Assessment of lymphadenopathy

Tests using latex agglutination or solid phase immunoassay are relatively specific. These tests tend to be less sensitive during the first few weeks of the infection.[48]Linderholm M, Boman J, Juto P, et al. Comparative evaluation of nine kits for rapid diagnosis of infectious mononucleosis and Epstein-Barr virus-specific serology. J Clin Microbiol. 1994 Jan;32(1):259-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC263013 http://www.ncbi.nlm.nih.gov/pubmed/8126196?tool=bestpractice.com The tests are also less sensitive in patients aged <12 years.[48]Linderholm M, Boman J, Juto P, et al. Comparative evaluation of nine kits for rapid diagnosis of infectious mononucleosis and Epstein-Barr virus-specific serology. J Clin Microbiol. 1994 Jan;32(1):259-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC263013 http://www.ncbi.nlm.nih.gov/pubmed/8126196?tool=bestpractice.com

Atypical lymphocytosis serves as one of the key diagnostic criteria, along with fever, pharyngitis, adenopathy and positive serological testing. These criteria call for at least 50% lymphocytes and 10% atypical lymphocytes.[49]Cai X, Ebell MH, Haines L. Accuracy of signs, symptoms, and hematologic parameters for the diagnosis of infectious mononucleosis: a systematic review and meta-analysis. J Am Board Fam Med. 2021 Nov-Dec;34(6):1141-56. https://www.doi.org/10.3122/jabfm.2021.06.210217 http://www.ncbi.nlm.nih.gov/pubmed/34772769?tool=bestpractice.com ​ One study showed increased sensitivity and specificity for diagnosing Epstein-Barr virus with increasing numbers of atypical lymphocytes on peripheral smear.[50]Brigden ML, Au S, Thompson S, et al. Infectious mononucleosis in an outpatient population: diagnostic utility of 2 automated hematology analyzers and the sensitivity and specificity of Hoagland's criteria in heterophile-positive patients. Arch Pathol Lab Med. 1999 Oct;123(10):875-81. http://www.ncbi.nlm.nih.gov/pubmed/10506437?tool=bestpractice.com

VCA-IgM in most patients is detectable with symptom onset; peaks at 2-3 weeks; becomes unmeasurable by 4 months. VCA-IgG peaks at 2-3 months; persists for life. Antibodies to EA rise in acute stage; become undetectable by 3-4 months; may re-appear with re-activation of EBV infection. Approximately 20% of clinically healthy people may have EA antibodies for years.[51]Centers for Disease Control and Prevention. ​Epstein-Barr virus and infectious mononucleosis: laboratory testing. Sep 2020 [internet publication]. https://www.cdc.gov/epstein-barr/laboratory-testing.html EBNA antibodies are not present in the acute phase; they develop after 8-16 weeks and persist for life.[51]Centers for Disease Control and Prevention. ​Epstein-Barr virus and infectious mononucleosis: laboratory testing. Sep 2020 [internet publication]. https://www.cdc.gov/epstein-barr/laboratory-testing.html ​ ​

The recombinant enzyme-linked immunosorbent assays (ELISAs) become positive 22-27 days after the acute infection. It should be followed by Western blot analysis for confirmation.

Earlier detection of HIV1 can be seen on plasma HIV RNA level (viral load) assays.[64]Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med. 1998 Jul 2;339(1):33-9. http://www.ncbi.nlm.nih.gov/pubmed/9647878?tool=bestpractice.com

The sensitivity and specificity of this test are similar to the standard immune assay. It should be followed by Western blot analysis, for confirmation.[65]Hammer SM. Clinical practice: management of newly diagnosed HIV infection. N Engl J Med. 2005 Oct 20;353(16):1702-10. http://content.nejm.org/cgi/content/full/353/16/1702 http://www.ncbi.nlm.nih.gov/pubmed/16236741?tool=bestpractice.com

Confirmatory test following a positive ELISA or rapid test. During the window period, the ELISA or rapid test result may be falsely negative or indeterminate.

p24 protein is present during high viral replication, and so is detectable in the blood during acute infection and again during late stages of infection. It can be used to detect acute infection during the window period between infection and a positive HIV-antibody ELISA test.

May be required for localised infection.

Results take 3 weeks.

Laboratory tests may help to distinguish herpes simplex virus from varicella zoster virus (VZV).

Chickenpox is a common childhood infection and shingles is commonly seen in older and immunocompromised patients.

Most commonly due to group A streptococcus (Streptococcus pyogenes) but may occur with staphylococci. Throat culture may take up to 48 hours.

Excisional biopsy is the diagnostic procedure of choice as preservation of lymph node architecture is crucial for proper diagnosis, especially when malignant aetiology such as lymphoma is suspected.

Hypoproliferative anaemia can be secondary to inflammation or bone marrow replacement, and often presents with normochromic, normocytic indices.

Alternatively, anaemia can result from autoimmune haemolysis (Coombs' test positive) associated with an underlying lymphoma.

