Internist in training Cliniques universitaires Saint-Luc, UCL Brussels, Belgium
Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a common condition that results from a small and/or quiescent secreting B-cell clone, completely asymptomatic, that requires only regular monitoring. Sometimes, although quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin. This situation refers to the concept of monoclonal gammopathy of clinical significance (MGCS). It is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. Here, we report a case of MGCS relying on manifestations of an acquired angioedema related to a monoclonal protein.
Methods: A 48-year-old male patient presented in February 2020 with a first attack of angioedema that manifested by a swelling of the hands, feet and lips, and abdominal pain, that resolved within 24 hours. Lab test documented a low C1 inhibitor level (below 16%) with low C1 inhibitor activity (19%), and very low C4 and C1q levels, leading to the diagnosis of acquired angioedema. The patient had no personal nor familial history of angioedema. Additional work-up encompassed serum and urine protein electrophoresis, free light chain assay, lymphocyte typing by flow cytometry, bone marrow aspiration and PET-CT but was not conclusive. Treatment successively included Tranexamic Acid, plasma exchanges, 4 infusions of Rituximab, Mycophenolate Mofetil without any improvement, persistent angioedema attacks occurring every 3 to 4 weeks.
Results: The patient was then referred to our center in September 2021. With subcutaneous injections of lanadelumab, an IgG1 Kappa monoclonal antibody directed against Kallikrein received on a compassionate use basis, he was freed from all symptoms till the program was stopped and attacks reoccurred. Additional work-up identified then an IgA Lambda monoclonal peak (1.9 g/L), with a discrete marrow infiltration, a situation considered as a MGCS. Treatment with SQ Daratumumab was proposed with the initial disappearance of any angioedema attack after the first 2 months of therapy, but relapses thereafter, persisting after 6 cycles of SQ Daratumumab. The patient was further rechallenged with lanadelumab with success.
Conclusions: We report a case of acquired angioedema, a rare form of MGCS, that exemplifies the difficulty to understand the relationship between a monoclonal component and the clinical manifestations of the disease, since a therapy targeting directly the clone was not efficacious in this setting. This case also highlights the spectrum of various disorders associated with MGUS.
