The Connective Diseases: The Rheumatologist’s Perspective

Abstract

The rheumatic diseases are an important category of chronic illness. Affecting many millions of Americans, these conditions are a leading cause of disability and contribute significantly to premature mortality in those afflicted. Given their prevalence, the rheumatic diseases contribute disproportionately to the population of patients who will require orthopedic surgery. This chapter presents a broad overview of these conditions, their underlying pathophysiology, and treatment.

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FormalPara Objectives

• To understand the importance and impact of these conditions on society and the health care system.

• To appreciate that such patients make up a significant proportion of an orthopedic practice.

• To appreciate the protean nature of these disorders and their varied pathophysiology.

• To understand the systematic approach to the differential diagnosis of these conditions is presented.

FormalPara Key Points

• Chronic rheumatic diseases represent a broad category of conditions that share a common feature: the destruction of cartilage and its consequences.

• While these conditions differ in their pathophysiology, the final common pathway is often the joint; hence, such patients frequently require orthopedic surgery.

• Classification of rheumatic diseases follows this organization: Osteoarthritis; Disorders of the Synovium (Rheumatoid Arthritis), Connective Tissue Diseases (Systemic Lupus Erythematosus, Systemic Sclerosis, Inflammatory Disease of the Muscle), Spondyloarthropathy (Ankylosing Spondylitis, Psoriatic Arthritis, Enteropathic Arthropathies), Vasculitides (Polymyalgia Rheumatica/Temporal Arteritis, Polyarteritis Nodosa, Microscopic Polyangiitis, Churg–Strauss, Wegener’s Granulomatosis), Metabolic Bone Disease (Osteoporosis), Crystal-Induced Arthropathies (Gout, Calcium Pyrophosphate Associated Arthropathy), Infectious Arthritis.

Introduction

Estimates of the prevalence of arthritis and the rheumatic diseases in general make evident the enormous impact that these conditions have on the US populace and the health care system in general. More than 21 % of US adults (46 million people) currently report physician-diagnosed arthritis. The National Arthritis Data Workup, an impressive collaborative effort from the Centers for Disease Control and Prevention, the National Institute of Health, the American College of Rheumatology, and the Arthritis Foundation, has published analyses that project an increase of physician-diagnosed arthritis to nearly 67 million people (an increase of 40 %) by the year 2030 [1]. While the majority of this health burden arises as a consequence of osteoarthritis, the entire span of the rheumatic diseases, such as rheumatoid arthritis, juvenile arthritis, spondlyarthropathies, systemic lupus erythematosus, systemic sclerosis, and primary Sjogren’s syndrome, contributes to the impact of this class of conditions. Already the leading cause of disability in the nation, the number of people with arthritis and arthritis-attributable limitation in activity is a serious public health issue. Such observations highlight the importance of effective interventions and programs to reduce the impact (loss of productivity, costs of therapy) of these chronic diseases. Ultimately, orthopedic intervention is required in many of these individuals to address the main issues of palliation of pain, inflammation, and further structural damage and disability compromising one’s quality of life. Factors such as an increased patient awareness of the benefits of surgery, improvements in surgical techniques, and the desire for an active life style have, in concert with the increasing prevalence of chronic arthritis, fueled the growth in utilization of orthopedic surgery. The orthopedic perspective and contemporary estimates concerning the rates of total joint replacement and spine surgery have been extensively reviewed in Chap. 2. This chapter introduces the broader spectrum of the rheumatic diseases as viewed by the Rheumatologist as such patients frequently require orthopedic intervention. Beginning with a review of the relevant pathobiology, a concise primer of the essential diseases is then presented.

Pathological Considerations

The elemental pathological process leading to orthopedic surgery is damage and gradual loss of the articular cartilage. However, all structures within the joint including the bones and connective tissue are affected. Osteoarthritis involves the joint in an asymmetric, localized pattern of involvement, with focal stress across the joint. This leads to misalignment and progressive alterations in load bearing relationships of the joint, resulting in the radiographic joint space narrowing and chronic joint damage. The structural changes occur in concert with biochemical abnormalities that ensue within the cartilage component, the underlying subchondral bone, joint capsule, and synovial membrane. Microscopically, biomechanical properties of the normal cartilage contain two main components: extracellular matrix (rich in type II, IX, and XI collagens and proteoglycans) and the chondrocytes lying within the matrix, responsible for maintaining homeostatic synthesis of the extracellular matrix components. The abnormal mechanical stress that occurs in OA causes alterations in chondrocyte metabolism and incites local inflammation by inducing synthesis of proteases, such as matrix metalloproteinase (MMP)-1, MMP-8, and MMP-13, and inflammatory mediators, such as interleukin (IL)-8, IL-6, prostaglandin E2, and nitric oxide [2]. The joint damage results from the metabolic imbalance due to accelerated cartilage degradation coupled with an insufficient reparative response. These processes incite localized tissue response consisting of inflammation of the joint lining and further loss of mechanical properties of the affected joint. Owing to the synthesis of metalloproteinases, there is gradual loss of the matrix components. Alterations of the proteoglycan content and structure then follow, and with continued deterioration in the cartilage and its load bearing capacity, stiffness and pain ensue, as nociceptive and proprioceptive receptors in the periosteum are activated due to the loss of the protective layer of the articular cartilage. Bone remodeling occurs in the underlying subchondral bone, causing sclerosis of the bone, formation of bone cysts, increased subchondral plate thickness, and reactive osteophyte formation at joint margins as a result of abnormal reparative process [3, 4].

