Because many organs can be affected by<unk> , the symptoms and signs vary greatly. Fatigue and bone pain are the most common symptoms at presentation. The CRAB criteria encompass the most common signs of<unk> : * Calcium: serum calcium >0.25<unk> ol/l (>1 mg/dl) higher than the upper limit of normal or >2.75<unk> ol/l (>11 mg/dl) * Renal insufficiency: creatinine clearance 1.77 mol/l (>2 mg/dl) * Anemia: hemoglobin value of >2g/dl below the lowest limit of normal, or a hemoglobin value Bone lesions: osteolytic lesions on skeletal radiography, CT, or PET/CT Bone pain Illustration showing the most common site of bone lesions in vertebrae Bone pain affects almost 70% of people with<unk>  and is the one of the most common symptoms.<unk>  bone pain usually involves the spine and ribs, and worsens with activity. Persistent, localized pain may indicate a pathological bone fracture. Involvement of the vertebrae may lead to spinal cord compression or kyphosis.<unk>  bone disease is due to the overexpression of receptor activator for nuclear factor κ B ligand (RANKL) by bone marrow stroma. RANKL activates osteoclasts, which resorb bone. The resultant bone lesions are lytic (cause breakdown) in nature, and are best seen in plain radiographs, which may show "punched-out" resorptive lesions (including the "raindrop" appearance of the skull on radiography). The breakdown of bone also leads to the release of calcium ions into the blood, leading to hypercalcemia and its associated symptoms. Anemia The anemia found in<unk>  is usually normocytic and normochromic. It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines. Impaired kidney function Impaired kidney function may develop, either acutely or chronically, and with any degree of severity. The most common cause of kidney failure in<unk>  is due to proteins secreted by the malignant cells.<unk>  cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys. Kidneys can be damaged by the effects of proteins or light chains. Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis, thereby contributing to kidney failure. Amyloidosis is a distant third in the causation. People with amyloidosis have high levels of amyloid protein that can be excreted through the kidneys and cause damage to the kidneys and other organs. Light chains produce myriad effects that can manifest as the Fanconi syndrome (type II kidney tubular acidosis). Infection The most common infections are pneumonias and pyelonephritis. Common pneumonia pathogens include S. pneumoniae, S. aureus, and K. pneumoniae, while common pathogens causing pyelonephritis include E. coli and other Gram-negative organisms. The greatest risk period for the occurrence of infection is in the initial few months after the start of chemotherapy. The increased risk of infection is due to immune deficiency. Although the total immunoglobulin level is typically elevated in<unk> , the majority of the antibodies are ineffective monoclonal antibodies from the clonal plasma cell. A selected group of people with documented hypogammaglobulinemia may benefit from replacement immunoglobulin therapy to reduce the risk of infection. Neurological symptoms Some symptoms (e.g., weakness, confusion, and fatigue) may be due to anemia or hypercalcemia. Headache, visual changes, and retinopathy may be the result of hyperviscosity of the blood depending on the properties of the paraprotein. Finally, radicular pain, loss of bowel or bladder control (due to involvement of spinal cord leading to cord compression) or carpal tunnel syndrome, and other neuropathies (due to infiltration of peripheral nerves by amyloid) may occur. It may give rise to paraplegia in late-presenting cases. When the disease is well-controlled, neurological symptoms may result from current treatments, some of which may cause peripheral neuropathy, manifesting itself as numbness or pain in the hands, feet, and lower legs. Mouth The initial symptoms may involve pain, numbness, swelling, expansion of the jaw, tooth mobility, and radiolucency.<unk>  in the mouth can mimic common teeth problems like periapical abscess or periodontal abscess, gingivitis, periodontitis, or other gingival enlargement or masses.
Multiple myeloma
Monoclonal gammopathy of renal significance  Monoclonal gammopathy of renal significance  1
Monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of renal significance
Smouldering myeloma
Waldenström macroglobulinemia
AL amyloidosis
Plasma cell leukemia