Chronic Fatigue Syndrome
Churg–Strauss Syndrome (Allergic Angiitis and Granulomatosis)
Giant Cell Arteritis
Osteoporosis in Older Adults
Scleroderma and Raynaud’s Phenomenon
Small-Vessel Vasculitis (Hypersensitivity Vasculitis)
Systemic Lupus Erythematosus
Bacterial arthritis can be classified as gonococcal, nongonococcal, or mycobacterial.
EPIDEMIOLOGY, ETIOLOGY, AND PATHOPHYSIOLOGY
Gonococcal arthritis: Neisseria gonorrhoeae is the most common organism causing bacterial arthritis, accounting for almost 75% of infections among healthy, sexually active adults. Disseminated gonococcal infection follows spread of infection from mucosal surfaces and is more common among women, especially during pregnancy, the immediately postpartum period, and within 1 week of menses. Also at risk are those with deficiencies of terminal complement components.
Nongonococcal infections: Most patients have one of the following risk factors: extremes of age, recent manipulation of or injury to a joint, chronic debilitating disease, a disease that alters joint integrity, immunosuppression, intravenous drug use, or prosthetic joints. Most organisms reach the joint through hematogenous spread, although extension from local soft tissue or bone can occur. Grampositive cocci predominate in healthy adults, the elderly, and those with suppressed immune systems. Polyarticular infection usually is caused by Staphylococcus aureus and occurs most often with rheumatoid arthritis, hemophilia, and immunocompromising states. Gram-negative bacilli are present in patients with neutropenia and those who use intravenous drugs. Staphylococcus epidermidis is present in early postoperative prosthetic joint infection. Patients with sickle cell disease often are infected with Salmonella organisms.
Gonococcal infection: Two forms have been described. The bacteremic form, resembling serum sickness, occurs in about two-thirds of patients and consists of polyarthralgia, tenosynovitis, and dermatitis. It begins with migratory polyarthralgia, fever, chills, and constitutional symptoms. Tendonitis or tenosynovitis may affect the wrists, fingers, ankles, or toes. The skin lesions are papular or pustular, usually on the torso and extremities. Genitourinary symptoms usually are absent. The second form is nonerosive, suppurative arthritis that usually is monarticular and affects the knees, feet, and ankles. The patient may have a fever, but rash and tenosynovitis usually are absent. Synovial fluid is inflammatory (white blood cell [WBC] count 30,000 to 100,000 cells per microliter). Either form can be associated with mild leukocytosis and a mild to moderate increase in erythrocyte sedimentation rate (ESR). The diagnosis is made through demonstration of the organism on a culture of mucosal surfaces (urehra, endocervix, rectum, or pharynx); blood, and synovial fluid. Blood culture results are positive in as many as 30% of cases in the bacteremic phase. Synovial fluid culture results are positive in about 50% of cases of purulent arthritis. The yield is higher on urogenital cultures, especially cervical cultures (80% to 90%).
Nongonococcal infection: Patients have an acute decrease in range of motion in a painful, warm, swollen joint. Signs of inflammation may be less impressive among patients with chronic disease. Most infections are monarticular and involve the knees (42%), hips (13%), and ankles and shoulders (10% to 12%). Fibrocartilaginous joints of the axial skeleton are involved in intravenous drug users. Signs of systemic infection are common but may be absent among persons with diabetes, the elderly, and persons with compromised immune systems. Infection should be suspected in rheumatoid arthritis when one or two joints are more inflamed than the other joints. The peripheral WBC count is normal in 40% to 50% of cases, but C-reactive protein level and ESR usually are strikingly elevated. Radiographs usually are normal but should be obtained to rule out underlying osteomyelitis. Blood culture results are positive in 30% to 50% of cases. All suspect joints should be aspirated before antibiotics are started. The synovial WBC count typically is more than 50,000 per microliter with more than 90% neutrophils. A Gram stain is positive in about 50% of cases, bacterial cultures in as many as 95%.
