Total Knee Arthroplasty in Patients with Juvenile Idiopathic Arthritis
RESEARCH ARTICLE

Total Knee Arthroplasty in Patients with Juvenile Idiopathic Arthritis

Jennifer R. Kallini1 , * Open Modal Antonia F. Chen2 Vivek M. Shah2
Authors Info & Affiliations
The Open Orthopaedics Journal • 03 Mar 2023 • RESEARCH ARTICLE • DOI: 10.2174/18743250-v17-e230202-2022-13
Previous Article | Next Article

Abstract

Medical and surgical management of knee pain in juvenile idiopathic arthritis (JIA) is rapidly evolving. It is important for the orthopaedic surgeon to remain informed. In this review, we discuss the recent trends in the surgical management of JIA in light of recent medical advances for the disease. The purpose of this article is to summarize current recommendations for TKA in patients with JIA.

Keywords: Juvenile idiopathic arthritis, Arthroplasy, Arthritis, Knee replacement, Patients, Joint pain.

1. INTRODUCTION

Knee pain affects patients of all ages. Up to 15% of the healthy pediatric population has presented to a physician complaining of musculoskeletal pain [1], and 1% of all children are evaluated for joint pain yearly [2]. Orthopaedic surgeons are often the first specialists to evaluate these patients, with one study revealing that up to 62% of children with juvenile idiopathic arthritis (JIA) were referred to an orthopaedist prior to a rheumatologist [3]. Therefore, although the etiology of pediatric joint pain is most commonly benign, orthopaedic surgeons should nevertheless have a thorough familiarity with the broad differential diagnosis for the complaint of knee pain.

The remainder of this article presupposes that a combination of clinical findings, laboratory tests, and advanced imaging has led to the diagnosis of JIA in a patient presenting with knee pain. The purpose of this article is to provide orthopaedic surgeons with an in-depth understanding of contemporary practices for total knee arthroplasty (TKA) in patients with JIA. As more long-term follow-up of TKA in JIA emerges, and as the recommendations for medical management of JIA evolve, so, too, have operative and perioperative recommendations been adjusted [4].

1.1. JIA Overview

The classification system for JIA has undergone three iterations of change since the 1970s. The International League of Associations of Rheumatologists most recently proposed that the term “juvenile rheumatoid arthritis” be made obsolete and replaced with the term “juvenile idiopathic arthritis,” or JIA [5]. JIA refers to persistent arthritis of unclear etiology lasting >6 weeks in patients <16 years old [6, 7]. The incidence and prevalence of juvenile arthritis are 10-20 patients per 100,000 individuals and 56-113 patients per 100,000 individuals, respectively [8]. The condition is most common in Caucasian females [9]. Over the course of 10 years, 50% of children with systemic or polyarticular disease and 40% with periarticular disease will experience active arthritis; 17% of all affected children will eventually need a walker [10].

Treatment is aimed at pain relief, disease control, and the prevention of damage and disability [9]. Medical management includes a combination of nonsteroidal anti-inflammatory medications [11], intra-articular steroid injections [12-14], steroid-sparing immunosuppressive disease-modifying antirheumatic drugs [DMARDs] (methotrexate [15-17], sulfasalazine [11, 15, 18], leflunomide [19], azathioprine, cyclosporine, and hydroxychloroquine), and biologic agents. Biologics are a relatively new category of medications and are mostly used off-label for the treatment of JIA. They include TNF-α inhibitors (etanercept [4], adalimumab, and infliximab [11]), interleukin antagonists [20], and other chimeric monoclonal antibodies [21, 22]. Systemic corticosteroids are rarely used in the treatment of JIA due to their many toxicities [12, 13], but they can be used in low doses as a bridging therapy while more slowly-acting DMARDs or biologics take effect.

The sequelae of untreated or poorly-controlled JIA include synovitis and joint contracture [23], bone overgrowth [24], leg-length discrepancy [25], growth retardation [26], muscular atrophy [9], atlanto-axial subluxation [27], and micrognathia [28]. For patients in whom medications have proven unsuccessful and the aforementioned complications have occurred, orthopaedic intervention is warranted. Possible operations include total joint arthroplasty, synovectomy, arthrodesis, and soft-tissue releases. For the knee joint in particular, TKA is recommended when persistent joint inflammation has led to joint damage, functional impairment, and constant pain [1, 29].

On a somewhat surprising note, a recent study exploring the incidence of operative intervention for JIA over time has revealed that the number of TKAs performed each year has remained relatively constant [30], despite the advent of newer biologic medications and non-biologic DMARDs. The authors postulated that the TKA rate may be falsely elevated due to increasing referrals to their study institutions. However, the authors also noted that orthopedists have trended towards earlier surgical intervention, no longer waiting for the patient to become non-ambulatory or severely impaired before proceeding with surgery [30]. Therefore, it may be the case that overall rates of TKA for JIA have not changed over the past few decades.

2. TKA IN JIA PATIENTS

2.1. Surgical Timing

The ideal surgical candidate for TKA is a patient who has reached skeletal maturity [31] in whom all attempts at conservative management have failed, and has monoarticular JIA of the knee; however, this more commonly occurs in osteoarthritis than JIA. In the event that a child has concurrent hip and knee pathology necessitating surgical intervention, it has been recommended to perform total hip arthroplasty before TKA [29, 32, 33]; the rationale for this is that, in fact, some knee pain may originate from the hip. Additionally, one can exercise a hip above an arthritic knee, but it is nearly impossible to exercise a knee below an arthritic hip.

