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Glucocorticoids (GCs) have powerful anti-inflammatory and immunomodulatory effects and are useful for treating many rheumatic diseases.Glucocorticoids work by inhibiting leukocyte access to infl amed tissues, interfering with the function of cells involved in the infl ammatory process, and suppressing the production of humoral factors such as cytokines and prostaglandins involved in immune infl ammatory processes.Glucocorticoids accomplish their effects by several mechanisms, including altering synthesis of proteins, releasing proteins from intracellular protein complexes that include GC receptors, and changing the properties of biological membranes.Initial GC dosage should be determined by the type and severity of the disease manifestation under treatment.■ Because of signifi cant toxicity associated with long-term GC use, doses of <7.5 mg daily are recommended only if required to control symptoms. [ABSTRACT FROM AUTHOR]

Osteonecrosis or vascular necrosis refers to the final result of a number of different pathways leading to bone death and ultimately to joint destruction. The femoral head is the most common site of osteonecrosis.Osteonecrosis develops bilaterally in more than 80% of cases. Besides the hip, the most common sites for necrosis are knees, shoulders, ankles, and elbows. ■ The most common risk factors for osteonecrosis are glucocorticoid use, excessive alcohol consumption, and cigarette smoking.The fi rst symptom associated with the disease is typically a deep, throbbing groin pain. This pain, usually intermittent and of gradual onset, occasionally appears abruptly.A variety of non-operative treatment interventions are available at some centers, including vasodilators, lipid-lowering agents, prostacyclin analogues, various types of anticoagulants, bisphosphonates, hyperbaric oxygen therapy, and extracorpeal shock wave therapy. Rigorous data on the effi cacy of these approaches are currently not available.There are currently four general categories of operative treatment options aimed toward preserving the femoral head and delaying (or preventing) total arthroplasty: (1) core decompression; (2) osteotomy; (3) nonvascularized bone grafting; and (4) vascularized bone grafting.■ Many patients eventually undergo total joint arthroplasty or resurfacing arthroplasty. [ABSTRACT FROM AUTHOR]

■Chondrodysplasias are inherited disorders of cartilage that affect its function as a template for bone growth.■Problems common to many chondrodysplasias are respiratory distress, osteoarthritis of the weightbearing joints, dental crowding, obesity, obstetrical difficulties, and psychological issues due to short stature.■The osteochondroses are a heterogeneous group of disorders in which localized non-inflammatory arthropathies result from regional disturbances of skeletal growth. [ABSTRACT FROM AUTHOR]

Systemic inflammatory disorder with noncaseating granulomatous inflammation in affected organs, commonly involving the lungs, eyes, skin, joints, lymph nodes, and upper respiratory tract.Diagnosis attained via consensus between the clinical presentation and natural history, pattern of major organ involvement, confirmatory biopsy, and response to therapy.■ When treatment is indicated, glucocorticoids remain the only recognized effective therapy for active sarcoidosis. [ABSTRACT FROM AUTHOR]

Complementary and alternative therapies are popular and widely used among patients with rheumatic and musculoskeletal diseases.Marketing and word of mouth, ready availability, and interest in "natural" treatments contribute to their popularity.■ Scientific basis and clinical trails of most therapies is limited or lacking. [ABSTRACT FROM AUTHOR]

Surgical treatments of arthritis and musculoskeletal diseases may be used to prevent progression, relieve pain, and/or improve joint function.The success of surgical interventions is dependent on careful considerations of pre-, intra-, and postoperative aspects of the surgery.■ Total joint replacements are now possible for most of the major joints affected and damaged by arthritis. [ABSTRACT FROM AUTHOR]

■Nonsteriodal anti-inflammatory drugs (NSAIDs) relieve inflammation and pain by inhibiting the production of prostaglandins.■Prostaglandin (PG) biosynthesis occurs via a three-enzyme cascade. Current NSAIDs inhibit the enzyme cyclooxygenase (COX), accounting for their efficacy and toxicity.■Pharmacologic properties of the different NSAIDs, including specificity for COX-1 or -2 and drug half-life, influence the toxicity profile.■The most important NSAID toxicities include gastrointestinal ulceration, asthma and allergic reactions, and effects on the kidneys, liver, and cardiovascular system.■Safe use of NSAIDs requires consideration of indi vidual comorbidities to choose the best agent, appropriate monitoring for toxicity, and use of appropriate gastroprotective agents. [ABSTRACT FROM AUTHOR]

