Journal Information
Vol. 93. Issue 4.
Pages 259-261 (01 October 2020)
Vol. 93. Issue 4.
Pages 259-261 (01 October 2020)
Scientific Letter
DOI: 10.1016/j.anpede.2019.12.011
Open Access
Juvenile idiopathic arthritis and Turner’s syndrome
Artritis idiopática juvenil y síndromede Turner
Patricia Lavillaa,
Corresponding author

Corresponding author.
, Ángela Manzanaresb, Elena Rabadána, Jaime de Inocenciob,c
a Servicio de Reumatología, Hospital Universitario Doce de Octubre, Madrid, Spain
b Unidad de Reumatología Pediátrica, Servicio de Pediatría, Hospital Universitario Doce de Octubre, Madrid, Spain
c Departamento de Salud Pública y Materno-Infantil, Universidad Complutense de Madrid, Madrid, Spain
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Tables (1)
Table 1. Published cases of patients with Turner syndrome and juvenile idiopathic arthritis.
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To the Editor:

Turner syndrome (TS), which is associated with complete or partial monosomy of the X chromosome, is one of the most frequent and best-known chromosomal disorders. In addition to the typical features, such as short stature and amenorrhoea, affected girls are at higher risk of having other diseases compared to the general population, including autoimmune disorders. The association of TS with autoimmune thyroiditis, type 1 diabetes and inflammatory bowel disease has been solidly established, but its association with juvenile idiopathic arthritis (JIA) is not as well understood. We present the cases of 3 girls with TS and JIA managed in our hospital whose diagnosis elicited uncertainty or unnecessary treatments and the results of a literature review that confirms that while the association is infrequent, it is nevertheless well established.

The 3 patients had a 45 × 0 karyotype. In 2 cases, the diagnosis was made in the neonatal period, and in 1 case it was made antenatally by means of amniocentesis. All 3 patients started growth hormone replacement therapy at age 3–4 years. All 3 received the diagnosis of TS years before JIA was diagnosed, and the history of TS had not been considered significant in any of them for the purpose of referral to rheumatology.

A girl aged 7 years was referred for evaluation of monoarthritis in the left knee identified a month prior. In December 2016, the patient underwent arthrocentesis for obtention of a synovial fluid sample that had features consistent with inflammation (13 500 white blood cells [WBCs]/mm3; 80% mononuclear cells; glucose concentration, 49 mg/dL, protein concentration, 4.8 g/dL). The patient received a diagnosis of JIA and treatment with intraarticular corticosteroids. Three months later she had a relapse in the same knee, leading to initiation of treatment with subcutaneous methotrexate (MTX), with a good response. The girl remained in remission for the following 12 months, so MTX was discontinued. After 5 months without treatment, in January 2019 the patient experienced a relapse in the left knee, leading to resumption of treatment with MTX. She is currently in remission.

The second case corresponded to a girl that had undergone surgical correction of tetralogy of Fallot that was haemodynamically stable and presented at age 5 years with arthritis in the right knee concurrent with a streptococcal infection (scarlet fever). Two weeks later she presented with arthritis in the contralateral knee and was admitted to receive intravenous antibiotherapy. She did not improve with treatment, so she was referred to the department of rheumatology for evaluation. Given the history and course of disease, with persistence of mild synovitis in the right knee, the patient received a diagnosis of oligoarticular JIA. She underwent arthrocentesis in both knees, with examination of synovial fluid revealing inflammatory features (WBC count, 9500 cells/mm3; 80% polymorphonuclear cells; glucose, 52 mg/dL, protein concentration, 5.3 g/dL). The patient received intraarticular corticosteroids and exhibited a partial response, which prompted initiation of subcutaneous MTX. She is currently in remission.

The third patient was a girl aged 6 years with a personal history of monoarthritis in the right knee and a previous arthrocentesis that had revealed inflammatory features in the synovial fluid (WBC count, 8700 cells/mm3; 60% mononuclear cells; glucose concentration, 66 mg/dL, protein concentration, 5.2 g/dL). She was referred to the department of rheumatology and given a diagnosis of oligoarticular JIA in January 2019. She has been treated with intraarticular corticosteroid injections and is currently in remission without treatment.

All 3 patients had negative results of tests for detection of antinuclear antibodies (ANA), rheumatoid factor (RF) and HLA-B27 antigen. None had associated uveitis or other autoimmune disorders.

There are previous descriptions of the association between X monosomy and JIA in the literature (Table 1). Most articles on the subject correspond to single case reports,1–3 although there are also case series4,5 of up to 18 patients.6 The largest case series corresponds to a multicentre study with participation of 28 rheumatology centres in Europe and North America and followup of approximately 15 000 patients with JIA. Based on the number of identified patients, the authors estimated that the prevalence of the association of TS and JIA was six times greater than expected.6 A more recent study using the Danish Cytogenetic Central Register that reviewed a cohort of 798 women with TS followed up for 12,461 person‐years concluded that these patients had double the risk of developing an autoimmune disease compared to the general population, with a standardized incidence ratio for JIA (ratio of the observed number of cases to the expected number of cases) of 4.4 (Jørgensen et al., Arthritis Rheum. 2010;62:658–666).

