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.