Unité d'Immunohématologie et Rhumatologie Pédiatriques, Hôpital des Enfants Malades, and
1 Service d'Immunologie Clinique, Hôpital Necker, Université Paris V, Paris
2 Service d'Anatomopathologie and
3 Service de Chirurgie Maxillo-Faciale et Stomatologie, CHU Amiens and
4 Service de Médecine Interne, Centre Hospitalier de Beauvais, Beauvais, France
SIR, Sjögren syndrome (SS) is a very rare condition in childhood. Only single case reports or small groups of patients have been reported in the literature [14]. SS has been reported occasionally during the course of systemic lupus erythematosus or other connective tissue diseases in childhood, including a few cases of polyarticular-onset juvenile idiopathic arthritis (JIA), but never, to our knowledge, during the course of oligoarticular-onset JIA (OA-JIA). OA-JIA is the most frequent chronic inflammatory rheumatic condition in childhood, occurring mostly in girls before the age of 4 yr [5]. Chronic iridocyclitis is a frequent complication. The presence of non-specific antinuclear antibodies is characteristic of OA-JIA [6]. We report the case of a patient suffering from typical OA-JIA who developed SS at the age of 14 yr.
This young woman was followed since the age of 18 months for OA-JIA. Iridocyclitis was discovered at arthritis onset. The treatment was a combination of acetylsalicylic acid 70 mg/kg/day, intra-articular injection with triamcinolone hexacetonide and intraocular dexamethazone drops. At 9 yr an extension of joint involvement occurred, with a maximum of nine affected joints. Methotrexate 0.5 mg/kg/week was used for 4 yr with an excellent effect. At the same time, the severity of eye involvement led to the administration of 10 mg prednisone on alternate days. The first episode of salivary gland swelling occurred at the age of 15 yr, associated with mouth dryness, cervical adenopathies and a recurrence of joint manifestations. Laboratory investigations showed ESR 56 mm/1st h, 4500 leucocytes/mm3, hypergammaglobulinaemia 19.5 g/l (normal range 612 g/l), creatinaemia 87.5 µmol/l, ANA>1/640 with anti-Ro 60 kDa SSA and anti-La SSB specificity (482 and 1813 c.p.m. respectively in radioligand assay), anti-DNA antibodies 29% (Farr technique, normally <20%), anti-dsDNA (ELISA) IgG 130 UE (normally <30 SU), IgM 10 SU (normally<30 SU), RF nephelometry assay 159 UI/ml (normally<15 UI/ml) and complement activity 106% (normally 100±50%). Salivary gland biopsy showed lesions of focal lymphocytic sialadenity grade IV (Chisholm and Mason score). Eye investigations showed superficial punctuated keratitis and an abnormal Schirmer test result. At 18 yr, renal involvement occurred with creatinaemia 184 µmol/l (normal range 50100 µmol/l) proteinuria 1 g/day, haematuria 550 erythrocytes/mm3. Kidney biopsy showed four sclerotic glomeruli out of 17, no amyloid deposit, mononuclear cell infiltrate in the interstitium with fibrotic lesions, no vasculitis, negative immunofluorescence for IgA, IgG, C3, C1q, C4, fibrinogen and lambda and kappa chains. An intravenous methyl prednisolone (10 mg/kg) bolus was given on three consecutive days, in association with 0.5 mg/kg/day oral prednisone, progressively tapered. Prednisone 12.5 mg/day (0.25 mg/kg/day) was subsequently reintroduced for salivary gland enlargement without renal manifestations. Currently, the patient's status is satisfactory. The retrospective studies of autoantibodies from frozen serum samples are shown in Table 1. The HLA phenotype was HLA A1-2, B8-65, DRB1*0301-07, DQB1*0202, DPB1*02012-0401.
|
Our patient was affected by early-onset OA-JIA with chronic iridocyclitis, the most common rheumatic disorder in childhood [5]. The course of JIA was typical until the age of 15 yr. Criteria for SS were met at 18 yr, with the presence of oral symptoms, infiltration of organs by lymphocytes, objective parotid gland involvement, positive anti-Ro 60 kDa SSA and anti-La SSB antibodies and the presence of significant levels of RF [7]. Our patient also had renal involvement. The retrospective study of frozen sera allowed us to estimate the switch of the antinuclear antibodies to antibodies specific for SS and the occurrence of RF at the age of 14 yr (Table 1).
In children, recurrent parotid swelling is the most frequent clinical hallmark of SS [4]. Diagnostic criteria are similar to those proposed in adults. The serological features consist of levels of antinuclear antibodies in most cases, associated with the presence of anti-RO SSA (80% of the patients) and of anti-La SSB (50% of the patients). Rheumatoid factors are significantly increased in half of the cases [4]. None of these markers are specific for SS [7]. In our patient, other autoimmune diseases could be excluded, particularly systemic lupus erythematosus, as the kidney biopsy did not show any immunofluorescent deposit.
OA-JIA is a well-defined entity in which the occurrence of another autoimmune disease after several years follow-up is exceptional. Chronic uveitis is the most common visceral complication. Our patient presented with this manifestation at disease onset and it persisted throughout the disease duration [5]. OA-JIA is RF-negative [5], as our patient was for many years. The long-term outcome of OA-JIA is related to joint disability and/or ocular impairment after more than 20 yr [8]. Association of HLA-A2 with OA-JIA has been reported. The most frequent HLA class II allelic associations are DRB1*08 (DR8), DRB1*11/12 (DR5), DPB1*0201, DQA1*0401 and *0501 (DW8), DQB1*0301 (DQ7) and DQB1*0402 (DQ4) [9]. The particular interest of our observation is the unusual outcome of the oligoarthritis, with the appearance of the first clinical symptom of SS at 15 yr preceded by a switch of the specificity of the ANA to anti-Ro SSA 60 kDa and anti-La SSB. In a long-term follow-up of juvenile rheumatoid arthritis (JRA), Stillman and Barry [10] reported 11 patients out of 204 developing SS. Eight had polyarticular and three had oligoarticular onset. However, age at onset varied from 9.4 to 16.4 yr, suggesting that the clinical profiles of these patients were not quite the same as that of our patient, whose disease started at 18 months. Furthermore, nine were seropositive for JRA. The HLA phenotype of our patient was compatible with SS and autoimmune diseases (HLA-A1-B8-DR3-DQ2 haplotype) and oligoarthritis (HLA-A2). Genetically, this suggests that this patient was at risk of developing SS.
Notes
Correspondence to: A.-M. Prieur, Unité d'Immunohématologie et Rhumatologie Pédiatriques, Hôpital Necker Enfants Malades, 149 rue de Sèvres 75743 Paris Cedex 15, France.
References