Ligament Laxity in Nonerosive Immune-Mediated Polyarthritis in Dogs: Five Cases (2009–2017)
ABSTRACT
Ligament laxity is a known complication of erosive immune-mediated polyarthritis (IMPA) in dogs. The purpose of this study was to describe the occurrence and clinical features of carpal or tarsal ligament laxity in cases of nonerosive IMPA in dogs for the first time. Five client-owned dogs with a diagnosis of nonerosive IMPA and carpal or tarsal ligament laxity in which the influence of corticosteroids was excluded were identified. Medical records were reviewed, and data including signalment, investigative findings, and treatment regimen (e.g., surgical management) was extracted. Primary care practices were contacted to obtain follow-up, and the data was descriptively analyzed. The affected joints were either carpi and tarsi (n = 3) or carpi only (n = 2). In three cases, surgical arthrodesis was performed. Three dogs were euthanized (1 mo, 12 mo, and 5 yr) as a result of the severity of clinical signs and poor control. In the four dogs surviving >6 mo, multiple episodes of relapse were recorded, and multimodal immunosuppression was needed. The prognosis for the dogs described was poor, with none achieving control of the disease without ongoing immunosuppressive therapy. Damage to soft-tissue periarticular structures may be related to prolonged clinical disease or a more severe presentation. Jaccoud’s arthropathy in humans with systemic lupus erythematosus may represent a homologous presentation.
Introduction
Immune-mediated polyarthritis (IMPA) is a common inflammatory disease in dogs. Clinical signs may include pain, stiffness, lameness, joint effusions, and pyrexia, which occur secondary to hypersensitivity reactions occurring in the synovial membrane and periarticular soft tissues, leading to inflammation of the affected joints.1,2 The carpal, tarsal, stifle, and elbow joints are most commonly affected.3 IMPA can be categorized as one of the four following subsets based upon associated disease processes. It is most commonly defined as idiopathic (type I); less commonly, it is associated with infectious disease (type II), gastrointestinal disease (type III), or neoplasia (type IV).4 IMPA is defined as nonerosive or erosive based on radiographic evidence of bone lysis in affected joints with erosive disease. The erosive form is associated with a worse prognosis, showing a poorer response to treatment than the nonerosive form.5 Erosive IMPA can be associated with joint instability (typically carpal and tarsal joints) secondary to damage to periarticular soft-tissue structures, leading to ligament laxity and joint collapse, which may necessitate arthrodesis.5,6
Ligament laxity is reported in nonerosive inflammatory polyarthritis in humans with systemic lupus erythematosus (in ∼5% of individuals), which is known as Jaccoud’s arthropathy.7,8 Jaccoud’s arthropathy is a syndrome that affects the metacarpophalangeal and interphalangeal joints, causing tendinopathies and reducible subluxations secondary to ligament laxity.8 Ligament rupture has also been reported in a small number of cases.9 Diagnosis is made based on compatible clinical signs, and a Jaccoud’s arthropathy index has been previously described in which a score is attributed on the basis of the presence of the described deformities and the number of affected digits.10 Some studies have suggested that Jaccoud’s arthropathy represents a late manifestation of longstanding inflammatory arthritis.11 MRI studies have shown both edematous and proliferative tenosynovitis as well as synovial hyperplasia, and these changes are associated with microvascular changes and perivascular monocytic inflammation.8,12 In contrast, to the authors’ knowledge, ligament laxity has not previously been described in cases of nonerosive IMPA in dogs. This case series describes the clinical features of nonerosive IMPA cases in which ligament laxity was identified as well as their management and outcome.
