1
Q
Leishmaniasis
A
Sandfly - tropic/subtropic/southern europe
Cutaneous - large painful ulcer
Visceral - enlarged spleen/liver, anemia
protzoan parasite > sandfly humans
2
Q
Lifecycle leishmaniasis and role of sandfly
A
injects infective promastigote (with flagellum) > go into macrophage > amastigote > replicates > ruptures macrophage
Leishmania is transmitted by sandflies as promastigotes, which are taken up by human macrophages, transform into amastigotes, and replicate. Sandflies ingest amastigotes during a blood meal, where they revert to promastigotes, completing the cycle.
3
Q
Dx and treatment leshmaniasis
A
Cutaneous papule - ulcer with heaped up border, can spontaneously heal.
Mucosal - membranes of nose and mouth, does not heal spontaneously. can present decades are lesions healed.
Visceral - fever, weakness, WL, hepatosplenomegaly, pancytopenia, hypergammaglobuinemia
Dx: skin biopsy, microscopy, PCR, Serology
Tx: Visceral: liposomal amphotercin B (renal toxic)
Cutaneous: miltefosine
Not a sterile cure > can relapse, esp if immunosuppressed
4
Q
T cruzi life cycle
A
triatomine bugs, reduvid bug
- red circle reaction
- same life cycle as leshmaniasis
5
Q
Chagas disease presentation, acute and chronic, and congenital
A
Acute > indeterminate (prelclinical) > determinate (clinical)
few months - flu like nonspecific symptoms (swollen eye, romanas sign)
Chronic phase - megacolon, megaesophagus, enlarged heart
6
Q
Diagnosis and treatment of T. cruzi infections
A
Acute infx: fever, chills, hepatosplenomegaly, unilateral palpebral swelling.
2 positive tests, acute blood smears, chronic serology antibody testing
tx: nifurtimox, benznidazole - treat everybody except advanced chagas cardiomyopathy and pregnancy/liver or renal dysfunction.
7
Q
T brucei life cycle and transmission by tsetse fly
A
Sleeping sickness
Tstse fly
8
Q
African trypanosmiasis clinical progression
Difference between TB gambiense and rhodesiene
A
TG - slow, chronic, WEST and central africa
- humans reservoir, pigs and cattle.
TR - EAST and south africa. Will have an inoculation chancre at the site of the fly bite.
- wild animals in the bush, careful with safari tourism in east africa
- transmitted mother to child, mechanical through insects, laboratories, sexual contact
Hemolytic stage»_space; crosses the BBB > meningoencephaltic stage (neuropsychiatric issues, disruption of sleep-wave cycle).
9
Q
Diagnosis of TG and TR
A
first stage no symptoms.
Blood smears - parasite in low number
lymph node/chancre aspirate
Tx: pentamidine
Control strategy: TG: humans, TR: cattle
10
Q
Presentation, diagnosis, tx of lymphatic filiarisis
A
Most are due to Wucheria bancrofti
can also be brugia malayi, b timori
- adult worm in lympathics > release microfilarie into the blood
- mosquito
- most have no symptoms > lymphedema, death of adult worm can trigger an inflammatory response > lymph dysfunction
Elephantitis
Tx: Diethylcarbamazine DEC
- if lymphedema and elephantitis unlikely to benefit from DEC > not actively infected with filarial parasite
Prevention - mass drug administration
- albendazole, ivermectin, DEC
11
Q
Wuchereria bancrofti
A
Mosquito > larvae into human > adult in lympathics > produce microfilarie that circulate into blood > mosquito ingests.
12
Q
Loa loa
A
Deer fly
13
Q
Onchocerciases
A
black fly
14
Q
Dracunculiasis
A
guinea worm - drinking unfiltered water
15
Q
Poxvirus, replication cycles, MOA of small pox antivirals
A
Large, brick shaped, enveloped virus
DsDNA - Huge
CYTOPLASMIC (DNA viruses are usually nuclear).
Small pox rash HY – all at the same stage of development, versus varicella which has different stages (vesicle, pustule, crust).
inhale virus - fever/body aches/ vomiting > rash > pustules > scabs > scars
16
Q
Vaccine strategies against small pox
A
Tecovirimat (TPoxx)
Inhibits Vp37 envelope protein
17
Q
Smallpox vs Mpox presentation
A
Mpox, face to face contact/physical contact
milder rash than Mpox
- Jynneos vaccine - non replicating live virus ** go to
ACAM2000 - replicating virus
18
Q
Ebola
A
Ebola: African fruit bat
contact with infectious fluid (blood, body fluids, bedding
abrupt onset 8-10 days after exposure
Severe viral hemorrhagic fever
PCR early in disease and confirm with serology
Tx: monoclonal antibody
Immazeb (3 Mabs), ebanga (single Mab)
Ebola vaccine - live recombinant virus vaccine
19
Q
Marburg virus
A
Marburg: egyptian rousette bat, fruit bat
- same as ebola, spillover from bat contact
- rest is the same as ebola, but no treatment, only supportive care at this time
20
Q
Lassa virus
A
reservoir: multimammate rat
- contact/inhaling rodent poop
- person to person
80% mild, 20% severe - hemorrhaging, RDS, shock
- can cause deafness
- IgM/IgG serology and PCR
Tx: Ribavirin (early in infection) and supportive care
KEEP A CAT - gets rid of rodents
Cook foods thoroughly, store container with lid, wash hands regularly
Enveloped, bisegmented negative-sense RNA (ebola is nonsegmented). Lassa virus is in the Arenavirus family, named for the “sandy” appearance of the virions caused by host ribosomes packaged inside the virus particle.
