Rheumatologic Disorders

Definition

Rheumatologic (or rheumatoid) disorders include much more than “arthritis” and encompass a large group (nearly 100) of disorders that affect bones, joints, and muscles. Arthritis is a nonspecific term that means “inflammation of the joints.” Often arthritis is used interchangeably with rheumatism or rheumatoid arthritis (RA) to denote aches, pains, and stiffness in the joints and muscles, but these terms are not synonymous nor inclusive. Rheumatologic disorders include RA, osteoarthritis (OA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), scleroderma (SD), Sjögren syndrome (SS), gout, ankylosing spondylitis, Lyme disease, giant cell arteritis (GCA or temporal arteritis), and fibromyalgia syndrome (FMS).

In this chapter, RA, OA, SLE, and SS are presented in more detail, and PsA, Lyme disease, GCA, and FMS are discussed to a lesser degree.

Rheumatologic disorders have significant personal and economic impact. According to the Arthritis Foundation, more than 40 million Americans have various forms of arthritis, and more than 8 million of them are considered “disabled.” In terms of its overall economic impact, arthritis costs the American economy more than $20 billion annually and accounts for nearly 30 million lost workdays per year.

COMPLICATIONS: Patients with rheumatic disease undergoing dental treatment may be at risk for infection, bleeding, drug interactions, and adverse effects. These events could prove serious. The dentist must be able to identify these patients, assess risk based on history and clinical findings, and work closely with the managing physician to develop a dental management plan that will be effective and safe for the patient.

Categories of Rheumatologic Disorders

Rheumatologic disorders can be classified into nine categories, defined by the predominantly affected tissues, such as joint, synovium, cartilage, or connective tissues ( Table 20.1 ). At each point in the evaluation (history, physical examination, and laboratory testing), it is important to identify the tissues involved.

TABLE 20.1
Classification of Musculoskeletal Diseases
Category Prototype(s) Useful Test(s) Treatment(s) *
Synovitis Rheumatoid arthritis Rheumatoid factor, ESR DMARDs and biologic agents
Autoimmune diseases ANA test Prednisone and immunosuppressive drugs
Enthesopathy Ankylosing spondylitis and spondyloarthropathies Sacroiliac radiographs NSAIDs, MTX, and biologic agents
Crystal-induced synovitis Gout Joint fluid crystal examination NSAIDs
CPPD (pseudogout) Radiographic chondrocalcinosis NSAIDs
Joint space disease Septic arthritis Joint fluid culture Antibiotics
Cartilage degeneration Osteoarthritis Radiographs of affected area NSAIDs, analgesics, and physical therapy
Osteoarticular disease Osteonecrosis Radiographs, magnetic resonance imaging Core decompression or prosthetic joint replacement
Inflammatory myopathy Polymyositis
Dermatomyositis
Inclusion body myositis
Muscle enzymes, electromyography, muscle biopsy Corticosteroids and immunosuppressive drugs
Local and regional conditions Tendonitis or bursitis Aspirate bursa if infection is suspected Local injections
General conditions Polymyalgia rheumatica Elevated ESR Corticosteroids
Fibromyalgia Normal ESR Aerobic exercise, stretches, and sleep medications
ANA, Antinuclear antibody; CPPD, calcium pyrophosphate crystal deposition disease; DMARD, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; MTX, methotrexate; NSAID, nonsteroidal antiinflammatory drug.

* Biologic agents include anti–tumor necrosis factor (anti–tumor necrosis factor) drugs and others.

Categories of Rheumatologic Disorders

Rheumatologic disorders can be classified into nine categories, defined by the predominantly affected tissues, such as joint, synovium, cartilage, or connective tissues ( Table 20.1 ). At each point in the evaluation (history, physical examination, and laboratory testing), it is important to identify the tissues involved.

TABLE 20.1
Classification of Musculoskeletal Diseases
Category Prototype(s) Useful Test(s) Treatment(s) *
Synovitis Rheumatoid arthritis Rheumatoid factor, ESR DMARDs and biologic agents
Autoimmune diseases ANA test Prednisone and immunosuppressive drugs
Enthesopathy Ankylosing spondylitis and spondyloarthropathies Sacroiliac radiographs NSAIDs, MTX, and biologic agents
Crystal-induced synovitis Gout Joint fluid crystal examination NSAIDs
CPPD (pseudogout) Radiographic chondrocalcinosis NSAIDs
Joint space disease Septic arthritis Joint fluid culture Antibiotics
Cartilage degeneration Osteoarthritis Radiographs of affected area NSAIDs, analgesics, and physical therapy
Osteoarticular disease Osteonecrosis Radiographs, magnetic resonance imaging Core decompression or prosthetic joint replacement
Inflammatory myopathy Polymyositis
Dermatomyositis
Inclusion body myositis
Muscle enzymes, electromyography, muscle biopsy Corticosteroids and immunosuppressive drugs
Local and regional conditions Tendonitis or bursitis Aspirate bursa if infection is suspected Local injections
General conditions Polymyalgia rheumatica Elevated ESR Corticosteroids
Fibromyalgia Normal ESR Aerobic exercise, stretches, and sleep medications
ANA, Antinuclear antibody; CPPD, calcium pyrophosphate crystal deposition disease; DMARD, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; MTX, methotrexate; NSAID, nonsteroidal antiinflammatory drug.

