Oral Presentation ARA-NSW 2019 - 41st Annual NSW Branch Meeting

“Uncommon Complications Of A Common Medication” Case report and literature review of iatrogenic immunodeficiency associated lymphoproliferative disease associated with methotrexate therapy (#15)

Karolina Kanczuga-Byszewski 1 , Georgette Goode 1
  1. Hunter New England Local Health District, Newcastle, NSW, Australia

 

 

Methotrexate remains the cornerstone of disease modifying anti-rheumatic drugs (DMARDS).  Side effects including liver dysfunction and blood dyscrasias are well recognized. This case illustrates an important and unusual complication in a patient with rheumatoid arthritis (RA).

 

A 64 year old female was treated with combination leflunomide and methotrexate for a 20 year history of seropositive RA. She presented to clinic with a 6 week history of  “lumps in the neck”. PET revealed multiple FGD avid nodes in the cervical and supraclavicular region. Lymph node biopsy confirmed a large B cell lymphoma, EBV positive, consistent with Iatrogenic Immunodeficiency Associated Lymphoproliferative disease (II-ALPD), most likely due to methotrexate.

 

Despite the cessation of DMARDs, her lymphadenopathy continued to progress. She also developed an acute kidney injury with active urinary sediment and nephrotic range proteinuria. Renal biopsy revealed a mesangiocapillary glomerulonephritis with the report considering the possibility of lupus nephritis due to almost full house immunofluorescence. She received1g IV pulsed methylprednisone with some clinical improvement. Her proteinuria and lymphadenopathy resolved with the introduction of rituximab. Follow up at 4 and 10 months shows ongoing remission with no evidence of renal impairment.

 

This is a case of methotrexate related II-ALPD complicated by glomerulonephritis, successfully treated with rituximab monotherapy. The case also illustrates the potential pitfalls of using classification criteria for purposes of clinical diagnosis. The renal changes in this case fulfill the SLICC criteria for SLE. Accepting and acting on a diagnosis of SLE would have led to inappropriate and potentially deleterious treatment.

 

 

  1. Masayoshi Harigai . Lymphoproliferative disorders in patients with rheumatoid arthritis in the era of widespread use of methotrexate: A review of the literature and current perspective. Modern Rheumatology. 2017; 8(1) 1-8. doi:10.1080/14397595.2017.1352477
  2. Yamada, K, Oshiro, Y, Okamura, S, Fujisaki, T, Kondo, S, Nakayama, Y, Suematsu, E, Tamura, K, Takeshita, M. Clinicopathological characteristics and rituximab addition to cytotoxic therapies in patients with rheumatoid arthritis and methotrexate‐associated large B lymphoproliferative disorders. Histopathology. 2015; 67, 70– 80. doi: 10.1111/his.12627
  3. Aggarwal, R. , Ringold, S. , Khanna, D. , Neogi, T. , Johnson, S. R., Miller, A. , Brunner, H. I., Ogawa, R. , Felson, D. , Ogdie, A. , Aletaha, D. and Feldman, B. M. Distinctions Between Diagnostic and Classification Criteria?. Arthritis Care & Research. 2015;67: 891-897. doi:10.1002/acr.22583