Successful needle placement for joint and soft tissue aspiration and injection requires clear understanding of anatomy.Aspiration of joint and soft tissue fluids may be important for diagnosis and treatment.■ Joint or soft tissue injections with corticosteroids may be beneficial for short- and long-term treatment. [ABSTRACT FROM AUTHOR]

Patients suffering with chronic diffuse pain who lack objective clinical and laboratory findings (e.g., fibromyalgia) frequently are dismissed as not having real pain, which only perpetuates their illness.There are four principal categories of pain: nociceptive pain, neuropathic pain, chronic pain of complex etiology, and psychogenic pain.Pain assessment should include attention to possible psychological and sociocultural factors that could be contributing to the pain experience.Diagnostic waffling, the ordering of frightening tests, excessive use of physical therapy modalities, activity limitation after minor trauma, and overly liberal work release are among the important factors that can convert what should be a selflimited acute pain condition into a chronic pain syndrome.If the clinician suspects fibromyalgia, validation of the patient's pain is important.Pharmacologic agents that may be useful in the management of individual pain syndromes include nonsteroidal anti-inflammatory drugs, opioids, muscle relaxants, antidepressants, antiepileptic medications, and topical agents.■ Physical therapy, cognitive-behavioral therapy, aerobic exercise, and complementary and alternative medicine approaches may all be useful in the management of pain in selected patients. [ABSTRACT FROM AUTHOR]

Self-management activities, such as participation in education programs and physical activity, are central to the nonpharmacological management of arthritisSelf-management education, physical activity, and weight loss have all demonstrated health benefi ts for people with arthritis.■ Evidence suggests that very few people with arthritis participate in self-management education. [ABSTRACT FROM AUTHOR]

Psychosocial factors are essential to a patient's vulnerability to the most important symptoms of rheumatic diseases, including pain and fatigue.Positive and negative emotions influence adaptation to rheumatic diseases with depression predictive of adverse outcomes.Cognitive factors, including a sense of control over illness, are of great importance to daily well-being. Interventions that improve self-efficacy improve pain and psychological functioning.■ Social factors also affect impact of diseases, with social resources and the ability to utilize them being a strong determinant of well-being among rheumatic disease patients. [ABSTRACT FROM AUTHOR]

In the care of disabled individuals, the current system of health care delivery and education largely focuses on a disease-centered medical model that fails to consider the role of society and the interaction of the disabled individual in that society over a lifespan.A more holistic approach to the care of disabled individuals considers the impact of environmental factors on the patient and provides a biopsychosocial orientation rather than a purely medical one.Holistic health approaches promote optimal function of the disabled person by considering not only the underlying rheumatic disease but the individual as a whole functioning person. Central to this health promotion is involvement of patient responsibility for his or her health and well being, including physical, psychological, social, and societal aspects.■ Multidisciplinary efforts are important to effective rehabilitation of patients disabled by rheumatic disease. Critical members of the multidisciplinary team are the rheumatologist, orthopedist, physical and occupational therapists, rehabilitation nurse, psychologist, social worker, and vocational rehabilitation specialist. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome is an uncommon but long recognized and high-impact regional musculoskeletal pain disorder.■ Current emphasis on pain sensitization mechanisms and earlier clinical recognition is facilitating management and improving outcomes. [ABSTRACT FROM AUTHOR]