* Biologic agents include anti–tumor necrosis factor (anti–tumor necrosis factor) drugs and others.

Pathophysiology and Complications

Structures commonly involved in rheumatologic disorders include the joint, the joint cavity, synovial fluid, and periarticular structures. The lining membrane, known as the synovium, consists of a thin layer of macrophages (type A cells) and fibroblasts (type B cells) with a sublining of rich, vascular, loose connective tissue. Hyaline cartilage overlies the bony endplates and provides a cushion to joint motion. The cartilage has high water content and obtains its nutrition solely from the synovial fluid, which is derived from the synovium primarily as an ultrafiltrate of plasma. The synovium also secretes specialized molecules into the synovial fluid, such as hyaluronic acid. An intact bony endplate is required to support the cartilage. The joint capsule and ligaments provide further support and blend with the periosteum. Periarticular anatomy is equally important and includes the tendons, bursae, and muscles associated with the joint.

Synovial inflammatory disorders, such as RA, begin in the synovium and secondarily damage the cartilage, joint capsule, and bone. Inflammation at entheses, the insertion sites of tendons or ligaments on bone, is characteristic of the spondyloarthropathies, such as ankylosing spondylitis. Crystal deposition disorders, such as gout or pseudogout, may also cause articular inflammation. Infections primarily involve the joint cavity (septic arthritis) or bone (osteomyelitis). OA is a noninflammatory, degenerative disease that begins in the cartilage and leads to cartilage loss, subchondral new bone formation, and marginal bony overgrowth. Osteonecrosis of bone may be associated with secondary cartilage damage after collapse of the bony endplate. Inflammatory diseases of the muscle usually manifest with painless proximal weakness. Periarticular inflammation may involve tendons or bursae, and these structures are common causes of pain and stiffness, often misinterpreted as arising from the joint itself. Fibromyalgia (FM; widespread muscle pain) is characterized by soft tissue pain with local tenderness in specific points but without abnormal blood studies.

Although the rheumatologic diseases comprise a group of more than 100 important diseases, this chapter is limited to a discussion of RA, OA, PsA, SLE, Lyme disease, FMS, temporal arteritis, and SS.

Rheumatoid Arthritis

Definition

Rheumatoid arthritis is an autoimmune disease of unknown origin characterized by symmetric inflammation of joints, especially of the hands, feet, and knees. The severity of the disease varies widely from patient to patient and fluctuates over time within the same patient. Disease onset usually occurs between ages 35 and 50 years. RA is more prevalent in women than in men by a 3 : 1 ratio.

Epidemiology

Prevalence is somewhat difficult to determine because of lack of well-defined markers of the disease; however, estimates range from 1% to 2% of the U.S. population.

Etiology

The cause of RA is unknown; however, evidence seems to implicate an interrelationship of infectious agents, genetics, and autoimmunity. One theory suggests that a viral agent alters the immune system in a genetically predisposed person, leading to destruction of synovial tissues. Although the disease can occur within families, suggesting a genetic component, specific associated genes have not been identified. Nevertheless, many people who develop RA have a genetic predisposition that occurs in the form of a tissue marker called HLA-DR4; however, not everyone with this tissue type develops the disease.

Pathophysiology and Complications

The fundamental abnormality of RA involves microvascular endothelial cell activation and injury. Primary changes occur within the synovium, which is the inner lining of the joint capsule ( Fig. 20.1 ). Edema of the synovium occurs followed by thickening and folding. This excessive tissue, composed of proliferative and invasive granulation tissue, is referred to as pannus. In addition, marked infiltration of lymphocytes and plasma cells into the capsule occurs. Eventually, granulation tissue covers the articular surfaces and destroys the cartilage and subchondral bone through enzymatic activity ( Fig. 20.2 ). This process also extends to the capsule and ligaments, causing distention and rupture. New bone or fibrous tissue then is deposited, resulting in loss of mobility.

