Pharyngitis And Lymphadenopathy Case Report Biology Essay

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Miss Chan was a 22 years old lady, a clinic clerk who was admitted to the Medical Unit of Queen Elizabeth Hospital on 15th May, 2010 with one week history of fever, sore throat, fatigue and epigastric discomfort. There was no cough, runny nose, chest pain or shortness of breath. Other abdominal and urinary symptoms were absent. There was no yellow discoloration of skin, dark urine or pale stool. She also complained of yellow vaginal discharge for three days.

She enjoyed good past health with no regular medications but had history of intake of seven doses of herbal medicine for general health in late April, 2010. Last dose was received on 23rd April, 2010. She did not smoke or drink and lived alone with no pet adopted. Hepatitis status was unknown. Suspicious food intake was absent. There was no piercing, tattooing, injection drug use or needle sharing. She had history of unprotected sexual intercourse before the onset of her illness with the same stable partner. Last menstrual period was 24th April, 2010 with normal menses. There was no history of recent travel or contact with sick persons.

On physical examination, she was hemodynamically stable with satisfactory oxygen saturation and low-grade pyrexia (37.6oC). There was no jaundice or pallor. The throat was mildly congested with no palatal petechiae or oral ulcer. Bilateral shotty tender cervical lymphadenopathy was detected without enlarged axillary or groin lymph nodes. Chest, cardiovascular and neurological examinations were unremarkable. Abdomen was soft and non-tender with no peritoneal sign or hepatosplenomegaly. Per rectal examination showed no mass or melena. There was no skin rash or joint swelling. Gynecological assessment indicated an uncomplicated vaginal discharge with no ano-genital lesion. Bedside pregnancy test was negative.

Laboratory investigations showed leucocytosis (12.7 x 109/L) with predominant lymphocytosis (6.6 x 109/L) (52% of total leucocytes) and 17% atypical lymphocytosis and mild thrombocytopenia (103 x 109/L). Liver function test showed anicteric hepatitic pattern of deranged liver function (total bilirubin 9 umol/L, ALP 187 IU/L, ALT 351 IU/L, AST 444 IU/L, GGT 246 IU/L) with normal clotting profile. Chest X-ray showed no definite consolidation and abdominal X-ray was unremarkable. Nasopharyngeal aspirate grew no respiratory virus, blood culture yielded no growth and high vaginal swab grew no pathogen. HAV IgM, HBsAg, anti-HCV, monospot test were all negative. Abdominal ultrasound revealed normal liver with no splenomegaly. The herbal formula was sent to the Hong Kong Poison Information Center for interpretation which commented that one of the drugs was a well-known hepatotoxic herb and the dosage used was within the therapeutic range and urine toxicology detected no herbal markers in the urine sample.

The clinical picture was compatible with heterophile negative infectious mononucleosis-like syndrome supported by laboratory findings. She was assessed by infectious disease team and managed with supportive treatment with adequate fluid, anti-pyretic and throat lozenges. Specific serology tests suggested showed positive EBV (Epstein-Barr virus) VCA (viral capsid antigen) IgM and negative EBV VCA IgG and negative CMV (cytomegalovirus) IgM and anti-HIV (human immunodeficiency virus) results. The diagnosis of infectious mononucleosis caused by EBV was confirmed. Symptoms improved with defervescence of fever. Liver function improved and thrombocytopenia resolved upon discharge.

During follow-up in Medical Specialist Out-Patient Clinic, her symptoms completely subsided with resolution of cervical lymphadenopathy and normalization of liver function. Second HIV antibody test remained negative.

Discussion: ** (total words for case history and discussion must be 1000-2000)

In summary, Miss Chan was a 22 years old young lady who presented with classical triad of fever, pharyngitis and lymphadenopathy of infectious mononucleosis supported by atypical lymphocytosis and positive EBV VCA IgM serology.

Infectious mononucleosis is a clinical syndrome associated with primary EBV infection. EBV is a herpes virus with a double-stranded DNA genome. EBV infection occurs predominantly through exposure to infected saliva and less commonly by sexual transmission. Natural EBV infection occurs only in humans resulting in life-long infection. Over 90% of adults worldwide will eventually acquire EBV developing latent infection of B-lymphocytes. Mononucleosis-like illnesses are similar presentations caused by other processes (1), (2), (3), (4), (5).