21
Q
Viral Hemorrhagic fevers
A
22
Q
Live recombinant ebola virus vaccine
A
23
Q
Tropical pulmonary eosinophilia (TPE) syndrome
A
Cough, fever, eosinophilia, high serum IgE (>1,000), positive antifiliaril antiodies
- peripheral microfilaremia is ABSENT in patients with TPE
Men, Asia
microfilariae in blood > thick smear, serology, ultrasound.
24
Q
Lymphatic filariasis
A
Avoid DEC if co-infection with Onchocerca or Loa loa (can worsen disease).
25
Filarial worms
Wuchereria/Brugia → lymphatics (→ elephantiasis).
Loa loa → subcutaneous tissue (→ Calabar swellings, eye worm).
Onchocerca → skin & eyes (→ dermatitis + blindness).
26
Ebola/Marburg/Lassa
Lassa = “Rodent & Ribavirin”; Ebola/Marburg = “Bat & Bleeding”)
27
HIV CNS Lesions
Non aids: HSV/VZV, encephalitis, neurosyphillis, brain abscess
AIDS opportunistic infections:
space occupying - toxoplasmosis, primary CNS lymphoma
Non space occupying: TB mengitis, cryptococcal menigintis, PML, HIV encephalitis
CNS and lung infections: Nocardia, mycobacteria (TB), fungal (cocci, histo, blasto, crypto), non-infectious like malignancy and autoimmune.
28
ART considerations for delayed initiation
Crypto meningitis → delay ART 4–6 weeks (avoid fatal IRIS).
Toxo encephalitis → start ART 2–3 weeks (safe + improves outcomes).
TB → CD4 <50: early ART (≤2 weeks); CD4 ≥50: wait up to 8 weeks.
TB meningitis → delay 8 weeks (CNS IRIS is very dangerous).
29
Explain Immune Reconstitution syndrome during ART initiation
30
Quick HIV CNS Lesions
Multiple ring-enhancing lesions → Toxoplasmosis (Tx: pyrimethamine+sulfadiazine).
Single ring-enhancing lesion → CNS lymphoma (EBV+, Tx: high-dose methotrexate).
Non-enhancing white matter lesions → PML (Tx: ART only).
Meningitis with ↑ opening pressure → Cryptococcus (Tx: amphotericin B + flucytosine).
31
Toxoplasmosis
Toxo gondii
- eating undercooked meat/shellfish/swallowing parasite from cat feces
- brain/eye anifestations
- only known definitive host - CAT (TOXO CAT)
CD4 < 50, serum IgG pos
Presentation: focal encephalitis, behavioral changes/ HA, extrapulmonary involvement like eyes, lungs
- MRI: contrast enhanced lesions in grey matter of cortex/basal ganglia
Tx: Pyrimethamine + sulfadiazine + leucovorin; start ART
32
Cryptococcus fungus
Crypto meningitis: Amphotericin B + flucytosine, then fluconazole; delay ART 4–6 wks
inhale > disseminates from lungs to CNS
- polysaccharide capsule, india ink ****
- Engagement ring on microscope
>>> can become pneumonia or meningitis
- neoformis - soil contaminted with pigeon droppings
- meningitis - CD4 < 100, subacute meningitis, umbillicated skin lesions/pulmonary infiltrates
Crypto meningitis - CSF will have low glucose and pleocytosis of lymphocytes, increased OP
- Serum in disseminated or CSF CrAg > 95%
Tx: Induction: IV amophtercin B plus oral flucytosine for two weeks
- LP KEY - repeat LP daily until symptoms improve 0 increased ICP is an issue
Consolidation: after negative CSF on repeat LP > Fluconazole 400 for 8 weeks
Maintenance: Fluconazole 200 daily for one year
ART: Delay 4-6 weeks after antifungal
33
Tuberculosis
Caused by Mycobacterium tuberculosis reaching the meninges via hematogenous spread or rupture of a subependymal tuberculous focus (Rich focus).
Chronic, progressive course → basilar meningitis.
Clinical features:
- CN palsys (3, 4, 6) plus meningitis signs
Tx: Induction: RIPE (Rifampin, Isonaizid, Pyrazinamide, Ethambutol) x 2 months
- add dexamethasone taper for 12 week
Continuation: INH and Rifampin (RI) for 7-10 months
- If CD4 < 50 - treat with ART within 2 weeks. Can delay to 4-8 weks if CD4 > 50 or 200.
If TB meningitis -- must delay 8 weeks for ART.
Still death/severe neurologic impairment with treatment.
34
HIV Antiretroviral
2 NRTIs (nucleoside reverse transcriptase inhibitors) --
zidovudine, lamivudine, emtricitabine, abacavir
-- PLUS a third drug from one category:
- integrase strand transfer inhibitor (efavirenz, nevirapine)
- non nucleoside reverse transcriptase inhibitor (olutegravir, elvitegravir, and raltegravir)
- protease inhibitor
Modern first-line: Biktarvy (BIC/TAF/FTC) or Triumeq (DTG/ABC/3TC).
Backbone = 2 NRTIs (TDF/FTC or ABC/3TC).
