Mononukleoza zakaźna
Diagnostyka i diagnoza
Mononukleoza zakaźna, wywołana przez wirusa Epsteina-Barr (EBV), charakteryzuje się klasyczną triadą objawów: gorączką, zapaleniem gardła oraz limfadenopatią, często z obecnością atypowej limfocytozy (>10%) i limfocytozy >40-50%. Diagnostyka opiera się na ocenie klinicznej oraz badaniach laboratoryjnych, w tym morfologii krwi z rozmazem, szybkim teście na przeciwciała heterofiliowe (monospot) oraz badaniach serologicznych przeciwko EBV (VCA-IgM, VCA-IgG, EBNA-IgG). Test monospot cechuje się czułością około 87% i swoistością 91%, jednak może dawać wyniki fałszywie ujemne, zwłaszcza w pierwszym tygodniu choroby i u dzieci poniżej 5 roku życia. W diagnostyce różnicowej należy uwzględnić zakażenia CMV, HIV, Toxoplasma gondii oraz paciorkowcowe zapalenie gardła.
Diagnostyka mononukleozy zakaźnej
Mononukleoza zakaźna to choroba wirusowa wywołana przez wirus Epsteina-Barr (EBV), charakteryzująca się klasyczną triadą objawów: gorączką, zapaleniem gardła i limfadenopatia/” title=”limfadenopatia” class=”to-tag” data-termid=”22952″>limfadenopatią, wraz z atypową limfocytozą. Diagnostyka mononukleozy zakaźnej opiera się na ocenie obrazu klinicznego oraz badaniach laboratoryjnych, które pomagają potwierdzić rozpoznanie.12
Obraz kliniczny w diagnostyce
Podejrzenie mononukleozy zakaźnej opiera się głównie na objawach klinicznych obserwowanych u pacjentów w wieku 15-30 lat, którzy zgłaszają się z bólem gardła i znacznym zmęczeniem. Podczas badania fizykalnego lekarz poszukuje charakterystycznych objawów, takich jak:34
- Powiększone węzły chłonne, szczególnie szyjne tylne lub zauszne
- Wyraźna limfadenopatia, w tym węzły pachowe i pachwinowe
- Wysiękowe zapalenie gardła
- Powiększenie śledziony i/lub wątroby
- Wybroczyny na podniebieniu
- Przetrwała gorączka
Obecność powiększonej śledziony (dodatni wskaźnik wiarygodności [LR+] 2,39), wybroczyn na podniebieniu (LR+ 1,32-11,40), limfadenopatii szyjnej tylnej (LR+ 3,16) oraz limfadenopatii pachowej lub pachwinowej (LR+ 3,05) jest umiarkowanie przydatna w potwierdzeniu rozpoznania mononukleozy zakaźnej.7
Badania laboratoryjne podstawowe
Podstawowe badania laboratoryjne zalecane w diagnostyce mononukleozy zakaźnej obejmują:89
- Morfologia krwi z rozmazem – w celu oceny obecności limfocytozy (>40-50% limfocytów) oraz atypowych limfocytów (>10%)
- Szybki test na obecność przeciwciał heterofiliowych (monospot)
- Badania czynności wątroby – podwyższone enzymy wątrobowe występują u ponad 90% pacjentów z mononukleozą zakaźną
Najbardziej pomocnymi parametrami hematologicznymi w potwierdzeniu mononukleozy zakaźnej są: liczba limfocytów >4 × 10⁹/L, limfocytoza >40-50% oraz atypowe limfocyty >40%. Parametry hematologiczne wykazują większą dokładność diagnostyczną w porównaniu z objawami podmiotowymi i przedmiotowymi.1213
Według kryteriów Hoaglanda, rozpoznanie mononukleozy zakaźnej opiera się na obecności co najmniej 50% limfocytów i co najmniej 10% atypowych limfocytów przy współistnieniu gorączki, zapalenia gardła i limfadenopatii, potwierdzone dodatnim testem serologicznym.14
Diagnostyka serologiczna
W diagnostyce serologicznej mononukleozy zakaźnej wykorzystuje się dwa główne rodzaje testów:15
Test na przeciwciała heterofiliowe
Test monospot (test na przeciwciała heterofiliowe) jest często stosowany jako test pierwszego rzutu w diagnostyce mononukleozy zakaźnej. Jest to szybki test aglutynacyjny, który wykrywa przeciwciała heterofiliowe skierowane przeciwko erytrocytom końskim lub baranim.1617
- Czułość testu wynosi około 87%, a swoistość 91% według przeglądów systematycznych
- Wyniki są zazwyczaj dostępne w ciągu godziny
- Przeciwciała heterofiliowe mogą być wykrywalne już od 4 dnia choroby, a do 21 dnia 90% pacjentów wykazuje dodatni wynik testu
- Test może być fałszywie ujemny w pierwszym tygodniu choroby (do 25% przypadków) oraz u dzieci poniżej 5 roku życia
Należy zaznaczyć, że CDC (Centers for Disease Control and Prevention) nie zaleca powszechnego stosowania testu monospot ze względu na jego niedokładność. Przeciwciała wykrywane przez ten test mogą być związane z innymi schorzeniami niż mononukleoza zakaźna.2223
Specyficzne testy na przeciwciała EBV
Testy na specyficzne przeciwciała przeciwko wirusowi Epsteina-Barr są bardziej wiarygodne w diagnostyce mononukleozy zakaźnej. Oznacza się:2425
- Przeciwciała IgM przeciwko antygenowi kapsydu wirusa (VCA-IgM) – obecne we wczesnej fazie zakażenia, zazwyczaj zanikają w ciągu 1-3 miesięcy
- Przeciwciała IgG przeciwko antygenowi kapsydu wirusa (VCA-IgG) – pojawiają się w ostrej fazie zakażenia i utrzymują się przez całe życie
- Przeciwciała IgG przeciwko antygenowi jądrowemu Epsteina-Barr (EBNA-IgG) – pojawiają się w fazie zdrowienia (3-4 miesiące po wystąpieniu objawów klinicznych) i utrzymują się przez całe życie
Obecność przeciwciał IgM przeciwko VCA wskazuje na pierwotne zakażenie EBV. Jest to najbardziej wartościowy marker serologiczny ostrego zakażenia EBV.2829
Specyficzne testy na przeciwciała EBV są zalecane w następujących sytuacjach:3031
- Gdy test monospot jest ujemny, ale objawy kliniczne silnie sugerują mononukleozę zakaźną
- U dzieci poniżej 5 roku życia (u których test monospot jest często fałszywie ujemny)
- W nietypowych przypadkach mononukleozy zakaźnej
- U kobiet w ciąży z objawami grypopodobnymi
- U pacjentów z obniżoną odpornością
| Profil przeciwciał | Interpretacja |
|---|---|
| VCA-IgM (+), VCA-IgG (+), EBNA-IgG (-) | Ostra infekcja EBV |
| VCA-IgM (-), VCA-IgG (+), EBNA-IgG (+) | Przebyta infekcja EBV |
| VCA-IgM (-), VCA-IgG (-), EBNA-IgG (-) | Brak infekcji EBV w przeszłości |
| VCA-IgM (+), VCA-IgG (+), EBNA-IgG (+) | Późna faza ostrej infekcji lub reaktywacja EBV |
Metody molekularne w diagnostyce
Badania molekularne, takie jak reakcja łańcuchowa polimerazy (PCR), są używane do wykrywania i/lub ilościowego oznaczania DNA wirusa EBV:36
- Testy te oferują wysoką czułość i swoistość w wykrywaniu EBV
- Ilościowe oznaczanie DNA EBV we krwi obwodowej jest częścią diagnostyki chorób limfoproliferacyjnych związanych z EBV
- Wykrywanie wysokiej liczby kopii genomu EBV (>10 000 IU/ml we krwi pełnej) może sugerować przewlekłe aktywne zakażenie EBV (CAEBV)
Należy jednak pamiętać, że wysokie miano DNA EBV może występować również w innych chorobach związanych z EBV, takich jak ostra mononukleoza zakaźna, oraz czasami u osób bez objawów klinicznych.39
Diagnostyka różnicowa
W diagnostyce różnicowej mononukleozy zakaźnej należy wziąć pod uwagę inne choroby o podobnym obrazie klinicznym:4041
- Cytomegalowirus (CMV) – może powodować zespół mononukleozopodobny
- Toxoplasma gondii – infekcja może naśladować mononukleozę zakaźną
- Ostre zakażenie HIV – może przebiegać z podobnymi objawami
