1. Pre-clinic Conference: Evaluation of Peripheral Eosinophila April 4-6, 2011 Michael K Mansour, MD, PhD

2. Heres a real case 35 yo presenting for routine primary care

3. Review of Immune Cells

4. Pathogen Innate Immunity Complete Immune Reaction B/T cells Draining Lymph nodes Antibody Cytokine Direct Killing

5. When are you concerned? Eosinophilia represents a large spectrum of disease Benign finding to life- threatening disease state Definition of clinically significant eosinophilia based on absolute number: – Mild = 500-1500 – Moderate = 1500-5000 – Severe = >5000

6. What accounts for the absolute number of eosinophils? Stimulation Production Consumption

7. Medications – NSAIDs – Antimicrobials (PCN, cephalosporin classes) – ASA – Beta-blockers Allergy – Asthma – Atopy – Nasal polyposis/ASA sensitivity Stimulation Production Consumption

8. Viruses – HIV – HTLV-1 Bacteria – Bartonella (cat-scratch fever) – Tuberculosis – Leprosy – Resolving scarlet fever – Syphilis Stimulation Production Consumption Fungi – Coccidomycoses – Aspergillus (ABPA) Parasites – Key is tissue invasion – Over 400 species – Strongyloides – Hookworm (Ancylostoma) – Schistosomiasis – Toxocara – Isopora – Dientamoeba

9. Disorders of bone marrow production – Hypereosinophilic syndrome – Mastocytosis Malignancy – Lymphoma (Hodgkin) – Leukemia (CEL) – Multiple solid tumors – Thymoma – Related to IL-5 production Stimulation Production Consumption Rheumatologic – Churg-Strauss syndrome – Wegeners granulomatosis – HyperIgE, facial deformities, dermatitis

10. Loss of eosinophils related to apotosis Downregulation of IL-5 Glucocorticoids key regulators of apotosis Steroid deficient states allow prolonged survival of eosinophils Stimulation Production Consumption

11. Evaluation…..is a journey; first phase Infectious Diseases – Microbiology evaluation 3 stool samples for O&P (2 at MGH >90% sensitivity) Specific serology for globe- specific travel HIV, Trep-sure, TST First question you ask is….have you traveled? Allergy – Review medications – Seasonal allergy – Atopy – Environmental testing – PFT YES! NO!

12. More rare diagnosis – Adrenal insufficiency Higher suspicion if physical suggests AI Vitals and routine blood work Malignancy – Non-resolving eosinophilia – Would need bone marrow evaluation Rheumatologic disorders maybe life-threatening – Always rely on physical exam to allow you the luxury of time – Keep an eye on end-organ damage – HES may have severe cardiac involvement with minimal peripheral eosinophilia Evaluation…..is a journey; second phase

13. Travel history Pre-1987 - Domestic USA trips 1987 (age 11) - United Kingdom, Ireland 1990 - Bermuda (very bad diarrhea) 1991 - Mexico, Jamiaca, Caymen Islands & Bahamas (cruise) 1992 - New Mexico 1994 - St. Maarten (spent a week), Germany 1997 - Aruba (week) 2000 - DC, Washington State, Alaska, Louisiana 2001 - Utah, Nevada 2002 - NC, TN, MS, AL, AR, GA 2003 - HI, FL (Key West) 2004 - St. Thomas, St. John, St. Lucia, Barbados, St. Maarten, Martinique (cruise but did eat in Barbados or Martinique)2005 - TX 2006 - Mexico (Acapulco - week, got sick), Netherlands, Norway, Sweden, Denmark, Finland, Russia, Estonia 2007 - CA, Greece --> got 'food poisoning' in Greece 2008 - Ireland, ME 2009 - DC, France, Italy 2010 - St. John, FL, UT Our case….

14. Eosinophilia represents a spectrum of disease Think of ABSOLUTE numbers (>400) First line question is have you traveled? The work-up may be a long journey Ask you friendly subspecialty colleagues for help ! Any sign of end-organ involvement should prompt a more rapid work-up Take Home Messages