THE UNFORTUNATE PERFECT STORM - SEPTIC SHOCK DUE TO CHRONIC IMMUNOSUPPRESIVE MEDICAL THERAPY AND MEDICATION-INDUCED LYMPHOMA
Authors: Ravichander Benjamin , Sangha Lillian , Guzman Adalberto , Ibarra Maria , Mishagina Irina 
Published: January 2023

Abstract

INTRODUCTION
Pharmacological treatment of Crohn's Disease (CD) involves immunomodulators such as adalimumab, a tumor necrosis factor (TNF) inhibitor and azathioprine, a purine analogue. These medications have risks associated with severe illness from infectious etiologies as well as lymphoma development. This is due to the immunosuppressive effect of the medications as well as a chronic inflammatory state(1). Anaplastic large-cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma (NHL). We present a rare case of sepsis and ALCL in a patient on immunomodulator therapy.

CASE DESCRIPTION
A 31-year-old G1P0 female at 19 weeks gestation with history of Crohn’s disease presents with abdominal pain. Her medications are adalimumab and azathioprine which were started one year ago due to poorly controlled CD resulting in anal fistulas. She was recently treated for right thigh folliculitis. This progressed to abdominal pain and right inguinal lymphadenopathy. She met SIRS criteria on presentation and was admitted to the intensive care unit for respiratory failure requiring intubation. Despite broad-spectrum antibiotics for pneumonia, she remained febrile with an increasing leukocytosis. Blood, lower respiratory, and fungal cultures, acid-fast staining, viral cultures and smears, and urine tests were negative for a source of infection. Commuted tomography (CT) of the abdomen and pelvis was significant for extensive retroperitoneal lymphadenopathy but found no infectious source. An excisional biopsy of the right groin lymph node was a preliminary read as Hodgkin's lymphoma (HL), but the initial immunohistochemical stain was consistent with NHL. Her immunomodulator therapy was stopped due to sepsis and her risk of lymphoma. She subsequently developed septic shock, acute renal failure requiring continuous renal replacement therapy, atrial fibrillation with rapid ventricular response, and suffered a spontaneous vaginal delivery of a 20-week stillborn baby. A final diagnosis of ALCL was confirmed by pathology. The molecular studies were significant for positivity for CD45, CD30, EMA, CD2, CD4, CD25, ALK1, granzyme B, perforin, and TIA1. She was started on brentuximab, cyclophosphamide, and prednisone.

DISCUSSION
ALCL is a rare subtype of NHL that accounts for roughly one percent of all NHL (3). The development of lymphomas occurs when the TNF alpha subunit binds to the cell surface. This inhibits both the apoptosis pathway and cytokine-mediated inhibition of CD30+ lymphoma cells resulting in cell proliferation (4). There is limited documentation of adalimumab or azathioprine associated ALCL and this association should be studied further. The patient suffered from severe consequences of her immunosuppression from her chronic immunomodulator therapy and immunosuppression from her malignancy resulting in septic shock with multiorgan failure.

Right inguinal lymph node biopsy showing atypical large lymphoid infiltrate, background small lymphocytes, plasma cells, and histiocytes. The large atypical cells are characterized by large irregular nuclei with occasional bilobed nuclei and horseshoe-shaped nuclei, multiple small nucleoli, and abundant amphophilic cytoplasm.