Anchor = INSTI (dolutegravir, bictegravir).
35
When to start ART
RIGHT AWAY
Except if
1. cryptococcal meningitis
2. TB meningitis
36
IRIS
intense inflammatory reaction to foreign antigens after rapid immunologic recovery
- if OI and ARV too close can cause it
- Tuberculosis, CMV retinitis, cryptococcus, etc
Pathophysiology: initiate ART > increase in CD4 count > rapidly increasing T cells (decreased apoptosis and lymphocyte redistribution) > this can lead to excess pathogen specific cellular response, and T reg cells decrease which regulates inflammation
- uncoupling of innate and acquired immunity
Pardoxical IRIS (within 3 months of ART) > Tx with steroids
- TB worseneing
If TB diagnosed during ART - unmasking IRIS, treat with RIPE
Give steroids, do not stop ART.
Initiation of ART: Start within two weeks or as soon as clinically stable in patients being treated for opportunistic infections, except in tuberculous meningitis, cryptococcal disease, and CMV retinitis.
37
Life cycle plasmodium
First grows in the liver after mosquito bite > cycles through RBCs > symptoms.
Sporozoite = infective form (mosquito → human).
Merozoite = infects RBCs, causes symptoms.
Hypnozoite (vivax/ovale) = dormant liver form, relapse.
Gametocyte = sexual form (human → mosquito).
✅ Summary Sentence:
Mosquito injects sporozoites → liver schizonts → merozoites infect RBCs (fever cycles) → gametocytes taken up by mosquito → sporozoites in salivary glands → repeat.
38
Clinical presentation of malaria
Classic - cold stage, hot stage, sweating stage - every 2 days typical or every 3 days for malariae
Severe malaria - cerebral, severe anemia, hemoglobinuria, coagulation issues, low blood pressure, ARDS.
virax and ovale relapsers
39
Five species of plasmodium differences depending presentation
Falciparum = fatal → severe, irregular fever, cerebral malaria
Vivax/ovale = relapse (hypnozoites in liver). Needs Duffy antigen is the receptor, whereas ovale does not.
Ovale is other relapser. Vivax Big RBC like IMAX, Ovale, oval RBC
Malariae = 72h fevers + nephrotic syndrome risk. 3 day cycle fevers. 3 A's - 3 day fevers
Knowlesi = daily fevers + zoonotic in Asia. Can rapidly progress
40
Malaria diagnosis, prevention, treatment
Microscopic analysis blood smear
- giemsa stain (parasites)
- need 3 sets 12-24 hours apart
PCR - confirm plasmodium species
RDT - another test ??
Artemisin based therapies (ACT)
- lumefantrine, mefloquine, piperaquine, amodiaquine or sulfadoxine pyrimethamine
41
antimalarial drug resistance impact
P. falciparum resists chloroquine via PfCRT mutation (efflux).
Resistance guides therapy choice → chloroquine for vivax/ovale in most regions, but ACTs for falciparum.
K13 mutations → emerging artemisinin resistance, major public health threat.
42
Malaria vaccine
Targets only P falciparum
Mosquirix
43
Malaria liver hypnozoites in liver
can relapse
44
Malaria
Anophele mosquitos
45
Primary vs secondary immune disorders
disorders within vs outside the immune system (e.g., secondary is like malnutrition, corticosteroids).
46
Primary ID
47
Phenotypes of inborn errors of immunity
48
Interpret cel quantification, flow cytometry, cellular function, serologic assays to classify forms of immune compromise
49
Mechanisms of immune dysregulation in primary ID
50
Therapeutic interventions to mitigate infection susceptibility
51
Immune system overview
52
Immune system table
53
Complement system
HY:
Opsonization → C3b tags pathogens for phagocytosis.
Chemotaxis → C5a recruits neutrophils (very high yield!).
Anaphylatoxins → C3a, C4a, C5a cause histamine release (mast cell degranulation).
MAC (C5b–C9) → forms pore in bacterial membranes → lysis (esp. Neisseria).
54
Complement table
Complement is part of the innate humoral system, but the classical pathway links it to adaptive immunity (antibodies). It opsonizes (C3b), recruits (C5a), inflames (C3a, C5a), and lyses (MAC).
55
SCID
In SCID, B cells may be present in number but cannot function without T cell help, so antibody production is defective. Immunoglobulin replacement provides passive protection until curative therapy like HSCT is done.
Newborn screen - undetectable TREC count
CBC - lymphopenia, TBNK panel, Immunoglobulins normal at first, but by 6 months lose maternal ones.
Normal at birth → symptoms appear early (first months).
Severe recurrent infections: bacterial, viral, fungal, protozoal.
Chronic diarrhea, failure to thrive, persistent oral thrush.
Absent lymphoid tissue (small or absent lymph nodes and tonsils
Tx: Hematopoietic stem cell transplant (HSCT) → curative (best if <3.5 months of age → ~94% long-term survival). IV immunoglobulins.
Pneumocystis prophylaxis (TMP-SMX). Avoid live vaccines (risk of severe disseminated infection).
