Outcome in Juvenile Rheumatoid Arthritis in India

[Guest guest]

Outcome in Juvenile Rheumatoid Arthritis in India

Indian Pediatrics 2004;41:180-184

Abstract:

Juvenile rheumatoid arthritis (JRA) leads to significant morbidity due

to continued disease activity and drug toxicity. Retrospective analysis

of patients with JRA seen at a tertiary care hospital between 1990-2000

was done. Data regarding the type of onset, course of disease, joints

involved, treatment received, drug toxicity and outcome at last visit

were retrived from case records. There were 214 children (76

oligoarticular, 93 polyarticular and 45 systemic onset) with 135 of them

being boys.

At last followup, with median disease duration of 6 years; 128 had

active disease, 58 had stable disease and 28 had inactive disease.

Polyarticular group had the worst outcome with only 3 of the 93 having

inactive disease (13/76 in oligo articular group and 12/45 in systemic

onset disease).

Intramuscular gold and D-Penicillamine were associated with significant

drug toxicity. Outcome of children with JRA in our country is poorer as

compared to developed countries.

Key words: Juvenile rheumatoid arthritis, DMARD.

Juvenile rheumatoid arthritis is the most common cause of chronic

arthritis in childhood. It is a heterogeneous disease with three onset

types i.e., polyarticular, pauciarticular and systemic onset disease(1).

The major morbidity is related to chronic synovitis and joint

destruction. Amyloidosis and drug toxicity also contribute to morbidity.

Studies in eighties suggested that most patients with JRA are free of

symptoms when they reach adulthood(2), but recent studies reflect a less

favorable outcome with almost 40% of them continuing to have active

disease at the end of 10 years(3-9).

The data available are difficult to compare, due to use of different

diagnostic criteria for defining patients, proportion of patients of

each subset of JRA in the study cohort and study setting (hospital or

primary care). Population based cohort studies with stringent criteria

and long term follow-up are the best for studying the natural history

and outcome of a disease but are tedious and time consuming. Even though

hospital based study especially those from tertiary care centres cannot

be true representatives of the outcome in a population yet they provide

the first step in this regard. As yet there are no data from India

regarding outcome of JRA.

Patients and Methods

All patients attending the out patient clinic of Department of Clinical

Immunology at our institution with JRA (ACR criteria)(1) who had atleast

1-year follow-up with us were included in the study.

Case records of all these patients were screened and information

regarding the type of disease, course of disease, drugs received, side

effects of drugs, outcome and complications of disease was retrieved.

Sjogren syndrome was diagnosed based on symptoms and signs of dry eyes

and dry mouth.

Interstitial lung disease was diagnosed either on chest X-ray or high

resolution CT scan along with restrictive pattern on pulmonary function

tests.

Valvular dysfunction was confirmed on echocardio-graphy and color doppler.

Diagnosis of nephropathy was based on kidney biopsy.

Amyloidosis was confirmed by rectal biopsy or abdominal fat pad aspiration.

All patients with active disease received non-steroidal

anti-inflammatory drugs (NSAIDs). Patients with polyarticular disease

refractory to NSAIDs received methotrexate (10-15 mg/m2/week),

D-penicillamine 125-250 mg/day, intramuscular gold (l mg/kg/week to a

maximum of 50 mg/week). Low dose prednisolone was used for control of

symptoms. Patients with systemic onset disease received prednisolone

(0.5-1.0 mg/kg/day) for control of symptoms if disease was refractory to

NSAIDs. Patients requiring corticosteroids for more than 3 months were

given methotrexate or azathioprine. In patients with mainly joint

symptoms other DMARDs were used as for polyarticular disease.

In oligoarticular disease intial management included NSAIDs and

intraarticular steroids. In patients with polyarticular course or

persistent arthritis, salazopyrine was used at a dose of 40-50

mg/kg/day, or other DMARDs as in polyarticular disease.

Outcome at last visit was assessed as active disease: persistent

synovitis despite treatment; stable disease: absence of symptoms but

requiring drugs, and inactive disease: absence of symptoms and off drugs

for at least 6 months.

Results

There were 214 children with 76 having oligoarticular type, 93 with

polyarticular and 45 with systemic onset disease. The detailed

demographic data are given in Table I.

The median duration of follow-up was 2 years. Among children with

pauciarticular disease, ankle (75%) and knee (63%) were the most

frequently involved joints, followed by sacroiliac (38%), wrist (28%),

hip (26%), cervical spine (10%), elbow and shoulders. Enthesitis was

seen in 7 patients whereas uveitis was present in 10 patients. IgA

nephropathy, diagnosed on kidney biopsy was present in one patient and

valvular heart disease (non rheumatic aortic regurgitation) was seen in

2 patients.