LDH is an important marker of disease activity in lymphomas. It is used routinely for prognosis in the determination of the international prognostic index and follicular lymphoma international prognostic index for patients with non-Hodgkin's lymphoma.[52]The International Non-Hodgkin's Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin lymphoma. N Engl J Med. 1993 Sep 30;329(14):987-94. http://content.nejm.org/cgi/content/full/329/14/987 http://www.ncbi.nlm.nih.gov/pubmed/8141877?tool=bestpractice.com [53]Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1;104(5):1258-65. http://bloodjournal.hematologylibrary.org/cgi/content/full/104/5/1258 http://www.ncbi.nlm.nih.gov/pubmed/15126323?tool=bestpractice.com

PET scanning using 18F-fluorodeoxyglucose (18F-FDG) activity was found to be more sensitive than CT scan evaluation for staging of malignant lymphomas.[54]Stumpe KD, Urbinelli M, Steinert HC, et al. Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma effectiveness and comparison with computed tomography. Eur J Nucl Med. 1998 Jul;25(7):721-8. http://www.ncbi.nlm.nih.gov/pubmed/9662594?tool=bestpractice.com [55]Isasi CR, Lu P, Blaufox MD. A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma. Cancer. 2005 Sep 1;104(5):1066-74. http://onlinelibrary.wiley.com/doi/10.1002/cncr.21253/pdf http://www.ncbi.nlm.nih.gov/pubmed/16047335?tool=bestpractice.com ​ PET or integrated PET/CT scans are useful in the staging of many subtypes of non-Hodgkin's lymphoma. One study showed detection of >97% of disease sites by PET scan in patients with malignant lymphoma.[56]Tsukamoto N, Kojima M, Hasegawa M, et al. The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and a comparison of (18)F-FDG-pet with (67)gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer. 2007 Aug 1;110(3):652-9. http://onlinelibrary.wiley.com/doi/10.1002/cncr.22807/full http://www.ncbi.nlm.nih.gov/pubmed/17582800?tool=bestpractice.com The intensity of 18F-FDG uptake, known as standardised uptake value, correlates with tumour aggressiveness in non-Hodgkin's lymphoma.[57]Schoder H, Noy A, Gonen M, et al. Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2005 Jul 20;23(21):4643-51. http://jco.ascopubs.org/cgi/reprint/23/21/4643.pdf http://www.ncbi.nlm.nih.gov/pubmed/15837966?tool=bestpractice.com

HIV patients are at high risk for development of lymphoma. In addition, lymphoma is considered an AIDS-defining diagnosis. One study found that 12% of patients with newly diagnosed malignant lymphoma are positive for HIV.[58]D'Addario G, Dieterle A, Torhorst J, et al. HIV testing and newly-diagnosed malignant lymphomas: the SAKK 96/90 registration study. Leuk Lymphoma. 2003 Jan;44(1):133-8. http://www.ncbi.nlm.nih.gov/pubmed/12691153?tool=bestpractice.com

As with HIV, hepatitis B and hepatitis C infections correlate with an increased risk for the development of malignant lymphoma. Moreover, treatment of lymphoma is associated with increased risk for reactivation of these viral illnesses.[59]Viswanatha DS, Dogan A. Hepatitis C virus and lymphoma. J Clin Pathol. 2007 Dec;60(12):1378-83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095565 http://www.ncbi.nlm.nih.gov/pubmed/18042694?tool=bestpractice.com [60]Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with hematological malignancies. Br J Haematol. 2007 Mar;136(5):699-712. http://www.ncbi.nlm.nih.gov/pubmed/17338776?tool=bestpractice.com

Excisional biopsy is the diagnostic procedure of choice as preservation of lymph node architecture is crucial for proper diagnosis, especially when a malignant aetiology such as lymphoma is suspected.

Eosinophilia can be seen in Hodgkin's lymphoma and is thought to be secondary to abnormal cytokine production.[61]Di Biagio E, Sanchez-Borges M, Desenne JJ, et al. Eosinophilia in Hodgkin's disease: a role for interleukin 5. Int Arch Allergy Immunol. 1996 Jul;110(3):244-51. http://www.ncbi.nlm.nih.gov/pubmed/8688671?tool=bestpractice.com

The haemoglobin level, white blood count, and lymphocyte count are an important part of the international prognostic score for patients with advanced Hodgkin's lymphoma.[62]Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin's disease: international Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med. 1998 Nov 19;339(21):1506-14. http://content.nejm.org/cgi/content/full/339/21/1506 http://www.ncbi.nlm.nih.gov/pubmed/9819449?tool=bestpractice.com

PET scanning using 18F-fluorodeoxyglucose activity was found to be more sensitive than CT scan evaluation for staging of malignant lymphomas, and specifically Hodgkin's lymphoma.[54]Stumpe KD, Urbinelli M, Steinert HC, et al. Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma effectiveness and comparison with computed tomography. Eur J Nucl Med. 1998 Jul;25(7):721-8. http://www.ncbi.nlm.nih.gov/pubmed/9662594?tool=bestpractice.com [55]Isasi CR, Lu P, Blaufox MD. A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma. Cancer. 2005 Sep 1;104(5):1066-74. http://onlinelibrary.wiley.com/doi/10.1002/cncr.21253/pdf http://www.ncbi.nlm.nih.gov/pubmed/16047335?tool=bestpractice.com

Biopsy site and technique will vary according to cancer type. In lung cancer, the use of endobronchial ultrasound-guided transbronchial needle aspiration might be useful to assess mediastinal and hilar lymphadenopathy without mediastinoscopy.[63]Varela-Lema L, Fernandez-Villar A, Ruano-Ravina A. Effectiveness and safety of endobronchial ultrasound-transbronchial needle aspiration: a systematic review. Eur Respir J. 2009 May;33(5):1156-64. http://erj.ersjournals.com/content/33/5/1156.full.pdf+html http://www.ncbi.nlm.nih.gov/pubmed/19407050?tool=bestpractice.com

Non-specific finding due to active inflammatory state.

Depressed level of C3 and C4 may be seen in severe cases due to immune complex consumption.

Depressed level of C3 and C4 may be seen in severe cases due to immune complex consumption. This is the classical immune complex disease.

Non-specific finding due to active inflammatory state.

Non-specific finding due to active inflammatory state.

The cerebrospinal fluid-to-serum ratio of HTLV-1 antibodies is >1.

