Childhood-onset Systemic Lupus Erythematosus With Trisomy X and the Increased Risk for Bone Complications: A Case Report

Abstract Background: Childhood-onset systemic lupus erythematosus is a multi-organ inflammatory autoimmune disease mediated by immune complexes with the age of onset before 18 years. Trisomy X is the most common female chromosomal abnormality and the role of an additional X chromosome in the development of systemic lupus erythematosus is well recognized. However, the potential complications and optimal management of childhood lupus with trisomy X remain unclear. Herein, we describe a case of childhood-onset systemic lupus erythematosus associated with severe bone complications presumably secondary to trisomy X.Case presentation: A 16-year-old Japanese girl was diagnosed with childhood-onset systemic lupus erythematosus and trisomy X. A chromosomal abnormality (47, XXX) was incidentally identified on bone marrow examination initially done to determine the cause of pancytopenia. She was initially treated with intravenous methylprednisolone pulse therapy and prescribed monthly cyclophosphamide, prednisolone, mycophenolate mofetil, and hydroxychloroquine as remission maintenance drugs. She developed generalized extremity pain that had been worsening over the course of the disease. Extremity magnetic resonance imaging performed 12 months after the treatment onset revealed multifocal avascular necrosis, and dual-energy X-ray absorptiometry revealed further deterioration and osteoporosis. High plasma levels of factor VIII were detected by additional tests for coagulation functions. Conclusions: An additional X chromosome has been reported to be associated with factor VIII and osteoporosis. Additionally, elevated plasma levels of FVIII is the risk factors for thrombosis, which leads to the risk of avascular necrosis. Patients with systemic lupus erythematosus complicated by trisomy X are at a higher risk of avascular necrosis and osteoporosis that can also manifest in childhood systemic lupus erythematosus.

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Childhood‐onset systemic lupus erythematosus with trisomy X and the increased risk for bone complications: a case report

Pediatric Rheumatology ◽

10.1186/s12969-021-00507-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Susumu Yamazaki ◽

Yuko Akutsu ◽

Asami Shimbo ◽

Masaki Shimizu ◽

Yuko Segawa ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Factor Viii ◽

Avascular Necrosis ◽

Lupus Erythematosus ◽

Chromosomal Abnormality ◽

Childhood Onset ◽

Systemic Lupus ◽

Trisomy X ◽

Bone Complications ◽

Onset Systemic Lupus Erythematosus

Abstract Background Systemic lupus erythematosus is a multi-organ inflammatory autoimmune disease; immune complexes are part of the pathogenesis, but not entirely responsible. Trisomy X is the most common female chromosomal abnormality and the role of an additional X chromosome in the development of systemic lupus erythematosus is well recognized. However, the potential complications and optimal management of childhood lupus with trisomy X remain unclear. Herein, we describe a case of childhood-onset systemic lupus erythematosus associated with severe bone complications presumably secondary to trisomy X. Case presentation A 16-year-old Japanese girl was diagnosed with childhood-onset systemic lupus erythematosus and trisomy X. A chromosomal abnormality (47, XXX) was incidentally identified on bone marrow examination initially done to determine the cause of pancytopenia. She had a persistent headache, fever　for six days, diffuse hair loss, mucosal ulcers, butterfly eruptions, and palmar erythema. Furthermore, thrombocytopenia, anemia, and erythrocyte fragmentation were detected, suggesting secondary thrombotic microangiopathy. She was initially treated with intravenous methylprednisolone pulse therapy and prescribed monthly cyclophosphamide for severe disease activity, prednisolone, mycophenolate mofetil, and hydroxychloroquine as remission maintenance drugs. She developed generalized extremity pain that had been worsening throughout the disease. Extremity magnetic resonance imaging performed 12 months after the treatment onset revealed multifocal avascular necrosis, and dual-energy X-ray absorptiometry revealed further decreased bone mineral density. High plasma levels of factor VIII were detected by additional tests for coagulation functions, and we suspected the possibility that factor VIII might cause avascular necrosis due to thrombosis. Currently, she is being treated with prednisolone and MMF for SLE. However, her extremity pain has not been managed effectively even under the administration of non-steroidal anti-inflammatory drugs and pregabalin. Conclusions An additional X chromosome has been reported to be associated with factor VIII and osteoporosis. Additionally, elevated plasma levels of FVIII is the risk factors for thrombosis, which leads to the risk of avascular necrosis. Patients with systemic lupus erythematosus complicated by trisomy X might be at a higher risk of avascular necrosis and osteoporosis that can also manifest in childhood systemic lupus erythematosus.

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Trisomy X in a patient with childhood-onset systemic lupus erythematosus

Journal of Translational Autoimmunity ◽

10.1016/j.jtauto.2020.100043 ◽

2020 ◽

Vol 3 ◽

pp. 100043

Author(s):

Fernanda B. Barbosa ◽

Nailu Angelica Sinicato ◽

Paulo Rogério Julio ◽

Ana Carolina Londe ◽

Roberto Marini ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Childhood Onset ◽

Systemic Lupus ◽

Trisomy X ◽

Onset Systemic Lupus Erythematosus

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Risk Factors for Symptomatic Avascular Necrosis in Childhood-onset Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.150464 ◽

2015 ◽

Vol 42 (12) ◽

pp. 2304-2309 ◽

Cited By ~ 9

Author(s):

Yelin Yang ◽

Sathish Kumar ◽

Lily Siok Hoon Lim ◽

Earl D. Silverman ◽

Deborah M. Levy

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Avascular Necrosis ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Organ Involvement ◽

Childhood Onset ◽

Systemic Lupus ◽

Cns Disease ◽

Onset Systemic Lupus Erythematosus

Objective.To examine the frequency and risk factors for symptomatic avascular necrosis (AVN) in childhood-onset systemic lupus erythematosus (cSLE).Methods.A single-center, nested, matched, case-control design was used. There were 617 patients with cSLE followed at the Hospital for Sick Children (SickKids) Lupus Clinic between July 1982 and June 2013 included in the study. The AVN cohort consisted of 37 patients identified with clinical findings of symptomatic AVN and diagnosis was confirmed by 1 or more imaging modalities. Three controls were matched to each patient with AVN by date and age at diagnosis. Baseline clinical, laboratory, and treatment characteristics were compared between patients with AVN and controls by univariable analyses and if statistically significant, were included in a multivariable logistic regression model.Results.A total of 37/617 patients (6%) developed symptomatic AVN in 91 joints during followup at SickKids. The mean duration to disease was 2.3 years. The hip was the most commonly involved joint (26/37, 70%). Compared with the matched non-AVN cohort, patients with AVN had a higher incidence of central nervous system (CNS) involvement and nephritis, required greater cumulative prednisone (PRED) from cSLE diagnosis to AVN, received a greater maximal daily PRED dose, and had more frequent use of pulse methylprednisolone therapy. Multivariable regression analysis confirmed major organ involvement (CNS disease and/or nephritis) and maximal daily PRED dose as significant predictors of symptomatic AVN development.Conclusion.Patients with cSLE with severe organ involvement including nephritis and CNS disease and higher maximal daily dose of PRED are more likely to develop symptomatic AVN.

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