Osteoarthritis is the most common cause of end-stage arthritis. Osteoarthritis may be primary, due to biochemical changes in the cartilage, or secondary to systemic disease affecting the cartilage, joint damage from pre-existing inflammatory joint disease, or trauma. It is a heterogeneous disease with various etiologies. Mechanical overload and imbalances lead to further cartilage degradation, processes that culminate in a failure of the mechanical functioning of the surrounding normal structures. Important adaptive responses such as subchondral sclerosis and osteophyte formation occur in response to joint overload and, if chronically present, cyst formation in the sub-articular bone may also result. Over time the osteophytes or bone spurs will lead to restricted range of motion.

Inflammatory arthritis, by contrast, is a constellation of diseases that target the synovium. Included in this class of disorders are such conditions as Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSa), and the Spondyloarthropathies (SpA). Common to all is the release of inflammatory mediators by the synovium leading to cartilage destruction. In contrast to osteoarthritis, mechanical overload is not a primary mechanism; as such, bone sclerosis or osteophyte formation is not seen. Rather, the inflammatory synovitis leads to a loss of cartilage matrix, marginal bony erosions, destruction of the joint capsule, and osteopenia.

Trauma is also important cause of joint destruction. Post-traumatic arthritis is initiated by cartilage damage at the time of injury or by secondary mechanical imbalances that result from fractures of juxta-articular bone. Abnormal loading conditions will subsequently lead to a wear-and-tear form of cartilage damage.

Osteonecrosis, also termed avascular necrosis, is another entity that may lead to joint arthritis. In this process the blood supply to the bone is compromised leading to necrosis of the bone supporting the articular surface. The most commonly affected joints are the hip, shoulder, and knee. As the disease progresses the necrotic bone may collapse leading to the loss of articular integrity and progressive cartilage deterioration.

Other conditions that may lead to joint damage include storage and deposition disorders (hemochromatosis, alkaptonuria, Wilson’s Disease, Gaucher’s Disease), crystal deposition diseases (chondrocalcinosis, gout), tumor (synovial chondromatosis), infectious (post-septic), and bleeding disorders (hemophilia).

Owing to the prominent involvement of joints and the musculoskeletal system, patients who acquire these often multi-systemic conditions frequently require orthopedic intervention. The protean clinical manifestations of these diseases, coupled with important medication-related management considerations, present challenges encompassing the span of perioperative medical practice. Indeed such patients are amongst the most challenging encountered in the perioperative setting [5, 6].

The Rheumatic Diseases

Table 3.1 presents a general classification of the rheumatic diseases.

Table 3.1 Classification of the rheumatic diseases

Osteoarthritis (OA)

The most common form of arthritis, osteoarthritis is a heterogeneous group of common conditions that share similar pathological and radiographic features, specifically loss of articular cartilage. It should be considered, furthermore, as an organ failure of the synovial joint, driven by a primary defect in any of its supporting tissues (ligaments, meniscus, subchondral bone, periarticular muscles, synovium, nerves, or articular cartilage) [7]. Therefore, there are expectantly many pathophysiological mechanisms of OA that alter the relationship between mechanical factors and tissue response of the synovial joint; however, a common end-stage is wherein all components of the joint fail. An age-related disorder, OA is uncommon before age 40 but increases in prevalence thereafter; by age 70 most people have pathological changes of OA though they may not be symptomatic. Other risk factors include female gender, ethnicity (>blacks), genetic predisposition, obesity (especially for knee OA), and trauma. The causes for primary or idiopathic osteoarthritis remains unclear; research has focused on the intra-articular alterations involving the articular cartilage and subchondral bone, and considerable interest has arisen in the role of the neuromuscular unit involved in joint motion, stability, and proprioception as contributing to the progression and/or predisposition to the development of OA [8, 9].

Osteoarthritis is a focal disease not affecting all joints equally; even within a given joint the involvement may be patchy and asymmetric. Its pathogenesis involves an incongruence between normal cartilaginous degradative and repair mechanisms, which results in a net loss of cartilage, bony hypertrophy, and osseous outgrowths (osteophytes). Its primary symptoms are use-related joint pain and stiffness (gelling). On physical examination, some combination of joint tenderness, crepitus, bony enlargement, malalignment, decreased range of motion, and joint effusion are usually noted. Treatment is mainly symptomatic (NSAIDS, analgesics, intra-articular injections). In those with severe disease, total joint arthroplasty is a common outcome. Radiographic findings include asymmetric joint space narrowing, subchondral sclerosis and cystic change, and marginal osteophytes (bony spurs) (Figs. 3.1 and 3.2). When the spine is predominantly involved, disk degeneration and facet joint arthritis results in symptomatic stenosis, necessitating decompression (and fusion) surgery in order to alleviate symptoms and restore a functional activity (Fig. 3.3a, b).

