Acta Paediatr 81:921-4.1992
Borrelia arthritis in Swedish children: clinical manifestations in 10 children S Hammers-Berggren, U Anderson' and G Stiernstedt Department of Infectious Diseases, Danderyd Hospital, Danderyd and Department of Pediatrics', S:t Goran's Hosphal. Stockholm. Sweden
Hammers-Berggren S, Anderson U, Stiernstedt G . Borrelia arthritis in Swedish children: clinical manifestations in 10 children. Acta Paediatr l992;8 1 :921-4. Stockholm. ISSN 0803-5253 Since 1986, serology against Borrelia burgdorferi has been performed on patients with arthritis admitted to the Division of Pediatric Rheumatology, S:t Goran's Hospital, Stockholm. We studied, retrospectively, the period 1986-88. Among 300 children with arthritis, 10 had positive titers against B. B. burgdorferi. Other causes of arthritis were excluded. The onset of Borrelia arthritis was throughout the year. Only 3 of the 10 children remembered an actual tick bite. No other manifestations of Lyme borreliosis were present simultaneously. The typical clinical picture was a relapsing unilateral arthritis of the knee. 0 Arthritis, Borrelia. children S Hammers- Berggren. Depariment of Infectious Diseases, Danderyd Hospital, 18288 Danderyd, Sweden
Lyme arthritis was first described in the USA by Steere et al. in 1976 (1). Most of the patients in the initial reports were children presenting with recurrent attacks of mono- or oligoarthritis, preceded by an erythema migrans in approximately 25% of the cases (2). In 1982, Burgdorfer et al. found the etiological agent of Lyme borreliosis, a spirochete later named Borrelia burgdorferi ( 3 ) . We now know that Lyme borreliosis may affect many organs, most often the skin, nervous system, joints and heart. In the USA, the reported frequency of arthritis has been rather high, whereas in Europe, arthritis is considered more uncommon. The number of published reports of the clinical features of Borrelia arthritis in Europe is still sparse (4-9). The aim of the present study was to describe the clinical picture and laboratory findings of Borrelia arthritis in Swedish children.
Material and methods Serum samples from all patients with arthritis admitted to the Division of Pediatric Rheumatology, S:t Goran Hospital, Stockholm, during the period 1986-88 were analyzed for antibodies against B. burgdorferi. An ELISA test with sonicated whole-cell antigen was used. The test procedure has been described previously (10). The ELISA titer was expressed as the optical density (OD) at 405 nm, multiplied by the serum dilution factor. IgM and/or IgG titers against B. burgdoferi of 2700, corresponding to the 98th percentile of titers obtained in sera from healthy individuals, were considered positive. A titer decline of at least 50% of initial titer levels against B. burgdorferi was considered significant. In all patients with a positive serology against B.
burgdorferi, serum samples were analyzed for antinuclear antibodies (ANA), rheumatoid factor (RF), antistreptolysin 0 titer and streptococcal anti-DNAse titer. Analysis was also performed with ELISA against Salmonella lipopolysaccharide BO and DO and against Yersinia enterocolitica type 3. Sedimentation rate and white blood cell count were analyzed in all patients. White blood cell count in synovial fluid was analyzed when arthrocentesis was performed. The records of the patients were reviewed retrospectively. Response to antibiotic therapy was defined as no relapse of arthritis within a follow-up period of six months after treatment.
Results Serum samples from approximately 300 children with arthritis were tested with serology against B. burgdorferi during the three-year study period. Ten patients (6 boys and 4 girls) aged 8-14 years had positive IgG titers. Two of the 10 children also had positive IgM titers (1 500 and 4500, respectively). IgG titer levels against B. burgdorferiin the 10 children are shown in Table 1. The majority of patients, (6/10) had high titers ( 22000). Three patients had moderately increased titers. Only patient had a slightly elevated titer. Seven of the 10 patients were admitted to the Division of Pediatric Rheumatology after referral from pediatric surgeons, 2 patients from general practitioners and 1 patient from a general pediatrician. Clinicalfeatures All 10 children were living in the Stockholm area. Three remembered an actual preceding tick bite within three months. None of the patients had noticed an erythema
922 S Hammers-Berggren el al. Table 1. Clinical and
ACTA PRDIATR 81 (1992)
laboratory data in 10 patients with Borrelia arthritis.
