Human Immunodeficiency Virus Lymphadenitis



Human Immunodeficiency Virus Lymphadenitis


Tariq Muzzafar, MBBS










Thin section transmission electron micrograph of HIV. The viral core is the dark area in the center. (Courtesy A. Harrison, P. Feorino, CDC Public Health Image Library, #10860).






This 3D rendering of HIV demonstrates the viral membrane (blue), the density between the membrane and core (yellow), and the capsid (red). (Courtesy J. Briggs, PhD.)


TERMINOLOGY


Abbreviations



  • Human immunodeficiency virus (HIV)


Synonyms



  • Acquired immune deficiency syndrome (AIDS) lymphadenitis


  • HIV lymphadenopathy


Definitions



  • Lymphadenitis caused by HIV infection


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • HIV-1 underwent single cross-species transmission from chimpanzees to humans 100 years ago



    • Virus diversified in humans into many genetic subtypes: A-D


  • Most sexually transmitted HIV infections are initiated by a single variant



    • Initial target cells are CD4(+) T cells


  • HIV, a retrovirus belonging to the lentivirus family has



    • 9 genes


    • 2 copies of single-stranded RNA in core


    • Reverse transcriptase generates double-stranded DNA copy that integrates into host genome



      • Covalently forms a provirus


    • Provirus can remain latent or be highly expressed, forming progeny viruses


  • Icosahedral structure with 72 external spikes composed of envelope proteins gp120 and gp41



    • Crucial for cell attachment and entry


  • HIV has tropism for CD4(+) T cells, monocytes, and follicular dendritic cells



    • gp120 binds with CD4 receptor and subsequently with chemokines CR5 and CXCR4



      • Leads to fusion of viral and cellular membranes and internalization of viral complex


  • 4 nucleocapsid proteins: p24, p17, p9, and p7


Pathogenesis of HIV Lymphadenopathy



  • High HIV antigen density, marked inflammation, and adhesion molecule expression by lymphocytes



    • Leads to lymphocyte sequestration


  • Exposure to increased cytokine levels results in lymphocyte death


  • Prolonged inflammation leads to fibrosis resulting in



    • Disrupted maturation of T cells


    • Decreased naive circulating CD4(+) T cells


  • Follicular dendritic cells in germinal centers entrap HIV


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 2.7 million new HIV infections per year in 2007 globally


    • Prevalence is stable at 0.8%


    • 33.2 million people have HIV infection or AIDS


    • 2 million deaths per year related to AIDS


  • Age



    • Patients 15-24 years old represent 45% of new HIV infections globally


    • Estimated 370,000 children < 14 years old were infected in 2007


    • 2 million children with HIV


  • Gender



    • No sex preference; stable globally


  • Ethnicity



    • Sub-Saharan Africa accounts for 67% of total people and 90% of children living with HIV



      • Predominantly heterosexual transmission in general population


      • Accounts for 75% of AIDS-related deaths



    • Asia overall has shown a trend toward a decrease in new HIV infections and an increase in AIDS-related deaths



      • National trends vary considerably


      • Recreational drug use, commercial sex work, and male-male sex are major factors in transmission


    • Eastern Europe and Central Asia have shown a rising trend in number of people living with HIV infection



      • Number of new infections has been slowing


      • Recreational drug use and commercial sex work are major factors in transmission


    • Western and Central Europe show stable trends



      • Heterosexual transmission is major mode of transmission


    • Caribbean basin, South and North America show stable trends



      • Male-male sex is major mode of transmission, followed by heterosexual transmission


      • Number of persons living with HIV infection has increased as result of therapy


Presentation



  • Acute (primary) phase of HIV infection



    • Can present as flu-like or mononucleosis type of syndrome with nonspecific symptoms



      • Findings: Fever, lymphadenopathy, skin rash, myalgia, arthralgia, headache, diarrhea, oral ulcers


      • Clinical diagnosis of acute HIV infection can be challenging


    • Usually lasts several weeks


    • Opportunistic infections can occur during transient CD4 lymphopenia



      • Most common: Oral and esophageal candidiasis


  • Chronic phase of HIV infection is characterized by dysregulated or suppressed immunity