- Wirusowe zapalenie wątroby – zwłaszcza w przypadkach z wyraźnymi objawami wątrobowymi
- Zapalenie gardła paciorkowcowe – często wymaga różnicowania z mononukleozą
W przypadku ujemnych wyników testów na przeciwciała heterofiliowe i specyficznych przeciwciał przeciwko EBV, które nie wskazują na ostre zakażenie, należy rozważyć inne przyczyny objawów podobnych do mononukleozy.44
Badania obrazowe
Rutynowe badania obrazowe nie są wskazane w diagnostyce mononukleozy zakaźnej. Jednak w niektórych przypadkach mogą być przydatne:45
- Ultrasonografia jamy brzusznej – może być pomocna w ocenie powiększenia śledziony i wątroby, szczególnie u sportowców i kobiet w ciąży, gdy dokładna diagnoza jest szczególnie ważna
- Tomografia komputerowa jamy brzusznej – rozważana w przypadkach podejrzenia powikłań, takich jak pęknięcie śledziony
Algorytm diagnostyczny
Na podstawie dostępnych danych można sformułować następujący algorytm diagnostyczny mononukleozy zakaźnej:4849
- Ocena objawów klinicznych i badanie fizykalne
- Wykonanie morfologii krwi z rozmazem (ocena limfocytozy i atypowych limfocytów)
- Przeprowadzenie testu monospot (na przeciwciała heterofiliowe)
- W przypadku ujemnego wyniku testu monospot, a utrzymującego się podejrzenia klinicznego:
- Powtórzenie testu monospot po 7-10 dniach (gdy pierwszy test wykonano we wczesnej fazie choroby)
- Wykonanie testów na specyficzne przeciwciała przeciwko EBV (VCA-IgM, VCA-IgG, EBNA-IgG)
- W przypadku ujemnych wyników badań serologicznych EBV, a utrzymujących się objawów:
- Rozważenie diagnostyki w kierunku innych przyczyn zespołu mononukleozopodobnego (CMV, HIV, Toxoplasma)
Limfocytoza ≥50% i atypowe limfocyty ≥10% wraz z dodatnim testem monospot są wystarczające do rozpoznania mononukleozy zakaźnej spowodowanej przez EBV.52
Postępowanie diagnostyczne w szczególnych przypadkach
W niektórych grupach pacjentów zaleca się specyficzne podejście diagnostyczne:53
- Dzieci – zaleca się bezpośrednie wykonanie specyficznych testów na przeciwciała EBV, ponieważ test monospot może być fałszywie ujemny
- Kobiety w ciąży – zaleca się specyficzne badania serologiczne EBV i morfologię krwi jako testy pierwszego rzutu
- Osoby z obniżoną odpornością – kompleksowa ocena serologiczna i molekularna zalecana w celu określenia stopnia i aktywności zakażenia
- Osoby starsze – specyficzna serologia EBV i morfologia krwi jako testy pierwszego rzutu
Podsumowanie diagnostyki
Diagnostyka mononukleozy zakaźnej opiera się na kombinacji obrazu klinicznego i badań laboratoryjnych. Najbardziej wartościowe w potwierdzeniu rozpoznania są:5657
- Charakterystyczne objawy kliniczne (gorączka, zapalenie gardła, limfadenopatia)
- Limfocytoza z obecnością atypowych limfocytów w rozmazie krwi obwodowej
- Dodatni wynik testu na przeciwciała heterofiliowe (monospot)
- Obecność przeciwciał IgM przeciwko antygenowi kapsydu wirusa EBV
W przypadkach wątpliwych lub u pacjentów z grupy ryzyka (dzieci, osoby starsze, pacjenci z obniżoną odpornością) zaleca się wykonanie specyficznych testów serologicznych na przeciwciała przeciwko EBV, które zapewniają wyższą czułość i swoistość w porównaniu z testem monospot.60
Prawidłowe rozpoznanie mononukleozy zakaźnej jest kluczowe nie tylko dla odpowiedniego postępowania terapeutycznego, ale również dla zalecenia odpowiednich ograniczeń aktywności fizycznej (ograniczenie sportów kontaktowych przez co najmniej 3-4 tygodnie od wystąpienia objawów) w celu zmniejszenia ryzyka pęknięcia śledziony.6162
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Materiały źródłowe
- #1 Infectious Mononucleosis – Infectious Diseases – Merck Manual Professional Editionhttps://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/infectious-mononucleosis
Infectious mononucleosis should be suspected in patients with typical symptoms and signs. Exudative pharyngitis, anterior cervical lymphadenopathy, and fever may be clinically indistinguishable from those caused by group A beta-hemolytic streptococci. However, posterior cervical or generalized adenopathy or hepatosplenomegaly suggests infectious mononucleosis. Moreover, detection of streptococci in the oropharynx does not exclude infectious mononucleosis. […] Laboratory diagnosis usually involves a complete blood count and EBV serologic testing. Lymphocytes that are morphologically atypical account for up to 30% of the white blood cells. […] Two serologic tests are used to diagnose acute EBV infection: Heterophile antibody testing and Specific EBV antibody testing. […] A positive heterophile antibody test in the appropriate clinical situation is generally sufficient to confirm the diagnosis of primary EBV. Alternatively, EBV antibody testing can be performed.
- #2 Infectious mononucleosis – Symptoms, diagnosis and treatment | BMJ Best Practice UShttps://bestpractice.bmj.com/topics/en-us/123
Infectious mononucleosis is characterized by the classic triad of fever, pharyngitis, and lymphadenopathy, along with atypical lymphocytosis. […] Positive serologic test for antibodies against EBV is usually diagnostic. […] The diagnosis „infectious mononucleosis” is primarily used when the syndrome is caused by EBV; „mononucleosis syndrome” should be used when the syndrome is caused by a non-EBV etiology. […] IM typically manifests in adolescents and young adults as a febrile illness with sore throat and enlarged lymph nodes. […] Key diagnostic factors include fever, pharyngitis, cervical or generalized lymphadenopathy, and malaise. […] 1st investigations to order include CBC, Epstein-Barr virus (EBV)-specific antibodies, and LFTs. […] Investigations to avoid include serum Monospot for EBV infection and ultrasonography of abdomen. […] Investigations to consider include real-time polymerase chain reaction (PCR) and CT of abdomen.
- #3 Epstein-Barr Virus Infectious Mononucleosis | AAFPhttps://www.aafp.org/pubs/afp/issues/2004/1001/p1279.html
Infectious mononucleosis should be suspected in patients 10 to 30 years of age who present with sore throat and significant fatigue, palatal petechiae, posterior cervical or auricular adenopathy, marked adenopathy, or inguinal adenopathy. […] An atypical lymphocytosis of at least 20 percent or atypical lymphocytosis of at least 10 percent plus lymphocytosis of at least 50 percent strongly supports the diagnosis, as does a positive heterophile antibody test. […] Patients with infectious mononucleosis should be withdrawn from contact or collision sports for at least four weeks after the onset of symptoms. […] Infectious mononucleosis is a clinical syndrome caused by Epstein-Barr virus (EBV) that is particularly common in adolescents and children. […] Typical features of infectious mononucleosis include fever, pharyngitis, adenopathy, malaise, and an atypical lymphocytosis.
