E. Estudios en bancos de sangre
VII. Materiales y Métodos
-Cancer of the myeloid progenitor (gives rise to all WBCs other than B/T and NK cells), where cells do not mature and do not die and take up the bone marrow space of other needed cells -Most common in first 2 years at life, peaks again in adolescence
Signs & symptoms
-From cell deficiencies: pallor, fatigue, dyspnea,
thrombocytopenia, petechiae, hematomas, bleeding, neutropenia with sepsis, cellulitis, pneumonia
-From hyperleukocytosis: obstruction of capillaries and small arteries with high numbers of blasts
-From CNS involvement: HA, AMS, CN issues -Leukemia cutis lesions
-DIC
-Tumor lysis syndrome
Workup
-Differentiate from ALL by peripheral smear showing Auer rods
Management -Aggressive chemo Prognosis
-Overall survival of 30% Chronic Lymphocytic Leukemia
-Clonal proliferation and accumulation of mature-appear B cells -The most commonly occurring leukemia
-Mostly occurs in those > 50, and more common in males -RAI system for staging
Signs & symptoms
-Fatigue, night sweats, weight loss, persistent infections, lymphadenopathy, hepatomegaly, splenomegaly Workup
-CBC showing lymphocytosis with WBCS > 20k with
concomitant anemia and peripheral smear showing mature small lymphocytes and cobblestone-appearing smudge cells
-Coexpression of CD19 and CD5 -High IgG
Management -Observation
-Chemo with tumor lysis prophylaxis -BMT
-Radiation for lymphadenopathy Prognosis
-Typically slow-growing, but has potential for Richter’s transformation to aggressive disease
-Worse prognosis with deletion of chromosome 17 -Average 5 year survival rate of 50%
Chronic Myelogenous Leukemia -Excess proliferation of the myeloblast or its progeny with no
negative feedback
-Usually occurs in young to middle age adults Categories
1.) Chronic: < 15% blast component of bone marrow or blood 2.) Accelerated: peripheral blood > 15% blasts or > 30% blasts + promyelocytes, or > 20% basophils
3.) Acute: when blasts comprise > 30% of BM
Signs & symptoms
-Fever, bone pain, LUQ pain with splenomegaly, weakness, night seats, bleeding & bruising, petechiae
Workup
-Detection of Philadelphia chromosome via FISH or RT-PCR -CBC showing leukocytosis and thrombocytopenia
Management -Chemo -BMT Prognosis
-Average survival is 6 years with treatment
Multiple Myeloma -Malignancy of plasma cells where replacement of
bone marrow leads to failure
-Etiology is unknown, but there is increased incidence with h/o pesticides, paper production, lather tanning, nuclear radiation exposure, and abnormalities of chromosome 13
-Multi-hit hypothesis that development of MM requires 2 oncologic events: MGUS (a common, age- related medical condition characterized by
accumulation of monoclonal plasma cells in the BM moderate IgG spike on electrophoresis) + 2nd
hit causing transition of MGUS to severe MM
Signs & symptoms
-Forms lytic lesions on bone bone pain, pathologic fx, and
hypercalcemia
-Renal failure from excretion of proteins
-Fatigue
-Recurrent infections -Spinal cord compression
-Hyperviscosity syndrome from high circulating Ig of all kinds
Workup
-Bone marrow biopsy shows > 5% plasma cells -Lytic lesions on metastatic bone survey x-ray series -Spikes in M protein in protein electrophoresis (differentiate from MGUS, where M protein level will still be WNL) -IgG and IgA spikes on electrophoresis
-Peripheral smear showing rouleaux formations (poker chips) -Urine has Bence-Jones proteins (produced by malignant plasma cells)
-Hypercalcemia -Anemia
Management -Chemotherapy
-Local radiation for pain control -Autologous BMT
-Bisphosphonates for hypercalcemia Prognosis
-Average survival with chemo is 3 years, 7 years for BMT
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LymphomaHodgkin Lymphoma Non-Hodgkin Lymphoma
-A group of cancers characterized by orderly spread of disease from one lymph node to another and by the development of systemic symptoms with advanced disease
-Extranodal presentation in the lung, liver, or BM in some cases -Peaks in adolescence and young adulthood, and in ages 50+ -Association with EBV
Signs & symptoms