Fig. 3.1

Radiograph of osteoarthritis in knees: varus deformity. X-ray of bilateral knees showing advanced, severe bilateral degenerative arthrosis most marked in the medial compartments bilaterally where there is bone on bone apposition. Tricompartmental osteophytosis is present. Bilateral varus deformity is noted

Fig. 3.2

Radiograph of osteoarthritis in knees: valgus deformity. Right knee shows severe degenerative arthrosis with tricompartmental osteophytes and lateral bone-on-bone apposition with marked valgus deformity. Left knee shows moderate degenerative arthrosis with small joint line osteophytes and moderate lateral compartment narrowing with valgus deformity

Fig. 3.3

(a, b) Radiograph of osteoarthritis of lumbar spine. There is a mild curvature of the lumbar spine convex right with multilevel degenerative disk disease with disk space narrowing, endplate sclerosis, and osteophytes at L4-5 and L5-S1

Disorders of the Synovium

Rheumatoid arthritis (RA) is the prototypical disorder primarily affecting the synovium. Whereas the normal synovium consists of a thin intimal lining layer, one to three cell layers thick, comprised of roughly equal proportions of different cell types (macrophage-like synviocytes or type A synoviocytes, and fibroblast-like synoviocytes or type B synoviocytes), in contrast the synovial tissue in RA is greatly hypertrophied (up to 8–10 cell layers thick) displaying increased numbers of both type A and B synoviocytes accompanied by mononuclear cell infiltration of the sublining below the intima transforming the milieu as the pot of inflammatory cytokines and proteases (Fig. 3.4a, b) [10, 11]. The subintimal region where the blood vessels are located become heavily infiltrated with inflammatory cells, including T and B lymphocytes, plasma cells, natural killer cells, macrophages, and mast cells. The hypertrophied synovium transforms into villous like projections, also called pannus, which protrude into the joint cavity and invade the juxtaposed articular cartilage and underlying bone, resulting in cartilage destruction bone erosions and ultimately compromising the integrity of each component of the joint (Fig. 3.5a, b). The destructive properties of the pannus are a result of: (1) increased synthesis of metalloproteinases and other proteinases by synovial fibroblasts and monocytes; (2) chrondrocyte activation by key cytokines (IL-1, TNF-α, and TGF-ß), resulting in decrease in collagen and proteogylcan synthesis; and (3) recruitment and differentiation of cells that express an osteoclast phenotype leading to focal bone erosions. It is hypothesized that the osteoclast differentiation from the macrophage lineage results in response to inflammatory mediators and cytokines (L-1, TNF-α, IL-17) produced by fibroblast-like synoviocytes in the rheumatoid synovium [12].

Fig. 3.4

(a) Normal synovial lining: This layer is usually only 1–3 cells thick, comprised of type A macrophage-like synoviocytes and type B fibroblast-like synovicytes. (b) Synovial lining in rheumatoid arthritis: This lining is greatly hypertrophied (8–10 cells thick) (Both used with permission from ACR Image Bank)

Fig. 3.5

Pannus formation in rheumatoid arthritis. (a) Normal synovium with thin intimal layer. (b) Synovium in RA showing hypertrophied synovial layer, increase infiltration by inflammatory cells, and angiogenesis. The pannus that develops invades into the joint cavity, articular cartilage and subchondral bone (Used with permission from Strand V, Kimberly R, Isaacs JD. Biologic therapies in rheumatology: lessons learned, future directions. Nat Rev Drug Discov 2007;6:75–92)

Rheumatoid arthritis is a chronic systemic inflammatory disease, driven by autoantibodies and immunologically overactive cells that primarily target the synovium as well as extra-articular tissues and organs. The etiopathogenesis of RA involves a complex interplay of genetic predisposition and probable environmental factors that trigger a cascade of intra-synovial immune response that perpetuates a pro-inflammatory milieu of cellular and molecular phenomena that lead to erosions of the cartilage and bone. Rheumatoid arthritis affects females more often than males (RR 3:1). Its peak onset is in the fourth to fifth decade. Usually RA presents insidiously over several weeks to months, with the initial pattern localized to inflammation of the smaller peripheral joints, typically symmetric in distribution, and often with concurrent systemic features of fatigue and generalized malaise. Uncontrolled joint inflammation, characterized by tenderness, swelling, and dysfunction, may lead to larger joint involvement, destruction of synovial joints, followed by deformities and loss of joint function (Fig. 3.6a, b). Extra-articular manifestations may arise but have become less common in the modern therapeutic era.

