The Case of the Kissing Disease

1. The Case of the Kissing Disease Angela Yee: Researched Hx Questions, Physical Examination, Pathophysiology Hemant Sharma: Researched Hx questions, Differential diagnosis with explanation, prognosis and patient education. Maria Reyes Diaz: Researched Hx. questions, interpretation of lab results, most likely diagnosis with explanation, management, prognosis and patient education Nipuni Ranepura: Researched Hx Questions, Lab investigations. Organized/Edited final slides June 16, 2014

2. Hematology Case 1: Overview •History •Physical Examination •Lab Investigations: results and interpretation •Assessment: DDx and most likely Dx •Management •Prognosis and Patient education

3. History 20 year old female complains of worsening fatigue over the last week or so, with associated sore throat and headaches. She also reports occasional fever and chills. She normally runs 3 miles per day, which she has been unable to do since the onset of symptoms.

4. Additional Relevant History Questions • When did her symptoms begin and has she had similar symptoms previously? • Does she have generalized or localized pain/discomfort? • Are menstrual periods normal and regular? • Is she taking any medication? • Is she up to date with her immunizations? • Has she had a recent hospitalizations? • What is her past medical, family and social history? • Has she been in contact with anyone that is/has been sick? • Has she travelled outside the country in the past 6 mos?

5. Physical Exam Erythema of the throat and tonsillar pillars. Cervical lymph nodes are swollen bilaterally, tender and mobile.

6. Laboratory Investigations RBC 5.24 x 1012/L Hgb 153 g/L Hct 46.2 % MCV 87.9 fL MCHC 332 g/L RDW 0.121 WBC 12.8 x 109/L Neutrophils 24 % Leukocytes 73% Monocytes 0% Eosinophils 3% Basophils 0% PLT 333 x 109/L Heterophil antibody screen positive Blood smear analysis normocytic, normochromic red blood cells. White blood cells are large with smudged chromatin pattern and reactive lymphocytes. Platelet morphology is normal

7. Interpretation of Lab Results(key findings) Leukocytosis and Lymphocytosis: canindicate infection Neutropenia: different etiologies Monocytopenia: rare but can occur with autoimmune disorders or hairy cell leukemia Positive Heterophile Test: Sensitive and specific test for detecting heterophile antibodies Reactive Lymphocytes/ atypical lymphocytes •  common in some viral infections (i.e EBV and CMV) Large WBC with smudged chromatin pattern: only significant when found in abundance

8. Differential Diagnosis with brief explanation of rationale • Infectious mononucleosis • Rubella • Streptococcal Pharyngitis • Acute Herpetic Pharyngotonsillitis • Toxoplasmosis • HIV

9. Most Likely Diagnosis with brief explanation of rationale • The patient is a 20 yr old female presenting with common symptoms of Infectious Mononucleosis. She presents with malaise, headache, fever, chills, sore throat and lymphadenopathy. Lab results further support the diagnosis of Infectious Mononucleosis. Results were positive for leukocytosis, neutropenia, monocytopenia, and a positive heterophile test which is often a sign of mononucleosis. Worsening symptoms over the period of one week and the absence of other cold symptoms make these findings suspicious for Infectious Mononucleosis.

10. Pathophysiology •  Transmitted through bodily secretions •  Virus infects B-lymphocytes •  B-lymphocytes target oropharynx, salivary glands, and the lymphoid • cells •  Activation of T-cells against the B-lymphocytes control infected • B-lymphocyte proliferation •  Infected B-lymphocytes enter bloodstream to spleen, liver, and • peripheral lymph nodes (clinical presentation) •  Initiation of acute infection and humoral immunity; EBV structural • proteins used to diagnose EBV •  Normal T-lymphocyte function •  Abnormal/ineffective T-lymphocyte function

11. Management •  There is no treatment to completely eradicate the virus •  Acetaminophen or NSAIDs • Therapy is focused on management of symptoms • Corticosteroids:if complicated IM • Acyclovir:Antiviral, not very effective not used • Antibiotics are NOT EFFECTIVE- amoxicillin & ampicillin are contraindicated • Rest • Mono causes extreme fatigue therefore adequate rest is important especially early in the infection process •  **Avoid strenuous physical activity for at least 3 weeks • Patients with IM are at risk for splenic rupture • Splenic rupture requires surgical intervention

12. Prognosis & Patient Education • Mononucleosis is generally a self-limiting disease and infection • typically subsides within 2 to 4 weeks. • Most people recover without any permanent health • consequences. Complete recovery may take months • Complications are rare but life threatening, often due to splenic • rupture. •  Patient to refrain from strenuous physical activity for first 3 weeks • Patient should avoid exposing other people to their body • secretions because EBV remains viable in patients with EBV • infectious mononucleosis for months. • Although complete isolation is not required the patient is • instructed to still take precautions such as; Avoid sharing drinking • glasses or utensils and avoid kissing.

