Indian Pediatrics 1999; 36:449-454 

Clinico-Immunological Profile of Juvenile Rheumatoid Arthritis at Chandigarh

JUVENILE rheumatoid arthritis (IRA) is the commonest rheumatological disorder of childhood(1). Although the exact incidence and prevalence figures of this disease are not available from our country, the condition has been reported from a number of centers in India(2-4). From these studies it appears that the disease profile in Indian children is somewhat different from that seen in the West. For instance chronic iridocyclitis which is reported to occur in up to 20% of children with pauciarticular IRA in the West(l), is extremely rare in India(2-4). Similarly anti- nuclear antibodies (ANA) are rarely found in Indian children. Some of the results of studies from India appear to be contradictory; while a few reports have found polyarticular type of IRA to be the commonest subtype(2,3), a series from Chennai has found pauciarticular type to be more common(4). The present study details the clinico-immunological profile of children with IRA seen in our center over the last 5 years and also highlights certain interesting findings seen in our patients.

Subjects and Methods

Children registered in the Pediatric Rheumatology and Immunology Clinic (PRC) were included in this study. All children fulfilled the American Rheumatism Association Juvenile Arthritis Criteria (ARA- JAC)(3), namely: (i) Age of onset <16 years; (ii) Persistent arthritis of one or more joints for at least 6 weeks; (iii) Exclusion of other diseases known to 'be associated with arthritis, (iv) Classification features in the first 6 months of onset of first symptom: (a) Systemic onset: Joint involvement with persistent/intermittent fever with or without rash or other organ involvement; (b) Pauciarticular onset: Arthiritis in four or fewer joints at on- set; and (c) Polyarticular onset: Arthritis in five or more joints at onset.

The medical records were analyzed with regard to details of clinical history and laboratory investigations.

Results

A total of74 patients, 48 boys and 26 girls with male female ratio 1.8:1 were included. Eleven (M:F = 4.5: 1) patients were of systemic onset type, 28 (M:F = 1.1: 1) were of polyarticular onset type and 35 (M:F = 2.8: 1) had pauciarticular onset disease. The mean age at onset of disease in systemic, pauciarticular and polyarticular onset JRA was 4.6:t3.1, 7.4:t3.1 and 7.0:t2.9 years,

respectively. Eleven patients (14.8%) were less than 5 years of age and the youngest was 9 months old. The salient clinical features of the three subtypes of JRA are shown in Table I. In pauciarticular onset JRA, knee, ankle and proximal interphalangeal joints were most commonly involved, whereas in polyarticular onset JRA wrist, elbow and ankle joints were more often involved (Table II). Temporomandibular joint was involved only in 3 patients of polyarticular onset type of JRA. Cervical spine was involved in 11 patients.

TABLE I

Clinical Features in Various JRA Subtypes
 

About three fourths of patients with systemic onset of JRA had hemoglobin less than 10 g/dl (Table III). Leukocytosis of> 10,000/cu mm was found in two third patients with systemic onset type and half of the polyarticular onset JRA. Almost all patients had erythrocyte sedimentation rate (ESR) of more than 20 mm in first hour. Rheumatoid factor was' positive in 2 patients of pauciarticular JRA. No patient from other subgroups had positive rheumatoid factor. ANA was positive only in one patient of systemic onset JRA. HLA B27 was positive in 4 out of 9 patients of pauciarticular onset JRA where this test was done.

TABLE II

Limb Joint Involvement in Various Subtypes of JRA

Figures in parentheses are percentages.

TABLE III

Hematological Parameters in JRA
 

Aspirin, naproxen, chloroquine and methotrexate were used in 63.5%, 44.5% 9.4% and 10.8% of patients, respectively. A short course of steroids was used in 25 (33.7%) patients who had severe illness. Of these 14 had systemic onset IRA, 7 had pauciarticular onset IRA and rest were of polyarticular onset type. Intra-articular steroids (triamcinolone) were used in two patients with pauciarticular disease having pre- dominantly knee joint involvement. Two of our patients with polyarticular onset disease developed secondary amyloidosis. One of these patients was on irregular treatment for 3 years and developed renal failure secondary to amyloidosis. This patient died due to septicemia and bleeding diathesis. The second patient was diagnosed to have amyloidosis on abdominal fat pad biopsy at 5 year follow up. He does not have renal function impairment till now.

Discussion

Although, juvenile rheumatoid arthritis is not a rare disease, its true frequency is not known in our country. In the West its incidence is reported to be 6-8 cases/1,00,000 population per year(5). JRA has been divided into various subgroups. This categorization helps in diagnosis, follow-up and subsequent care of these children(6). The commonest type of JRA in our experience is pauciarticular onset type JRA-a finding which is in consonance with an earlier study( 4). However other workers from India have found polyarticular JRA to be more common(2,3). Although, it is difficult to provide an explanation for these differences, it may be related to the different genetic backgrounds of the populations under study. It is known that some HLA haplotypes are closely associated with certain subtypes'of JRA(1). All patients with pauciarticular onset disease were males and had onset of disease in late childhood, so they can be considered to have pauciarticular type 2 disease.

