Reactive arthritis induced by intravesical BCG therapy for bladder cancer: our clinical experience and systematic review of the literature

Autoimmun Rev. 2013 Oct;12(12):1150-9. doi: 10.1016/j.autrev.2013.06.017. Epub 2013 Jun 29.


Objective: Intravesical instillation of BCG (ivBCG) is an effective and safe immunotherapy of bladder carcinoma but it may have, as side effect, a reactive arthritis (ReA). The authors describe 5 cases observed during their own clinical experience along with the updated review of the literature on this topic.

Methods: Seventy-three papers were present in the world literature, each reporting almost 1 case for a total of 112 patients. However, the review focused on 61 papers, selected on the basis of reporting suitable for a correct clinical evaluation; thus, a total of 89 patients, including the cases observed in our clinic, were carefully analyzed.

Results: Among the 89 patients identified 73 were males and 16 females. Europe is the geographical area with the higher number of reports, namely 80.6% of the papers including 74.2% of the patients. The Mediterranean area accounts for 62.9% of the papers and 59.6% of the cases. The symptoms of ReA appeared after a mean number of instillations of 5.8. Polyarthritis was present in 55.1%, oligoarthritis in 37.0% and monoarthritis in 7.9%. Polyarthritis was symmetric in 51.0% and asymmetric in 49.0% of the cases; oligoarthritis was symmetric in 33.3% and asymmetric in 66.7% of the cases. Overall, an asymmetric distribution of arthritis was present in 59.6%. Knee and ankle were the joints most frequently involved. The antigen HLA B27 was positive in 42.6%. The synovial fluid analysis was defined as flogistic-aseptic in 71.9% of the patients. Arthritis was recovered within 6months in 93.2% of the cases and in 70.5% of the patients within the first two months. NSAIDs and corticosteroids, alone or in conjunction with other drugs, are used in 65.1% and in 40.4% of the cases, respectively. The clinical features of ivBCG ReA are compared with ReA from other triggering agents, from which it differs for some clinical aspects and overlaps for others.

Conclusions: Compared with a previous report, this review allows to modify some figures of this topic as a reduced prevalence of polyarthritis (from 70% to 55.1%) and of spinal and sacroiliac involvement; polyarthritis remains the more frequent clinical pattern of ivBCG ReA that, however, is characterized by rather asymmetrical distribution and involvement of the large joints of lower limbs. A definite linkage to HLA B27 is present, although without prognostic value. Moreover, arthritis is aseptic, has a latency time from antigen exposure, and is associated with extra-articular features as commonly observed in ReA from other triggering agents. Arthritis is usually benign and rarely develops into a chronic form. NSAIDs and/or corticosteroids are largely effective. Noteworthy, the overall clinical picture of arthritis triggered by ivBCG emerging from this updated review is comparable to that of ReA from other bacterial agents.

Keywords: Antigen HLA B27; Intravesical BCG; Polyarthritis; Reactive arthritis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Administration, Intravesical
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis, Reactive / diagnosis
  • Arthritis, Reactive / drug therapy
  • Arthritis, Reactive / etiology*
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / adverse effects*
  • Europe
  • HLA-B27 Antigen / analysis
  • Humans
  • Immunotherapy*
  • Prohibitins
  • Urinary Bladder Neoplasms / complications*
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / therapy*


  • Anti-Inflammatory Agents, Non-Steroidal
  • BCG Vaccine
  • HLA-B27 Antigen
  • PHB2 protein, human
  • Prohibitins