Patient No. Sex (M/F) Age at diagnosis (years) Affected joints at diagnosis
1 F 14 Left knee
No. of arthritis attacks before diagnosis 3 Duration of relapsing arthritides (months) I Sedimentation rate (mm/h) 20 Borrelia IgG titers at diagnosis 700-990 I 000- I990 2 2000 X Antinuclear antibodies Neg Rheumatoid factor 1/20 Antibiotic treatment and response See Fig. 1 Other treatment ia steroids synovectomy Follow-up time without symptoms after last treatment regime (months) 28
2 M 12 Both knees
3 F 9 Right knee, elbow, wrist
M 10 Left knee
5 M 8 Left knee
F 8 Both knees
7 F 10 Right knee
M 12 Right knee
9 M 8 . Left knee, Right elbow
10 M 13 Left knee
2
3
I
2
3
1
4
2
2
I 30
9 4
40
12
4 40
-
8 11
9 17
24
5
X
X
Neg nd
Neg Neg
X 1/25 1/20
X nd Neg
Neg nd
X Neg nd
4
6
32
8
18
X
X X Neg Neg
Neg 1 /20
X Neg nd
-
NSAID
ia steroids, NSAID
-
NSAID
NSAID
-
-
-
11
10
18
24
14
16
15
10
18
Neg= Negative; nd = not done; ia = intra-articular; NSAID = non-steroidal anti-inflammatory drugs.
was the preliminary diagnosis and in the remaining 8 patients, unspecified aseptic arthritis was suspected. None received antibiotics before the results of serology against B. burgdorferi were obtained. Antibiotic treatment is summarized in Fig. 1. The 8 patients who responded to initial treatment were all symptomless without any relapse during a median follow-up time of 14.5 months (range 10-24 months). None of the responders had received intra-articular steroids before antibiotic therapy. The 2 non-responders had both received intra-articular steroid injections before antibiotic treatment. Both these patients developed a long course with relapsing arthritides and received repeated antibiotic treatments (Fig. 1). One of the patients responded after treatment with ceftriaxone 1 g bid for 14 days, one year after initial treatment and had no further relapses during 18 months follow-up. The other nonresponder improved after synovectomy 15 months after initial treatment and remained well during a follow-up Laboratory jindings period of 28 months. Serum samples from 9 of the 10 Median sedimentation rate was 19 mm/h (range 4-40 patients showed a significant decrease in IgG titer mm/h). White blood cell count was normal in all during follow-up, although 5 of 10 patients still had patients. Synovial fluid from the knee joint was obtained positive IgG titers against B. burdorferi 1 1-28 months from 7 patients and showed 2-44 x lo9(median 12 x lo9) (median 15 months) after antibiotic treatment or surleucocytes/l, with 2 75% polymorphnuclears in all gery. The increased IgM titers in 2 patients also declined patients. R F was slightly increased to 1/20 (reference significantly. value < 1/20) in 3 patients and ANA was positive at a level of 1/25 (reference value < 1/10) in I patient. An Xray of the knee was made in 7 children and showed only soft tissue affection with effusion of joints. migrans. Onset of arthritis occurred all year round. Two patients had fever, fatigue and malaise; the remaining 8 children had no accompanying symptoms. One girl had suffered from stiff neck six months before the onset of arthritis, but lumbar puncture performed when the diagnosis of Borrelia arthritis was made showed no abnormalities. No other neurological symptoms were reported or noticed in any of the patients. The number of arthritis attacks is shown in Table 1. Eight patients had at least two attacks of arthritis before diagnosis, whereas 2 patients had just one single attack. On admission to the Division of Pediatric Rheumatology, 8 patients still had ongoing arthritis, while 2 patients had improved after arthrocentesis. Affected joints are shown in Table 1. Six patients had monoarthritis, 4 had oligoarthritis and all 10 had gonarthritis. Four patients had accompanying arthralgias.
