Immunological and Inflammatory Symptoms

1 Flu-Like Symptoms

Many ME/CFS patients experience chronic or recurrent flu-like symptoms even in the absence of active infection.

Sore Throat.

  • Persistent or recurrent sore throat without infection
  • Tender, swollen throat sensation
  • May worsen with exertion or during PEM

Tender Lymph Nodes.

  • Painful, swollen lymph nodes (cervical, axillary, inguinal)
  • Lymphadenopathy without evidence of infection
  • Lymph node tenderness worsening during crashes

Low-Grade Fever and Chills.

  • Recurrent low-grade fever (37.5–38°C)
  • Subjective fever sensation even when temperature normal
  • Chills and cold intolerance
  • Night sweats
  • Temperature dysregulation (alternating hot/cold)

Mechanism. Flu-like symptoms reflect chronic immune activation and cytokine production, even without active infection. Elevated inflammatory markers suggest ongoing immune system dysregulation.

2 Infection Susceptibility and Viral Reactivation

Recurrent Infections.

  • Frequent upper respiratory infections
  • Recurrent urinary tract infections
  • Skin infections
  • Sinus infections
  • Longer recovery from infections compared to pre-illness

Viral Reactivation.

  • Reactivation of latent herpesviruses (EBV, HHV-6, CMV, VZV)
  • Elevated herpesvirus antibody titers (note: structural antigen IgG — VCA, EBNA-1 — reflects long-lived plasma cell output from primary infection decades earlier, not necessarily current viral activity; see Section HSV Dormancy-Undormancy Probe — Structural Limitations for interpretation)
  • Recurrent cold sores or shingles
  • Chronic viral symptoms

Mechanism. ME/CFS patients show evidence of immune exhaustion: T-cells are functionally impaired and unable to maintain control over latent infections. This creates susceptibility to new infections and reactivation of dormant viruses.

3 Allergies and Mast Cell Activation

New or Worsening Allergies.

  • Development of new food allergies or intolerances
  • Worsening seasonal allergies
  • Reactions to previously tolerated substances
  • Oral allergy syndrome (cross-reactivity with pollen)

Mast Cell Activation Syndrome (MCAS) Features.

  • Flushing and skin rashes (urticaria, hives)
  • Angioedema (swelling of face, lips, tongue)
  • Anaphy-laxis or anaphy-lactoid reactions
  • Gastrointestinal symptoms (nausea, diarrhea, abdominal pain)
  • Respiratory symptoms (wheezing, throat tightness)
  • Cardiovascular symptoms (tachycardia, hypotension)
  • Neurological symptoms (brain fog, headache)
  • Triggered by heat, cold, stress, exertion, foods, medications, or chemicals

Mechanism. An estimated 30–50% of ME/CFS patients show features of mast cell activation syndrome. Mast cells become hyper-reactive, de-granulating in-appropriately and releasing histamine and other in-flammatory mediators.