Table 1.

Published cases of patients with Turner syndrome and juvenile idiopathic arthritis.

Author (year of publication)  N  Karyotype  Age at diagnosis of TS  Age at diagnosis of JIA  Age at onset of joint symptoms  JIA oligo/poly  ANA  RF  HLA-B27  Affected joints  Bone erosion  Other autoimmune diseases 
Kohler et al (1981)  46Xi (Xq)  14 years  15 years  15 years  Oligo  NA  NA  Pos  Knees and 2 MCPs  NA  Crohn disease 
    45X/46XX mosaicism  15 years  15 years  15 years  Oligo  NA  NA  NA  Left knee  NA  Crohn disease 
Balestrazzi et al (1986)  45X/46XX mosaicism  8 years  8 years  6 years  Oligo  1/160  NA  NA  Left knee., right 2nd finger, left 3rd finger.  NA  No 
Foeldvari et al (1997)  45X/46XX mosaicism  10 years  16 years  8 years  Poly  NA  NA  Pos  Hands, wrists, elbows, knees and hips  No  No 
Zulian et al (1998)  18  11 Oligo, 45X (n = 6), 45X/46XX (n = 2), other (n = 3)  1 month-17 years (mean 5 years and 5 months)  1,7−12 years (mean 5 years and 8 months)  NA  Oligo  Pos 8/11  Neg 8/8  Neg in 5/5  Knee (11/11), ankle (4/11), MCP/PIP (2/11), elbow (1/11)  No  NA 
    7 Poly, 45X (n = 6) and 45X/46XX  8 months-16 years (mean 6 years and 1 month)  15 months-4.6 years (mean 3 years and 3 months)  NA  Poly  Pos 1/7  Pos 1/7  Neg in 1/1  Knee 6/7, hip 6/7, ankle 5/7, wrist 3/7, cervical spine 1/7  Yes  NA 
Wilhborg et al (1999)  45X/46X (Xq) mosaicism  9 years  12 years  3 years  Poly  Neg  Neg  NA  Hands, wrists, knees, cervical and lumbar spine  Yes (feet)  No 
    45X/46X (Xq) mosaicism  6 years  15 months  15 months  Poly  Neg  Neg  NA  Hands, elbows, knees and feet  yes (carpals, ulna, elbows, metatarsals)  No 
    45X  1 month  9 years  9 years  Poly  Neg  Neg  NA  MCP, PIP, carpal bones, wrists, elbow, knees  Yes  No 
Inamo et al (2000)  45X/46XX mosaicism  NA  14 years  14 years  Poly  Neg  Neg  NA  bilateral PIPs, right elbow, wrists, right knee and ankle  NA  Diabetes mellitus, Hashimoto disease 

ANA, antinuclear antibodies; MCP, metacarpophalangeal joint; NA, data not available; Neg, negative; Oligo: oligoarticular; PIP, proximal interphalangeal joint; Poly: polyarticular; Pos, positive; RF, rheumatoid factor; TS, Turner syndrome.

The presentation of arthritis in JIA may be oligoarticular (up to 4 affected joints) or polyarticular (5 or more affected joints), with variability in the detection of ANA and HLA-B27 antigen and the presence of bone erosion. Additional autoimmune disorders are frequently reported, especially inflammatory bowel disease in HLA-B27-positive patients.

In conclusion, the prevalence of JIA in girls with TS is greater than expected for a random association. This must be taken into account in the evaluation of patients with TS that develop musculoskeletal manifestations suggestive of arthritis (joint swelling, limping or morning stiffness).

P. Balestrazzi, G.F. Ferraccioli, U. Ambanelli, G. Giovannelli.
Juvenile rheumatoid arthritis in Turner’s syndrome.
Clin Exp Rheumatol, 4 (1986), pp. 61-62
I. Foeldvari, A. Wuesthof.
Delayed diagnosis of juvenile rheumatoid arthritis in a girl with Turner’s syndrome.
Clin Exp Rheumatol, 15 (1997), pp. 701-703
Y. Inamo.
Juvenile arthritis in Turner’s syndrome.
Clin Exp Rheumatol, 18 (2000), pp. 267-268
J.A. Kohler, D.B. Grant.
Crohn’s disease in Turner’s syndrome.
Br Med J (Clin Res Ed), 282 (1981), pp. 950
C.E.M. Wihlborg, P.S. Babyn, R. Schneider.
The association between Turner’s syndrome and juvenile rheumatoid arthritis.
Pediatr Radiol, 29 (1999), pp. 676-681
F. Zulian, H.R. Schumacher, A. Calore, D.P. Goldsmith, B.H. Athreya.
Juvenile arthritis in Turner’s syndrome: a multicenter study.
Clin Exp Rheumatol, 16 (1998), pp. 489-494

Please cite this article as: Lavilla P, Manzanares Á, Rabadán E, de Inocencio J. Artritis idiopática juvenil y síndromede Turner. An Pediatr (Barc). 2020;93:259–261.

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