Discussion
Treatment and follow-up In 2 of 10 patients, juvenile rheumatoid arthritis (JRA)
A positive titer against B. burgdorferi is no definite proof of the etiology of the patient’s arthritis. First, if the 98th
ACTA
Borrelia arthritis in Swedish children
P EDIATR 81 (1992) 7 ( patient no. 2. 3. 5. 6. 7. 9, 10 )
PcG i.v.
------
9 patients
-----
1 ( patient no. 1 )
responded
oral doxycycline (28 days)
--- oral doxycycline (50 days)
'.
(100-150mg/kg, lodays)
923
--- ceftriaxone (14 days) --- oral PcV (3 months)
--- synovectomy --- responded
1 ( patient no. 4 )
oral doxycycline (15 days)
--- oral PcV (4,5 months)
--- ceftriaxone (14 days) --- responded
Doxycycline oral
---
1 patient
----
( patient no. 8 )
responded
( 1 00mgx2.10 days, 1OOmgxl ,20 days )
Fig. 1 . Antibiotic treatment in 10 patients with Borrelia arthritis.
percentile is used there is still a 2% possibility of a false positive result. Second, epidemiological studies have shown that increased titers against B. burgdorferi, probably due to earlier clinical or subclinical exposure, are common in certain areas around Stockholm (1 1). However, the fact that the majority of the patients had high increased titer, far above titers seen in asymptomatic individuals, supports B. burgdorferi as the cause of arthritis in our patients. Consequently, this study shows that B. burgdorferi is one cause of arthritis in Swedish children. However, the frequency seems rather low, which is in agreement with other Scandinavian publications reporting Borrelia arthritis in children and adults ( 5 , 779). The clinical features and laboratory findings of Swedish children with Borrelia arthritis are similar to
those with Lyme arthritis described in the USA (2, 12, 13) and Borrelia arthritis patients reported previously from Europe (4-9). The most typical symptom was a recurrent arthritis of the large joints, especially the knee. The lack of a preceding erythema migrans might be explained by the fact that the study was retrospective. We observed low positive ANA and RF titers in a few children, but do not consider these titers as markers for JRA since similar findings have previously been reported from the USA in children with Lyme arthritis (12). This autoantibody formation may have been caused by polyclonal B-lymphocyte activation by the spirochete. In none of the patients was Borrelia arthritis suspected on clinical symptoms only probably because of a lack of a history of associated typical symptoms of Lyme
924
S Hammers-Berggren et al.
borreliosis, such as erythema migrans and facial palsy. In the present study, the children with Borrelia arthritis were aged 8-14 years. The highest incidence of monoarthritis of the knee due to JRA occurs between 24 years of age. Thus in elderly children with monoarthritis of the knee of unknown etiology, Borrelia arthritis may constitute a larger proportion of aseptic gonarthritis than in younger children. Because of the small number of patients with Borrelia arthritis in this study, no definite conclusions of response to antibiotic treatment could be drawn. However, the cure rate of iv penicillin G seems to be high, similar to that reported from the USA (14). Oral doxycycline was given to one of the patients in this study and might be an alternative in children older than eight years of age. Amoxycillin, together with probenecid, has also been reported to be effective in the treatment of Borrelia arthritis (15). When evaluating the clinical response to antibiotic treatment it is also important to remember that the disease might be self-limiting. According to Steere, the number of untreated patients who continued to have attacks of arthritis decreased by about 10-20% each year (16). Steere has also reported that therapeutic failure in some patients might be explained by genetic factors, as he found an increased frequency of HLA-DR4 in non-responders (1 6 ) . Development of chronic Lyme arthritis was shown to be associated with HLA-DR2 and HLA-DR4 (16). However, other authors have been unable to confirm this observation (17). The possibility that preceding intra-articular steroid injections may predict antibiotic treatment failure has been reported by others (14, 18). We do not know the reason for this, but one suggestion may be that the administration of intra-articular corticosteroids inhibits the formation of the macrophage-activating factor, gamma interferon. The consequence would be a persistence of intracellular bacterial antigen, selectively retained by macrophages, with reduced bacterial degradation capacity. Release of lipopolysaccharide and other bacterial products would initiate and maintain the synovitis by inducing monokine production (1 9). The results from the present study show that B. burgdorferi can be the etiologic agent of arthritis in Swedish children. We recommend serology against B. burdorferi to be performed in patients with mono- or oligoarthritis of unknown etiology. Furthermore, B. burgdorferi as the cause of arthritis should be excluded before the administration of intra-articular corticosteroids. When Borrelia arthritis is present, adequate antibiotic therapy should precede a possible need for intra-articular corticosteroids.
