What symptoms would an older adult with hyperproteinemia and a low anion gap, potentially indicating multiple myeloma, likely experience?

Multiple Myeloma: Clinical Presentation and Symptoms

An older adult with hyperproteinemia and low anion gap suggestive of multiple myeloma will most likely present with the classic "CRAB" criteria symptoms: bone pain, fatigue from anemia, symptoms of renal dysfunction, and manifestations of hypercalcemia. 1, 2

Cardinal Symptoms (CRAB Criteria)

The International Myeloma Society defines symptomatic multiple myeloma by end-organ damage manifesting as:

Bone Involvement

• Bone pain is the most common presenting symptom, typically affecting the back, ribs, and long bones 3, 4
• Pathologic fractures may occur, particularly vertebral compression fractures 2
• Lytic bone lesions are present in approximately 79% of patients at diagnosis 5
• Important caveat: In elderly patients, distinguish sudden-onset bone pain (suggesting active myeloma) from progressive osteoporosis with longstanding history (more likely benign) 6

Anemia Manifestations

• Fatigue, weakness, and malaise are extremely common, occurring in 73% of patients at presentation 5, 4
• Pallor may be evident on examination 6
• The anemia is normochromic and normocytic with hemoglobin <10 g/dL or ≥2 g/dL below normal 6, 2
• Critical distinction: In elderly patients, exclude other causes including iron, B12, or folate deficiency, anemia of chronic disease, or myelodysplastic syndrome before attributing anemia solely to myeloma 6

Renal Dysfunction Symptoms

• Renal impairment occurs in 19-50% of patients at diagnosis 6, 5
• Symptoms include nausea, vomiting, decreased urine output, and confusion from uremia 4
• Serum creatinine >2 mg/dL or estimated creatinine clearance <40 mL/min defines renal insufficiency 6, 2
• Diagnostic pitfall: Mild creatinine elevation with nonselective proteinuria may be due to diabetes or hypertension rather than myeloma in elderly patients 6

Hypercalcemia Manifestations

• Serum calcium >11.5 mg/dL causes polyuria, polydipsia, constipation, nausea, and progressive dehydration 1, 2
• Confusion, lethargy, and altered mental status may occur with severe hypercalcemia 4
• Muscle weakness and fatigue are prominent 1
• Important consideration: Coincidental hyperparathyroidism should be excluded, especially when lytic lesions are absent and hypercalcemia is mild but stable 6

Additional Common Symptoms

Infectious Complications

• Recurrent infections occur due to immunoparesis from suppression of normal immunoglobulin production 2, 4
• Bacterial infections, particularly pneumonia and urinary tract infections, are frequent 4

Neurologic Symptoms

• Peripheral neuropathy may be present, manifesting as numbness, tingling, or pain in extremities 6
• Spinal cord compression can occur from vertebral collapse, causing weakness, sensory changes, or bowel/bladder dysfunction 4

Less Common Presentations

• Hyperviscosity syndrome (rare): blurred vision, headache, bleeding, and neurologic symptoms when M-protein is very high 3
• Bleeding tendency from thrombocytopenia: petechiae, easy bruising, epistaxis 6
• Weight loss and night sweats may occur 4

Physical Examination Findings

• Pallor from anemia 6
• Bone tenderness on palpation 4
• Petechiae or purpura if thrombocytopenic 6
• Organomegaly (hepatomegaly, splenomegaly) is uncommon in typical myeloma but may occur 6
• Lymphadenopathy is rare in standard myeloma 6

Asymptomatic vs. Symptomatic Disease

Critical distinction: Patients with smoldering (asymptomatic) myeloma have M-protein ≥3 g/dL and/or bone marrow plasma cells ≥10% but lack CRAB criteria symptoms and do not require immediate treatment 6. These patients should be observed at 3-6 month intervals rather than treated 6.

Context-Specific Presentation

In the specific scenario of hyperproteinemia with low anion gap:

• The low anion gap results from the cationic properties of the monoclonal immunoglobulin 2
• This patient would likely exhibit symptoms from the underlying CRAB criteria, particularly bone pain, fatigue from anemia, and potentially renal dysfunction 1, 2
• The hyperproteinemia itself may cause hyperviscosity symptoms if severe, though this is uncommon 3