Absolute contraindications to TKA include severe hyperextension deformity, Charcot neuropathic arthropathy, or systemic or local knee infection. A relative contraindication is a skeletal immaturity, as physeal disturbance can precipitate growth arrest or progressive angular deformity [32]. It has, therefore, been recommended to delay TKA in children with marked growth potential [29]. However, it is important to consider that children may have open epiphyseal plates that exhibit irregularity and narrowing; these children likely do not have significant growth remaining and may be candidates for TKA [29]. Some authors even contend that TKA may be indicated regardless of patient age since prolonged preoperative morbidity portends worse outcomes and postoperative function [34, 35].

2.2. Perioperative Management

Patients with JIA can be difficult to manage in the perioperative period. The protean extraarticular manifestations of JIA, and the potent systemic effects of the medications used in these patients, pose challenges for medical management [36, 37].

2.3. Preoperative Evaluation

Radiographs of both hips and knees should be taken in the anteroposterior and lateral views preoperatively. Dedicated patellofemoral radiographs and standing films should also be obtained to assess overall limb alignment. It is crucial to obtain several views of the operative knee, as flexion contractures can cause the knee to appear artificially large at some angles [32].

Radiographs in JIA may reveal soft-tissue swelling, osteopenia with thin cortices, loss of joint space and severe cartilage destruction without osteophytes, erosions, epiphyseal overgrowth, and an increased metaphyseal diameter with decreased diaphyseal and intramedullary canal width [32, 38]. It is important to template the choice of prosthesis preoperatively with the goal of preserving as much native bone stock as possible.

Though not discussed in this article, it is imperative for these patients to undergo comprehensive cardiac, renal, and cervical spine evaluations. Thorough evaluation of the upper extremities is also warranted, particularly if walking aids will be required postoperatively.

2.4. Medication Management

Compared to the general population, patients with JIA have higher rates of infection [39] since most of these patients are treated with immunosuppressive agents, which increase the risk of infection and delayed wound healing. However, complete cessation of immunosuppressive agents in the perioperative period could precipitate disease flare and necessitate the administration of corticosteroids [37]. Therefore, careful consideration and interdisciplinary care must be employed to optimize the use of immunosuppressants in the perioperative period.

2.5. Non-biologic DMARDs

2.5.1. Methotrexate

Methotrexate is the most rigorously studied DMARD used in JIA. Several retrospective studies have found no difference in rates of postoperative infection or delayed wound healing in JIA patients who discontinued methotrexate preoperatively versus those who did not [40-43]. One study further subdivided the cohorts, looking at whether there was a difference in postoperative complications when discontinuing low-dose methotrexate more than one month before surgery, discontinuing within four weeks of surgery, or continuing through the operative period; no differences were found [40]. Another retrospective study by Murata et al reproduced these findings but also showed that there was no difference in the incidence of disease flareups whether methotrexate was discontinued or not [44].

While a number of prospective studies have also shown no difference in infection or wound healing complications whether methotrexate was discontinued or not [45-47], other studies have yielded different results. One small prospective study of 32 patients demonstrated increased infection risk in patients who continued methotrexate, with no difference in the rate of disease flareups [48]. Paradoxically, another prospective study showed decreased postoperative infection rates in patients who continued methotrexate through the perioperative period; there was also a decreased rate of flareups in this group [49]. Of note, these patients were on 7.5-10 mg of methotrexate weekly, a lower dose than is currently recommended for JIA [50].

The American College of Rheumatology/American Association of Hip and Knee Surgeons’ (ACR/AAHKS) official 2017 guidelines recommend the continuation of methotrexate throughout the perioperative period (Goodman et al., 2017, 2011).

2.5.2. Leflunomide

The data for continued use of leflunomide in the perioperative period are conflicting. One randomized controlled trial demonstrated no increased risk of infection when holding leflunomide [51], while another prospective study showed a higher risk of postoperative wound complication when leflunomide was continued [46].

The ACR/AAHKS official 2017 guidelines recommend continuing leflunomide though the time of surgery [52]. However, some physicians still prefer to hold leflunomide two days prior to surgery [36]. In the event of a leflunomide-related adverse event, cholestyramine may be administered to facilitate leflunomide clearance [53].

2.5.3. Hydroxychloroquine

Data for perioperative hydroxychloroquine administration is also lacking, with just one prospective study illustrating no difference in postoperative infection rates [45]. Current ACR/AAHKS guidelines recommend continuing hydroxychloroquine through the perioperative period [36, 52, 54, 55].

2.5.4. Azathioprine and Sulfasalazine

Recommendations for azathioprine or sulfasalazine administration have not been officially agreed upon in the literature. One retrospective study demonstrated an association between azathioprine use and postoperative infection when univariate analysis was done, but there was no association using multivariate analysis [41]. Another retrospective study paradoxically demonstrated a lower risk of postoperative infection with the continuation of sulfasalazine perioperatively [41]. Therefore, some physicians prefer discontinuing azathioprine and sulfasalazine two days before surgery [36], while others choose to continue or only hold them on the day of surgery [37, 54, 55]. The ACR/AAHKS guidelines recommend continuing these medications through surgery [52].

2.5.5. Tacrolimus

Tacrolimus is a macrolide calcineurin inhibitor initially developed and used to prevent organ transplant rejection reactions [56]. However, tacrolimus has since proven effective in the management of inflammatory arthridities via three distinct mechanisms: (1) decreases inflammation by inhibiting synovial cell prostaglandin E2 production [57]; (2) regulates matrix metalloproteinase 13 synthesis in rheumatoid synovium [58]; (3) increases systemic levels of corticosteroids by competitively inhibiting P-glycoprotein binding sites on lymphocytes, of which corticosteroids are the substrate [59, 60].

