Pediatric Lupus—Are There Differences in Presentation, Genetics, Response to Therapy, and Damage Accrual Compared with Adult Lupus?

Some complement deficiencies predispose to systemic lupus erythematosus (SLE) early in life. Currently, there are no known unique physiologic or genetic pathways that can explain the variability in disease phenotypes. Children present with more acute illness and have more frequent renal, hematologic, and central nervous system involvement compared to adults with SLE. Almost all children require corticosteroids during the course of their disease; many are treated with immunosuppressive drugs. Mortality rates remain higher with pediatric SLE. Children and adolescents accrue more damage, especially in the renal, ocular and musculoskeletal organ systems. Conversely, cardiovascular mortality is more prevalent in adults with SLE.

An estimated 10% to 20% of patients experience the onset of systemic lupus erythematosus (SLE) before adulthood. More precise estimates are difficult due to a lack of a clear age limit for the diagnosis of pediatric SLE. The maximum age at diagnosis most commonly used to define pediatric SLE is 16 years but ages range from 14 to 20 years in various studies. This review article explores the differences and similarities between pediatric SLE and adult (aSLE), using studies that provide a direct comparison between groups. Issues pertaining to neonatal SLE are not addressed.

Gender ratio and disease onset

Albeit uncommon, onset of pediatric SLE is described even in children younger than 2 years of age. The female-to-male ratio of pediatric SLE changes from 4:3 with disease onset during the first decade of life to 4:1 during the second decade to 9:1 in aSLE and decreases to 5:1 in SLE commencing after age 50.

Pediatric SLE often presents with more acute and severe disease features than aSLE, based on studies providing direct comparisons. Almost all published research suggests a higher frequency of renal, neurologic, and hematologic involvement with pediatric SLE than with aSLE at the time of diagnosis. In a Canadian inception cohort of 67 pediatric SLE patients, the average disease activity score, as measured by the SLE Disease Activity Index, was 16.8 at diagnosis but only 9.3 in the comparison group of 131 patients with aSLE ( P = .0001). The most pronounced differences in disease activity between aSLE and pediatric SLE pertain to the renal or neurologic organ systems.

Despite widely variable estimates, fever and lymphadenopathy are more frequently described with pediatric SLE than aSLE in studies directly comparing both groups ( Table 1 ). Conversely, adults with SLE more commonly present with arthritis than children with SLE. When comparing prepubertal to postpubertal onset of pediatric SLE, the former group presents more often with hemolytic anemia and renal involvement whereas in the latter group cutaneous and musculoskeletal features are more common at disease onset. As with aSLE, approximately one-third of the children and adolescents with SLE present with anemia, thrombocytopenia, or lymphopenia at the time of SLE onset. On the contrary, leukopenia is more common in pediatric SLE than aSLE at onset (31% to 35% vs 18%), and 49% of children with SLE as compared to 18% to 65% of aSLE patients test Coombs positive at the time of diagnosis. Equally frequent in pediatric SLE and aSLE at the time of initial presentation (5% to 20%) are anti-Smith (anti-Sm), antiribonucleoprotein (anti-RNP), anti-Ro, and anti-La antibodies, as suggested by one study.

Table 1

Clinical and laboratory features in pediatric and adult systemic lupus erythematosus at disease onset ^a

Study	Carreno 1999 ^b			Font 1998 ^c
Clinical Findings	pedSLE (n = 49)	aSLE (n = 130)	P Value	pedSLE (n = 34)	aSLE (n = 396)	P Value
Fever	20	15	NS	41	21	0.006
Lymphadenopathy	—	—	—	6	0.5	0.03
Malar rash	22	16	NS	44	35	NS
Discoid lupus	—	—	—	0	3	NS
Subcutaneous cutaneous lupus	—	—	—	0	3	NS
Livedo reticularis	—	—	—	3	0.5	NS
Oral ulcers	—	—	—	9	13	NS
Photosensitivity	—	—	—	23	20	NS
Arthritis	22	39	<0.05	65	62	NS
Arthalgias	26	23	NS	—	—	—
Myositis	—	—	—	3	4	NS
Nephropathy	—	—	—	20	9	0.04
Neurologic involvement	—	—	—	0	6	NS
Chorea	—	—	—	3	0	NS
Serositis	—	—	—	12	13	NS
Pleuritis	6	6	NS	—	—	—
Lung involvement	—	—	—	0	1	NS
Hemolytic anemia	—	—	—	9	3	NS
Thrombocytopenia	—	—	—	12	9	NS
Vasculitis	8	2	NS	—	—	—
Cutaneous vasculitis	—	—	—–	—	—	—
Raynaud phenomenon	8	8	NS	12	16	NS
Thrombosis	—	—	—	0	1	NS
Sicca syndrome	—	—	—	0	0.5	NS