The prevalence of amyloid diseases varies in different geographic areas. Alzheimer's disease is the most common form of localized amyloidosis, while AL amyloidosis is the most common systemic form of amyloidosis in the United States, while AA amyloidosis is the most common form worldwide.Amyloid fibrils resemble a woven cable and are deposited in tissues depending of the specific causative protein. Amyloid deposits do not cause an inflammatory reaction, but interfere with the function of surrounding tissues.Clinical manifestations vary according to the type of amyloid disease.Diagnosis is made by recognition of deposits with a characteristic "apple green" birefringence under polarizing microscopy and the specific subunit protein by immunohistochemistry.■ Treatment is directed toward reducing production of aberrant proteins or surgical removal of amyloid deposits or affected organs. [ABSTRACT FROM AUTHOR]

Some unusual arthropathies are caused by deposition of normal material, such as metal ions, or storage of abnormal material, such as lipids.Hemochromatosis, ochronosis, and Wilson's disease are characterized by cellular deposition of the normal metal ions: iron, calcium, and copper, respectively.■ In Gaucher's disease, Fabry's disease, Farber's disease, and multicentric reticulohistiocytosis, rheumatic manifestations result from cellular storage of abnormal lipids. [ABSTRACT FROM AUTHOR]

The genes that specify the hundreds of proteins involved in connective tissue have been mapped.The heritable disorders of connective tissue (HDCT) show both considerable variability within and among families and genetic heterogeneity.■ Phenotypes used: (1) disorders of fibrous elements, such as osteogenesis imperfecta and Marfan′s syndrome, (2) disorders of proteogylcan metabolism, such as mucopolysaccharidoses, (3) dysostoses and osteochondrodysplasias, such as achondroplasia, and (4) inborn errors of metabolism, such as homocystinuria. [ABSTRACT FROM AUTHOR]

The most common primary neoplasms of the joint are pigmented villonodular synovitis and synovial chondromatosis and a diagnosis is best made using magnetic resonance imaging (MRI).Other primary lesions are rare and include lipoma arborescens, synovial hemangiomas, intracapsular chondromas, and synovial chondrosarcomas.■Secondary neoplasms of the joint are synovial sarcoma and giant cell tumors.■ The malignancies that metastasize to bone also may invade the articular space. [ABSTRACT FROM AUTHOR]

Hypertrophic osteoarthropathy is characterized by abnormal proliferation of skin and bone at the distal parts of the extremities.Clinical features include bulbous deformity of the tips of the digits (conventionally known as clubbing) and periostosis of the tubular bones.The development of hypertrophic osteoarthropathy may indicate the presence of a significant internal illness, often a pulmonary malignancy or inflammatory disease of the lung.■ Abnormal vascular endothelial growth factor expression may play a central role in the pathogenesis of this condition. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) histopathology differs from rheumatoid arthritis (RA), with the most striking difference in the characteristic of the synovial vasculature.Psoriatic arthritis is triggered by interaction between genetic and environmental factors with initiating events occurring in the skin and/or gut.Cellular immunity and cytokines, including tumor necrosis factor alpha (TNF-alpha), are important mediators of PsA.■ Osteoclasts are important mediators of dysregulated bone remodeling in PsA. [ABSTRACT FROM AUTHOR]

Diagnosis is one of exclusion and is suggested by the characteristic febrile pattern, evanescent rash, organomegaly, elevated white blood cell count, and a markedly elevated serum ferritin, serum IL-18 when available, and a reduced glycosylated fraction of ferritin.A predominance of T-helper cell (Th1) cytokines such as interleukin (IL)-2, IL-6, IL-18, interferon gamma, tumor necrosis factor (TNF) alpha have been reported in persons with active adult Still's disease and therapy against these cytokines is an active area of investigation.■ Most have a chronic course with morbidity arising from a polyarthritis. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) is a rare disease that occurs worldwide in all age groups and affects men and women equally.An associated rheumatologic or hematologic disorder is seen in over 30% of patients with RP. Inflammation of cartilaginous structures with lymphocytic infiltration and association with anticollagen antibodies are consistent with an autoimmune pathogenesis.The characteristic clinical findings are acute painful swelling and redness of the external ear, nasal cartilage, and laryngotracheal cartilage. Nonerosive arthritis, ocular inflammation, vestibular symptoms, and involvement of the heart and kidney also occur.Diagnosis is made on clinical grounds, though cartilage biopsy may be useful.Treatment with nonsteriodal anti-inflammatory drugs (NSAIDs) or corticosteroids may control inflammation, but immunosuppressive and biologic treatments may be required for severe disease.■ Laryngotracheal involvement is a serious complication that may require tracheostomy. [ABSTRACT FROM AUTHOR]