Though few investigators have studied the use of tacrolimus in JIA specifically, one rigorous prospective study by Wang et al. examined patients with JIA treated with prednisolone versus prednisolone plus tacrolimus for a minimum of 12 months. Following 12 months of treatment, the tacrolimus group displayed decreased erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell (WBC) levels when compared to the prednisolone-only group. Additionally, the dose of prednisolone required for symptom abatement was lower for the tacrolimus group compared to the prednisolone-only group [61].

While there is no consensus on the perioperative timing of tacrolimus dosing in JIA, the ACR/AAHKS have based their recommendations off of the transplant surgery literature [62, 63]. In mild/moderate disease severity, the recommendation is to hold tacrolimus for one week preoperatively and resume 3-5 days postoperatively. In severe disease, the medication can be continued at the current dose [52].

2.5.6. Cyclosporine A

Similar to tacrolimus, cyclosporin A has increasingly been used as an adjunctive treatment for patients who fail methotrexate monotherapy [64]. Multiple studies have reported the safety and efficacy of cyclosporin A and methotrexate or prednisone coadministration [65-67]. Ravelli et al. followed 17 patients with JIA for at least six months following methotrexate and cyclosporin A treatment, and 47% of patients demonstrated improvement in at least three of six core disease severity outcome variables as defined by Giannini et al [68]: 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) ESR. In this study, 41% of patients experienced side effects, though none severe enough to warrant cyclosporin A discontinuation [65].

In another investigation, Ruperto et al. conducted an open-ended phase IV post-marketing surveillance study on patients with polyarticular JIA who had received cyclosporin A in addition to methotrexate or prednisone. These authors found that 61% of patients continued to rate their symptoms as moderate to severe and elected to discontinue cyclosporin A due to lack of efficacy. About 17% of patients additionally chose to discontinue the medication due to severe side effect profile [67]. Therefore, evidence supporting the use of cyclosporin A in JIA is variable; a controlled clinical trial is needed for more robust information.

While there is, again, no consensus on the perioperative timing of cyclosporin A dosing in JIA, ACR/AAHKS recom-mendations are drawn from transplant surgery literature [62, 63]. In mild/moderate disease severity, the recommendation is to hold cyclosporin A for one week preoperatively and resume 3-5 days postoperatively. In severe diseases, the medication can be continued at the current dose [52].

2.6. Biologic Agents

2.6.1. TNF-α Inhibitors

TNF-α inhibitors are relatively new agents and are still undergoing investigation for on-label use in JIA. One retrospective multivariate analysis of patients undergoing an orthopaedic surgery for arthritic joints showed an association between severe postoperative infection (deep wound infection, septic arthritis, osteomyelitis) and TNF-α inhibitor use (odds ratio [OR] 5.3) [69]. Johnson et al. looked specifically at the effect of TNF-α inhibitor use in 248 patients undergoing 268 TKAs; these authors found no statistically significant difference in infection rates in the anti-TNF group versus the group without anti-TNF [70]. Of note, the one deep joint infection requiring implant removal was a patient in the anti-TNF group.

However, when comparing postoperative complications in patients taking these biologics versus those taking DMARDs, there are mixed results. Retrospective multivariate logistic regression analyses have revealed independent associations between postoperative wound complications in patients taking DMARDs (OR 5.9) or TNF-α inhibitors (OR 9.8) [71]. The question, then, is whether TNF-α inhibitors pose more of a postoperative risk to than do DMARDs. One prospective study showed reduced rates of postoperative infectious and wound complications in patients taking TNF-α inhibitors rather than DMARDs [72], while another illustrated no difference between the two [73]. Still another retrospective study showed that patients taking TNF-α inhibitors had an increased risk of surgical site infection and deep vein thrombosis (DVT) relative to those taking DMARDs [74]. Larger prospective studies are necessary to better understand the risk of perioperative complications in patients being treated with TNF-α inhibitors for JIA.

A number of retrospective studies have been done to investigate the need to discontinue TNF-α inhibitor administration perioperatively. Five such studies showed no increased risk of surgical site infection regardless of TNF-α inhibitor discontinuation [41, 70, 75-77]. Another study confirmed these findings but also reported an increased risk of JIA flare in the discontinuation group [78]. One retrospective series of 52 patients showed no association between the last TNF-α inhibitor dose and surgical site infection risk [79].

The guidelines for preoperative TNF-α inhibitor management are variable [80, 81]. Some practitioners have argued against overarching recommendations, instead urging surgeons to weigh the risk of postoperative wound complications against the risk of disease flareup upon medication discontinuation [82]. Specific guidelines from the American College of Rheumatology/American Association of Hip and Knee Surgeons are to stop all biologic agents prior to surgery and to schedule the surgery at the end of the dosing cycle. Medications should be resumed no sooner than two weeks after the date of the surgery, and only in the absence of impaired wound healing, surgical site infection, or systemic infection [52]. Because data from studies on other biologic medications are sparse [83-86], these guidelines have been applied to all biologics.

2.7. Operative Management

2.7.1. Review of the Orthopedic Literature

Twelve studies with a total of 407 patients and 632 TKAs for JIA were identified and reviewed; a summary of the findings can be seen in Table 1. Consistent over the decades is the observation that TKA for JIA yields notable improvements in ambulation status and range of motion, significant pain relief, and enhanced quality of life.

Studies published prior to 2000, which is when widespread utilization of DMARDs for JIA took hold, do generally report high levels of patient satisfaction. This is likely because functional disability rather than the pain was the primary indication for TKA, and uncontrolled disease precipitates functional decline; furthermore, this surgical intervention tends to restore function quite drastically. While overall survival rates in most of these studies exceeded 95% at five years, they were not entirely devoid of complications. Most complications and revisions were due to component loosening or the need for arthroscopic manipulation under anesthesia (MUA) for stiffness/arthrofibrosis.