Materials and Methods
Case Selection
The databases of Langford Vets Small Animal Referral Hospital and Davies Veterinary Specialists were searched to identify cases of nonerosive IMPA presenting between 2009 and 2017 in which ligament laxity of the carpal or tarsal joints was described. The medical records of these cases were reviewed, and primary care practices were contacted to obtain follow-up. Cases with joint laxity in the stifle or coxofemoral joints were excluded as it was considered impossible to differentiate them from primary cruciate disease or hip dysplasia. Cases were excluded if they had received prednisolone above a physiological dose in the 3 mo prior to onset of ligament laxity in order to exclude iatrogenic hyperadrenocorticism as a cause of ligament laxity.13
Nonerosive IMPA was diagnosed on the basis of cytological evidence of increased cellularity and neutrophilic inflammation (>10% neutrophils identified by cytological total and differential cell counts) in synovial fluid aspirated from multiple joints in the absence of evidence of intra- or extracellular bacteria and the absence of erosive changes on radiography or computed tomography (CT) imaging.5,14 IMPA was then categorized according to criteria previously described by Bennett.4 Ligament laxity was defined based upon recorded physical examination findings including palmigrade or plantigrade stance of the carpi or tarsi when weight bearing and increased range of motion of these joints during board-certified orthopedic specialist examination.
Medical Records Review
For each case, signalment, body weight, clinical signs, and concurrent diseases at onset of signs were recorded. Clinical features recorded included treatment received prior to referral, radiographic findings, type of IMPA according to Bennett’s modified classification system, treatment received following diagnosis, joints affected by ligament laxity, dates of onset of ligament laxity, details of surgical management of ligament laxity if performed, and the length of available follow-up and outcome.4
Results
Signalment
Five dogs were identified with carpal or tarsal ligament laxity. The details of the cases are presented in Table 1. A range of sex and neuter statuses, breeds, body weights, and body condition scores were identified. Age at the onset of signs ranged from 1 yr, 9 mo to 8 yr, 2 mo.
Clinical Features
All five dogs had diagnostic investigations as part of screening for potential triggers for IMPA. Hematology, serum biochemistry, urine analysis, and thoracic imaging (radiographs, n = 4; CT, n = 1) were performed in all cases, and abdominal imaging was performed in four cases (radiographs, n = 2; ultrasound, n = 1; CT and ultrasound, n = 1) with no clinically significant changes identified. Infectious disease testing was performed in all cases. Serological testing was performed for Borrelia spp. (n = 2), Leishmania antibody (n = 1), and Ehrlichia (n = 1). Synovial fluid polymerase chain reaction was performed for Borrelia spp. (n = 3) and Bartonella spp. (n = 1), and blood polymerase chain reaction was performed for Anaplasma phagocytophilum (n = 1). Infectious disease screening was negative in all cases. Joint culture was performed in one case and was negative.
Additional diagnostics included urine culture (n = 3), serum protein electrophoresis (n = 1), C-reactive protein measurement (n = 3), rheumatoid factor (n = 2), cerebrospinal fluid analysis (n = 1), cobalamin and folate measurement (n = 1), basal cortisol (n = 1), fecal parasitology and culture (n = 1), and periarticular soft-tissue biopsy (n = 1). No significant abnormalities were identified on additional diagnostic testing. Periarticular soft-tissue biopsy identified fibrous and fibroblastic tissue with mild perivascular inflammation. One dog had a history of chronic gastrointestinal disease and was classified as type III. In the remaining cases, no triggers were identified, and they were classified as type I (n = 4).4
Two dogs presented with ligament laxity affecting both the carpi and tarsi bilaterally (Figure 1), and one dog presented with bilateral carpal ligament laxity. One dog presented with ligament laxity in a single carpal joint. One dog presented with unilateral carpal ligament laxity and developed contralateral carpal laxity within 5 mo. Two dogs had soft-tissue thickening of multiple joints but no palpable effusions; the remaining cases presented with multiple joint effusions.
Citation: Journal of the American Animal Hospital Association 55, 4; 10.5326/JAAHA-MS-6920
Ligament laxity developed after prednisolone therapy was stopped in all dogs in whom IMPA had been previously diagnosed and treated (n = 2; 4 and 7 mo after prednisolone withdrawal). One of these dogs was on ciclosporin as sole therapy at the time of ligament laxity onset.
