Rheumatology International

, Volume 39, Issue 2, pp 353–357 | Cite as

Granuloma annulare development in a patient with rheumatoid arthritis treated with tocilizumab: case-based review

  • Eleftherios Pelechas
  • Alexandra Papoudou-Bai
  • Paraskevi V. Voulgari
  • Alexandros A. DrososEmail author
Cases with a Message


Granuloma annulare (GA) is the most common non-infectious disease. Despite the fact that it is a benign disease, it can be associated with a variety of disorders and certain drugs including biological disease-modifying anti-rheumatic drugs (bDMARDs). A 50-year-old man with a history of rheumatoid arthritis refractory to methotrexate, hydroxychloroquine and infliximab was treated with tocilizumab (TCZ), an interleukin-6 receptor antagonist, 162 mg subcutaneously every week. The patient responded very well to TCZ treatment with a decrease of acute phase reactants and reduction of disease activity score for 28-joints count. However, 3 months later he developed erythematous polycyclic eruptions affecting the lower extremities consistent with a diagnosis of GA which was confirmed by a skin biopsy. TCZ has been discontinued and the patient was treated with prednisone presenting complete resolution of skin manifestations after 4 weeks. This is the first case of GA development during TCZ treatment. Thus, we review the literature and discuss the relevant cases of GA development in patients treated with bDMARDs. When dealing with patients treated with these agents, all physicians should be aware of possible adverse events and the potential development of such complications.


Granuloma annulare Rheumatoid arthritis Interleukin-6 inhibitors Tocilizumab 


Author contributions

EP: acquisition and analysis of the data, and manuscript drafting. AP-B: analysis and interpretation of the histological data. PVV: acquisition, analysis and interpretation of the data. AAD: review of the manuscript and final approval.

Compliance with ethical standards

Conflict of interest

E. Pelechas, Alexandra Papoudou-Bai, Paraskevi V. Voulgari, and Alexandros A. Drosos declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from our patient included in the study.


  1. 1.
    Kaltsonoudis E, Pelechas E, Voulgari PV, Drosos AA. (2018) Unmet needs in the treatment of rheumatoid arthritis. An observational study and a real-life experience from a single university center. Semin Arthritis Rheum. (epub ahead of print) Google Scholar
  2. 2.
    Flouri ID, Markatseli TE, Boki KA et al (2018) Comparative analysis and predictors of 10-year tumor necrosis factor inhibitors drug survival in patients with spondyloarthritis: first-year response predicts longterm drug persistence. J Rheumatol 45(6):785–794CrossRefGoogle Scholar
  3. 3.
    Exarchou SA, Voulgari PV, Markatseli TE, Zioga A, Drosos AA (2009) Immune-mediated skin lesions in patients treated with anti-tumour necrosis factor alpha inhibitors. Scand J Rheumatol 38:328–331. CrossRefGoogle Scholar
  4. 4.
    Sfikakis PP, Iliopoulos A, Elezoglou A, Kittas C, Stratigos A (2005) Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum 52:2513–2518CrossRefGoogle Scholar
  5. 5.
    Markatseli TE, Kaltsonoudis ES, Voulgari PV, Zioga A, Drosos AA (2009) Induction of psoriatic skin lesions in a patient with rheumatoid arthritis treated with rituximab. Clin Exp Rheumatol 27:996–998Google Scholar
  6. 6.
    Kaltsonoudis E, Zikou AK, Voulgari PV, Konitsiotis S, Argyropoulou MI, Drosos AA (2014) Neurological adverse events in patients receiving anti-TNF therapy: a prospective imaging and electrophysiological study. Arthritis Res Ther 16:R125. CrossRefGoogle Scholar
  7. 7.
    Voulgari PV, Markatseli TE, Exarchou SA, Zioga A, Drosos AA (2008) Granuloma annulare induced by anti-tumour necrosis factor therapy. Ann Rheum Dis 67:567–570CrossRefGoogle Scholar
  8. 8.
    Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD (2011) Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int 31:1409–1417. CrossRefGoogle Scholar
  9. 9.
    Alexander JS, Paniker PU (2006) A ring-shaped eruption. Am J Med 119:125–127CrossRefGoogle Scholar
  10. 10.
    Keimig EL. Granuloma, Annulare (2015) Granuloma annulare. Dermatol Clin 33:315–29. CrossRefGoogle Scholar
  11. 11.
    Devos SA, Van Den Bossche N, De Vos M, Naeyaert JM (2003) Adverse skin reactions to anti-TNF-alpha monoclonal antibody therapy. Dermatology 206:388–390CrossRefGoogle Scholar
  12. 12.
    Ratnarathorn M, Raychaudhuri SP, Naguwa S (2011) Disseminated granuloma annulare: a cutaneous adverse effect of anti-TNF agents. Indian J Dermatol 56:752–754. CrossRefGoogle Scholar
  13. 13.
    Viguier M, Richette P, Bachelez H, Wendling D, Aubin F (2010) Paradoxical cutaneous manifestations during anti-TNF-alpha therapy. Ann Dermatol Venereol 137:64–71. quiz 63, 78 – 9.CrossRefGoogle Scholar
  14. 14.
    Bonomo L, Ghoneim S, Levitt J (2017) A case of granuloma annulare associated with secukinumab use. Case Rep Dermatol Med 2017:5918708. Google Scholar
  15. 15.
    Clark ML, Tobin CA, Sutton A, Missall TA. Granuloma annulare in the setting of secukinumab. Case Rep Dermatol Med 2018:5175319.
  16. 16.
    Piette EW, Rosenbach M (2016) Granuloma annulare: clinical and histologic variants, epidemiology, and genetics. J Am Acad Dermatol 75(3):457–465. CrossRefGoogle Scholar
  17. 17.
    Sand FL, Thomsen SF (2015) Off-label use of TNF-alpha inhibitors in a dermatological university department: retrospective evaluation of 118 patients. Dermatol Ther 28:158–165. CrossRefGoogle Scholar
  18. 18.
    Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, Bütikofer L, Seitz M, Reichenbach S (2016) Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 387:1921–1927. CrossRefGoogle Scholar
  19. 19.
    Samson M, Audia S, Fraszczak J et al (2012) Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis. Arthritis Rheum 64(11):3788–3798CrossRefGoogle Scholar
  20. 20.
    Martinez-Taboada VM, Alvarez L, RuizSoto M et al (2008) Giant cell arteritis and polymyalgia rheumatica: role of cytokines in the pathogenesis and implications for treatment. Cytokine 44(2):207–220CrossRefGoogle Scholar
  21. 21.
    Sfikakis PP, Kollias G (2003) Tumor necrosis factor biology in experimental and clinical arthritis. Curr Opin Rheumatol 15:380–386CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Rheumatology Clinic, Medical SchoolUniversity of IoanninaIoanninaGreece
  2. 2.Department of Pathology, Medical SchoolUniversity of IoanninaIoanninaGreece

Personalised recommendations