SPECIFIC INFECTIOUS ARTHRITIS 114 represented the second most common cause of acute disability. The literature regarding the association of backache and selected upper extremity rheumatic syndromes and patterns of joint usage in industrial settings was noted to be almost entirely anecdotal and the need for carefully designed, prospective studies in “industrial rheumatology” was stated (H6). The costs of medical care in a university rheumatic disease clinic were found to be high when compared to physicians’ services elsewhere, reflecting the combination of teaching, research, and patient care involved, as well as the possible greater complexity of cases (H107). In a survey conducted in California it was found that no county approached the level of 4.7 rheumatologists per 100,000 population recommended by the Manpower Report of the Arthritis Foundation (overall the number of rheumatologists was only one-fourth of that recommended) (Y 15). Nevertheless, in many areas the supply appeared to be capable of meeting the demand for rheumatologic services. The professional, institutional, and administrative resources in a large, nonmetropolitan community (Redding, California) appeared to be adequate for the local care of arthritis patients, although the referral pattern was judged to be poorly developed and there was little perceived need for a trained rheumatologist in the community (Y 14). Evaluation of the use of “health visitors” in the rehabilitation of patients with various chronic diseases including rheumatoid arthritis revealed a number of benefits, including a lower rate of readmission to the hospital (C84). By use of a patient log, it was found that the great majority of patients seen by 4 rheumatologists had rheumatic complaints, most frequently musculoskeletal pain and back syndromes, although rheumatoid arthritis and osteoarthritis were also common (A127). A questionnaire was used to evaluate patient understanding of terms commonly employed in discussions with patients in an arthritis clinic (M215). It was assumed that knowledge of the nature and treatment of a disease might lead to better compliance and cooperation, although it was noted that sociobehavioral factors might be of greater importance. Renewed efforts at patient education would be required if greater knowledge of disease in clinic patients is considered desirable. Education An Arthritis Foundation task force evaluating the teaching of clinical rheumatology in the nation’s medical schools recommended that high priority be given to establishing a rheumatology section in every school (L165). It was further recommended that efforts be made to evaluate the quality of teaching and to correct any deficiencies that might be found. A brief report dealt with the activities of an international workshop on rheumatologic education of the primary care physician at the undergraduate, postdoctoral, and continuing educational levels (R 170). It was noted that at the postdoctoral level principles of total health care need to be taught by competent rheumatologists in tertiary care rheumatic disease units with comprehensive ambulatory care facilities. It was stated that efforts to educate the practicing physician in rheumatology have overemphasized factual, nonpragmatic knowledge and have paid too little attention to measures affecting patient outcome (F117). The practicing physician was observed to overinvestigate, overreact therapeutically, utilize medication incorrectly, and fail to educate the patient. One recommended method for dealing with these problems was the use of algorithms or decision charts based on clinical data systems. Guidelines for the training of subspecialists in rheumatology were outlined (A82). Various lecturing techniques for teaching rheumatology to nurses were evaluated and somewhat better results obtained when a preliminary questionnaire, handouts, or blackboard teaching were used (W200). It was emphasized that teaching should attempt to influence skills and attitudes as well as knowledge. SPECIFIC INFECTIOUS ARTHRITIS Despite the advent of antibiotics, the literature on infectious arthritis continues to expand, not contract. Excellent clinical descriptions of syndromes caused by various agents are being presented, particularly with re- gard to the pathogenesis of gonococcal arthritis and an arthritis of presumed infectious etiology, Lyme arthritis. Diagnostic approaches are being utilized with greater sophistication and newer methods are being evaluated, SPECIFIC INFECTIOUS ARTHRITIS such as radioisotopic scans and procedures for the detection of microbial antigens in serum or synovial fluid. Therapy is becoming less empirical. Surgical reconstruction of previously damaged joints is being explored with success despite reservations about reactivation of the infection. However, much still remains to be learned. Although the formation of immune complexes, an inevitable byproduct of almost all infections, has begun to be highlighted as a mechanism that contributes to inflammation, information about the pathophysiology of infectious arthritis remains meager. Clinical material woefully lacks any description of the pathology of the joint lesion. Experimental models of infectious arthritis are but rarely employed to gain insight into the manner by which the joint becomes infected and handles the invading pathogen. An issue of Clinics in Rheumatic Diseases p o l . 4, No. 1) was devoted to a review of various aspects of infectious arthritis: diagnostic procedures (N 18,R 190, S283), treatment plans (C 146,S246,424), selected aspects of pathophysiology (P113,Ql,S106,T44), and specific microorganisms that cause infectious arthritis, including staphylococci (W 17 l), Neisseria (M339), Gram-negative bacilli (G136), mycobacteria and fungi (G137), and viruses (S45). In addition, other comprehensive articles offered an excellent variety of materials. These included a general overview of infectious arthritis (W33), and more specific information on arthritides caused by Gram-negative bacilli (B64), mycobacteria (H 153), fungi (B65, C113), and viruses (H245,P117). Two articles highlighted the disease in children (F46,S63). Pathophysiology Pathology. Limited studies are available concerning the morphology of infected synovium and other joint structures in infectious arthritis. One report carefully described the methods that should be used in investigation and offered data in some types of infectious arthritis (S106). Experimental arthritis. The destructive effect of staphylococcal arthritis on cartilage was evaluated after salicylate administration in a rabbit model (B211). Serum levels of salicylate that achieved a mean value of 12.5 mg/dl did not protect cartilage from damage. Immune response. Immune complexes have been found in the serum and tissue of patients with infectious disease. Viral hepatitis antigen and/or antibody have been detected in some patients who developed vascu- 115 litis. Circulating immune complexes have now been described in gonococcal arthritis (W9), meningococcal arthritis (L33), and Lyme arthritis (S354,355). To determine whether patients with Reiter's disease have an unusual immune response to bacterial products, lymphocyte transformation was studied after stimulation by various Neisseria and other bacterial antigens (R136). Various degrees of response were obtained with different antigens, particularly with Neisseria antigens. No convincing evidence for pathogenicity, however, was found for these substances upon lymphocytes obtained from patients or controls, possibly because most of the patients but not the controls had had prior gonorrheal disease. The impaired host. Well recognized as a predisposing condition for infectious arthritis is the presence of a debilitating illness such as rheumatoid arthritis (RA) (G45), Still's disease in an adult (H58), heroin addiction (B64), and immunodeficiency states such as hypogammaglobulinemia (W58). Clearcut genetic markers that might indicate vulnerability to infection, however, have rarely been sought. In terms of propensity to viral infection, no specific HLA marker was recognized in 33 patients who had developed a recurring, episodic arthropathy after receiving a rubella vaccine (G235). [Further investigation of host factors ought to prove useful. In bacterial infections a tendency toward systemic infection by Neisseria microorganisms has been shown to exist in persons with genetic complement deficiencies of C6, C7, or C8. Ed.] Care must be exercised in assuming that back disease in someone who carries B27 is necessarily due to ankylosing spondylitis. A case was reported to emphasize this point. Back complaints in this patient were the result of a disc-space infection due to S aureus (E71). Although reactive forms of arthritis are associated with B27 and some of these attacks are related to an exfra-articular infection with a Gram-negative bacillus, in no instance has the joint disease been caused by direct bacterial invasion of the joint. Septic inoculation of the joint. Most instances of joint infection result from septicemia that arises from a primary site elsewhere. A case of an unusual primary infection was described in which a contraceptive intrauterine device became the source of seeding of a streptococcal microorganism (B255). A similar mechanism for a gonococcal infection was reported in the Twenty-Third Rheumatism Review. Direct inoculation of the joint from adjacent bone that has become infected is another, albeit rare, route of bacterial entry into the joint. In children some 116 joints such as the hip and shoulder include within their synovial cavity a portion of the metaphysis. In these joints, osteomyelitis that commonly begins