Sensitivity is highest 3-14 days after rash onset.[66]Helfand RF, Heath JL, Anderson LJ, et al. Diagnosis of measles with an IgM capture EIA: the optimal timing of specimen collection after rash onset. J Infect Dis. 1997 Jan;175(1):195-9. https://academic.oup.com/jid/article/175/1/195/826182 http://www.ncbi.nlm.nih.gov/pubmed/8985220?tool=bestpractice.com

Measles RNA can be detected by RT-PCR from throat or nasopharyngeal swabs. Best yield is obtained when samples are collected on days 1-3 of the rash, but virus may still be detected up to 10-14 days after rash onset.[67]Centers of Disease Control and Prevention. Measles (rubeola): specimen collection, storage, and shipment. Feb 2022 [internet publication]. https://www.cdc.gov/measles/lab-tools/rt-pcr.html ​​

Useful if initial IgM test is not informative. Convalescent titres are drawn 3-4 weeks after acute titres.

It may take 6-24 weeks following initial infection to develop positive serology for hepatitis C.

Detects viral load within 2 weeks of infection. It can also be used as a baseline to measure response to treatment.

Alanine aminotransferase may be raised in acute hepatitis C infection.

Liver histology is done to determine the severity of liver damage and degree of fibrosis, and to aid treatment choice.

Sensitivity 82% to 95% in immunocompetent patient.[37]Lamps LW, Scott MA. Cat-scratch disease: historic, clinical, and pathologic perspectives. Am J Clin Pathol. 2004 Jun;121(suppl 1):S71-80. http://www.ncbi.nlm.nih.gov/pubmed/15298152?tool=bestpractice.com

Biopsy of lymph node or skin lesion can provide a definite diagnosis. Warthin-Starry silver stain can detect B henselae in biopsy specimens.[37]Lamps LW, Scott MA. Cat-scratch disease: historic, clinical, and pathologic perspectives. Am J Clin Pathol. 2004 Jun;121(suppl 1):S71-80. http://www.ncbi.nlm.nih.gov/pubmed/15298152?tool=bestpractice.com

Combining serology and PCR may increase detection.[68]Allizond V, Costa C, Sidoti F, et al. Serological and molecular detection of Bartonella henselae in specimens from patients with suspected cat scratch disease in Italy: a comparative study. PLoS One. 2019;14(2):e0211945. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211945 http://www.ncbi.nlm.nih.gov/pubmed/30735549?tool=bestpractice.com

Evidence of unrecognised pulmonary TB or evidence of old healed TB (e.g., upper lobe fibrosis) may be present; such abnormalities should prompt sputum collection for smear, culture, and nucleic acid amplification testing.

Sputum specimen should be tested in patients with suspected extrapulmonary TB, as active pulmonary TB is seen in 15% to 20% of patients with extrapulmonary TB.[69]Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82. http://www.ncbi.nlm.nih.gov/pubmed/11948050?tool=bestpractice.com [70]Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78. http://www.ncbi.nlm.nih.gov/pubmed/4050833?tool=bestpractice.com [71]Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1237539/pdf/westjmed00272-0024.pdf http://www.ncbi.nlm.nih.gov/pubmed/855317?tool=bestpractice.com

Culture of Mycobacterium tuberculosis typically takes several weeks (up to 8), decisions on treatment are usually made before culture results are known.​​

Microscopy should be performed on specimens collected from sites of suspected extrapulmonary TB.[72]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):e1-33. https://academic.oup.com/cid/article/64/2/e1/2629583 http://www.ncbi.nlm.nih.gov/pubmed/27932390?tool=bestpractice.com ​​[73]Nataraj G, Kurup S, Pandit A, et al. Correlation of fine needle aspiration cytology, smear and culture in tuberculous lymphadenitis: a prospective study. J Postgrad Med. 2002 Apr-Jun;48(2):113-6. https://www.jpgmonline.com/article.asp?issn=0022-3859;year=2002;volume=48;issue=2;spage=113;epage=6;aulast=Nataraj http://www.ncbi.nlm.nih.gov/pubmed/12215692?tool=bestpractice.com

Although NAATs were originally designed and approved for respiratory specimens, they may also be requested on specimens from other sites where involvement of TB is suspected (e.g., cerebrospinal fluid, lymph node aspirate, lymph node biopsy, pleural fluid, peritoneal fluid, pericardial fluid, synovial fluid, or urine).[72]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):e1-33. https://academic.oup.com/cid/article/64/2/e1/2629583 http://www.ncbi.nlm.nih.gov/pubmed/27932390?tool=bestpractice.com [74]World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240089488 ​​​

Polymerase chain reaction for Mycobacterium tuberculosis can increase the sensitivity of FNA.[75]Singh KK, Muralidhar M, Kumar A, et al. Comparison of in house polymerase chain reaction with conventional techniques for the detection of Mycobacterium tuberculosis DNA in granulomatous lymphadenopathy. J Clin Pathol. 2000 May;53(5):355-61. https://www.doi.org/10.1136/jcp.53.5.355 http://www.ncbi.nlm.nih.gov/pubmed/10889817?tool=bestpractice.com ​​In the US, use of NAATs for extrapulmonary specimens is not approved by the Food and Drug Administration, and use would be off-label.

