What are the diagnostic and treatment approaches for B symptoms (unexplained fever, night sweats, and significant unintentional weight loss)?

Diagnostic and Treatment Approaches for B Symptoms

B symptoms, defined as unexplained fever >38°C, drenching night sweats, and unintentional weight loss >10% of body weight within 6 months, require prompt evaluation as they often indicate underlying lymphoma or other serious conditions. 1

Diagnostic Approach

Initial Evaluation

• Complete history and physical examination focusing on:
  • Duration and pattern of fever, night sweats, and weight loss 1
  • Associated symptoms (fatigue, pruritus, alcohol intolerance) 1
  • Thorough examination of all lymphoid regions, spleen, and liver 1

Laboratory Studies

• Complete blood count with differential and platelets 1
• Erythrocyte sedimentation rate (ESR) 1
• Comprehensive metabolic panel including:
  • Lactate dehydrogenase (LDH) 1
  • Liver function tests 1
  • Alkaline phosphatase 1
  • Albumin 1
  • C-reactive protein (CRP) 1
• Serum protein electrophoresis with immunofixation 1
• Viral screening (HBV, HCV, HIV) 1

Imaging

• Chest X-ray (especially if large mediastinal mass suspected) 1
• Contrast-enhanced CT scan of neck, chest, abdomen, and pelvis 1
• PET/CT scan (skull base to mid-thigh) - essential for initial staging 1
  • Should be performed no longer than 1 month before starting therapy 1
  • Particularly important for evaluating bone marrow involvement 1

Tissue Diagnosis

• Excisional lymph node biopsy is preferred 1
  • Core needle biopsy may be adequate if diagnostic 1
  • Fine-needle aspiration alone is insufficient except in unusual circumstances 1
• Bone marrow biopsy if:
  • PET/CT is negative but cytopenias are present 1
  • PET/CT is unavailable 1

Common Etiologies of B Symptoms

Lymphomas

• Classical Hodgkin Lymphoma (cHL) 1
  • Characterized by Reed-Sternberg cells 1
  • Immunophenotype: CD30+, CD15+, CD20-/+ (weak), CD45- 1
• Non-Hodgkin Lymphoma (NHL) 1
  • Diffuse Large B-Cell Lymphoma (DLBCL) 1
  • Marginal Zone Lymphomas (MZL) 1
  • Nodal Marginal Zone Lymphoma (NMZL) - 10-20% present with B symptoms 1

Other Conditions

• Waldenström's Macroglobulinemia 1
• Follicular Lymphoma (when symptomatic) 1
• Infections (tuberculosis, HIV, endocarditis) 2
• Autoimmune disorders 2
• Solid malignancies 2

Treatment Approach

General Principles

• Treatment should target the underlying cause 1
• For lymphomas, treatment depends on histologic type and stage 1
• Resolution of B symptoms is an important treatment goal and indicator of response 1

Treatment Based on Lymphoma Type

Classical Hodgkin Lymphoma

• Limited stage (I-II):
  • 2-3 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved-field radiotherapy 1
• Advanced stage (III-IV):
  • 6 cycles of ABVD or
  • Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) 1, 3

Non-Hodgkin Lymphoma

• DLBCL: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 3
• Marginal Zone Lymphoma: Treatment depends on site and extent 1
• Follicular Lymphoma with B symptoms: Chemoimmunotherapy (rituximab plus chemotherapy) 1

Waldenström's Macroglobulinemia

• B symptoms are a clinical indication for initiating therapy 1
• Treatment options include rituximab-based regimens or ibrutinib 1

Monitoring and Follow-up

• Regular assessment of symptom resolution during treatment 1
• PET/CT for response evaluation at end of treatment 1
• Long-term surveillance for:
  • Disease recurrence 3
  • Treatment complications 3
  • Secondary malignancies 3

Important Considerations

• B symptoms often indicate more advanced disease and may be associated with poorer prognosis 1
• Avoid corticosteroids before diagnosis as they can mask lymphoma 2
• Consider age-appropriate vaccinations due to immunosuppression from underlying disease 3
• In elderly patients or those with comorbidities, treatment toxicity must be carefully balanced against efficacy 3