within the metaphysis may break directly into the joint space since penetration through the epiphysis is blocked by the avascular epiphyseal cartilage. After obliteration of the growth plate at maturity, vascular anastomoses are formed between the metaphysis and the epiphysis. These communicate with the joint capsule and synovium and thereafter osteomyelitis in the metaphysis can extend via such channels into the joint. An adult developed septic arthritis in this fashion (Al52). A sympathetic sterilejoint effusion may form because of the presence of infection in a contiguous structure. Such an event occurs in the joints of children and sometimes of adults who have an acute juxtaarticular osteomyelitis (A152,S63). A sterile synovial fluid effusion was also detected in the tibiotalar joint of a patient with a culture-positive gonorrheal infection in the adjacent subtalar joint (B10). [Similar effusions occur in bursae from an adjacent septic joint or from a cellulitis. Caution must be exercised in performing an arthrocentesis if sepsis is present in the surrounding soft tissue. In this dilemma it is prudent to defer aspiration for a few days while the cellulitis is being treated with appropriate antibiotics. Whether these sterile fluids represent the consequences of passage of immune complexes or other inflammatory mediators from one compartment into an adjacent compartment is not known. Ed.] Involvement of specific musculoskeletal structures Glenohumeral joint. Although the glenohumeral joint is commonly involved, information on the clinical characteristics, radiologic manifestations, and therapeutic results of infection of this specific joint is sparse. Eight septic shoulder joints in 7 patients were studied (A134,M105). The staphylococcus was the invading microorganism in 4 and a Gram-negative bacillus in 3 joints. Most of the patients had an underlying chronic illness that predisposed to infection. Standard radiographs initially showed normal results, but subsequent abnormalities included demineralization, joint space narrowing and superior subluxations in 3 and inferior subluxations in 1. The arthrogram demonstrated rotator cuff tendon ruptures in 4, which presumably occurred as a consequence of the infection. Such a rupture may occur in patients with uninfected RA as well. Recovery was the rule and many of the patients required only needle aspiration for drainage. Permanent disability was associated with delay in treatment. SPECIFIC INFECTIOUS ARTHRITIS Sternoarticular joints. Records at a large general hospital revealed 8 patients from whom enteric Gramnegative bacilli had been isolated from a sternoarticular joint (B63). Seven had been long-term intravenous heroin abusers. The onset was insidious and treatment delayed. In 3 patients no fluid could be obtained despite repeated aspirations. Open synovial biopsy yielded the offending microorganism in all 8. Pseudomonas aeruginosa was present in 4. Erosive and destructive bone changes, best seen on tomograms, were found in all patients. A perisynovial and/or retrosternal abscess was found in 5. As a consequence of abscess formation and osteomyelitis, surgical debridement was required in all 8 patients. Why Pseudomonas infection, as reported in this and earlier studies, favors implantation in the sternoclavicular or sternochondral joints is not known. Knee. An inability to fully extend one or both knees on arising in the morning with gradual improvement during the day has been labeled the “catcher’s crouch syndrome” (S327). Eleven children suffered recurrent episodes of such knee stiffness after a rubella vaccination more than 5 years previously. This complaint presumably arises from trapping of a piece of inflamed, hypertrophied synovium in the posterior aspect of the knee between opposing joint surfaces. In one child, such a phenomenon was demonstrated arthroscopically. Intervertebral disc-space. The disc-space does not become infected directly but from a focus in the adjacent vertebral endplate. The process spreads through the disc and may involve the opposite endplate. Therefore, this disease is really a form of vertebral osteomyelitis in which the disc-space component predominates. Symptoms in a group of 41 children with this problem included difficulty in walking and abdominal and back pain ( W 8 5 ) . A correct diagnosis was often delayed. Thus, children with abdominal complaints were exposed to multiple investigative procedures for intraabdominal disease before the disc-space infection was recognized. Even when back pain was present, particularly in the teenage group, a possible infectious etiology was not considered but rather an epiphysitis (Scheuermann’s disease). Disc-space pathology was accurately and rapidly established by the use of the technetium 99m polyphosphate bone scan. In this series only 34% of the patients had a positive culture (in all cases, a staphylococcus) from either the blood or the disc tissue. A presumptive diagnosis was made in the remaining patients on clinical grounds (disc-space narrowing, fever, and elevated sedimentation rate) and a rapid response to antibiotic therapy. The authors wisely SPECIFIC INFECTIOUS ARTHRITIS suggested that treatment for infection be instituted early before the result of culture is obtained. Vertebra. Two patterns of symptoms emerge based on whether the microorganism that infects the vertebra is a tuberculous or a nontuberculous bacterium, the latter usually being a staphylococcus (03, P42). In both types, the pathogenesis is similar, that is, hematogenous seeding of the vertebral body. In tuberculous spondylitis, destruction of the disc-space is less likely to occur. In coccidioidal spondylitis, the contiguous cartilagenous surfaces are less readily destroyed than in tuberculous infection, but vertebral bone is more rapidly destroyed (W89). Cultures from blood or the lesion itself may show negative results in pyogenic spondylitis. A good response to therapy can help to confirm the diagnosis. The low thoracic and the lumbar spines are the usual sites of infection of either type of microorganism, the most common site being L 1. Appropriate antibiotic treatment alone may be sufficient. Spinal decompression and/or fusion is reserved for neurologic or other complications. The magnitude of kyphosis is not related to the development of paraplegia since some individuals can develop paraplegia with only minimal deformity. Surgery is also carried out to drain paravertebral abscesses (03,P42,W 163). Extraarticular synovial structures. Both bursae and tendon sheaths may become infected by the same broad spectrum of infectious agents that invade joints. Involvement of tendons at the wrist by Mycobacterium szulgai caused a carpal tunnel syndrome (S390). Tendon rupture had not occurred 3 months after onset when debridement and carpal tunnel release were performed. Bursa1 infection commonly occurs at the elbow and knee. Functional impairment does not occur since neither cartilage nor tendon are present in the bursa1 sac and extension by direct contiguity to an adjacent joint like the elbow or the knee usually does not happen. In a group of 12 patients, antibiotic treatment and needle aspiration were successful in 5 of 7 so treated (T54).Five underwent surgical incision and drainage, but 2 of these still had a draining sinus at the time of discharge. Fascia. Necrotizing fascitis developed in 14 patients, 6 of whom had a prior ischiorectal abscess, 5 abdominal surgery, and 1 each, a fractured pelvis, diabetic peripheral vascular disease, and repeated suprapubic aspiration of urine (T38). The adjacent subcutaneous tissue had undergone extensive necrosis and radical dissection was required to eradicate the infection. Coliform species predominated in the lesions, with occasional enterococci and streptococci. 117 Local factors predisposing to infection Penetrating injury. Puncture wound of the knee in a child caused a septic arthritis due to 2 Enterobacter species (L58). Thorn synovitis: sterile or infectious. A number of case reports have appeared indicating that penetration of the joint space by plant thorns or sea urchin spines can cause an inflammatory sterile monarthritis. The geographic distribution of plants and sea life influences the type and frequency of injury. The black thorn (Prunus spinous) more commonly causes this injury in England; the date palm (Phoenix dactylifera and Phoenix canariensis) (C2 17,K5,S406) and the sentinel palm ( Washingtonia filifera) are major offenders in southern California and the Southwest, as is the Yucca aloifolia, commonly called the “Spanish bayonet.” In other areas of the country the hawthorn, the black locust plant (Robinia pseudoacacia) (B50), and the common rose thorn may be associated with such injuries. The spine of the sea urchin is a factor in coastal areas (C217). In some patients bacteria are also introduced into the joint at the same time as the foreign body, creating a septic arthritis. In a series of 5 patients with plant thorn synovitis, 3 developed a superimposed infection, one due to a staphylococcus, another to a paracolon bacillus, and a third to an alpha-hemolytic streptococcus (S406). When sepsis has been found, the prior introduction of a foreign body may be overlooked. At injury, when the plant thorn is removed, a small fragment may break off and be left behind, causing a chronic synovitis. A l l residual foreign material must be removed, usually by surgery, to effect a cure. Hemophilia. Septic arthritis is an unusual complication of hemophilia. This complication occurred in the previously damaged hip of a 32-year-old hemophiliac, the microorganism being Staphylococcus aureus (H194). In the previous 10 years, 