Table 1.
Summary of literature on TKA in JIA patients.
Ref/Year # Knees
(pts) 		CR / PS % Cemented Ave Age (yr) Ave F/U (yr) % Survival % Pain-free XR Result Complications
Heyse et al., 2014 [30] 349 (219) Both 99 29 12 10 yr: 95%
20 yr: 82%		 n/r n/r 18 revisions for loosening, 4 infections, 1 patellar revision, 2 periprosthetic fractures, 3 MUA, 2 vascular complications requiring amputations
Malviya et al., 2010 [97] 34 (20) Both n/r 35 M 16 58.5 (20-yr estimate) n/r n/r 3 periprosthetic fractures, 1 delayed wound healing (on MTX + etanercept), 1 revision for infection, 6 revisions for loosening
Jolles et al., 2008 [98] 22 (14) PS 80 33 8 100 100 5 knees, >2 mm lucency 1 MUA
Thomas et al., 2005 [99] 17 (10) PS 100 22 6 100 n/r n/r 2 transient regional pain syndromes, 1 revision for malalignment
Palmer et al., 2005 [100] 15 (8) PR 80 17 15.5 80 100 2 knees, valgus deformity 3 revisions for component loosening, 2 intraoperative fractures, 1 periprosthetic fracture, 1 transient peroneal palsy
Parvizi et al., 2003 [101] 25 (13) Both 84 17 10.7 92 92 6 knees, incomplete lucency; 1 knee, >2 mm lucency 2 revisions for loosening, 1 LOA, 2 MUA, 1 revision for malalignment, 1 component exchange
Lybick et al., 2000 [91] 77 (52) CR 5 33 3-13 99 n/r 14 tibias, <1.5 mm lucency 1 revision for loosening
Boublik et al., 1993 [90] 22 (14) CR 45 26 10.5 100* 95 2 knees, 1 mm lucency 1 patella revision
Carmichael et al., 1986 [94] 25 (13) Both 100 20 5 100 8 10 knees, <1 mm lucency 1 revision for loosening, 11 MUA
Rydholm et al., 1985 [102] 17 (11) n/a 100 25 5 65 82 11 knees with lucencies 1 patella revision, 4 revisions for loosening, 1 revision for malalignment; 2 skin necroses, 1 dehiscence, 4 peroneal palsies, 2 patella subluxations, 1 patella dislocation
Sarokhan et al., 1983 [29] 29 (17) Both 100 23 5 97 97 9 knees, <1 mm lucency 4 patella revisions; 1 infection, 1 tibial subluxation, 1 peroneal palsy, 21 MUA
Ranawat et al., 1983 [103] 29 (16) PS 100 23 3 97 90 13 knees, partial lucency; 3 knees, 2 mm lucency 1 deep infection, 2 transient peroneal palsies
Abbreviations: Ref = reference. pts = patients. CR = cruciate-retaining. PS = PCL-substituting. Ave = average. yr = years. XR = X-ray. n/r = not reported. MUA = manipulation under anesthesia. MTX = methotrexate. LOA = lysis of adhesions.

When analyzing results published after the year 2000, outcomes again appear excellent. This is despite the fact that surgeons opted for earlier surgical intervention, as surgeons no longer waited for patients to become non-ambulatory or severely impaired before proceeding with surgery [30]. Therefore, it can be reasonably inferred that the quality of life has improved for nonoperatively managed patients with JIA due to advancements in medical management and that outcomes of surgery have likewise improved as the preoperative quality of life baseline has been elevated. A difference is noted, however, in the distribution of complications. The primary complication in this cohort of patients was an infection, possibly due to the immunosuppressive effects of methotrexate and other DMARDs. Component loosening, thought to be due to a high activity level in these patients, was the second most common complication [30]. Again, the high activity level in patients with JIA seems to be a new phenomenon attributable to medication advancements. In the early 2000s, Rojer et al. specifically discussed that JIA most often affects multiple joints and is severely debilitating, so there is little absolute gain, but significant relative functional gain, following TKA. The supposition that component loosening can be attributed to increased activity would indicate that there is now significant functional gain in patients undergoing concomitant medical and surgical management for JIA.

2.8. Cemented versus Cementless

One of the primary concerns for young patients with JIA undergoing TKA is their relatively poor bone quality [87, 88]. For this reason, one important goal for orthopedists is to preserve as much bone stock as possible during TKA [30]. Some surgeons have advocated the use of press-fit components rather than cement, as the former operative technique obviates the need for excessive reaming. Not only does this preserve bone, but it also affords shorter operative times, protection from the generation of cement debris, and the potential to achieve biologic fixation [89]. Indeed, both Lybick et al. and Boublik et al. reported over 99% survival and significant patient satisfaction at four-year follow-up after cementless TKA for JIA [90, 91]. Prudhon et al. compared 11-year outcomes of cemented versus cementless TKA in an elderly population with a combination of diagnoses (osteoarthritis, rheumatoid arthritis, and posttraumatic arthritis), and the authors found no difference in survivorship between cemented and cementless groups [89]. However, the literature is lacking in decades-long follow-up for cementless TKA in JIA patients. One potential concern is that the severe osteopenia in JIA may sometimes not allow for press-fit cementless components [30, 90]. Therefore, cemented TKA remains the gold standard in these patients [30].