Several rapid NAATs are available for the diagnosis of TB and some are also able to detect genes encoding resistance to TB drugs.[74]World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240089488

One Cochrane review found the lateral flow urine lipoarabinomannan (LF-LAM) assay to have a sensitivity of 42% in diagnosing TB in HIV-positive individuals with TB symptoms, and 35% in HIV-positive individuals not assessed for TB symptoms.[76]Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420. https://www.doi.org/10.1002/14651858.CD011420.pub3 http://www.ncbi.nlm.nih.gov/pubmed/31633805?tool=bestpractice.com [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in symptomatic HIV‐positive adults?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2824/fullShow me the answer [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in unselected HIV‐positive adults (symptomatic or asymptomatic)?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2825/fullShow me the answer​​​​​ WHO recommends that LF-LAM can be used to assist in the diagnosis of active TB in HIV-positive adults, adolescents, and children with signs and symptoms of TB, or in those with advanced HIV or who are seriously ill.[77]Knapp JS, Back AF, Babst AF, et al. In vitro susceptibilities of isolates of Haemophilus ducreyi from Thailand and the United States to currently recommended and newer agents for treatment of chancroid. Antimicrob Agents Chemother. 1993 Jul;37(7):1552-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC188012 http://www.ncbi.nlm.nih.gov/pubmed/8363390?tool=bestpractice.com

Culture would still be required for drug susceptibility testing (DST).

Culture may take 2-4 weeks.

VDRL and RPR may be non-reactive in secondary syphilis.

Enzyme immunoassay or immunofluorescence assay may be used.[78]Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for healthcare providers, sixth edition. 2022 [internet publication].​ https://www.cdc.gov/ticks/tickbornediseases ​​[79]Maurin M. Francisella tularensis, tularemia and serological diagnosis. Front Cell Infect Microbiol. 2020;10:512090. https://www.frontiersin.org/articles/10.3389/fcimb.2020.512090/full http://www.ncbi.nlm.nih.gov/pubmed/33194778?tool=bestpractice.com ​​ Increase in antibody titre usually occurs 2-4 weeks after onset of symptoms.

Indirect immunofluorescence antibody test. A single elevated antibody titre is not sufficient to confirm acute infection with a rickettsial pathogen.[80]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016 May 13;65(2):1-44. http://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com

Leukocyte count and haemoglobin are usually normal.

Ordered when diagnosis first suspected; normal results do not rule out Rocky Mountain spotted fever, but markedly abnormal results (e.g., severe thrombocytopaenia) may impact on patient management decisions.

Provides a rapid diagnosis; useful for patients who are severely ill.

Definitive test. A positive culture gives a definitive diagnosis of coccidioidomycosis because there is no colonised state.

Sensitive test.

NAAT may be performed on urine and lymph node specimens, as well as swabs of the urethra, rectum, cervix, and genital ulcers.

Primary, secondary, and tertiary forms exist. Necrotising lymphadenitis may be present.

The immunoperoxidase method, which uses anti-sera to T gondii, is used on tissue sections, and Wright-Giemsa staining is used for specimens on slides.

Can be ordered when assessing for acute infection.

A negative test rules out acute infection.

A positive test does not rule in acute infection.

Many commercially available tests have high false-positive rates (up to 60%), and IgM can remain detectable for many months after initial infection.

Positivity of ANA is one of the diagnostic criteria for SLE.

Presence of autoantibodies such as ds-DNA, antiphospholipid and anti-SM antibodies is one of the diagnostic criteria for SLE.

Haematological abnormalities serve as one of the diagnostic criteria for SLE.

Presence of protein is a sign for renal involvement. This is one of the diagnostic criteria for SLE.

Seen in 70% to 80% of patients. Limited sensitivity since the test may be positive in many other connective tissue diseases.

Sensitivity of 67%, specificity of 95%. Predictive value for development of a disease with severe erosive features.[81]Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007 Jun 5;146(11):797-808. http://www.ncbi.nlm.nih.gov/pubmed/17548411?tool=bestpractice.com

Anaemia may occur in the presence of chronic disease. Platelet count may be elevated as an acute phase reactant. Leukocytosis may be present during active disease or treatment with steroid.

MRI is more sensitive than plain radiography. One study found MRI imaging to be 7 times more sensitive than plain radiography.[82]Klarlund M, Ostergaard M, Jensen KE, et al. Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis. Ann Rheum Dis. 2000 Jul;59(7):521-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1753194 http://www.ncbi.nlm.nih.gov/pubmed/10873961?tool=bestpractice.com

10% of patients with Sjogren's syndrome present with a lymphoproliferative disorder. Lymph node biopsy and histopathology are therefore advised.

Biopsy should be obtained from the most accessible organ. Once biopsy is obtained, special stains for acid fast bacilli, fungus and other organisms are required to rule out an infectious aetiology.[83]Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. http://www.ncbi.nlm.nih.gov/pubmed/18032765?tool=bestpractice.com

The disease stage is classified according to chest x-ray findings; however, these stages fail to correlate with the clinical disease.[83]Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. http://www.ncbi.nlm.nih.gov/pubmed/18032765?tool=bestpractice.com

In the acute stage, a mild-to-moderate normochromic anaemia is observed, along with a moderate-to-alarmingly elevated WBC count with a left shift. During the subacute stage, platelet count elevation is the outstanding marker. It begins to rise in the second week and continues to rise during the third week, usually with levels of up to 1 million/microlitre, but counts as high as 2 million/microlitre are occasionally observed.

During the acute stage, many acute phase reactant markers, such as the ESR, CRP, serum ferritin, and alpha-1-antitrypsin, are significantly elevated. These tests tend to return to normal levels at the end of the subacute phase toward the convalescent phase.

During the acute stage, many acute phase reactant markers, such as the ESR, CRP, serum ferritin, and alpha-1-antitrypsin, are significantly elevated. These tests tend to return to normal levels at the end of the subacute phase toward the convalescent phase.

Coronary artery abnormalities (mainly aneurysms) develop in approximately 20% to 25% of untreated patients.