Fig. 3.6

(a) Radiographic changes of advanced rheumatoid arthritis. (b) Rheumatoid involvement of the metacarpal and proximal interphalangeal joints bilaterally. There is fusion of the carpal joints bilaterally. The radiocarpal joints are fused. The carpal metacarpal joints are fused. Joint space narrowing, mild proliferative changes and erosions are noted in the MP and PIP joints. There is relative sparing of the DIP joints

Products of the human leukocyte antigen (HLA) region of Class II genes of the major histocompatibility complex (MHC) play an important role in the susceptibility and pathogenesis of RA. Individuals who are HLA DRB4 positive are more likely to develop severe disease, marked by erosions of the joints, deformity and disability. The concept of “shared epitope” refers to a common structural domain that consists of 5-amino acid sequence (QKRAA) found on several HLA-DR4 alleles, which has been shown to confer susceptibility to RA [13]. Early in the development of disease, T-lymphocyte infiltration occurs in the synovial tissue, followed by proliferation of the synovial lining; over time synovial infiltration by B-cells, macrophages, and fibroblasts follows and, in response to the production of various chemotactic factors, granulocytes migrate into the joint space discharging pro-inflammatory substances increasing vascular permeability and perpetuating the inflammatory response.

Relevant laboratory studies include markers of the inflammatory response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Rheumatoid factors are autoantibodies directed against the Fc portion of immunoglobulin G (IgG), and are found in 75–80 % of RA patients during the course of their illness. The immune complexes deposit into joints and tissues, exacting inflammation and damage. RF lacks specificity as levels may be elevated in certain infectious states (hepatitis, human immunodeficiency virus (HIV), endocarditis), malignancy (multiple myeloma), and also other connective tissue diseases (systemic lupus erythematosus (SLE), primary Sjogren’s syndrome, scleroderma, myositis) [14]. Detection of anti-CCP antibodies has been shown to have greater specificity (95–97 %), with similar sensitivity to RF for the diagnosis of RA [15, 16]. More recently, Anti-citrullinated protein antibodies (ACPA) have emerged as a distinctive subset of patients with RA [17]. It has been shown to be a strong prognostic indicator for both the development of RA in the preclinical stage, as well as predictor of the extent of joint destruction [18–20]. Seropositivity for ACPA at baseline has been associated with subsequent structural damage in the setting of more persistent synovitis. ACPA status has become an important autoantibody biomarker for both diagnostic and prognostic value.

The therapeutic armamentarium of RA includes combinations of symptomatic therapies such as non-steroid inflammatory drugs (NSAIDS) and corticosteroids, nonbiologic disease modifying anti-rheumatic drugs (DMARDs) including methotrexate, leflunomide, sulfasalazine, and biological DMARDs, such as tumor necrosis factor (TNF) blockers (infliximab, etanercept, adalimumab, and more recently golimumab and certolizumab), interleukin-1 (IL-1) blockade (with anakinra), IL-6 receptor blockade (with tocilizumab), T cell co-stimulation blockade (with abatacept), and B cell depletion (with rituximab). Non-biologic and biologic DMARDs have demonstrated major effects on inflammation as well as the tempering the pace of structural damage in the chronic course of this illness. An important consideration in the perioperative setting, however, is that many of these medications can complicate surgical interventions increasing the risk of postoperative infection and impairing wound healing (Chap. 22).

Connective Tissue Diseases

The most common of these conditions is Systemic Lupus Erythematosus (SLE), a prototypical autoimmune disease driven by autoantibodies which target multiple organ systems including joints, skin, and kidneys. This condition occurs mainly in woman during their reproductive years (female to male ratio of 10:1), and disproportionately affects minorities, more commonly affecting African Americans, Asians, and Latinos (prevalence of 1:250–1:500), compared to Caucasians (1:2,000) [21, 22]. A hallmark is the diverse clinical expression and undulating course of this condition. The relapsing-remitting pattern of disease, along with the clinical heterogeneity, makes SLE one of the challenging autoimmune disorders not only to diagnose but also to treat. The most prevalent and severe manifestation of systemic involvement is renal disease (lupus nephritis), though other important manifestations involving the musculoskeletal, cutaneous, and neurologic systems frequently arise in the course of this illness. Constitutional symptoms (fever, fatigue, malaise) are the most common presenting complaints and herald the onset of disease flares. Often, the temporal sequence of organ involvement and the severity of its course are unpredictable. While its cause remains unknown, autoantibodies directed at cell nuclei and their constituents (antinuclear antibodies [ANA], anti-double stranded DNA [dsDNA] antibody) are hallmarks of this condition and are believed important to the pathogenesis of the disease. Deposition of immune complexes on a variety of target organs results in tissue injury from inflammation, thrombosis from premature infarction of blood vessels, and/or vasculitis. Multiple mechanisms are at play and lupus pathogenesis is complex due to nonlinear immune pathways. However, the formation of pathogenic autoantibodies as well as its defective clearance signals a dysregulated immune response with activation of the complement cascade, immune cell types (B cells, T cells), cytokines (type I interferon-α), and proteins involved in the inflammatory response. While hereditary and environmental susceptibility factors are believed important in the pathogenesis, pregnancy and certain drugs are also known disease precipitants.