2.9. Posterior Cruciate Ligament-Substituting versus Posterior Cruciate Ligament-Retaining

There are opposing opinions for PCL-substituting (PS) TKA versus Cruciate retaining (CR) TKA, though literature specific to JIA patients is lacking. The remainder of this section will cite articles in which PS versus CR was compared in patients with RA, with a small contingent being JIA patients. Those who support using PS argue that this technique allows for more congruency of articular surfaces and better deformity correction, owing to the excellent outcomes observed at 10-year follow-up [92]. PS also minimizes polyethylene wear, which may contribute to TKA survivorship in these patients [93]. Carmichael et al. suggested that the PS technique aids in the correction of severe flexion contracture, therefore advocating its use in patients for whom flexion contractures prove debilitating [94]. In 1996, Laskin et al. published a six-year follow-up series of patients who underwent PS versus CR, and they ultimately advocated that PS should uniformly be done. The authors found a significantly increased incidence of posterior instability and recurvatum deformity in the CR group, necessitating revision. At the time of revisions, these authors saw a grossly absent PCL with Grade 1 synovial reaction in a number of patients in the initial CR group [95].

Orthopedists who support the CR technique argue that there are several advantages afforded by retention, including increased joint stability and better absorption of shear forces. Additionally, CR allows for femoral rollback, which helps with patients’ postoperative mobility (i.e. better ability to climb stairs, climb uphill, cycle) and improves the quality of life [30]. Data on long-term outcomes of the CR technique are promising. In 1999, Schai et al. published an 11-year follow-up study on CR TKA in 52 patients (81 knees) with adult RA or JIA. The average postoperative range of motion for the JIA group was 107 degrees, and survivorship was nearly 100% for all components. Contrary to Laskin et al.’s findings, Schai et al. reported subjective stability and <6 mm of clinical anteroposterior laxity in 98% of patients. The authors concluded that the CR technique is effective for TKA for JIA [96].

3. CONCLUSION

TKA in patients with JIA poses challenges unique to this disease. As medical management for JIA rapidly evolves, and as more literature on long-term outcomes of TKA emerges, it is imperative for the orthopaedic surgeon to remain current and informed. Though the field is ever-improving, current results of TKA in JIA can be extremely dramatic and gratifying.

LIST OF ABBREVIATIONS

JIA = Juvenile Idiopathic Arthritis
TKA = Total Knee Arthroplasty
DMARDs = Disease-Modifying Antirheumatic Drugs
ESR = Erythrocyte Sedimentation Rate
CRP = C-Reactive Protein
WBC = White Blood Cell
MUA = Manipulation Under Anesthesia
PS = PCL-Substituting
CR = Cruciate Retaining

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

The author declares no conflict of interest, financial or otherwise.

