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Wiener klinische Wochenschrift

, Volume 126, Issue 3–4, pp 126–129 | Cite as

Does tocilizumab contribute to elevation of rheumatoid factor and induction of paradoxical syaloadenitis in rheumatoid arthritis patients?

  • Dušanka Martinović Kaliterna
  • Jure AljinovićEmail author
  • Dijana Perković
  • Daniela Marasović Krstulović
  • Ivanka Marinović
  • Tonko Vlak
case report

Summary

A 56-year-old woman, treated with tocilizumab (TCZ) for 8 months for severe rheumatoid arthritis (RA), was admitted to the hospital due to the swelling and tenderness of parotid glands. The patient was diagnosed with seropositive erosive RA in 1988, and treated with different disease modifying antirheumatic drugs (DMARDs) that were used together with a low dosage of glucocorticoides, followed by biologic therapy with infliximab and adalimumab which also proved to be inefficient. The patient had an excellent initial response on TCZ therapy. After 8 months, she was presented with an extreme enlargement of parotid glands. Bacterial, viral, and granulomatous diseases were excluded. A spectrum of autoantibodies including anti-Ro and anti-La showed normal values, expect for slightly elevated anti-cyclic citrullinated peptide (anti-CCP) and extreme elevation of the rheumatoid factor (RF) to 10,100 IU/ml. The biopsy of salivary glands was done and histological specimen showed limphoplasmocytic syaloadenitis. Tocilizumab therapy was stopped and the dosage of glucocorticoids and methotrexate (MTX) was raised. After 6 weeks, the patient was in better condition with slightly lower levels of RF (9,010 IU/ml). We hypothesise that in this patient, TCZ stimulated RF hyper production which can induce a paradoxical secondary syaloadenitis in RA.

Keywords

Rheumatoid arthritis Interleukin 6 Rheumatoid factor Tocilizumab Syaloadenitis 

Trägt eine Therapie mit Tocilizumab zur Erhöhung des Rheumafaktors und zur Induktion einer paradoxen Sialadenitis bei einer Patientin mit rheumatoider Arthritis bei?

Zusammenfassung

Eine 56-jährige Frau, die wegen einer rheumatoiden Arthritis (RA) 8 Monate lang mit Tocilizumab (TCZ) behandelt worden war, wurde wegen angeschwollener schmerzhafter Parotiden aufgenommen. Die Diagnose einer RA war im Jahre 1988 gestellt worden. Sie war mit verschiedenen Krankheits-modulierenden Antihreumatica in Kombination mit niedrig dosierten Glukokortikoiden, gefolgt von den Biologika Infliximab und Adalimumab erfolglos behandelt worden. Anfänglich sprach die Patientin hervorragend auf TCZ an. Nach 8 Monaten präsentierte sie sich allerdings mit stark angeschwollenen Parotiden. Bakterielle, virale und granulomatöse Erkrankungen konnten ausgeschlossen werden. Das Spektrum der Autoantikörper inklusive anti-Ro, und anti-La war bis auf gering erhöhte anti CCP normal. Nur der Rheumafaktor (RF) war mit 10.100 IU/ml extrem erhöht. Die Histologie des Punktats aus der Parotis ergab eine lymphoplasmozytäre Sialadenitis. Die Therapie mit TCZ wurde angesetzt. Die Therapie mit Metothrexat und Glukokortikoiden wurde dosismäßig erhöht. 6 Wochen später war die Patientin in einem besseren Zustand. Der RF war etwas gesunken (9010 IU/ml). Wir stellen die Hypothese auf, dass bei dieser Patientin das TCZ eine überschießende Produktion des RF auslöste, was zu einer paradoxen sekundären Sialadenitis bei RA führen kann.

Schlüsselwörter

Rheumatoide Arthritis Interleukin 6 Rheuma Faktor Tocilizumab Sialadenitis 

Notes

Acknowledgments

We are grateful to PhD Ivana Karaman, MD for providing the histological picture.

Conflict of interest

The authors report no conflicts of interest.

References

  1. 1.
    Fonseca JE, Santos MJ, Canhao H, Choy E. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev. 2009;8(7):538–42.PubMedCrossRefGoogle Scholar
  2. 2.
    Tamura T, Udagawa N, Takahashi N, Miyaura C, Tanaka S, Yamada Y, et al. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc Natl Acad Sci USA. 1993;90(24):11924–8.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Alessandri C, Bombardieri M, Papa N, Cinquini M, Magrini L, Tincani A, et al. Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann Rheum Dis. 2004;63(10):1218–21.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Kawashiri SY, Kawakami A, Iwamoto N, Fujikawa K, Aramaki T, Tamai M, et al. In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline. Mod Rheumatol. 2011;21(4):370–4.PubMedGoogle Scholar
  5. 5.
    Yoshimoto K, Tanaka M, Kojima M, Setoyama Y, Kameda H, Suzuki K, et al. Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjogren’s syndrome. Arthritis Res Ther. 2011;13(5):R170.Google Scholar
  6. 6.
    Patel AM, Moreland LW. Interleukin-6 inhibition for treatment of rheumatoid arthritis: a review of tocilizumab therapy. Drug Des Devel Ther. 2010;4:263–78.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Pham T, Claudepierre P, Constantin A, de Bandt M, Fautrel B, Gossec L, et al. Tocilizumab: therapy and safety management. Joint Bone Spine. 2010;77(Suppl 1):3–100.CrossRefGoogle Scholar
  8. 8.
    Campbell L, Chen C, Bhagat SS, Parker RA, Ostor AJ. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford). 2011;50(3):552–62.CrossRefGoogle Scholar
  9. 9.
    Singh JA, Wells GA, Christensen R, Tanjong Ghogomu E, Maxwell L, Macdonald JK, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011(2):CD008794.Google Scholar
  10. 10.
    Edwards CJ. IL-6 inhibition and infection: treating patients with tocilizumab. Rheumatology (Oxford). 2012;51(5):769–70.CrossRefGoogle Scholar
  11. 11.
    Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis. 2011;70(12):2148–51.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Tishler M, Yaron I, Shirazi I, Yossipov Y, Yaron M. Increased salivary interleukin-6 levels in patients with primary Sjogren’s syndrome. Rheumatol Int. 1999;18(4):125–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Tishler M, Yaron I, Geyer O, Shirazi I, Naftaliev E, Yaron M. Elevated tear interleukin-6 levels in patients with Sjogren syndrome. Ophthalmol. 1998;105(12):2327–9.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Dušanka Martinović Kaliterna
    • 1
    • 3
  • Jure Aljinović
    • 2
    Email author
  • Dijana Perković
    • 1
  • Daniela Marasović Krstulović
    • 1
  • Ivanka Marinović
    • 2
  • Tonko Vlak
    • 2
  1. 1.Department of Rheumatology and Clinical ImmunologyUniversity Hospital Center Split, School of Medicine in SplitSplitCroatia
  2. 2.Department of Rehabilitation Medicine and RheumatologyUniversity Hospital Center Split, School of Medicine in SplitSplitCroatia
  3. 3.Department of Rheumatology and Clinical ImmunologyUniversity Hospital SplitSplitCroatia

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