Polyarticular juvenile idiopathic arthritis – epidemiology and management approaches

Figures & data

Table 1 Classification of chronic arthritis of childhood

Organization	European League Against Rheumatism (EULAR)^Citation4	American College of Rheumatology (ACR)^Citation5	International League of Associations for Rheumatology (ILAR)^Citation1
Criteria name	Juvenile chronic arthritis	Juvenile rheumatoid arthritis	Juvenile idiopathic arthritis
Year	1977	1986	1997, revised 2001
Age of onset	<16 years	<16 years	<16 years
Duration	≥3 months	≥6 weeks	≥6 weeks
Subsets	1. Pauciarticular: <5 joints	1. Polyarthritis: ≥5 inflamed joints	1. Systemic
	2. Polyarticular: >4 joints, RF−	2. Oligoarthritis (pauciarticular disease): <5 inflamed joints	2. Oligoarthritis
	3. Systemic: arthritis with characteristic fever		a. Persistent
	4. Juvenile rheumatoid arthritis: >4 joints, RF+	3. Systemic onset: arthritis with characteristic fever	b. Extended
	5. Juvenile ankylosing spondylitis		3. Polyarthritis: RF−
	6. Juvenile psoriatic arthritis		4. Polyarthritis: RF+
			5. Psoriatic arthritis
			6. Enthesitis-related arthritis
			7. Undifferentiated
			a. Fits no other category
			b. Fits more than one category

Abbreviations: RF−, rheumatoid factor negative; RF+, rheumatoid factor positive.

Table 2 Epidemiologic studies of polyarticular juvenile arthritis

Country	Year	Percentage of all arthritis			Incidence per 100,000		Prevalence per 100,000		Girls:boys		Mean age at onset (years)		Criteria
		Polyarticular	RF−	RF+	RF−	RF+	RF−	RF+	RF−	RF+	RF−	RF+
Germany^Citation23	2001	9.0%	–	–	0.28	–	1.64	–	6:1	–	–	–	EULAR
US (MN)^Citation24	1993	12.0%	–	–	1.67	–	13.6a	–	2:1	–	–	–	ACR
Spain^Citation25	2010	12.4%a	10.3%a	2.1%a	0.70	0.10	3.70	0.70	14:1a	3:0	7.1a	11.3	ILAR
UK^Citation16	2008	15.8%	13.4%	2.4%	–	–	–	–	3.5:1	4.9:1	6.7	11.6	ILAR
US (MN)^Citation26	1996	17.0%	–	–	2.00	–	–	–	2.7:1	–	5.8	–	ACR
France^Citation27	2010	18.7%	16.7%	2.0%	–	–	2.60	0.31	8:0	1:0	9.4	–	ILAR
Belgium^Citation28	1993	20.0%	–	–	–	–	33.4	–	–	–	–	–	EULAR
Finland^Citation20	2001	20.0%	20.0%	0.0%	4.00	–	–	–	–	–	–	–	EULAR
France^Citation29	2006	22.4%	22.4%	0.0%	0.71	–	4.40	–	6.5:1	–	6.7	–	ILAR
Costa Rica^Citation30	1995	23.0%	–	–	1.24	–	–	–	1.5:1	–	–	–	EULAR
Canada^Citation17	2005	23.7%	20.6%	3.1%	–	–	–	–	2.4:1	7.5:1	6.3	11.1	ILAR
Spain^Citation31	2001	24.0%	22.4%	1.6%	–	–	–	–	3.6:1	2:0	4.5 (M)	11.3 (M)	ILAR
Estonia^Citation32	2007	24.0%	19.5%	4.5%	–	–	16.3	3.80	1.6:1	8:1	9.7	10.2	ILAR
Estonia^Citation21	2007	25.0%	20.6%	4.4%	4.40	0.90	–	–	2:1	6:1	9.9	11.5	ILAR
Japan^Citation33	1997	25.0%	12.5%	12.5%	–	–	–	–	–	–	–	–	ACR
Germany^Citation34	2001	28.5%	25.6%	2.9%	–	–	–	–	3.9:1	4:1	5.3	11.5	ILAR
India^Citation35	2010	28.9%	17.4%	11.5%	–	–	–	–	1.6:1	8:1	11.5 (M)	13.0 (M)	ILAR
Egypt^Citation36	2013	29.5%	21.2%	8.3%	–	0.72	–	0.28	1.6:1	2:1	9.1	11.5	ILAR
Canada^Citation37	1995	34.9%	–	–	1.85	–	–	–	–	–	–	–	ACR
Sweden^Citation38	1995	35.0%a	29.2%a	5.8%a	2.24	0.46	18.7	10.3	2:1	8:1	9.0 (M)	–	EULAR
Turkey^Citation39	2008	37.2%	30.6%	6.6%	–	–	–	–	0.8:1	2.3:1	5.7	10.4	ILAR
South Africa^Citation40	2013	41.0%	26.9%	14.1%	–	–	–	–	–	–	8.0 (M)	10.0 (M)	ILAR
Kuwait^Citation41	1990	42.0%	–	–	–	–	–	–	–	–	–	–	EULAR
Zambia^Citation42	2013	46.1%	34.6%	11.5%	–	–	–	–	1.7:1	9:1	10.7	11.0	ILAR
Czech Republic^Citation43	2006	50.0%	–	–	6.50	–	–	–	2:0	–	9.5	–	ILAR
India^Citation44	1994	51.7%	34.8%	16.9%	–	–	–	–	1.6:1	–	11.0	–	EULAR
Nigeria^Citation45	2010	57.0%	–	–	–	–	–	–	–	–	–	–	ILAR