693 cases of acute hemarthroses without infection had been treated at this same center. Because the patient had developed antibodies to Factor VIII, surgical intervention was contraindicated. Conservative therapy with antibiotics and immobilization controlled the infection and allowed a return to relatively normal function. Avascular necrosis of the femoral head. Four patients with avascular necrosis of the femoral head, secondary to renal transplantation and corticosteroids in 3 and systemic lupus erythematosus (SLE) and corticosteroids in 1, had superimposed joint infections (H4).All were treated with intravenous antibiotics and frequent joint aspirations, with resolution of the infection. Infre- 118 quent instances of sepsis in this type of joint damage have been reported in the past. Clinical and radiographic findings may not be helpful. Only suspicion of infection and early aspiration of the involved joint can lead to the correct diagnosis. Such suspicion was engendered in this group by the presence of fever and the finding of a primary site of infection in the skin or bowel in 3 of the 4 patients. Infections of bone and joints in children Several general reviews of infections of bone and joints in children were published (F46,J 13,5463). Sterile inflammatory joint disease may mimic septic arthritis. Children with a benign process tended to have a lower temperature and sedimentation rate, and a migratory arthralgia or a previous history of joint complaints, more elbow involvement, and a lower synovial fluid cell count. However, in a given case no single finding was discriminatory. Only a positive blood and/ or joint fluid culture was truly diagnostic (M280). Synovial fluid leukocyte counts are not always helpful. Six children, 3 of whom met the criteria for juvenile rheumatoid arthritis (JRA) had no evidence of infection by smear or culture of the joint fluid although the synovial fluid leukocyte counts were greater than 88,000 cells/ mm3, and in 2 greater than 100,000 cells/mm3 (B13). [Despite these unusual cases, leukocyte counts above 100,000 cells/mm’ are strongly associated with sepsis. In fact, a trial of an appropriate antibiotic may be a wise decision initially even if another cause for the arthritis is found later. Ed.] Osteomyelitis. Infection in bone contrasts in several respects to infection of the joint. Osteomyelitis occurs more commonly than septic arthritis in children 2 years and older. Gram-positive microorganisms, primarily staphylococci and streptococci, cause almost all the culture-positive cases of osteomyelitis. Gram-negative bone infections are almost always associated with open wounds or patients with sickle cell anemia. In septic arthritis, however, Haemophilus influenzae is the most common microorganism detected in children between 6 months and 2 years of age whereas S aureus and the streptococci predominate in the older child. In almost a third of the septic arthritis patients, no agent was found, a percentage higher than that seen in osteomyelitis (F46). Similar findings were reported in another series (Nl). The diagnosis of osteomyelitis can be confirmed by needle aspiration of the subperiosteum or, if pus is not obtained, aspiration from within the medullary cavitv (F46). Osteomyelitis can be differentiated from cel- SPECIFIC INFECTIOUS ARTHRITIS lulitis by a bone scan. It is the authors’ practice, once pus is demonstrated, to take the patient to surgery for drainage, although they recognize that the question of early open drainage versus medical treatment alone is controversial since no data are available from a controlled prospective study. In another group of 23 children with acute osteomyelitis, antibiotic treatment begun within 48 hours of the onset of symptoms produced satisfactory results without surgery (513). Antibiotic treatment alone was also utilized with success in 7 children with subacute osteomyelitis, the only surgical procedure being a diagnostic biopsy. Septic arthritis of the hip. Medical treatment for septic arthritis is entirely satisfactory in children, except for infection of the hip joint where immediate surgical intervention is recommended (F46,J 13,S63). In one of the largest series reported to date, 21 infants with involvement of 24 hip joints were evaluated 11 to 30 years (mean 17 years) after infection (H23). Infection had occurred in 15 in their first month of life and in 6 up to the age of 7 months. Treatment consisted of incision and drainage in 10, repeated aspiration and installation of antibiotics in 6, and antibiotic therapy alone in 4 hips. Although these data do not support the unique value of any one method of treatment during the acute stage, the authors subscribe to the generally accepted principle of early incision and drainage and appropriate and ample antibiotic therapy. The long-term consequences of hip infection in children have not been extensively studied but the outlook does not seem benign. Of these 24 hips, all 10 patients whose disease had resulted in complete loss of the head and neck of the femur had infection due to Staphylococcus aureus. Of 5 with preservation of the femoral head, none had infection by this organism. In the other 9 with a deformed small head and neck, the causative microorganisms were staphylococci in about half. Thus, a particularly bad prognosis appears to be associated with staphylococcal infection of the hip joint in children. The 14 hips with either no or only moderate femoral head destruction usually remained located after closed reduction and immobilization. If this procedure failed, open reduction was successful, provided the femoral component of the joint was large enough to fill the acetabulum. In the case of 10 joints without any residual femoral head-neck component, iliac dislocation occurred. Six of these patients underwent trochanteric arthroplasty. Two joints redislocated and 1 subluxated. The remaining 3 remained in place, but with limited motion, and 1 of the 3 became painful, requiring arthrodesis. Of these 21 patients, 4 also had involvement SPECIFIC INFECTIOUS ARTHRITIS of otherjoints, including 1 child with a total of 10 joints: both hips, both shoulders, both wrists, both ankles, the right elbow, and right femur. Except for this last patient, who was left with deformities in the shoulders, none of these children had deformity at any site except the hip. Arthrography of the septic hip joint in children may or may not be helpful in evaluating the degree of bone damage. Push-pull x-rays were regarded as a more reliable method of assessing the location of the femoral head in the acetabulum, but only surgical exploration gave definite evidence of the actual amount of hip destruction (H23). In another report, however, arthrography was said to be helpful in defining cartilagenous deformity, subluxation, and contracture of the capsular structures (G 1 10). Axial skeletal infection. As noted earlier, discspace infection is a form of vertebral osteomyelitis in which disc involvement predominates. Forty-one children with symptomatic narrowing of the disc-space due to infection had fever and an elevated sedimentation rate, but a correct diagnosis had been delayed (W85). A technetium 99m polyphosphonate bone scan proved reliable and accurate. In another patient the technetium bone scan gave negative results, whereas a gallium-67 scan identified a disc-space infection in the lower lumbar spine (N74). Eight weeks after intensive antibiotic therapy, standard roentgenographic studies demonstrated narrowing of the L4-5 intervertebral space. Technetium 99m polyphosphonate scans were also useful in demonstrating sacroiliac pyarthrosis in children (M244). Viral arthritis. Unrecognized virus infections probably cause many transient, nonrecurring episodes of arthralgia but remain undiagnosed. The 3 major viral causes of arthritis in children are rubella, both natural and vaccine-induced, viral hepatitis Cjoint symptoms have been reported only in adolescents and not in younger children), and certain arboviruses not found in the western hemisphere (Chikungunya and O’nyongnyong in Africa and epidemic polyarthritis or Ross River arthritis in Australia). Many other viruses, including mumps, varicella, variola, and Epstein-Barr virus, can cause an arthritis but less often in children than in adults (P117). Three new cases of varicella arthritis were described (B249,D102) to add to only 4 others now in the literature. Mycoplasma arthritis. A newborn infant with infection of the hip due to M sominis had a good response to treatment with tetracycline (V38). Fungal arthritis. Candidiasis represents a serious 119 problem in the neonatal period. In a review of infection by this agent in all age groups, the propensity for involvement of infants was striking. Nine of 19 cases occurred in patients less than 6 months old. Predisposing factors included serious underlying illnesses, prolonged intravenous feeding, and hyperalimentation (B65,304). It should be remembered, however, that umbilical artery catherization may induce septicemia and joint infection by agents other than Cundidu. Three infants developed neonatal septic arthritis due to S aureus after these difficulties (B63,64). Radiographic changes in infectious arthritis Diffuse soft tissue swelling, bone demineralization, lytic and sclerotic osseous lesions, and periosteal elevation of the adjacent bone are findings that may be seen on standard radiographs in infectious arthritis. A complete review of these changes and the techniques for their demonstration was published (N 18). Standard films taken early in the disease and even later may shown normal findings or fail to reveal the full extent of the pathology. Tomography may sometimes overcome these difficulties (B63,64). Fluoroscopy and arthrograms. A painful hip after either partial or total hip joint replacement may be caused by infection, loosening or breakage of the prosthesis with or without infection, or a fracture in the bone. Differentiation of these causes of pain is difficult. A procedure involving culture of joint fluid obtained by aspiration under fluoroscopic control, followed, if necessary, by an arthrogram was recommended to help resolve this problem (M 157). Fluoroscopy demonstrated loosening of a femoral endoprosthesis in several patients. Arthrograms carried out in others revealed several with loose acetabular components and 1 broken femoral stem. In infants with infections of the hip the value of an arthrogram in assessing the postinfectious status of the joint was not clear (see previous section on infectious arthritis in childhood). Arthrography of the glenohumeral joint in septic arthritis was helpful in revealing rupture of the rotator cuff. Dye escaped from the true joint cavity through the rupture into the subacromial bursa. In addition, the arthrogram showed considerable protrusion of the joint space into the deltoid (A134,M105). These studies and 1 other of an infection of sternoclavicular joints (B63) demonstrate the marked potential for joint capsule destruction in pyogenic arthritis. 