Gonococcal infection: Patients improve dramatically within 48 hours of beginning treatment with antibiotics. Therapy is initiated with intravenous antibiotics until the fever has resolved and the symptoms are controlled (typically 3 to 4 days in the bacteremic form and 7 to 10 days in the suppurative form) followed by a week of oral antibiotics. Because of increasing antibiotic resistance, intravenous therapy with ceftriaxone (1 g per day) is recommended initially, with a switch to penicillin if the strain is susceptible. Oral therapy consists of cefuroxime or ciprofloxacin (500 mg twice a day), and should be accompanied by doxycycline (100 mg twice a day), because genitourinary coinfection with Chlamydia trachomatis occurs in as many as 40% of cases. Daily aspiration may be needed for the first few days to ensure adequate response to therapy.
Nongonococcal infection: Treatment consists of parenteral antibiotics and drainage of the affected joint. Initial antibiotic therapy is directed at the most likely organism and may be modified when culture results are available. Intravenous therapy for 2 to 4 weeks is recommended to be followed by 2 to 4 weeks of oral therapy. Drainage is accomplished by means of daily joint aspiration, although immediate surgical intervention is needed for infection of the hip and shoulder and for unresponsive organisms in a damaged joint. The mortality are is 5% to 10%; complete function is recovered by 50% to 70% of patients. Rheumatoid arthritis is associated with a worse prognosis.
CHRONIC FATIGUE SYNDROME
Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue and a variety of other systemic symptoms.
EPIDEMIOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY
CFS predominantly affects young women. The reported prevalence of chronic fatigue in the general population is 1% to 3%. Because CFS often follows a viral illness and shows some laboratory evidence of immune system activation, some investigators consider it to be a host response to triggering or persistent viral infection. However, studies of viruses, including Epstein–Barr virus, have been disappointing. Another view is that CFS and fibromyalgia are clinical correlates of a shared sleep disturbance.
The onset of CFS is abrupt, often in the aftermath of a viral illness. Profound fatigue, sore throat, tender adenopathy found through the history rather than documented at examination, headache, and an array of neurologic symptoms, such as mild memory impairment or sensory disturbances, characterize the condition. Unrefreshing sleep, depression, and fibromyalgic tender points often are present. The diagnostic criteria for CFS are shown in Table 185.2.
DIFFERENTIAL DIAGNOSIS AND LABORATORY FINDINGS
Medical conditions to be ruled out include anemia, chronic infection, including HIV infection, liver disease, hypothyroidism, chronic adrenal insufficiency, and systemic lupus erythematosus. Laboratory investigation should include a complete blood cell count, erythrocyte sedimentation rate, liver enzyme levels, thyroid-stimulating antibody, antinuclear antibody, and a chest radiograph. For selected patients, HIV screening and cortisol levels before and after adrenal stimulation are indicated. In CFS, all results should be normal.
PROGNOSIS AND MANAGEMENT
Therapy for CFS is similar to that for fibromyalgia—reassurance, physical exercise, aerobic conditioning, and tricyclic antidepressants. Acyclovir is ineffective.
CHURG–STRAUSS SYNDROME (ALLERGIC ANGIITIS AND GRANULOMATOSIS)
DEFINITION, EPIDEMIOLOGY, AND PATHOPHYSIOLOGY
Churg–Strauss syndrome (CSS) is a rare hypereosinophilic, granulomatous disorder that affects small and medium-sized vessels. It has a predilection for smaller arteries, arterioles, capillaries, and venules. There is no clear sex preference, and persons of any age may be affected. Pathologic studies reveal intra- or extravascular granulomas and inflammatory lesions rich in eosinophils.
Systemic vasculitis occurs in the setting of asthma or allergic rhinitis. Asthma usually precedes the features of vasculitis by months to years, but both processes may begin simultaneously. Apart from asthma and eosinophilia, CSS is similar to Wegener’s granulomatosis (WG) in that it can affect the upper and lower airways and kidneys. However, the allergic nasal and sinus disease of CSS generally is not destructive, and the pulmonary manifestations are more likely to be fleeting infiltrates and less likely to be nodules. The degree of blood and tissue eosinophilia in CSS usually is more marked than in WG, and the renal involvement usually is milder. Coronary arteritis, myocarditis, and gastrointestinal involvement are more frequent in CSS than in WG.