Our patient illustrates a common presentation of infectious mononucleosis in young adults. Although flu-like symptoms are common in adults, infectious mononucleosis should be suspected in adolescents and young adults (10 to 30 years of age) who present with fever, pharyngitis and lymphadenopathy (4). It is because in developed countries like Hong Kong and higher socio-economic groups, primary EBV infection is shifted to later ages. Due to improvement in economic and sanitary conditions over past decades, EBV infection in early childhood become less common and more children are susceptible as they reach adolescence and early adulthood. 50-74% develop symptoms consistent with infectious mononucleosis in adolescence and early adulthood. On the contrary, in developing countries and lower socioeconomic groups, most EBV infections occur in early childhood (1 to 5 years of age). Primary infections in young children are often asymptomatic and typical symptoms of infectious mononucleosis are uncommon. Primary EBV infections are rare in the first year of life because of high maternal seroprevalence and the protective effect of passively transferred maternal antibodies. The risk of developing symptomatic infection drops 100 fold by age 35 or older (1), (2), (3), (5).

Classical clinical features of infectious mononucleosis include moderate to high fever (>37.5oC), subacute pharyngitis, bilateral tender posterior cervical lymphadenopathy, which typically begin after a 4- to 8-week incubation and often heralded by a 3- to 5-day prodrome of non-specific symptoms (2), (3). Common symptoms and signs include lymphadenopathy (cervical or generalized) (94%), pharyngitis (84%), malaise (82%), fever (76%) and splenomegaly (52%). Less common symptoms and signs include palatal petechiae (25-50%), myalgia (20%), hepatomegaly (12), rash (10%), jaundice (9%) and arthralgia (2%) (3). Morbilliform rash is common in patients with infectious mononucleosis treated with ampicillin or amoxicillin (up to 95%) and other beta-lactam antibiotics (40-60%) (1).

Laboratory evidence shows atypical lymphocytosis (>10% total leucocytes) (90%), mild transaminitis (2-3x normal) (90%), heterophile positive (85-90%), lymphocytosis (70%) and mild thrombocytopenia (25-50%) (3).

In infectious mononucleosis, liver involvement is usually mild and resolves spontaneously. Typically, mild transaminitis is noted consistent with parenchymal injury rather than cholestatic liver disease due to decreased bile flow. Hyperbilirubinemia and jaundice are uncommon (6), (7). In our patient, the anicteric hepatitic pattern of impaired liver function is more likely to be contributed by infectious mononucleosis than herbs-induced hepatitis because of the classical presentation of infectious mononucleosis and prolonged period between last dose of herbs and clinical presentation.

Hoagland’s criteria are the most widely cited diagnostic criteria for infectious mononucleosis: at least 50% lymphocytes and at least 10% atypical lymphocytes in the presence of fever, pharyngitis and lymphadenopathy and confirmed by a positive serological test (4). For diagnostic accuracy, in patients with clinically suspected infectious mononucleosis, >50% lymphocytosis and >10% atypical lymphocytosis has 61% sensitivity and 95% specificity whereas heterophile antibody test has 71-95% sensitivity and 82-99% specificity and antibodies to VCA and EBNA (Epstein-Barr virus nuclear antigen) have 95-99% sensitivity and 89-99% specificity (3).

Heterophile antibody test (monospot test) is a rapid test for infectious mononucleosis. Primary EBV infection induces a heterogeneous group of circulating heterophile (IgM) antibodies. This test relies on the agglutination of horse or sheep erythrocytes by these heterophile antibodies. Up to 90% adolescents and adults with infectious mononucleosis have detectable heterophile antibodies. The antibodies develop within the first week after the onset of symptoms, peak between 2 and 5 weeks and can be detected at low levels up to 12 months later. The heterophile antibody test may be false negative in up to 25% of patients in the first week of symptoms when antibody levels are below the limit of detectability. 10% adults with infectious mononucleosis will be persistently heterophile negative which can be diagnosed by detection of EBV VCA IgM antibodies. EBV-specific antibodies are more sensitive and specific for infectious mononucleosis. EBV VCA IgM is commonly detected on presentation with symptoms and disappears within 4 to 8 weeks and is not detected in association with chronic infection. EBV VCA IgG may be detectable at the time of or shortly after presentation and persists at reduced levels throughout life. EBNA IgG is usually not detectable until several weeks after the onset (1), (3), (7).