Among these 76 patients, 13 had inactive disease, 24 had stable disease

and 39 had active disease. Fifty seven continued to have pauciarticular

course while 14 of them changed into a polyarticular type and 5 evolved

into juvenile ankylosing spondylitis.

In polyarticular disease, the joints involved were knees (87%), ankle

(85%), wrist (81%), small joints of hands (69%), elbow (68%), shoulder

(57%), hips (22%) and temporomandibular joint (5%). Extra-articular

manifestations included Sjogren’s syndrome in 2, small vessel vasculitis

in 3, uveitis in 4 and interstitial lung disease in 2 patients. One

patient had anterior atlanto-axial dislocation detected on cervical

spine radiograph without any neurological deficit. Among these, 31 (33%)

had rheumatoid factor and 4 had antinuclear antibodies in their sera.

All continued to have polyarticular disease except one patient who

developed inflamma-tory bowel disease.

Three had inactive disease, 26 had stable disease and 64 had active

disease at last follow-up. Patients with active disease had higher

baseline ESR value (54.8 mm vs 41.6 mm), longer duration of disease

(58.9 months vs 33.5 months) and presence of deformities (p <0.05) as

compared to those with stable or inactive disease at last follow-up.

In systemic onset type, all patients had fever whereas 24 had skin rash,

40 had lymphadenopathy and 41 had hepato-splenomegaly. The joints

involved were wrist (66%), elbow (58%), knee (60%), ankle (50%), small

joints of hands (42%). The mean ESR and CRP were 64 and 11.7 mg/dL

respectively. Anti-nuclear antibody was not present in any patient.

Among 45 children with systemic onset disease, 12 had inactive disease,

8 had stable disease and 25 had active disease. Two children developed

proteinuria due to secondary amyloidosis and were treated with

cyclophosphamide and predniso-lone (Table II). Proteinuria improved

partly with this treatment.

After a median disease duration of 6 years, 60% of patients continued to

have active arthritis, while 27% had stable disease and only 13% had

inactive disease.

The incidence of side effects with various agents were as follows:

NSAIDs (11%), oral prednisolone (23%), low dose methotrexate (13.5%),

intramuscular gold (5%), D-Pencillamine (20%), sulphasalazine (7%),

chloroquine (10%). Major side effects were more with D-Penicillamine and

intramuscular gold (Table III).

Discussion

In our study 87% of patients had active or stable disease after a median

disease duration of 6 years. In contrast, in a population based

study(3,4) from Sweden 49% of 124 patients had active or stable disease

at a median disease duration of 7.1 years. However, that study had a

poor representation of cases with systemic and polyarticular disease

(3.2% and 29% respectively) while in our study they constituted almost

65% of the study population. Systemic onset and polyarticular disease

are associated with higher long- term morbidity(3).

Another study(5) involving 506 consecutive patients with juvenile

chronic arthritis and having a median disease duration of 8.8 years at

follow-up found that remission rates were 45% for pauciarticular

disease, 35% for systemic onset disease and only 20% in the

polyarticular group. As our study was not limited to patients with new

onset disease, most patients already had persistent disease at the time

of presentation to this hospital and would be expected to have a worse

prognosis(6).

An overall response rate of 92% with drugs is encouraging even though

only 55% had a complete response. The complete response rate was

significantly less in polyarticular disease. Polyarticular disease

especially seropositive group has the least response to drugs(3).

However, we did not find any difference in the seropositive and

seronegative group.

Complications like uveitis are thought to have a significant impact on

outcome(10) in JRA. Incidence of uveitis was low in our study i.e. 2.2%

and none of the child had impaired vision due to uveitis. Previous

studies from India(1112) and Costa Rica(13) have also reported a low

prevalence of uveitis in patients with JRA.

Due to delay in therapy as well as continued disease activity, 2

patients with systemic onset disease developed secondary amyloidosis.

Our incidence of 1% is similar to previously reported low prevalence in

USA(14). However, studies from UK, with long term followup and use of

radionuclide scans have reported an incidence of 5-9% (10,15). It is

most frequent in patients with systemic onset disease as was seen in our

patients.

Drug toxicity was minimal with methotrexate but significant with gold

and D-penicillamine as has been reported earlier(16). Methotrexate due

to its superior efficacy-toxicity ratio has emerged as the single most

important DMARD in JRA. The 10% incidence of rash with sulphasalazine in

our study was less compared to 23% reported from Western countries(16)

and could be related to difference in genetic background.