Beyond the clinical complexity of diagnosis and tracking the course of illness, the challenge often becomes offering treatment modalities that strike the fine balance between immunosuppression and immune dysregulation. Corticosteroids and immunosuppressants remain the mainstay of therapy. Since their introduction in 1950s, corticosteroids have altered the management of most rheumatic diseases and have led to gradual improvements in the morbidity and mortality of lupus patients. However, there are major toxicities from long term corticosteroid use, which includes the infectious risks, its deleterious effects on bone health, and its disturbances to glucose homeostasis. Thus, antimalarials (plaquenil or hydroxychloroquine), nonsteroidal anti-inflammatory drugs (NSAIDs), azathioprine (Imuran^®), methotrexate, cyclosporine, mycophenolate mofetil (Cellcept^®), and cyclophosphamide (Cytoxan^®) have been utilized for their steroid-sparing and immunosuppressive effects. In addition, a new monoclonal antibody to a soluble B-lymphocyte stimulator, known as belimumab (Benlysta^®) has recently been approved by the US Food and Drug Administration (FDA) for the treatment of autoantibody (ANA and/or dsDNA) positive SLE patients who have mild to moderate disease despite standard therapy.

As will be discussed, avascular necrosis or osteonecrosis is seen relatively commonly (4–15 %) in SLE patients who have received high doses of corticosteroid therapy for serious organ involvement. Although the pathogenesis of osteonecrosis remains unclear, the final common pathway of subchondral bone destruction involves a compromise of blood flow preventing essential nutrients and normal reparative processes, leading to further osteocyte death [23]. AVN accounts for a numerically small but important indication for total joint replacement, particularly of the hip, knee, and shoulder in SLE patients (Fig. 3.7). Owing to an inherent and drug-induced immunosuppression, patients with SLE are also at increased risk for the development of septic arthritis, the acute therapy of which may require input from the orthopedic surgeon.

Fig. 3.7

Avascular necrosis of the hip in systemic lupus erythematosus. The R hip reveals extensive avascular necrosis involving almost the entire articular portion of the femoral head, with mild collapse of the superior femoral head. This has elicited a moderate degree of edema within the proximal right femur as well as a joint effusion of the right hip joint. Avascular necrosis also affects the greater trochanter

Another important condition of the connective tissue is that commonly known as systemic sclerosis (scleroderma). Scleroderma exits in two major and distinct forms: localized scleroderma (LSc), which is confined to the skin and subcutaneous tissues and systemic sclerosis (SSc), which almost always has internal organ involvement, but may be limited or diffuse in its cutaneous distribution on the basis of extent of skin thickening; limited disease is defined as skin thickening that affects the distal extremities below the elbows and/or below the knees, and to a lesser extent face and neck involvement, where as diffuse cutaneous disease refers to extensive skin sclerosis affecting the proximal limbs, trunk, face, and neck regions. Rarely, systemic sclerosis can also present as SSc sine scleroderma with the typical vascular and fibrotic features of systemic disease but without any cutaneous involvement.

Localized scleroderma, an entity that is distinct from limited scleroderma, includes dermatologic conditions such as morphea (circumscribed patches of thickened skin), linear scleroderma, pansclerotic morphea, or mixed scleroderma; rarely are there extracutaneous manifestations. Localized and limited scleroderma should be thought of as two distinct diseases with different clinical manifestations and prognosis (Fig. 3.8). In limited cutaneous sclerosis, formerly termed as CREST syndrome (calcinosis of the digits, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasis), patient generally have prominent vasculopathic phenotype. One of the most characteristic clinical manifestation of vascular dysfunction is Raynaud’s phenomenon, which is due to arterial vasoconstriction in the digits precipitated by cold or stress, manifested by the triphasic color changes (white (pallor) → blue (acrocyanosis) → red (reperfusion hyperemia)). Pulmonary vascular disease, primarily pulmonary arterial hypertension is more commonly seen in limited cutaneous disease, affecting up to 40 % of patients. In systemic sclerosis, clinical manifestations arise as a consequence of an obstructive vasculopathy involving the small vessels, the pathological accumulation of collagen in the skin and other organ systems resulting in fibrosis, and autoimmunity as evidenced by a number of associated autoantibodies. Often a severely debilitating disease, pulmonary parenchymal disease (interstitial fibrosis) has become the most common form of death for such patients [24]. There is no effective treatment for this disorder. An important complication of this condition is the ischemic digit, usually the finger, due to an obliterative vasculopathy and vasospasm in which the caliber of blood vessels narrows and irreversible tissue loss may ensue. Chronic ischemia may lead to digital ulcers, gangrene, tapering of fingers due atrophy of underlying soft tissue, and skin changes referred to as sclerodactyly (localized thickening and tightness of the digit). A consequence of the vascular obstructive and vasospastic elements of this disease, SSc manifestations in the hand may require the participation of a hand surgeon experienced in microsurgical revascularization, digital arterial reconstruction to improve digital vascular perfusion, and peripheral sympathectomy to relieve pain. There also may be a role of surgery for advanced SSc affecting the hand, in which chronic ischemia and fibrosis may lead to atrophy and contractures of the digits, nail deformities, and calcinosis (Fig. 3.9a, b); however, surgical benefits should be balanced with risks of impaired wound healing and the progressive course of SSc [25]. Important perioperative surveillance/screening of pulmonary disease (pulmonary arterial hypertension and/or pulmonary fibrosis) is imperative in SSc patients, especially if dyspnea is present.