REFERENCES

1
Goodman JE, McGrath PJ. The epidemiology of pain in children and adolescents: a review. Pain 1991; 46(3): 247-64.
2
Kunnamo I, Kallio P, Pelkonen P. Incidence of arthritis in urban finnish children: A prospective study. Arthritis Rheum 1986; 29(10): 1232-8.
3
Cuesta IA, Kerr K, Simpson P, Jarvis JN. Subspecialty referrals for pauciarticular juvenile rheumatoid arthritis. Arch Pediatr Adolesc Med 2000; 154(2): 122-5.
4
Stoll ML, Cron RQ. Treatment of juvenile idiopathic arthritis: a revolution in care. Pediatr Rheumatol Online J 2014; 12(1): 13.
5
Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31(2): 390-2.
6
Bovid KM, Moore MD. Juvenile idiopathic arthritis for the pediatric orthopedic surgeon. Orthop Clin North Am 2019; 50(4): 471-88.
7
Ilowite NT. Current treatment of juvenile rheumatoid arthritis. Pediatrics 2002; 109(1): 109-15.
8
Cakmak A, Bolukbas N. Juvenile rheumatoid arthritis: physical therapy and rehabilitation. South Med J 2005; 98(2): 212-6.
9
Sheets R, Chang J, Radhakrishna S. Arthritis. In: Martus J, Ed. Orthopaedic Knowledge Update. Rosemont, IL: American Academy of Orthopaedic Surgeons 2016; pp. 203-11.
10
Miller ML, Kress AM, Berry CA. Decreased physical function in juvenile rheumatoid arthritis. Arthritis Rheum 1999; 12(5): 309-13.
11
Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: Initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken) 2011; 63(4): 465-82.
12
Cassidy J, Petty R. Textbook of Pediatric Rheumatology Expert Consult. 6th ed. London, UK: Elsevier Health Sciences 2010.
13
Cavallo S, April KT, Grandpierre V, Majnemer A, Feldman DE. Leisure in children and adolescents with juvenile idiopathic arthritis: A systematic review. PLoS ONE 2014; 9(10): e104642.
14
Jennings H, Hennessy K, Hendry GJ. The clinical effectiveness of intra-articular corticosteroids for arthritis of the lower limb in juvenile idiopathic arthritis: a systematic review. Pediatr Rheumatol Online J 2014; 12(1): 23.
15
Coulson EJ, Hanson HJM, Foster HE. What does an adult rheumatologist need to know about juvenile idiopathic arthritis? Rheumatology (Oxford) 2014; 53(12): 2155-66.
16
Davis JM III, Matteson EL. My treatment approach to rheumatoid arthritis. Mayo Clin Proc 2012; 87(7): 659-73.
17
Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012; 64(5): 625-39.
18
Kessler EA, Becker ML. Therapeutic advancements in juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol 2014; 28(2): 293-313.
19
Silverman E, Mouy R, Spiegel L, et al. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med 2005; 352(16): 1655-66.
20
Ringold S, Weiss PF, Beukelman T, et al. 2013 Update of the 2011 American college of rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children With systemic juvenile idiopathic arthritis and tuberculosis screening among C. Arthritis Rheum 2013; 65(10): 2499-512.
21
Chatzidionysiou K, Lie E, Nasonov E, et al. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries. Ann Rheum Dis 2011; 70(9): 1575-80.
22
Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: Results of the randomized phase 3 CADMUS study. J Am Acad Dermatol 2015; 73(4): 594-603.
23
Kitchen B, Sanchez HB, Wagner RA. Shortening femoral osteotomy with stemmed resurfacing total knee arthroplasty for severe flexion contracture in Juvenile Rheumatoid Arthritis. J Orthop 2015; 12(2): 118-21.
24
Goupille P, Fouquet B, Cotty P, Goga D, Valat JP. Direct coronal computed tomography of the temporomandibular joint in patients with rheumatoid arthritis. Br J Radiol 1992; 65(779): 955-60.
25
Sherry DD, Stein LD, Reed AM, Schanberg LE, Kredich DW. Prevention of leg length discrepancy in young children with pauciarticular juvenile rheumatoid arthritis by treatment with intraarticular steroids. Arthritis Rheum 1999; 42(11): 2330-4.
26
Bacon MC, White PH, Raiten DJ, et al. Nutritional status and growth in juvenile rheumatoid arthritis. Semin Arthritis Rheum 1990; 20(2): 97-106.
27
Hospach T, Maier J, Müller-Abt P, Patel A, Horneff G, von Kalle T. Cervical spine involvement in patients with juvenile idiopathic arthritis - MRI follow-up study. Pediatr Rheumatol Online J 2014; 12(1): 9.
28
Larheim TA, Haanæs HR. Micrognathia, temporomandibular joint changes and dental occlusion in juvenile rheumatoid arthritis of adolescents and adults. Eur J Oral Sci 1981; 89(4): 329-38.
29
Sarokhan AJ, Scott RD, Thomas WH, Sledge CB, Ewald FC, Cloos DW. Total knee arthroplasty in juvenile rheumatoid arthritis. J Bone Joint Surg Am 1983; 65(8): 1071-80.
30
Heyse TJ, Ries MD, Bellemans J, et al. Total knee arthroplasty in patients with juvenile idiopathic arthritis. Clin Orthop Relat Res 2014; 472(1): 147-54.
31
Mancuso CA, Ranawat CS, Esdaile JM, Johanson NA, Charlson ME. Indications for total hip and total knee arthroplasties. J Arthroplasty 1996; 11(1): 34-46.
32
Goodman SB. Total joint replacement of the lower extremity in patients with juvenile idiopathic arthritis 2014; 2(1): 3-12.
33
Lee JK, Choi CH. Total knee arthroplasty in rheumatoid arthritis. Knee Surg Relat Res 2012; 24(1): 1-6.
34
Crowder AR, Duffy GP, Trousdale RT. Long-term results of total knee arthroplasty in young patients with rheumatoid arthritis. J Arthroplasty 2005; 20(7)(Suppl. 3): 12-6.
35
Kennedy LG, Newman JH, Ackroyd CE, Dieppe PA. When should we do knee replacements? Knee 2003; 10(2): 161-6.
36
Goodman SM, Figgie MP, MacKenzie CR. Perioperative management of patients with connective tissue disease. HSS J 2011; 7(1): 72-9.
37
Krause ML, Matteson EL. Perioperative management of the patient with rheumatoid arthritis. World J Orthop 2014; 5(3): 283-91.
38
Tafaghodi F, Aghighi Y, Rokni Yazdi H, Shakiba M, Adibi A. Predictive plain X-ray findings in distinguishing early stage acute lymphoblastic leukemia from juvenile idiopathic arthritis. Clin Rheumatol 2009; 28(11): 1253-8.
39
Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: A population-based study. Arthritis Rheum 2002; 46(9): 2287-93.
40