120 Other techniques. Xerography can diminish intermediate densities in soft tissues. Its use was suggested, but not actually carried out, for the demonstration of plant material such as a palm thorn in patients with palm thorn synovitis (K5). Another approach to identification of such plant material was the use of POlarized light microscopy. Examination of tissue obtained at arthrotomy revealed a birefringence pattern which helped demonstrate the presence of the thorn (C2 17). Myelogram. Cord compression from tuberculous or pyogenic spondylitis can be evaluated by myelogram. Its use helped define the extent of the surgical intervention required to remove damaged bone and disc material impinging on the cord (03). Radiographic differentiation of infectious arthritis from prior arthritic disease. Infectious arthritis occurs more often in the rheumatoid joint than in the normal joint. Although radiographic changes of both diseases can be similar, some radiologic findings may distinguish between these 2 processes. Eighteen patients with longstanding RA who developed a superimposed pyarthrosis were reviewed (G45). Subtle differences were found. A large, symmetrical joint effusion and fatpad edema in the knee or ankle and a more rapid destruction of joint cartilage or bone to a degree disproportionate to other joints involved by RA, particularly when compared to the contralateral joint, were findings helpful in detecting a superimposed pyarthrosis. Although these findings may be suggestive, the destructive changes are late and identification of the infecting organism is the only sure means of discovering the infection. Nucleographic scanning techniques Bone and joint scanning techniques continued to prove of value. An extensive review described current scanning techniques utilizing either technetium 99m polyphosphonate or gallium-67 to distinguish whether the anatomical site of the infection is a cellulitis, osteomyelitis, or septic arthritis (N 18). Gallium-67 concentrates at sites of inflammation because of its affinity for serum proteins, such as transferrin, haptoglobulin, and albumin, which also accounts for its accumulation in leukocytes. Transferrin-bound gallium-67 can in turn be taken up by tissue lactoferrin. Technetium 99m, on the other hand, reflects an increase in tissue blood flow and/or binding to the bone crystal, calcium apatite. Of interest was the unexpected uptake of gallium-67 in 2 patients with agranulocytosis (cell counts SPECIFIC INFECTIOUS ARTHRITIS below lOO/mm’) (D88). In both cases the isotope concentrated in tissues at the site of inflammation-the lung in the first patient with pneumonia and the perineum in the second patient with a perirectal abscess. In the absence of granulocytes, other inflammatory cells (such as lymphocytes) or noncellular proteins (such as transferrin or tissue lactoferrin) might have concentrated the isotope. This observation may be particularly helpful in the evaluation of patients with Felty’s syndrome in whom infection is considered. In 8 children with low back, hip, or lower limb pain who were subsequently shown to have a pyogenic infection of the sacroiliac joint, scintigraphic examination by technetium 99m was positive in all cases (M244). Routine roentgenograms were initially abnormal in only 2 cases, while in the other 6, up to 6 weeks passed before significant changes occurred. Similarly, negative roentgenograms, but a positive technetium bone scan, were noted in a 14-year-old girl with unilateral sacroiliac joint involvement (R77). The same results were obtained in patients with spondylitis, whether the condition involved primarily the body of the vertebra or the intervertebral disc-space (P42,W85). In those with intervertebral disc-space infection in whom complaints were not noted in the back but rather in the abdomen, the technetium 99m scan permitted an early diagnosis with the avoidance of much unneccesary evaluation with lumbar punctures, myelograms, gastrointestinal x-rays, or intravenous pylograms (W85). Gallium-67 and technetium 99m scans were compared in patients with cellulitis, osteomyelitis, or septic arthritis (L157). In acute osteomyelitis and septic arthritis both scans were positive, but in active cellulitis only the gallium scan was positive. Later, when the septic arthritis had come under control, the gallium scan more nearly reflected this clinical improvement by becoming normal, whereas the technetium scan persisted as a positive finding. Similarly, in inactive osteomyelitis the gallium scan proved negative, whereas the technetium scan remained positive. Sequential gallium scans thus may prove fruitful in monitoring activity. In a single case report, the technetium 99m bone scan failed to detect an intervertebral disc-space infection in a 4-year-old boy 1 month after onset of symptoms, although the gallium-67 scan did (N74). The cause of the negative technetium scan was unexplained and at variance with most other experiences. Other diagnostic tests in infectious arthritis Comprehensive reviews of conventional techniques for the identification of infecting microorganisms SPECIFIC INFECTIOUS ARTHRITIS (S283) and of newly available techniques just coming into clinical practice (R190) were published. These describe the methods that can be applied to serum or joint fluid specimens of patients with infectious arthritis. Markedly raised synovial fluid leukocyte counts greater than 50,000/mm3 may occasionally occur in patients without evidence of infectious arthritis (B 13). Although patients with inflammatory arthritides such as RA or gout may have greatly elevated leukocyte counts, such patients should be considered as having an infection until proved otherwise. A sterile synovitis of the hip is seen in children. Such inflammatory but noninfectious disease can also be confused with a septic process. Aspiration of joint fluid may prove useful since lower cell counts are usually present in these forms of arthritis, although counts over 100,000 have occasionally been recorded (M280). In the viral arthritides, on the other hand, counts may be quite low. Patients with echovirus infections had counts as low as 2,250/mm3, of which 45% were polymorphonuclear cells; those with adenovirus infection 4,000 to 24,800; those with rubella from 14,500 to 27,000; and a patient with vaccinia 44,000 (B176). Histologic and microbiologic examination of joint tissue may be critical for a diagnosis in some patients. An excellent review of techniques available for closed and open biopsies, as well as a review of the types of pathology that may be revealed from such tissue examination, was presented (S106). In some individuals with Gram-negative bacilli infection, particularly drug abusers, fluid could not be obtained from the joint, but the offending microorganism could be cultured from biopsy material (B63). Tissue from open synovial biopsy was superior to joint fluid for obtaining a positive culture in patients with sporotrichosis arthritis (C226). Tissue culture recovery of viruses may be less successful. An echovirus was recovered from the throat and rectal swab culture, but no virus could be recovered from either synovial fluid or synovium during the acute phase of the illness (B176). Depression of synovial fluid glucose values has long been appreciated in the diagnosis of bacterial arthritis. In some patients with gonococcal arthritis, however, such reductions of glucose levels may not be dramatic. Recently a rise of synovial fluid lactic acid has been reported in individuals with bacterial arthritis (B250,S 146). Unfortunately in patients with gonococcal arthritis in whom a reliable clue to infection is often sorely needed, a definite rise of lactic acid did not always occur. Sympathetic synovial effusions may occur in in- 121 dividuals with sepsis in adjacent tissues. In osteomyelitis of the metaphysis area of a long bone, a sterile effusion may exist in an adjacent joint (S63). Similar sympathetic effusions may exist in bursae next to infected synovial cavities (B10). [The mechanism for the production of such an effusion is unknown. However, its presence may divert attention away from the true site of infection. Furthermore, from a technical standpoint, it is important not to aspirate fluid from possibly sterile joints or bursae at the outset if the needle track must