- #4 Mononucleosis – Diagnosis & treatment – Mayo Clinichttps://www.mayoclinic.org/diseases-conditions/mononucleosis/diagnosis-treatment/drc-20350333
Your doctor may suspect mononucleosis based on your signs and symptoms, how long they’ve lasted, and a physical exam. He or she will look for signs such as swollen lymph nodes, tonsils, liver or spleen, and consider how these signs relate to the symptoms you describe. […] If there’s a need for additional confirmation, a monospot test may be done to check your blood for antibodies to the Epstein-Barr virus. This screening test gives results within a day. But it may not detect the infection during the first week of the illness. A different antibody test requires a longer result time, but can detect the disease even within the first week of symptoms. […] Your doctor may use other blood tests to look for an elevated number of white blood cells (lymphocytes) or abnormal-looking lymphocytes. These blood tests won’t confirm mononucleosis, but they may suggest it as a possibility.
- #5 Infectious Mononucleosis: Diagnosis and Treatment : Emergency Care BChttps://emergencycarebc.ca/clinical_resource/clinical-summary/infectious-mononucleosis-diagnosis-and-treatment/
Infectious mononucleosis (IM) typically occurs between the ages of 15-24 (most often at 16-20 years). […] 90% of IM cases are caused by Epstein-Barr virus (EBV); other causes include cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), human immunodeficiency virus (HIV), adenovirus, and toxoplasmosis. […] IM typically resolves within 2-4 weeks of onset; 20% of people will have persistent symptoms (sore throat, fatigue) at 1 month. […] Classic Signs and Symptoms: Fever. Fatigue. Pharyngitis with tonsillar enlargement. Posterior and anterior cervical chain lymphadenopathy. […] It can be difficult to distinguish from streptococcal pharyngitis. Predictors of IM in the presence of sore throat were palatal petechiae (specificity 0.95; positive LR, 5.3), lymphadenopathy (posterior cervical, axillary, or inguinal, specificity 0.82-0.91; positive LR, 3.0-3.1), and splenomegaly (specificity 0.71-0.99; positive LR, 1.9-6.6).
- #6 Accuracy of Signs, Symptoms, and Hematologic Parameters for the Diagnosis of Infectious Mononucleosis: A Systematic Review and Meta-Analysis | American Board of Family Medicinehttps://www.jabfm.org/content/34/6/1141
Background: The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. […] This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard. […] The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. […] Most of the clinical findings have limited diagnostic value in ruling out the disease when absent.
- #7 Accuracy of Signs, Symptoms, and Hematologic Parameters for the Diagnosis of Infectious Mononucleosis: A Systematic Review and Meta-Analysis | American Board of Family Medicinehttps://www.jabfm.org/content/34/6/1141
Background: The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. […] This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard. […] The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. […] Most of the clinical findings have limited diagnostic value in ruling out the disease when absent.
- #8 Infectious Mononucleosis: Rapid Evidence Review | AAFPhttps://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html
Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. […] Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. […] The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. […] Laboratory testing is crucial in confirming infectious mononucleosis. […] Initial testing for acute infectious mononucleosis should include complete blood count with differential and a rapid heterophile antibody test. […] The heterophile antibody latex agglutination test (monospot) is an inexpensive, rapid test with 87% sensitivity and 91% specificity reported in a systematic review.
- #9 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) Workup: Approach Considerations, Laboratory Studies, Imaging Studieshttps://emedicine.medscape.com/article/222040-workup
Epstein-Barr virus (EBV) should be suspected in adolescents or young adults presenting with sore throat, fever, and malaise, accompanied by lymphadenopathy and pharyngitis on physical examination. The diagnosis is supported by the presence of lymphocytosis and increased circulating atypical lymphocytes; however, confirmation should be obtained through a heterophile antibody test or EBV-specific antibody testing as noted below or heterophile antibody if above tests are not readily available. […] Confirmatory testing is particularly useful to inform patients about potential risks associated with infectious mononucleosis, such as splenic rupture or airway obstruction. The timing of test ordering is crucial, as it can impact diagnostic accuracy. […] When IM is clinically suspected testing with WBC with differential and further confirmatory test for EBV is suggested. […] Accurate diagnosis requires correlating serological and molecular test results with clinical presentation. For instance, the presence of anti-VCA IgM and absence of anti-EBNA IgG suggest a primary EBV infection. Conversely, the presence of anti-EBNA IgG indicates past infection.
- #10 Infectious Mononucleosis: Symptoms and Treatment | Doctorhttps://patient.info/doctor/infectious-mononucleosis
Infectious mononucleosis (IM) is usually a self-limiting infection, most often caused by Epstein-Barr virus (EBV), which is a human herpes virus. […] The annual incidence is approximately 5 cases per 1,000 persons. […] Children younger than 12 years, and immunocompromised at any age: check EBV viral serology after the person has been ill for at least 7 days. […] Glandular fever is likely if monospot test positive or the FBC has more than 20% atypical or 'reactive’ lymphocytes, or more than 10% atypical lymphocytes and the lymphocyte count is more than 50% of the total white cell count. […] EBV IM can be diagnosed using a variety of unrelated non-EBV heterophile antibodies and specific EBV antibodies. […] Following IM caused by EBV, 70-90% of patients produce IM heterophile antibodies (antibodies against an antigen produced in one species that react against antigens from other species).
- #11 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) Workup: Approach Considerations, Laboratory Studies, Imaging Studieshttps://emedicine.medscape.com/article/222040-workup
Mild transient thrombocytopenia is common in EBV infectious mononucleosis. However, severe or persistent thrombocytopenia should prompt consideration of alternative diagnoses, such as acute HIV or other viral infections. […] Abnormal liver function tests (LFTs) are observed in more than 90% of EBV infectious mononucleosis cases.
- #12 Accuracy of Signs, Symptoms, and Hematologic Parameters for the Diagnosis of Infectious Mononucleosis: A Systematic Review and Meta-Analysis | American Board of Family Medicinehttps://www.jabfm.org/content/34/6/1141
Hematologic parameters were more accurate than symptoms and signs. […] The most helpful hematologic parameters for ruling in IM include lymphocytes greater than 4 109/L and greater than 40% to 50%, or atypical lymphocytes greater than 40%. […] The absence of any lymphadenopathy was moderately helpful to rule out IM. […] The likelihood of IM is appreciably increased by several examination findings. […] The diagnostic odds ratio (DOR) estimates the overall diagnostic accuracy of each index test. […] The highest DORs for the diagnosis of IM were atypical lymphocytes greater than 40% (DOR, 355; 95% CI, 7.43-622), followed by a combination of atypical lymphocytes greater than 10% and lymphocytes greater than 50% (DOR, 81.2; 95% CI, 19.1-216), and then absolute lymphocyte counts greater than 4 109/L (DOR, 30.6; 95% CI, 6.53-99.4).
- #13 Accuracy of Signs, Symptoms, and Hematologic Parameters for the Diagnosis of Infectious Mononucleosis: A Systematic Review and Meta-Analysis | American Board of Family Medicinehttps://www.jabfm.org/content/34/6/1141
The hematologic parameters were more accurate for diagnosing IM compared with the patients’ symptoms and signs. […] The combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% (LR+, 50.40; 95% CI, 8.43-162.00) are very useful to rule in disease. […] Well-designed prospective studies are needed to investigate the role of the clinical findings and office-based tests among patients within a week of disease onset and evaluate the natural history of IM to help clinicians better understand the course of the disease.
- #14 Epstein-Barr Virus Infectious Mononucleosis | AAFPhttps://www.aafp.org/pubs/afp/issues/2004/1001/p1279.html
Hoaglands criteria for the diagnosis of infectious mononucleosis are the most widely cited: at least 50 percent lymphocytes and at least 10 percent atypical lymphocytes in the presence of fever, pharyngitis, and adenopathy, and confirmed by a positive serologic test. […] Infectious mononucleosis should be suspected and a diagnostic evaluation obtained in febrile patients who have sore throat plus splenomegaly, palatal petechiae, or posterior, axillary, or inguinal adenopathy. […] A positive result of a heterophile antibody test also is strong evidence in favor of a diagnosis of infectious mononucleosis. […] A negative result of an antibody test, particularly during the first week of illness, may indicate that the patient does not have infectious mononucleosis. […] The accuracy of diagnostic tests for infectious mononucleosis is summarized in […] The syndrome is characterized by an absolute and relative lymphocytosis and an increased proportion of atypical lymphocytes. […] More sensitive tests have been developed that detect VCA-IgG and VCA-IgM. […] A negative result is strong evidence against the diagnosis of infectious mononucleosis.