    • HIV infection can generally be latent for a number of years


    • Eventually patients develop symptoms and abnormalities related to low CD4(+) count



      • Polyclonal hypergammaglobulinemia


      • Altered levels of cytokines (e.g., IL-6, TNF-α) and activation markers (e.g., CD38 on T cells)


      • Opportunistic infections: Mycobacterium tuberculosis, Pneumocystis jiroveci (formerly known as P. carinii)


      • Neoplasms: Lymphomas, Kaposi sarcoma


  • ˜ 50% of HIV(+) patients with lymphadenopathy are asymptomatic



    • Usually, lymph node biopsy shows follicular hyperplasia


Laboratory Tests



  • Acute (primary) phase of HIV infection



    • Leukopenia, thrombocytopenia, elevated serum transaminase level


    • Viremia at high titers; CD4(+) T cells and monocytes infected


    • 3rd generation enzyme immunoassays used in clinical practice and in blood banks in USA do not detect HIV antibodies until 3-7 weeks after infection


  • Chronic phase of HIV infection



    • Drop in CD4(+) counts to < 200/mm3


    • Findings related to specific opportunistic infections


  • Diagnosis of acute infection is established by demonstrating



    • High viral load


    • p24 antigen in patient with typical clinical features and negative or indeterminate HIV serologic test


  • Serologic testing



    • Based on detection of IgG against HIV antigens in serum



      • p24, a nucleocapsid protein


      • gp120 and gp41, envelope proteins


    • Centers for Disease Control (CDC) criteria for positive serology include



      • Antibodies to gp120 plus antibodies to either gp41 or p24


    • Antibodies to gp41 and p24 antigens are 1st detectable serologic markers following HIV infection



      • IgG antibodies appear 6-12 weeks following infection in most patients (by 6 months in 95%)


      • Antibodies persist for life


    • Results are reported as positive, negative, or indeterminate



    • Criteria for a positive test: Repeatedly positive enzyme immunoassay test followed by a positive Western blot analysis



      • Positive test should be confirmed by repeat testing or corroborating laboratory data


    • Accuracy of HIV serologic testing is high



      • 99.3% sensitivity and 99.7% specificity according to CDC survey


    • Rapid tests can be done at point of care and read by provider



      • High diagnostic accuracy comparable to standard serological tests and much cheaper


      • Results can be available in minutes


Treatment



  • Drugs



    • Highly active antiretroviral therapy (HAART)



      • Increases disease-free survival by suppressing viral replication and improving immunologic function


    • Indications for HAART



      • History of AIDS-defining illness, CD4 count < 350 cells/mm3, pregnant women, and HIV-associated nephropathy


    • Syndrome resembling primary HIV infection occurs in patients 2-4 weeks after HAART is discontinued



      • Fever, lymphadenopathy, and rash; plasma viremia rises and CD4(+) counts fall


Prognosis



  • HIV infection can be indolent for years but will eventually become lethal without HAART


  • Lymph nodes in HIV(+) patients show histologic progression without therapy, from follicular hyperplasia to lymphocyte depletion


  • Lymph node biopsy findings in HIV(+) patients correlate, in part, with outcome



    • Patients with follicular hyperplasia or mixed pattern have



      • Longer survival


      • Lower incidence of opportunistic infections


    • Patients with lymphocyte depletion have very poor prognosis


  • HIV(+) patients have increased risk of non-Hodgkin and Hodgkin lymphoma



    • HAART has reduced risk of non-Hodgkin lymphoma but not Hodgkin lymphoma


MACROSCOPIC FEATURES


General Features



  • Enlarged lymph nodes in follicular hyperplasia


  • Small, shrunken lymph nodes in lymphocyte depletion



    • Often not biopsied but detected at autopsy


MICROSCOPIC PATHOLOGY


Histologic Features

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Human Immunodeficiency Virus Lymphadenitis
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