Delayed diagnosis of Angioimmunoblast T-cell lymphoma presenting with type II Cryoglobulinemia and acute kidney injury: a case report and narrative review of the literature.

BACKGROUND: Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia, autoantibodies and systemic involvement in AITL has often led to a delay in diagnosis or even misdiagnosis in practice. We herewith present a case of AITL that primarily presented with acute kidney injury associated with type II Cryoglobulinemia, the underlying cause was only identified 8 months after the emergence of initial symptoms. CASE PRESENTATION: A 67-year old woman presented with 2-month history of intermittent joint pain and a 3-day history of bilateral lower limb edema and acute kidney injury. Initial laboratory investigations showed marked hypocomplementemia with positive autoantibodies of ANA, anti-cardiolipin-IgM and direct antiglobulin. The serum and urinary Immunofixation and serum cryoglobulin tests were negative, while the serum free κ to λ light chain ratio was 0.231. A renal biopsy showed a diffuse proliferative glomerulonephritis with intracapillary pseudothrombi formation. There were orderly arranged microtubular structures of 20-35 nm in diameter in the subendothelial and mesangial area on electron microscopy. Shortly afterwards, the patient developed tingling affecting her finger tips and weak hands and legs. A diagnosis of cryoglobulinemia complicated with cryoglobulinemic glomerulonephritis and polyneuropathy was made. She responded well to methylprednisolone, plasma exchange and rituximab. However, 3 months later, she presented with generalized pruritic rash, weight loss, and inguinal lymphadenopathy. A subsequent inguinal excisional lymph node biopsy at month 8 revealed AITL as the underlying disease. CONCLUSIONS: AITL and its associated B cell dysregulation can give rise to autoimmunity and cryoglobulinemia which may conceal itself as the underlying disorder. In various clinical scenarios of auto-immune diseases, it is advisable that the clinicians should take into consideration the multi-faceted lymphoma.

Activation of NMDA receptor is associated with up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive inputs in rats.

Cyclooxygenases-2 (COX-2) in the spinal dorsal horn is up-regulated and plays an important role in pain and hyperalgesia induced by nociceptive stimulation. The mechanisms involved in the up-regulation of spinal COX-2 during nociceptive stimulation are yet not well understood. Because the important role of NMDA and its receptor in transmission of nociceptive information in the spinal cord, activation of the spinal NMDA receptor might contribute to the up-regulation of spinal COX-2 expression. The present study was undertaken to demonstrate the above hypothesis by observing changes of COX-2 expression in the spinal dorsal horn in rats subjected to formalin test and intrathecal administration of NMDA, a selective NMDA receptor agonist, in conditions with or without presence of MK-801, an antagonist of NMDA receptor, using methods of Western blotting, reverse transcription polymerase chain reaction and immunohistochemistry. The results showed that intrathecal injection of MK-801, a noncompetitive antagonist of NMDA receptor, significantly suppressed the up-regulation of the COX-2 expression and characteristic pain behavior responses evoked in formalin test. Whereas, intrathecal injection of NMDA significantly up-regulated the expression of COX-2 in the spinal dorsal horn in a time course corresponding to that of nociceptive behavioral responses elicited by the intrathecal NMDA administration. In addition, the up-regulation of the COX-2 expression induced by the intrathecal NMDA was dose-dependent and blocked by prior administration of MK-801. These findings proved that activation of NMDA receptor is associated with the up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive stimulation in rats.