaemic necrosis of the femoral condyles has been infrequently described in foals (Hance et al. 1993; Rogerson 2008). Hance et al. (1993) described 8 cases of ‘Type III’ lesions with extensive loss of the articular surface and underlying subchondral bone. These authors described coagulative necrosis of both cartilage and bone along the osteochondral junction, surrounded by a zone of granulation tissue. These changes were interpreted as consistent with an ischaemic event, although the specific cause was not apparent. It was suggested that the disease may be a severe variant of osteochondrosis. However, it is now generally accepted that osteochondrosis in horses is primarily a disease of the growth cartilage (Carlson et al. 1995; Ytrehus et al. 2007; Olstad et al. 2011) rather than subchondral bone. Avascular necrosis (AVN) of bone is a syndrome in man that has some similarities to the condition in foals (Lafforgue 2006). It manifests as ephiphyseal necrosis and can affect the femoral head or condyles. In AVN, disruption to the vascular supply of the bone and cartilage occurs, but multiple different causes exist. In human adults, microfractures within the femoral neck or subchondral fractures are believed to disrupt the vascular supply, but some cases occur without detectable fractures. Thrombi, fat emboli and increased bone marrow pressure are some of the proposed causes of intraluminal or extraluminal vascular obstruction (Lafforgue 2006; Bullough 2010). Necrosis of the femoral condyles has been reported most commonly in foals with a history of sepsis (Hance et al. 1993; Rogerson 2008). Coagulopathy is a known risk factor in man and this may help explain the association between sepsis and the disease in foals (Lafforgue 2006).
The few previous reports have described unilateral lesions in the medial femoral condyle (Hance et al. 1993; Rogerson 2008). This case report describes the disease in a foal following sepsis and severe hypoxaemia. Unusually, this foal had lesions affecting both the lateral and medial condyle of the right hindlimb and the lateral femoral condyle of the left hindlimb. Ultrasonographic and computed tomography (CT) findings are also reported. Better description of the clinical, imaging and pathological features of this condition should aid our understanding of the disease.
A 4-week-old Thoroughbred filly foal weighing 66 kg presented to Rossdales Equine Hospital for evaluation of right hindlimb lameness. The foal had been hospitalised in the Peter Rossdale Foal Unit for the first 7 days of life for treatment of severe perinatal asphyxia syndrome and sepsis (modified sepsis score 14 [Brewer 1988]). The foal required intensive care including i.v. fluids, plasma, parenteral nutrition, oxygen insufflation, blood pressure support (dobutamine), antimicrobials (ticarcillin-clavulanate), antioxidants (vitamin E, allopurinol, magnesium sulphate), gastroprotectants (omeprazole, sucralfate) and respiratory stimulants (caffeine). At age 12 h, severe hypoxaemia (PaO2 49 mmHg, reference range [rr] 7–90 mmHg) developed, which was refractory to high rates of intranasal oxygen supplementation (15 l/min) and suspected to be due to pulmonary hypertension. The foal responded well to intensive care and was ambulatory 3 days after admission. At age 5 days a mild (1/5) right hindlimb lameness and femoropatellar joint effusion were noted. A synovial fluid sample had a normal total nucleated cell count (0.72 × 109/l, rr 0–2 × 109/l) and mildly increased total protein content (36 g/l, rr <20 g/l) consistent with a nonseptic reactive synovitis. Radiographs did not reveal changes typical of the presence of osteomyelitis or septic synovitis. The foal was discharged with a short course of trimethoprim-sulphadiazine and instructions to continue box rest. The foal's degree of lameness worsened following discharge and she became lethargic and unwilling to rise. She was re-evaluated at age 4 weeks.
A general physical examination was unremarkable with the exception of severe effusion of the right femoropatellar and medial femorotibial joints. Moderate effusion of the left stifle was also noted. The foal was 4/5 lame in the right hindlimb and was unwilling to trot. When forced to trot, the foal adopted a ‘bunny-hopping’ hindlimb gait. Haematalogy and serum biochemistry revealed a mild hyperfibrinogenaemia (5.2 g/l, rr 1.5–4.2 g/l), but no other significant abnormalities.
Caudocranial and lateromedial radiographic projections of the right stifle were obtained using a gantry-mounted x-ray generator and computed radiography (CR) systema. There was complete loss of the joint space in the medial compartment of the femorotibial joint (Fig 1). The medial femoral condyle contained areas of bone sclerosis and lysis. Soft tissue swelling was visible on the lateral and medial aspects of the stifle, with material of variable radiodensity visible medially, suspected to have been displaced from the medial femorotibial joint.
Ultrasonographs of the right stifle were obtained using an ultrasonographic unit and 12 MHz linear transducerb. Severe effusion of all 3 joint compartments with synovial proliferation was detected. Ultrasonography of the medial aspect of the femorotibial joint revealed collapse of the joint space and abaxial displacement of the medial meniscus from its normal anatomical location (Fig 2).
