Arthropathies. Rheumatoid Arthritis.

Introduction

The arthropathies form a heterogeneous group of inflammatory and degenerative joint diseases. The orthopedic surgeon encounters these conditions in many contexts: assessment of new joint pain in the clinic, management of established joint destruction with surgical reconstruction, perioperative management of patients on disease-modifying medications, and the long-term care of patients whose underlying disease will continue to affect multiple joints over a lifetime. This chapter, synthesizing content from Apley & Solomon’s, Miller’s Review, and Netter’s Concise Orthopaedic Anatomy, addresses rheumatoid arthritis (the most consequential inflammatory arthritis from a surgical perspective), the seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease-associated arthritis), crystal arthropathies (gout, pseudogout), other inflammatory arthropathies (juvenile idiopathic arthritis, systemic lupus erythematosus), and the principles of medical and surgical management.

Rheumatoid Arthritis (RA)

Epidemiology and Pathogenesis Rheumatoid arthritis is a chronic systemic autoimmune disease characterized by symmetric inflammatory arthritis of small and large joints, with extra-articular manifestations affecting multiple organ systems. The prevalence is approximately 0.5-1% of adults globally, with female predominance of approximately 3:1. The peak age of onset is the fourth to sixth decade, although both juvenile and elderly onset forms occur. The principal genetic susceptibility maps to the HLA-DR4 and related alleles in the major histocompatibility complex; environmental triggers including smoking, periodontal disease (particularly Porphyromonas gingivalis infection), and various respiratory exposures contribute. The pathogenesis involves dysregulated immune activation with formation of autoantibodies (rheumatoid factor — RF, an IgM against the Fc portion of IgG; anti- citrullinated peptide antibodies — ACPA, an antibody to citrullinated proteins generated by the enzyme PAD4), persistent activation of T cells, recruitment and proliferation of synovial fibroblasts and macrophages, and production of inflammatory cytokines (TNF-α, IL-6, IL-1, others) that drive synovial hyperplasia, pannus formation, and progressive destruction of cartilage and bone. Clinical Features The classical presentation is of insidious onset of symmetric small-joint pain and stiffness, most prominently in the hands (metacarpophalangeal and proximal interphalangeal joints, with sparing of the distal interphalangeal joints), feet (metatarsophalangeal joints), and wrists. Morning stiffness lasting more than an hour is characteristic and reflects the inflammatory nature of the disease. Larger joints (knees, hips, shoulders, elbows) are

affected in addition to small joints, particularly as the disease progresses. Constitutional symptoms — fatigue, low-grade fever, weight loss — are common. The classical hand deformities of established rheumatoid arthritis include: ulnar deviation of the fingers at the MCP joints; swan neck deformity (PIP hyperextension with DIP flexion); boutonnière deformity (PIP flexion with DIP hyperextension); volar subluxation of the MCP joints; carpal collapse with radial deviation of the wrist; and the various thumb deformities classified by Nalebuff. The cervical spine is involved in 30-90% of patients with established disease, with the principal manifestations being atlantoaxial instability (from erosion of the transverse ligament of the atlas), basilar invagination (cranial settling), and subaxial subluxations. Extra-articular manifestations include rheumatoid nodules, vasculitis, pleural and pulmonary disease, pericarditis, Felty’s syndrome (the triad of RA, splenomegaly, and neutropenia), keratoconjunctivitis sicca, episcleritis, and amyloidosis. Diagnosis The 2010 ACR/EULAR classification criteria for RA assess: joint involvement (number and type of involved joints — small joints carry more weight than large joints, with more involved joints carrying more points); serology (rheumatoid factor and anti-CCP antibody, with both negative scoring 0, either weakly positive scoring 2, either strongly positive scoring 3); acute-phase reactants (CRP, ESR); and symptom duration (≥6 weeks). A score of 6/10 or higher establishes the diagnosis of RA in a patient with at least one joint with definite clinical synovitis. Imaging Plain radiographs in early RA may show only soft-tissue swelling and periarticular osteopenia. As the disease progresses, characteristic changes appear: marginal erosions (at the sites of synovial attachment, “bare areas” of bone not covered by articular cartilage); symmetric joint-space narrowing; periarticular osteopenia; soft-tissue swelling around the joints; ulnar deviation at the MCPs; and the various deformities described above. The Larsen and Sharp scoring systems are used in research and clinical assessment of disease progression. MRI and ultrasound are increasingly used in early RA for detection of subclinical synovitis and pre-erosive disease; both modalities have substantially higher sensitivity than plain radiographs for early disease. The cervical spine in RA deserves specific imaging assessment: flexion-extension lateral radiographs to identify atlantoaxial subluxation (the atlas-dens interval — ADI — should be <3 mm in adults; >9 mm indicates significant instability with risk of cord compression); CT for bony assessment; MRI for cord assessment in patients with neurological symptoms or with instability on plain radiographs. Medical Treatment The medical treatment of RA has been transformed over the past three decades by the introduction of methotrexate as a foundational disease-modifying antirheumatic drug