ACTA PRDIATR SI (1992)
References 1 Steere AC, Malawista SE, Snydman DR, Andiman WA. A cluster
of arthritis in children and adults in Lyme, Connecticut. Arthritis Rheum 1976;19:824 2 Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis. An epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 1977;20:7- 17 3 Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP. Lyme disease-a tick-borne spirochetosis? Science 1982;216:1317-19 4. Gerster JC, Gyggi S, Perroud H, Bovet R. Lyme arthritis appearing outside the United States: a case report from Switzerland. BMJ 1981;283:951-2 5. Stiernstedt G, Granstrom M. Ixodes ricinus spirochete infection as the cause of postinfectious arthritis in Sweden. Scand J Rheum 1985;14:336-42 6. Herzer P, Wilske B. Lyme arthritis in Germany. Zentralbl Bakteriol Microbiol Hyg (A) 1986;263:268-74 7. Hovmark A, Asbrink E, Olsson I. Joint and bone involvement in Swedish patients with Ixodes ricinus-borne Borrelia infection. Zentralbl Bakteriol Mikrobiol Hyg (A) 1986;263:275-84 8. Huaux JP, Bigaignon G, Stadtsbaeder S, Zangerle’ PF, Nagant de Deuxchaisnes C. Pattern of Lyme arthritis in Europe: report of 14 cases. Ann Rheum Dis 1988;47:164-5 9. Kryger P, Hansen K, Vinterberg H, Pedersen FK. Lyme borreliosis among Danish patients with arthritis. Scand J Rheum 1990;19:77-8 1 10. Stiernstedt G, Granstrom M, Hederstedt B, Skoldenberg B. Diagnosis of spirochetal meningitis by enzyme linked immunosorbent assay and indirect immunofluorescence assay in serum and cerebrospinal fluid. J Clin Microbiol 1985;21:819-25 1 1 . Gustafson R, Svenungsson B, Gardulf A, Stiernstedt G, Forsgren M. Prevalence of tick-borne encephalitis and Lyme borreliosis in a defined Swedish population. Scand J Infect Dis 1990;22:297-306 12. Eichenfield AH, Goldsmith DP, Benach JL. et al. Childhood Lyme arthritis: Experience in an endemic area. J Pediatr 1986;109~753-8 13. Culp RW, Eichenfield AH, Davidson RS, Drummond DS, Christofersen MR, Goldsmith DP. Lyme arthritis in children. J Bone Joint Surg 1987;69-A:96-9 14. Steere AC, Green J, Schoen RT, et al. Successful parenteral penicillin therapy of established Lyme arthritis. N Engl J Med 1985;3122369-74 15. Steere AC. Medical progress: Lyme disease. N Engl J Med 1989;321:586-96 16. Steere AC. Clinical definitions and differential diagnosis in Lyme arthritis. Scand J Infect Dis 1991;(Suppl 77):514 17. Herzer P. Joint manifestation in Lyme borreliosis in Europe. Scand J Infect Dis 1991;(Suppl 77):55-63 18. Dattwyler RJ, Vokman DJ, Halperin JJ, Luft BJ. Treatment of late Lyme borreliosis-randomised comparison of ceftriaxone and penicillin. Lancet 1988;1:1191-4 19. Habicht GS, Beck G, Benach JL. Lyme disease. Sci Am 1987;257:60-5 Received July 5, 1991. Accepted Jan. 20, 1992
Borrelia arthritis in Swedish children: clinical manifestations in 10 children S Hammers-Berggren, U Anderson' and G Stiernstedt Department of Infectious Diseases, Danderyd Hospital, Danderyd and Department of Pediatrics', S:t Goran's Hosphal. Stockholm. Sweden
Hammers-Berggren S, Anderson U, Stiernstedt G . Borrelia arthritis in Swedish children: clinical manifestations in 10 children. Acta Paediatr l992;8 1 :921-4. Stockholm. ISSN 0803-5253 Since 1986, serology against Borrelia burgdorferi has been performed on patients with arthritis admitted to the Division of Pediatric Rheumatology, S:t Goran's Hospital, Stockholm. We studied, retrospectively, the period 1986-88. Among 300 children with arthritis, 10 had positive titers against B. B. burgdorferi. Other causes of arthritis were excluded. The onset of Borrelia arthritis was throughout the year. Only 3 of the 10 children remembered an actual tick bite. No other manifestations of Lyme borreliosis were present simultaneously. The typical clinical picture was a relapsing unilateral arthritis of the knee. 0 Arthritis, Borrelia. children S Hammers- Berggren. Depariment of Infectious Diseases, Danderyd Hospital, 18288 Danderyd, Sweden
