Methotrexate-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder causing hypercalcaemia

Abstract

Hypercalcaemia is a rare but potentially life-threatening consequence of malignancies. Solid cancers, such as lymphomas, increase serum calcium primarily through parathyroid hormone-related protein or ectopic production of 1alpha-hydroxylase. We present a case of 56-year-old woman with Sjogren’s syndrome and psoriasis in the setting of chronic methotrexate (MTX) use who developed worsening hypercalcaemia and symptoms suggestive of lymphoma. Pathology results diagnosed her with MTX-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD). This case reminds clinicians that chronic MTX use is associated with LPDs and can ultimately lead to hypercalcaemia. The patient’s MTX and other immunosuppressive medications were stopped, and her calcium corrected with fluids and calcitonin. At her 8-month follow-up postdischarge, the patient was asymptomatic with normal laboratory results and in partial clinical remission.

Malignancy risk ofnon‐biologicimmunosuppressive therapies: A review of the literature withevidence‐basedtreatment recommendations

“…MTX therapy has been implicated in the development of EBV‐positive B‐cell lymphoproliferative disease in case series (LoE 4) and reports (LoE 5) of patients with dermatomyositis, 63–68 psoriasis, 69–71 Sjogren's syndrome, 71 mycosis fungoides 72 and Sézary syndrome 72 . For some patient cases mentioned, once MTX was discontinued, the B‐cell lymphoma spontaneously resolved 64–67,71,72 …”

“…72 For some patient cases mentioned, once MTX was discontinued, the B-cell lymphoma spontaneously resolved. [64][65][66][67]71,72 Grade C. Low-dose MTX may be associated with increased risk of malignancy; however, there are inconsistencies in the available literature. There are a few reported cases of EBV-positive B-cell lymphoproliferative disease in those taking MTX.…”

Iatrogenic immunodeficiency-associated lymphoproliferative disorder presenting as small bowel perforation

“…IA-LPD is a rare side effect of long-term immunosuppression therapy, and methotrexate (MTX) is the most commonly associated medication reported in the literature 3–7. About half of the patients with MTX-associated lymphoproliferative disorder (MTX-LPD) present with extranodal disease 5.…”