The metabolic myopathies are a heterogeneous group of diseases characterized by impaired skeletal muscle energy production.Primary metabolic myopathies are associated with genetic defects in glycogen and lipid metabolism.Secondary types occur with abnormal production of parathyroid, thyroid, and cortisol production and vitamin D defi ciency.■ Symptoms occur mainly during or shortly after exercise and include pain, weakness, and cramping, and can result in myoglobinuria due to muscle necrosis. [ABSTRACT FROM AUTHOR]

Hereditary periodic fever syndromes are autoinflammatory diseases characterized by episodes of fever with serosal, synovial, and/or skin inflammation.Familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) are inherited in an autosomal recessive manner and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID) are dominantly inherited.■ Colchicine and biologic therapies such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) receptor agonists are successful in the treatment of some of these inherited diseases. [ABSTRACT FROM AUTHOR]

Septic joints signal the presence of a potentially life-threatening infection. For nongonococcal joint infections, the mortality rate among adults ranges from 10% to greater than 50%.The most common pathway to a septic joint is through hematogenous seeding from an extra-articular site of infection, for example, pneumonia, pyelonephritis, or skin infection.The causes of adult nongonococcal septic arthritis are Gram-positive cocci (75%-80%) and Gram-negative bacilli (15%-20%). Staphylococcus aureus is most common organism in both native and prosthetic joint infections.Arthrocentesis and synovial fluid analysis are the cornerstones for the diagnosis of septic arthritis. If the synovial fluid white blood cell (WBC) count is extremely high (e.g., >100,000/mm3), treatment for presumed septic arthritis shouldbe initiated pending culture result of the fluid.Cell count, differential, Gram stain, culture, and examination for crystals are the crucial tests to be performed on synovial fluid. This boils down to the 3 Cs: cell count, culture, and crystals.In the setting of nongonococcal septic arthritis, Gram stains of infected synovial fluid are positive only 60% to 80% of the time. Blood cultures are positive in approximately 50% of patients.In cases of suspected septic arthritis, antibiotic treatment should begin immediately once proper samples for microbiologic studies have been collected.■ Selection of the initial antibiotic approach is guided by the result of the synovial fluid Gram stain and the organisms most likely to be responsible for the infection, based upon the clinical scenario. [ABSTRACT FROM AUTHOR]

