Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

Monoclonal gammopathy of undetermined significance combined with renal damage is named monoclonal gammopathy of renal significance. There are few reports about IgA vasculitis in patients with monoclonal gammopathy of undetermined significance. Here, we report a case of monoclonal gammopathy of renal significance, who had manifestations of IgA vasculitis, including purpura, gastrointestinal bleeding and joint pain. The patient had elevated serum creatinine levels, prompting further investigation through immunofixation electrophoresis and bone marrow aspiration biopsy. Immunofixation electrophoresis showed IgA-λ-type monoclonal immunoglobulin, while the bone marrow aspiration biopsy suggested plasmacytosis. Kidney biopsy indicated membranous hyperplastic glomerulonephritis, light and heavy chain deposition, IgA-λ. The patient was diagnosed with monoclonal gammopathy of renal significance. In light of the elevated serum creatinine, the patient was treated with chemotherapy regimen (bortezomib +cyclophosphamide +dexamethasone). After chemotherapy, there was no significant improvement in the patient's renal function. Subsequently, the patient experienced abdominal pain, skin purpura, joint pain and severe gastrointestinal bleeding. Gastroenteroscopy did not find the exact bleeding position. Angiography revealed hyperplasia of left jejunal artery. Surgical operation found that the bleeding site was located between the jejunum and ileum, where scattered hemorrhagic spots and multiple ulcers were present on the surface of the small intestine, with the deepest ulcers reaching the serosal layer. And the damaged intestine was removed during the operation. Intestinal pathology showed multiple intestinal submucosal arteritis, rusulting in intestinal wall necrosis and multiple ulcers. Considering intestinal lesions as gastrointestinal involvement of IgA vasculitis, methylprednisolone was used continually after the operation, and the patient's condition was improved. However, after half a year, the patient suffered a severe respiratory infection and experienced a recurrence of serious gastrointestinal bleeding. It was considered that the infection triggered the activity of IgA vasculitis, accompanied by gastrointestinal involvement. Finally, the patient died from gastrointestinal bleeding. The present case represented a patient with monoclonal gammopathy of renal significance and IgA vasculitis, prominently presenting with renal insufficiency and severe gastrointestinal bleeding, making the diagnosis and treatment process complex. Patients with IgA monoclonal gammopathy who presented with abdominal pain, purpura, and arthralgia should be vigilant for the possibility of concomitant IgA vasculitis. The treatment of cases with IgA vasculitis combined with monoclonal gammopathy of renal significance was rather challenging. Plasma cell targeting therapy might be an effective regimen for IgA vasculitis with monoclonal gammopathy. However, patients with poor renal response to the treatment indicated poor prognosis.
Humans ; Cyclophosphamide/administration & dosage* ; Gastrointestinal Hemorrhage/etiology* ; IgA Vasculitis/complications* ; Immunoglobulin A ; Intestine, Small/pathology* ; Kidney/pathology* ; Kidney Diseases/pathology* ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Necrosis ; Paraproteinemias/complications* ; Vasculitis/etiology*

A 62-year-old female visited our clinic with progressively decreased vision in both eyes beginning 12 years prior. Idiopathic corneal opacity in all layers of the cornea was found in both eyes. One year later, we performed penetrating keratoplasty on the undiagnosed right eye. During post-surgical follow-up, corneal edema and stromal opacity recurred, and penetrating keratoplasty was performed two more times. The patient's total serum protein level, which had previously been normal, was elevated prior to the final surgery. She was diagnosed with monoclonal gammopathy of undetermined significance. We made a final diagnosis of monoclonal gammopathy-associated crystalline keratopathy after corneal biopsy. Monoclonal gammopathy-associated crystalline keratopathy is difficult to diagnose and may lead to severe visual loss. A systemic work-up, including serologic tests like serum protein or cholesterol levels, is needed in patients with unexplainable corneal opacity.
Corneal Edema/etiology/*metabolism/physiopathology/surgery ; Corneal Neovascularization/etiology/*metabolism/physiopathology/surgery ; Corneal Opacity/etiology/*metabolism/physiopathology/surgery ; Crystallins/*metabolism ; Female ; Humans ; Keratoplasty, Penetrating ; Microscopy, Electron ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance/*complications/pathology ; Reoperation ; Visual Acuity