3.Discussion
The patient presented with elevated lipid levels upon admission, with a total cholesterol of 10.44 mmol/L (normal range: 2.8-5.6 mmol/L) and triglycerides of 28.45 mmol/L (normal range: 0.45-1.70 mmol/L). Blood routine tests showed a red blood cell count of 2.79×1012/L and hemoglobin of 98 g/L. Coagulation profile revealed an APTT of 54.8 s, fibrinogen of 1.23 g/L, and a prothrombin time of 22.6 s. The initial diagnosis included: 1. Anemia to be further investigated, 2. Severe hyperlipidemia, and 3. Coagulation dysfunction, with no consideration of multiple myeloma (MM) at first. Subsequently, an elevation in globulins was noticed, and MRI indicated bone changes. Further screening through serum protein electrophoresis revealed the presence of M protein. Following immunofixation electrophoresis, bone marrow biopsy, flow cytometry, FISH, and other relevant examinations, the diagnosis was confirmed as multiple myeloma, DS stage II, and R-ISS stage III. In this case, the significantly elevated lipid levels, coupled with the patient’s frequent social engagements, could easily be mistaken for hyperlipidemia resulting from an unhealthy lifestyle, potentially leading to misdiagnosis. The awareness of abnormal globulin elevation, along with abnormal coagulation mechanisms, emphasized the importance of focused screening for hematological disorders, ultimately leading to the accurate diagnosis of MM.
According to recent research findings, IgA type multiple myeloma (MM) is closely associated with the occurrence of hyperlipidemia. In IgA MM, the M protein in serum protein electrophoresis often appears in the α2 region, and flame-shaped cells are observed in the bone marrow[9, 10]. This type of MM is frequently accompanied by renal impairment, as well as elevated cholesterol and hyperlipidemia . Dyslipidemia, as an independent laboratory indicator, is often linked to lipid metabolism abnormalities, such as hypercholesterolemia, hypertriglyceridemia, and even chylomicronemia syndrome. Clinically, dyslipidemia is often associated with manifestations such as xanthomas, hyperviscosity syndrome, and atherosclerosis[11-13]. Therefore, these findings suggest the importance of closely monitoring the connection between hyperlipidemia and MM in clinical practice. Hyperlipidemia can serve as a significant laboratory indicator, especially for IgA type MM.
There is currently no definitive consensus on the mechanism underlying the association between multiple myeloma (MM) and hyperlipidemia[6, 14, 15]. It is widely believed that the monoclonal immunoglobulin produced by malignant proliferation interacts with serum lipoproteins, tissue receptors, and lipoprotein lipase, leading to a reduced clearance rate of lipoproteins. Corsini et al. reported a case of monoclonal gammopathy of undetermined significance (MGUS) containing LDL (low-density lipoprotein) receptor antibodies[16]. Nozaki et al. confirmed this observation, demonstrating that IgA monoclonal immunoglobulin in an MM patient binds to LDL, leading to hyperlipidemia [17]. Kilgore et al. isolated Fab fragments of IgA from MM patients, showing binding activity to LDL, which hindered the LDL receptor pathway, impeding normal lipoprotein metabolism[18].Cortese compared the metabolism of intermediate-density lipoprotein (IDL) and LDL in two male MM patients with hyperlipidemia. Compared to the control group, MM patients exhibited impaired metabolism of IDL, the process of IDL transitioning to LDL, and the binding capacity of LDL to receptors. These studies suggest that the monoclonal immunoglobulins, especially IgA in MM patients, may disrupt the interaction between LDL and its receptors, thereby disrupting lipid metabolism. LDL plays a crucial role in transporting cholesterol from the liver to other organs for utilization, and obstruction of the LDL pathway results in cholesterol accumulation in the bloodstream, leading to hyperlipidemia. In this case, the MM patient presented with an elevated LDL level of 3.54 mmol/L (normal range: 0-3.12 mmol/L), consistent with literature reports. This elevation may be attributed to the disruption of the LDL pathway metabolism by IgA monoclonal immunoglobulins, leading to hyperlipidemia. However, some propose that MM cells rely on exogenous cholesterol for survival, and LDL-cholesterol serves as a crucial anti-apoptotic agent[19]. Hence, it is also plausible that hyperlipidemia induces abnormal lipid metabolism in the body, triggering the production of monoclonal immunoglobulins and eventually developing into MM. Currently, the prevailing theory suggests that MM induces hyperlipidemia, but the causal relationship between the two awaits further investigation[20].
In conclusion, this article reports on a case of IgA type multiple myeloma (MM) accompanied by hyperlipidemia. Severe hyperlipidemia may trigger atherosclerosis and cardiovascular diseases, thereby exacerbating the condition of MM and complicating clinical treatment. When patients exhibit hyperlipidemia, clinicians should emphasize the correlation with MM, especially IgA type MM, based on laboratory tests and clinical indicators. Early detection and intervention are crucial to address the challenges posed by the coexistence of hyperlipidemia and MM, as severe hyperlipidemia can potentially worsen the prognosis, leading to increased difficulty in clinical management.