There are no specific serologic tests. Erythrocyte sedimentation rate often is elevated. Diagnosis is best achieved with a combination of clinical findings and biopsy of symptomatic or abnormal structures.
The response to high doess of prednisone (about 1 mg per kilogram per day) often is prompt. Cytotoxic agents such as cyclophosphamide should be reserved for patients with severe or progressive disease.
Fibromyalgia is a clinical syndrome characterized by fatigue and widespread musculoskeletal pain and stiffness in the setting of normal laboratory and radiologic findings.
EPIDEMIOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY
Fibromyalgia predominantly affects women. It is believed to be a self-maintained neuropsychiatric disturbrance in which environmental or endogenous stress affects nonrapid eye movement during sleep. This disturbance in sleep causes pain amplification, depression, and fatigue. It may be associated with a variety of systemic illnesses, such as systemic lupus erythematosus, hypothyroidism, and Lyme disease.
A typical patient reports fatigue, widespread pain, and stiffness. Sleep disturbance involves repeated awakening and greater fatigue on rising in the morning than on retiring at night. The patient may have symptoms of associated conditions, such as depression, migraine, irritable bowel syndrome, orthostatic intolerance, and temporomandibular joint pain. The examination reveals multiple, symmetric tender points (Table 185.1). In contrast to normal tenderness, the tenderness of fibromyalgia is characterized by an exaggerated emotional response, withdrawal of the tender part, and worsening of pain after examination. Examination often reveals the presence of previously unknown tender areas.
Laboratory and radiographic findings are normal unless an associated disease causes an abnormality.
PROGNOSIS AND MANAGEMENT
Low doses of amitriptyline (25 mg at night) tend to improve the sleep pattern and diminish the pain. To decrease the pain further and restore endurance, a structured exercise program, particularly involving swimming or rhythmic dance, is recommended. Sympathetic support is helpful; patients need to understand that the condition is not crippling. Tender points often persist despite symptomatic improvement.
GIANT CELL ARTERITIS
DEFINITION, EPIDEMIOLOGY, AND PATHOPHYSIOLOGY
Giant cell arteritis (GCA) is sterile granulomatous inflammation of large and medium-sized arteries. It is diagnosed among persons older than 50 years; the mean age is 70 years in most series. Women are affected 2 to 3 times more than men. There is an association with polymyalgia rheumatica (PMR); between 30% and 50% of patients with GCA also have features of PMR.
GCA most often involves the temporal artery. New onset of severe headaches, scalp or temporal artery tenderness, acute monocular visual loss, and claudication of the muscles of mastication are among the common features. Systemic symptoms, such as fever, also are common, as are manifestations of PMR (discomfort of the hip and shoulder girdles). Some patients have inflammatory arthritis of the peripheral joints.
There are no specific serologic tests. The erythrocyte sedimentation rate (ESR) usually is markedly elevated. The combination of typical clinical findings and an elevated ESR allows a clinical diagnosis, even without temporal artery biopsy. However, because it generally does not cause considerable morbidity, biopsy often is performed when clinical features are not entirely classic. Positive biopsy results occur among only 50% to 80% of patients considered likely to have GCA, depending on the size of the biopsy specimen, the clinical features of the illness, and whether bilateral samples have been obtained. A biopsy specimen that provides enough information for a diagnosis can be obtained even after more than 1 week of glucocorticoid therapy. A clinical diagnosis should be questioned if dramatic improvement does not occur within 72 hours after the initiation of glucocorticoid therapy.
Prednisone (0.7 to 1.0 mg per kilogram per day) reduces symptoms within 1 to 2 days and often eliminates symptoms within 1 week. After about 1 month, a slow taper usually can be initiated. Unfortunately, the ESR does not always normalize with disease control, so it should not be relied on as the only measure of disease activity. Patients with disease that responds incompletely to glucocorticoids or that relapses with glucocorticoid taper often are treated with cytotoxic or immunosuppressive agents, although the efficacy of this approach has not been demonstrated in controlled trials.