Icteric and anicteric hepatitis can develop, with mild elevations in aminotransferase values observed in 40% of patients. Elevated alanine aminotransferase levels can indicate a more serious course. Bilirubin levels are elevated in 10% of patients.

Will show a mild-to-moderate sterile pyuria of urethral origin in 50% of patients.

Looks for cardiomegaly in the case of pericarditis, myocarditis or subclinical pneumonitis. Should be performed to assess baseline findings and to confirm any clinical suspicion of congestive heart failure.

Needs to be obtained to evaluate for various conduction abnormalities. Children with KD may also have acute infarction. Tachycardia, a prolonged PR interval, ST-T wave changes and a decreased voltage of R waves may indicate myocarditis. Q-wave or ST-T-wave changes may indicate myocardial infarction.

Free-breathing 3-dimensional coronary magnetic resonance angiography may accurately define coronary artery aneurysms in patients with KD. Cardiovascular magnetic resonance is useful for demonstrating coronary artery aneurysms and other coronary pathology.[84]Dorfman AL, Geva T, Samyn MM, et al. SCMR expert consensus statement for cardiovascular magnetic resonance of acquired and non-structural pediatric heart disease. J Cardiovasc Magn Reson. 2022 Jul 21;24(1):44. https://jcmr-online.biomedcentral.com/articles/10.1186/s12968-022-00873-1 http://www.ncbi.nlm.nih.gov/pubmed/35864534?tool=bestpractice.com

A subset of patients with KD, especially those with findings of large or giant coronary artery aneurysms (>8 mm in diameter), may require cardiac catheterisation and angiography to further characterise these abnormalities, although care should be taken when considering invasive arteriography in the presence of ongoing systemic inflammation since complication rates (such as catheter-related myocardial infarction) may be higher.

Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) may be present in KD.[42]May B, Rossiter A, and Heyworth P. Core biopsy and FNA: a comparison of diagnostic yield in lymph nodes of different ultrasound determined malignant potential. Journal of Global Oncology. 2018 Sept;4(suppl 2):37s.​ However, these do not automatically confirm the diagnosis as they may be associated with a wide variety of cardiac and non-cardiac causes.

May be necessary if liver or gallbladder dysfunction is suspected.

In case of testicular involvement in males, a scrotal sonogram to evaluate for epididymitis should be performed. Epididymitis is an inflammatory process that can occur in various vasculitides and affects boys aged 9-14 years. It can be observed in younger boys with Henoch-Schonlein purpura and KD.

May be needed in patients who present with high fever and nuchal rigidity. Some patients may have aseptic meningitis. Aseptic meningitis could be one of the adverse effects of intravenous immunoglobulin treatment.

Excisional or incisional biopsy is preferred for definitive diagnosis.[85]National Comprehensive Cancer Network. Castleman disease​ [internet publication]. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1518 ​ ​The hyaline vascular subtype is more common (90% of cases) than the plasma cell subtype.[7]Brown JR, Skarin AT. Clinical mimics of lymphoma. Oncologist. 2004;9(4):406-16. https://theoncologist.onlinelibrary.wiley.com/doi/full/10.1634/theoncologist.9-4-406 http://www.ncbi.nlm.nih.gov/pubmed/15266094?tool=bestpractice.com

Immunohistochemistry panel should include kappa/lambda, CD20, CD3, and HHV8 latency-associated nuclear antigen.[85]National Comprehensive Cancer Network. Castleman disease​ [internet publication]. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1518 Additional markers may be useful. Epstein-Barr virus-encoded RNA in situ hybridisation-immunophenotyping is an essential diagnostic test.

HHV-8 is largely limited to multicentric disease, mainly in patients with HIV.[7]Brown JR, Skarin AT. Clinical mimics of lymphoma. Oncologist. 2004;9(4):406-16. https://theoncologist.onlinelibrary.wiley.com/doi/full/10.1634/theoncologist.9-4-406 http://www.ncbi.nlm.nih.gov/pubmed/15266094?tool=bestpractice.com [14]Lomas OC, Streetly M, Pratt G, et al. The management of Castleman disease. Br J Haematol. 2021 Nov;195(3):328-37. https://onlinelibrary.wiley.com/doi/10.1111/bjh.17688 http://www.ncbi.nlm.nih.gov/pubmed/34340261?tool=bestpractice.com

A small percentage (about 2.5%) will develop Hodgkin's lymphoma.[7]Brown JR, Skarin AT. Clinical mimics of lymphoma. Oncologist. 2004;9(4):406-16. https://theoncologist.onlinelibrary.wiley.com/doi/full/10.1634/theoncologist.9-4-406 http://www.ncbi.nlm.nih.gov/pubmed/15266094?tool=bestpractice.com

Most commonly used diagnostic test. The preferred test is capture enzyme-linked immunosorbent assay. The sensitivity of commercial assays approaches 100% and the specificity ranges from 77% to 96%.[87]Dimech W, Panagiotopoulos L, Francis B, et al. Evaluation of eight anti-rubella virus immunoglobulin g immunoassays that report results in international units per milliliter. J Clin Microbiol. 2008 Jun;46(6):1955-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2446858 http://www.ncbi.nlm.nih.gov/pubmed/18434559?tool=bestpractice.com Positive tests should be confirmed by measurement of anti-rubella IgG in paired acute and convalescent sera, viral culture, or nucleic acid amplification.

Acute serum should be collected as early as possible (ideally within 7-10 days of symptom onset). A convalescent-phase serum sample should be taken 2-3 weeks later.

