Treatment:
Gonococcal Arthritis
Initial treatment consists of ceftriaxone (1 g IV or IM every 24 h) to cover possible penicillin-resistant organisms. Once local and systemic signs are clearly resolving and if the sensitivity of the isolate permits, the 7-day course of therapy can be completed with an oral agent such as ciprofloxacin (500 mg twice daily) if sensitivity allows. If penicillin-susceptible organisms are isolated, amoxicillin (500 mg three times daily) may be used.Sup-purative arthritis usually responds to needle aspiration of involved joints and 7-14 days of antibiotic treatment. Arthroscopic lavage or arthrotomy is rarely required. Patients with DGI should be treated for Chlamydia trachomatis infection unless this infection is ruled out by appropriate testing.
It is noteworthy that arthritis symptoms similar to those seen in DGI occur in meningococcemia. A dermatitis-arthritis syndrome, purulent monarthritis, and reactive polyarthritis have been described. All respond to treatment with IV penicillin.
Spirochetal Arthritis
Lyme Disease
Lyme disease due to infection with the spirochete Borrelia burgdorferi causes arthritis in up to 70% of persons who are not treated. Intermittent arthralgias and myal-gias—but not arthritis—occur within days or weeks of inoculation of the spirochete by the Ixodes tick. Later, there are three patterns of joint disease: (1) Fifty percent of untreated persons experience intermittent episodes of monarthritis or oligoarthritis involving the knee and/or other large joints. The symptoms wax and wane without treatment over months, and each year 10-20% of patients report loss of joint symptoms. (2) Twenty percent of untreated persons develop a pattern of waxing and waning arthralgias. (3) Ten percent of untreated patients develop chronic inflammatory synovitis resulting in erosive lesions and destruction of the joint. Serologic tests for IgG antibodies to B. burgdorferi are positive in >90% of persons with Lyme arthritis, and a PCR-based assay detects Borrelia DNA in 85%.
Treatment:
Lyme Arthritis
Lyme arthritis generally responds well to therapy.A regimen of oral doxycycline (100 mg twice daily for 30 days), oral amoxicillin (500 mg four times daily for 30 days), or parenteral ceftriaxone (2 g/d for 2-4 weeks) is recommended. Patients who do not respond to a total of 2 months of oral therapy or 1 month of parenteral therapy are unlikely to benefit from additional antibiotic therapy and are treated with anti-inflammatory agents or synovectomy. Failure of therapy is associated with host features such as the HLA-DR4 genotype, persistent reactivity to OspA (outer-surface protein A), and the presenceofhLFA-1 (human leukocytefunction-associated antigen 1),which cross-reacts with OspA.
Syphilitic Arthritis
Articular manifestations occur in different stages of syphilis. In early congenital syphilis, periarticular swelling and immobilization of the involved limbs (Parrot’s pseudoparalysis) complicate osteochondritis of long bones. Clutton’s joint, a late manifestation of congenital syphilis that typically develops between the ages of 8 and 15 years, is caused by chronic painless synovitis with effusions of large joints, particularly the knees and elbows. Secondary syphilis may be associated with arthralgias; with symmetric arthritis of the knees and ankles and occasionally of the shoulders and wrists; and with sacroiliitis. The arthritis follows a subacute to chronic course with a mixed mononuclear and neutrophilic synovial-fluid pleocytosis (typical cell counts, 5000-15,000^L). Immunologic mechanisms may contribute to the arthritis, and symptoms usually improve rapidly with penicillin therapy. In tertiary syphilis, Charcot’s joint is a result of sensory loss due to tabes dorsalis. Penicillin is not helpful in this setting.
Mycobacterial Arthritis
Tuberculous arthritis accounts for ~1% of all cases of tuberculosis and for 10% of extrapulmonary cases. The most common presentation is chronic granulomatous monarthritis. An unusual syndrome, Poncet’s disease, is a reactive symmetric form of polyarthritis that affects persons with visceral or disseminated tuberculosis. No mycobacteria are found in the joints, and symptoms resolve with antituberculous therapy.
Unlike tuberculous osteomyelitis, which typically involves the thoracic and lumbar spine (50% of cases), tuberculous arthritis primarily involves the large weightbearing joints, in particular the hips, knees, and ankles, and only occasionally involves smaller non-weight-bearing joints. Progressive monarticular swelling and pain develop over months or years, and systemic symptoms are seen in only half of all cases. Tuberculous arthritis occurs as part of a disseminated primary infection or through late reactivation, often in persons with HIV infection or other immunocompromised hosts. Coexistent active pulmonary tuberculosis is unusual.