FIG 20.1
The joint surface (top) has lost its cartilage and consists of granulation tissue with scar tissue. Subchondral bone shows degenerative changes and areas of necrosis.
(Courtesy of A. Golden, Lexington, KY.)

FIG 20.2
A micrograph of a pannus resulting from severe synovitis in rheumatoid arthritis. The pannus is eroding articular cartilage and bone (arrow) .
(Courtesy of Richard Estensen, MD, Minneapolis, MN.)

The sequence of pathologic events begins with a synovitis that stimulates immunoglobulin G (IgG) antibodies. These antibodies form antigenic aggregates in the joint space, leading to the production of rheumatoid factor (RF; autoantibodies). RF then complexes with IgG complement, a process that produces an inflammatory reaction that injures the joint space. The key drivers of RA include proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6).

An associated finding in 20% of patients with RA is the presence of subcutaneous nodules, which are commonly found around the elbow and finger joints. These nodules are thought to arise from the same antigen–antibody complex that is found in the joint. Antigen-mediated vasculitis confined to small- and medium-sized vessels also may occur.

Rheumatoid arthritis is a pleomorphic disease with variable expression. The most progressive period of the disease occurs during the earlier years; thereafter, it slows. Onset is gradual in more than 50% of patients, and as many as 20% follow a limited course that abates within 2 years. Approximately 10% of patients with RA who do not receive adequate treatment experience relentless crippling that leads to nearly complete disability. The remainder follows a polycyclic or progressive course. The long-term prognosis for individuals with abrupt onset of disease is similar to that for those with gradual disease onset. The course and severity of RA are unpredictable, but the disorder is characterized by remissions and exacerbations. For most patients, however, the disease is a sustained, lifelong problem that can be managed to allow a normal or nearly normal life.

The life expectancy of persons with severe RA is shortened by 10 to 15 years. This increased mortality rate usually is attributed to infection, pulmonary and renal disease, and gastrointestinal bleeding.

Many complications may accompany RA, including skin ulcers, muscle atrophy, keratoconjunctivitis sicca (SS), digital gangrene, temporomandibular joint (TMJ) involvement, pulmonary interstitial fibrosis, pericarditis, amyloidosis, anemia, thrombocytopenia, neutropenia, and splenomegaly (Felty syndrome).

Clinical Presentation

The usual onset of RA is gradual and subtle ( Table 20.2 ), and the disorder is commonly preceded by a prodromal phase of general fatigue and weakness with joint and muscle aches. Characteristically, these symptoms come and go over varying periods. Then, painful joint swelling, especially of the hands and feet, occurs in several joints and progresses to other joints in a symmetric fashion ( Fig. 20.3 ). Joint involvement persists and gradually progresses to immobility, contractures, subluxation, deviation, and other deformities. Characteristic features include pain in the affected joints aggravated by movement, generalized joint stiffness after inactivity, and morning stiffness that lasts longer than 1 hour. The joints most commonly affected are fingers, wrists, feet, ankles, knees, and elbows. Multiple joint changes noted in the hands include a symmetric spindle-shaped swelling of the proximal interphalangeal (PIP) joints, with dorsal swelling and characteristic volar subluxation of the metacarpophalangeal (MCP) joint (see Fig. 20.3 ). TMJ involvement occurs in up to 75% of RA patients. Because of the variable rate of progression and pain intensity, the median period between onset of symptoms of RA and its diagnosis is 36 weeks.

TABLE 20.2
Comparison of the Clinical Features of Rheumatoid Arthritis and Osteoarthritis
Rheumatoid Arthritis Osteoarthritis
Multiple symmetric joint involvement Usually one or two joints (or groups) involved
Significant joint inflammation Joint pain usually without inflammation
Morning joint stiffness lasting longer than 1 hour Morning joint stiffness lasting less than 15 minutes
Symmetric, spindle-shaped swelling of PIP joints and volar subluxation of MCP joints and Bouchard’s nodes of PIP joints Heberden nodes of DIP joints
Systemic manifestations (fatigue, weakness, malaise) No systemic involvement
DIP, Distal interphalangeal; MCP, metacarpophalangeal; PIP, proximal interphalangeal.

FIG 20.3
Hands of a patient with advanced rheumatoid arthritis.
(From Damjanov I: Pathology for the health professions, ed 4, St. Louis, 2012, Saunders.)

Extraarticular manifestations include rheumatoid nodules, vasculitis, skin ulcers, SS, interstitial lung disease, pericarditis, cervical spine instability, entrapment neuropathies, and ischemic neuropathies. The American Rheumatism Association has developed revised criteria for the diagnosis and classification of RA to be used in clinical trials and epidemiologic studies ( Box 20.1 ). These criteria have high specificity (89%) and sensitivity (91%–94%) compared with control participants when used to classify patients with RA. For the diagnosis of RA to be made, four of seven criteria must be met.