Rubella virus can be isolated from the nasopharynx, throat, urine, blood and cerebrospinal fluid from about 1 week before, to 2 weeks after, the onset of rash. Viral isolation is important from an epidemiological perspective and should be attempted if rubella is strongly suspected. Specimens should be obtained as early in the course of the illness as possible. Information is available from the Centers for Disease Control and Prevention. CDC laboratory protocols: rubella Opens in new window

Used initially to establish diagnosis when lesions are present. Highest yield if vesicles can be unroofed and the base of an ulcer can be scraped with a Dacron swab. Swab placed into a viral transport medium.

Performed when lesions are present. Highest yield if vesicles can be unroofed and the base of an ulcer can be scraped with a Dacron swab. Swab placed into PCR buffer. Higher sensitivity than viral culture.[88]Wald A, Huang ML, Carrell D, et al. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003 Nov 1;188(9):1345-51. https://academic.oup.com/jid/article/188/9/1345/802202 http://www.ncbi.nlm.nih.gov/pubmed/14593592?tool=bestpractice.com

Performed when lesions are present. Highest yield if vesicles can be unroofed and the base of an ulcer can be scraped with a Dacron swab. Swab placed into a viral transport medium.[89]Reina J, Saurina J, Fernandez-Baca V, et al. Evaluation of a direct immunofluorescence cytospin assay for the detection of herpes simplex virus in clinical samples. Eur J Clin Microbiol Infect Dis. 1998 Jul;17(7):532-4. http://www.ncbi.nlm.nih.gov/pubmed/9764563?tool=bestpractice.com

Ordered to establish infection with HSV, and in STD screening.[90]Brown ZA, Gardella C, Wald A, et al. Genital herpes complicating pregnancy. Obstet Gynecol. 2005 Oct;106(4):845-56. http://www.ncbi.nlm.nih.gov/pubmed/16199646?tool=bestpractice.com If negative and a primary infection is still suspected, repeat test in 6-12 weeks.[91]Guerry SL, Bauer HM, Klausner JD, et al. Recommendations for the selective use of herpes simplex virus type 2 serological tests. Clin Infect Dis. 2005 Jan 1;40(1):38-45. https://academic.oup.com/cid/article/40/1/38/306011 http://www.ncbi.nlm.nih.gov/pubmed/15614690?tool=bestpractice.com

May be useful, especially if the classical appearance is seen. Gram staining has very low sensitivity (5% to 63%) and low specificity (51% to 91%).[92]Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137-57. https://journals.asm.org/doi/epdf/10.1128/cmr.2.2.137 http://www.ncbi.nlm.nih.gov/pubmed/2650859?tool=bestpractice.com ​​[93]Alfa M. The laboratory diagnosis of Haemophilus ducreyi. Can J Infect Dis Med Microbiol. 2005 Jan;16(1):31-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095004 http://www.ncbi.nlm.nih.gov/pubmed/18159525?tool=bestpractice.com

Diagnostic standard, despite relatively low sensitivity (53% to 92%). Grown on two kinds of media: gonococcal agar supplemented with 2% bovine haemoglobin and 5% fetal calf serum (GC-HgS) or Mueller-Hinton agar supplemented by 5% chocolate horse blood (MH-HB). Colonies are non-spore-forming, non-mucoid; may be translucent to opaque with tan, yellowish or yellowish-grey coloration. Strains are catalase-negative, oxidase- and beta-lactamase-positive, and require X factor, but not V factor, for growth. Characteristically highly self-adherent and can be 'nudged' intact across the agar.[92]Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137-57. https://journals.asm.org/doi/epdf/10.1128/cmr.2.2.137 http://www.ncbi.nlm.nih.gov/pubmed/2650859?tool=bestpractice.com ​​​[93]Alfa M. The laboratory diagnosis of Haemophilus ducreyi. Can J Infect Dis Med Microbiol. 2005 Jan;16(1):31-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095004 http://www.ncbi.nlm.nih.gov/pubmed/18159525?tool=bestpractice.com [94]Lubwama SW, Plummer FA, Ndinya-Achola J, et al. Isolation and identification of Haemophilus ducreyi in a clinical laboratory. J Med Microbiol. 1986 Sep;22(2):175-8. http://www.ncbi.nlm.nih.gov/pubmed/3489097?tool=bestpractice.com

More sensitive and specific than other methods in multiple studies. Sensitivity as high as 98% and specificity 53% to 90%. Primarily used in reference labs.[95]Totten PA, Kuypers JM, Chen CY, et al. Etiology of genital ulcer disease in Dakar, Senegal, and comparison of PCR and serologic assays for the detection of Haemophilus ducreyi. J Clin Microbiol. 2000 Jan;38(1):268-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88707 http://www.ncbi.nlm.nih.gov/pubmed/10618099?tool=bestpractice.com [96]Patterson K, Olsen B, Thomas C, et al. Development of a rapid immunodiagnostic test for Haemophilus ducreyi. J Clin Microbiol. 2002 Oct;40(10):3694-702. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC130854 http://www.ncbi.nlm.nih.gov/pubmed/12354868?tool=bestpractice.com [97]Orle KA, Gates CA, Martin DH, et al. Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus types 1 and 2 from genital ulcers. J Clin Microbiol. 1996 Jan;34(1):49-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC228728 http://www.ncbi.nlm.nih.gov/pubmed/8748271?tool=bestpractice.com [98]Morse SA, Trees DL, Htun Y, et al. Comparison of clinical diagnosis and standard laboratory and molecular methods for the diagnosis of genital ulcer disease in Lesotho: association with human immunodeficiency virus infection. J Infect Dis. 1997 Mar;175(3):583-9. http://www.ncbi.nlm.nih.gov/pubmed/9041329?tool=bestpractice.com [99]Mackay IM, Harnett G, Jeoffreys N, et al. Detection and discrimination of herpes simplex viruses, Haemophilus ducreyi, Treponema pallidum, and Calymmatobacterium (Klebsiella) granulomatis from genital ulcers. Clin Infect Dis. 2006 May 15;42(10):1431-8. https://academic.oup.com/cid/article/42/10/1431/278293 http://www.ncbi.nlm.nih.gov/pubmed/16619156?tool=bestpractice.com [100]Chui L, Albritton W, Paster B, et al. Development of the polymerase chain reaction for diagnosis of chancroid. J Clin Microbiol. 1993 Mar;31(3):659-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC262837 http://www.ncbi.nlm.nih.gov/pubmed/8458959?tool=bestpractice.com