- #15 Infectious Mononucleosis – Infectious Diseases – Merck Manual Professional Editionhttps://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/infectious-mononucleosis
Infectious mononucleosis should be suspected in patients with typical symptoms and signs. Exudative pharyngitis, anterior cervical lymphadenopathy, and fever may be clinically indistinguishable from those caused by group A beta-hemolytic streptococci. However, posterior cervical or generalized adenopathy or hepatosplenomegaly suggests infectious mononucleosis. Moreover, detection of streptococci in the oropharynx does not exclude infectious mononucleosis. […] Laboratory diagnosis usually involves a complete blood count and EBV serologic testing. Lymphocytes that are morphologically atypical account for up to 30% of the white blood cells. […] Two serologic tests are used to diagnose acute EBV infection: Heterophile antibody testing and Specific EBV antibody testing. […] A positive heterophile antibody test in the appropriate clinical situation is generally sufficient to confirm the diagnosis of primary EBV. Alternatively, EBV antibody testing can be performed.
- #16 Heterophile Antibody Test: Quick Diagnosis for Mono and EBV – The Kingsley Clinichttps://thekingsleyclinic.com/resources/heterophile-antibody-test-quick-diagnosis-for-mono-and-ebv/
The Heterophile antibody test, commonly referred to as the Monospot test, is a diagnostic tool used to identify infectious mononucleosis, a condition frequently caused by the Epstein-Barr virus (EBV). […] This test plays a crucial role in detecting heterophile antibodiesâspecialized proteins produced by the immune system in response to certain infections. […] The Heterophile antibody test is a blood test designed to detect heterophile antibodies in the body. […] If these antibodies are detected, it usually indicates an active or recent Epstein-Barr virus infection. […] However, it is important to note that the test is not always definitive. […] Because of these limitations, healthcare providers may recommend additional diagnostic tests, such as a complete blood count (CBC) or a specific Epstein-Barr virus antibody test, to confirm the diagnosis.
- #17 Heterophile Antibody Test: Quick Diagnosis for Mono and EBV – The Kingsley Clinichttps://thekingsleyclinic.com/resources/heterophile-antibody-test-quick-diagnosis-for-mono-and-ebv/
In summary, the Heterophile antibody test is a quick and effective screening tool for mononucleosis. […] The Heterophile antibody test is a vital diagnostic tool in healthcare for several reasons. […] Early diagnosis through this test allows healthcare providers to recommend effective management strategies, such as rest, hydration, and over-the-counter medications to alleviate symptoms. […] By confirming the presence of heterophile antibodies, the Monospot test ensures patients receive the correct treatment and avoid unnecessary antibiotics, which are ineffective against viral infections like mono. […] The Heterophile antibody test, also known as the Monospot test or Epstein-Barr virus test, is primarily used to diagnose conditions associated with heterophile antibodies in the blood.
- #18 Infectious Mononucleosis: Rapid Evidence Review | AAFPhttps://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html
Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. […] Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. […] The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. […] Laboratory testing is crucial in confirming infectious mononucleosis. […] Initial testing for acute infectious mononucleosis should include complete blood count with differential and a rapid heterophile antibody test. […] The heterophile antibody latex agglutination test (monospot) is an inexpensive, rapid test with 87% sensitivity and 91% specificity reported in a systematic review.
- #19 Infectious Mononucleosis: Diagnosis and Treatment : Emergency Care BChttps://emergencycarebc.ca/clinical_resource/clinical-summary/infectious-mononucleosis-diagnosis-and-treatment/
Clinical diagnosis alone may be sufficient; consider the following investigations if a definitive diagnosis is desired. […] Heterophile antibody test (Monospot test) and a CBC with diff. […] Absolute lymphocytosis â¥4Ã10â¹/L, relative lymphocytosis â¥50%, and/or atypical lymphocytes â¥10%, and a positive Monospot = IM due to EBV. […] Patients with negatives tests are unlikely to have IM. […] EBV Antibody Test: Patients negative for anti-VCA IgM are highly unlikely to have EBV infection, and may require further testing for CMV, HHV-6, and HIV. […] False Negative Monospot: within the first week of symptom onset and if age <5 years old. [...] False Positive Monospot: Autoimmune disease, toxoplasmosis, rubella, lymphoma, cytomegalovirus, and acute HIV.
- #20 Heterophile, Mono Screen | Test Detail | Quest Diagnosticshttps://testdirectory.questdiagnostics.com/test/test-detail/654/heterophile-mono-screen?p=r&cc=MASTER
Heterophile antibodies, in patients with infectious mononucleosis, may be present as early as the fourth day of illness, and by the twenty-first day of illness, 90% of patients will exhibit a positive test. The Epstein-Barr virus causes infectious mononucleosis. […] Methodology: Agglutination […] Reference Range(s): Negative […] Alternative Name(s): Mono Screen, Infectious Mononucleosis […] Preferred Specimen(s): 1 mL serum […] Minimum Volume: 0.2 mL […] Transport Container: Transport tube […] Transport Temperature: Room temperature […] Specimen Stability: Room temperature: 4 days, Refrigerated: 7 days, Frozen: 30 days […] Reject Criteria: Gross hemolysis ⢠Grossly lipemic.
- #21 Azthena logo with the word Azthenahttps://www.news-medical.net/health/Diagnosis-of-glandular-fever.aspx
Diagnosis of glandular fever is primarily based on history of signs and symptoms of the infection, physical examination and is confirmed by blood tests. […] History taking is followed by a detailed physical examination. The physician detects classical features like an inflamed throat, swollen lymph nodes and tonsils and enlarged spleen and liver. […] Blood tests to detect glandular fever include different types of antibody tests. […] Antibody tests are usually positive during the phase where glands are enlarged. […] If glandular fever is suspected then the test should be repeated after the glands are swollen. […] Patients with infectious mononucleosis commonly (85-90%) have heterophile antibodies. […] The results may be falsely negative in 25% cases in the first week, 5-10% cases in second week and 5% cases in the third week of illness.
- #22 Laboratory Testing for Epstein-Barr Virus (EBV) | Epstein-Barr Virus and Infectious Mononucleosis | CDChttps://www.cdc.gov/epstein-barr/php/laboratories/index.html
Laboratory testing can help distinguish whether someone is susceptible to EBV infection or has a recent or past infection. […] EBV antibody tests are not usually needed to diagnose infectious mononucleosis. However, specific antibody tests may be needed to for people who: […] The Monospot test is not recommended for general use. The antibodies detected by Monospot can be caused by conditions other than infectious mononucleosis. […] At best, the Monospot test may indicate that a person has a typical case of infectious mononucleosis but does not confirm the presence of EBV infection.
- #23 How Mononucleosis Is Diagnosedhttps://www.verywellhealth.com/how-is-mono-diagnosed-1191844
However, the CDC says the monospot test is no longer recommended because it produces too many inaccurate results. […] More extensive antibody tests may be done if the illness symptoms aren’t typical for mononucleosis or you have been ill for more than four weeks. […] Your healthcare provider will consider your symptoms and other tests to distinguish between EBV mono and other conditions.
- #24 Epstein-Barr Virus – EBV | Choose the Right Testhttps://arupconsult.com/content/epstein-barr-virus
EBV-specific serology can also be used in the place of heterophile antibody testing as an initial test. […] Molecular evaluation by nucleic acid amplification (e.g., polymerase chain reaction [PCR]) and histologic examination with in situ hybridization (ISH) are used for the diagnosis and monitoring of EBV-related lymphoproliferative diseases and cancers. […] Heterophile antibody testing (also known as Monospot) is often used as a first-line test in the diagnosis of Epstein-Barr virus (EBV) infectious mononucleosis (IM). […] Negative heterophile antibody test results (in patients of any age) must be followed with EBV-specific serology testing. […] Serologic assays for EBV-specific antibodies are necessary to diagnose asymptomatic EBV infection and can confirm a diagnosis in symptomatic patients.