Jain A, Witbreuk M, Ball C, Nanchahal J. Influence of steroids and methotrexate on wound complications after elective rheumatoid hand and wrist surgery. J Hand Surg Am 2002; 27(3): 449-55.
41
Kadota Y, Nishida K, Hashizume K, et al. Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients. Mod Rheumatol 2016; 26(1): 68-74.
42
Kasdan ML, June L. Postoperative results of rheumatoid arthritis patients on methotrexate at the time of reconstructive surgery of the hand. Orthopedics 1993; 16(11): 1233-5.
43
Perhala RS, Wilke WS, Clough JD, Segal AM. Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. Arthritis Rheum 1991; 34(2): 146-52.
44
Murata K, Yasuda T, Ito H, Yoshida M, Shimizu M, Nakamura T. Lack of increase in postoperative complications with low-dose methotrexate therapy in patients with rheumatoid arthritis undergoing elective orthopedic surgery. Mod Rheumatol 2006; 16(1): 14-9.
45
Bibbo C, Anderson RB, Davis WH, Norton J. The influence of rheumatoid chemotherapy, age, and presence of rheumatoid nodules on postoperative complications in rheumatoid foot and ankle surgery: analysis of 725 procedures in 104 patients [corrected]. Foot Ankle Int 2003; 24(1): 40-4.
46
Fuerst M, Möhl H, Baumgärtel K, Rüther W. Leflunomide increases the risk of early healing complications in patients with rheumatoid arthritis undergoing elective orthopedic surgery. Rheumatol Int 2006; 26(12): 1138-42.
47
Sany J, Anaya JM, Canovas F, et al. Influence of methotrexate on the frequency of postoperative infectious complications in patients with rheumatoid arthritis. J Rheumatol 1993; 20(7): 1129-32.
48
Carpenter MT, West SG, Vogelgesang SA, Jones DEC. Postoperative joint infections in rheumatoid arthritis patients on methotrexate therapy. Orthopedics 1996; 19(3): 207-10.
49
Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis 2001; 60(3): 214-7.
50
Loza E, Martinez-Lopez JA, Carmona L. A systematic review on the optimum management of the use of methotrexate in rheumatoid arthritis patients in the perioperative period to minimize perioperative morbidity and maintain disease control. Clin Exp Rheumatol 2009; 27(5): 856-62.
51
Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S. Examination of the risk of continuous leflunomide treatment on the incidence of infectious complications after joint arthroplasty in patients with rheumatoid arthritis. J Clin Rheumatol 2003; 9(2): 115-8.
52
Goodman SM, Springer B, Guyatt G, et al. 2017 American College of Rheumatology/American Association of hip and knee surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis Rheumatol 2017; 69(8): 1538-51.
53
Jenks KA, Stamp LK, O’Donnell JL, Savage RL, Chapman PT. Leflunomide-associated infections in rheumatoid arthritis. J Rheumatol 2007; 34(11): 2201-3.
54
Akkara Veetil BM, Bongartz T. Perioperative care for patients with rheumatic diseases. Nat Rev Rheumatol 2012; 8(1): 32-41.
55
Pieringer H, Stuby U, Biesenbach G. Patients with rheumatoid arthritis undergoing surgery: how should we deal with antirheumatic treatment? Semin Arthritis Rheum 2007; 36(5): 278-86.
56
Dutta S, Ahmad Y. The efficacy and safety of tacrolimus in rheumatoid arthritis. Ther Adv Musculoskelet Dis 2011; 3(6): 283-91.
57
Sasakawa T, Sasakawa Y, Ohkubo Y, Mutoh S. FK506 inhibits prostaglandin E2 production from synovial cells by suppressing peripheral blood mononuclear cells. Int Immunopharmacol 2005; 5(7-8): 1291-7.
58
Migita K, Miyashita T, Maeda Y, et al. FK506 suppresses the stimulation of matrix metalloproteinase 13 synthesis by interleukin-1β in rheumatoid synovial fibroblasts. Immunol Lett 2005; 98(2): 194-9.
59
Suzuki K, Saito K, Tsujimura S, et al. Tacrolimus, a calcineurin inhibitor, overcomes treatment unresponsiveness mediated by P-glycoprotein on lymphocytes in refractory rheumatoid arthritis. J Rheumatol 2010; 37(3): 512-20.
60
Tsujimura S, Saito K, Nawata M, Nakayamada S, Tanaka Y. Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis. Ann Rheum Dis 2007; 67(3): 380-8.
61
Wang D, Chen X, Li Z. Treatment of patients with systemic‑onset juvenile idiopathic arthritis with tacrolimus. Exp Ther Med 2019; 17(3): 2305-9.
62
Klement MR, Penrose CT, Bala A, Wellman SS, Bolognesi MP, Seyler TM. How do previous solid organ transplant recipients fare after primary total knee arthroplasty? J Arthroplasty 2016; 31(3): 609-615.e1.
63
Palmisano AC, Kuhn AW, Urquhart AG, Pour AE. Post-operative medical and surgical complications after primary total joint arthroplasty in solid organ transplant recipients: a case series. Int Orthop 2017; 41(1): 13-9.
64
Wallace CA. On beyond methotrexate treatment of severe juvenile rheumatoid arthritis. Clin Exp Rheumatol 1999; 17(4): 499-504.
65
Ravelli A, Moretti C, Temporini F, et al. Combination therapy with methotrexate and cyclosporine A in juvenile idiopathic arthritis. Clin Exp Rheumatol 2002; 20(4): 569-72.
66
van Dijkhuizen EHP, Bulatović Ćalasan M, Pluijm SMF, et al. Prediction of methotrexate intolerance in juvenile idiopathic arthritis: a prospective, observational cohort study. Pediatr Rheumatol Online J 2015; 13(1): 5.
67
Ruperto N, Ravelli A, Castell E, et al. Cyclosporine A in juvenile idiopathic arthritis. Results of the PRCSG/PRINTO phase IV post marketing surveillance study. Clin Exp Rheumatol 2006; 24(5): 599-605.
68
Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997; 40(7): 1202-9.
69
Giles JT, Bartlett SJ, Gelber AC, et al. Tumor necrosis factor inhibitor therapy and risk of serious postoperative orthopedic infection in rheumatoid arthritis. Arthritis Rheum 2006; 55(2): 333-7.
70
Johnson BK, Goodman SM, Alexiades MM, Figgie MP, Demmer RT, Mandl LA. Patterns and associated risk of perioperative use of anti-tumor necrosis factor in patients with rheumatoid arthritis undergoing total knee replacement. J Rheumatol 2013; 40(5): 617-23.
71
Momohara S, Kawakami K, Iwamoto T, et al. Prosthetic joint infection after total hip or knee arthroplasty in rheumatoid arthritis patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs. Mod Rheumatol 2011; 21(5): 469-75.