Aspiration of the involved joint yields fluid with an average cell count of 20,000^L, with ~50% neutrophils. Acid-fast staining of the fluid yields positive results in fewer than one-third of cases, and cultures are positive in 80%. Culture of synovial tissue taken at biopsy is positive in ~90% of cases and shows granulomatous inflammation in most. DNA amplification methods such as PCR can shorten the time to diagnosis to 1 or 2 days. Radiographs reveal peripheral erosions at the points of synovial attachment, periarticular osteopenia, and eventually joint-space narrowing. Therapy for tuberculous arthritis is the same as that for tuberculous pulmonary disease, requiring the administration of multiple agents for 6-9 months. Therapy is more prolonged in immunosuppressed individuals, such as those infected with HIV.
Various atypical mycobacteria found in water and soil may cause chronic indolent arthritis. Such disease results from trauma and direct inoculation associated with farming, gardening, or aquatic activities. Smaller joints, such as the digits, wrists, and knees, are usually involved. Involvement of tendon sheaths and bursae is typical. The mycobacterial species involved include Mycobacterium marinum, M. avium-intracellulare, M. terrae, M. kansasii, M.fortuitum, and M. che-lonae. In persons who have HIV infection or are receiving immunosuppressive therapy, hematogenous spread to the joints has been reported for M. kansasii,M. avium-intracellulare, and M. haemophilum. Diagnosis usually requires biopsy and culture, and therapy is based on antimicrobial susceptibility patterns.
Fungal Arthritis
Fungi are an unusual cause of chronic monarticular arthritis. Granulomatous articular infection with the endemic dimorphic fungi Coccidioides immitis, Blastomyces dermatitidis, and (less commonly) Histoplasma capsulatum (Fig. 20-2) results from hematogenous seeding or direct extension from bony lesions in persons with disseminated disease. Joint involvement is an unusual complication of sporotrichosis (infection with Sporothrix schenckii) among gardeners and other persons who work with soil or sphagnum moss. Articular sporotrichosis is six times more common among men than among women, and alcoholics and other debilitated hosts are at risk for polyarticular infection.
Candida infection involving a single joint—usually the knee, hip, or shoulder—results from surgical procedures, intraarticular injections, or (among critically ill patients with debilitating illnesses, such as diabetes mellitus or hepatic or renal insufficiency, and patients receiving immunosuppressive therapy) hematogenous spread. Candida infections in IV drug users typically involve the spine, sacroiliac joints, or other fibrocartilaginous joints. Unusual cases of arthritis due to Aspergillus species, Cryptococcus neoformans, Pseudallescheria boydii, and the dematiaceous fungi have also resulted from direct inoculation or disseminated hematogenous infection in immunocompromised persons.
The synovial fluid in fungal arthritis usually contains 10,000-40,000 cells^L, with ~70% neutrophils. Stained specimens and cultures of synovial tissue often confirm the diagnosis of fungal arthritis when studies of synovial fluid give negative results. Treatment consists of drainage and lavage of the joint and systemic administration of an antifungal agent directed at a specific pathogen. The doses and duration of therapy are the same as for disseminated disease. Intraarticular instillation of amphotericin B has been used in addition to IV therapy.
Viral Arthritis
Viruses produce arthritis by infecting synovial tissue during systemic infection or by provoking an immunologic reaction that involves joints. As many as 50% of women report persistent arthralgias and 10% report frank arthritis within 3 days of the rash that follows natural infection with rubella virus and within 2-6 weeks after receipt of live-virus vaccine.
FIGURE 20-2
Chronic arthritis caused by Histoplasma capsulatum in the left knee. A. A man in his 60s from El Salvador presented with a history of progressive knee pain and difficulty walking for several years. He had undergone arthroscopy for a meniscal tear 7 years before presentation (without relief) and had received several intraarticular glucocorticoid injections. The patient developed significant deformity of the knee over time, including a large effusion in the lateral aspect. B. An x-ray of the knee showed multiple abnormalities, including severe medial femorotibial joint-space narrowing, several large subchondral cysts within the tibia and the patellofemoral compartment, a large suprapatellar joint effusion, and a large soft-tissue mass projecting laterally over the knee. C. MRI further defined these abnormalities and demonstrated the cystic nature of the lateral knee abnormality. Synovial biopsies demonstrated chronic inflammation with giant cells, and cultures grew H. capsulatum after 3 weeks of incubation. All clinical cystic lesions and the effusion resolved after 1 year of treatment with itraconazole. The patient underwent a left total knee replacement for definitive treatment.
