2015 L9 Case 8 AI Man with no fingers

Infectious Mononucleosis

Also known as Glandular Fever in UK English, caused by Epstein-Barr Virus (EBV) with a long incubation period of about 6 weeks.

• Causes lymphocytosis and reactive morphological change

• Common in adults and children

• Generally self-limiting but therapy may be needed, and symptoms may persist (post-viral syndrome)

Epstein Barr Virus (EBV)

A member of the human herpes virus family and dsDNA virus that causes infections, particularly in B-lymphocytes, and establishes persistent infections. Endemic, easily spread through saliva.

Strep Throat

• caused by Group A strep

• sore throat, fever, difficulty swallowing, swollen tonsils

• diagnose with throat swab for culture or rapid strep test

• rapid treatment v important to avoid chronic complications

Human Immunodeficiency Virus (HIV)

A retrovirus that mainly infects T-helper cells and can lead to immunocompromise and various opportunistic infections.

• primary infection: mild flu, lymphadenopathy

• asymptomatic phase: can persist for 10 years, pt becomes severely immunocompromised when CD4+ cells fall

• contaminated via bodily fluids

• also affects other things such as kaposi sarcoma and pneumocystis

• zoonotic

Kaposi Sarcoma

A type of cancer that can occur in patients with HIV due to severe immunocompromise.

Lymphocytosis

An increase in the number of lymphocytes in the blood, often associated with infections like Infectious Mononucleosis.

Pneumocystis

A type of fungus that can cause pneumonia, particularly in immunocompromised individuals, such as those with HIV/AIDS. It is commonly referred to as Pneumocystis jirovecii.

History of a Virus

• 1981: cases revolving impaired immunity recorded in the US - particularly pneumocystis and Kaposi’s

• initially named GRID, then renamed as AIDS in 1982

• 1983: HIV first isolated by Barre-Sinoussi and Montagnier (Nobel Prize Winners)

• Crossed species barrier in early 20th century in area around Congo

Haematological Malignancies

Either leukaemia or lymphoma, very common and variable prognosis

• Leukaemia primarily affects the bone marrow and results in the overproduction of abnormal WBC that spill into the bloodstream.

• Involve various types of WBC, including lymphocytes (as in lymphocytic leukaemia) or myeloid cells (as in myeloid leukaemia).

• leukopenia, leucocytosis

• Lymphoma affects lymphoid tissues, such as lymph nodes and the spleen.

• Arise from lymphocytes and are categorized into two main types: Hodgkin lymphoma, which is characterized by the presence of Reed-Sternberg cells, and Non-Hodgkin’s lymphoma, which encompasses a wider variety of lymphomas. Both conditions have their unique clinical features and treatment options.

Acute Myeloid Leukaemia

• 1/3 of leukaemia in adults

• severe factors associated e.g. aromatic solvents, ionising radiation

• failure of bone marrow, invasion of vital organs and metabolic imbalance

Acute Lymphocytic Leukaemia

• most common in children

• lymphocyte precursors have little cytoplasm that stains a deep blue

Hodgkin Lymphoma

A cancer derived from B-lymphocytes, characterized by the presence of Reed-Sternberg cells.

Reed-Stemberg Cells

• Derived from B cells

• Dont express antibodies

• Large cells

• Bi-lobed/multi-nucleated cells

• CD30 and 15 positive

Non-Hodgkin’s Lymphoma

A heterogeneous group of lymphomas that derive from lymphocytes, accounting for 85% of lymphoma cases. Have been attempts to classify them

• The Rappaport Classification system (1965)

• The Working Formulation (1982)

• The WHO system (2016)

Hodgkin vs Non Differential

• FBC and WCC

• Blood film

• lactate dehydrogenase

• Monospot

• qPCR

• throat swab for culture

Lactate Dehydrogenase (LDH)

A non-specific marker that may indicate malignancy when elevated in blood samples.

Reactive Lymphocytes

Larger-than-normal lymphocytes observed in blood smears, indicative of activation due to infections.

Cytotoxic T Lymphocytes (CTLs)

A subtype of T lymphocytes that play a crucial role in eliminating virus-infected cells.

Monospot Test

A rapid diagnostic test used to detect heterophile antibodies in Infectious Mononucleosis.

• detect antigen in serum

• antibodies impregnated into test strip react w antigens, forming coloured lines

• heterophile antibodies, pan-reactive antibodies that binds to RBC

• poor specificity and sensitivity in acute infections because of this, result in false positives due to the presence of other infections or conditions that also produce these antibodies.

Viral Antigen Test

Tests that identify specific antigens from viruses, useful in diagnosing conditions like HIV.

AIDS

Acquired Immunodeficiency Syndrome, the late stage of HIV infection characterized by severe immune system damage.

Post-viral syndrome

A condition where symptoms persist for many months following resolution of an acute viral infection.

Lymphopenia

An absolute reduction in lymphocytes, which can be caused by various factors including drugs and viral infections.

• non-malignant can be caused by drugs, viral infections, malaria, etc.

HIV Diagnosis

• Serological methods (ELISA), Viral antigen, host antibody response

• Molecular methods (RT-PCR)

HIV Management

Antiretroviral drugs reduce viral load until it is effectively un-transmittable. Combination therapies are preferred.

Entry Inhibitor

Antiretroviral, inhibits HIV ability to bind to CCR5 (chemokine receptor type 5), protein on WBC cell surface

Nucleotide (-side) reverse-transcriptase inhibitor

Antiretroviral, acts as a chain terminating analogues

Non-nucleoside RT inhibitor

Antiretroviral, non-competitive inhibitors of RT enzyme

Protease Inhibitor

Antiretroviral, prevents mature virions from budding from infected cell

Integrase Inhibitor

Antiretroviral, prevents integration of viral DNA into host cell genome

EBV and malignancy

• associated w a lot of pathologies resulting from persistent infection

• autoimmune diseases e.g. MS

• associated with a lot of malignanacy

• efforts now in place to develop EBV vaccine

Biopsies

• only done if blood film indicated malignancy

• FBC, blood film and monospot are sufficient

Drugs and Lymphopenia

• Cytotoxic chemotherapy - target and kill cells, but may also affect normal cells esp. those in bone barrow > reduction in lymphocytes

• NSAID - affect bone marrow function and lymphocyte survival

• Folate inhibitors - folate necessary for DNA synthesis in proliferating cells, can reduce lymphocyte production

• Antibiotics e.g. trimethoprim - affect bone marrow function and lymphocyte survival

• Biological inhibitors e.g. anti-TNFα - can predispose patients to lymphopenia by affecting immune cell signaling and function, leading to a decrease in lymphocyte numbers.

• Anti-coagulants e.g. phenytoin - while primarily an anticonvulsant, has been associated with lymphopenia through mechanisms that may involve bone marrow suppression and reduced lymphocyte production.