Box 20.1
Criteria for the Diagnosis of Rheumatoid Arthritis

  • Morning stiffness

  • Arthritis of three or more joint areas

  • Arthritis of hand joints

  • Symmetric arthritis

  • Rheumatoid nodules

  • Serum rheumatoid factor

  • Radiographic changes

Adapted from Arnett FC, Edworthy SM, Bloch DA, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum 31:315-324, 1988.

Laboratory and Diagnostic Findings

Laboratory tests are not pathognomonic or diagnostic of RA, although they are used in conjunction with clinical findings to confirm the diagnosis. Laboratory findings most commonly seen in RA include an increased erythrocyte sedimentation rate (ESR), the presence of C-reactive protein (CRP), a positive RF (in 85% of affected patients), and a hypochromic microcytic anemia. In patients with Felty syndrome (RA with splenomegaly), a marked neutropenia may be present.

Autoantibodies to cyclic citrullinated proteins (CCPs) are helpful in the diagnosis of RA. Anti-CCP antibodies are highly associated with RA. They occur in 70% to 80% of patients with RA as well as in some other forms of inflammatory arthritis. These antibodies may appear before any signs or symptoms of RA and therefore may prove beneficial as early screening markers for earlier diagnosis and intervention of RA.

The American College of Rheumatology (ACR) has established criteria for the diagnosis of RA (see Box 20.1 ), the classification of severity by radiography, functional classes, and the definition of remission. Although they were not designed for managing individual patients, these criteria are useful as a frame of reference and for describing clinical phenomena.

By definition, the diagnosis of RA cannot be made until the disease has been present for at least several weeks. Many extraarticular features of RA, the characteristic symmetry of inflammation, and the typical serologic findings may not be evident during the first few months after disease onset. Therefore, the diagnosis of RA usually is presumptive early in its course.

Although extraarticular manifestations may dominate in some patients, documentation of an inflammatory synovitis is essential for a diagnosis. Inflammatory synovitis can be documented by demonstration of synovial fluid leukocytosis, defined as white blood cell (WBC) counts greater than 2000/µL, histologic evidence of synovitis, or radiographic evidence of characteristic erosions.

Medical Management

Treatment of RA focuses on use of antiinflammatory drugs and disease-modifying antirheumatic drugs (DMARDs), which are helpful in controlling disease and limiting joint damage. The treatment approach to RA is, by necessity, mostly palliative because no cure yet exists for the disease. The ultimate aims of management are to achieve disease remission and maintain or regain functional activity.

Clinical tools for monitoring the patient’s well-being and the efficacy of therapy include self-assessment of the duration of morning stiffness and severity of fatigue, as well as functional, social, emotional, and pain status, as measured by a health assessment questionnaire. A patient-derived global assessment based on a visual analogue scale is a simple and effective means of recording patient well-being. The number of tender and swollen joints is a useful measure of disease activity, as is the presence of anemia, thrombocytosis, and elevated ESR or CRP. Serial radiographs of target joints, including the hands, are useful in assessing disease progression.

Patient education is essential early in the disease course and on an ongoing basis. Patients are best served by a multidisciplinary approach with early referral to a rheumatologist and other specially trained medical personnel, including nurses, counselors, and occupational and physical therapists who are skilled and knowledgeable about RA. Appropriate medical care of patients with RA encompasses attention to smoking cessation, immunizations, prompt treatment of infections, and management of comorbid conditions such as diabetes, hypertension, and osteoporosis. Remission is elusive, however, so more practical treatment goals are to reduce joint inflammation and swelling, relieve pain and stiffness, and facilitate and encourage normal function. These goals are accomplished through a basic treatment program that consists of patient education, rest, exercise, physical therapy, and various nonsteroidal antiinflammatory drugs (NSAIDs) and DMARDs.

The major goals of therapy are to reduce joint damage; relieve pain, swelling, and fatigue; improve joint function; and prevent disability and disease-related morbidity. These goals are constant throughout the disease course, although emphasis may shift to address specific patient needs.

Drugs for the management of RA have been traditionally, but imperfectly, divided into two groups: those used primarily for the control of joint pain and swelling and those intended to limit joint damage and improve long-term outcome ( Table 20.3 ). Symptoms of pain and swelling in RA are mediated, at least in part, by intense cytokine activity. NSAIDs inhibit proinflammatory prostaglandins and are effective treatments for pain, swelling, and stiffness, but they have no effect on the disease course or on risk of joint damage. On the other hand, antiinflammatory properties have been noted for several DMARDs, which are used principally to control disease and to limit joint damage. These drugs include methotrexate and biologic response modifiers with actions targeted against specific cytokines, such as TNF-α. Corticosteroids are powerful, nonspecific inhibitors of cytokines and have been demonstrated to effectively delay joint erosion.

