Constitutional Symptoms and Their Differential Diagnosis

Constitutional Symptoms: Overview - Body's Red Flags

• Definition: Non-specific systemic indicators: fever, weight loss, fatigue, night sweats, anorexia. Signal underlying disease.
• General Approach:
  • History: Detail B symptoms (lymphoma).
  • Exam: Thorough physical.
  • Labs: CBC, ESR/CRP, LFT, RFT, TSH, urinalysis.

⭐ The presence of B symptoms (fever, night sweats, weight loss) in lymphoma significantly impacts staging and prognosis.

Fever: Investigation & Differentials - Heat of Battle

• Definition: Oral temp >37.8°C (100.0°F), Core temp >38.3°C (101.0°F).
• Fever Patterns: Sustained, Intermittent, Remittent, Hectic, Pel-Ebstein. Offer clues but have limited specific diagnostic utility. 📌 Mnemonic: SIR HP (Sustained, Intermittent, Remittent, Hectic, Pel-Ebstein).
• Differential Diagnosis (DDx): Key categories:
  • Infections: TB, malaria, typhoid, UTI, pneumonia.
  • Malignancies: Lymphoma, leukemia, RCC, HCC.
  • Autoimmune/Inflammatory: SLE, RA, vasculitis, Still's disease.
  • Drug fever.
  • Miscellaneous: PE, DVT, gout, IBD, sarcoidosis.
• Fever of Unknown Origin (FUO): Petersdorf & Beeson criteria: Fever >38.3°C (on several occasions), duration >3 weeks, no diagnosis after 1 week of inpatient investigation or 3 outpatient visits.

⭐ Pel-Ebstein fever, a cyclical fever pattern, is classically associated with Hodgkin's lymphoma.

FUO Diagnostic Approach (Indian Context)

Weight Loss: Unintentional Shedding - The Great Shrink

• Significant: >5% body weight loss in 6-12 months or >4.5 kg.
• Causes:
  • Malignancy (GI, lung, hematologic)
  • Chronic infections (TB, HIV, fungal)
  • Endocrine (hyperthyroidism, uncontrolled DM, adrenal insufficiency)
  • GI disorders (malabsorption, IBD, PUD)
  • Psychiatric (depression, anorexia nervosa)
  • Severe organ dysfunction (CHF, CKD, COPD)
  • Medications, Substance abuse
• Initial Evaluation: History (diet, meds, psych), Physical Exam (seek red flags: lymphadenopathy, organomegaly, masses).

⭐ Occult malignancy is a leading cause of unexplained involuntary weight loss in the elderly, particularly GI and lung cancers.

Fatigue & Malaise: Chronic Drain - Energy Vampires

• Fatigue: Subjective lack of physical/mental energy.
• Malaise: General feeling of discomfort or illness.
• Differential Diagnosis (Energy Vampires):
  • Infections: Chronic (TB, HIV, EBV, CMV, endocarditis)
  • Endocrine: Hypothyroidism, adrenal insufficiency, DM, hypogonadism
  • Hematologic: Anemia
  • Malignancy
  • Psychiatric: Depression, anxiety, somatization
  • Autoimmune: SLE, RA
  • Neuromuscular: MS, myasthenia gravis
  • Sleep disorders: OSA
  • Medications: Beta-blockers, sedatives
  • Chronic Organ Failure: Cardiac, renal, hepatic
  • Chronic Fatigue Syndrome (ME/CFS)
• Red Flags: New/progressive fatigue, unexplained weight loss, persistent fever, lymphadenopathy, focal neurological signs.

⭐ Fatigue is a common presenting symptom of hypothyroidism and often improves significantly with thyroid hormone replacement.

Night Sweats & Anorexia: Damp & Diminished - Ominous Duo

• Night Sweats: Drenching sweats, requiring change of bedclothes, not solely due to warm environment.
  • Key Causes: Infections (TB - classic, HIV, endocarditis), Malignancies (lymphoma - B symptom, leukemia), Endocrine (hyperthyroidism, pheochromocytoma), Medications (antidepressants, antipyretics), Autoimmune.
• Anorexia: Loss of appetite.
  • Key Causes: Often overlaps weight loss causes (malignancy, chronic infections, GI disorders, depression, uremia). Differentiate from sitophobia (fear of eating due postprandial pain).

⭐ Drenching night sweats, especially when accompanied by fever and weight loss, are a strong indicator for investigating tuberculosis or lymphoma in the Indian context.

High‑Yield Points - ⚡ Biggest Takeaways

• Fever of Unknown Origin (FUO): >3 weeks, >38.3°C, undiagnosed after 1 week inpatient workup.
• Significant weight loss: >5% in 6-12 months; suspect malignancy, TB, hyperthyroidism.
• Fatigue: Differentiate from weakness; consider anemia, hypothyroidism, chronic infections, depression.
• Night sweats: Often with FUO; classic for TB, lymphoma, menopause.
• Pallor: Suggests anemia; investigate nutritional deficiencies, chronic disease, blood loss.
• Lymphadenopathy: Localized vs. generalized; consider infections, malignancy (lymphoma), autoimmune diseases.