56
Immune deficiencies
https://next.amboss.com/us/article/tM0Xqg?utm_medium=chatgpt-plugin&utm_source=chatgpt#Z8396e8d853ea3918736b6bfa197c4ce7
57
Digeorge 22q11.2
T cell
Think DiGeorge in a child with congenital heart disease + cleft palate + recurrent infections + hypocalcemia. Diagnostic hallmark is 22q11 deletion with absent thymic shadow on CXR.
abnormal development: 3rd and 4th pharyngeal pouches → hypoplastic thymus and parathyroid glands
- Cardiac anomalies: conotruncal defects (tetralogy of Fallot, truncus arteriosus, interrupted aortic arch, VSD/ASD)
- Anomalous facies: small jaw, dysplastic ears, prominent nasal bridge.
- Thymus aplasia/hypoplasia: → T-cell deficiency → recurrent viral, fungal, PCP infections
- Cleft palate.
- Hypoparathyroidism → hypocalcemia → seizures, tetany
- Chromosome 22 involvement.
CMP - hypocalcemia: Hypocalcemia in DiGeorge syndrome is due to hypoplastic/absent parathyroid glands from 3rd/4th pouch maldevelopment, causing ↓ PTH and ↓ calcium.
Tx: all the protective stuff plus thymic replacement
58
SCID = “bubble boy” → profound infections, absent lymphocytes (T always ↓, B/NK vary).
DiGeorge = T-cell deficiency plus hypocalcemia + heart defects. B/NK are preserved in number.
In SCID, the defect is in lymphocyte precursors, so you must replace the bone marrow (HSCT). In DiGeorge, precursors are normal but the thymus is absent, so a thymus transplant can reconstitute T-cell function.
59
X linked agammaglobulinemia
BOY, BTK, FH of MEN having it, XLR
Leukocytosis (left shift) -- Left shift leukocytosis in XLA isn’t part of the primary disease, but it often appears during infections because neutrophils are mobilized normally even though B cells and antibodies are absent.
- Deficient in all of the globulins
- pre-B cells cannot mature into mature B cells.
Result:
- Absent mature B cells in blood/lymphoid tissue.
- Very low immunoglobulins (all classes: IgG, IgA, IgM, IgE, IgD).
- Normal T cells → intact cellular immunity.
Infants are protected until ~6 months by maternal IgG. After that → recurrent bacterial infections: Sinopulmonary (otitis media, pneumonia, sinusitis).
GI infections (Giardia lamblia → chronic diarrhea).
Absent tonsils and lymph nodes (no germinal centers).
Viral/fungal infections are less common (T cells intact).
60
Chronic granulomatous disease
NBT test - positive purple/blue -- NADPH working (fails to turn blue >> CGD)
- NADPH oxidase deficiency >> impaired respiratory burst, macrophage and neutrophil ingest but can't kill.
DHR test >> decreased green which shows defective ROS
XLR, CYBB mutation
Recurrent, severe infections with catalase-positive organisms:
Bacteria: Staph aureus, Serratia, E. coli, Klebsiella, Pseudomonas, Nocardia.
Fungi: Aspergillus, Candida.
Granuloma formation (skin, GI/GU tract).
Lymphadenitis (necrotizing lymph node), pneumonia, osteomyelitis, abscesses.
Interferon-γ therapy in CGD works by activating macrophages and enhancing alternative killing pathways, improving pathogen clearance even though NADPH oxidase is defective.
61
CVID
Chronic diarrhea, recurrent sinopulmonary infx
CBC and TBNK panel normal
Duodenal biopsy -- villous atrophy and lymphoid aggregates
Low IgG, Low IgA, normal IgM
B cells present, but fail to become plasma cells
CTLA4 insufficiency
↓ IgG, IgA, IgM.
↓ plasma cells.
Normal B- and T-cell counts on flow cytometry.
Functional: poor response to vaccines/immunizations.
Tx: IVIG, antibiotics, avoid live vaccines, HSCT,
62
CVID
PIK3CD GOF = hyperactive PI3Kδ → lymphoproliferation, infections, lymphoma → treat with PI3Kδ inhibitors (leniolsib)
CTLA-4 deficiency = immune checkpoint defect → Treg dysfunction + autoimmunity → treat with abatacept.
Both cause “CVID-like” hypogammaglobulinemia, but the autoimmunity is much stronger in CTLA-4 deficiency.
63
Hyper IgE
Sever evzema, recurrent infx
CBC - eosinophilia, high IgE, decreased Th17 so impaired recruitment of neutrophils to site of infection
Autosomal dominant (STAT3)
Recurrent cold abscesses, baby teeth, coarse face, eczema, fractures.
64
Adalimumab
Anti TNF
TNF-α = “master inflammatory cytokine” → fever, inflammation, granulomas, septic shock.
TNF-β (lymphotoxin) = made by lymphocytes, overlaps with TNF-α but also essential for lymphoid tissue development.
TEST FOR TB
65
Arizona and cocciodioidomycosis
Coccidioidomycosis (endemic)
TNF-α is critical for granuloma formation and fungal containment.
Blocking TNF-α with biologics like adalimumab impairs granuloma maintenance → higher risk of disseminated coccidioidomycosis.
Dissemination is often severe and life-threatening, especially CNS disease (meningitis).
66
Paroxysmal nocturnal hemoglobunuria
Blood cells usually express CD55 >> without will become susceptible to complement mediated hemolysis
Hemolysis: dark urine in morning, fatigue, anemia, jaundice.
Thrombosis: esp. hepatic, portal, cerebral veins (major cause of mortality).
Bone marrow failure: pancytopenia, aplastic anemia, possible evolution to AML.