- #25 Epstein-Barr Virus – EBV | Choose the Right Testhttps://arupconsult.com/content/epstein-barr-virus
EBV-specific serology testing may also be used to diagnose EBV IM in place of a heterophile antibody test. […] Molecular evaluation by nucleic acid amplification (e.g., polymerase chain reaction [PCR]) is often preferred over serology testing in cases of reactivation, but serologic assays may be more sensitive and specific in cases of acute EBV infection. […] The heterophile antibody test (Monospot) is a standard diagnostic test for EBV IM in patients with symptoms of IM. […] Negative results should be followed by serologic assays to identify specific EBV antigens and to confirm the presence of EBV infection. […] EBV-specific antibody testing for immunoglobulin G (IgG)- and IgM-class antibodies to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) can be used to follow up on negative or positive heterophile antibody test results.
- #26 Epstein-Barr Virus Antibody Panel | Test Detail | Quest Diagnosticshttps://testdirectory.questdiagnostics.com/test/test-detail/6421/epstein-barr-virus-antibody-panel?p=r&cc=MASTER
Epstein-Barr Virus Antibody Panel – Primary infection by EBV causes infectious mononucleosis, usually a self-limiting disease in children and young adults. […] VCA-IgM is typically detectable at clinical presentation, then declines to undetectable levels within a month in young children and within 3 months in other individuals. […] VCA-IgG is typically detectable at clinical presentation, and persists for life. […] EBNA IgG typically appears during convalescence (3-4 months after clinical presentation) and remains detectable for life. […] Alternative Name(s) EBV Comprehensive, Infectious Mononucleosis Panel.
- #27 Infectious Mononucleosis – Infectious Diseases – Merck Manual Professional Editionhttps://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/infectious-mononucleosis
EBV-specific antibody testing is highly sensitive. The presence of IgM antibodies to the EBV viral capsid antigen (VCA) indicates primary EBV infection (these antibodies disappear within 3 months after infection). […] If EBV antibody titers are negative or indicate remote infection (ie, positive for IgG antibodies and negative for IgM antibodies), other diagnoses that can present with similar symptoms (eg, acute HIV infection, CMV infection) should be considered.
- #28 Diagnosis and treatment of infectious mononucleosis – PubMedhttps://pubmed.ncbi.nlm.nih.gov/8116521/
Infectious mononucleosis is caused by the Epstein-Barr virus (EBV) and most commonly affects young adults from 15 to 35 years of age. The diagnosis is made by accurate assessment of clinical, hematologic and serologic manifestations of the illness. Manifestations include the classic triad of fever, pharyngitis and cervical lymphadenopathy; lymphocytosis with a predominance of atypical lymphocytes; a positive heterophil (Monospot) antibody test; and in some cases, serologic evidence of EBV-specific antibodies produced against antigens related to the virus. […] The most valuable serologic finding is the presence of IgM antibody to EBV viral capsid antigen, which is found during acute primary EBV infection. […] Infectious mononucleosis is considered a self-limited illness, but it may result in serious complications involving the pulmonary, ophthalmologic, neurologic and hematologic systems. […] Treatment is focused on managing the symptoms, unless more severe disease involving other organ systems occurs.
- #29 Infectious mononucleosis – Knowledge @ AMBOSShttps://www.amboss.com/us/knowledge/infectious-mononucleosis/
There is no standardized diagnostic approach to infectious mononucleosis. […] Infectious mononucleosis can be diagnosed clinically, but laboratory studies are usually performed. […] EBV serology is the most reliable way to diagnose infection but is usually slow and expensive. […] Staged testing is often performed as an alternative: Order supportive laboratory studies (e.g., CBC, monospot test). […] Request EBV serology if findings are inconclusive. […] EBV serology is the most reliable laboratory study to diagnose infectious mononucleosis. […] The presence of anti-VCA IgG without anti-VCA IgM indicates past infection. […] The following studies have low specificity but can support the diagnosis in patients with clinical features of infectious mononucleosis. […] Monospot (heterophile antibody) test: a latex agglutination rapid test that uses red blood cells from horses to detect heterophile antibodies against EBV.
- #30 Laboratory Testing for Epstein-Barr Virus (EBV) | Epstein-Barr Virus and Infectious Mononucleosis | CDChttps://www.cdc.gov/epstein-barr/php/laboratories/index.html
Laboratory testing can help distinguish whether someone is susceptible to EBV infection or has a recent or past infection. […] EBV antibody tests are not usually needed to diagnose infectious mononucleosis. However, specific antibody tests may be needed to for people who: […] The Monospot test is not recommended for general use. The antibodies detected by Monospot can be caused by conditions other than infectious mononucleosis. […] At best, the Monospot test may indicate that a person has a typical case of infectious mononucleosis but does not confirm the presence of EBV infection.
- #31 Epstein-Barr Virus – EBV | Choose the Right Testhttps://arupconsult.com/content/epstein-barr-virus
Epstein-Barr virus (EBV), a pervasive virus that infects over 90% of the worlds population by adulthood, causes infectious mononucleosis (IM) in immunocompetent individuals and lymphoproliferative disease in immunocompromised patients. […] Early and accurate diagnosis of EBV IM is important so that a targeted treatment plan can be developed and the inappropriate use of antibiotics can be avoided. […] Several different tests and methods are available to diagnose EBV infection and the resulting diseases. Rapid heterophile antibody testing (also referred to as Monospot) is often used as a first-line test in the diagnosis of EBV IM because it is inexpensive and has a fast turnaround. […] However, false-negative results can occur in young children and early in the course of the illness, necessitating follow-up testing by EBV-specific serology.
- #32 Epstein-Barr Virus (EBV) Antibody Tests – Testing.comhttps://www.testing.com/tests/epstein-barr-virus-ebv-antibody-tests/
To help diagnose infectious mononucleosis (mono); to distinguish between an Epstein-Barr virus (EBV) infection and another illness with similar symptoms; to help evaluate susceptibility to EBV […] Blood tests for Epstein-Barr virus (EBV) antibodies are used to help diagnose EBV infection, the most common cause of infectious mononucleosis (mono), if a person is symptomatic but has a negative mono test. […] People with mono are typically diagnosed by their symptoms and the findings from a complete blood count (CBC) and a mono test (which tests for a heterophile antibody). About 25% of those with mono do not produce heterophile antibodies and will have a negative mono test; this is especially true with children. Tests for EBV antibodies can be used to determine whether or not the symptoms these people are experiencing are due to a current infection with the EBV virus.
- #33https://bpac.org.nz/bt/2012/october/glandular.aspx
A full blood count, when combined with findings from a clinical examination, can be highly suggestive of glandular fever. […] Heterophile antibody tests are used to confirm that glandular fever is due to acute EBV infection and to therefore rule out other causes of raised atypical lymphocyte counts. […] If an initial FBC and heterophile tests fail to indicate glandular fever, specific EBV serology may be requested. […] Specific EBV serology and FBC are recommended as the first-line tests for women who are pregnant, people who are immunocompromised, children and older people. […] Other causes should be considered when a patient, with suspected glandular fever, has an atypical presentation or risk factors for other causes are present. History, clinical presentation and, when indicated, testing may be required to help differentiate between the causes of infectious mononucleosis.
- #34 Lab Diagnosis of Epstein–Barr Virushttps://www.pidjournal.com/abstractArticleContentBrowse/PID/34685/JPJ/fullText
An accurate diagnosis of infectious mononucleosis (IM), typically resulting from the EpsteinBarr virus (EBV), is often achievable through an assessment of clinical, hematologic, and serologic features. […] The PaulBunnell test assesses the agglutination of sheep red blood cells by patient sera, while the monospot test gauges the agglutination of horse red blood cells following serum preabsorption with guinea pig cells. […] The diagnostic gold standard for IM involves EBV-specific antibodies, specifically IgM and IgG directed against viral capsid antigens (VCA). These antibodies provide high sensitivity (97%) and specificity (94%), proving particularly valuable in cases where patients suspected of IM show negative heterophile test results or do not align with classic diagnostic criteria. […] In summary, while IgM and VCA antibody positivity indicates a probable acute EBV infection, the diagnosis is reinforced by the presence of IgM and VCA and the absence of IgG and EBNA antibodies.