Reserved for cases in which culture is not diagnostic. Does not distinguish current from past infection. Useful for seroprevalence studies.[92]Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137-57. https://journals.asm.org/doi/epdf/10.1128/cmr.2.2.137 http://www.ncbi.nlm.nih.gov/pubmed/2650859?tool=bestpractice.com ​​[101]Elkins C, Yi K, Olsen B, et al. Development of a serological test for Haemophilus ducreyi for seroprevalence studies. J Clin Microbiol. 2000 Apr;38(4):1520-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC86480 http://www.ncbi.nlm.nih.gov/pubmed/10747137?tool=bestpractice.com

Not used routinely due to difficulty in culturing H ducreyi, lack of standardisation and lack of interpretive guidelines. Reserved for cases in which response to antibiotic therapy is poor. Studies have shown in vitro resistance to tetracyclines, sulphonamides, penicillins, and amoxicillin/clavulanate. Most isolates remain susceptible to rifamycins, quinolones, macrolides, and streptomycin.[77]Knapp JS, Back AF, Babst AF, et al. In vitro susceptibilities of isolates of Haemophilus ducreyi from Thailand and the United States to currently recommended and newer agents for treatment of chancroid. Antimicrob Agents Chemother. 1993 Jul;37(7):1552-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC188012 http://www.ncbi.nlm.nih.gov/pubmed/8363390?tool=bestpractice.com [92]Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137-57. https://journals.asm.org/doi/epdf/10.1128/cmr.2.2.137 http://www.ncbi.nlm.nih.gov/pubmed/2650859?tool=bestpractice.com ​​​​[102]Roy-Leon JE, Lauzon WD, Toye B, et al. In vitro and in vivo activity of combination antimicrobial agents on Haemophilus ducreyi. J Antimicrob Chemother. 2005 Sep;56(3):552-8. http://jac.oxfordjournals.org/cgi/reprint/56/3/552 http://www.ncbi.nlm.nih.gov/pubmed/16046468?tool=bestpractice.com

Can provide a more timely diagnosis during the acute phase, if available. Can be amplified from serum, urine, aqueous humour, and other tissues; however, the best specimen is serum.

Direct visualisation of spirochetes in blood or urine specimens. Likely to be positive in acute phase.

Dark field examination has poor sensitivity (40.2%) and specificity (61.5%).

Leptospires can be isolated from blood during the first 7-10 days (acute or initial stage).

Leptospires can be isolated from CSF during the first 7 -10 days (acute or initial stage).

Acute and convalescent sera taken 2 weeks apart.

ELISA is commonly used for early diagnosis.

Pulmonary involvement present during immune phase in leptospirosis.[103]Vijayachari P, Sugunan AP, Shriram AN. Leptospirosis: an emerging global public health problem. J Biosci. 2008 Nov;33(4):557-69. http://www.ncbi.nlm.nih.gov/pubmed/19208981?tool=bestpractice.com [104]Chawalparit O, Charoensak A, Niwattayakul K, et al. Radiographic chest findings and clinical correlations in leptospirosis. J Med Assoc Thai. 2007 May;90(5):918-24. http://www.ncbi.nlm.nih.gov/pubmed/17596046?tool=bestpractice.com ​ Cases in which chest x-ray detects air-space nodules have been associated with severe leptospirosis.[104]Chawalparit O, Charoensak A, Niwattayakul K, et al. Radiographic chest findings and clinical correlations in leptospirosis. J Med Assoc Thai. 2007 May;90(5):918-24. http://www.ncbi.nlm.nih.gov/pubmed/17596046?tool=bestpractice.com

Cardiac monitoring also recommended during treatment.

HRCT scan of the chest is more sensitive than chest x-ray in identifying interstitial fibrosis.[105]Blum T, Kollmeier J, Ott S, et al. Computed tomography for diagnosis and grading of dust-induced occupational lung disease. Curr Opin Pulm Med. 2008 Mar;14(2):135-40. http://www.ncbi.nlm.nih.gov/pubmed/18303423?tool=bestpractice.com

Should be performed if the patient has shortness of breath not explained by the chest x-ray or pulmonary function test results.

Serum IgG4 levels are normal in a substantial percentage of patients with clinicopathologic diagnoses of IgG4-related disease.[106]Wallace ZS, Deshpande V, Mattoo H, et al. IgG4-related disease: clinical and laboratory features in one hundred twenty-five patients. Arthritis Rheumatol. 2015 Sep;67(9):2466-75. https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.39205 http://www.ncbi.nlm.nih.gov/pubmed/25988916?tool=bestpractice.com [107]Carruthers MN, Khosroshahi A, Augustin T, et al. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015 Jan;74(1):14-8. https://ard.bmj.com/content/74/1/14 http://www.ncbi.nlm.nih.gov/pubmed/24651618?tool=bestpractice.com [108]Hao M, Liu M, Fan G, et al. Diagnostic value of serum IgG4 for IgG4-related disease: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2016 May;95(21):e3785. https://journals.lww.com/md-journal/Fulltext/2016/05240/Diagnostic_Value_of_Serum_IgG4_for_IgG4_Related.43.aspx http://www.ncbi.nlm.nih.gov/pubmed/27227950?tool=bestpractice.com ​ Elevated serum IgG4 is no longer considered essential to the diagnosis of IgG4-related disease.​​[109]Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020 Jan;72(1):7-19. https://onlinelibrary.wiley.com/doi/10.1002/art.41120 http://www.ncbi.nlm.nih.gov/pubmed/31793250?tool=bestpractice.com