Lyme arthritis was first described in the USA by Steere et al. in 1976 (1). Most of the patients in the initial reports were children presenting with recurrent attacks of mono- or oligoarthritis, preceded by an erythema migrans in approximately 25% of the cases (2). In 1982, Burgdorfer et al. found the etiological agent of Lyme borreliosis, a spirochete later named Borrelia burgdorferi ( 3 ) . We now know that Lyme borreliosis may affect many organs, most often the skin, nervous system, joints and heart. In the USA, the reported frequency of arthritis has been rather high, whereas in Europe, arthritis is considered more uncommon. The number of published reports of the clinical features of Borrelia arthritis in Europe is still sparse (4-9). The aim of the present study was to describe the clinical picture and laboratory findings of Borrelia arthritis in Swedish children.
Material and methods Serum samples from all patients with arthritis admitted to the Division of Pediatric Rheumatology, S:t Goran Hospital, Stockholm, during the period 1986-88 were analyzed for antibodies against B. burgdorferi. An ELISA test with sonicated whole-cell antigen was used. The test procedure has been described previously (10). The ELISA titer was expressed as the optical density (OD) at 405 nm, multiplied by the serum dilution factor. IgM and/or IgG titers against B. burgdoferi of 2700, corresponding to the 98th percentile of titers obtained in sera from healthy individuals, were considered positive. A titer decline of at least 50% of initial titer levels against B. burgdorferi was considered significant. In all patients with a positive serology against B.
burgdorferi, serum samples were analyzed for antinuclear antibodies (ANA), rheumatoid factor (RF), antistreptolysin 0 titer and streptococcal anti-DNAse titer. Analysis was also performed with ELISA against Salmonella lipopolysaccharide BO and DO and against Yersinia enterocolitica type 3. Sedimentation rate and white blood cell count were analyzed in all patients. White blood cell count in synovial fluid was analyzed when arthrocentesis was performed. The records of the patients were reviewed retrospectively. Response to antibiotic therapy was defined as no relapse of arthritis within a follow-up period of six months after treatment.
Results Serum samples from approximately 300 children with arthritis were tested with serology against B. burgdorferi during the three-year study period. Ten patients (6 boys and 4 girls) aged 8-14 years had positive IgG titers. Two of the 10 children also had positive IgM titers (1 500 and 4500, respectively). IgG titer levels against B. burgdorferiin the 10 children are shown in Table 1. The majority of patients, (6/10) had high titers ( 22000). Three patients had moderately increased titers. Only patient had a slightly elevated titer. Seven of the 10 patients were admitted to the Division of Pediatric Rheumatology after referral from pediatric surgeons, 2 patients from general practitioners and 1 patient from a general pediatrician. Clinicalfeatures All 10 children were living in the Stockholm area. Three remembered an actual preceding tick bite within three months. None of the patients had noticed an erythema
922 S Hammers-Berggren el al. Table 1. Clinical and
ACTA PRDIATR 81 (1992)
laboratory data in 10 patients with Borrelia arthritis.