The prevalence of Behçet's disease is highest in countries of the eastern Mediterranean, the Middle East, and East Asia.Aphthous oral ulcers are usually the first and most persistent clinical feature of Behçet's disease. Aphthous ulcers also occur frequently on the genitals (e.g., the scrotum or vulva).Uveitis-either anterior or posterior-is common in Behçet's disease and a source of major morbidity.Many forms of central nervous system disease may occur in Behçet's disease. These include aseptic meningitis and white matter lesions in the brainstem.Human leukocyte antigen (HLA)-B51 is a strong risk factor for Behçet's disease.The diagnosis of primary angiitis of the central nervous system is predicated upon either biopsy evidence of vasculitis or angiographic findings suggestive of vasculitis in the setting of other compelling features, for example, strokes demonstrated by magnetic resonance imaging or the findings of a cerebrospinal fluid pleocytosis.The diagnosis of primary angiitis of the central nervous system should never be made on the basis of an angiogram alone.Patients with benign angiopathy of the central nervous system are predominantly female, tend to present acutely with headache (with or without focal symptoms), and have normal or near normal cerebrospinal fluid.Cogan's syndrome refers to the association of inflammation in both the eyes and ears: specifically, the occurrence of nonsyphilitic interstitial keratitis and immune-mediated inner ear disease, resulting in audiovestibular dysfunction.Any type of ocular inflammation may occur in Cogan's syndrome (e.g., scleritis, uveitis, orbital pseudotumor). The inner ear disease associated with this condition often leads to deafness.■ In erythema elevatum diutinum, skin lesions consist of purple, red, or brown plaques and often have an annular or nodular appearance. The skin lesions have a predilection for the extensor surfaces of the distal extremities and often overlie joints, but may be generalized. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with early and gradually progressive lacrimal and salivary dysfunction.Secondary SS occurs in association with other autoimmune disorders, the most common of which is rheumatoid arthritis.Minor salivary glands and lacrimal glands in SS exhibit a particular pattern of periductal lymphocytic infiltration known as focal lymphocytic sialadenitis.About 90% of patients with SS are women.Sjögren's syndrome is very common, with a community prevalence of pSS ranging from 0.1% to 0.6% of all individuals.The major eye problem in SS is keratoconjunctivitis sicca, leading to xerophthalmia. The principal oral manifestation of SS is decreased salivary gland production, leading to xerostomia and a predilection for dental caries.Extraglandular manifestations of SS include arthralgias, thyroiditis, renal involvement (leading to renal tubular acidosis), peripheral neuropathy, cutaneous vasculitis, and lymphoma.The risk of lymphoma in pSS is approximately 5%.Most patients with SS develop increased circulating polyclonal immunoglobulins and autoantibodies. These autoantibodies include two fairly specific antibodies directed against the Ro (SS-A) and La (SS-B) antigens.■ Anti-Ro and -La antibodies may be associated with fetal heart block during the pregnancies of women with SS. [ABSTRACT FROM AUTHOR]

Major pathology consists of focal inhomogeneous infl ammation with injury, death, and repair of muscle cells.Each subgroup of myositis has characteristic changes on microscopy and immunochemistry.■ Etiology is still unclear but selected environmental exposures in genetically predisposed hosts have been found. [ABSTRACT FROM AUTHOR]

An acquired cause of hypercoagulability; 50% of antiphospholipid syndrome (APS) patients have systemic lupus erythematosus (SLE).Antiphospholipid syndrome predisposes to both venous and arterial thrombosis. The most common venous thrombosis is deep venous thrombosis; the most common arterial thrombosis is stroke.Antiphospholipid syndrome predisposes to miscarriage and other pregnancy morbidity.Antiphospholipid syndrome may cause thrombocytopenia.■ Antiphospholipid syndrome is diagnosed by persistent antiphospholipid antibody: lupus anticoagulant; anticardiolipin; and anti-beta 2 glycoprotein I. [ABSTRACT FROM AUTHOR]

Global management of systemic lupus erythematosus (SLE) importantly includes education, photoprotection, maintaining good physical conditioning, appropriate immunization, and identifying and treating risk factors for cardiovascular disease.Many traditional treatments are available for the nonorgan manifestations of SLE, including nonsteriodal anti-infl ammatory drugs (NSAIDs), corticosteroids, and antimalarials.Treatment of severe organ involvement typically requires immunosuppressive agents.■ Targeted biologic therapies are under development that may change treatment algorithms in the future. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of calcium pyrophosphate dihydrate (CPPD) are unknown, though there is an increasing prevalence of radiographic chondrocalcinosis with age, and trauma may predispose to the disease. Several metabolic diseases are associated with CPPD.Overproduction of extracellular pyrophosphate in abnormal cartilage matrix contributes to CPPD.Acute pseudogout is the inflammatory host response to CPPD crystals shed from cartilaginous tissues. Because of the common occurrence of these crystals in osteoarthritic cartilage, there is a strong association of pseudogout with osteoarthritis (OA).There are multiple clinical manifestations of CPPD, including pseudogout, pseudo-osteoarthritis, pseudo-rheumatoid arthritis, pseudo-neuropathic arthropathy, and asymptomatic chondrocalcinosis (lanthanic CPPD).Diagnosis is made by identifying CPPD crystals in synovial fluid of affected joints.There is no practical way to remove calcium pyrophosphate crystals from the joints and symptomatic treatment is with nonsteroidal anti-inflammatory drugs (NSAIDs), colchicines, and local or systemic glucocorticoids.■ Basic calcium phosphate crystals (BCP) frequently deposit in articular tissues and may involve dysregulation of extracellular pyrophosphate homeostasis. BCP crystals can cause diverse clinical conditions including destructive arthritis (Milwaukee shoulder) and calcific periarthritis/tendonitis. [ABSTRACT FROM AUTHOR]