TABLE 20.3
Drugs Used in the Management of Rheumatologic Disorders
Drug(s) (Trade Name) Dental and Oral Considerations
SALICYLATES
Aspirin, Ascriptin, Bufferin, Anacin, Ecotrin, Empirin Prolonged bleeding but not usually clinically significant
NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Ibuprofen (Motrin), fenoprofen (Nalfon), indomethacin (Indocin), naproxen (Naprosyn), meclofenamate (Meclomen), piroxicam (Feldene), sulindac (Sulindac), tolmetin (Tolectin), diclofenac (Voltaren), flurbiprofen (Ansaid), diflunisal (Dolobid), etodolac (Lodine), nabumetone (Relafen), oxaprozin, ketorolac Prolonged bleeding but not usually clinically significant; oral ulceration, stomatitis
CYCLOOXYGENASE-2 INHIBITORS
Celecoxib
Rofecoxib
None
TUMOR NECROSIS FACTOR-α INHIBITORS
Etanercept
Infliximab
None
INJECTABLE GLUCOCORTICOIDS
Triamcinolone hexacetonide Adrenal suppression, masking of oral infection, impaired healing
Triamcinolone acetonide
Prednisolone tebutate
Methylprednisolone acetate
Dexamethasone acetate
Hydrocortisone acetate
Triamcinolone diacetate
Betamethasone sodium phosphate and acetate
Dexamethasone sodium phosphate
Prednisolone sodium phosphate
SYSTEMIC GLUCOCORTICOIDS
Hydrocortisone, cortisone, prednisone, prednisolone, dexamethasone, methylprednisolone (Deltasone, Meticorten, Orasone, Articulose-50, Delta-Cortef, Medrol) Adrenal suppression, masking of oral infection, impaired healing
DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
ANTIMALARIAL AGENTS
Hydroxychloroquine, quinine, chloroquine (Plaquenil) None
PENICILLAMINES
Cuprimine, Depen None
GOLD COMPOUNDS
Gold sodium thiomalate (Auranofin), aurothioglucose (Myochrysine Ridaura, Solganal) Increased infections, delayed healing, prolonged bleeding, oral ulcerations
Aralen Increased infections, delayed healing, prolonged bleeding, glossitis, stomatitis
Sulfasalazine
Azulfidine Increased infections, delayed healing, prolonged bleeding, intraoral pigmentation
IMMUNOSUPPRESSIVES
Azathioprine, cyclophosphamide Increased infections, delayed healing, prolonged bleeding
Methotrexate, cyclosporine, chlorambucil (Imuran, Cytoxan, Rheumatrex) Increased infections, delayed healing, prolonged bleeding, stomatitis

Many different drugs are used in the treatment of patients with RA. Some are used primarily to ease the symptoms of RA; others are used to slow or stop the course of the disease and to inhibit structural damage. Most of these drugs fall into one of the following categories.

NSAIDs

These drugs effectively reduce arthritis pain and inflammation. NSAIDs, including aspirin, constitute the cornerstone of treatment. A common approach is to start a patient on three 5-grain tablets four times a day and then to adjust the dosage on the basis of patient response. The most common sign of aspirin toxicity is tinnitus. If this occurs, dosage is decreased. In addition to aspirin, many NSAIDs are available for use (see Table 20.3 ). Some of the more common NSAIDs include cyclooxygenase (COX)-2 inhibitors, namely, celecoxib (Celebrex), ibuprofen (Motrin, Advil, Rufen, Nuprin), naproxen (Naprosyn, Aleve), sulindac (Clinoril), tolmetin (Tolectin), fenoprofen (Nalfon), piroxicam (Feldene), diclofenac (Voltaren), flurbiprofen (Ansaid), diflunisal (Dolobid), etodolac (Lodine), and nabumetone (Relafen). All NSAIDs can cause a qualitative platelet defect that may result in prolonged bleeding, especially when given in high doses. The effects of aspirin are irreversible for the life of the platelet (10–12 days); thus, this effect continues until new platelets have replaced the old. The effect of the other NSAIDs on platelets is reversible and lasts only as long as the drug is present in the plasma (see Chapter 24 ). Celecoxib (Celebrex), a COX-2 inhibitor, is designed to be safer for the stomach. In addition to NSAIDs, a variety of other drugs can be used to treat patients with RA (see Table 20.3 ).