Episodes of symmetric inflammation of fingers, wrists, and knees uncommonly recur for >1 year, but a syndrome of chronic fatigue, low-grade fever, headaches, and myalgias can persist for months or years. IVIg has been helpful in selected cases. Self-limited monarticular or migratory polyarthritis may develop within 2 weeks of the parotitis of mumps; this sequela is more common among men than women. Approximately 10% of children and 60% of women develop arthritis after infection with parvovirus B19. In adults, arthropathy sometimes occurs without fever or rash. Pain and stiffness, with less prominent swelling (primarily of the hands but also of the knees, wrists, and ankles), usually resolve within weeks, although a small proportion of patients develop chronic arthropathy About 2 weeks before the onset ofjaundice, up to 10% of persons with acute hepatitis B develop an immune complex-mediated, serum sickness-like reaction with maculopapular rash, urticaria, fever, and arthralgias. Less common developments include symmetric arthritis involving the hands, wrists, elbows, or ankles, and morning stiffness that resembles a flare of rheumatoid arthritis. Symptoms resolve at the time jaundice develops. Many persons with chronic hepatitis C infection report persistent arthralgia or arthritis, both in the presence and in the absence of cryoglobulinemia. Painful arthritis involving larger joints often accompanies the fever and rash of several arthropod-borne viral infections, including those caused by chikungunya, O’nyong-nyong, Ross River, Mayaro, and Barmah Forest viruses. Symmetric arthritis involving the hands and wrists may occur during the convalescent phase of infection with lymphocytic choriomeningitis virus. Patients infected with an enterovirus frequently report arthralgias, and echovirus has been isolated from patients with acute polyarthritis.
Several arthritis syndromes are associated with HIV infection. Reactive arthritis with painful lower-extremity oligoarthritis often follows an episode of urethritis in HIV-infected persons. HIV-associated reactive arthritis appears to be extremely common among persons with the HLA-B27 haplotype, but sacroiliac joint disease is unusual and is seen mostly in the absence of HLA-B27. Up to one-third of HIV-infected persons with psoriasis develop psoriatic arthritis. Painless monarthropathy and persistent symmetric polyarthropathy occasionally complicate HIV infection. Chronic persistent oligoarthritis of the shoulders, wrists, hands, and knees occurs in women infected with human T cell lymphotropic virus type I. Synovial thickening, destruction of articular cartilage, and leukemic-appearing atypical lymphocytes in synovial fluid are characteristic, but progression to T-cell leukemia is unusual.
Parasitic Arthritis
Arthritis due to parasitic infection is rare. The guinea worm Dracunculus medinensis may cause destructive joint lesions in the lower extremities as migrating gravid female worms invade joints or cause ulcers in adjacent soft tissues that become secondarily infected. Hydatid cysts infect bones in 1-2% of cases of infection with Echinococcus granulosus. The expanding destructive cystic lesions may spread to and destroy adjacent joints, particularly the hip and pelvis. In rare cases, chronic synovitis has been associated with the presence of schistosomal eggs in synovial biopsies. Monarticular arthritis in children with lymphatic filariasis appears to respond to therapy with diethylcarbamazine, even in the absence of microfilariae in synovial fluid. Reactive arthritis has been attributed to hookworm, Strongyloides, Cryptosporidium, and Giardia infection in case reports, but confirmation is required.
Postinfectious or Reactive Arthritis
Reactive arthritis (Chap. 9), a reactive polyarthritis, develops several weeks after ~1% of cases of nongonococcal urethritis and 2% of enteric infections, particularly those due to Yersinia enterocolitica, Shigella flexneri, Campylobacter jejuni, and Salmonella species. Only a minority of these patients have the other findings of classic reactive arthritis, including urethritis, conjunctivitis, uveitis, oral ulcers, and rash. This triad of arthritis, urethritis, and conjunctivitis was formerly known as Reiter’s syndrome, which is an eponym now of historical interest only. Studies have identified microbial DNA or antigen in synovial fluid or blood, but the pathogenesis of this condition is poorly understood.
Reactive arthritis is most common among young men (except after Yersinia infection) and has been linked to the HLA-B27 locus as a potential genetic predisposing factor. Patients report painful, asymmetric oligoarthritis affecting mainly the knees, ankles, and feet. Low-back pain is common, and radiographic evidence of sacroiliitis is found in patients with long-standing disease. Most patients recover within 6 months, but prolonged recurrent disease is more common in cases following chlamydial urethritis. Antiinflammatory agents help to relieve symptoms, but the role of prolonged antibiotic therapy in eliminating microbial antigen from the synovium is controversial.
