Epidemiology and risk factors for avascular necrosis in childhood systemic lupus erythematosus in a Taiwanese population

Abstract

Childhood-onset systemic lupus erythematosus (SLE) is associated with greater disease activity, more aggressive course, and high rates of organ damage. The prolonged use of corticosteroids in childhood SLE contributes to increased morbidity, including avascular necrosis (AVN). We conducted this retrospective study using claims data from the Taiwan National Health Insurance Research Database, enrolling 1,472 children with newly-diagnosed SLE between 2005 and 2013. The mean age at the diagnosis of SLE was 15.5 ± 3.3 years, and the female to male ratio was 6.2:1. Thirty-nine patients (2.6%) developed symptomatic AVN during a mean follow-up of 4.6 ± 2.5 years. In multivariate analysis, the risk of AVN was higher in the patients with a daily prednisolone dose between 7.5 mg and 30 mg (HR 7.435, 95% CI 2.882–19.178, p < 0.001) and over 30 mg (HR 9.366, 95% CI 2.225–39.418, p = 0.002) than in those with a dose ≤ 7.5 mg/day. In addition, AVN was inversely correlated with the use of hydroxychloroquine > 627 days (HR 0.335, 95% CI 0.162–0.694, p = 0.003). In conclusion, high daily doses of prednisolone were associated with a significant risk of AVN, whereas the use of hydroxychloroquine > 627 days conferred an advantage. We suggest that the judicious use of corticosteroids combined with hydroxychloroquine might be a promising preventive strategy for AVN.

Glucocorticoid‐induced osteonecrosis in systemic lupus erythematosus patients

“…A recent retrospective study of the Taiwanese population involved 1472 children newly diagnosed with SLE, and 1364 of these patients had DMARDs as a part of their management. 98 Although the patients did not have statistically different usages of DMARD's between the ON and non‐ON groups, the cumulative duration of hydrocychloroquine use was significantly correlated with ON. Association between the use of biologic DMARDs, including Bellimumab 121 and Rituximab, and ON in SLE patients has not been established yet, although Rituximab, an anti‐CD20 antibody, has been suggested as a cause of medication‐related ON of the jaw.…”

“…Glucocorticoid exposure is a well‐recognized risk factor for ON in SLE patients (Table 1 ). 15 , 16 , 17 , 34 , 35 , 39 , 40 , 41 , 43 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 54 , 55 , 56 , 57 , 58 , 59 , 64 , 65 , 66 , 67 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 In particular, the correlation between ON and the doses of glucocorticoid (GC) therapy has been identified in many studies (Table 1 ) and higher doses of GC therapy have been cited as one of the strongest predictive factors for developing ON. Twenty‐four of 49 studies shown in Table 1 found a significant correlation between the dose of GC therapy and the occurrence of ON in patients with SLE.…”

Corticotrophins, corticosteroids, and prostaglandins

“…The prolong use of corticosteroids in patients with childhood systemic lupus erythematosus (SLE) was shown to increase morbidity and including avascular necrosis (AVN) which is defined as the death of bone due to compromised blood flow. In a retrospective study of 1472 children (mean age 15.5 ± 3.3 years) with newly-diagnosed SLE, 39 patients (2.6%) developed symptomatic AVN during a mean follow-up of 4.6 ± 2.5 years ( Tsai et al, 2020 ) [M]. The multivariate analysis showed that the risk of AVN was higher taking higher dose prednisolone (7.5–30 mg) (HR 7.435, 95% CI 2.882–19.178, P < 0.001) and greater than 30 mg/day (HR 9.366, 95% CI 2.225–39.418, P = 0.002) than in those with a dose ≤ 7.5 mg/day.…”

Identify differential inflammatory cellular and serology pathways between children and adult patients in the lupus registry

“…[ 9 ] Very few clinical studies have compared age-difference SLE characteristics, [ 10 ] but have obtained a similar result, which is that the younger the age of SLE patients, the more severe the disease is. A national-wide healthy insurance registry study analyzed the characteristics of avascular necrosis in childhood SLE [ 11 ] and found 1472 children with newly-diagnosed SLE between 2005 and 2013 in Taiwan. This finding may reflect a significant financial burden if the disease activity is not well-controlled among these SLE children.…”