In reactive arthritis (ReA), exposure of the host to infectious agents leads to the development of an infl ammatory arthritis and other manifestations of systemic disease in the absence of an ongoing infectious process.Approximately 50% of ReA and undifferentiated oligoarthritis cases can be attributed to a specific pathogen by a combination of culture and serology. The predominant organisms are Chlamydia, Salmonella, Shigella, Yersinia, and Campylobacter species.The annual incidence of ReA, found to be 28/100,000 individuals in one study, may exceed that of rheumatoid arthritis.In a study of 91 individuals exposed to food-borne Salmonella enteritidis, 17 (19%) individuals developed ReA. Other studies have estimated the frequency of ReA following exposure to potential etiologic agents to be on the order of 10%.Reactive arthritis characteristically involves the joints of the lower extremities in an asymmetric, oligoarticular pattern.A dactylitis ("sausage digit") pattern in the feet is typical of ReA.Enthesopathy (inflammation at the sites of insertion of tendons and ligaments into bone) and anterior uveitis are often found in ReA, as in other seronegative spondyloarthropathies.Cutaneous manifestations of ReA include: keratoderma blenorrhagicum, a papulosquamous rash affecting the palms and soles; nail dystrophy; circinate balanitis, characterized by shallow ulcers on the glans or the shaft of the penis; and oral ulcers, typically painless.Enteropathic spondyloarthritis is the inflammatory arthritis that often accompanies ulcerative colitis or Crohn's disease.The peripheral arthritis of enteropathic spondyloarthritis is typically pauciarticular, asymmetric, and migratory. It has a predilection for joints of the lower extremities.■ The axial disease of enteropathic spondyloarthritis is indistinguishable clinically from that of primary ankylosing spondylitis. [ABSTRACT FROM AUTHOR]

Youth with juvenile idiopathic arthritis (JIA) require special attention to managing growth abnormalities, both local and general, as well as osteopenia.Adherence to medical regimens is often suboptimal and can be improved by paying attention to educational, organizational, and behavioral approaches■ Management of youth with JIA should take in account the psychological, educational, and transition to adulthood issues to maximize their outcome. [ABSTRACT FROM AUTHOR]

Ongoing assessment of rheumatoid arthritis (RA) should include evaluation of tender and swollen joints, acute phase reactants [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], subjective evaluation of pain and overall disease activity, functional limitations, and radiographs.The treatment goal in RA is early and effective control of synovitis to prevent joint damage, disability, and secondary consequences of chronic inflammation such as cardiovascular disease.Symptomatic relief of pain and swelling can be achieved using nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids.Disease-modifying drugs, such as methotrexate, should be initiated within the first 3 to 6 months of disease and, in most cases, effective control of disease activity will require more than one medication.If RA cannot be controlled with one or more conventional therapies, biologic treatments such as antitumor necrosis factor (TNF) drugs should be used.■ Knowledge of drug toxicities and institution of appropriate monitoring is required to effectively manage RA patients. [ABSTRACT FROM AUTHOR]

Most rheumatic disease are caused by a combination of genes and environment, with genetic variation predisposing or protecting and environmental factors initiating and maintaining a disease state.Variations in genes can occur as single nucleotide polymorphisms in coding or noncoding regions and leading to different alleles. Point mutations are rare variations occurring at less than 1% minor allele frequency. Deletion, insertion, repeated sequences of different lengths, and copy number polymorphisms are also responsible for differences in genes.Haplotypes, blocks of polymorphisms inherited together more often than expected by chance, can be used to identify disease-causing variants and provide information on recombination, population structure, and evolutionary pressures.Association of genes with disease can be performed using linkage studies or association studies. Association studies can determine the odds ratio of a particular gene variant being associated with a particular disease, but require large numbers of samples from affected and unaffected individuals.■ Linkage studies are most useful for monogenic traits with high penetrance where extended family information is available. If a particular gene has only a subtle effect, linkage studies are limited in use. [ABSTRACT FROM AUTHOR]