DEFINITION AND EPIDEMIOLOGY
Gout is a heterogeneous group of disorders characterized by hyperuricemia, recurrent acute arthritis, joint destruction, tophi (painless, firm masses of urate crystals in and around joints or in soft tissue), renal damage, and uric acid urolithiasis. Acute gouty arthritis primarily affects middle-aged and elderly men and less commonly affects elderly women.
ETIOLOGY AND PATHOPHYSIOLOGY
Only about 20% of patients with hyperuricemia (serum urate level greater than 7 mg per deciliter for men and greater than 6 mg per deciliter for women) ever have gout. Nevertheless, a high serum level of uric acid, the end product of purine metabolism, is a prerequisite for the development of gout. Increased urate production (responsible for less than 10% of cases of gout) can be primary (idiopathic, genetic), secondary to elevated degradation of adenosine triphosphate (ethanol intake, tissue hypoxia, exercise, glycogen storage disease), secondary to increased nucleic acid turnover (blood dyscrasia, malignant tumor, psoriasis), or secondary to excessive purine intake. Decreased renal excretion (responsible for about 90% of cases of gout) can be caused by increased tubular reabsorption (diabetes insipidus, dehydration, diuretics) or decreased tubular secretion (inherited defect, acute ethanol intoxication, ketoacidosis, starvation, lead toxicity, and drugs such as salicylates, diuretics, ethambutol, and cyclosporine). Hyperuricemia leads to crystal deposition in joints and eventually (e.g., after 20 to 30 years of sustained hyperuricemia) may incite acute local inflammation. Local trauma and sudden increases or decreases in serum urate levels are known precipitating factors.
Acute and chronic gout: The basic pattern is one of acute attacks of exquisitely painful arthritis. At first, such attacks typically are monarticular and associated with few constitutional symptoms. Later the attacks may be polyarticular and associated with fever. Attacks eventually recur at shorter intervals and resolve incompletely. In at least one-half of initial attacks, the first metatarsophalangeal joint is affected (podagra); 90% of persons with gout have acute attacks in the great toe at some time. Next in order of frequency as sites of initial involvement are the insteps, ankles, heels, wrists, finger, and elbows. The first attack commonly begins at night. Within a few hours, the affected joint becomes hot, dusky red, and extremely tender, and the symptoms may progress to resemble those of bacterial cellulitis. Symptoms usually peak within 24 hours.
Between attacks, there–typically is complete remission of symptoms. About 75% of patients have a second attack within 2 years. When the patient has no symptoms, the diagnosis can be uncertain. After many years, a stage of chronic gout develops. Deposits of monosodium urate around the joints increase and cause erosive changes, chronic swelling, and pain. Visible tophi occur after an average of 12 years of gout and may be located in the helix of the ear; on the ulnar surface of the forearm; in the fingers, hands, knees, and feet; or in the olecranon bursa. Eventually there may be severe joint destruction and deformation.
Renal diseases: Urate nephropathy is attributed to the deposition of monosodium urate crystals in the interstitium of the medulla and is associated with chronic hyperuricemia. It is rarely associated with clinically significant renal disease. Acute uric acid nephropathy is acute renal failure related to the formation of uric acic crystals in the collecting tubules, pelvis, or ureter. It is associated with markedly elevated urinary uric acid levels, most commonly in conditions of high cell turnover, such as leukemia, lymphoma, or the tumor lysis syndrome that sometimes accompanies chemotherapy. Uric acid calculi account for about 10% of all stones and occur in 10% to 25% of all patients with gout.
During episodes of acute gout, serum urate levels may be spuriously normal or low and are unreliable for diagnosis. The condition is best diagnosed by means of examination of synovial fluid from the acutely inflamed joint under a polarizing microscope for negatively birefringent monosodium urate crystals in neutrophils. The crystals appear as needles with blunted ends. The synovial fluid leukocyte count ranges from 5,000 per microliter to 100,000 per microliter. With chronic disease tophi accumulate and produce soft-tissue densities on radiographys. Bony erosions typically consist of a round or oval shape, a sclerotic border, a punched-out appearance, and an overhanging edge of bone. Urinary uric acid excretion more than 800 to 1,000 mg per day while a normal diet is being consumed clearly shows that uric acid overproduction as the cause of hyperuricemia.
