Waldenström's Disease Complicated by Recurrent Meningococcal Arthritis

CASE REPORT

A 74-year-old man was admitted to our hospital with cough, chills, confusion, and pain of a few days' duration in the left knee. On admission, he was in poor general condition and lethargic, with a stiff neck. He had purpuric skin lesions on his lower limbs. His left knee and both wrists were swollen and painful. Laboratory tests revealed a high white blood cell (WBC) count (36,200/mm³, 22% nonsegmented neutrophils) and an increased erythrocyte sedimentation rate (137 mm per h). Cerebrospinal fluid examination showed 5,400 WBC/mm³ (90% polymorphonuclear leukocytes) with intracellular gram-negative diplococci. Synovial fluid from the left knee was inflammatory (140,000 WBC/mm³, 88% polymorphonuclear leukocytes), with gram-negative diplococci. Both the synovial fluid and blood cultures grew Neisseria meningitidis serotype B:15:P1.16. A diagnosis of meningococcal arthritis with meningitidis and meningococcemia was established. The patient's condition improved with intravenous penicillin.

Additional laboratory tests revealed a spike in the gamma region and identified an immunoglobulin M κ chain (IgMκ) monoclonal paraprotein (concentration, 6.94 g/liter; N, 0.29 to 3.29 g/liter). IgA and IgG levels were within the normal range (0.88 and 7.17 g/liter, respectively). In the absence of constitutional symptoms and of anemia, the patient was considered to have a smoldering form of Waldenström's disease and was discharged without additional treatment. Evaluation of his complement system (C3, C4, and CH50) was within normal limits.

Eight years later, the patient was admitted for an acute arthritis of the right wrist. He did not exhibit any sign of meningism and had no purpuric skin lesion. Blood tests showed a WBC count of 20,500/mm³. Synovial and blood cultures grew N. meningitidis serotype B:−:P1.4,12. A diagnosis of primary meningococcal arthritis was established. His condition improved with intravenous ceftriaxone. The values of blood immunoelectrophoresis disclosed an increase of IgM levels compared with those obtained during the first episode of meningococcal arthritis (IgG, 8.8 g/liter; IgA, 1.6 g/liter; IgM, 11.12 g/liter).

Neisseria is a rare cause of arthritis, occurring in approximately 2% of bacterial arthritis cases (4). Arthritis is reported in 1.6 to 16% of meningococcal infections (2), and three different clinical presentations have been described (12), the most frequent being arthritis during acute meningococcemia, followed by arthritis in the presence of chronic meningococcemia and primary meningococcal arthitis, which is rare.

The patient in this report presented two separate episodes of meningococcal arthritis; the first was associated with acute meningococcemia, and the second presented as primary meningococcal arthritis. The recurrence of meningococcal arthritis has not been described previously and is highly suggestive of an impaired immune response. Indeed, an increased occurrence of meningococcal infection in patients with decreased host defenses, including systemic lupus erythematosus (1, 8, 13, 14), deficiencies in complement components (1, 3, 11, 14), AIDS (7, 14), and multiple myeloma (6, 14), has been reported. An association between Waldenström's disease and meningococcal arthritis has not been reported so far. However, it is likely that the mechanisms favoring the occurrence of superimposed infection in Waldenström's disease would be similar to those in multiple myeloma, including a decreased concentration of immunoglobulins and a decreased leukocyte number (5, 6). The laboratory tests performed with our patients did not disclose any obvious cause of immunodeficiency. However, the presence of an impaired humoral response cannot be formally ruled out by the results of immunoelectrophoresis. Decreased neutrophil adherence has also been reported as a possible cause of superimposed infection in patients with multiple myeloma but was not tested in this case (5). The reactivation of a chronic meningococcal infection can be excluded, since this patient was free of symptoms for several years between the two episodes of meningococcal arthritis and had two different serotypes of N. meningitidis.

Meningococcal arthritis is rare. Among 256 cases of proven infectious arthritis (positive culture) found by reviewing microbiology laboratory records at the University Hospital of Geneva from 1989 to 2000, only six were diagnosed as meningococcal arthritis (2%). This frequency is in accordance with previous studies (4, 10). The clinical characteristics of our patients are presented in Table1. In addition to the patient described above, four patients had arthritis in the presence of acute meningococcal disease with typical skin lesions including a petechial rash, and one was known to have had an IgGλ multiple myeloma for 10 years. One 15-month-old child had acute monoarthritis, consistent with the diagnosis of primary meningococcal arthritis. The higher frequency of arthritis during acute meningococcal infection is in accordance with previous reports. Indeed, among 2,043 patients with acute meningococcal disease, 10.8% developed arthritis (12). In contrast, primary meningococcal arthritis is rare and predominantly observed in early childhood (2, 12). The higher prevalence of primary meningococcal arthritis in infants coincides with an overall increased frequency of meningococcal infection (9, 15), which has been related to the low titer of serum antibodies bactericidal forN. meningitidis observed during the first 2 years of life (15). This relative deficiency of the immune system may favor the occurrence of primary meningococcal arthritis in children. Thus, the occurrence of primary meningococcal arthritis in a 74-year-old patient was probably favored by an immunodeficiency secondary to Waldenström's disease. Furthermore, one of our patients suffering from multiple myeloma and meningococcal arthritis clearly presented with an immunodeficiency, since she had a monoclonal IgGλ paraprotein (40.7 g/liter) with low IgA (0.11 g/liter) and IgM (0.15 g/liter) levels in plasma.

For many years, N. gonorrhoeae has been considered a frequent cause of infectious arthritis, particularly in young adults (10). However, N. gonorrhoeae was detected in only two synovial fluid samples during a period of 11 years in our hospital. A decline in the number of arthritis cases due to N. gonorrhoeae compared to those due to N. meningitidishas also been reported by others (10). This change is probably related to an overall decrease in gonococcal infections secondary to the prevention of AIDS and other sexually transmissible diseases.

In conclusion, this is the first report of recurrent meningococcal infection in a patient with Waldenström's disease. Physicians should suspect the presence of an impaired immune response in patients with meningococcal arthritis.