Discussion
In contrast to adults, malignancy in pediatric-onset patients with SLE has been less extensively studied. In the study of Bernatsky, 14 invasive cancers were found; among these cases, there was no case of primary central nervous system lymphoma [1]. PCNSL is a rare form of extranodal non-Hodgkin lymphoma [2,3]. Its association with SLE was described for the first time by Lipsmeyer in 1972 [4]. Recent studies suggest a relatively high prevalence of auto immune diseases among primary CNS patients [5]. In a scandinavian study, 29% of primary CNS lymphoma patients had an underlying auto immune disease [6]. In the study of Kaulen, the systemic lupus erythematous (SLE) is the most auto immune disease associated with this lymphoma. The relationship between lymphoma and SLE has not been clearly elucidated. It might be a long term exposure to immunosuppressants or persistence of high disease activity [7]. Immunosuppressive agents might lead to lymphoma by direct mutagenesis or by disturbing immune surveillance [2]. In a case based review, 18 English papers of PCNSL in patients with SLE were descried [8]. Their ages varied from 20 to 60 years. Eleven cases were treated with Mycophenolate Mofetil and the others were treated by other immunosuppressive therapy or Prednisolone only. The duration between the diagnosis of SLE and PCNSL varied from 1 to 30 years [7]. Our patient was diagnosed with lupus nephritis since 4 years and was treated by Predisolone, Cyclophosphamide and Mycophenolate Mofetil. The link between Mycophenolate Mofetil and PCNSL has been studied in recent decades. It seems that the development of PCNSL in SLE patients may occur as a result of impaired immune surveillance and compromised T-cell activity resulting from the immunosuppressant leading to persistence of EBV. It was reported that decrease in the activity of cytotoxic CD8T cells by producing interferon gamma for suppression EBV reactivation, triggers the induction of EBV infected β cells and/or high expression of viral gene in some patients with SLE [9].To our knowledge, our case is the first pediatric case of diffuse large cell CNS lymphoma associated with lupus nephritis after treatment with Mycophenolate Mofetil for 4 years. However, in our patient, PCNSL seems to be multifactorial: High activity disease and the use of two immunosuppressive treatments which are Cyclophosphamide and Mycophenolate Mofetil.
In conclusion, clinicians should consider PCNSL in child with SLE presenting with neurological symptoms and the diagnosis must be confirmed by brain biopsy.
Acknowledgements: Published with written consent of the patient
Conflict of interest : The authors declare that they have no competing interest
Author contributions: Drs Ouns Naija, Farah Krifi contributed to the first draft of the manuscript. Drs Ouns Naija, Farah Krifi, Yossra Hammi and Dr Meriem Jrad contributed to the literature search, analysis and interpretation of the data. Tahar Gargah and Ines Chelly gave final approval. All authors read and approved the final manuscript.
Patient consent: Obtained