(DMARD) and by the subsequent development of biological agents and targeted small- molecule therapies. The current “treat-to-target” paradigm aims for remission or low disease activity as quickly as possible, with serial assessment of disease activity and aggressive escalation of therapy as needed. The principal classes of medication include: Conventional DMARDs: Methotrexate (the anchor drug, with established efficacy in slowing erosive disease and improving long-term outcomes), sulfasalazine, hydroxychloroquine, leflunomide. Biological DMARDs: TNF-α inhibitors (infliximab, etanercept, adalimumab, certolizumab, golimumab); IL-6 inhibitors (tocilizumab, sarilumab); B-cell depletion (rituximab); T-cell co-stimulation inhibitors (abatacept); IL-1 antagonists (anakinra, canakinumab). Targeted synthetic DMARDs: Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, upadacitinib). Corticosteroids: Used as bridge therapy during DMARD initiation, for inflammatory flares, and in selected refractory cases at the lowest possible dose. The orthopedic surgeon must be familiar with the perioperative management of these agents, with the current consensus being to hold most biological therapies for 1-2 dosing intervals before surgery to reduce infection risk, while continuing methotrexate through surgery in most cases. Surgical Treatment of RA Joints The principal surgical procedures for the RA joints include: Synovectomy: Performed open or arthroscopically for joints with refractory active synovitis without significant cartilage destruction. The procedure is now less commonly performed than in the pre-biological era, as effective medical treatment has substantially reduced the burden of unresponsive synovitis. When performed, the role is principally for the wrist, elbow, knee, ankle, and occasionally the MTP joints, with the goal of reducing pain and disease activity while preserving the joint. Joint reconstruction and arthrodesis: Various procedures address established deformities — particularly the wrist (total wrist arthrodesis or partial wrist fusion, distal ulnar resection — Darrach procedure — or hemiresection-interposition arthroplasty, ulnar head replacement), the thumb (CMC arthroplasty, MP arthrodesis for type IV thumb deformity), the fingers (MCP arthroplasty with silicone implants, PIP arthrodesis or arthroplasty), and the forefoot (resection arthroplasty of the lesser MTP joints with arthrodesis or arthroplasty of the first MTP). Joint replacement: Total joint arthroplasty addresses end-stage destruction of the major joints. The principles of THA and TKA in RA patients follow the general principles described in the relevant chapters, with attention to: the often-younger age of the patient; the simultaneous involvement of multiple joints (which may dictate the sequence of

operations); the perioperative management of biological therapy; the increased infection risk; and the specific deformities and bony defects often encountered. Total shoulder arthroplasty (anatomic or reverse, depending on rotator cuff status — RA frequently produces rotator cuff destruction making reverse arthroplasty appropriate), total elbow arthroplasty, and total ankle arthroplasty are all options for RA-affected joints. Cervical spine surgery: Atlantoaxial fusion (C1-C2) for symptomatic atlantoaxial instability or with ADI >9 mm; occipitocervical fusion for basilar invagination; subaxial fusions for instability. The cervical spine surgery in RA is technically demanding because of the poor bone quality, the deformities, and the medical complexity of the patients.