Acute gout can be controlled with indomethacin or another nonsteroidal antiinflammatory agent (NSAID), although these agents should be avoided by patients with renal failure. Oral colchicine also is effective but commonly causes diarrhea, abdominal pain; and vomiting. Intra-articular or oral glucocorticoids are used to manage polyarticular attacks. With treatment, attacks may last 2 to 7 days; uncontrolled attacks may last several weeks. Therapy for hyperuricemia (to lower urate level to less than 6.8 mg per deciliter) is beneficial in preventing recurrent attacks, chronic gout, and renal complications. However, because such treatment can aggravate acute attacks, it is prudent to wait 4 to 6 weeks after an attack to initiate therapy and to use NSAIDs or daily colchicine concurrently for a few weeks. A uricosuric drug such as probenecid or a xanthine oxidase inhibitor such as allopurinol provides good long-term control. Allopurinol is preferred for patients known to overproduce urate, for those who undergo unsuccessful treatment with uricosuric agents, for those with a creatinine clearance of less than 60 mL per minute, and for those with uric acid nephrolithiasis or tophi. Asymptomatic hyperuricemia less than 13 mg per deciliter does not require therapy, although prophylaxis with allopurinol is indicated before chemotherapy among patients at risk for acute uric acid nephropathy due to tumor lysis syndrome.
DEFINITION, EPIDEMIOLOGY, AND PATHOPHYSIOLOGY
Henoch–Schönlein purpura is a type of systemic, small-vessel vasculitis that predominantly affects postcapillary venules. Children of any age can be affected; adults are affected less often. There is no sex preference. IgA is the predominant immunoglobulin in circulating and tissue-deposited immune complexes.
In almost 70% of cases among children, upper respiratory infection precedes Henoch–Schönlein purpura by 1 to 3 weeks. Among adults, there usually is no association. The syndrome is characterized by an urticarial or purpuric rash that is most striking in gravity-dependent areas. Other common features include fever (75%), gastrointestinal pain or bleeding (70%), musculoskeletal symptoms (68%), and glomerulonephritis (45%). Gastrointestinal manifestations are less common among adults.
There are no specific serologic tests. The diagnosis usually can be made on the basis of signs and symptoms, although skin or renal biopsy sometimes is necessary. IgA and complement deposition is characteristic.
Most patients do well without glucocorticoid or immunosuppressive treatment. These agents should be used, however, if a patient has severe abdominal pain, peritoneal inflammation, gastrointestinal bleeding, or aggressive glomerulonephritis.
Idiopathic inflammatory myopathy is a group of conditions characterized by symmetric proximal muscle weakness and evidence of nonsuppurative inflammation in skeletal muscle. The group includes polymyositis, dermatomyositis, myositis with associated connective tissue disease, myositis with associated malignant disease, inclusion body myositis, and focal myositis.
ETIOLOGY AND PATHOGENESIS
The cause is unknown, but these disorders are believed to develop in genetically susceptible persons as a result of immune-mediated processes that might be triggered by environmental factors such as viral infections.
PREVALENCE AND EPIDEMIOLOGY
These are uncommon diseases. The age at onset for the group as a whole has a bimodal distribution, with a peak at 10 to 15 years of age and another at about 50 years of age. Myositis associated with malignant disease and inclusion body myositis are more common after 50 years of age. Blacks are affected more than whites, and women twice as often as men (in inclusion body myositis, however, the ratio is reversed).
Symmetric proximal muscle weakness is the dominant feature. It can be accompanied by myalgia and tenderness. Atrophy may develop over time. Systemic symptoms include malaise, fatigue, morning stiffness, arthralgia, anorexia, weight loss, and low-grade fever.
Polymyositis: The onset usually is insidious. Involvement of the proximal shoulder and pelvic girdles is most common; the neck flexors and pharyngeal muscles also may be involved. Facial and bulbar muscle weakness is rare, and ocular muscle involvement does not occur. Cardiac involvement is uncommon, but heart block, supraventricular arrhythmia, or cardiomyopathy may develop and cause palpitations, syncope, or heart failure. Interstitial pulmonary fibrosis, arthralgia, and Raynaud’s phenomenon are more common among patients with a myositis-specific autoantibody.