- #35 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) Workup: Approach Considerations, Laboratory Studies, Imaging Studieshttps://emedicine.medscape.com/article/222040-workup
Epstein-Barr virus (EBV) should be suspected in adolescents or young adults presenting with sore throat, fever, and malaise, accompanied by lymphadenopathy and pharyngitis on physical examination. The diagnosis is supported by the presence of lymphocytosis and increased circulating atypical lymphocytes; however, confirmation should be obtained through a heterophile antibody test or EBV-specific antibody testing as noted below or heterophile antibody if above tests are not readily available. […] Confirmatory testing is particularly useful to inform patients about potential risks associated with infectious mononucleosis, such as splenic rupture or airway obstruction. The timing of test ordering is crucial, as it can impact diagnostic accuracy. […] When IM is clinically suspected testing with WBC with differential and further confirmatory test for EBV is suggested. […] Accurate diagnosis requires correlating serological and molecular test results with clinical presentation. For instance, the presence of anti-VCA IgM and absence of anti-EBNA IgG suggest a primary EBV infection. Conversely, the presence of anti-EBNA IgG indicates past infection.
- #36 Epstein-Barr Virus – EBV | Choose the Right Testhttps://arupconsult.com/content/epstein-barr-virus
Given that antibodies often appear later in the course of illness, repeat testing in 10-14 days may be helpful if results are equivocal. […] Serologic testing may also be useful in the evaluation for certain EBV-associated malignancies, but its application is limited. […] Nucleic acid amplification testing such as PCR can offer high sensitivity and specificity and is used to detect and/or quantify EBV DNA. […] Peripheral blood EBV viral load by PCR is part of the diagnostic workup for EBV-associated lymphoproliferative diseases and EBV-associated PTLD. […] In patients with lymphoproliferative lesions of the head and neck, ISH for EBV-encoded RNA transcripts should be routinely performed because it is the most sensitive available test to detect EBV in this setting.
- #37https://link.springer.com/article/10.1007/s12185-023-03660-5
Chronic active EpsteinBarr virus disease (CAEBV), formerly named chronic active EpsteinBarr virus infection, is characterized by systemic inflammation and clonal proliferation of EpsteinBarr virus (EBV)-infected T or NK cells. […] Diagnosis of CAEBV now requires confirmation of a high copy number of EBV genome and EBV-infected T or NK cells. An EBV DNA load10,000 IU/mL in whole blood is proposed as the diagnostic cutoff value for CAEBV in this updated guideline. […] In 2022, the Ministry of Health Labor and Welfare research team in Japan revised the diagnostic criteria for CAEBV. In these revised diagnostic criteria, confirmation of elevated number of EBV genomes and EBV-infected T/NK cells are required for the diagnosis of CAEBV because the available evidence suggests that CAEBV is associated with the proliferation of EBV-infected T/NK cells.
- #38 Infectious Mononucleosis | MDedgehttps://medauth2.mdedge.com/content/infectious-mononucleosis
Testing for EBV-specific IgM and IgG antibodies against viral capsid antigen (VCA), early antigen (EA), and the Epstein-Barr virus nuclear antigen proteins (EBNA) is 97% sensitive and 94% specific for a diagnosis of IM. […] A quantitative real-time PCR assay, which detects EBV viral load, can also be used to test blood or plasma for acute infection.
- #39https://link.springer.com/article/10.1007/s12185-023-03660-5
The threshold values of EBV DNA load for diagnosing CAEBV have not been established. […] Based on these findings and simplicity of specimen preparation, EBV DNA load10,000 IU/mL in whole blood is proposed as the diagnostic cutoff value for CAEBV in this updated guideline. However, high EBV DNA load is also observed in patients with other EBV-associated diseases, such as infectious mononucleosis and EBV-HLH, and occasionally in individuals without any clinical manifestations. Thus, CAEBV cannot be distinguished from other diseases based solely on EBV DNA loads. […] EBV-infected cell lineage must be identified for the diagnosis of CAEBV as well as for differential diagnosis of other EBV-associated disorders, because CAEBV is primarily linked to the proliferation of EBV-infected T/NK cells. […] Definitive morphological findings of CAEBV have not been established. Therefore, EBER-ISH studies, which can detect even a few EBV-positive cells in a small tissue specimen, are crucial for the diagnosis of CAEBV.
- #40 Infectious mononucleosis – Wikipediahttps://en.wikipedia.org/wiki/Infectious_mononucleosis
By blood film, one diagnostic criterion for infectious mononucleosis is the presence of 50% lymphocytes with at least 10% reactive lymphocytes (large, irregular nuclei), while the person also has fever, pharyngitis, and swollen lymph nodes. […] A differential diagnosis of acute infectious mononucleosis needs to take into consideration acute cytomegalovirus infection and Toxoplasma gondii infections.
- #41 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) Workup: Approach Considerations, Laboratory Studies, Imaging Studieshttps://emedicine.medscape.com/article/222040-workup
If heterophile antibody tests are negative and EBV-specific antibodies are not indicative of acute infection, consider other causes of mononucleosis-like symptoms, such as cytomegalovirus (CMV), toxoplasmosis, or human herpesvirus 6 (HHV-6). […] The complete blood cell (CBC) count is more valuable for ruling out alternative diagnoses that mimic infectious mononucleosis than for providing specific diagnostic information. While leukocytosis is typical in infectious mononucleosis, a normal or decreased white blood cell (WBC) count suggests an alternative diagnosis. Lymphocytosis often accompanies infectious mononucleosis, peaks during the first few weeks of illness, and gradually returns to normal. Similarly, atypical lymphocytes follow the same timeline as lymphocytosis. A relative atypical lymphocyte counts of 20% in patients with fever, pharyngitis, and lymphadenopathy strongly suggests Epstein-Barr virus (EBV) infectious mononucleosis.
- #42 Mononucleosis (Kissing Disease): Symptoms, Causes, & Treatmenthttps://www.webmd.com/a-to-z-guides/understanding-mononucleosis-causes
Your doctor can usually diagnose mononucleosis based on your symptoms. They might also check for swelling in your tonsils, lymph nodes, liver, or spleen. […] Doctors can confirm a mono diagnosis with blood tests, including: […] This test lets your doctor look at your white blood cells to see whether any of them are unusual or whether you have more than usual. […] This test can show your doctor whether your immune system has created certain proteins in response to EBV. […] Mononucleosis and strep throat have some of the same symptoms, such as a sore throat, fever, and swollen lymph nodes. But while mono is usually caused by a virus, strep throat is caused by streptococcus bacteria. You can also have strep throat at the same time as mono.
- #43 Infectious Mononucleosis: Symptoms, Diagnosis and Treatment CUNhttps://www.cun.es/en/diseases-treatments/diseases/infectious-mononucleosis
The diagnosis of infectious mononucleosis (kissing disease) is made by the clinical picture and by the alterations in the blood: increase of leukocytes (white cells) being typical the lymphocytosis and the predominance of atypical lymphocytes. […] There is a moderate elevation of transaminases in 50% of the patients. […] Serological studies that demonstrate the presence of some antibodies (heterophile antibodies) and the study of specific antibodies for the Epstein-Barr virus (EBV) are also used. […] These studies help to differentiate this disease from others that can be treated with a similar clinic, caused by other agents such as: cytomegalovirus, toxoplasma gondii, hepatitis virus, AIDS virus, etc.