go through a surrounding region of cellulitis. After the cellulitis is brought under control, joint aspiration can be attempted. Ed.] Infectious arthritis due to specific microorganisms Gonococcal arthritis. Reiter’s syndrome may sometimes be confused with gonococcal arthritis (M129,S145). The findings in 30 patients with acute gonococcal arthritis were contrasted with those in an equal number of patients with Reiter’s syndrome (M 129). Acute Reiter’s syndrome was characterized by an arthritis and a tenosynovitis usually confined to the lower extremities, recurrent knee effusions, low back pain, characteristic mucocutaneous lesions, conjunctivitis, and genitourinary inflammation. Gonococcal arthritis was characterized by high fever, a migratory polyarthralgia with the arthritis or tenosynovitis initially confined to the upper extremities, typical cutaneous lesions, and dramatic defervescence after penicillin therapy. Massive recurrent effusion of the knee, often exceeding 100 ml and recalcitrant to nonsteroidal antiinflammatory drugs, was seen only in patients with Reiter’s disease. These effusions responded best to intraarticular steroid injections. Soft tissue swelling of the interphalangeal joints of the feet resembling a “cocktail sausage” and an acute anterior uveitis were identified only in patients with Reiter’s syndrome. Laboratory data were of limited diagnostic help. In only 7 of 30 patients with gonococcal arthritis were gonococci identified by Gram stain or cultured in the synovial fluid. Furthermore, genitourinary gonorrhea was coincidently present in 6 of the 30 patients with acute Reiter’s syndrome as detected by a positive genital Gram stain smear, only 1 of which was confirmed by a positive culture. A detailed review of the clinical spectrum and management of gonococcal arthritis was published (M339). Lymphocytes of patients with Reiter’s disease were stimulated by the products of gonococcal, men- 122 ingococcal, and other bacterial cultures (R 136). Pathogenic gonococcal antigens stimulated the lymphocytes of patients with Reiter’s disease to a greater degree than those of controls but the magnitude of the response was not striking. These results are difficult to interpret especially since many of the patients with Reiter’s had a history of prior gonococcal infection. Virulent gonococci possess surface pili that permit attachment to receptors on the surface of the polymorphonuclear phagocyte. Despite such attachment, phagocytosis does not occur and the bacteria are not killed. On the other hand nonvirulent gonococci do undergo phagocytosis and killing. Thus, escape from engulfment by the phagocytic vacuole in which enzymes, free oxygen radicals, and other substances can destroy the bacterium constitutes one essential requirement for pathogenicity. In these studies, the role of serum factors was minimized by the use of a human serum deficient in C7. Such a serum allowed opsonization of bacteria by C3 but not bacteriolysis by the terminal or membrane attack sequence of the complement cascade (D74). The importance of nullifying the action of the membrane attack sequence of complement proteins was highlighted by the observation that persons genetically deficient in any one of its major components, C6, C7, or C8, are unusually vulnerable to disseminated Neisseria disease. Such victims are in jeopardy not only from the ability of the virulent gonococcus to escape effective phagocytosis but also from their inherited and serum-related bacteriocidal deficiency. Most urogenital gonococcal infections in women are symptomatic rather than asymptomatic (J45,M 130). Abdominal pain and signs of pelvic inflammatory disease were the major symptoms. In one study 1.4% (4 individuals) developed a disseminated gonococcal infection. Although only 39% in the same study had either no symptoms or such nonspecific symptoms as a vaginal discharge, these individuals still constituted an important reservoir of infection (M 130). Gonococcal arthritis is not unusual in pregnancy (M178). In fact, 4 of the 30 cases in 1 series occurred at this time (M129). In males, asymptomatic gonorrhea constitutes about the same percentage of cases of infection as in females, contrary to the widely held belief that the disease in men is almost always symptomatic (C220,G93,J51). In a population of 302 males with uncomplicated urethritis due to N gonorrhoeae evaluated prospectively, approximately 1% (3 individuals) developed disseminated gonococcal infection (M266). A higher proportion of gonococci isolated from asymptomatic men, in contrast to those with symptoms, had unique nutritional re- SPECIFIC INFECTIOUS ARTHRITIS quirements for arginine, hypoxanthine, and uracil. These microorganisms are sensitive to penicillin and tend to be responsible for the disseminated form of gonococcal infection (C220). Gonococci resistant to penicillin were simultaneously reported in 1975 in the Philippines and in Liverpool, England (W121) and in 1976 in the United States (S304). These penicillinase-producing gonococci are usually isolated from patients with uncomplicated urogenital gonorrhea. Only occasionally have isolates been reported from patients with disseminated gonococcal infection. One such case was a serviceman with gonococcal arthritis acquired in the Philipines (L59). To date such penicillin-resistant isolates are sensitive to spectinomycin in a dose of 2.0 grams intramuscularly. Penicillinase production results from the acquisition of a previously unrecognized plasmid that bears considerable homology to the plasmid responsible for penicillinase production in Hemophilus influenme. The plasmid can be transferred between gonococci and coliform bacteria (S304). The conclusions that may be drawn from these and earlier studies are that disseminated gonococcal infection arises more often from the asymptomatic carrier of the microorganism than from the patient with acute genitourinary disease and that the virulent microorganisms associated with dissemination tend to belong to subgroups that have unique nutritional requirements and to be susceptible to the action of penicillin. The immune response to gonococcal infection assumes importance on 2 accounts. The first relates to the development of circulating immune complexes and their potential for pathogenicity in disseminated gonococcal infection and the second to the use to which antibodies and other immune responses against the gonococcus can be put for diagnosis. Immune complexes were found in the sera of 13 of 17 patients with disseminated disease but in only 3 of 20 patients with local gonococcal infection and in 4 of 40 normal persons (W9). The immune complexes were 19s or larger in size and their levels correlated with serum complement abnormalities suggestive of complement activation. In another study, persons with acute gonococcal urethritis had antibodies reacting to cytoplasmic gonococcal antigens and a presumed gonococcal antigen in their serum (K190). A patient with a noninfectious effusion in the tibiotalar joint was described from whom N gonorrhoeae was cultured from the adjacent subtalar joint (B 10). The mechanism for a sterile sympathetic joint effusion seen in this patient and occasionally in other individuals with septic arthritis is not clear. It may represent a joint in SPECIFIC INFECTIOUS ARTHRITIS which an infectious process had been aborted or to which noninfectious inflammatory mediators had been carried from the nearby infected joint. A second aspect of the immune response relates to its use in diagnosis. Unfortunately no practical test has yet been devised to confirm the presence of active disease. An editorial carefully outlined the conditions that should be met before any test that measures a gonococcal antibody response is approved for clinical practice (D8). First, the purpose of the test must be stated. Is it to be used as a survey instrument of various population groups, or as a method for case finding, or as a diagnostic tool in patients with symptoms? Culture techniques are still recommended for the diagnosis of urogenital gonorrhea, although in individuals with gonococcal arthritis a serologic test would be invaluable since less than half the patients with this presumptive diagnosis have a positive culture of either the joint fluid or the blood. Cost effectiveness is still another question. In screening and case finding a serologic test might have to be repeated on frequent occasions since recurrences of the disease are frequent. Finally, the sensitivity, specificity, predictive value, and reproducibility have to be assessed. As an example, if a test with a 99% sensitivity and a 90% specificity were used in screening, it would have a predictive value of only 16.8% of identifying a person with gonorrhea in the population. Meningococcal arthritis. The arthritis associated with meningococcemia was reviewed (M339). In 1 study, 4 patients developed an acute oligoarthritis at a time when the systemic or meningeal infection seemed to be improving (P127). The initial diagnoses were rheumatic fever, RA, gonococcemia, and systemic vasculitis. Only after positive blood cultures were returned with the correct diagnosis ascertained. No joints suffered permanent damage. In these patients and in 1 other patient (L33), culture results of joint fluid were negative. In the case of the latter patient, white blood cells from the joint fluid demonstrated meningococcal antigen, antibody, and complement within their cytoplasm by immunofluorescent techniques, and immune complexes and decreased complement proteins were found in the synovial fluid. These observations support a possible role for immune complexes as a contributing cause of the