The limitations of our study are retrospective collection of data,

tertiary care hospital source, lack of functional assessment and use of

older classification. Older classification has been used as patients

diagnosed before 1997 have been analyzed and retrospective

reclassification has its own problems. Still this study serves to

reflect that our children with JRA are not receiving optimum care at

peripheral level and an early referral is needed to improve the outcome.

We also need a long term, population inception cohort based study with

use of standardized instruments for measuring outcome including impact

on growth and childhood health assessment questionnaire.

Contributors: AA was involved in conception design, analysis, manuscript

revision and final approval. VA and DD helped in acquisition of data,

analysis, manuscript drafting and final approval. RM helped in design,

revision and final approval of manuscript.

Funding: None.

Competing Interests: None stated.

Key Messages

• Two third of patients with JRA, seen at tertiary care hospital

continue to have active disease at a median of 6 years after disease onset.

• Polyarticular disease has the worst outcome.

• Methotrexate is a safe disease modifying anti-rheumatoid drug in

patients with JRA.

Amita Aggarwal, Vikas Agarwal, Debasish Danda and Ramnath Misra

From the Department of Immunology, Sanjay Gandhi Postgraduate Institute

of Medical Sciences, Lucknow 226 014, India.

Correspondence to: Amita Aggarwal, Associate Professor, Department of

Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences,

Lucknow 226 014, India.

Manuscript received: August 28, 2002, Initial review completed: May 9,

2003; Revision accepted: June 26, 2003.

References:

1. Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ Jr, Fink CW, et

al. A study of classification criteria for the diagnosis of Juvenile

rheumatoid arthritis. Arthritis Rheum 1986; 29: 274-281.

2. Siegel DM, Braun J. Juvenile arthritis. Primary care 1983; 20: 883-893.

3. Gare BA, Fasth A. The natural history of juvenile chronic arthritis:

a population based cohort study.I. Onset and disease process. J

Rheumatol1995; 22: 295-307.

4. Gare BA, Fasth A. The natural history of juvenile chronic arthritis:

A population based cohort study. II. Outcome. J Rheumatol 1995; 22: 308-319.

5. Fantini F, Gerloni V, Gattinara M, Bergomi P, Mazzoti J, Arnoldi C,

et al. Remission in juvenile chronic arthritis: a cohort study of 506

consecutive cases (abstract). Arthritis Rheum 1996; 39 (suppl): S58.

6. Flato B, Aasland A, Vinje O, Foffe O. Outcome and predictive factors

in juvenile rheumatoid arthritis and juvenile spondylo-arthropathy. J

Rheumatol 1998; 25: 366- 375.

7. Graham TB, Lovell DJ. Outcome in pediatric rheumatic disease. Curr

Opin Rheumatol1997; 9: 434-439.

8. Wallace CA, Levinson JE. Juvenile rheumatoid arthritis: Outcome and

treatment for the 1990’s. Rheum Dis Clin North Am 1991; 17: 891-905.

9. Minden K, Kiessling U, Listing J, Niewerth M, Doring E, Meincke J, et

al. Prognosis of patients with juvenile chronic arthritis and juvenile

spondyloarthropathy. J Rheumatol 2000; 27: 225-2263.

10. Packham JC, Hall MA. Long term followup of 246 adults with juvenile

idiopathic arthritis: Functional outcome. Rheumatology (Oxford) 2002;

41: 1428-1435.

11. Singh S, Salafia M, Kumar L, Minz R, Datta U, Sehgal S.

Clinico-immunological profile of juvenile rheumatoid arthritis at

Chandigarh. Indian Pediatr 1999; 36: 449-454.

12. Aggarwal A, Misra R. Juvenile chronic arthritis in India: Is it

different from that seen in Western countries? Rheumatol Int 1994; 14:

53-56.

13. Arguedas O, Fasth A, Andersson-Gare B. A prospective population

based study on outcome of juvenile chronic arthritis in Costa Rica. J

Rheumato1 2002; 29: 174-183.

14. Pachman LM, Pozanski AK. Juvenile (rheumatoid) arthritis. In:

Koopman WJ, editor. Arthritis and Allied Conditions. 13th ed.

Philadelphia: and Wilkins; 1996, 1155-1177.

15. J, Vouyiouka O, Ansell BM, Hall A, Woo P. Amyloidosis in

juvenile chronic, arthritis: A morbidity and mortality study. Clin Expl

Rheumatol1993; 11: 85-90.

16. Furst DE. Toxicity of antirheumatic medications in children with

juvenile arthritis. J Rheumatol1992; 19 (supp133): 11-15.

17. Wallace CA. The use of methotrexate in childhood rheumatic diseases.

Arthritis Rheum 1998; 41: 381-391.