Migratory polyarthritis and fever constitute the usual presentation of acute rheumatic fever in adults (Chap. 6). This presentation is distinct from that of poststreptococcal reactive arthritis, which also follows infections with group A Streptococcus but is not migratory, lasts beyond the typical 3-week maximum of acute rheumatic fever, and responds poorly to aspirin.
Infections in Prosthetic Joints
Infection complicates 1-4% of total joint replacements. The majority of infections are acquired intraoperatively or immediately postoperatively as a result of wound breakdown or infection; less commonly, these joint infections develop later after joint replacement and are the result of hematogenous spread or direct inoculation. The presentation may be acute, with fever, pain, and local signs of inflammation, especially in infections due to S. aureus, pyogenic streptococci, and enteric bacilli. Alternatively, infection may persist for months or years without causing constitutional symptoms when less virulent organisms, such as coagulase-negative staphylococci or diphtheroids, are involved. Such indolent infections are usually acquired during joint implantation and are discovered during evaluation of chronic unexplained pain or after a radiograph shows loosening of the prosthesis; the ESR and C-reactive protein level are usually elevated in such cases.
The diagnosis is best made by needle aspiration of the joint; accidental introduction of organisms during aspiration must be meticulously avoided. Synovial fluid pleocytosis with a predominance of polymorphonuclear leukocytes is highly suggestive of infection, since other inflammatory processes uncommonly affect prosthetic joints. Culture and Gram’s stain usually yield the responsible pathogen. Use of special media for unusual pathogens such as fungi, atypical mycobacteria, and Mycoplasma may be necessary if routine and anaerobic cultures are negative.
Treatment:
Prosthetic Joint Infections
Treatment includes surgery and high doses of parenteral antibiotics, which are given for 4-6 weeks because bone is usually involved. In most cases, the prosthesis must be replaced to cure the infection. Implantation of a new prosthesis is best delayed for several weeks or months because relapses of infection occur most commonly within this time frame. In some cases, reimplantation is not possible, and the patient must manage without a joint, with a fused joint, or even with amputation. Cure of infection without removal of the prosthesis is occasionally possible in cases that are due to streptococci or pneumococci and that lack radiologic evidence of loosening of the prosthesis. In these cases,antibiotic therapy must be initiated within several days of the onset of infection, and the joint should be drained vigorously either by open arthrotomy or arthro-scopically. In selected patients who prefer to avoid the high morbidity associated with joint removal and reimplantation, suppression of the infection with antibiotics may be a reasonable goal. A high cure rate with retention of the prosthesis has been reported when the combination of oral rifampin and ciprofloxacin is given for 3-6 months to persons with staphylococcal prosthetic joint infection of short duration.This approach, which is based on the ability of rifampin to kill organisms adherent to foreign material and in the stationary growth phase, requires confirmation in prospective trials.
Prevention
To avoid the disastrous consequences of infection, candidates for joint replacement should be selected with care. Rates of infection are particularly high among patients with rheumatoid arthritis, persons who have undergone previous surgery on the joint, and persons with medical conditions requiring immunosuppressive therapy. Perioperative antibiotic prophylaxis, usually with cefazolin, and measures to decrease intraoperative contamination, such as laminar flow, have lowered the rates of perioperative infection to <1% in many centers.After implantation, measures should be taken to prevent or rapidly treat extraarticular infections that might give rise to hematogenous spread to the prosthesis. The effectiveness of prophylactic antibiotics for the prevention of hematogenous infection following dental procedures has not been demonstrated; in fact, viri-dans streptococci and other components of the oral flora are extremely unusual causes of prosthetic joint infection. Accordingly, the American Dental Association and the American Academy of Orthopaedic Surgeons do not recommend antibiotic prophylaxis for most dental patients with total joint replacements. They do, however, recommend prophylaxis for patients who may be at high risk of hematogenous infection, including those with inflammatory arthropathies, immunosuppression, Type 1 diabetes mellitus, joint replacement within 2 years, previous prosthetic joint infection, malnourishment, or hemophilia. The recommended regimen is amoxicillin (2 g PO) 1 h before dental procedures associated with a high incidence of bacteremia. Clindamycin (600 mg PO) is suggested for patients allergic to penicillin.