arthritis. Gram-positive coccal arthritis. An excellent review of arthritis due to staphylococci and other Grampositive coccal microorganisms was presented (W 171). Staphylococci are the major cause of nongonoccal arthritis in both children and adults and are especially implicated in the joint infections seen in patients with RA. 123 Arthritis due to a group A, beta-hemolytic streptococcus developed in a patient with an endometritis caused by a contaminated intrauterine device (B255). Arthritis due to Gram-negative bacilli. General features of this type of infection were the ease with which the primary site of infection is recognized in contrast to infections from, Gram-positive cocci, the frequent association with joints previously damaged, and finally, preference for hosts who had suffered an immunologic impairment (G 136). Case reports of arthritis due to specific Gramnegative rods continued to appear. These often highlight the fact that the compromised host is a ready victim. A patient with cirrhosis of the liver developed arthritis of the knee due to E coli (P63). Arthrotomy and closed tube drainage were ultimately required to restore knee function to normal but the patient died because of progressive liver failure. A 36-year-old man with late-onset Still's disease presented with recurrent febrile periods (H58). He developed septic arthritis due to Proteus mirabilis in his hip, a joint that had been previously damaged by his rheumatoid disease. Despite an initial good clinical result with antibiotic therapy, the microorganism was again cultured from the joint 6 months later at the time of a successful total hip joint replacement. In confirmation of several recent reports, infections with 2 particular Gram-negative bacilli were frequently cited as the cause of arthritis in heroin addicts; Serratia marcescens was noted in 1 patient (020) and Pseudomonas aeruginosa in 6 of 8 patients (B63). In 3 reports children were the victims of Enterobacter joint sepsis. A premature infant developed infection of multiple joints with Enterobacter cloacae (G 169). The microorganism had entered the bloodstream from an indwelling intravenous catheter. A nail injury introduced E cloacae and E hafniae (L58). Enterobacter agglomerans was inoculated into the knee at the same time the joint was penetrated by a black locust plant thorn (B50). A patient with bilateral shoulder involvement secondary to sepsis with Aeromonas hydrophilia was successfully treated (M105). In contrast to 2 previous reports of infection from this organism, this patient did not have leukemia. Among 3 patients with systemic infection caused by Pasteurella multocida, 1 developed septic arthritis (564). This patient was an alcoholic with cirrhosis of the liver and congestive heart failure who later died as a result of the liver disease. Salmonella were cultured from several patients with joint disease. 124 In 1 report, Salmonella typhimurium was grown from the knee fluid of a patient with long-standing RA who had received a total knee replacement 5 years earlier (R4). Appropriate antibiotic treatment permitted control of the infection without the need to remove the prosthesis. In another instance, a 14-year-old girl had right sacroiliac joint involvement as determined by a technetium 99m'bone scan (R77). She had a history of severe pain in the lower back radiating into the right leg. Salmonella okatie was cultured from the blood and stool. Infection by this Salmonella serotype has not been reported previously. Finally, Yersinia enterocolitica was grown from the joint fluid, blood, and sputum of a middle-aged man with septic arthritis and presumed septic pulmonary emboli (T26). He had no gastrointestinal complaints that might have been related to infection with this microorganism. Typing for HLA-B27 was not done, but this genetic marker is more closely associated with a reactive arthritis than with an actual infection per se. Arthritis due to syphilis. Six patients had subacute synovitis and back pain (G62). Roseola, loss of hair, or lymphadenopathy were present but were not properly interpreted as signs of secondary syphilis at the outset. The serologic reaction to syphilis was strongly positive and focused attention on the disease. In each case the rheumatic complaints cleared with specific therapy. Only rarely is joint tissue examined during secondary syphilis. Synovial needle biopsies in 3 patients provided tissue for electron microscopy (S 106). Structures compatible with the Treponema pallidum microorganism were found within areas of tissue necrosis. Arthritis due to mycoplasma. Mycoplasma species have been implicated as possible causes for such diseases of unknown etiology as RA, but the evidence to support this claim is flawed because tissue culture cell lines are often contaminated by these agents. An interesting study indicated that many Mycoplasma species have endogenous hypoxanthine phosphoribosyltransferase activity (V18). By use of a mammalian cell line deficient in this enzyme, the presence of a contaminating mycoplasma could be recognized by the emergence of enzyme activity in the culture. Actual infection of the joint by Mycoplasma species was reported in 2 patients. A 40-year-old postpartum patient developed septic arthritis in the hip after delivery (V38). Mycoplasma hominis was cultured from both the genital tract and synovial fluid. In the other, a teenage boy with primary hypogammaglobulinemia, an infection of the knee due to Ureaplasma urealyticum developed. Four years earlier a swollen ankle had oc- SPECIFIC INFECTIOUS ARTHRITIS curred. In both patients, good results were obtained after treatment with a tetracycline antibiotic, a drug to which microplasmas are sensitive (W58). Arthritis due to mycobacteria. Infections of bones and joints due to tuberculosis or to atypical forms of Mycobacteria species are infrequent. A comprehensive review appeared (G137). The pattern of skeletal involvement due to tuberculosis was assessed in 2 groups of 100 patients selected at different times from a Norwegian hospital population (P58). The first group was selected during a single year, 1936, but the second group had to be recruited over a 6-year period, 1969-1975, since fewer patients had contracted this disease in these later years. The more recent pattern of disease involved a much older age group, often individuals in their fifties and sixties, single rather than multiple lesions, and less frequent involvement of the spine and sacroiliac joints. In another series, 21 documented cases of newly diagnosed tuberculosis seen over a 10-year period were culled from the hospital records of a large clinic in Pennsylvania (W170). The initial diagnosis was often erroneous, except for those patients with spinal lesions who accounted for less than half the group. The presentation in the others was usually monarticular. Radiograms showed progressive joint destruction. Elevated sedimentation rates and positive skin tests were helpful clues, but only culture and histologic examination of joint tissue established the correct diagnosis. Chemotherapy was effective. Surgery was required only for patients whose spinal lesions were causing a neurologic deficit. Approximately half of all bone and joint tuberculosis involved the spine in a series of Chinese patients (03). Kyphosis and cord compression were the most feared complications. An anterior fusion operation was used for stabilization of a kyphotic deformity. Multiplestaged operations using a halo-pelvic apparatus were found to be the best treatment to correct an established kyphosis. Poncet's disease is the eponym used to describe joint disease of a noninfectious etiology in patients with tuberculosis. Its pathophysiology is not clear. A 5-yearold boy with oligoarthritis had a positive tuberculin skin test, hilar adenopathy, and a linear pulmonary density as evidence of primary tuberculosis (B177). The joint fluid was not examined. Antituberculous therapy healed both the joint and the lung lesion. Joint involvement in this child may represent an aspect of immune complex deposition during the course of tuberculous lung disease, but the coincidental possibility of an unrelated articular disease cannot be excluded. SPECIFIC INFECTIOUS ARTHRITIS Serum electrophoresis in patients with bone and joint tuberculosis revealed the expected, nonspecific rise of alpha 2 and gamma globulins (P154). Streptomycin and ethambutol entered infected joints and cold abscesses of patients with tuberculosis when administered by mouth (T101). Their concentration in the cold abscess was only a third to a half that in serum, in contrast to their equal concentrations in synovial fluid and serum. Atypical mycobacteria have been recognized since the late nineteenth century. The pathologic lesions that they produce are similar to those produced by the classic tubercle bacillus. Unlike M tuberculosis, atypical mycobacteria are relatively insensitive to the usual antituberculous drugs when tested in vitro, lack guinea pig pathogenicity, and have different characteristics of culture. Subgroups are distinguished by color production and ease of growth on culture. Patients continue to be described with bone and joint infections due to these agents. Two patients developed arthritis after Mfortuitum infection (H29). In both, the organism seems to have been introduced into the musculoskeletal system by direct inoculation, as noted in several earlier reports of infection by this agent. In the first, osteomyelitis developed at the site of a comminuted fracture and in the second at the site of penetration by a piece of galvanized sheet metal. A 58-yearold man with SLE developed septic arthritis due to M avium (H153). This