Patient No. Sex (M/F) Age at diagnosis (years) Affected joints at diagnosis
1 F 14 Left knee
No. of arthritis attacks before diagnosis 3 Duration of relapsing arthritides (months) I Sedimentation rate (mm/h) 20 Borrelia IgG titers at diagnosis 700-990 I 000- I990 2 2000 X Antinuclear antibodies Neg Rheumatoid factor 1/20 Antibiotic treatment and response See Fig. 1 Other treatment ia steroids synovectomy Follow-up time without symptoms after last treatment regime (months) 28
2 M 12 Both knees
3 F 9 Right knee, elbow, wrist
M 10 Left knee
5 M 8 Left knee
F 8 Both knees
7 F 10 Right knee
M 12 Right knee
9 M 8 . Left knee, Right elbow
10 M 13 Left knee
2
3
I
2
3
1
4
2
2
I 30
9 4
40
12
4 40
-
8 11
9 17
24
5
X
X
Neg nd
Neg Neg
X 1/25 1/20
X nd Neg
Neg nd
X Neg nd
4
6
32
8
18
X
X X Neg Neg
Neg 1 /20
X Neg nd
-
NSAID
ia steroids, NSAID
-
NSAID
NSAID
-
-
-
11
10
18
24
14
16
15
10
18
Neg= Negative; nd = not done; ia = intra-articular; NSAID = non-steroidal anti-inflammatory drugs.
was the preliminary diagnosis and in the remaining 8 patients, unspecified aseptic arthritis was suspected. None received antibiotics before the results of serology against B. burgdorferi were obtained. Antibiotic treatment is summarized in Fig. 1. The 8 patients who responded to initial treatment were all symptomless without any relapse during a median follow-up time of 14.5 months (range 10-24 months). None of the responders had received intra-articular steroids before antibiotic therapy. The 2 non-responders had both received intra-articular steroid injections before antibiotic treatment. Both these patients developed a long course with relapsing arthritides and received repeated antibiotic treatments (Fig. 1). One of the patients responded after treatment with ceftriaxone 1 g bid for 14 days, one year after initial treatment and had no further relapses during 18 months follow-up. The other nonresponder improved after synovectomy 15 months after initial treatment and remained well during a follow-up Laboratory jindings period of 28 months. Serum samples from 9 of the 10 Median sedimentation rate was 19 mm/h (range 4-40 patients showed a significant decrease in IgG titer mm/h). White blood cell count was normal in all during follow-up, although 5 of 10 patients still had patients. Synovial fluid from the knee joint was obtained positive IgG titers against B. burdorferi 1 1-28 months from 7 patients and showed 2-44 x lo9(median 12 x lo9) (median 15 months) after antibiotic treatment or surleucocytes/l, with 2 75% polymorphnuclears in all gery. The increased IgM titers in 2 patients also declined patients. R F was slightly increased to 1/20 (reference significantly. value < 1/20) in 3 patients and ANA was positive at a level of 1/25 (reference value < 1/10) in I patient. An Xray of the knee was made in 7 children and showed only soft tissue affection with effusion of joints. migrans. Onset of arthritis occurred all year round. Two patients had fever, fatigue and malaise; the remaining 8 children had no accompanying symptoms. One girl had suffered from stiff neck six months before the onset of arthritis, but lumbar puncture performed when the diagnosis of Borrelia arthritis was made showed no abnormalities. No other neurological symptoms were reported or noticed in any of the patients. The number of arthritis attacks is shown in Table 1. Eight patients had at least two attacks of arthritis before diagnosis, whereas 2 patients had just one single attack. On admission to the Division of Pediatric Rheumatology, 8 patients still had ongoing arthritis, while 2 patients had improved after arthrocentesis. Affected joints are shown in Table 1. Six patients had monoarthritis, 4 had oligoarthritis and all 10 had gonarthritis. Four patients had accompanying arthralgias.
Discussion
Treatment and follow-up In 2 of 10 patients, juvenile rheumatoid arthritis (JRA)
A positive titer against B. burgdorferi is no definite proof of the etiology of the patient’s arthritis. First, if the 98th
ACTA
Borrelia arthritis in Swedish children
P EDIATR 81 (1992) 7 ( patient no. 2. 3. 5. 6. 7. 9, 10 )
PcG i.v.
------
9 patients
-----
1 ( patient no. 1 )
responded
oral doxycycline (28 days)
--- oral doxycycline (50 days)
'.