Seronegative Spondyloarthropathies

The seronegative spondyloarthropathies are a group of inflammatory joint diseases characterized by sacroiliitis and axial inflammation, asymmetric peripheral arthritis (often of the lower extremities), enthesitis (inflammation at the sites of tendon and ligament attachment to bone), absence of rheumatoid factor, and association with the HLA-B27 gene. Ankylosing Spondylitis (AS) Ankylosing spondylitis is the prototype of the seronegative spondyloarthropathies, characterized by chronic inflammation of the axial skeleton (sacroiliac joints, spine, hip joints) with progressive ankylosis. The condition affects approximately 0.1-0.5% of the population, with male predominance (approximately 2:1) and onset typically in the second and third decades. HLA-B27 is present in 90-95% of patients. Presentation is with insidious onset of chronic inflammatory back pain in young adults — pain worse with rest and better with activity, morning stiffness lasting hours, and progressive limitation of spine motion. The disease progresses through stages: bilateral sacroiliitis (the earliest and most characteristic finding); progressive ankylosis of the spine with formation of syndesmophytes (vertical bony bridges between adjacent vertebrae); ultimate “bamboo spine” appearance on radiographs with complete fusion of the spine. Extra-articular manifestations include uveitis (the commonest, in approximately 25-40% of patients), psoriasis, inflammatory bowel disease, aortic regurgitation, and pulmonary fibrosis. Treatment combines NSAIDs (the foundation of medical therapy, with substantial symptomatic benefit), TNF-α inhibitors (which have been shown to improve symptoms and possibly slow radiographic progression), IL-17 inhibitors (secukinumab, ixekizumab), physical therapy (the most important non-pharmacological intervention, with daily exercises to maintain spine mobility and prevent fixed deformity), and management of associated conditions. Orthopedic considerations in AS include: the ankylosed spine is markedly more fragile and more prone to fracture from low-energy trauma (the “carrot stick” fracture); these fractures are highly unstable and often missed initially because of the diffuse spine disease that obscures fracture lines on imaging; CT and MRI should have low threshold of use in any AS patient with new back pain after even minor trauma; the kyphotic deformity of

advanced AS may require corrective spinal osteotomy (pedicle subtraction osteotomy is the standard) to restore sagittal balance and forward-looking gaze; total hip arthroplasty for hip involvement is technically more demanding than in primary OA because of the ankylosis and altered hip mechanics, but produces good functional outcomes. Psoriatic Arthritis Psoriatic arthritis is the inflammatory arthropathy associated with psoriasis. Patterns of joint involvement include: asymmetric oligoarthritis (most common); symmetric polyarthritis (resembling RA); distal interphalangeal-predominant disease (the characteristic pattern involving the DIP joints, often with adjacent psoriatic nail changes); spondylitis (sacroiliac and spinal involvement, often with asymmetric “skip-pattern” syndesmophytes in contrast to the symmetric pattern of AS); and arthritis mutilans (severe destructive joint disease with “telescoping” digits). Treatment is similar to RA but with attention to the skin disease, with TNF-α inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, and JAK inhibitors having particular roles. Reactive Arthritis Reactive arthritis is an acute inflammatory arthritis arising after gastrointestinal or genitourinary infection (classically Chlamydia trachomatis, Salmonella, Shigella, Campylobacter, Yersinia). The “Reiter triad” of arthritis, urethritis, and conjunctivitis is the classical presentation but is often incomplete. The arthritis is typically an asymmetric oligoarthritis of the lower extremities, with associated enthesitis, dactylitis, and sometimes sacroiliitis. Most cases resolve over weeks to months with NSAID treatment; chronic cases require DMARD therapy. Inflammatory Bowel Disease-Associated Arthritis Inflammatory bowel disease (ulcerative colitis and Crohn’s disease) is associated with peripheral arthritis (typically migratory and following the activity of the bowel disease) and axial arthritis (sacroiliitis and spondylitis indistinguishable from primary AS). Treatment includes management of the underlying bowel disease and DMARDs appropriate to the joint pattern.