The differential diagnoses of infectious mononucleosis include mononucleosis-like illnesses caused by non-EBV viral etiologies [primary infection with CMV, human herpes virus 6 (HHV-6), HIV], bacterial infections (Streptococcus pyogenes), protozoal diseases (Toxoplasma gondii) and non-infectious causes (sarcoidosis, Hodgkin’s lymphoma) (1), (2), (3). A systemic approach is essential to detect the etiology. Besides comprehensive history and physical examination, an algorithm is suggested to guide laboratory diagnosis. Patients with clinically suspected infectious mononucleosis should first have heterophile antibody test. If positive, it is highly suggestive of infectious mononucleosis caused by EBV but does not exclude the possibility of other infections like HIV. If negative, a complete blood picture with differential is helpful. Marked lymphocytosis (>50%) with atypical lymphocytosis (>10%) suggests heterophile-negative infectious mononucleosis caused by EBV. Specific serology for EBV VCA IgM and IgG antibodies or second heterophile antibody test should be sent for confirmation. If negative, serological tests for CMV and HHV-6 should be checked for two other main viral etiologies. Negative results should prompt a reassessment of patient’s history and symptoms for other less common diagnoses and appropriate testing (2), (4).

Like in our patient, she presented with classical features of infectious mononucleosis. However, the heterophile antibody test is negative. Complete blood picture with differential shows marked lymphocytosis and atypical lymphocytosis. So, specific serological tests are done to determine the etiology showing positive EBV VCA IgM and negative CMV IgM. As a result, the diagnosis of heterophile-negative infectious mononucleosis caused by EBV is made. Moreover, in view of risk factors of acute HIV infection (sexually active and history of unprotected sexual intercourse), she is also tested for HIV (1), (2).

Infectious mononucleosis is usually self-limited. The mainstay of treatment is supportive care including adequate hydration and nutrition, acetaminophen, non-steroidal anti-inflammatory agents for fever and myalgia; throat lozenges or sprays or gargling with a 2% lidocaine solution for sore throat (1), (3), (4), (8).

Specific treatment has a limited role and is not recommended for routine treatment of infectious mononucleosis. Anti-viral therapy is not recommended. Randomized controlled trials showed that acyclovir had a transient reduction in oropharyngeal shedding at the end of therapy but provided no significant or consistent clinical benefit. Corticosteroids are not indicated for uncomplicated infectious mononucleosis because of insufficient evidence but may be helpful in the management of severe complications like severe pharyngeal edema with respiratory compromise and hemolytic anemia (1), (3), (4), (8).

Serious complications of infectious mononucleosis are rare and usually come after the onset of the illness. Complications include upper airway obstruction, neurological abnormalities (encephalitis, Guillain-Barre syndrome), splenic rupture, hemolytic anemia, thrombocytopenia, acute interstitial nephritis, myocarditis and cardiac conduction abnormalities. Rare deaths are mostly attributed to neurological sequelae and splenic rupture (3), (4), (7).

Fatigue, myalgia and hypersomnia may persist for several months after the acute infection has resolved. But most patients will recover without sequelae and return to normal activities within two months after the onset of symptoms (4). Patients may excrete high levels of EBV in their saliva in the year after the onset of infectious mononucleosis but special precautions against EBV transmission are not necessary because most people are EBV-seropositive (1). Splenic rupture is the widely feared complication of infectious mononucleosis but the risk estimated is 0.1% only and most splenic ruptures reported have occurred within three weeks after diagnosis. These data suggest that athletes with infectious mononucleosis are advised not to participate in contact or collision sports for a minimum of three to four weeks after the onset of symptoms and until they are asymptomatic (1), (3), (4). The above information and advice can be given to our patient before discharge.

Tables and Figures: (not more than 2)

Reference: (not more than 10)**

Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med 2010;362:1993-2000

Hurt C, Tammaro D. Diagnostic evaluation of mononucleosis-like illnesses. Am J Med 2007;120:911.e1-8

Auwaerter PG. Infectious mononucleosis: return to play. Clin Sports Med 2004;23:485-97

Ebell MH. Epstein-Barr virus infectious mononucleosis. Am Fam Physician 2004;70:1279-87

Vetsika EK, Callan M. Infectious mononucleosis and Epstein-Barr virus. Expert Rev Mol Med 2004;6:1-16

Hinedi TB, Koff RS. Cholestatic hepatitis induced by Epstein-Barr virus infection in an adult. Dig Dis Sci 2003;48:539-41

Lawee D. Mild infectious mononucleosis presenting with transient mixed liver disease: case report with a literature review. Can Fam Physician 2007;53:1314-6

Gershburg E, Pagano JS. Epstein-Barr virus infections: prospects for treatment. J Antimicrob Chemother 2005;56:277-81

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