One case presenting with carpal and tarsal ligament laxity bilaterally was receiving a physiological dose of prednisolone (0.07 mg/kg q 24 hr) at the time of the onset of ligament laxity as part of therapy for previously diagnosed dermatitis and rhinitis. There were no recent dose changes and no clinical signs consistent with hyperadrenocorticism. Prednisolone was withdrawn 3 wk prior to the diagnosis of IMPA.
Radiographic Findings
In four dogs, imaging was available for all the joints affected by ligament laxity; in one dog with bilateral carpi and tarsal involvement, only orthogonal views of the right carpus were obtained. No erosive lesions were identified. Serial radiographs of affected joints were available over a period of 7 mo to 3 yr for three cases, and there was no development of erosive changes.
Treatment
Therapy to treat the IMPA was instituted following diagnosis in all dogs. Initial therapies included prednisolone 0.9–2 mg/kg q 24 hr (n = 4) and combined prednisolone 1.6 mg/kg q 24 hr and ciclosporin 3.3 mg/kg q 24 hr (n = 1).
Surgical Intervention
Three cases underwent surgical management for ligament laxity. Arthrodesis of the calcaneoquartal joint and contralateral pancarpal arthrodesis had been performed in one case prior to the onset of the described carpal ligament laxity, for which arthrodesis was not required. The other two cases underwent staged bilateral pancarpal arthrodesis, which was performed at the recommendation of board-certified specialist orthopedic surgeons to address ongoing lameness associated with a palmigrade stance despite evidence of control of joint inflammation on serial synovial fluid cytology from multiple joints (n = 1) and medial instability in the left carpus and non-weight-bearing lameness associated with a marked palmigrade stance (n = 1). In this case, serial synovial fluid cytology identified ongoing joint inflammation at the time of the second pancarpal arthrodesis, and adjunctive immunosuppression was introduced with ciclosporin. Arthrodesis improved limb function and reduced lameness in both cases.
Outcome/Long-Term Follow-Up
Follow-up was available for all five cases (range 1 mo to 5 yr). None of the reported cases achieved resolution of disease to allow tapering of immunosuppression, and all dogs required lifelong immunosuppressive medication. Two dogs were euthanized prior to serial arthrocentesis as a result of a combination of severe clinical signs of IMPA and bilateral carpal and tarsal joint laxity, financial limitations to escalation, or change of immunosuppressive therapy (prednisolone, n = 1; prednisolone and ciclosporin, n = 1). In one case, bilateral carpal and tarsal arthrodeses were considered indicated because of bilateral palmigrade and plantigrade carpal and tarsal stance with associated lameness and reduced mobility, but the owners elected euthanasia (within 12 mo of diagnosis). The other case was euthanized within 1 mo of diagnosis, before serial synovial fluid cytology to assess control of IMPA and prior to consideration of surgical intervention.
The three cases with survival >12 mo had multiple recorded relapse episodes (documented by serial synovial fluid analysis performed as a result of IMPA clinical sign recurrence), and multimodal immunosuppressive therapy was ultimately required. The following combinations of immunosuppressive therapy were used: prednisolone and ciclosporin (n = 2); ciclosporin and leflunomide (n = 1); and ciclosporin, leflunomide, and prednisolone (n = 1). Surgical arthrodesis of multiple joints was performed in two cases.
Euthanasia occurred in one additional case after 5 yr of poorly controlled disease despite combined therapy with immunosuppressive prednisolone, ciclosporin, and leflunomide. In this case, previous surgical arthrodesis had successfully controlled ligament laxity; however, the dog was euthanized at the owner’s request because of the progression of signs of IMPA as a result of the side effects associated with existing multimodal immunosuppressive medication.