case, as well as most of the 46 other cases from the literature, was insidious in onset; intraarticular steroids have been used as a treatment modality in almost half the reported cases. In only 15% was the diagnosis made by culture of the joint or bursa1 fluid; in the other 85% culture of tissue obtained at biopsy was required for diagnosis. Antituberculous drugs and/or surgical debridement were effective but relapses were frequent so that long-term observation was essential. Tenosynovitis in 1 patient and monarticular septic arthritis in another were found to be due to infection with M kansasii (D131). A patient with Fanconi’s pancytopenia since birth developed synovitis and osteomyelitis of the wrist due to M terrae (E20). Another patient developed a carpal tunnel syndrome due to M szulgai, a saprophyte present in tap water (S390). All these patients responded to surgical debridement and antituberculous drug therapy. Fungal arthritis. Mycetoma, like the actinomycetes that are seen in tropical rather than in temperate climates, cause monarticular disease. Grotesque deformities with sinus tracts may result. Other fungi produce findings that mimic those due to agents like the I25 mycobacteria. Since fungi have special requirements for culture, the usual diagnostic techniques may be unrewarding (E27). The major types of fungal arthritis were reviewed (G 137). Candida commonly cause fungal arthritis. Five of 9 patients with candidiasis had evidence of fungemia from 1 to 24 weeks before inoculation had occurred in the joint (B65). At the onset of fungemia, a high fever, a papular erythematous skin lesion, and severe diffuse muscle tenderness were present. The skin lesions were nonspecific and resembled those seen in other forms of septicemia such as disseminated gonococcal disease or meningococcemia. Biopsy of the skin lesion, and more particularly the skeletal muscle, showed the hyphal and yeast forms of Candida within areas of tissue necrosis (532). Commonly the victim of this infection is an infant, often premature, receiving parenteral nutrition by a central venous catheter, or a patient of any age with a systemic disorder such as a connective tissue disease or a malignancy, or under treatment with corticosteroid, immunosuppressive, or antibiotic drugs (B65,304, F 15,19,L79,S307).Periarticular bone involvement as revealed by lytic lesions (B304,L79) or irregular areas of bone destruction (B65,S307) was frequently the site from which the joint became infected. Treatment consisted of the use of amphotericin B and 5-fluorocytosine. Good results were obtained with the former agent, (B65) but individual case reports indicate that 5-fluorocytosine alone (B304,19,S307) or with a small dose of amphotericin B may produce clinical remission. Drainage by needle aspiration alone was sufficient in some patients, but open drainage was used in others. Sporotrichosis arthritis has 2 distinct clinical presentations: a unifocal form in which joint involvement is the sole manifestation of infection and a multifocal form in which multiple joints are involved along with the skin and other tissues. Often the patient does not have a history of gardening. Of 7 patients with sporotrichosis arthritis, 6 had joint infection alone; 1 with myelofibrosis had joint and skin involvement (C226). Three of these patients and 1 other (M279) had their disease in 3 or more joints. Another patient with primary lung involvement had arthritis of the knee (B248). The correct diagnosis in 1 series was delayed for up to 25 months, an error that resulted in such severe joint damage that arthrodesis was required in 4 of 7 patients (C226). Tissue from an open synovial biopsy provided a positive culture more often than did synovial fluid, but not in every case. Fungal forms could rarely be seen on histologic examination of tissue. Treatment with amphotericin B and surgical 126 debridement of the affected joint was successful in most patients. Because of the indolent nature of this disease, it is especially easy to confuse oligoarticular sporotrichosis arthritis with RA. Pulmonary involvement occurs in the systemic form of each disease. Roentgenographic findings of the joints may also be similar. In sporotrichosis arthritis, however, fistulas may form between the joint and the overlying skin. Infection of the bone and joints in the course of disseminated coccidioidomycosis often resembles a tuberculous infection. One of the more dramatic presentations is coccidioidal spondylitis (W89,163). Of 12 patients with spinal involvement, 8 recovered with no evidence of active infection on examination 11 years after onset; 1 developed neurologic impairment 23 years later from a slowly developing lumbosacral lesion with instability of the spine; 1 died with quadriplegia; 1 had a residual paraplegia; and 1 patient without evidence of active disease of the spine died 5 years after onset from coccidioidal meningitis. The 3 patients with neurologic impairment had not undergone spinal fusion. Most of the others had undergone that operation with drainage of abscesses and debridement of infected bone (W 163). In a few instances medical treatment alone was sufficient (W89,163). Monarticular joint involvement, without juxtaarticular osteomyelitis, is uncommon in coccidioidomycosis. Four patients had this type of involvement (R66). Treatment with amphotericin B was inconclusive. Surgical arthrodesis was considered necessary to totally eradicate the infection. Cryptococcosis occurs predominantly in bone and less often in the joints of patients with an underlying debilitating systemic disease. The port of entry is usually the respiratory tract. The lungs and central nervous system are most often affected. Three cases were added to 56 others reported in the literature (C113). Culture of tissue removed at biopsy or of fluid from an abscess or the joint identified the microorganism. Amphotericin B, sometimes in combination with 5-fluorocytosine, was used in treatment but adequate surgical exploration and curettage were needed for cure and to prevent subsequent osseous spread of the infection. Toxoplasmosis. Two cases of polytenosynovitis involving the wrists and ankles were thought to be due to toxoplasmosis, a protozoal infection of humans and several other mammals, particularly the cat (V32). In 1 patient, mouse inoculation of joint tissue revealed the presence of toxoplasma. In the other, the diagnosis was based on a positive serologic test. In both patients medical treatment with sulfonamide was successful. Although involvement of the skeletal system by tox- SPECIFIC INFECTIOUS ARTHRITIS oplasmosis is rare, this complication can occur in both the congenital and acquired forms of the disease. Viral arthritis. Virus infections commonly cause generalized musculoskeletal complaints but specific joint symptoms are infrequent and then usually acute and self-limited. Three virus diseases, however, have a significant arthritic component: rubella, viral hepatitis, and the illness due to certain arboviruses not found in the western hemisphere (Chikungunya and Onyongnyong in Africa and epidemic polyarthritis or Ross River arthritis in Australia). Less commonly mumps, varicella, vaccinia, and adenovirus disease cause arthritis (H245,P117,S45). Symptoms of rubella arthritis closely resemble those of RA. The long-term evaluation of patients who had either the natural disease or the arthritis associated with the rubella vaccine now indicates that rare individuals can develop a persistent polyarthritis. In the few instances in which synovial fluid was studied, rubella antigen could not be demonstrated. Some of the patients with chronic arthritis gradually lost their symptoms, but a few had persistent joint complaints (M131,S327). A statistical correlation between individuals who developed a recurrent or episodic arthropathy after receiving a rubella vaccine and an HLA-A or B antigen, including HLA-B27, could not be convincingly demonstrated although the A2, B12 haplotype appeared to be more frequent (G245). [Studies should be carried out to determine if a relationship exists between rubella arthropathy and the DRw-4 antigen since this particular antigen has been associated with RA. Its presence in uniquely high amounts in patients with chronic rubella arthritis would lend support to the view that some forms of RA might indeed have been the result of a prior infection with the rubella virus. Ed.] During acute viral hepatitis, a variety of skin rashes are produced. These are attributed to immune complex deposition in the skin. In support of this hypothesis, a patient with an erythematous maculopapular and purpuric rash demonstrated immunoglobulin and complement, but not hepatitis B surface antigen, in the skin lesions (W76). HBsAg and low complement values were noted in the serum. A striking frequency of either HBsAg or its antibody was found in the serum and cryoprecipitates of patients with essential mixed cryoglobulinemia (L96). Electron microscopy of 4 cryoprecipitates showed structures resembling hepatitis B viral structures. The arthritis of chicken pox is rare. An episodic aseptic arthritis was noted in several children with this disease. The arthritis disappeared spontaneously in 5 to SPECIFIC INFECTIOUS ARTHRITIS 6 days without antimicrobial therapy (B249,D 102, P157). In only 1 report to date has a culture of synovial fluid revealed the virus (P157). Echovirus 9 was isolated from the throat and rectal swab specimens of an adult patient with fever, myalgia, and acute polyarthritis (B 176). All symptoms resolved spontaneously within a week, except for the arthritis which required 3 months for complete resolution. The synovial fluid was mildly