Dermatomyositis: Patients have all the features of polymyositis and also have cutaneous features, which may predate the onset of weakness by as much as 4 years. The classic changes are Gottron’s papules (violaceous scaly areas over the knuckles, elbows, and knees) and heliotrope discoloration of the eyelids or periorbital regions. Other rashes also occur. Among some patients, the rash and muscle weakness tend to remit and flare up together; among others, there is no apparent connection.
Myositis with other connective tissue diseases: Muscle weakness may accompany systemic lupus erythematosus, scleroderma, mixed connective tissue disease, Wegener’s granulomatosis, polyarteritis nodosa, and giant cell arteritis. The myopathic features may be indistinguishable from those of polymyositis.
Myositis with malignant disease: The association is somewhat controversial but seems more likely with dermatomyositis than with polymyositis. With the exception of ovarian cancer among women with dermatomyositis, the sites and types of tumors are the same as those among other patients of the same age and sex.
Inclusion body myositis: Lower extremity weakness tends to predominate; the distinctive clinical feature is involvement of distal muscles. Myalgia and muscle tenderness are uncommon. Dysphagia occurs among about one-third of patients.
Conditions that can mimic idiopathic inflammatory myopathy include neurologic disorders (muscular dystrophy, myasthenia gravis, amyotrophic lateral sclerosis, Eaton–Lambert syndrome), infectious disease (toxoplasmosis, viral infection, trichinosis), electrolyte disorders (hyponatremia, hypocalcemia, hypokalemia, hypophosphatemia, hypomagnesemia), exposure to toxins and medications, inborn errors of metabolism (mitochondrial myopathy, carnitine deficiency, glycogen storage diseases), sarcoidosis, and chronic fatigue syndrome.
LABORATORY STUDIES AND DIAGNOSTIC TESTS
Serum levels of muscle enzymes (creatine kinase, aldolase) are elevated and can be used to gauge disease activity and the response to therapy. The erythrocyte sedimentation rate is mildly increased in about 50% of patients. Anemia is uncommon. Most patients have circulating autoantibodies such as Jo-1 and SRP. Electromyographic changes suggestive of inflammatory myopathy include the triad of increased insertional activity, fibrillations, and sharp positive waves. Patients with inclusion body myositis also may have neuropathic features. In 10% of cases, the electromyogram is normal. Magnetic resonance imaging can be used to establish the extent of disease and to localize sites for biopsy. The characteristic changes at biopsy include degenerating and regenerating fibers, fibrosis, and an endomysial inflammatory infiltrate with lymphocytes surrounding and invading nonnecrotic fibers. Inclusion body myositis also shows lined vacuoles on histologic examination and filamentous inclusions at electron microscopic examination.
PROGNOSIS AND MANAGEMENT
Treatment involves physical therapy, glucocorticoids, and early detection of pulmonary fibrosis and swallowing abnormalities. Prednisone is given in a single morning dose of about 1 mg per kilogram (2 mg per kilogram in severe cases). It is continued until strength improves, usually over weeks to months. The medication is then tapered gradually over many months. Glucocorticoids produce a response among 90% of patients and complete remission among 50% to 75%. If there has been no remission after 6 to 12 weeks, a second agent such as azathioprine or methotrexate should be added. The cutaneous manifestations of dermatomyositis may respond to hydroxychloroquine. Myositis associated with malignant disease or connective tissue disease generally responds to therapy for the associated condition. Inclusion body myositis can be refractory to therapy.
DEFINITION AND EPIDEMIOLOGY
Lyme disease (LD) is a multisystem inflammatory condition caused by spirochetes known collectively as Borrelia burgdorferi and spread by Ixodes ticks. About 90% of cases in the United States occur in the following states: Massachusetts, Connecticut, Rhode Island, New York, New Jersey, Pennsylvania, Minnesota, Wisconsin, and California. Most cases occur during the late spring, summer, and early fall. It takes 48 hours or more after tick attachment for LD to be spread; even in areas where 40% of adult Ixodes ticks carry B. burgdorferi, LD develops among only about 1% of people who are bitten. Only about 30% of patients recall being bitten by a tick.