Tx: Eculizumab: monoclonal antibody against C5 → blocks terminal complement activation, reducing hemolysis and thrombosis risk.
eculizumab risk of meningitis (neisseria)
67
Ocrelizumab
Anti CD20, makes it harder for B cells to become mature.
Leads to secondary hypogammaglobulinemia in some patients because:
Plasma cells aren’t directly depleted, but long-term B-cell depletion reduces antibody renewal.
IgM tends to fall first; IgG and IgA can also decline over time.
This can result in recurrent infections (respiratory, urinary).
68
pneumocystis
TMP-SMX
PJP is a fungus - lacks ergestrol so not effective to use azole
TMP-SMX (trimethoprim-sulfamethoxazole):
Blocks folate synthesis (dihydrofolate reductase and dihydropteroate synthase inhibition).
Effective against Pneumocystis because it relies on folate metabolism.
69
FCr engagement
When antibodies bind an antigen, their Fab region attaches to the pathogen.
The Fc region sticks out and can be recognized by FcRs on immune cells.
This bridges innate and adaptive immunity:
Antibodies provide specificity.
FcR-bearing cells provide effector functions.
70
ANA by IFA
Titer The more dilute and still seeing the antibody, the more positive. So high titer is really dilute, but worse
Pattern: E.g., SLE is often ANA homogenous and speckled
71
Suspicion for SLE or other autoimmune
ANA > ELISA for specific antibodies
72
Anti dsDNA
Anti SMITH (highest specificity)
SLE antibodies, both assoc with lupus nephritis
Trend over time, correlate with disease activity
73
Anti RHO/SSA and Anti LLA/SSB
Assoc with Sjorgen's and overlaps with SLE (e.g., cutaneous lupus)
74
anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein I
Antiphospholipid
Think hypercoagulability
75
Systemic scleroderma
Anti centromere
Antitopoisomerase (Anti Scl 70)
CREST mnemonic:
Calcinosis cutis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
Main complication: pulmonary arterial hypertension.
2. Diffuse cutaneous systemic sclerosis (dcSSc)
Widespread skin thickening (trunk, proximal limbs).
Early visceral involvement: lungs (interstitial lung disease, pulmonary fibrosis), kidneys (renal crisis), heart, GI tract.
76
SLE
Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein I)
77
Anti jo
Anti–Jo-1 is an autoantibody against histidyl–tRNA synthetase, seen in polymyositis/dermatomyositis and defining antisynthetase syndrome (myositis, ILD, arthritis, Raynaud, mechanic’s hands).
78
ANCA
c-ANCA = GPA (PR3)
p-ANCA = MPA, EGPA (MPO)
79
Complement deregulation
80
Complement deregulation and mechanism
81
Hypocomplementemia
Genetic: deficiency in C1, C4, C3 -- risk of encapuslated bacteria (s pneumo, H influenza). C5-C9 - neisseria infection risk
Persistent activation: SLE, Lupus nephritis (low C3, C4)
82
Evaluate for complement deficiency
CH50
AH50
CH50 - CLASSICAL measure
AH50 - ALTERNATIVE measure
83
Low CH50
deficiency in classical pathway
C1, C2, C4 or inhibitors
This is classical AND alternative
If it is NORMAL AH50 and low CH50, most likely classical that is the issue.
84
Low AH50
deficiency in the alternative pathway
- TERMINAL/ALTERNATIVE
- especially if NORMAL ch50
85
LOW CH50
AND
LOW AH50
deficiency in the terminal pathway C5-C9
86
CH50 and AH50
Low CH40, Normal AH50 - classical deficiency
Normal CH50, Low AH50 - alternative pathway deficiency
Low CH50, Low AH50 - terminal pathway deficiency
87
Classification SLE
ANA > 1:80
>10 points of constitituional ,renal (e.g., proteinuria), low complement, mucocutaneous, SLE anbx (anti dsdna, anti-smith), antiphospholipid antibodies (e..g, anticardiolipin, anti b2 glycoprotein, lupus anticoagulant), joints, neuropsych
-Proteinuria > 0.5
Lupus nephritis
Oral ulcers
acute pericarditis/leural effusion
Leukopenia WBC <4,000
low platelets (<100,000
Autoimmune hemolysis - low haptoglobin, elevated indirect bilirubin, elevated LDH, positive comb test
ESR high but CRP usually normal in lupus, can help distinguish lupus from infection.
88
3 mechanisms of immune dysregulation lupus
89
Antiphospholipid antibodies
Lupus anticoagulant
Anticardiolipin antibody
Anti–β2 glycoprotein I antibody
can cause anti phospholipid syndrome - secondary complication of lupus.
90
Acute cutaneous
Malar rash, spares nasolabial folds
PHOTOSENSITIVE
91
Chronic cutaneous
Discoid rash
common in sun exposed areas
panniculitis - tender under skin
Chilblains - pain toes to cold
92
Can see serositis in SLE
pleuritis, pericarditis, etc
93
SLE heart
Libmann sack endocarditis (deposition on values in the heart from the antibodies)
94
Lupus labs
ESR high, CRP normal → lupus flare (unless serositis/infection complicates).
Low complement (C3/C4) → immune complex activity, esp. nephritis.
Cytopenias (anemia, leukopenia, thrombocytopenia) are part of classification criteria.
Urinalysis + creatinine are essential for detecting lupus nephritis early.
Prolonged aPTT with clots → antiphospholipid antibodies.
