Infectious mononucleosis Made Extremely Simple!!!

A brief description of a very common illness causing fever, rash and sore throat. Blood profile is altered. Commonly seen in adults as well as young children. Extremely useful for doctors, medical students, MD, dermatologists, pediatricians and Nurses.

1. Epstein Barr Virus Infections:

2. General description of disease domain: Infection in early childhood : Virus spreads by contact with saliva on fingers or fomites , Usually seen in economically disadvantaged societies. Infection is usually asymptomatic or mild. Infection in Adults: Seen in more developed communities, Kissing is the usual route of infection (hence the name: Kissing Disease), also occasional droplet spread may also occur.

3. Basic biology: Epstein–Barr virus is a γ herpesvirus that usually infects B lymphocytes and occasionally T lymphocytes, monocytes or squamous epithelial cells. The virus has a tropism towards cells that express complement receptor 2 on their surface. Through this the virus is able to bind and gain entry into the cell. Pathophysiology : In the oro ‐pharynx, liberation of virus into the saliva from localized differentiated B cells explains the spread of infection between individuals. Primary infection, whether clinical or subclinical, is followed by lifelong persistence of the virus in a latent state in resting memory B cells where the virus is quiescent. In cases of immune compromise, viral replication starts again. Latent EBV is associated with nasopharyngeal carcinoma and various B lymphoproliferative lesions later in life. Occasionally, the primary viral infection does not settle and a state of chronic active infection develops.

4. Infectious Mononucleosis:

5. Introduction and general description: Infectious mononucleosis is a Triad of acute febrile illness with phyrangitis and cervical lymphadenopathy . Also called Glandular Fever or Kissing Disease.

6. Epidemiology: Incidence and prevalence An incidence of 500/100 000 per year is reported from the USA. Incubation Period: 1-2 months 

7. Clinical Features: Prodrome : A prodrome of fatigue, myalgia and malaise may persist for 2 weeks before the onset of fever, exudative phyangitis and lymphadenopathy .

8. Clinical features Contd : Early physical Findings: Fever: low grade with malaise and fatigue Lymphadenopathy : especially cervical lymphadenopathy Exudative pharyngotonsillitis : which doesn’t get better with antibiotics Rash: appears between the fourth and sixth days. Macular or maculopapular eruption of the trunk or upper arms, involving the face and forearms ,thighs and legs occasionally. Fades in a few days to a week. If ampicillin or amoxicillin is taken during the course of the illness, an extensive maculopapular or morbilliform eruption develops in over 90% of cases, 7–10 days after the start of treatment. Most marked on extensor surfaces and pressure areas. A similar effect is occasionally seen with penicillin, tetracyclines and azithromycin Palatal petechiae : A distinctive feature of the disease. Occurs at the junction of soft and hard palate Appears on 2 nd or 3 rd day of fever. Periorbital edema: Bilateral upper lid edema. Also called Hoagland Sign Relative bradycardia noted but it is not a constant finding.

9. Later physical findings: Hepatomegaly , Jaundice, Uvular edema,  Splenomegaly and tenderness and, rarely (1-2%), findings associated with splenic rupture.

10. Differential diagnosis:

11. Complications and co‐morbidities: Cold agglutinins responsible for transient cold urticaria which may rarely be severe enough to result in ulceration. Splenic rupture and encephalitis are life‐threatening complications. Upper airway obstruction due to hypertrophy of lymphoid tissue.

12. Associations: Gianotti–Crosti syndrome: Epstein–Barr virus is associated with this eruption, which results from reaction to viral infection in childhood Lipschütz ulcers: Painful genital ulceration usually in adolescents without venereal infection Associated with primary EBV infection. Ulcers are sloughy , often multiple and develop in association with malaise, fever and inguinal lymphadenopathy . Heal spontaneously but somewhat slowly. Haemophagocytic syndrome ( haemophagocytic lymphohistiocytosis ): (a) It most commonly affects children and adolescents. (b) Infection of T lymphocytes or natural killer (NK) cells triggers T‐cell proliferation and overactivity of NK cells with overproduction of cytokines, especially interferon‐α and TNF‐α. (c) Investigations show a high viral EBV load in blood as well as elevated acute phase reaction proteins. (d) Features are fever, followed by the pancytopenia with coagulation defects and multiorgan failure. Lymphadenopathy , hepatosplenomegaly and haemorrhage into the lungs and bowel, meningitis or encephalitis. maculopapular rash with epidermal necrosis or nodules with granulomatous inflammation (e) Treatment: full supportive care; rapid commencement of immunosuppressive as well as antiviral therapy (f) Prognosis is often poor.

13. Kikuchi’s histiocytic necrotizing lymphadenitis: Also called Histiocytic necrotizing lymphadenitis, Is a benign and self-limited disease that mainly affects young women. Patients present with localized lymphadenopathy , fever, and leukopenia . May be associated with EBV Other Reactive dermatoses : Erythema multiforme Erythema nodosum Erythema annulare centrifugum Acute pityriasis lichenoides Chronic bullous disease of childhood Papular pruritic gloves and socks A predominantly facial eruption resembling inflammatory granuloma annulare

14. Disease course and prognosis: Acute disease clears within a month Cervical lymphadenopathy may take 3 months to settle. Relapsing episodes of malaise, fatigue, fever and lymphadenopathy , but no recurrent skin eruption. Reactivation of the latent infection is associated with the development of oral hairy leukoplakia in immune suppression and with drug hypersensitivity syndrome or DRESS

15. Investigations: General Tests: Lymphocytosis with at least 10% atypical cells seen on blood film in acute infection Deranged liver function tests indicate hepatocellular damage which may lead to jaundice Specific Tests: Heterophile antibodies (using Paul- Bunnell Test or Monospot Test) Agglutinate sheep or horse red blood cells, Become positive in 90% of patients after 1–2 weeks, so are not useful in the early stages of the infection. False negative results are more common, False positives (for instance in several other infectious diseases and also lymphomas and leukaemias ). Specific EBV Serology: Antibodies to viral antigens can be detected in early infection (early antigen, EA, and viral capsid antigen, VCA). IgM VCA appears in early infection and persists for 4-6 weeks; also appearing on reactivation IgG VCA appear at clinical presentation but persist throughout life. Antibodies to the EBV nuclear antigen A, EBNA , are detectable 6-12 weeks after infection and persist for life. PCR: to detect viral DNA or RNA RT‐PCR in blood or tissue In situ hybridization of tissue

16. Atypical lymphocyte in the centre has a classical so called “Ballerina skirt” appearance with scalloped margins and indentations by the surrounding red blood cells. The cytoplasm is vacuolated. 

17. Diagram showing duration of tests against a timeline. Black color marking the onset of the test positivity.

18. Management: Symptomatic treatment of pyrexia and sore throat. Rest and recuperation Oral antiviral treatment has no effect on the acute disease. If the skin eruption is symptomatic, an emollient and moderately potent topical steroid may be used, but clearance is usually within a week even when not treated.

19. Prodrome Lasts 2 weeks Onset of Fever, Lymphadenopathy and phyrangitis marking the onset of acute infection. Lasting a month Day 2 or 3 of fever: Appearance of palatal petechiae Incubation Period: 1-2 months Day 4 th -6 th : M aculopapular Rash. Infectious Mononucleosis Timeline:

20. Summary of Infectious Mononucleosis:

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