The immune system can be divided into innate and adaptive subsystems whose inappropriate activation leads to autoinfl ammatory and autoimmune diseases, respectively. Many rheumatic diseases are a combination of both processes.The innate immune system is activated by specific receptors that recognize patterns associated with pathogens, which activate a program of infl ammation involving hundreds of genes.Cells of the innate immune system, including dendritic cells, natural killer (NK) cells, mast cells, eosinophils, and basophils, activate and modulate the adaptive immune response, directly combat pathogens, and respond to allergens.The adaptive immune response depends on antigen recognition by T and B cells, whose cell surface receptors are highly variable to respond to environmental insults. Normally, adaptive immune cells are tolerant to self.Different subsets of T lymphocytes, including Thelper, cytotoxic T cells, and T-regulatory cells, modulate the immune response to effectively combat pathogens yet limit autoimmunity. Dysregulation of T-cell function is seen in autoimmune disease.■ Antibody-producing B lymphocytes recognize and present soluble antigens. Autoantibodies contribute signifi cantly to autoimmune diseases. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a soft tissue pain syndrome that affects 4% of the population of the United States.American College of Rheumatology (ACR) criteria for the classification of FM include a history of chronic widespread pain involving all four quadrants of the body and the axial skeleton, plus the presence of 11 of 18 tender points on physical examination.A variety of nonspecific symptoms are often present in FM. These include fatigue (often worsened by physical activity), paresthesias, irritable bowel complaints, migraine headaches, and deficits of attention and memory.Patient education about FM is a fundamental part of the treatment process. A variety of Internet-based Web sites are available for patients.Exercise is a crucial element of therapy. A regular exercise program should be considered to be a full part of the pharmacological armamentarium.■ Tricyclic antidepressant (TCA) agents, such as cyclobenzaprine and amitriptyline, are usually the first-line pharmacologic treatment. [ABSTRACT FROM AUTHOR]

Conventional radiographs are the initial imaging agent of choice for most rheumatic conditions. For most forms of arthritis, no additional imaging studies are required.Trabecular bone and small bone erosions are visualized well by conventional radiography.Weight-bearing views of the knees are important in the evaluation of significant knee osteoarthritis.Computed tomography (CT) is superior to conventional radiographs in the assessment of certain joint conditions, including many cases of tarsal coalition, sacroiliitis, osteonecrosis, and sternoclavicular joint disease.High resolution CT of the lungs is an essential adjunct to the evaluation of many inflammatory rheumatic diseases, for example, systemic sclerosis, systemic vasculitis, and other disorders associated with signs of interstitial lung disease.Magnetic resonance imaging (MRI), which has superior imaging capabilities of soft tissue and bone marrow lesions, is the study of choice for a host of musculoskeletal diagnoses, including meniscal tears of the knee, spinal disc herniations, osteonecrosis, osteomyelitis, skeletal neoplasms, and others.■ Bone densitometry plays a crucial role in the diagnosis and treatment of osteopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

Forty-six million people have doctor-diagnosed arthritis and by 2030 it is projected to be 67 million, or 25% of the US population.Arthritis is the number one cause of disability and costs the United States an estimated 128 billion annually.Public health focuses on the assessment and reduction of health burden in the population.■ Three types of prevention strategies can be applied to arthritis. [ABSTRACT FROM AUTHOR]

Paget's disease affects 1% of the US population over the age of 40 years and is a chronic disorder of adult skeleton characterized by increased resorption and deposition of bone resulting in replacement of the normal matrix with softened and enlarged bone.Most adults with Paget's disease are asymptomatic and diagnosis is found on x-ray of the bones.Bone pain, fracture, and nerve impingement can occur due to enlarging and poorly constructed bone matrix.■ Potent and generally safe suppressive agents have been developed and have resulted in a more aggressive approach to therapy. [ABSTRACT FROM AUTHOR]