Fig. 3.8

Schematic diagram for classification of scleroderma

Fig. 3.9

(a) Calcinosis and contracture in scleroderma. (b) There are flexion contractures of the PIP joints bilaterally. There are soft tissue calcifications around the wrists, hands and distal forearms bilaterally. There is acroosteolysis with loss of the terminal tufts of distal phalanges at multiple fingers

A less common but important third form of the connective tissue disease include the inflammatory diseases of the muscle—dermatomyositis (DM) and polymyositis (PM). These represent another heterogeneous group of disorders, and they share the clinical features of a progressive skeletal muscle weakness and fatigue and a decrease in endurance. Disease-specific autoantibodies are also frequently found but ultimately the diagnosis is made by muscle biopsy that demonstrates an inflammatory infiltrate. Treatment includes corticosteroids, IVIG, and immunosuppressive therapy with medication such as Methotrexate. These diseases rarely require orthopedic intervention.

Spondyloarthropathies

The Spondyloarthropathies (SpA) comprise a group of inflammatory disorders with overlapping clinical manifestations and a shared genetic marker (HLA-B27). Ankylosing Spondylitis (AS), with its prominent back (axial) involvement, is the protypical condition but other disorders such as Psoriatic Arthritis (PsA), the enteropathic arthropathies, and Reactive Arthritis are now categorized similarly. Patients who present with clinical features suggestive, but not diagnostic, of SpA are labeled as “undifferentiated” spondyloathropathy. In contrast, those with well defined clinical features have been referred to in the past as “seronegative” spondyloarthropathy. This designation implies the genetic, clinical, and pathophysiologic characteristics of these conditions, while making reference to the absence of rheumatoid factor. In their fullest expression, these conditions are characterized by three distinctive features: the soft tissue phenomenon of enthesitis and a true arthritis involving the axial and peripheral skeleton.

The first distinguishing feature of the spondyloarthropathies is the presence of enthesopathy, an inflammation of the boney insertion points of tendons, ligaments, or the joint capsule. Enthesitis is responsible for the multiple spinal and peripheral manifestations characteristic of this class of rheumatic conditions in which pain, stiffness, and restriction develops at sacroiliac and other spinal joints. Extraspinal enthesitis commonly affect the Achilles tendon insertions to the calcaneous and plantar fascia. A second trademark of these conditions is the presence of axial arthritis (i.e., sacroilitis and spondylitis). Inflammatory synovitis and capsular enthesitis at the sacroiliac joints (SI) results in sacroilitis; similarly inflammation of the entheses associated with paraspinal ligaments ultimately leads to spondylitis. Such involvement also accounts for the involvement of the intervertebral disks, symphysis pubis, manubrioclavicular and sternoclavicular joints. These conditions are brought to their fullest expression with the addition of peripheral joint involvement, an uncommon feature in AS but commonly seen in PsA or reactive arthritis. Various patterns are commonly seen and vary according to the associated disease process. For instance, in AS, the shoulder and hips are most frequently involved. In contrast, an asymmetric lower extremity oligoarthritis (knee, ankle) is more commonly seen in Reactive Arthritis while distal interphalangeal joint disease usually denotes PSa. An important feature of the SpAs is the “sausage” digit or dacyllitis, an inflammatory process involving a small joint synovitis combined with an enthesitis of the tendon sheaths, insertions and various other supporting tissues of the digit (fingers or toes). Combined, these processes produce the sausage-like swelling a finding virtually pathognomonic of the spondyloarthropathies.

As the prototypical disease among the spondyloarthropathies, the symptoms of AS usually begin in the third or fourth decade of life with the gradual onset of inflammatory back pain. It predominantly affects men at much higher frequency than women (ratio of 9:1). Signs and symptoms of spinal involvement predominate and the inflammatory (as opposed to mechanical) nature of the condition is suggested by a number of features: age < 40 years, insidious onset, duration of <3 months, marked morning stiffness, and improvement with activity. Patients often complain of back pain at nighttime. Sacroilitis, a common initial feature, presents as pain in buttocks which may radiate down the legs and/or hip pain. In a minority of patients, peripheral oligoarthritis and/or enthesitis accompany the axial involvement. Concurrent constitutional features of fatigue, weight loss, and depression often may be present. Progressive involvement of the entire spine occurs over years, resulting in spinal pain, stiffness, and severe restriction of the spine (Fig. 3.10). Family history often reveals others with early onset back pain or inflammatory problems in the eye (uveitis, iritis). Diagnosis of AS should be predominately based on the clinical presentation of a usually a young man (before the age of 40 years) who presents with chronic inflammatory back pain. The New York criteria of 1968, modified New York Criteria 1984 criteria, and the most recent European Spondyloarthropathy Study Group criteria outline important clinical and radiographic features; however, the classifications have low sensitivity in detecting early disease (Fig. 3.11; [26–28]).

