Immunology Flashcards
(32 cards)
What conditions are associated with p-ANCA? (6)
“My Personal Computer Is Really Good! … So I permanently-ANCHORED (p-ANCA) it to my desk”
Microscopic Polyangiitis (MPA)
PAN
Churg-Strauss (EGPA/Eosinophilic GPA)
IBD - esp ULCERATIVE COLITIS
RPGN - Rapidly progressive Glomerulonephritis (necrotising / cresenteric GN)
Goodpastures Syndrome (= anti GBM disease)
6 points on Polyarteritis Nodosa (PAN).
- Medium vessel vasculitis, affects MALES > Females
- Renal involvement (60%), TESTICULAR (pain), GI, MSK manifestations, peripheral neuropathy, skin manifestations (livedo, purpura), constitutional symptoms
- ** NEVER INVOLVES THE LUNGS!!! **
- Associated with HEPATITIS B.
- Invx: Do a Mesenteric and Renal Angiography to look for vasculitis in renal or Mesenteric vessels. Hep B serology. complement c3/4 = normal. Biopsy affected tissues.
- Mx is with Steroids, CTX and treat Hep B
Mnemonic for Wegeners Granulomatosis.
What are the clinical features?
What is the Mx for acute disease, relapsed disease and maintenance?
(“WE CAN PASS this wRITTen exam!”
= WEgeners = cANCA (cytoplasmic) = pR3 = RITUXIMAB)
clinical manifestations:
E - ENT
L - Lungs
K - Kidney (haematuria, rapidly-progressive GN / PAUCI-immune)
PE/DVT (20x increased risk)
More likely to relapse than MIcroscopic Polyangiitis.
Diagnosis:
C- ANCA pos, PR3 Ab specificity on ELISA
Biopsy: necrotising GRANULOTMATOUS inflammation
Positive Urine sediment
MANAGEMENT:
1. Rituximab and Prednisone
(Rituximab as good as CTX, but less side effects)
2. IVIG if RPGN present
- Relapse –> CTX, then AZA.
Maintenance: AZA or MTX (only if CTX used)
What are the diagnostic features of Microscopic Polyangiitis?
MPA = p-ANCA (perinuclear staining) = MPO
A NECROTISING small vessel vasculitis.
Clinical features:
(“Malaysia Pacific Airlines flies to K.L.” = MPA –> Kidney > Lungs)
- KIDNEY (Glomerulonephritis +/- RPGN)»_space; Lung (alveolitis / haemoptysis)
- Biopsy: NECROTISING Pauci-immune inflammation of small vessels
- Positive urine Sediment
- small percentage also anti-GBM antibody positive (Goodpastures)
Mx:
- Rituximab and Prednisone
- PLASMAPHERESIS improves renal outcomes
- Maintenance: AZA / MTX (only if CTX used)
What are the diagnostic features of Churg-Strauss?
What is the management?
Churg Strauss = EGPA = EOSINOPHILIC granulomatosis with Polyangiitis
(Strauss was an A-PLUS, Nazi composer)
(A = asthma, N= neuro)
** HLA DRB4 association **
Churg Strauss = An ASTHMA “plus” syndrome = Asthma + Neuro
Clinical features:
- Churg Strauss = p-ANCA positive in 50%
- Asthma & Eosinophilic pneumonia PLUS Neuropathy (peripheral neuropathy, mononeuritis multiplex)
- Other “plus” features are: +/- Glomerulonephritis, cardiac/ coronary arteritis, myocarditis, dermatological features eg purpura.
- BIOPSY = GRANULOMAS AND EOSINOPHILS / Eosinophilic infiltrates, thrombosis in small vessels, fibrinoid necrosis
MANAGEMENT IS PREDNISONE ONLY.
Patient with fever, haemoptysis and positive urine sediment. p-ANCA positive. What are the DDx?
DDx for p-ANCA positivity are: MPA, PAN, Churg, IBD, RPGN, Goodpastures.
DDx based on clinical features are: MPA or Goodpastures
Not PAN as PAN never involves the lungs.
Not Churg Strauss as no Asthma/eosinophilia
Not IBD or RPGN - doesn’t account for all of symptoms
NEED TO DIAGNOSE WITH A RENAL BIOPSY
- -> anti GBM (linear staining) = Goodpastures
- -> necrotising pauci-immune inflammation = MPA
Goodpastures = Pulmonary haemorrhages and RPGN
May be p-ANCA positive
What conditions are associated with Cryoglobulinaemia?
Cryoglobulinaemia associated with:
- lymphoproliferative disorders (type I)
- Hep C (type II / mixed CGA) - acute HepC
- autoimmune syndromes (type III) - SLE, Sjogrens, PAN, RA
- infections VIRAL - CMV, EBV, HIV, or BACTERIAL - endocarditis, Lyme, Syphilis
- Renal transplants
- idiopathic
What are the symptoms of Type II / Mixed Cryoglobulinaemia?
What tests would you order?
Note - Type II / Mixed CG is the most common CG (accounts for 50-60%)
Symptoms: ("This is a MIXED up, PUGLy CHAP")
Palpable purpura
Urticaria
GN
LYmphadenopathy
CHRONIC RENAL DISEASE in the long run
Hepatosplenomegaly
Arthralgias
Palpable purpura (repeated for emphasis!)