In both dogs in whom carpal arthrodesis is described, successful arthrodesis was ultimately achieved; however, revision surgery was needed in one case in whom skin dehiscence occurred over the plate 10 mo postoperatively secondary to a lick granuloma. Initial follow-up radiographs 6 wk postoperatively showed satisfactory progression of pancarpal arthrodesis; however, the radiocarpal joint space was still visible, and disuse osteopenia was reported. Following removal of the plate, carpal instability developed, and pancarpal arthrodesis was repeated. Successful stabilization of the joint was subsequently achieved; however, wound breakdown and associated infection were reported in the postoperative period but were managed with antibiotics. This dog was receiving immunosuppressive treatment for IMPA at the time of both surgeries (ciclosporin and leflunomide). The other dog reported was not immunosuppressed at the time of either surgery; no complications were reported.
Discussion
Ligament laxity has been previously considered a feature unique to erosive IMPA; however, these cases show that this can occur in nonerosive disease. The poor response to treatment and inability to achieve remission in these cases is analogous to the typically more aggressive disease seen in erosive IMPA.
The proposed mechanism for the development of ligament laxity in this cohort is that these cases represent a population of nonerosive IMPA cases with more severe inflammation, possibly extending to include the periarticular structures, with associated damage of the ligamentous support of the joint as is seen in erosive disease. Considering that in humans, ligament laxity is seen following more chronic disease courses, it could also be argued that extension to involve the periarticular soft tissue structures arises as a result of chronic poorly controlled disease.11 In two cases described here, ligament laxity developed soon after the diagnosis of IMPA, suggesting that chronicity of IMPA is not a contributing factor to development of ligament laxity in all cases. Delayed detection of clinical signs or extended time to diagnosis of IMPA cannot be completely excluded, and if present, this would alter the apparent temporal association between onset of IMPA and onset of ligament laxity. If ligament laxity represents an end stage of poorly controlled disease, more aggressive treatment earlier in the course of disease may be indicated.
The limitations of this study are associated with its retrospective nature and small case numbers. Ideally, additional diagnostic investigations would have been performed to more thoroughly exclude underlying causes or triggers of IMPA as well as additional causes of ligament laxity aside from IMPA such as hyperadrenocorticism. Although infectious disease screening was not complete, country of origin and lack of travel history meant index of suspicion of vector-borne disease was low. Additionally, the diagnosis of ligament laxity was limited to physical examination by specialist orthopedic surgeons. Although advanced imaging was available of affected joints in all cases to exclude erosive disease, stress views were not performed. A clinical diagnosis of carpal ligament laxity is based on visual assessment in comparison with the contralateral limb and with normal anatomy for the breed if the disease is bilateral. Calcaneoquartal joint instability, secondary to failure of the plantar ligament, is apparent as a mechanical alteration of the mid tarsus in the sagittal plane, and again, comparison with the contralateral tarsal joint is diagnostic (the difference between tarsi in unilateral disease is evident when weightbearing and is evident on manipulation).15 The diagnosis of ligament laxity can be made on the basis of physical examination findings; however, stress radiographs demonstrating hyperextension or collateral ligament laxity are useful for confirmation.15 Kinematic studies have demonstrated normal maximum angles of extension of 12–18° extension of the carpus; the functional angle of the tarsus is considered to be 135–145° extension when standing.16–18
Conclusion
Ligament laxity can be seen in both erosive and nonerosive IMPA. In nonerosive IMPA, development of ligament laxity was associated with severe disease and a poor prognosis more homologous to the clinical course previously described for erosive IMPA, in which multiple immunosuppressive therapies were used and controlled disease without relapse episodes could not be achieved. Proposed mechanisms for development of ligament laxity in nonerosive disease are that this may represent a subgroup of dogs with more marked inflammatory disease or that the loss of ligament support is the result of chronic, poorly controlled disease.
(A) Carpal and tarsal hyperextension in a shar pei with nonerosive immune-mediated polyarthritis. (B) Carpal hyperextension in a shar pei with nonerosive immune-mediated polyarthritis.
Contributor Notes
