What are the symptoms of Waldenstrom macroglobulinemia?

Symptoms of Waldenström Macroglobulinemia

The most common symptoms of Waldenström macroglobulinemia (WM) include fatigue related to anemia, B symptoms (fever, night sweats, weight loss), hyperviscosity syndrome, neuropathy, and organomegaly. 1

Common Clinical Manifestations

Constitutional Symptoms

• B symptoms:
  • Fever
  • Night sweats
  • Weight loss
  • Fatigue (often related to anemia)

Hematologic Manifestations

• Cytopenias:
  • Anemia (median hemoglobin value at diagnosis is 10 g/dL) 2
  • Thrombocytopenia

Hyperviscosity-Related Symptoms

• Neurological manifestations:
  • Headaches
  • Blurry vision
  • Visual loss
  • Confusion
  • Somnolence (in severe cases)
  • Syncope 3
• Ophthalmologic findings:
  • Retinal venous engorgement ("sausaging")
  • Retinal hemorrhages
  • Retinopathy (can be severe and potentially lead to vision loss) 3
• Mucosal bleeding:
  • Epistaxis (nosebleeds)
  • Oronasal bleeding 2

Lymphoid Tissue Involvement

• Lymphadenopathy (15% of patients) 2
• Hepatomegaly (20% of patients) 2
• Splenomegaly (15% of patients) 2

Neurological Manifestations

• Peripheral neuropathy (common in WM)
  • Typically presents as slowly progressing, demyelinating, symmetrical sensory peripheral neuropathy
  • Often initially affects the feet 1
  • May be associated with anti-myelin-associated glycoprotein (anti-MAG) antibodies

Immunologic Complications

• Cold agglutinin disease:
  • Hemolytic anemia
  • Acrocyanosis
  • Raynaud's phenomenon
• Cryoglobulinemia:
  • Raynaud-like symptoms
  • Acrocyanosis
  • Ulcerations of extremities 1

Renal Manifestations

• Renal insufficiency (rare)
• Tubulointerstitial nephritis (rare) 3

Rare Manifestations

• Amyloidosis (uncommon complication)
  • Can affect kidneys, heart, liver, and peripheral nerves 1
• Gastrointestinal symptoms
  • Nausea
  • Dysgeusia 3

Clinical Indications for Treatment

Not all patients with WM require immediate treatment. The following symptoms/findings indicate the need for therapy:

• Recurrent fever, night sweats, weight loss, fatigue
• Hyperviscosity syndrome
• Symptomatic or bulky lymphadenopathy (≥5 cm)
• Symptomatic hepatomegaly and/or splenomegaly
• Symptomatic organomegaly or tissue infiltration
• Peripheral neuropathy due to WM
• Cytopenias (hemoglobin <10 g/dL, platelets <100 × 10^9/L)
• Amyloidosis
• Symptomatic cryoglobulinemia
• Cold agglutinin disease 1, 4

Diagnostic Approach for Suspected WM

When these symptoms are present, the following diagnostic tests should be performed:

• Complete blood count
• Serum chemistry including LDH and albumin
• Serum protein electrophoresis with immunofixation
• IgM quantification
• Beta-2 microglobulin level
• Bone marrow aspiration and biopsy with testing for MYD88L265P mutation (present in ~90% of WM cases)
• Imaging studies (CT or MRI) to document organomegaly/adenopathies 1

Important Clinical Pitfalls

1. Hyperviscosity syndrome requires immediate intervention with plasmapheresis followed by systemic therapy to prevent serious neurological complications 1

2. IgM flare can occur after rituximab treatment, potentially exacerbating hyperviscosity symptoms - consider plasmapheresis before rituximab in patients with high IgM levels 1

3. Neuropathy in WM may have multiple causes - consultation with a neurologist is strongly recommended as neuropathy may not always be WM-associated 1

4. Retinopathy can be severe and potentially lead to vision loss, but may recover completely with proper treatment 3

5. Renal failure is rare but can occur and may require hemodialysis 3

By recognizing these diverse symptoms early, appropriate diagnostic testing can be initiated promptly, leading to earlier diagnosis and treatment of WM, potentially preventing serious complications such as hyperviscosity syndrome.