Synovial fluid from the medial femorotibial joint had a mildly increased total nucleated cell count (4 × 109/l, rr 0–2 × 109/l) and total protein (32 g/l, rr <20 g/l). Cytological evaluation revealed nondegenerate PMNs and reactive synviocytes and lymphocytes consistent with a nonseptic synovitis. Analysis of synovial fluid from the lateral femorotibial joint were considered within normal limits.
The foal was anaesthetised and placed in dorsal recumbency with the limbs positioned in full, but not forced flexion. Helical CT images, collimated to a slice thickness of 1 mm, were acquired of the femorotibial articulations of both hindlimbs using a Siemens Volume Zoom M 4-slice helical CT scannerc. The rotation time was 0.75 s and the feed/rotation time 3.5 mm. The scan length was 26 cm and scan direction caudocranial. The images were exported to a DICOMd workstation and manipulated using Osirix version 3.3.2 32bitd. The 2D data set was reconstructed using soft tissue and bone optimised algorithm into multi-planar reformatted and volume rendered images for full evaluation of the femorotibial articulations.
The cancellous bone of the medial femoral condyle in the right hindlimb and the lateral femoral condyle in the left hindlimb (Fig 3) was hyperattenuating. An irregular linear radiolucent region was evident in the right medial femoral condyle just proximal to the articular surface and there was a similar, though less well defined, loss of density in the lateral femoral condyle of the left hindlimb. Complete collapse of the lateral femorotibial joint space was detected, with the articular surfaces of the femoral and tibial condyles apposing each other (Fig 4).
Based on the severity of the lameness and the lesions detected by imaging, euthanasia was recommended. However, due to a reluctance of the owner to subject the foal to euthanasia it was discharged from the hospital with instructions to administer oral meloxicam (0.6 mg/kg bwt per os b.i.d.) and continue strict box rest. The foal was subjected to euthanasia 7 days after the initial imaging was performed.
At gross post mortem examination, there was marked periarticular oedema around the right stifle, with a large excess of clear dark yellow watery synovial fluid and thickening of the joint capsule and synovium. Cartilage was completely absent from the right medial femoral condyle, with fragmentation and extensive loss of the exposed subchondral bone (Fig 5). Osteochondral fragments were embedded within the joint capsule. The caudomedial aspect of the lateral condyle was affected to a lesser extent, with an osteochondral flap separating from exposed subchondral bone. The opposing articular surfaces of the tibia had central areas of cartilage loss and eburnation, corresponding to areas in contact with the exposed condylar bone. The left stifle contained a smaller excess of synovial fluid. The left lateral condyle had similar changes to the right medial condyle, and the left medial condyle was grossly normal. All other appendicular joints were within normal limits.
The distal femur was sectioned with a band-saw at approximately 5 mm intervals in the frontal plane. Multiple regions were samples for histopathological examination, concentrating on areas where the flap of articular epiphyseal cartilage complex remained present (to avoid areas affected by secondary eburnation from contact with the tibia). Sections through the trochlear ridges were also processed. After formalin fixation, the bone was decalcified with hydrochloric acid (Decalcifier II)e prior to routine paraffin embedding. Sections with a thickness of 5 µm were stained with haematoxylin and eosin, and toluidine blue. Histologically, there was separation of the articular-epiphyseal growth complex (region a, Fig 6a, b) from subchondral bone. Vascular channels within this detached cartilage were often degenerate and necrosis of chondrocytes was evident surrounding some of these vessels (Fig 6e) and sometimes also at the proximal margin of the detached cartilage (not shown). The underlying osteochondral junction was replaced by a band of partially mineralised necrotic debris in which both fragments of bone and cartilage were present. Necrotic bone was also identified at the junction with more intact trabecular bone (Fig 6f). The necrotic areas were often surrounded by extensive areas of fibrosis, vascular proliferation and osteoclastic activity. No significant inflammatory infiltrates were detected in any of the sections examined. One degenerate vascular channel was detected extending through the osteochondral junction, filled with red blood cells and fibrillar eosinophilic material (Fig 6c).
This case report describes a case of ischaemic necrosis of the cartilage and bone of the femoral condyles in a young Thoroughbred filly. Severe stifle lameness in young foals is most commonly a direct result of septic arthritis or osteomyelitis (Firth 1983; Smith et al. 2004). The stifle is also commonly affected by osteochondrosis lesions, usually affecting the trochlear ridges of the femur, the intertrochlear groove or the patella (Dik et al. 1999; Walmsley 2003). Disease of the femoral condyles is only rarely reported (Stowater et al. 1986).
In a previous report of 20 foals with lesions in the caudal femoral condyles, 8 had severe lesions similar to those described in this case (Hance et al. 1993). In these cases, separation of an osteochondral fragment from the medial femoral condyle had led to exposure of large areas of the subchondral bone. Histological evaluation of these lesions revealed marked coagulative necrosis of both subchondral bone and cartilage, with a pattern suggestive of an ischaemic aetiology.
Osteochondrosis is believed to be caused by a failure of endochondral ossification (Jeffcott 1991; Ytrehus et al. 2007). Differing theories exist as to the exact pathogenesis but one major hypothesis is that failure of cartilage canals leads to ischaemic necrosis of growth cartilage (Carlson et al. 1995). The epiphyseal cartilage canal blood supply to the distal femur has been described in foals (Olstad et al. 2008) and its anatomy is suspected to render vessels vulnerable to failure. This is suspected to be intricately involved in the pathogenesis of osteochondrosis in foals.