Note:

a Range reported with upper limit displayed in table.

Abbreviations: ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; ILAR, International League of Associations for Rheumatology; RF−, rheumatoid factor negative; RF+, rheumatoid factor positive; M, median reported instead of mean; MN, Minnesota; –, not applicable.

Table 3 Human leukocyte antigen alleles associated with polyarticular juvenile idiopathic arthritis

Allele	Subtype	Association
A2^Citation68,Citation69	RF−	Susceptibility for early onset
DPB1*03^Citation68,Citation71	RF−	Susceptibility
DRB1*01^Citation70	RF−	Susceptibility
DRB1*0101^Citation70	RF+	Susceptibility, shared with adult RA
DRB1*04^Citation68,Citation72	RF+	Susceptibility
DRB1*0401^Citation71^–^Citation73	RF−	Protective
DRB1*0401^Citation70	RF+	Susceptibility, shared with RA
DRB1*0404^Citation70	RF+	Susceptibility
DRB1*0405^Citation70	RF+	Susceptibility
DRB1*0408^Citation70	RF+	Susceptibility shared with RA
DRB1*07^Citation72,Citation73	RF−, RF+	Protective
DRB1*08^Citation68,Citation72,Citation73	RF−	Susceptibility for late onset
DRB1*1103^Citation73	RF−	Susceptibility for early onset
DRB1*1104^Citation73	RF−	Susceptibility for early onset
DRB1*1402^Citation70	RF+	Susceptibility, shared with adult RA
DRB1*1501^Citation73	RF−	Protective
DQA1*02^Citation68,Citation72	RF+	Protective
DQA1*03^Citation68,Citation72	RF+	Susceptibility
DQA1*04^Citation68,Citation72	RF−	Susceptibility
DQA1*05^Citation72	RF+	Susceptibility
DQB1*03^Citation68	RF+	Susceptibility
DQB1*03^Citation72	RF−	Protective

Abbreviations: RA, rheumatoid arthritis; RF−, rheumatoid factor negative; RF+ rheumatoid factor positive.

Table 4 Medications for treatment of polyarticular juvenile idiopathic arthritis

Medication	Mechanism of action	Route	Type
Abatacept	Binds to CD80/CD86 and inhibits T-cell costimulatory signal	IV, SQ	Biologic
Adalimumab	TNF inhibitor	SQ	Biologic
Etanercept	TNF inhibitor	SQ	Biologic
Glucocorticoids	Decreases transcription of cytokines; many others	Oral, IA	Other
Infliximab	TNF inhibitor	IV	Biologic
Leflunomide	Pyrimidine synthesis inhibitor	Oral	DMARD
Methotrexate	Dihydrofolate reductase inhibitor; inhibits DNA synthesis; many others	Oral, SQ	DMARD
NSAIDs	Blocks prostaglandin formation	Oral	Other
Rituximab	Binds CD20 on B-cells	IV	Biologic
Sulfasalazine	Interferes with formation of leukotrienes and prostaglandins, causes accumulation of adenosine; inhibits bacterial growth; others proposed	Oral	DMARD
Tocilizumab	IL-6 inhibitor	IV, SQ	Biologic

Abbreviations: DMARD, disease modifying antirheumatic drug; IA, intra-articular; IL, interleukin; IV, intravenous; NSAIDs, nonsteroidal anti-inflammatory drugs; SQ, subcutaneous.

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