Fig. 3.10

Spinal radiograph in severe anklyosing spondylitis. There is complete fusion of the sacroiliac joints bilaterally and axial joint space narrowing of both hip joints. In the spine, bridging syndesmophytes are noted focally at L2-3 on the right as well as T10-11 on the right and T9-10 on the left

Fig. 3.11

Criteria for diagnosing ankylosing spondylitis

In contrast, patients with Psoriatic Arthritis are also often young, but rather than spinal disease, the more typical presentation is that of an asymmetric oligoarthritis in conjunction with other characteristic features such as destructive DIP involvement, nail changes, sausage digits and the aforementioned peripheral enthesopathy (often the Achilles tendon or plantar fasciitis). For those that do have spondyloarthropathy of PsA, the asymmetric involvement of sacroilitis can distinguish that from the spondyloarthropathy of AS, which classically affects both sacroiliac joints. Also, approximately a third of patients with psoriasis will develop PsA; the majority of patients develop psoriasis years prior to inflammatory musculoskeletal features; however, there is a group of patients (15–20 %) in whom the joint disease precedes the skin disease [29]. With respect to the enteropathic disease entities, this form of inflammatory arthritis develops in patients with Crohn’s Disease or Ulcerative Colitis. Sacroilitis is common and the peripheral joint arthritis tends to take the form of a large joint inflammatory process that follows the clinical activity of the underlying gastrointestinal disease. The pattern of arthritis is variable; it is commonly asymmetric but can present in a migratory or additive fashion, and tends to be non-erosive. Lastly, there is Reactive Arthritis. Formerly known as “Reiter’s Syndrome,” this is a clinical syndrome of arthritis coupled with extra-articular features seen in susceptible individuals following a genitourinary or gastrointestinal infection. Such individuals develop a seronegative, inflammatory arthritis arising weeks after the antecedent infection accompanied by ocular (conjunctivitis, uveitis), mucocutaneous (oral ulcers, balanitis, keratoderma blennorrhagicum), gastrointestinal (dysenteric), and genitourinary manifestations (urethritis, cervicitis). Infectious agents most often implicated include Chlamydia, Salmonella, Campylobacter, Yersinia, and Shigella species. These organisms are rarely cultured from the joint fluid or synovial tissue, and hence the designation reactive. The peripheral joint involvement is usually an asymmetric lower extremity oligoarthritis, though as with the other spondyloarthropathies, sausage digits (dactylitis) are also a common feature. Axial involvement is uncommon and distinguishable from AS spondyloarthropathy by its predominate asymmetric pattern of sacroilitis and paramarginal syndesmophytes. Lastly, patients may present with features suggestive (seronegative oligoarthritis and enthesitis) but not diagnostic of these conditions. In such patients the diagnostic designation is that of an undifferentiated spondyloarthropathy.

Once difficult to treat, new biologic therapies such as tumor necrosis factor (TNF) inhibitors have markedly improved the clinical course and symptomatic experience of patients suffering with these conditions. Nonetheless, given the peripheral joint involvement seen in these conditions, patients who suffer from these conditions ultimately may require total joint arthroplasty.

Vasculitides

The term vasculitis refers to several diseases involving inflammation of the blood vessels with resultant tissue necrosis and organ-failure. The spectrum of disease is broad with overlapping features. While its classification systems had historically relied on eponyms, it is now categorized according to the size of the involved blood vessels. Polymyalgia rheumatica and temporal arteritis are amongst the best known examples but also included are such conditions as polyarteritis nodosa, granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), Churg–Strauss syndrome (also known as allergic granulomatosis and allergic angiitis) to name a few. Treatment paradigms rely on corticosteroids and immunosuppressants. Orthopedic intervention is rarely needed in the course of these conditions.

Metabolic Bone Disease

Osteoporosis is a widely recognized disorder of skeletal muscle characterized by low bone mass and microarchitectural deterioration of bone, increasing its fragility and susceptibility to fracture. Pathophysiologically comprised of a heterogeneous group of disorders, osteoporosis is characterized by a net loss of bone (bone resorption activity dominating over bone formation activity) resulting in a decrease in the overall density of mineralized bone (Fig. 3.12). Such osteoporotic fractures that result due to the inability of the bone to absorb the traumatic load may have devastating consequences for patients and, with the aging of the population, have become so common as to constitute a threat to public health. Owing to the causal association between this condition and fracture of the hip and the importance of bone quality in osseous healing, it is one of the most important rheumatic diseases now encountered on orthopedic services.

Fig. 3.12

Common causes of osteoporosis

The aim of osteoporotic screening and treatment is to prevent fractures. Presently, the dual X-ray absorptiometry (DXA) has become the diagnostic tool for osteoporosis. Adopted by the World Health Organization (WHO) and using population standards, osteoporosis is defined in a patient with a bone density measurement of the spine that is >2.5 standard deviations below the mean of the standard 35 year old population in the appropriate gender (as defined by the T score). Osteopenia is defined as a T score between 1.0 and 2.5 standard deviations the bone density of a standard 35-year old population. Additionally, the Z score provides an evaluation of bone density as it relates to age-matched controls. While bone density is a primary indicator of bone quality, there are other structural and material factors, such as bone macro- and micro-architecture, degree of mineralization and micro-damage accumulation, and bone turnover that influence overall bone quality [30]. Indeed in the orthopedic surgical setting its implications extend to such considerations as the achievement of boney fusion after spinal surgery as well as the anticipated longevity of total joint replacement.

