Background Interleukin-6 (IL-6) has been reported to be related with the pathogenesis of sjogren's syndrome (SS). However, there is no report clinically describing in detail that IL-6 inhibition is effective for SS.
Objectives We evaluated the efficacy of tocilizumab (TCZ) for the patient with SS complicated with rheumatoid arthritis (RA).
Methods Tocilizumab was administered at 8mg/kg every 4 weeks. Clinical, laboratory and image data were obtained from the records in our hospital.
Results A 39-year-old woman was diagnosed as SS in 1997 and treated with 3 g/day of sodium bicarbonate and 3600 mg/day of potassium citrate because she was complicated with renal tubular acidosis (RTA) and hypokalemia. Her complaints were dry mouth and arthralgia. Laboratory findings under usage of sodium bicarbonate and potassium citrate were as follow: WBC 8600/mm3, Hb 12.1 g/dl, BUN 12 mg/dl, Cr 0.7 mg/dl, CRP 2.2 mg/dl, Na 138 mEq/l, K 3.5 mEq/l, and Cl 109 mEq/l. Antinuclear antibody titer was 1:320 with speckled pattern, and anti-SS-A and anti-SS-B antibodies was positive. RF and anti-CCP antibody were 45 IU/ml and >100 U/ml, respectively. Urine beta-2-MG level was markedly elevated to 15800 mg/l. Shirmer's test was positive (right: 3mm, left: 1mm). Salivary flow rate in gum test was 0.29 ml/min and lip biopsy revealed extensive lymphocytic infiltration with fibrotic changes in salivary gland. Majority of infiltrating cells was T cells, in which, CD4+ T cells were predominantly seen rather than CD8+ T cells. Cytoplasma of duct and infiltrating cells were stained with anti-IL-6 antibody. Specimen of renal biopsy was almost comparable to that of lip biopsy including immuostaining. Regarding her RA, SJC, TJC and DAS28-CRP were 19, 23 and 6.38, respectively.
Tocilizumab treatment was started in July, 2009 because she was refractory to conventional DMARDs and side effects. Tocilizumab normalized CRP at week 12. At week 24, TJC, TJC and DAS28-CRP improved to 4, 2 and 2.38 respectively and, thereafter, in remission. Salivary flow rate increased from 0.22 ml/min at baseline to 0.81 ml/min at week 24 in gum test. Urinary beta-2-MG decreased from 15800 mg/l to 1210 mg/l, thereafter, improved in normal level, while serum beta-2-MG levels did not change during 24 weeks of tocilizumab therapy. Second lip biopsy was performed after 2 years of tocilizumab therapy. Infiltration of inflammatory cells almost disappeared and cytoplasma of duct and residual cells were not stained with anti-IL-6 antibody. Ophthalmological consultation confirmed slightly improvement of Shirmer's test (right: 4mm, left: 4mm) after 4 years of tocilizumab treatment. Tocilizumab therapy continued its efficacy for SS and RA and no side effect has been shown over 4 years.
Conclusions This is the first report indicating the efficacy of tocilizumab for the patient with SS complicated with RA. Tocilizumab may be effective for preventing dysfunction of the salivary gland and inhibiting interstitial nephritis and, therefore, may be one candidate for SS patients with RA.
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Disclosure of Interest None declared
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