PRIMARY MENINGOCOCCAL ARTHRITIS

Abstract

Since the first description of epidemic spinal meningitis in 1805,1 infection with Neisseria meningitidis continues to be a cause of worldwide epidemic disease. The clinical spectrum of meningococcal infection ranges from asymptomatic carriage to fulminant sepsis, with meningitis and septicemia as well-recognized clinical presentations. However, the ability of the organism to cause focal disease is often overlooked. The three cases presented here highlight the importance of recognizing the wider spectrum of disease caused by the organism. Meningococcal infection must be considered in the diagnosis of any child who presents with arthritis with or without rash, even if afebrile on presentation. Case 1. A previously healthy 4-year-old boy was hospitalized with a 24-h history of malaise, lethargy, fever, vomiting, rash and refusal to bear weight. He had not received any antimicrobial agents before admission. On examination, although irritable, he was afebrile and nontoxic in appearance. He had a generalized erythematous rash with palpable purpura. This was most marked on his extremities and was associated with swelling and tenderness of his feet. His right hip was held in flexion and movements were painful and restricted. Examination of other joints was normal. The white blood cell count (WBC) was 15.6 × 109/l with an absolute neutrophil count (ANC) of 9.3 × 109/l, and the erythrocyte sedimentation rate was 75 mm/h (Westergren method). Two sets of blood cultures obtained on the day after admission, before antimicrobial treatment, were sterile. On Day 2 after hospitalization his rash resolved. His right hip remained painful. An open aspiration was performed on the third hospital day. Frank pus was obtained and antibiotic therapy with cefuroxime and flucloxacillin was commenced. Group C N. meningitidis, susceptible to penicillin was isolated from the hip aspirate. Penicillin was substituted. He received a total of 19 days of antibiotic therapy and made an uneventful recovery. Case 2. An 18-month-old girl was admitted to hospital with a 3-day history of fever, vomiting, anorexia, irritability and rash on both hands. Her left hip and knee were painful and she refused to bear weight. She had not received any antibiotic treatment at home. On physical examination she was afebrile and nontoxic in appearance. Her rash had faded. There was swelling and effusion of her left knee, movements of which were restricted and painful. Her WBC was 12.5 × 109/l and the ANC was 6.43 × 109/l. The next day a needle aspiration of her left knee yielded pus. Treatment with flucloxacillin and sodium fucidate was initiated. Group B N. meningitidis was recovered from the aspirate and treatment was changed to penicillin. She was treated for 14 days and made an uneventful recovery. Case 3. A 12-year-old boy was hospitalized with a 2-day history of low grade fever and malaise and a 1-day history of pain in his right thumb and left knee. On the morning of admission he developed a rash and complained of pain in his right eye. He had not received antibiotic treatment. On examination he was nontoxic in appearance. He had a low grade fever of 37.9°C. Conjunctivitis of the right eye and a generalized erythematous rash, with palpable purpura on the abdomen and extremities, were noted. Neurologic examination was normal and meningeal signs were absent. His left knee was swollen and tender and movements were restricted. On evaluation his WBC was 19.8 × 109/l, ANC 16.8 × 109/l and erythrocyte sedimentation 63 mm/h. CSF examination was normal and no organisms were recovered from the eye culture. Treatment with intravenous ampicillin and chloramphenicol was initiated. Later that day his left knee joint was aspirated yielding 20 ml of pus. The stained smear revealed Gram-negative diplococci with 90% polymophonuclear cells, but cultures were sterile. Group C N. meningitidis was isolated from blood cultures drawn before antibiotic therapy. He received 14 days of antibiotic treatment but his clinical recovery was complicated by the recurrence of pain and swelling of his left knee on Day 14. After readmission to the hospital an effusion of his left knee was aspirated and was sterile. He was again given parenteral antibiotic therapy. Eight days into his second admission, arthroscopy and synovial biopsy were performed, confirming the presence of active synovitis. Serum circulatory immune complexes were markedly elevated at 1480 μg/ml (n = <200). Additional laboratory investigations included WBC 19.4 × 109/l, ANC 13.2 × 109/l and normal immunoglobulin and complement values. Blood cultures were sterile. Discussion. Arthritis is a recognized manifestation of meningococcal disease, occurring in 2 to 10% of reported series.2, 3 It is more common in adults than in children4, 5 and is a rare primary disease manifestation in children. The pathogenesis of meningococcal arthritis is varied resulting in several different clinical presentations the most frequently recognized of which is the immunomediated form of arthritis that occurs during the recovery from meningococcal infection, typically from Day 5 of illness.2, 4, 6 Large joints are usually involved4, 5 and effusions are sterile. The arthritis is a result of the host's immunologic response to the bacterium, leading to immune complex deposits within the joint.2, 4-7 Elevated serum circulating immune complexes have been demonstrated.2, 4, 5, 7 This type of arthritis is exemplified by the late onset of arthritis in Case 3. Direct bacterial invasion of the synovium results in a septic meningococcal arthritis which can develop as part of the acute meningococcal sepsis syndrome or during the course of chronic meningococcemia. It can also occur as a primary meningococcal arthritis. As described by Schaad5 this entity primarily affects males, an observation also made by Likitnukul et al.3 in a review of arthritis complicating bacterial meningitis. Two-thirds of cases are monoarthritic, mainly affecting the knee joint. The polyarthritic form also involves primarily the large joints, and 30% of patients had an associated erythematous maculopapular skin rash. The organism, N. meningitidis, was isolated from the purulent synovial fluid in 80 to 90%, from the blood in 40% and from the throat in 30% of cases. All three cases reported fulfill the diagnostic criteria for primary meningococcal arthritis. Joint symptoms predominated at presentation, with large joints being affected in all three cases. Symptoms of malaise and lethargy preceded the onset of joint involvement, and all three cases had a rash. N. meningitidis was cultured from the purulent joint fluid in the first two cases. In Case 3, although Gram-negative diplococci were seen in the pus evacuated from the knee, the organism did not grow. However, joint aspiration was performed after initiation of antimicrobial therapy. Group B N. meningitidis was cultured from this patient's blood. Case 3 also fulfills the diagnostic criteria for immunomediated arthritis, with the recurrence of arthritic symptoms on Day 14 of illness. The presence of elevated serum circulating immune complexes and evidence of chronic synovitis on synovial biopsy support this diagnosis. Allergic complications of meningococcal infection, including late onset arthritis, are more common with Group C N. meningitidis. In a review by Edwards and Baker4 Group B N. meningitidis was found to be intermediate in its potential for causing immunomediated complications. The three reported cases highlight the need to recognize the wider spectrum of disease associated with N. meningitidis. Although reported to be a rare form of meningococcal disease, primary meningococcal arthritis accounted for 8% of cases of meningococcal infection presenting to our institution between 1994 and 1995. The diagnosis should be suspected in a child presenting with arthritis and a rash. Michelle Dillon, M.B., B.Ch., M.R.C.P.I. Clare Nourse, M.B., B.Ch., M.R.C.P.I. Frank Dowling, M.B., B.Ch., F.R.C.S.I. Patrick Deasy, M.B., B.Ch., F.R.C.P.I. Karina Butler, M.B., B.Ch., F.R.C.P.I. Our Lady's Hospital For Sick Children (MD, FD, PD, KB); Department of Paediatrics; University College Dublin (CN); Dublin, Ireland