In this case, and those reported by Hance et al. (1993), extensive degeneration of cartilage as well as subchondral bone was identified. This is unusual, as osteochondrosis in horses is considered primarily a disease of the cartilage (Ytrehus et al. 2007; Olstad et al. 2011). It is also interesting that in this foal no lesions were detected in the trochlear ridges, the distal intermediate ridge of the tibia or any of the other sites more commonly affected by osteochondrosis. It is therefore unclear whether the necrosis in this case could represent a severe form of osteochondrosis in which initial vascular injury at the level of the epiphyseal growth cartilage extended to include the subchondral bone. Alternatively, more widespread ischaemic injury may have resulted from initial vascular injury at a deeper level within the subchondral bone, with consequent degeneration of the cartilage canal vessels. This would be more akin to AVN, which is considered to be a primary disease of bone. Avascular necrosis is caused by local ischaemia and failure of the blood supply to bone. Osteochondrosis is caused by a failure of endochondral ossification, probably related to ischaemia from a failure of the cartilage canal system. It seems possible that in terms of aetiology, a degree of crossover may exist between these 2 conditions, depending on the site and extent of vascular injury. The lesions in this case were advanced in both limbs, and examination at an earlier timepoint may help to clarify the intiating pathology.
Further study of this condition will be necessary to identify its exact aetiology, which may well be multifactorial. The bilateral nature of the lesions suggests that the lesions are more likely to have a ‘systemic’ cause rather than, for example, being consequent to local trauma and microfractures of subchondral bone (Lafforgue 2006). This foal had experienced severe systemic illness prior to the onset of this disease and this is similar to cases in previous reports (Hance et al. 1993; Rogerson 2008). Sepsis is intricately linked to coagulopathy and inflammatory cytokines activate endothelium to a more pro-thrombotic state (Weiss and Rashid 1998). Activation of endothelium and the coagulation cascade can predispose horses to disseminated intravascular coagulation (Weiss and Rashid 1998). In cases of human AVN, hypercoagulability has been identified as a risk factor, leading to intra-luminal obstruction of blood vessels and necrosis of bone (Lafforgue 2006). As part of this foal's severe systemic illness, it suffered a period of severe hypoxaemia. It is suspected that this may have worsened the effects of already reduced perfusion to the femoral condyles and other tissues.
No other bones or joints were affected and it is not known why the disease manifests only in the femoral condyles. In man, the long bone epiphyses are the sites most commonly affected, although the femoral head is more frequently affected than the femoral condyles (Lafforgue 2006). The anatomy of the cartilage canal system to the femoral condyles in foals may predispose the bones to necrosis due to failure of the blood supply (Olstad et al. 2008).
The medial femoral condyle has been affected in all previously reported cases (Hance et al. 1993; Rogerson 2008). In this foal, the lateral condyle of the left stifle was affected in addition to the medial condyle of the right stifle. Subchondral bone cysts, which are considered a manifestation of osteochondrosis, affect the medial condyle almost exclusively and this is again considered to be related to the anatomy of the blood supply (Olstad et al. 2008). It is possible that the severity of this foal's systemic illness contributed to the presence of mulitfocal lesions.
In cases of human AVN, the disease is considered multifactorial and many other risk factors exist that were not present in this case (alcoholism, high doses of glucocorticoids etc.) (Lafforgue 2006). Genetic factors are considered to be very important in man and this may help explain why the disease occurs only rarely in foals when the incidence of sepsis is relatively high.
This case report also highlights the usefulness of CT in the diagnosis of the condition. Ultrasound and radiographs were not able to define the extent of the condition fully and CT proved to be extremely useful in defining the extent of the disease and the grave prognosis in this case. Computed tomography should be considered a useful adjunctive tool in the diagnosis of the condition.
The prognosis for this condition is extremely poor, although short-term survivors have been reported (Hance et al. 1993). The prognosis for this foal was grave based on the severity of the lesions. Prevention of this condition is difficult based on the sporadic occurrence of the disease. However, it would be interesting to know whether earlier and more rapid control of the foal's systemic disease and hypoxaemia could have prevented the condition.
In conclusion, necrosis of the femoral condyles should be considered as a cause of lameness in foals that have a history of sepsis or severe systemic disease and have lameness localised to the stifle region. This report documents an unusual case affecting both stifles and the lateral condyle. The aetiology of this rare condition is uncertain. The presence of bone and cartilage necrosis, in the absence of an inflammatory response, suggests an ischaemic aetiology. The condition may be a severe form of osteochondrosis, with necrosis not only affecting the cartilage but extending to the subchondral bone. Alternatively, it may be a separate type of disorder, more akin to AVN of bone. From the few accounts of previous similar cases in foals, preceding sepsis and perhaps coagulopathy may be factors in initiating the disease. The outcome in this case was poor due to the extent of the lesions. Computed tomography should be considered as a useful adjunctive tool for the diagnosis of the condition.