(100-150mg/kg, lodays)
923
--- ceftriaxone (14 days) --- oral PcV (3 months)
--- synovectomy --- responded
1 ( patient no. 4 )
oral doxycycline (15 days)
--- oral PcV (4,5 months)
--- ceftriaxone (14 days) --- responded
Doxycycline oral
---
1 patient
----
( patient no. 8 )
responded
( 1 00mgx2.10 days, 1OOmgxl ,20 days )
Fig. 1 . Antibiotic treatment in 10 patients with Borrelia arthritis.
percentile is used there is still a 2% possibility of a false positive result. Second, epidemiological studies have shown that increased titers against B. burgdorferi, probably due to earlier clinical or subclinical exposure, are common in certain areas around Stockholm (1 1). However, the fact that the majority of the patients had high increased titer, far above titers seen in asymptomatic individuals, supports B. burgdorferi as the cause of arthritis in our patients. Consequently, this study shows that B. burgdorferi is one cause of arthritis in Swedish children. However, the frequency seems rather low, which is in agreement with other Scandinavian publications reporting Borrelia arthritis in children and adults ( 5 , 779). The clinical features and laboratory findings of Swedish children with Borrelia arthritis are similar to
those with Lyme arthritis described in the USA (2, 12, 13) and Borrelia arthritis patients reported previously from Europe (4-9). The most typical symptom was a recurrent arthritis of the large joints, especially the knee. The lack of a preceding erythema migrans might be explained by the fact that the study was retrospective. We observed low positive ANA and RF titers in a few children, but do not consider these titers as markers for JRA since similar findings have previously been reported from the USA in children with Lyme arthritis (12). This autoantibody formation may have been caused by polyclonal B-lymphocyte activation by the spirochete. In none of the patients was Borrelia arthritis suspected on clinical symptoms only probably because of a lack of a history of associated typical symptoms of Lyme
924
S Hammers-Berggren et al.
borreliosis, such as erythema migrans and facial palsy. In the present study, the children with Borrelia arthritis were aged 8-14 years. The highest incidence of monoarthritis of the knee due to JRA occurs between 24 years of age. Thus in elderly children with monoarthritis of the knee of unknown etiology, Borrelia arthritis may constitute a larger proportion of aseptic gonarthritis than in younger children. Because of the small number of patients with Borrelia arthritis in this study, no definite conclusions of response to antibiotic treatment could be drawn. However, the cure rate of iv penicillin G seems to be high, similar to that reported from the USA (14). Oral doxycycline was given to one of the patients in this study and might be an alternative in children older than eight years of age. Amoxycillin, together with probenecid, has also been reported to be effective in the treatment of Borrelia arthritis (15). When evaluating the clinical response to antibiotic treatment it is also important to remember that the disease might be self-limiting. According to Steere, the number of untreated patients who continued to have attacks of arthritis decreased by about 10-20% each year (16). Steere has also reported that therapeutic failure in some patients might be explained by genetic factors, as he found an increased frequency of HLA-DR4 in non-responders (1 6 ) . Development of chronic Lyme arthritis was shown to be associated with HLA-DR2 and HLA-DR4 (16). However, other authors have been unable to confirm this observation (17). The possibility that preceding intra-articular steroid injections may predict antibiotic treatment failure has been reported by others (14, 18). We do not know the reason for this, but one suggestion may be that the administration of intra-articular corticosteroids inhibits the formation of the macrophage-activating factor, gamma interferon. The consequence would be a persistence of intracellular bacterial antigen, selectively retained by macrophages, with reduced bacterial degradation capacity. Release of lipopolysaccharide and other bacterial products would initiate and maintain the synovitis by inducing monokine production (1 9). The results from the present study show that B. burgdorferi can be the etiologic agent of arthritis in Swedish children. We recommend serology against B. burdorferi to be performed in patients with mono- or oligoarthritis of unknown etiology. Furthermore, B. burgdorferi as the cause of arthritis should be excluded before the administration of intra-articular corticosteroids. When Borrelia arthritis is present, adequate antibiotic therapy should precede a possible need for intra-articular corticosteroids.
ACTA PRDIATR SI (1992)
References 1 Steere AC, Malawista SE, Snydman DR, Andiman WA. A cluster
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