Crystal Arthropathies

Gout Gout is an inflammatory arthropathy caused by deposition of monosodium urate crystals in joints and periarticular tissues. The condition affects approximately 1-3% of adults in developed countries, with male predominance and increasing prevalence with age, particularly in association with obesity, hypertension, renal disease, and the modern Western diet. Hyperuricemia (serum urate >7 mg/dL or 416 μmol/L) is the necessary precondition but is not sufficient — the great majority of hyperuricemic individuals never develop clinical gout.

The classical presentation is the acute gouty attack: sudden onset of severe pain, swelling, warmth, and erythema in a single joint, most commonly the first MTP joint (podagra). Other joints commonly involved include the midfoot, ankle, knee, wrist, and the small joints of the hand. The pain is among the most severe in clinical medicine; patients describe inability to tolerate even the weight of a bedsheet on the affected joint. Untreated attacks resolve over 1-2 weeks; recurrent attacks become more frequent over time and may involve more joints. Chronic tophaceous gout — the late stage of inadequately treated disease — produces deposits of crystals (tophi) in joints, periarticular tissues, and other sites, with associated joint destruction and renal disease. Diagnosis is confirmed by aspiration of the affected joint with demonstration of needle- shaped negatively birefringent monosodium urate crystals under polarized light microscopy. Serum urate may be normal or low during an acute attack (because of the urate’s deposition in the joint), so a normal urate level does not exclude the diagnosis. Treatment of the acute attack uses NSAIDs (first-line), colchicine, and oral or intra-articular corticosteroids. Treatment of chronic disease uses urate-lowering therapy: allopurinol (a xanthine oxidase inhibitor, first-line); febuxostat (an alternative xanthine oxidase inhibitor); probenecid (a uricosuric agent, less commonly used); and pegloticase (a recombinant uricase enzyme, used for refractory disease). The target serum urate level during chronic therapy is <6 mg/dL (360 μmol/L) for most patients and <5 mg/dL for those with tophi or recurrent attacks. Calcium Pyrophosphate Deposition Disease (Pseudogout) Pseudogout — calcium pyrophosphate deposition (CPPD) disease — is the crystal arthropathy caused by deposition of calcium pyrophosphate dihydrate crystals in joints. The acute attack of pseudogout closely resembles acute gout but typically affects the knee (the commonest single site), wrist, or shoulder rather than the first MTP. Chondrocalcinosis — calcification of the menisci and articular cartilage visible on plain radiographs — is the characteristic radiographic finding and may be present without clinical attacks. Aspiration demonstrates rhomboid-shaped weakly positively birefringent crystals. Treatment of acute attacks is similar to that of gout: NSAIDs, colchicine, corticosteroids. There is no specific long-term preventive therapy analogous to urate-lowering therapy for gout. CPPD disease is also associated with a chronic destructive arthropathy in some patients, sometimes producing severe joint destruction (the so-called “Milwaukee shoulder” being the classical example of CPPD-associated rapid joint destruction).

Juvenile Idiopathic Arthritis (JIA)

Juvenile idiopathic arthritis is the chronic arthritis of childhood, defined by onset before age 16 and persistence of joint symptoms for more than 6 weeks. Several subtypes are recognized: oligoarticular JIA (the commonest, with fewer than 5 joints involved in the first 6 months); polyarticular JIA (≥5 joints involved); systemic-onset JIA (Still’s disease, with prominent constitutional features); psoriatic JIA; enthesitis-related arthritis (the juvenile counterpart of seronegative spondyloarthropathies); and undifferentiated JIA.