All series on JRA from India (including ours) have reported a male preponderance in contrast to a female preponderance reported elsewhere(l-4). While it is possible that this male preponderance may represent a biological characteristic of the disease seen in India, another explanation may be related to the fact that in our country, boys are cared for much more than girls by their parents. Consequently they are more likely to be brought to hospital for treatment than girls. This phenomenon may be as relevant for JRA as it is for many other chronic diseases in our country.

The age of onset of JRA is usually 1-3 years and the disease is unusual below 6 months of age. It appears that JRA in India has a somewhat later age of onset as compared to the West. The mean age of onset in present series for systemic, pauciarticular and polyarticular onset JRA was 4.6:t3.1, 7.4:t3.1 and 7.0:t 2.9 years, respectively. These figures are comparable to earlier series(2,3). However, the mean age of onset for the three subtypes of JRA in. the Chennai series was 6.1, 12 and 10.5 years, respectively(4). Unlike studies from western countries, we had a very low incidence of uveitis (Table IV). Uveitis could be detected only in one patient in spite of routine slit lamp examination of all patients by an ophthalmologist. Low frequency of uveitis has been a uniform finding in all Indian series reported so far. Occurrence of uveitis is closely related to ANA positivity(6), which again is reported to be very low in Indian children with JRA. Thus low rates of ANA positivity and infrequent occurrence of uveitis are certain unique features of the disease as seen in India. Rheumatoid nodules were present in 5.4% patients. Other Indian workers have reported rheumatoid nodules in 3-8% patients(3,4) but a series(2) found these in only 0.8%. In the western literature, rheumatoid nodules have been reported in up to 10% of such patients(1).

TABLE IV

Clinico-Immunological Profile of JRA in Various Studies

Rheumatoid factor (RF) positivity is seen in 15-20% children with lRA(1). Two Indian series(2,3) have also reported similar figures. However, we found rheumatoid factor positivity in only two (2.7%) patients. This could be because of greater proportion of pauciarticular disease in our series as compared to polyarticular predominance seen by other Indian workers(2,3). Rheumatoid factor positivity is seen more often in polyarticular IRA(l). We performed RF by latex agglutination and differential sheep cell agglutination technique. It is known that some children with IRA have IgA rheumatoid factor and if special immunological techniques are used to detect this, rheumatoid factor positivity rates automatically go up. Rheumatoid factor positivity is said to be closely associated with occurrence of rheumatoid nodules(1). However, in our series none of the four children who had rheumatoid nodules were positive for rheumatoid factor.
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HLA B27 positivity has been reported in upto 9% patients with IRA(7). It has been associated with male sex, older age at disease onset and in children with pauciarticular disease(7). In our series, HLA-B27 positivity was seen in 4 out of 9 children with pauciarticular IRA where this investigation was carried out. All were males and had disease onset after the age of 9 years. These patients are being followed up for development of ankylosing spondylitis(8).

One of the common causes of mortality in children with IRA relates to developement of secondary amyloidosis, a complication which is believed to occur in 5% of patients with this disease(1). However none of the Indian studies on IRA have documented amyloidosis. We diagnosed amyloidosis in 2 of our children(9). Both of these children had polyarticular disease, poorly responsive to therapy. At our center screening for amyloidosis is done by fine needle aspiration biopsies of abdominal fat pad.

Non steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment of IRA. Aspirin is the most useful NSAID in the treatment of IRA as it is safe, effective and economical. We have used aspirin in majority of patients and have not noticed any major side effects. Naproxen is another useful alternative therapy because of its prolonged half life allowing twice a day dosing(10).

Second line agents in the management of IRA are disease modifying antirheumatic drugs which are used when NSAIDs alone are not effective in controlling the disease(11). Methotrexate is the most frequently used drug of this category(l2). We have used methotrexate in 8 patients with good response. Long term followup will reveal whether or not there will be toxicity and side effects. Chloroquine can be used only in older children, because it is difficult to monitor visual fields in young subjects. Even in such patients chloroquine was never found to be very useful in inducing remission. Glucocorticoids have been used for acute and severe life threatening disease, for rapidly progressive disease and uveitis. We have frequently used short courses of steroids in severely symptomatic patients and have found them to be quite effective. Intra-articular steroids are useful for monoarticular arthritis or in a child with polyarticular disease where a single joint is resistant to systemic therapy(1). Our experience with intra-articular steroids is however, very limited.