-Painless, firm lymphadenopathy (often supraclavicular and cervical areas), mediastinal mass causing cough or SOB, fever, weight loss
Workup
-Peripheral smear showing Reed-Sternberg cells -CT scans of chest, abdomen, and pelvis -PET scan
-BM biopsy -Lymph node biopsy Management -Chemo
-Low dose radiation Prognosis
-Overall survival 90% but there are 3 separate risk groups
-A diverse group of blood cancers that include any kind of lymphoma except Hodgkin (includes CLL, Waldenstrom’s, and multiple myeloma)
-Associated with congenital or acquired immunodeficiency -Single or multiple areas of involvement
-Low, intermediate, and high grades -Incidence increases with age Signs & symptoms
-Lymphadenopathy hydronephrosis, bowel obstruction, jaundice, wasting, SVC syndrome -Abdominal pain
-Fever, weight loss, night sweats -Edema
Workup
-CBC and smear are usually normal -Lymph node biopsy
-CT scans of chest, abdomen, and pelvis Management -Systemic chemo Prognosis -70-90% survival rate INFECTIOUS DISEASE Cryptococcosis -Cryptococcus neoformans
-Invasive fungal infection that is becoming increasingly prevalent in the immunocompromised population (AIDS, prolonged steroids, organ transplant, malignancy, sarcoidosis) -Associated with soil frequented by birds and with rotting vegetation
-Worldwide distribution
Signs & symptoms
-Pulmonary infections solitary, non-calcified nodules -Meningoencephalitis: seen in HIV, sx occur over 1-2 weeks,
Workup
-Must culture organism from CSF for definitive dx of meningitis but can presumptively ID with CSF Ag testing Treatment
-Amphotericin B and flucytosine for meningitis Pulmonary Histoplasmosis
-Histoplasma capsulatum
-The most prevalent endemic mycosis in the US
-Associated with bird and bat droppings, chicken coops, farm buildings, abandoning buildings, caves, wood lots
-Most infections will be asymptomatic or self-limiting
Signs & symptoms
-Symptoms begin weeks to months following exposure -Pneumonia with mediastinal or hilar lymphadenopathy -Mediastinal or hilar masses
-Pulmonary nodule -Cavitary lung disease
-Pericarditis with mediastinal lymphadenopathy -Arthritis or arthralgia + erythema nodosum -Dysphagia from esophageal narrowing -SVC syndrome
-With dissemination: fever, fatigue, weight loss, GI, CNS, adrenal manifestations Differential -Sarcoidosis -TB -Malignancy Workup
-CXR looks just like sarcoid -Histo serologies
-Special stains on biopsy specimens -EIA: urine, blood, or BAL Management
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HIV-Progresses from primary infection with seroconversion clinical latency early symptomatic disease AIDs -Transmission is mostly heterosexual in developing countries while both MSM and heterosexual in the US
-Patients are most infectious during primary infection
Signs & symptoms
-Only lymphadenopathy during asymptomatic disease -May have mononucleosis-like syndrome during primary infection
-Febrile illness -Aseptic meningitis
Workup
-Serologies are + 3-7 weeks after infection -Drug resistance testing
-Definition of AIDS is when CD4 count drops to < 200 Management
-Large debate about aggressive treatment of primary infection vs waiting until disease is symptomatic
Lyme Disease -Borrelia burgdorferi with a tick vector
-Transmission usually does not occur until 72 hours after attachment Signs & symptoms
-Early localized disease: erythema migrans ~1 mo after exposure, nonspecific viral syndrome -Disseminated disease: acute neurologic or cardiac involvement weeks to months after tick bite (AV blocks
-Late disease: years after disease; arthritis, subtle encephalopathy or polyneuropathy -HA, fatigue, arthralgias may persist for months after treatment but don’t represent active disease
Workup
-Dx can be clinical if erythema migrans is present (serologies will be neg) -Serologies will be + during early disseminated disease
Management
-Treat with doxycycline, amoxicillin, or cefuroxime, for 10-21 days for erythema migrans, 14-21 days for facial nerve palsy, 28 days for meningitis or arthritis
-IV antibiotics needed for patients with cardiac symptoms or late neurologic disease -No evidence for extended-course antibiotics for presumed chronic Lyme
