Rheumatology Advance Access originally published online on December 13, 2005
Rheumatology 2006 45(2):238-240; doi:10.1093/rheumatology/kei175
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LETTER TO THE EDITOR |
Renal tubular acidosis, arthritis and autoantibodies: primary Sjögren's syndrome in childhood
Department of Paediatric Rheumatology, North Bristol NHS Trust and Royal National Hospital for Rheumatic Diseases, Southmead Hospital, Bristol, 1 Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol and 2 Department of Paediatrics, Morriston Hospital, Swansea, UK
Correspondence to: A. V. Ramanan, Department of Paediatric Rheumatology, North Bristol NHS Trust and Royal National Hospital, for Rheumatic Diseases, Bath, UK. E-mail: avramanan{at}hotmail.com
SIR, Primary Sjögren's syndrome (PSS) is rare in the paediatric population [1, 2]. We describe an 8-yr-old female who presented with arthritis, distal renal tubular acidosis and an autoantibody profile suggestive of Sjögren's syndrome without sicca symptoms.
An 8-yr-old female first presented in November 2004. Her symptoms started 9 months previously with swelling, pain and morning stiffness of her left ankle and knee, and pain in her wrists and hands. She was treated with ibuprofen and started physiotherapy. The pain improved but stiffness remained. In the following 9 months she had intermittent pain and swelling of her left ankle and knee with persistent pain and swelling of her wrists and hands, with morning stiffness until lunchtime. She had a poor appetite and no energy but no history of rashes, pyrexia, mouth ulcers or hair loss. She had a history only of eczema and no family history of note.
On examination, her weight and height were on the 50th centile. Skin, mouth and nails were normal but she had evidence of dental caries. The rest of the systemic examination was normal. She had evidence of multiple swollen joints. All PIPs, all DIPs, both wrists and ankles showed evidence of active synovitis. She was unable to make a fist and wrist flexion and extension were restricted to 50%.
Initial investigations revealed mild anaemia, raised platelet count and erythrocyte sedimentation rate (iu/ml). She had an autoantibody profile on two occasions 6 months apart. Her rheumatoid factor titre was extremely high. Antinuclear antibody was positive on both occasions, and double-stranded DNA was positive on one occasion (77) and equivocal on the second occasion (45). Both anti-SS-A(Ro) and anti-SS-B(La) were positive on both occasions (Table 1). She received three pulses of methylprednisolone (20 mg/kg) on three consecutive days and was started on oral methotrexate (10 mg/m2). She also received intensive physiotherapy and occupational therapy.
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She was reviewed 2 months later. Her energy levels had improved but she continued to have a poor appetite. On examination, she had widespread active synovitis as before and had had only temporary respite after the pulsed methylprednisolone.
Further investigations revealed a polyclonal increase in immunoglobulins (Igs) but particularly increased IgG1. Crithidia luciliae and anti-CCP (cyclic citrullinated peptide) tests were negative. She had an initial positive HIV test that, when repeated, revealed a false positive result secondary to her circulating autoantibodies. Viral serology for Epstein–Barr virus, cytomegalovirus and parvovirus and hepatitis screen were negative.
At that time she developed dehydration and hypokalaemia with a potassium level of 1.9 mmol/l. Further results revealed metabolic acidosis with a normal anion gap and urine pH >5.5, consistent with a diagnosis of distal renal tubular acidosis (RTA). She also had evidence of mild proteinuria with a protein/creatinine ratio of 0.06 mg/mmol (normal <0.02), and a raised retinol-binding protein/creatinine ratio of 57.7 µg/mmol (normal <15). There was normal tubular reabsorption of phosphate and no glycosuria. She was stabilized with intravenous fluids and potassium supplements.
Ophthalmological assessment revealed no abnormalities but Schirmer and Rose Bengal tests were not performed. Ultrasonography of the salivary glands was performed using an ATL 5000 ultrasound system with a linear 5–12 MHz probe. This showed the typical features of established Sjögren's syndrome, involving the parotid, submandibular and sublingual glands symmetrically (Fig. 1). These features are of diffuse hypoechoic areas throughout the gland parenchyma from cystic dilatation of ducts, with no normal stroma identified. The main ducts were not dilated. Arthritis, poor dentition, RTA, positive autoantibody profiles consisting of high rheumatoid factor titres and positive anti-SS-A(Ro) and anti-SS-B(La) and the ultrasound findings supported the clinical diagnosis of PSS. This was supported by positivity for 
-fodrin IgG (44.4 U/ml), which is thought to be a more specific marker for Sjögren's syndrome. She is currently being managed with methotrexate and hydroxychloroquine.
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PSS is a chronic autoimmune disease characterized by progressive lymphocytic and plasma cell infiltration of the exocrine glands, predominantly salivary and lacrimal, with varying degrees of systemic involvement [3]. Chronic inflammation compromises the glands’ function and leads to xerostomia and xerophthalmia. Extraglandular manifestations, such as arthritis, erythema annulare, vasculitis, pulmonary fibrosis, renal tubular acidosis, membranous nephropathy (in adults) and neuropathy, occur in a minority of patients.
Our patient was diagnosed with PSS. She presented with the clinical findings of arthritis, distal renal tubular acidosis and poor dentition. Her investigations revealed positive anti-SSA and anti-SSB antibodies. The diagnosis was further supported by positive anti--fodrin antibody and ultrasound findings. It has been reported that an autoantibody to -fodrin, a major component of the membrane cytoskeleton, is specifically detected in the serum of paediatric patients with Sjögren's syndrome of childhood onset [4]. Quantitative assessment of salivary gland ultrasonography has been shown to be a very useful method for evaluating salivary gland involvement in PSS [5]. A biopsy of the salivary gland was not performed in view of the overwhelming evidence from the above investigations.
PSS is a rare diagnosis in childhood but it should be considered in children with arthritis and a positive autoantibody profile even in the absence of sicca symptoms.
The authors would like to thank Dr Mike Bradley, consultant radiologist, for his help and advice.
The authors have declared no conflicts of interest.
References
- Cimaz R, Casadei A, Rose C, Bartunkova J, Sediva A. Primary Sjögren syndrome in the paediatric age: a multicentre survey. Eur J Pediatr 2003;162:661–5.[CrossRef][Web of Science][Medline]
- Anya J, Ogawa N, Talan N. Sjögren's syndrome in childhood. J Rheumatol 1995;22:1152–8.[Web of Science][Medline]
- Nikitakis NG, Rivera H, Lariccia C, Papadimitriou J, Sauk JJ. Primary Sjögren syndrome in childhood: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:42–7.[Web of Science][Medline]
- Kobayashi I, Kawamura N, Okano M, et al. Anti-alpha-fodrin autoantibody is an early diagnostic marker for childhood primary Sjögren's syndrome. J Rheumatology 2001;28:363–5.
[Abstract/Free Full Text] - Salaffi F, Argalia G, Carotti M, Giannini FB, Palombi C. Salivary gland ultrasonography in the evaluation of primary Sjögren's syndrome. Comparison with minor salivary gland biopsy. J Rheumatol 2000;27:1229–36.[Web of Science][Medline]
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