95
CRP
Driven by IL-6
96
Lupus workup
97
SLE
Driven by interferon alpha beta
98
Lupus diagnosis
99
Anti RNP
Anti-RNP (anti-U1 ribonucleoprotein) antibodies are present in ~30–40% of SLE patients but are not specific. In very high titers, they define mixed connective tissue disease (MCTD), which overlaps SLE, systemic sclerosis, and polymyositis.
MCTD is an overlap syndrome of SLE, systemic sclerosis, and polymyositis, defined by high-titer anti–U1 RNP antibodies, presenting with mixed features such as Raynaud, arthritis, myositis, and pulmonary disease.
100
Lupus nephritis
Full house” IF staining → IgG, IgA, IgM, C3, C1q all present.
“Wire-loop lesions” → subendothelial immune complex deposits in Class IV.
Subepithelial deposits → seen in Class V (membranous).
101
All patients
Hydroxychloroquinone
plus/minus steroids
hydroxychloroquinolone not very immunosuppressive - antigen/antibody interfering
START IV methyl prednisone > oral CS and taper > HydroxyCLQL > steroid sparing immunosuppressant like azathiprine, mycophenolate, rituximab, ccyclophosphamide, etc
SUN PROTECTION
102
SLE
TYPE 1 INTERFERON DISEASE
103
Complement
104
SLE
Genetic and environmental (UV, EBV, drug -nduced)
All three mechanisms — immune complex deposition, neutrophil dysregulation, and T-cell activation/exhaustion — are known to contribute to the pathogenesis of SLE.
105
Immune mechanisms of dysregulation in SLE
1. Overproduction of proinflammatory cytokines (e.g., Type 1 interferon)
2. Defects in apoptotic clearance >> autoantigens
3. Complent activation and deposition (e.g., kidneys)
4. Increased and dysregulated neutrophil apoptosis
5. dysregulated adaptive immune cells > production of autoantibodies
106
CGD
A 3-year-old with recurrent Serratia osteomyelitis should be evaluated for Chronic Granulomatous Disease using the DHR assay, which tests neutrophil oxidative burst.
107
T cell activation
T cell activation requires two signals: (1) TCR binding antigen–MHC, and (2) CD28–B7 co-stimulation. Cytokines then direct T cell differentiation. Without co-stimulation, T cells become anergic to prevent autoimmunity.
Il-2 and Il-12
108
Cytokines
Pro-inflammatory: IL-1, IL-6 , TNF-a
Anti-inflammatory: IL-10, TGF-B
Anti, ten, T-beta
109
T cells
110
B cell development
111
B cells
112
C3b
opsonization
113
Complement system
114
Hypersensitivity reactions
Type 1 - IgE, seconds - minutes
Type 2 - cytotoxic antibody mediated, incompatible blood transfusion, hyperacute rejection - minutes to hours
Type 3 - immune complex - SLE, days
Type 4 - T cell activated - days - GVHD, contact dermatitis
115
WAS
Wiskott-Aldrich = X-linked, WAS gene mutation → defective cytoskeleton → triad of thrombocytopenia, eczema, infections; labs show ↓ IgM, ↑ IgA/IgE. also easy bruising and bleeding
116
Chediak higashi
impaired granule release due to LYST > affects melanin production
Complication >> hemophagocytic lymphohistiocytosis (HLH). HLH is overactivation of immune system
- grey silver hair and frequent infections
- low neutrophils, and with retained granules
HLH Tx: dexamethasone, etopsoide, intrathecal methotrexate
117
Abscess w/o pus
LAD
LAD: No pus at all (neutrophils can’t exit blood).
Hyper-IgE: Abscesses present, but “cold” (non-inflamed) because neutrophil recruitment is defective.
118
Cold abscess
Hyper IgE
LAD: No pus at all (neutrophils can’t exit blood).
Hyper-IgE: Abscesses present, but “cold” (non-inflamed) because neutrophil recruitment is defective.
119
Bullous pemphigoid vs pemphigus vulgaris
120
Hematologic malignancy
121
Chemo drugs
122
Cytokine release syndrome
CART
Activation and destruction of monocytes, macrophages, and
lymphocytes-> increase of inflammatory cytokines (incl IL-6)
Treatment: supportive care and tocilizumab for severe CRS
Neutralizes IL-6, interrupts the inflammatory process
Consider glucocorticoids
CARTCan also cause neurotoxicity
123
JAK inhibitors
RA
Dx Dx Interactions – via CYP3A4 (ketoconazole) and CYP2C19 (fluconazole)
124
HIV meds
125
PCA aneurysm
CN III
Down and out and blown pupil
PS and motor (EWN nucleus for PS)
126
Trigeminal nerve spinal nucleus
Pain/temperature in the face
127
CN 7 facial
facial muscle innervation
PS lacrimal/salivary glands
Special sensory taste ant 2/3 tongue
128
Horner syndrome
miotic pupil (constricted)
ptosis
anhidrosis
PICA stroke
129
UMN
Weakness, spascicity, increased reflexes, present babinski
130
LMN
Weakness
decreased tone
decreased reflexes
atrophy and fasciculations
absent babinski
131
Strokes
Wallenberg > PICA stroke (medullar)
132
Neuronal injury
Microglia and astrocytes respond
133
Dead neurons
134
Astrocyte markers
GFAP
Acquaporin 4
135
GBM
pseudopalisading necrosis
Glioblastoma multiforme (GBM, WHO grade IV astrocytoma) — the most common primary malignant brain tumor in adults.