- #44 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) Workup: Approach Considerations, Laboratory Studies, Imaging Studieshttps://emedicine.medscape.com/article/222040-workup
If heterophile antibody tests are negative and EBV-specific antibodies are not indicative of acute infection, consider other causes of mononucleosis-like symptoms, such as cytomegalovirus (CMV), toxoplasmosis, or human herpesvirus 6 (HHV-6). […] The complete blood cell (CBC) count is more valuable for ruling out alternative diagnoses that mimic infectious mononucleosis than for providing specific diagnostic information. While leukocytosis is typical in infectious mononucleosis, a normal or decreased white blood cell (WBC) count suggests an alternative diagnosis. Lymphocytosis often accompanies infectious mononucleosis, peaks during the first few weeks of illness, and gradually returns to normal. Similarly, atypical lymphocytes follow the same timeline as lymphocytosis. A relative atypical lymphocyte counts of 20% in patients with fever, pharyngitis, and lymphadenopathy strongly suggests Epstein-Barr virus (EBV) infectious mononucleosis.
- #45 Infectious Mononucleosis: Rapid Evidence Review | AAFPhttps://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html
The absence of atypical lymphocytosis supports the accuracy of a negative heterophile antibody test result. […] Viral capsid antigen (VCA) immunoglobulin G (IgG) and IgM testing can be helpful if heterophile antibody test results are negative but clinical suspicion is high. […] VCA testing may be helpful when accurate diagnosis is particularly important, such as in competitive athletes and pregnant patients. […] Routine imaging is not indicated in the diagnosis of infectious mononucleosis. […] Current guidelines advise restricting all athletic activity for three weeks following symptom onset to reduce the risk of splenic rupture.
- #46 Infectious mononucleosis – Symptoms, diagnosis and treatment | BMJ Best Practice UShttps://bestpractice.bmj.com/topics/en-us/123
Infectious mononucleosis is characterized by the classic triad of fever, pharyngitis, and lymphadenopathy, along with atypical lymphocytosis. […] Positive serologic test for antibodies against EBV is usually diagnostic. […] The diagnosis „infectious mononucleosis” is primarily used when the syndrome is caused by EBV; „mononucleosis syndrome” should be used when the syndrome is caused by a non-EBV etiology. […] IM typically manifests in adolescents and young adults as a febrile illness with sore throat and enlarged lymph nodes. […] Key diagnostic factors include fever, pharyngitis, cervical or generalized lymphadenopathy, and malaise. […] 1st investigations to order include CBC, Epstein-Barr virus (EBV)-specific antibodies, and LFTs. […] Investigations to avoid include serum Monospot for EBV infection and ultrasonography of abdomen. […] Investigations to consider include real-time polymerase chain reaction (PCR) and CT of abdomen.
- #47 Infectious mononucleosis, Epstein Barr virus, glandular feverhttps://dermnetnz.org/topics/infectious-mononucleosis
Infectious mononucleosis presents typically in 75% of young adults; 15% have an atypical presentation, and infection in 10% is asymptomatic. […] The clinical features and a positive heterophile test are usually sufficient to diagnose infectious mononucleosis. […] Heterophile antibodies become positive 2-9 weeks after infection; the sensitivity is 70-92% in the first two weeks. […] Immunoglobulin (Ig)M to viral capsid antigen (VCA) during the active phase of infectious mononucleosis is found in 75% of patients and usually disappears within 4-6 weeks. […] Other tests evaluate EBV early antigen (EA) and nuclear antigen (EBNA). […] High EBV loads are found by polymerase chain reaction (PCR) in the oral cavity and blood during the acute cell lytic phase. […] Abdominal ultrasonography can evaluate hepatosplenomegaly.
- #48 Mononucleosis-Like Syndromehttps://mobile.fpnotebook.com/ID/Virus/MnclsLkSyndrm.htm
Step 1: Monospot Test (heterophile Antibody) Positive […] Diagnose Epstein-Barr Virus […] […] […] Lymphocytosis 50% and Atypical lymphocytes 10% may be sufficient alone to diagnose Mononucleosis without further testing […] […] […] VCA IgM positive: Diagnose Epstein-Barr Virus […] […] […] EBV IgM Positive: Diagnose Epstein-Barr Virus […] […] […] CMV IgM Positive: Diagnose CMV-Induced Mononucleosis
- #49 Infectious Mononucleosis: Diagnosis and Treatment : Emergency Care BChttps://emergencycarebc.ca/clinical_resource/clinical-summary/infectious-mononucleosis-diagnosis-and-treatment/
Clinical diagnosis alone may be sufficient; consider the following investigations if a definitive diagnosis is desired. […] Heterophile antibody test (Monospot test) and a CBC with diff. […] Absolute lymphocytosis â¥4Ã10â¹/L, relative lymphocytosis â¥50%, and/or atypical lymphocytes â¥10%, and a positive Monospot = IM due to EBV. […] Patients with negatives tests are unlikely to have IM. […] EBV Antibody Test: Patients negative for anti-VCA IgM are highly unlikely to have EBV infection, and may require further testing for CMV, HHV-6, and HIV. […] False Negative Monospot: within the first week of symptom onset and if age <5 years old. [...] False Positive Monospot: Autoimmune disease, toxoplasmosis, rubella, lymphoma, cytomegalovirus, and acute HIV.
- #50 Diagnosing and Treating Mononucleosishttps://www.uspharmacist.com/article/diagnosing-and-treating-mononucleosis
Mono is primarily diagnosed based on the symptoms and can be confirmed with blood tests for specific antibodies. […] Epstein-Barr virus-induced IM should be suspected when an adolescent or young adult complains of sore throat, fever, and fatigue and also has lymphadenopathy and pharyngitis on physical examination. […] Supportive evidence of EBV infection is derived from the observation of lymphocytosis and increased circulating atypical lymphocytes along with a positive heterophile antibody test (a rapid test for antibodies produced against EBV). […] Patients with suspected IM based upon history and physical examination should have a white blood cell count with differential and a heterophile test. […] If the heterophile test is positive, no further testing is necessary if the clinical scenario is compatible with typical IM.
- #51 Diagnosing and Treating Mononucleosishttps://www.uspharmacist.com/article/diagnosing-and-treating-mononucleosis
If the heterophile test is negative but there is still a strong clinical suspicion of EBV infection, the monospot test can be repeated since testing can be negative early in clinical illness. […] Other rapid diagnostic tests use enzyme-linked immunosorbent assay (ELISA) techniques. The sensitivity and specificity of the rapid kits approach 85% to 100%. […] The first laboratory finding in association with IM is lymphocytosis, defined as an absolute count 4500/microliter or, on peripheral smear, a differential count 50%. […] Common laboratory findings include an absolute or relative lymphocytosis, an increased proportion of atypical lymphocytes, and elevated aminotransferases.
- #52 Infectious Mononucleosis: Diagnosis and Treatment : Emergency Care BChttps://emergencycarebc.ca/clinical_resource/clinical-summary/infectious-mononucleosis-diagnosis-and-treatment/
Clinical diagnosis alone may be sufficient; consider the following investigations if a definitive diagnosis is desired. […] Heterophile antibody test (Monospot test) and a CBC with diff. […] Absolute lymphocytosis â¥4Ã10â¹/L, relative lymphocytosis â¥50%, and/or atypical lymphocytes â¥10%, and a positive Monospot = IM due to EBV. […] Patients with negatives tests are unlikely to have IM. […] EBV Antibody Test: Patients negative for anti-VCA IgM are highly unlikely to have EBV infection, and may require further testing for CMV, HHV-6, and HIV. […] False Negative Monospot: within the first week of symptom onset and if age <5 years old. [...] False Positive Monospot: Autoimmune disease, toxoplasmosis, rubella, lymphoma, cytomegalovirus, and acute HIV.
- #53https://bpac.org.nz/bt/2012/october/glandular.aspx
A full blood count, when combined with findings from a clinical examination, can be highly suggestive of glandular fever. […] Heterophile antibody tests are used to confirm that glandular fever is due to acute EBV infection and to therefore rule out other causes of raised atypical lymphocyte counts. […] If an initial FBC and heterophile tests fail to indicate glandular fever, specific EBV serology may be requested. […] Specific EBV serology and FBC are recommended as the first-line tests for women who are pregnant, people who are immunocompromised, children and older people. […] Other causes should be considered when a patient, with suspected glandular fever, has an atypical presentation or risk factors for other causes are present. History, clinical presentation and, when indicated, testing may be required to help differentiate between the causes of infectious mononucleosis.
