Pathogeneisis of Fever 
  • Endogenous Pyrogen: 
  • Exogenous Pyrogen: microbial products, microbial toxins, whole microorganisms (viruses ). Eg. 
    • Lipopolysaccharide (endotoxin) produced by gram negative bacteria 
    • Enterotoxin of S aureus 
    • Gp A and B streptococcal toxins (aka Superantigens) 
  • Pyrogenic Cytokines 
    • IL1, IL6, TNF, and Ciliary Neurotropic Factor (member of IL6 family), IFN-alpha. 
      • Note: Fever is a prominent side effect of IFN-alpha used in the treatment of hepatitis
    • These cytokines trigger the hypothalamus to raise the set point to febrile levels 
Regulation of Body Temperature
  • Controlled in Hypothalamus 
    • Preoptic Hypothalamus
    • Posterior Hypothalamus 
  • There are 2 kinds of signals 
    • From peripheral nerves (warmth, or cold)
    • From the temperature of the blood bathing the region
  • Mean Oral Temp : 36.8 +-0.4 
  • Low at 6 am, higher at 4-6 pm 
  • Definition: AM temperature > 37.2 (98.9); PM temperature 37.7 (99.9) defines fever. 
    • Thus, normal daily variation is 0.5 C or 0.9 F. But, in patients who are recovering from illness this variation can be > 1 degree C. 
  • Rectal temperature is 0.4 C or 0.7 F higher than oral temperature 

Causes of FUO

Causes of Recurrent FUO 

Case Discussion: 
71 yo AAM with hx of SCL, present with fever of 1 day. 101 F. Persist. Started on Vanc and Zosyn. Fever persists. ANC 650. Neupogen given. ANC > 1500. Fever persists. Procalcitonin: > 100, CRP > 30, Ferritin > 10,000, NK cell increased by 43 %, IL-2 receptor elevated. Has Splenomegaly that is same as it was 3 years back. Pan CT is normal except for few mediasteinal LN. BM Bxp is normal. Scheduled steroids is started, fever subsides for few days, before fever recurs. All cx are negative. What to do? 
Patient has few monocytes in the circulation. 

Could this be systemic mastocytosis. Less likely. Below is the symptoms and clinical disease manifestations of Mast cell disease. It releases histamines, and many symptoms are related to that. 

Could this be Malignant Histiocytosis? What is histiocytosis? http://emedicine.medscape.com/article/958026-clinical#b4

The histiocytoses encompass a group of diverse disorders characterized by the accumulation and infiltration of variable numbers of monocytes, macrophages, and dendritic cells in the affected tissues. 

The classification of histiocytic disorders the World Health Organization (WHO) has proposed is as follows:

  • Class I - Langerhans cell histiocytosis
  • Class II
  • Class III
    • Malignant histiocytic disorders
    • Acute monocytic leukemia (FAB M5). Could this be monocytic leukemia or lymphoma? 
    • Malignant histiocytosis
    • True histiocytic lymphoma

Heat Stroke vs Heat Exhuastion