Corticosteroids

Corticosteroids, including prednisone, prednisolone, and methylprednisolone, are potent and quick-acting antiinflammatory medications. These medications provide immediate control of inflammation while waiting for NSAIDs and DMARDs take effect. Because of the risk of side effects with corticosteroids, they are prescribed for as short a time as possible and in doses as low as possible.

DMARDs

Disease-modifying antirheumatic drugs, through various mechanisms, actually modify the course of the disease. The most commonly used DMARD for RA is methotrexate. Other frequently used DMARDs include hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine, Azulfidine EN-Tabs), leflunomide (Arava), and azathioprine (Imuran).

An individual diagnosed with RA is likely to be prescribed a DMARD fairly early in the course of the disease because studies have demonstrated that starting these drugs early can help prevent irreparable joint damage.

Biologic Agents

Biologic agents are highly targeted DMARDs that in many ways have revolutionized the management of RA. Biologics have been shown to help slow progression of RA when all other treatments have failed to do so. Aggressive RA treatment is known to help prevent long-term disability from RA.

A list of biologic drugs can be seen in Table 20.4 . There are currently nine such agents approved for RA: abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), golimumab (Simponi), and rituximab (Rituxan). Each of the biologics targets a specific molecular mediator in the inflammation cascade. Cimzia, Enbrel, Humira, Remicade, and Simponi block a cytokine called TNF-α and are referred to as TNF inhibitors or blockers. Kineret targets a cytokine called IL-1. Orencia inhibits the activation of T cells. Rituxan targets CD20 thereby inactivating B cells. Actemra blocks a cytokine called IL-6. IL-6 is a proinflammatory cytokine that is usually increased in most rheumatologic disorders. The biologic agents etanercept and infliximab (and other TNF-α inhibitors) have been shown to be highly effective in the treatment of patients with early RA relative to the “gold standard” agent, methotrexate. Although costly and difficult to administer (requiring an injectable route), etanercept (e.g., Enbrel, Immunex) has been shown to significantly reduce symptoms of RA and to more effectively slow joint damage when compared with methotrexate. Likewise, infliximab (Remicade), which also is costly and requires administration by the intravenous (IV) route, when used with methotrexate significantly reduced RA symptoms and slowed joint damage to a greater extent than that achieved with methotrexate therapy alone.

TABLE 20.4
General Categories of Drugs to Treat Rheumatologic Disorders
There are many different drugs used in the treatment of rheumatologic disorders. Some are used primarily to ease the symptoms, and others are used to slow or stop the course of the disease and to inhibit structural damage. Most of these drugs fall into one of the following categories:

  • Nonsteroidal antiinflammatory drugs (NSAIDs) include more than a dozen different medications—some available over the counter, some available by prescription only—used to help ease arthritis pain and inflammation. NSAIDs include such drugs as ibuprofen (Advil, Motrin), ketoprofen (Actron, Orudis KT), and naproxen sodium (Aleve), among others. If you have had or are at risk of stomach ulcers, your doctor may prescribe celecoxib (Celebrex), a type of NSAID called a cyclooxygenase-2 inhibitor, which is designed to be safer for the stomach.

  • Corticosteroids: Corticosteroid medications, including prednisone, prednisolone, and methylprednisolone, are potent and quick-acting antiinflammatory medications. They may be used in patients with rheumatoid arthritis (RA) to get potentially damaging inflammation under control while waiting for NSAIDs and DMARDs (below) to take effect. Because of the risk of side effects with these drugs, doctors prefer to use them for as short a time as possible and in doses as low as possible.

  • Disease-modifying antirheumatic drugs (DMARDs): DMARDs are drugs that work slowly to actually modify the course of the disease. In recent years, the most commonly used DMARD for rheumatoid arthritis is methotrexate. But there are about a dozen others that fall into this category. They include hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine, Azulfidine EN-Tabs), leflunomide (Arava), and azathioprine (Imuran).

    Patients diagnosed with RA today are likely to be prescribed a DMARD fairly early in the course of their disease because doctors have found that starting these drugs early on can help prevent irreparable joint damage that might occur if their use was delayed.

  • Biologic agents: The newest category of medications used for rheumatoid arthritis is a subset of DMARDs called biologic response modifiers, or biologics. There are currently nine such agents approved for RA: abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), golimumab (Simponi), and rituximab (Rituxan).

    Each of the biologics blocks a specific step in the inflammation process. Cimzia, Enbrel, Humira, Remicade, and Simponi block a cytokine called tumor necrosis factor-α (TNF-α) and therefore often are called TNF inhibitors. Kineret blocks a cytokine called interleukin-1 (IL-1). Orencia blocks the activation of T cells. Rituxan blocks B cells. Actemra blocks a cytokine called interleukin-6 (IL-6).