Crystal-Induced Arthropathies

Owing to fluid shifts and dehydration, gout (uric acid) and pseudo-gout (Ca²⁺ pyrophosphate) deposition in peripheral joints occurs frequently after surgery. As such, they are common management problems in the postoperative period, as discussed in Chap. 10. The archetypal presentation of these conditions is well known to clinicians taking the form of the sudden onset of severe pain, swelling and erythema, usually of a single joint, most often the first metatarsophalangeal joint. Other joints are not uncommon, however; the tarsometatarsal joint and ankle are frequent sites as are the knee and wrist. The latter are frequently seen in Ca²⁺ pyrophosphate crystal deposition (CPPD). Diagnosis is premised on the demonstration of pathognomonic crystals within the synovial fluid as seen via polarized light microscopy; that is, the negatively strongly birefringent, needle-shaped monosodium urate crystal in the case of gout versus the positively weakly birefringent, rhomboid crystal of CPPD (Fig. 3.13a, b). In the postoperative setting, treatment involves the oral administration of nonsteroidal anti-inflammatory drugs, short courses of corticosteroids (or ACTH), or intra-articular injections of such steroids. Because of the potential for gastrointestinal side effects, oral colchicine is a less favored medication after surgery.

Fig. 3.13

(a) Gout: monosodium urate crystals. Strongly negative birefringent, needle-shaped crystals aspirate from tophaceous deposit. Crystals are yellow when parallel (blue when perpendicular) to the long axis of the first order red compensator on polarized light microscopy consistent with gout. (b) Pseudo-gout: calcium pyrophosphate dehydrate (CPPD) crystals. Weakly positive birefringent, rhomboid-shaped or polymorphic crystals aspirated from joint of a patient with pseudo-gout. Crystals are typically blue when parallel (yellow when perpendicular) to the long axis of the first order red compensator on polarized light microscopy consistent with pseudo-gout (Both used with permission from ACR Image Bank)

Another form of crystalline disease is calcium hydroxyapatite crystal deposition disease, a common entity best characterized as “calcific tendinitis” most frequently affecting the shoulder, but also affecting other sites such as the hips, wrists, and feet. This syndrome is typically recognized by recurrent pain due to the pathologic peri- and/or intra-articular buildup of calcific material around the tendons/joints, which occurs as primary (or idiopathic) or as a secondary process due to various disease processes including renal disease, collagen vascular disease, metabolic disorders, or trauma. Hydroxyapatite crystals are small, amorphous, and nonbirefringent in polarized light, thereby making it difficult to diagnose with light microscopy; diagnosis is made on the basis of radiographic findings of calcium deposits in the typical periarticular and tendinous sites and concomitant clinical symptoms (Fig. 3.14). Rarely requiring surgical intervention, treatment of hydroxyapatite deposition disease involves conservative measures, such as nonsteroidal anti-inflammatory medications (NSAIDs), intra-articular steroid injections, and physical therapy.

Fig. 3.14

Calcific tendonitis of shoulder. Amorphous calcific deposit on supraspinatus tendon near its insertion site at the greater tuberosity (Used with permission from ACR Image Bank)

Infectious Arthritis

Invasion of a joint by pyogenic bacteria is responsible for rapidly progressive joint destruction, osteomyelitis and potentially systemic spread of the infection. The majority of such infections arise from hematogenous spread of offending bacteria to the affected joint(s). Predisposing factors include IV drug use, in-dwelling catheters, the use of immunosuppressive medication, and a host of disease processes that suppress immunity. Important examples of the latter include diabetes mellitus, chronic inflammatory arthritis, HIV infection, and alcoholism, to name a few.

The major pathogens are the gram-positive cocci (usually Staphylococcal species) accounting for >75 % of cases. Staphylococcus aureus is the most common offending agent, followed by streptococci and pneumococci; Staphylococcus epidermidis is often seen in the setting of prosthetic joint infection, rarely arising in the native joint. Gram-negative organisms, though a much less common cause of septic arthritis, are more often encountered in intravenous drug abusers. Associated with a purulent joint fluid (WBC > 50,000, predominately granulocytes), a definitive diagnosis requires the demonstration of bacteria in the joint fluid. Antibiotic therapy logically follows from culture of the synovial fluid. Prompt diagnosis and treatment is vital in order to achieve optimal recovery. Repeated joint aspiration (needle or arthroscopic) may be required serially early in the treatment process. Removal of the prosthesis is often required followed by a course (6 weeks) of intravenous antibiotic therapy and ultimately reimplantation.

Summary

The chronic rheumatic diseases represent a broad category of conditions that share a common feature, the destruction of cartilage and its consequences. While these conditions differ in their pathophysiology, the final common pathway is often the joint hence such patients frequently require orthopedic surgery. Presented herein is a short summary of the important conditions, presenting their broad range of clinical expression the purpose of which is the education of the readership. A second chapter in this book presents the clinical approach to the assessment of such patients prior to undergoing surgery.

Summary Bullet Points

• The chronic rheumatic diseases are prevalent conditions with a major impact on society and the health care system.

• Given their prevalence and the involvement of the joints, such patients may make up a significant proportion of an orthopedic patient population.

• The rheumatic diseases share one central feature: the destruction of joints.

• Although a disparate group of disorders, a systematic approach to the differential diagnosis of these conditions is presented.