inflammatory. Attempts to isolate the virus from synovial fluid and synovium during the acute phase of the illness were unsuccessful. An epidemic of Chikungunya in a rural area of South Africa indicated that the virus had been transmitted by the mosquito, Aedes furcifer, from the baboon, the animal considered to be the primary vertebrate host (M 149). Lyme arthritis. Several years ago, a patient in Old Lyme, Connecticut reported to the State Health Department that physicians in her community had diagnosed 12 cases of juvenile rheumatoid arthritis (JRA). This substantial cluster of cases in a small area led physicians at Yale University down a trail of investigation whose end is still not in sight. A new clinical syndrome, called Lyme arthritis, has been established (K38). The same disease exists in several other areas of the country, although most studies to date have centered upon patients from the New England area. A characteristic skin lesion, erythema chronicum migrans, typically lasting about 3 weeks, initiates the disease. It begins as a red macule or papule that expands to cover a large area, sometimes with central clearing. Associated symptoms include malaise, fatigue, chills and fever, vomiting, sore throat, headache, stiff neck, backache, myalgias, neuropathies, and myocardial conduction abnormalities. Many of the patients suddenly develop a monarthritis or oligoarthritis 1 to 4 weeks after the onset of the skin lesion. Occasionally an arthritis appears without a skin lesion. The arthritis is migratory, most commonly in the knees, but sometimes persists for months. Serum cryoprecipitates with elevated serum IgM levels and elevated sedimentation rates are characteristic features of the group (S354,355, 356). In field studies, patients with the disease observed ticks on cats or farm animals or tick bites on themselves more often than did well patients in the same community. Some patients had been bitten by ticks at the actual site of the initial skin lesion. The tick, Zxodes scapularis, is commonly found in the same region as the disease. Indeed, 1 patient retrieved such a tick after having been bitten (S353,W20). Although the 127 skin lesion, erythema chronicum migrans, has been known in Europe for more than half a century it has been observed in America only for the past 2 decades. Perhaps its appearance coincides with the introduction of a potential infectious agent such as a virus into a natural reservoir from which it could be spread by a tick vector. On the Pacific coast a patient developed the same skin lesion without arthritis. Another Ixodes species, Zpacijicus, was the probable vector. This individual has a rising antibody titer to measles virus but the significance of this observation is unclear. Other patients with the syndrome of Lyme arthritis are being reported from the Pacific coast and from an area in central Wisconsin. Antibiotic therapy Criteria were defined for the appropriate selection of antibiotic drugs in the treatment of patients with infectious arthritis. The initial choice was based on clinical findings, age of the patient, and the results of the examination of the Gram smear of joint fluid. After a culture report was obtained, the selection or dose of the drug could be altered. When a smear showed Gram negative bacilli, gentamicin was the preferred antibiotic, except in young infants who should receive ampicillin, on the expectation that the infection may be due to Haemophilus inJuenzae. For Gram-negative cocci, penicillin G was used and for Gram-positive cocci, nafcillin was chosen. When no organisms were seen, the problem was more difficult. A combination of antibiotics, nafcillin and gentamicin might be used (C146). For infections due to P aeruginosa, gentamicin may need to be supplemented by carbenicillin (B64). For most fungal infections amphotericin B can be used (B65,C226,F15). In candidiasis, 5-fluorocytosine can be added or may be the only drug used since cures have been reported with this agent (19,L79,S307). Almost all currently used antibiotics have now been shown to cross from the bloodstream into the joint and to achieve roughly equal concentrations in both compartments in a few hours. Therefore the delivery of the antibiotic to the joint can be assured, provided that an adequate blood level is obtained. Indications for intraarticular instillation of the antibiotic may still exist, possibly for new agents whose pharmacokinetics have not yet been established or for patients with resistant infections in whom blood or synovial fluid levels of the antibiotic have not been determined. Such levels, however, can be measured in most clinical laboratories 128 within a few days and, if adequate, intraarticular instillation can be abandoned. Synovial fluid concentrations of amphotericin B were demonstrated in a patient with Candida tropicalis arthritis (F 15). Both cephalexin (527) and cefazolin (S116) readily crossed into either synovial fluid or bone after intravenous administration. Similarly, lincomycin was detected in plasma, synovial fluid, and bone of patients subsequently undergoing total hip replacement (P39). In 60 patients with bone and joint infections secondary to Gram-negative bacilli, amikacin was administered parenterally. Thirty patients had Pseudomonas infections and 15 others were infected with multiple pathogens including Pseudomonas. Amikacin proved to be effective, and bone and synovial fluid levels of this drug were found to be in the therapeutic range (S119). In 79 consecutive cases of skeletal tuberculosis, the concentration of streptomycin and ethambutol was analyzed in fluid obtained from the diseased joints of 14 patients and from the cold abscesses or spinal osseous lesions in 65 patients. Although there was a wide range of concentrations, both drugs penetrated freely into the tuberculous joints. Their concentration in cold abscesses, however, was only one-half to one-third that of their concentration in serum. Nevertheless, even this lower concentration was still higher than was needed for control of the infection (T101). Some new and commonly used antibiotics were examined with regard to their ability to penetrate joint fluid in normal and E coli-infected rabbit knee joints. A simple method of measuring antibiotic concentration in very small amounts of synovial fluid was developed. Cephalothin, cefazolin, cefoxitin, carbenicillin, amikacin, and gentamicin all penetrated synovial fluid effectively, achieving peak concentrations within 30 minutes to 1 hour. Synovial fluid antibiotic concentration at 2 hours was equal to or higher than simultaneous serum levels. Penetration of all antibiotics studied was satisfactory for use against their normally intended pathogens (S117). Surgical considerations in infectious arthritis Open versus closed drainage procedures. The literature continues to present divergent views concerning the merits of open or closed drainage of infected joints. However a consensus is beginning to emerge. Less and less often is the view expressed that an infected joint must always be drained surgically at the outset, even in SPECIFIC INFECTIOUS ARTHRITIS a compromised host with a severe pyogenic infection (M 105,S246). The only unequivocal exception seems to be an infection of the hip of children, which should be incised a n d drained as soon as possible (F46,H23,J 13,S63). If after 4 to 7 days of treatment, closed drainage has not been effective in bringing about at least partial resolution of the signs of inflammation within the joint, open drainage should be considered. Open drainage is more likely to be required in patients who have infections due to Gram-negative bacilli (B65,S 1 19,246) or fungal infections (C113,226,R66,W163). In addition, infections due to tuberculous or atypical mycobacteria, perhaps because they are so often diagnosed late, may require open drainage or debridement. Examples are tuberculosis of the spine with cord compression (03) or tuberculous tenosynovitis for removal of accumulated debris (S390). Before surgery is carried out to repair an irreversibly damaged postinfectious joint, aspiration of joint fluid is mandatory to rule out persistence of any infection. Such aspiration may be done by needle aspiration or arthrotomy. In the case of the hip, fluoroscopic control may assist proper placement of the needle (M157). If an unstable hip results after complete control of the septic process in a child, surgical exploration is indicated at about 1 to 2 years of age (H23). Open reduction should be performed if there is a sufficient head-neck femoral residue to achieve stable reduction; otherwise, a trochanteric arthroplasty is the procedure of choice followed by a varus osteotomy if there is progressive subluxation. If successful, this procedure will provide a stable joint with less leg length discrepancy and a greater range of motion than would follow the natural consequence of a dislocation. Such surgery will not interfere with the option for total joint replacement if such a procedure is indicated at a later age. Reports are now beginning to appear that document the successful implantation of a total hip prosthesis in patients who have recovered from septic arthritis (H58,M156). Ten patients with a history of previous hip joint sepsis, including 1 with tuberculosis, had good results from a total hip replacement using acrylic cement after a followup period ranging from 6 months to over 3 years (M 156). Such replacement techniques can probably be attempted for the restoration of other joints as well. Caution should be maintained to be sure that no evidence of infection remains. Most surgeons seem to wait at least a year after the infection has become quiescent.