    Because these agents target specific steps in the process, they do not wipe out the entire immune response as some other RA treatments do, and in many people, a biologic agent can slow, modify, or stop the disease even when other treatments have not helped much.

  • Janus kinase (JAK) inhibitors: A new drug, tofacitinib (Xeljanz) is being compared to biologics. However, it is part of a new subcategory of DMARDs known as JAK inhibitors that block Janus kinase, or JAK, pathways, which are involved in the body’s immune response. Unlike biologics, it can be taken orally.

These agents are administered by injection or IV infusion and usually have side effects. The most common side effect seen with biologics is pain and rash at the injection site. This occurs in fewer than 30% of patients. Because biologics given by infusion (in the vein) have the potential to cause an allergic infusion reaction, patients are monitored during infusions. Symptoms of infusion reactions include flulike illness, fever, chills, nausea, and headache. Biologics have also been implicated in increased infections in patients using them. In fact, one study found that patients taking high-dose biologics were nearly 2.5 times more likely to have a serious infection than control participants.

As with any drugs that suppress the immune system, biologic therapy poses some increased to infections and other diseases. People taking biologics should seek immediate medical attention if they develop persistent fever or unexplained symptoms. Vaccinations that prevent infections should be considered before taking biologics. While taking biologic medications, people should not receive live vaccines.

Janus-Associated Kinase Inhibitors

Tofacitinib (Xeljanz) is a janus-associated kinase inhibitor that disrupts cytokine and growth factor signaling pathways, thereby effectively reducing inflammation.

Prosthetic Joints

A potential long-term complication of chronic RA (also OA and other types, including fractures that do not heal and avascular necrosis) is the ultimate destruction of particular joint structures to the degree that the joint must be replaced with synthetic materials.

Patients who have recently received a prosthetic joint (particularly the knee) are at increased risk (up to nine times more likely) to have a thromboembolic event (including a possible myocardial infarction) within 1 month of the implant, and they are also more likely to have a pulmonary embolism for several years after their implant. Patients with prosthetic joints (most commonly, hip and knee replacement, followed by shoulder, elbow, wrist, and ankle) often are encountered in dental practice; when this occurs, a question concerning the need for antibiotic prophylaxis to prevent infection of the prosthesis can arise.

Dental Management

Depending on which joints are involved, patients may not be comfortable in a supine position in the dental chair. Consideration should be given to providing a more upright chair position, using neck, back, and leg supports, and scheduling short appointments ( Box 20.2 ).

Box 20.2
Dental Management Considerations in Patients With Rheumatoid Disorders

P: Patient Evaluation and Risk Assessment (See Box 1.1 )

  • Evaluate and determine whether rheumatoid or joint disorder exists.

  • Obtain medical consultation if disease is poorly controlled or undiagnosed or if the diagnosis is uncertain.

Potential Issues and Factors of Concern

A
Analgesics If patient is taking aspirin or another NSAID or acetaminophen, be aware of dosing and the possibility that pain may be refractory to some analgesics; dosing and analgesic choices may need to be modified in consultation with the physician.
Antibiotics Provide antibiotic prophylaxis if needed in accordance with ADA (2015) guidelines (see Boxes 20.3 and 20.4 ).
Anesthesia No issues
Allergy Allergic reactions or lichenoid reactions are possible in patients taking many medications.
B
Bleeding Excessive bleeding may occur if major surgery is performed on patients who take aspirin or other NSAIDs. Bleeding usually is not clinically significant and can be controlled with local hemostatic measures.
Blood pressure No issues
C
Chair position Ensure comfortable chair position. Consider shorter appointments, and use supports as needed (e.g., pillows, towels).
D
Devices Patients who have a prosthetic joint replacement should be managed according to ADA (2003) guidelines (see Boxes 20.3 and 20.4 ).
Drugs Obtain blood cell count with differential if surgery is planned for patients taking gold salts, penicillamine, antimalarials, or immunosuppressives. If patient is taking corticosteroids—secondary adrenal suppression is possible (see Chapter 15 ).
E
Equipment No issues
Emergencies If surgery is performed, supplemental techniques may be necessary to control bleeding.
F
Follow-up Monitor dental and periodontal health; routine follow-up evaluation is appropriate.

ADA, American Dental Association; NSAID, nonsteroidal antiinflammatory drug.

Dental appointments should be kept as short as possible, and the patient should be allowed to make frequent position changes as needed to accommodate joint pain and immobility (see Box 20.2 ). The patient also may be more comfortable in a sitting or semisupine position, as opposed to a supine one. Physical supports, such as a pillow or a rolled towel, may be used to provide support for deformed limbs, joints, or the neck.

