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