-Can give single dose doxycycline for prophylaxis if attached tick is identified, estimated to be present > 36 hours, local tick Borrelia infection rate > 20%
Cholera -Vibrio cholerae
-US cases are only acquired overseas or via consumption of contaminated seafood
Prevention
-Dukoral vaccine available
Signs & symptoms -Severe, watery diarrhea -Vomiting
Workup
-Stool Gram stain for curved Gram neg rods -PCR for toxinogenic strains
Management
-Begin treatment before definitive diagnosis! -Rehydration
-Antibiotics: doxycycline, FQ if resistant Mycobacterial Disease
-Mycobacterium tuberculosis -Mycobacterium leprae
-Non-tuberculous mycobacteria: MAC, Mycobacterium kansasii, Mycobacterium abscessus
Signs & symptoms
-MAC: pulmonary disease with cough, fatigue, malaise, weakness, dyspnea, chest discomfort, occasional hemoptysis -M. kansasii presents as lung disease that is very similar to TB -Superficial lymphadenitis
-Disseminated disease in the immunocompromised -Skin and soft tissue infection from direct inoculation
Workup
-Sputum or BAL culture Management
-3 drug regimen for 12 months+
Amebiasis -Entamoeba histolytica
Signs and symptoms
-Intestinal amebiasis has a subacute onset of 1-3 weeks with mild diarrhea or dysentery, abdominal pain, bloody stools, can have fulminant colitis with bowel necrosis perf and peritonitis or toxic megacolon
-Extraintestinal manifestations present as liver abscesses or pulmonary, cardiac, or brain involvement
Workup
-Serology or Ag testing along with parasitic stool exam Management
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Toxoplasmosis-Toxoplasma gondii
-Acquired via ingestion of contaminated meat or cat poop, through vertical transmission, or via blood transfusion or organ transplantation
-High amount of seroprevalence in US as 30-40% of household cats are infected
Prevention
-AIDS pts should be given prophylaxis
Signs & symptoms
-Majority of adult infections are asymptomatic -Fevers, chills, sweats
-Cervical lymphadenopathy
-Can have reactivation illness during times of immunosuppression
-In HIV can have encephalitis
-With vertical transmission there is congenital toxo syndrome
Workup
-Serology (IgM will be + within 1 week and may persist for years, IgG persists for lifetime)
-Brain MRI for HIV patients showing ring-enhancing lesions Management
-Pyrimethamine + sulfadiazine for cerebral toxoplasmosis
Syphilis -Treponema pallidum
-Most cases are MSM
Signs & symptoms
-Primary/acute infection lasts 5-6 weeks: contagious chancre, painless rubbery regional lymphadenopathy, followed by generalized lymphadenopathy
-Secondary infection 6 weeks-6 months after exposure (not all pts will develop this): fever, malaise, HA, arthralgias, bilateral papulosquamous rash on the palms and soles, alopecia, denuded tongue, condyloma lata
-Tertiary infection occurs in disease > 4 years’ duration: end organ manifestations, CV symptoms, gummas, neurosyphilis -Latent infection has no clinical manifestations but serology will be reactive
Workup
-Remember that negative tests do not exclude a diagnosis of syphilis
-Darkfield microscopy of chancre sample -LP for neurosyphilis
-Direct fluorescent antibody testing
-Serology: RPR (has a 3-6 week latency period)
-HIV test recommended as syphilis facilitates this infection Management
-Mandatory reporting within 24 hours -Penicillin G
-Recheck serologies at 6 and 12 months after treatment to look for fourfold reduction in titer
Cytomegalovirus -Transmission may be sexual, close contact, or blood and tissue
exposure
-HIV patients and transplant patients are at increased risk of reactivation disease
Signs & symptoms
-Generally asymptomatic or nonspecific in immunocompetent host
-Can have CMV mononucleosis with fever (distinguish from EBV by absence of lymphadenopathy and pharyngitis) -Rare associations with colitis, encephalitis, myocarditis -Can have reactivation in critically ill patients
Workup -CBC shows lymphocytosis -PCR test -Serologies -Viral culture Management
-Antivirals only for immunocompromised with severe manifestations