The most significant complications associated with RA are drug related (see Table 20.3 ). Aspirin and other NSAIDs can interfere with platelet function and cause prolonged bleeding; however, this effect alone generally is not found to be of clinical significance unless another bleeding problem is present. A patient who is taking both aspirin and a corticosteroid may be at greater risk for bleeding (see Chapter 24 ). The risk is not great, however, and patients usually can be treated as long as curettage or surgery is performed conservatively in small segments, with attention to good techniques (see Chapter 24 ).

Patients who are taking gold salts, penicillamine, sulfasalazine, or immunosuppressive agents are susceptible to bone marrow suppression, which can result in anemia, agranulocytosis, and thrombocytopenia. If a patient has not undergone recent laboratory testing, a complete blood cell count with a differential WBC count should be ordered. Abnormal results should be discussed with the patient’s physician. Patients being treated with corticosteroid therapy are at risk for a number of adverse effects (see Table 20.3 ), including adrenal suppression (see Chapter 15 ).

Late Prosthetic Joint Infection

Rarely, patients who have had a joint replaced may acquire an infection of the artificial joint. It appears that wound contamination or skin infection (staphylococci) is the source of the vast majority of late prosthetic joint infections (LPJIs). Only a few cases of LPJI have been remotely associated with bacteria (streptococci) found in the oral cavity. Most of these infections were more likely to result from physiologically occurring bacteremia or bacteremia caused by acute or chronic infection rather than from invasive dental procedures. Unfortunately, many orthopedic surgeons have persisted in requesting that patients continue to receive antibiotic prophylaxis for all dental procedures despite the lack of evidence.

In 2012, a panel of experts convened by the American Dental Association Council on Scientific Affairs developed an evidence-based clinical practice guideline (CPG) on the use of prophylactic antibiotics in patients with prosthetic joints who are undergoing dental procedures. This CPG is intended to clarify the “Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures: Evidence-based Guideline and Evidence Report,” which was developed and published by the American Academy of Orthopaedic Surgeons and the American Dental Association. The 2014 panel based the current CPG on literature search results and direct evidence contained in the comprehensive systematic review published by the 2012 panel, as well as the results from an updated literature search. The 2014 panel identified four case-control studies. The 2014 panel judged that the current best evidence failed to demonstrate an association between dental procedures and prosthetic joint infection (PJI). This panel also presented information about antibiotic resistance, adverse drug reactions, and costs associated with prescribing antibiotics for PJI prophylaxis. The panel made the following clinical recommendation:

In general, for patients with prosthetic joint implants, prophylactic antibiotics are not recommended prior to dental procedures to prevent prosthetic joint infection. The practitioner and patient should consider possible clinical circumstances that may suggest the presence of a significant medical risk in providing dental care without antibiotic prophylaxis, as well as the known risks of frequent or widespread antibiotic use. As part of the evidence-based approach to care, this clinical recommendation should be integrated with the practitioner’s professional judgment and the patient’s needs and preferences.

An important study by Berbari and colleagues evaluated both preoperative and postoperative factors associated with PJI. The most clinically relevant of these factors were postoperative, especially wound drainage after arthroplasty (odds ratio [OR], 1/4 18.7; 95% confidence interval [CI], 7.4–47.2). Other postoperative factors associated with PJI were wound hematoma after arthroplasty (OR, 1/4 2.5; 95% CI, 1.3–9.5) and postoperative urinary tract infection (OR, 1/4 2.7; 95% CI, 1.04–7.1). The OR for surgical site infection could not be calculated because there were no PJIs among the control participant. Thus, the patients at the highest risk of developing PJI had drainage, an infection, or both after undergoing arthroplasty. There were no data regarding whether use of prophylactic antibiotics decreased the risk of developing PJIs in patients with these specific postoperative conditions. Other conditions, as defined by Berbari and colleagues, with significant ORs (ranging from 1.8 to 2.2) for PJI independent of dental procedures, were preoperative factors that included prior operation or arthroplasty on the index joint, diabetes mellitus, and being immunocompromised (defined as RA, current use of systemic steroids or immunosuppressive drugs, diabetes mellitus, presence of a malignancy, or a history of chronic kidney disease).

2015 Summary of American Dental Association and the American Academy of Orthopedic Surgeons

In January 2015, the results of this task force along with rationale and clinical guidelines were published in the Journal of the American Dental Association. Table 20.5 summarizes the recommendations for the management of patients with prosthetic joints who are undergoing dental procedures.

Sep 3, 2018 | Posted by in General Dentistry | Comments Off on Rheumatologic Disorders
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