72
Bibbo C, Goldberg JW. Infectious and healing complications after elective orthopaedic foot and ankle surgery during tumor necrosis factor-alpha inhibition therapy. Foot Ankle Int 2004; 25(5): 331-5.
73
Hirano Y, Kojima T, Kanayama Y, et al. Influences of anti-tumour necrosis factor agents on postoperative recovery in patients with rheumatoid arthritis. Clin Rheumatol 2010; 29(5): 495-500.
74
Kawakami K, Ikari K, Kawamura K, et al. Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor- blockers: perioperative interruption of tumour necrosis factor- blockers decreases complications? Rheumatology (Oxford) 2010; 49(2): 341-7.
75
Kubota A, Nakamura T, Miyazaki Y, Sekiguchi M, Suguro T. Perioperative complications in elective surgery in patients with rheumatoid arthritis treated with biologics. Mod Rheumatol 2012; 22(6): 844-8.
76
Neven N, Vis M, Voskuyl AE, et al. Adverse events in patients with rheumatoid arthritis treated with infliximab in daily clinical practice. Ann Rheum Dis 2005; 64(4): 645-6.
77
Ruyssen-Witrand A, Gossec L, Salliot C, et al. Complication rates of 127 surgical procedures performed in rheumatic patients receiving tumor necrosis factor alpha blockers. Clin Exp Rheumatol 2007; 25(3): 430-6.
78
Haegele KF, Buechner NJ, Stueckle CA, Rump LC, Weiner SM. Weight loss with purpura and pain at the distal femora. Ann Rheum Dis 2005; 64(9): 1373-4.
79
Hayata K, Kanbe K, Chiba J, Nakamura A, Inoue Y, Hobo K. Clinical factors related to the efficacy and complications of orthopedic surgery for rheumatoid arthritis with infliximab. Int J Rheum Dis 2011; 14(1): 31-6.
80
Ledingham J, Deighton C. British Society for Rheumatology Standards, Guidelines and Audit Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNF blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology (Oxford) 2005; 44(2): 157-63.
81
Meunier PJ. Introduction • the epidemiological and therapeutic challenges of osteoporosis. Rev Rhum 2005; 3.
82
Ding T, Ledingham J, Luqmani R, et al. BSR and BHPR rheumatoid arthritis guidelines on safety of anti-TNF therapies. Rheumatology (Oxford) 2010; 49(11): 2217-9.
83
Godot S, Gottenberg JE, Paternotte S, et al. Safety of surgery after rituximab therapy in 133 patients with rheumatoid arthritis: data from the autoimmunity and rituximab registry. Arthritis Care Res (Hoboken) 2013; 65(11): 1874-9.
84
Hirao M, Hashimoto J, Tsuboi H, et al. Laboratory and febrile features after joint surgery in patients with rheumatoid arthritis treated with tocilizumab. Ann Rheum Dis 2009; 68(5): 654-7.
85
Momohara S, Hashimoto J, Tsuboi H, et al. Analysis of perioperative clinical features and complications after orthopaedic surgery in rheumatoid arthritis patients treated with tocilizumab in a real-world setting: results from the multicentre TOcilizumab in Perioperative Period (TOPP) study. Mod Rheumatol 2013; 23(3): 440-9.
86
Nishida K, Nasu Y, Hashizume K, et al. Abatacept management during the perioperative period in patients with rheumatoid arthritis: report on eight orthopaedic procedures. Mod Rheumatol 2014; 24(3): 544-5.
87
Stagi S, Cavalli L, Signorini C, et al. Bone mass and quality in patients with juvenile idiopathic arthritis: longitudinal evaluation of bone-mass determinants by using dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Arthritis Res Ther 2014; 16(2): R83.
88
Tsao A, Pesut T, Peacock C, Tucci M, Buckhalter RA. Bone sparing surgical options for total hip replacement. Biomed Sci Instrum 2003; 39: 284-8.
89
Prudhon JL, Verdier R. Cemented or cementless total knee arthroplasty? SICOT J 2017; 3: 70.
90
Boublik M, Tsahakis PJ, Scott RD. Cementless total knee arthroplasty in juvenile onset rheumatoid arthritis. Clin Orthop 1993.
91
Lybick CO, Belt EA, Kauppi MJ, Savolainen HA, Lehto MUK. Survivorship of AGC knee replacement in juvenile chronic arthritis 13-year follow-up of 77 Knees. J Arthroplasty 2000; 15(2): 166-70.
92
Laskin RS. Total condylar knee replacement in patients who have rheumatoid arthritis. A ten-year follow-up study. J Bone Joint Surg Am 1990; 72(4): 529-35.
93
Tanzer M, Smith K, Burnett S. Posterior-stabilized versus cruciate-retaining total knee arthroplasty. J Arthroplasty 2002; 17(7): 813-9.
94
Carmichael E, Chaplin DM. Total knee arthroplasty in juvenile rheumatoid arthritis. A seven-year follow-up study. Clin Orthop Relat Res 1986; (210): 192-200.
95
Laskin RS, O’Flynn HM. The Insall Award. Total knee replacement with posterior cruciate ligament retention in rheumatoid arthritis. Problems and complications. Clin Orthop Relat Res 1997; (345): 24-8.
96
Schai PA, Scott RD, Thornhill TS. Total knee arthroplasty with posterior cruciate retention in patients with rheumatoid arthritis. Clin Orthop Relat Res 1999; 367(367): 96-106.
97
Malviya A, Foster HE, Avery P, Weir DJ, Deehan DJ. Long term outcome following knee replacement in patients with juvenile idiopathic arthritis. Knee 2010; 17(5): 340-4.
98
Jolles BM, Bogoch ER. Quality of life after TKA for patients with juvenile rheumatoid arthritis. Clin Orthop Relat Res 2008; 466(1): 167-78.
99
Thomas A, Rojer D, Imrie S, Goodman SB. Cemented total knee arthroplasty in patients with juvenile rheumatoid arthritis. Clin Orthop Relat Res 2005; &NA;(433): 140-6.
100
Palmer DH, Mulhall KJ, Thompson CA, Severson EP, Santos ERG, Saleh KJ. Total knee arthroplasty in juvenile rheumatoid arthritis. J Bone Joint Surg Am 2005; 87(7): 1510-4.
101
Parvizi J, Lajam CM, Trousdale RT, Shaughnessy WJ, Cabanela M. Total knee arthroplasty in young patients with juvenile rheumatoid arthritis. J Bone Joint Surg Am 2003; 85(6): 1090-4.
102
Rydholm U, Boegårrd T, Lidgren L. Total knee replacement in juvenile chronic arthritis. Scand J Rheumatol 1985; 14(4): 329-35.
103
Ranawat CS, Bryan WJ, Inglis AE. Total knee arthroplasty in juvenile arthritis. Arthritis Rheum 1983; 26(9): 1140-4.