Other histo features: pleomorphic astrocytes, mitotic figures, endothelial proliferation.
Molecular: IDH-wildtype (classic GBM), EGFR amplification, PTEN loss.
136
Treatment MS
137
Treatment MG
avoid amingoglycoside antibiotics (gentamicin), and inhalational anesthetics
Tx: symptoms -- pyridostigmine, immune modulation - prednisone, IVIG, azathioprine, mycophenolate, eculizumab
Myasthenic crisis: PLEX, IVIG
- hold anticholinesterases because they increase bronchial secretions and use caution with steroids
138
Treatment for pain management, headache, neuropathy
139
Status epilepticus approach
Bolus benzo (midazolam or lorazepam)
Second line: Phenytoin or fosphenytoin (avoid rapid push cardiotoxic), valproic acid, leviteracetam
Third line: propofol, mildazolam, barbiturates, ketamine
140
Thrombolytics, AC and AP for stroke
NO BLEED > systemic lytics and if within 4.5 hours.
if out of 4.5 hours and LVO > thrombectomy
tPA within 4.5 hours if no contraindications.
Mechanical thrombectomy up to 24h for large vessel occlusion.
Aspirin ASAP (if not giving tPA).
Anticoagulation only for cardioembolic sources (timing depends on infarct size).
Hemorrhagic stroke → reverse anticoagulation, lower BP, neurosurgical eval.
141
Alzheimer's treatment
Donepezil (ACHei inhibitor to increase acetylcholine)
Rivastigmine
Memantine (NMDA receptor antagonist (helps slow alzheimers)
Adacunumab (mAB that targets beta amyloid)
- can cause AIRA edema and hemosederin deposition
142
Parkinson's treatment
First line carbidopa/levodopa (dopamine precursor)
second line: Pramipexole, ropinirole (dopamine agonist). Can use monoamine oxidase B inhibitors (selegine)
Bromicriptine
143
Benzos
Gaba A agonist
144
Levetiracetam (calcium channel)
phosphenytoin (sodium channel)
Valproate (MOA unknown)
Phosphenytoin (PURPLE GLOVE)
Valproate - hyperammonemia and hepatoxic
145
General anesthesia
Ketamine, propofol, midazolam, phenobarbatal, thiopental
146
Huntington's
VMAT inhibitor
deplete dopamine
Terabenzaine
Antipsychotics like olanzapine, Risperidone
147
Alzheimers Huntingtons and Parkinsons disease treatment
148
If giving tpa hold aspirin for 24 hours
If no tpa give within first 24 hours
early better
149
DOAC - rivaroxaban, apixaban, edoxaban
Factor Xa
PCC, adexanet reversal
150
Dabigatran - thrombin
reversal with idarucizumab
151
Warfarin
Vitamin K epoxide reductase
Vitamin K
PCC
152
Secondary prevention of strokes
153
Acute goal for tpa HTN
< or equal to 185/110
do not give tpa to very high BP
- labetolol
- Nicardipine
154
MS treatment
IVIG, plasmapheresis, methylpredinosone, prednisone
Rituximab, ocrelizumab, natalizumab (PML)
Symptom management
- baclofen (GABA B receptor) helps with spasciticity
- Tizanidine (alpha 2 agonist, helps with spascicity)
155
Pain
Ketamine NMDA
VSCC - gabapentin, pregabalin (alpha 2 delta)
156
Headache
Ketorolac - NSAID
Diphenhydramine - Antihistamine
Sumatriptan - Serotonin
TH - Topiramate, amitriptline
Migraine - topirimate, beta blocker, valproate
TN - carbamazepine
157
LR6(SO4)3
LR
SO
158
west nile virus
ssRNA Birds
159
Cryptococcus meningitis
VERY high opening pressure
160
Meropenem
CNS instrumentation infection
161
Meningitis empiric coverage
162
Neuro infectious
163
Neurosyphillis
penicillin daily IV continuous infusion for 10-14 days
164
WNV flaccid myelitis vs GBS
WNV flaccid paralysis = anterior horn cell disease → asymmetric motor weakness, no sensory loss, CSF pleocytosis.
GBS = autoimmune demyelination → symmetric ascending weakness, sensory involvement, albuminocytologic dissociation.
165
NMOSD
AREA POSTREMA SYNDROME - VOMITING
Optic neuritis and transverse myelitis
Antiaquaporin 4 diagnosis
- tx: steroids, rituximab, eculizumab, ravilizumab
MS = Dawson’s fingers, OCBs, typical young adult women.
NMOSD = AQP4+, severe bilateral optic neuritis, longitudinal cord lesions, area postrema syndrome.
MOGAD = MOG+, can mimic NMOSD or ADEM, better prognosis.
ADEM = kids, post-viral, encephalopathy + widespread MRI lesions, monophasic.
166
Anti hu antibodies
paraneoplastic snrome with SCLC
167
Anti LGI1
Most common presentation is
limbic encephalitis with
characteristic faciobrachial dystonic
seizures and hyponatremia.
LGI1 antibodies target a VGKC-associated protein → autoimmune limbic encephalitis with memory loss, seizures, FBDS, and hyponatremia. Responds to immunotherapy.