The orthopedic implications of JIA include: limb-length discrepancy from accelerated or arrested growth at the affected joint physis; joint contractures; specific deformities (knee flexion contracture, ankle equinus, hip flexion); cervical spine involvement (particularly atlantoaxial subluxation and ankylosis); and the late development of end-stage joint destruction requiring arthroplasty in young adults. The medical management has been transformed by modern biological therapies, with substantial improvement in joint outcomes compared with the pre-biological era. Orthopedic surgery in JIA includes synovectomy, joint preservation procedures, leg-length equalization (epiphysiodesis or lengthening), corrective osteotomies for malunion or fixed deformity, and joint replacement in advanced disease. The technical demands of joint replacement in JIA patients are substantial because of the small bone size, the deformities, and the soft-tissue contractures.

Other Arthropathies

Systemic Lupus Erythematosus (SLE) SLE produces a polyarthritis that resembles RA but with less destructive disease in most cases. The classical “Jaccoud arthropathy” of SLE produces hand deformities similar to RA (MCP subluxation, ulnar deviation) without underlying bony erosion — these are “soft” reducible deformities. The principal orthopedic concerns are: avascular necrosis of multiple joints (particularly the femoral and humeral heads), often in association with corticosteroid therapy; antiphospholipid antibody syndrome with thrombotic complications; and perioperative management of immunosuppression. Hemophilic Arthropathy Hemophilic arthropathy results from repeated hemarthroses in patients with hemophilia A (factor VIII deficiency) or B (factor IX deficiency). Recurrent hemarthroses produce synovial proliferation, cartilage destruction, and joint deformity. The knee, ankle, and elbow are most commonly affected. Modern factor replacement therapy has substantially reduced the severity of hemophilic arthropathy, with prophylactic factor administration largely preventing recurrent hemarthroses. Orthopedic surgery in hemophilia requires careful perioperative coordination with hematology for factor replacement. Synovial Chondromatosis Synovial chondromatosis is a metaplastic proliferation of cartilaginous and osseous loose bodies within a joint. The condition typically affects the knee, hip, or elbow, presents with mechanical symptoms and progressive arthritis, and is treated by arthroscopic or open removal of loose bodies and synovectomy. Pigmented Villonodular Synovitis (PVNS) / Tenosynovial Giant Cell Tumor PVNS, now called tenosynovial giant cell tumor (TGCT), is a benign neoplastic proliferation of the synovium causing joint destruction. The diffuse form affects entire joints (most commonly the knee); the localized form produces nodular intra-articular lesions.

Treatment is surgical excision, with recurrence being common in diffuse disease. The CSF1R inhibitor pexidartinib has been approved for refractory disease.

Summary and Take-Home Points

The arthropathies form a heterogeneous group of inflammatory and crystal-induced joint diseases. Rheumatoid arthritis, the most consequential from a surgical perspective, is a chronic systemic autoimmune disease characterized by symmetric small-joint arthritis with characteristic hand deformities and cervical spine involvement (particularly atlantoaxial instability). The medical management has been transformed by methotrexate, biological agents, and JAK inhibitors, with surgical management focused on synovectomy, joint preservation, arthrodesis, and joint replacement for end-stage disease. The seronegative spondyloarthropathies — ankylosing spondylitis, psoriatic arthritis, reactive arthritis, IBD-associated arthritis — share axial inflammation, peripheral arthritis, enthesitis, and HLA-B27 association; ankylosing spondylitis specifically produces the bamboo spine with characteristic fracture vulnerability and may require corrective spinal osteotomy for severe kyphotic deformity. The crystal arthropathies — gout and pseudogout — produce acute and chronic joint inflammation managed by NSAIDs, colchicine, and disease-specific therapies (urate-lowering for gout). Across all arthropathies, the orthopedic surgeon’s role includes coordination with rheumatology, perioperative management of medications, and surgical procedures appropriate to the specific joint and disease pattern.