13. References Aspectsin, C. & Saccomano, S.J. Clinician Reviews: Infectious mononucleosis. Quadrant Healthcom, Inc. 2013; 23.6: 42. ALQEP: Hematology Morphology Critique [Internet]. [Updated 2004 May; Cited 2014 Jun 10]; Available from: http://www.cpsa.ab.ca/Libraries/pro_qofc_alqep_critiques/Critique_04-05-S.pdf?sfvrsn=0. Auwaerter, Paul. Patient information: Infectious mononucleosis (mono) in adults and adolescents (Beyond the Basics). [uptodate]. updated July 2013. cited June 2014. Accessed from http://www.uptodate.com/contents/infectious-mononucleosis-mono-in-adults-and-adolescents-beyond-the-basics Cunha, B.A. Infectious Mononucleosis: History [Internet]. [Updated 2014 Mar 30; cited 2014 Jun 10]; Available from: http://emedicine.medscape.com/article/222040-clinical#a0216. Cunha, B.A. Infectious Mononucleosis: Pathophysiology [Internet]. [Updated 2014 Mar 30; cited 2014 Jun 10]; Available from: http://emedicine.medscape.com/article/222040-overview#a0104. Cunha, B.A. Infectious Mononucleosis: Physical [Internet]. [Updated 2014 Mar 30; cited 2014 Jun 10]; Available from: http://emedicine.medscape.com/article/222040-clinical#a0217. Epstein-Barr virus and Infectious Mononucleosis. January 7, 2014; Available at: http://www.cdc.gov/epstein-barr/index.html Kaye, K.M. Infectious Mononucleosis [Internet]. [Updated 2013 July; cited 2014 Jun 10]; Available from: http://www.merckmanuals.com/professional/infectious_diseases/herpesviruses/infectious_mononucleosis.html. Marshall A. Lichtman. Monocytosis and Monocytopenia http://accessmedicine.mhmedical.com/content.aspx?bookid=358&sectionid=39835891&jumpsectionID=39847801

14. MediaLab incorporated. Smudge cells. Updated 2014. Cited June 2014. Accessed from http://www.medialabinc.net/spg48905/smudge_cells.aspx Merk Manual. Infectious Mononucleosis. Updated April 2013. Cited June 2014. Accessed from http://www.merckmanuals.com/professional/infectious_diseases/herpesviruses/infectious_mononucleosis.html?qt=Heterophil%20antibody%20test&alt=sh Merck Manual. Lymphocytic Leukocytosis. Updated January 2013. Cited June 2014. Accessed from http://www.merckmanuals.com/home/blood_disorders/white_blood_cell_disorders/lymphocytic_leukocytosis.html?qt=leukocytosis&alt=sh Merck Manual. Monocyte Disorders. Updated January 2013. Cited June 2014. Accessed from http://www.merckmanuals.com/home/blood_disorders/white_blood_cell_disorders/monocyte_disorders.html?qt=%20Monocytopenia%20&alt=sh Merck Manual. Neutropenia. Updated January 2013. Cited June 2014. Accessed from http://www.merckmanuals.com/home/blood_disorders/white_blood_cell_disorders/neutropenia.html Patient information: Infectious mononucleosis (mono) in adults and adolescents (Beyond the Basics). Updated July 2013. Cited June 2014. Accessed from http://www.uptodate.com/contents/infectious-mononucleosis-mono-in-adults-and-adolescents-beyond-the-basics Reddy, M. Smudge cells: clarifying the diagnosis [Internet]. [Updated 2007 Feb; Cited 2014 Jun 10]; Available from: http://www.parkhurstexchange.com/hematology/2007-02-15?zid= Salvaggio, MR. Herpes Simplex. January 25, 2012; Available at: http://emedicine.medscape.com/article/218580-clinical Vorvick, L.J. Mononucleosis [Internet]. [Updated 2012 May 15; cited 2014 Jun 10]; Available from: http://www.nlm.nih.gov/medlineplus/ency/article/000591.htm.