168
NMDAR encephilitis
viral prodrome > nonspecific psych symptoms > insomnia and seizures
Psych → seizure → movement disorder → autonomic instability → coma (stepwise progression).
Ovarian teratoma = classic trigger.
Unlike HSV encephalitis (which it mimics), CSF shows lymphocytic pleocytosis but cultures negative.
Treat early → good prognosis. Rituximab and steroids
FIRST LINE STEROIDS, can consider plasma exchange
169
Rituximab
Hep B reactivation risk
170
Bilateral INO = MS until proven otherwise in a young patient; in older patients, think brainstem stroke.
171
Subfalcine herniation
can cause an ACA stroke
172
Uncal herniation
Ipsilateral CNIII and PCA compression,
contralateral hemiparesis
173
Lacunar strokes
small, associated with HTN
174
Hemorrhages
175
Hemorrhage management
Warfarin > 4-factor prothrombin complex concentrate (4fPCC)
➧ DOAC > andexanet alfa, 4fPCC
Keep BP < 140
176
If still can't stop seizures
Midazolam
Propofol
Ketamine
177
Lipohyalinosis lacunar stroke
178
Increase contractility
Beta agonists: dobutamine, dopamine
PD3i: milrinone
cardiac glycosides: digoxin
increase intracellular calcium
179
Heart drugs
180
Pressors
Norepinephrine (α1>β1): first-line septic shock; ↑SVR, modest
↑inotropy
* Epinephrine (β1/β2/α1): anaphylaxis; refractory shock; ↑lactate.
* Phenylephrine (pure α1): rescue if tachyarrhythmias/AF with RVR and
low SVR.
* Vasopressin (V1): add-on to NE to spare catecholamine; useful in
acidosis/hypoxia.
181
Antiarrhythmics
Class I - sodium
Class II - beta blockers
Class III - potassium
class IV - calcium
182
Class 1
183
Class 3
Amiodorone
IV for VF/VT/Arrest
Tachyarrhythmias and Vfib
Affect thyroid, drug interactions
BITCH
- blue skin
- ILD
- Thyroid
- Corneal/Cutaneous
- Hepatic/Hypotension
Soltalol
(Afib)
184
Class 4
Verapimil
Diltiazam
Nicardipine
185
Digoxin
Yellow vision
Good for rate control if hypotension or CHF
Toxicity see pic
186
Atropine
blocks muscarinic receptors
187
Isoproterenol
Beta AGONIST
good for heart block, brady cardia
188
Reduce afterload
Venous dilator
NG
Side effect: reflex tachycardia
189
Arteriol vasodilators
Hydralazine
compensatory tachycardia
increase in cgmp
190
labetolol (alpha beta)
Nicardipine (CCB)
Nitroprusside
Reduce afterload
Good for HTN emergency
NP can cause cyanide toxicity
191
ACEi/ARB/ARNi
All neurohumoral reduce afterload
Lisinopril
Losartan
Sacubatril-valsartan
Angioedema side effect in ACE, not ARB, ARNi
192
Aldosterone antagonist
Spironolactone
193
HF
194
antiarrhythmics
Stable AF with rapid ventricular response → first-line = IV β-blocker (metoprolol, esmolol) or non-DHP CCB (diltiazem, verapamil) for rate control. Digoxin is slower/adjunct, amiodarone and flecainide are for rhythm control.
195
Legionella Pneum
Azithromycin
Legionella pneumonia typically presents with high fevers, relative bradycardia, as well as typical
pneumonia symptoms (hypoxia, dyspnea, cough). It can also have gastrointestinal manifestations
(nausea, emesis, diarrhea) and neurologic sequelae such as agitation and/or confusion,
196
Macrolides
Macrolides can be used for community acquired pneumonia, and treatment of nontuberculous
mycobacteria (such as M. Avium complex). Erythromycin in particular can be used as a GI
promotility agent. Macrolides are also used for treatment of chlamydial urethritis/cervicitis,
though doxycycline is now the preferred agent for this. Clarithromycin is also used in some
regimens for treatment of H. pylori.
197
Staph aureus
Staphylococcus aureus is β-hemolytic, catalase+, coagulase+. Always think abscesses, endocarditis, osteomyelitis, pneumonia, food poisoning.
198
Vancomycin binds D ala D ala
MRSA
- resistance D ala D lac
- Red man syndrome
199
Daptomycin
Empiric staph aureus blood stream infx
Rhabdomyolysis side effect
200
Ampicillin
covers listeria
201
Pip tazo
Pseudomonas coverage
202
Vancomycin
IV for MRSA & resistant Gram+ infections, oral for C. diff. Toxicities: nephrotoxicity, ototoxicity, red man syndrome.
203
Hosp acquired pneumonia
Vanc
Pip tazo
treat at home with levofloxacin for pseudomonas coverage
204
Fluoroquinolones
Tendon rupture
205
Lactose fermenters
E coli
Kleibsella
Enterobacter
206
Linezolid
Good MRSA coverage
- serotonin syndrome
207
Metronidazole
Anaerobes below diaphragm
Disulfiram reaction
208
RIPE
R - red orange color
I - neuropathy/Vitamin B6
P - hepatotoxicity
E - red green discoloration
209
MRI imaging
T1 = “anatomy” → fat bright, CSF dark.
T2 = “pathology” → water bright (CSF, edema).
FLAIR = “T2 minus CSF” → CSF dark, pathology bright → best for periventricular or cortical lesions
ASC Midterm
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