- #54 Epstein-Barr Virus (EBV) Antibody Tests – Testing.comhttps://www.testing.com/tests/epstein-barr-virus-ebv-antibody-tests/
EBV antibody tests may be ordered when someone has symptoms suggesting mono but a negative mono test and when a pregnant woman has flu-like symptoms and her healthcare provider wants to determine whether the symptoms are due to EBV or another microbe. […] If someone is positive for VCA-IgM antibodies, then it is likely that the person has an EBV infection and it may be early in the course of the illness. If the individual also has symptoms associated with mono, then it is most likely that the person will be diagnosed with mono, even if the mono test was negative. […] Care must be taken when interpreting results of EBV antibody testing. The signs and symptoms as well as the medical history of the person tested must be taken into account. A healthcare practitioner may consult a specialist in infectious diseases, specifically one who is experienced with EBV testing.
- #55 Associations between past infectious mononucleosis diagnosis and 47 inflammatory and vascular stress biomarkers | Scientific Reportshttps://www.nature.com/articles/s41598-025-95276-4
We identified 604 individuals within this cohort who had received a diagnosis of infectious mononucleosis (IM), ascertained using hospital records or self-reported in questionnaires administered as part of the DBDS protocol. […] After Bonferroni correction, we observed no significant associations between IM diagnosis and plasma biomarker concentration. […] This revealed a significant association with log median normalized CRP levels (Effect (95% CI)=1.47 (1.241.67), p-value=1.43104, adjusted p-value=0.02). […] It is established that CRP levels are elevated in the acute phase of IM but, to our knowledge, long-term CRP elevations following IM have not been previously described. […] The observed association is therefore unlikely to be driven by this factor. […] CRP is a widely recognized marker of inflammation, and the observation that women exhibit heightened CRP levels for up to a decade post-IM suggests a sustained inflammatory response. […] In conclusion, when assessing plasma biomarker levels in individuals with a history of IM diagnosis, we observed a transient association with increased CRP levels in females. No long-term changes in plasma biomarker levels were observed beyond 10 years post-diagnosis.
- #56 Infectious mononucleosis – Knowledge @ AMBOSShttps://www.amboss.com/us/knowledge/infectious-mononucleosis/
There is no standardized diagnostic approach to infectious mononucleosis. […] Infectious mononucleosis can be diagnosed clinically, but laboratory studies are usually performed. […] EBV serology is the most reliable way to diagnose infection but is usually slow and expensive. […] Staged testing is often performed as an alternative: Order supportive laboratory studies (e.g., CBC, monospot test). […] Request EBV serology if findings are inconclusive. […] EBV serology is the most reliable laboratory study to diagnose infectious mononucleosis. […] The presence of anti-VCA IgG without anti-VCA IgM indicates past infection. […] The following studies have low specificity but can support the diagnosis in patients with clinical features of infectious mononucleosis. […] Monospot (heterophile antibody) test: a latex agglutination rapid test that uses red blood cells from horses to detect heterophile antibodies against EBV.
- #57 Infectious Mononucleosis | MDedgehttps://medauth2.mdedge.com/content/infectious-mononucleosis
Infectious mononucleosis (IM), commonly known as kissing disease, is a viral syndrome resulting from an acute infection with Epstein-Barr virus (EBV). […] Describe the use of heterophile antibody testing and EBV serology testing to confirm a diagnosis of IM. […] A complete blood count will reveal hyperlymphocytosis ( 50%), an elevated white blood cell count (usually ranging from 10,000 to 20,000/mL in most patients), and at least 10% atypical lymphocytes. […] In the symptomatic patient, a positive result on the monospot, a rapid test for heterophile antibodies, is 85% sensitive and 94% specific for IM. […] Because IM represents infection with EBV, serologic testing for EBV is accurate, highly specific, and recommended for use when IM is strongly suspected, particularly in infants and younger children.
- #58 Infectious mononucleosis – Symptoms, diagnosis and treatment | BMJ Best Practicehttps://bestpractice.bmj.com/topics/en-gb/123
Infectious mononucleosis is characterised by the classic triad of fever, pharyngitis, and lymphadenopathy, along with atypical lymphocytosis. […] Positive heterophile antibody test and serological test for antibodies against EBV are usually diagnostic. […] IM typically manifests in adolescents and young adults as a febrile illness with sore throat and enlarged lymph nodes. Atypical lymphocytosis and a positive heterophile antibodies test are usually observed. […] Key diagnostic factors include presence of risk factors, fever, pharyngitis, cervical or generalised lymphadenopathy, and malaise. […] 1st investigations to order include FBC, heterophile antibodies, Epstein-Barr virus (EBV)-specific antibodies, and LFTs. […] Investigations to consider include real-time polymerase chain reaction (PCR), ultrasonography of abdomen, and CT of abdomen.
- #59 About Infectious Mononucleosis (Mono) | EBV and Mono | CDChttps://www.cdc.gov/epstein-barr/about/mononucleosis.html
Healthcare providers typically diagnose infectious mononucleosis based on symptoms. […] Laboratory tests are not usually needed to diagnose infectious mononucleosis. However, specific tests may be needed for patients who do not have a typical case of infectious mononucleosis. […] The blood work of patients who have infectious mononucleosis due to EBV infection may show: More white blood cells (lymphocytes) than normal, Unusual looking white blood cells (atypical lymphocytes), Fewer than normal neutrophils or platelets, Abnormal liver function.
- #60 Epstein-Barr Virus – EBV | Choose the Right Testhttps://arupconsult.com/content/epstein-barr-virus
Given that antibodies often appear later in the course of illness, repeat testing in 10-14 days may be helpful if results are equivocal. […] Serologic testing may also be useful in the evaluation for certain EBV-associated malignancies, but its application is limited. […] Nucleic acid amplification testing such as PCR can offer high sensitivity and specificity and is used to detect and/or quantify EBV DNA. […] Peripheral blood EBV viral load by PCR is part of the diagnostic workup for EBV-associated lymphoproliferative diseases and EBV-associated PTLD. […] In patients with lymphoproliferative lesions of the head and neck, ISH for EBV-encoded RNA transcripts should be routinely performed because it is the most sensitive available test to detect EBV in this setting.
- #61 Infectious Mononucleosis: Rapid Evidence Review | AAFPhttps://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html
The absence of atypical lymphocytosis supports the accuracy of a negative heterophile antibody test result. […] Viral capsid antigen (VCA) immunoglobulin G (IgG) and IgM testing can be helpful if heterophile antibody test results are negative but clinical suspicion is high. […] VCA testing may be helpful when accurate diagnosis is particularly important, such as in competitive athletes and pregnant patients. […] Routine imaging is not indicated in the diagnosis of infectious mononucleosis. […] Current guidelines advise restricting all athletic activity for three weeks following symptom onset to reduce the risk of splenic rupture.
- #62 Epstein-Barr Virus Infectious Mononucleosis | AAFPhttps://www.aafp.org/pubs/afp/issues/2004/1001/p1279.html
Infectious mononucleosis should be suspected in patients 10 to 30 years of age who present with sore throat and significant fatigue, palatal petechiae, posterior cervical or auricular adenopathy, marked adenopathy, or inguinal adenopathy. […] An atypical lymphocytosis of at least 20 percent or atypical lymphocytosis of at least 10 percent plus lymphocytosis of at least 50 percent strongly supports the diagnosis, as does a positive heterophile antibody test. […] Patients with infectious mononucleosis should be withdrawn from contact or collision sports for at least four weeks after the onset of symptoms. […] Infectious mononucleosis is a clinical syndrome caused by Epstein-Barr virus (EBV) that is particularly common in adolescents and children. […] Typical features of infectious mononucleosis include fever, pharyngitis, adenopathy, malaise, and an atypical lymphocytosis.