L31: Fever and lymphadenopathy Flashcards
Causes of lymphadenopathy
- (Regional) proliferation of lymphocytes in response to local infection
- (Regional) cells metastasis to node (usually no fever)
- (Regional or diffuse) proliferation of malignant lymphocytes (lymphoma, usually no fever)
- (Diffuse) inflammation within lymph nodes from killing of lymphocytes infected with virus (most common)
Investigations after noticing lymphadenopathy
- Adjacent infection? (boils, cellulitis)
- Adjacent cancer? (breast, lung skin)
- Features of lymph node (fine needle aspiration with histology or cytology)
- Evidence of infection that target lymphoid cells
Infections of lymph nodes
Bacterial:
(swollen, tender lymph nodes in just one area)
- S. aureus
- Mycobacterium tuberculosis
Viral: (enlarged lymph nodes throughout body) - Epstein barr virus (EBV) - Cytomegalovirus (CMV) - Human immunodeficiency virus (HIV)
Herpes viruses
- DNA viruses
- Acute infection then latent infection (asymptomatic) or chronic infection
Viruses:
- Herpes simplex virus (cold sores)
- Varicella zoster virus (chicken pox, shingles)
- EBV
- CMV (less severe glandular-fever like)
Acute EBV infection
= glandular fever, infective mononucleosis, “kissing disease”
- Minor illness when acquired as a child (common in childhood, transmitted from adults)
- More severe illness in adolescents/adults
- Virus transmitted in saliva
- Incubation period of 4-6wks, illness for 1-2wks
- Fever, sore throat, cervical adenopathy, malaise, fatigue
- Recovery but persistent salivary excretion of EBV
Diagnosis of EBV and CMV
- Lymphocytosis (>50% of WBCs)
- Atypical lymphocytes (>10% of lymphocytes)
- Abnormal liver function tests
Paul Bunnell monospot test = detects “heterophile” antibodies which bind to guinea pig, sheep, horse RBCs but not EBV
EBV: specific EBV serology detects antibodies that bind to EBV (detects EBV antigen)
CMV: detection of antibodies (IgM or IgG) to CMV or detection of CMV in blood
Acute HIV infection
- Epidemiological risk for HIV infection (e.g. men having sex with men, injecting drugs)
- Recent (3-6 weeks) exposure
- Glandular-fever like illness
- Persistant viraemia and virus in genital secretions
- Presence of antibodies to HIV in blood
HIV structure and replication
- 2 strands of RNA surrounded by protein cylinder, covered by viral envelope (lipid bilayer) with proteins embedded
- gp120 proteins attach to CD4 molecules on T helper cells
- Viral envelope fuses with cell membrane
- Viral RNA copied to DNA (by reverse transcriptase) and incorporated into host cell DNA
- Viral DNA copied into mRNA, translated into proteins
- Assembly of viral proteins and viral RNA and HIV buds off host cell (then HIV matures into infectious virus)
HIV pathogenesis
- 10^9 T helper lymphocytes produced per day
- HIV infects T helper lymphocytes
- Infected cell produces 10^9 HIV particles per day
- Productively infected cells are killed by cytotoxic T lymphocytes
Rapid evolution of HIV
- Continuous production (10^9/day) of HIV
- Highly error-prone copying of HIV RNA by reverse transcriptase
- No proof-reading for errors
- Generation of wide range of mutant viruses each day
Time course of untreated HIV infection
- Viral load increases for weeks after infection
- Cytotoxic T lymphocytes recognise and kill HIV producing cells (from 2-3wks after infection) = drop in HIV level and T helper lymphocyte level
- Killing of infected lymphocytes causes brief glandular-fever like illness at ~4-6wks
- Level of HIV remains stable for years
- T lymphocyte number continues to decline until severe
- ~10yrs AIDS illnesses (level of HIV rises)
Diagnosis of HIV
- Detection of antibodies to HIV in blood:
- Screening test (ELISA)
- Confirmatory test (Western blot) - Detect HIV genome in blood (PCR - expensive, slow)
ELISA
= enzyme linked immunosorbent assay
- HIV antigen stuck to base of ELISA wells
- Serum sample added (antibody in serum attaches to HIV antigen)
- Anti-human antibody with adherent enzyme added (attaches to serum antibody)
- Reagent added - cleaved by enzyme on anti-human antibody = colour change (darker = high antibodies to HIV)
AIDS
= acquired immunodeficiency syndrome
When CD4 count very low - susceptible to range of illnesses uncommon in people without immune deficiency (tend to be lymphocyte dependent illnesses)
AIDS defining illnesses
- Pneumonia (pneumocystis jiroveci)
- Brain abscesses (toxoplasma gondii)
- Oesophagitis (candida albicans)
- Meningitis (cryptococcus neoformans)
- Mycobacterium tuberculosis
- Kaposi’s sarcoma (lesions)
- CNS lymphoma
- Cytomegalovirus retinitis