Early, localized disease: Erythema migrans occurs among 50% to 80% of patients, usually less than 1 month after the tick bite. It expands over a few days, often with central clearing, and is most often found in or near the axilla or groin. Half of all patients have multiple lesions caused by spirochetemia. Patients also may have fatigue, malaise, headache, myalgia, arthralgia, and lymphadenopathy.
Early, disseminated disease: This stage occurs days to months after the tick bite and can occur with no antecedent erythema migrans or documented tick bite. Musculoskeletal symptoms are common and include migratory polyarthritis or arthralgia and fibromyalgia. Neurologic findings, which occur among 10% of untreated patients, include lymphocytic meningitis, cranial nerve palsy (especially of the seventh cranial nerve), and radiculoneuritis. About 8% of untreated patients have carditis, including mild myopericarditis and any degree of heart block, which usually begins to resolve during or even before the initiation of therapy.
Chronic or late disease: Late disease occurs months to years after infection and may not be preceded by other features of LD. About 80% of untreated patients have musculoskeletal symptoms, including arthralgia, intermittent arthritis, and chronic monarthritis, usually in the knee. The other feature is tertiary neuroborreliosis, which is characterized by encephalopathy, cognitive dysfunction, and peripheral neuropathy. Acrodermatitis chronica atrophicans may occur.
Enzyme-linked immunosorbent assay (ELISA) and Western blot techniques are used to detect antibodies to B. burgdorferi. The results suggest exposure but alone do not provide enough information for a diagnosis. The diagnosis is made on clinical grounds, and the test results are used only for confirmation. False-positive ELISA results can occur with other spirochetal diseases (e.g., syphilis), rheumatologic diseases (e.g., rheumatoid arthritis), and other infections (e.g., endocarditis Epstein–Barr disease). Positive and equivocal ELISA results therefore necessitate corroboration with Western blot results. The ELISA result may not become positive for 6 to 8 weeks and may never become positive if the patient receives antibiotic therapy early in the course. Antibody levels may stay elevated for years after successful treatment.
Timely antibiotic therapy prevents progression to later stages of disease, although it may not decrease the duration or severity of many of the features of early LD. Early, localized disease can be controlled with 3 to 4 weeks of oral doxycycline or amoxicillin. The later stages require intravenous therapy for 2 to 4 weeks; third-generation cephalosporins, penicillin G, and chloramphenicol can be used. There is no evidence that prolonged therapy or oral therapy after intravenous therapy is helpful. Fewer than 10% of patients with early LD have a Jarisch–Herxheimer reaction within the first days of therapy (a worsening of many of the signs and symptoms). This usually lasts for less than a day and is never fatal. Because studies suggest that the risk of contracting LD from a known tick bite is small, prophylactic therapy is not recommended.
DEFINITION AND EPIDEMIOLOGY
Osteoarthritis (OA) is a joint disease characterized by progressive loss of articular cartilage and reactive changes in the underlying bone. OA is the most common form of arthritis. Risk factors include increasing age, female sex, African-American race, obesity, trauma, abnormal joint biomechanics, prior inflammatory joint disease, and metabolic disorders such as hemochromatosis and acromegaly.
OA is thought to be primarily a disease of the articular cartilage and subchondral bone with mild secondary inflammation in the synovial membrane. Proliferation of cartilage at the margins of the joint and subsequent endochondral ossification lead to formation of the osteophytes, the radiologic hallmark of OA.
History: The typical patient with OA is middle-aged or elderly and has a gradual onset of pain and stiffness accompanied by loss of function. The joints most commonly involved include the distal and proximal interphalangeal joints of the hands, first carpometacarpal, cervical or lumbar intervertebral joints, first metatarsophalangeal, knees, and hips. The pain usually is mild, is worsened by use of the involved joints, and improves or is relieved with rest. Pain at rest and nocturnal pain are features of severe disease or of local inflammation. Morning stiffness is common, but the duration is considerably shorter (often less than 30 minutes) than in active rheumatoid arthritis. Gel phenomenon, stiffness after inactivity, is common and resolves within several minutes. In many instances, pain and stiffness are modified by weather changes, generally worsening with damp, cool, rainy weather.