The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria recommend a combination of clinical, serologic, radiologic, and pathologic features to facilitate a diagnosis of IgG4-related disease; however, the criteria are not intended for use in clinical practice as the basis of establishing the diagnosis and failure to fulfill the criteria should not prevent management of the condition accordingly.[109]Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020 Jan;72(1):7-19. https://onlinelibrary.wiley.com/doi/10.1002/art.41120 http://www.ncbi.nlm.nih.gov/pubmed/31793250?tool=bestpractice.com

Sausage-shaped pancreas and periaortitis affecting the infrarenal aorta are strongly suggestive of IgG4-related disease; however, radiologic findings in isolation (without clinical, serologic, or pathologic data) is not sufficient for clinical diagnosis.[109]Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020 Jan;72(1):7-19. https://onlinelibrary.wiley.com/doi/10.1002/art.41120 http://www.ncbi.nlm.nih.gov/pubmed/31793250?tool=bestpractice.com

The ACR/EULAR classification criteria recommend a combination of clinical, serologic, radiologic, and pathologic features to facilitate a diagnosis of IgG4-related disease; however, the criteria are not intended for use in clinical practice as the basis of establishing the diagnosis and failure to fulfill the criteria should not prevent management of the condition accordingly.[109]Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020 Jan;72(1):7-19. https://onlinelibrary.wiley.com/doi/10.1002/art.41120 http://www.ncbi.nlm.nih.gov/pubmed/31793250?tool=bestpractice.com

Examples include (but not limited to) lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and dramatic IgG4+ plasma cell infiltrates.[110]Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012 Sep;25(9):1181-92. https://www.modernpathology.org/article/S0893-3952(22)02980-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/22596100?tool=bestpractice.com

The ACR/EULAR classification criteria recommend a combination of clinical, serologic, radiologic, and pathologic features to facilitate a diagnosis of IgG4-related disease; however, the criteria are not intended for use in clinical practice as the basis of establishing the diagnosis and failure to fulfill the criteria should not prevent management of the condition accordingly.[109]Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020 Jan;72(1):7-19. https://onlinelibrary.wiley.com/doi/10.1002/art.41120 http://www.ncbi.nlm.nih.gov/pubmed/31793250?tool=bestpractice.com

Testing should be conducted in patients with suspected infection as soon as possible.[111]World Health Organisation. ​Clinical management and infection prevention and control for monkeypox: interim rapid response guidance. Jun 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1 ​ Offer testing to any person who meets the case definition for a suspected or probable case.[112]World Health Organization. Diagnostic testing for the monkeypox virus (‎MPXV)‎: interim guidance​. May 2024. [internet pulication]. https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1 ​ The recommended specimen type is skin lesion material.[112]World Health Organization. Diagnostic testing for the monkeypox virus (‎MPXV)‎: interim guidance​. May 2024. [internet pulication]. https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1 [113]UK Health Security Agency. ​Mpox: diagnostic testing. May 2022 [internet publication]. https://www.gov.uk/guidance/monkeypox-diagnostic-testing [114]Centers for Disease Controla and Prevention. ​Guidelines for collecting and handling specimens for mpox testing. Sep 2024 [internet publication]. https://www.cdc.gov/mpox/hcp/diagnosis-testing/collecting-specimens.html?CDC_AAref_Val=https://www.cdc.gov/poxvirus/mpox/clinicians/prep-collection-specimens.html ​​

Testing is available at regional public health laboratories. There are currently no commercial assays available.

Following a cluster of sexually transmitted clade I infections identified in 2023 (due to the newly identified clade Ib variant), clade confirmation is recommended in all individuals who test positive for mpox.[113]UK Health Security Agency. ​Mpox: diagnostic testing. May 2022 [internet publication]. https://www.gov.uk/guidance/monkeypox-diagnostic-testing [115]McQuiston JH, Luce R, Kazadi DM, et al. U.S. Preparedness and response to increasing clade I mpox cases in the democratic republic of the Congo - United States, 2024. MMWR Morb Mortal Wkly Rep. 2024 May 16;73(19):435-40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115432 http://www.ncbi.nlm.nih.gov/pubmed/38753567?tool=bestpractice.com

Point-of-care tests may be available in some countries.

he clinical features of mpox may easily be confused with an STI. Therefore, it is important to comprehensively evaluate patients presenting with genital or perianal ulcers for STIs. Co-infections are possible, and the presence of an STI does not rule out mpox.[116]Centers for Disease Control and Prevention. Clinical overview of mpox. Sep 2024 [internet publication]. https://www.cdc.gov/mpox/hcp/clinical-overview/index.html

Consider a CT scan of the abdomen/pelvis in patients with severe anorectal proctitis.

Order while the patient is in isolation and prior to antibiotic therapy, if there is suspicion of bacterial superinfection of cutaneous lesions or bacterial infection in a very sick patient.

Order in all patients with suspected infection if there is a recent history of travel to a malaria-endemic area. Always rule out co-infection with malaria in any febrile patient who has been to a malaria-endemic area, especially in the 3 weeks prior to the onset of fever.

An antigen detection test poses less of an infection hazard to laboratory staff than preparation of thick and thin films. The laboratory must first be notified of the risk of mpox and secure transportation of specimens organised as per local policies