( –> an Immune complex vasculitis with MULTI-ORGAN involvement)
TESTS:
1. C3/4 = LOW C4 (c3 is variable) / HYPOCOMPLEMENTAEMIA
2. Hep C serology (80% have HCV RNA positive / anti Hep
C antibody neg = ie.acute HepC)
3. IgM and IgG = MIXED monoclonal IgM and polyclonal IgG
4. Cryoglobulin titre = positive, RF = positive, ESR = positive (point 4 is found in all the Cryos)
5. LFTs (elevated)
6. WCC / Platelets - Falsely elevated due to cryoprecipitation
7. Biopsy of the affected tissue
What tests are positive in Cryoglobulinaemia?
What is the management of Cryoglobulinaemia?
Cryoprecipitate
Hypocomplemetaemia - consumed C4
RF
ESR
LFTs - elevated
WCC - falsely elevated due to cryoprecipitation
Platelets - falsely elevated due to cryoprecipitation
MANAGEMENT:
- Treat underlying disease eg. Hep C for Mixed CGA, Cancer for type I etc.
- NSAIDS NSAIDS NSAIDS for symptoms
- Prednisone + CTX (+/- Plasmapheresis)
Don’t confuse cryoglobulins with cold agglutinins.
What are the differences?
Cryoglobulins are PROTEINS in serum or plasma that precipitate on exposure to cold.
(note cryofibrinogens only present in plasma)
Cold Agglutinins are IgM ANTIBODIES to RBCs.
Cold Agglutinins are associated with "MMMM cold ice cream" Measles Mumps Mono (EBV / infectious mononucleosis) Mycoplasma
What defines Type I and Type III Cryoglobulinaemia?
Type I (10%)
- MONOCLONAL IgM (the only monoclonal Cryoglobulinaemia)
- associated with Waldenstroms, Multiple myeloma, lymphoproliferative disease
- Hyperviscosity and thrombosis
Type III (25-30%)
- POLYCLONAL IgG
- may be asymptomatic
- associated with Autoimmune syndromes - SLE, sjogrens, inflammatory Bowel disease, PAN, RA
= Type II (mixed) and Type III are immune complex vasculidities with multi-organ involvement
What is Icatibant?
Icatibant is a Bradykinin receptor antagonist (renders bradykinin less effective)
Used in Bradykinin-mediated angioedema.
other Mx is supportive, Intubation etc, stop OCP
What is Felty’s Syndrome?
RA with unexplained splenomegaly and neutropaenia.
Where can you find PAMPs and DAMPs?
PAMPs- viruses and bacteria only.
DAMPs (Danger associated molecular patterns) are released by dying cells. Examples of DAMPs are: ATP Heat shock proteins Uric acid/ Monosodium urate crystals (= NOD like receptor on inflammasones) DNA Hyaluronan fragments Heparin
What are the contraindications to anti TNF biologic therapy?
If someone is found to have TB, what is the management prior to starting anti TNF?
Contraindications:
- active infections
- chronic infections such as chronic Osteomyelitis, Bronchiectasis, optic neuritis
- heart failure (as anti-TNFs worsen heart failure in patient with CCF)
If someone is found to be positive for TB screening (Q Gold, CXR), can still have anti-TNF but need TB treatment first.
LATENT TB:
9 MONTHS of ISONIAZID MONOTHERAPY.
commenced 4-6weeks prior to anti-TNF agent, then continue course.
ACTIVE TB:
NEEDS FOUR-DRUG TB REGIMEN (R.I.P.E)
Commenced at least 2 months prior to anti-TNF agent.
Side effects of anti-TNF agents?
Lupus Lymphomas Infections MS TB reactivation Teratogenic * NON-melanoma skin cancers * Heart failure - worsening of HF in those with pre-existing HF
What are the ENCAPSULATED organisms?
“SHiNKS”
Streptococcus pneumoniae Haemophilus influenzae B (HiB) Nisseria Meningitidis Klebsiella pneumoniae Salmonella
- these are susceptible to antibodies rather than the cell-mediated response
- patients with asplenia (sickle cell disease or functional asplenia) and complement deficiency are more susceptible to sepsis from these organisms due to impaired opsonisation.
What is the most important warning sign that a patient has a primary immunodeficiency?
Family history of a primary immunodeficiency is the most important!
Most commonly caused by antibody deficiency, and CVID is the most common primary immunodeficiency in adults.
10% familIal.
Likely polygenic.
CD19 and 20 deficiency (B cell surface markers)
Occurs in the YOUNG, 2 peaks: Childhood and age 20’s
How does CVID manifest? (4 main points)
CVID = a lack of antibody response (B cell deficiency –> Ab deficiency)
- Recurrent sinopulmonary infections
- sinusitis, bronchitis
- bronchiectasis
- otitis, tonsillitis
- pneumonia - Recurrent GI infections
- infective diarrhoea - Giardia, Campy
- malabsorption (mimics Coeliac) - Increased RISK OF NON-HODGKINS LYMPHOMAS by 400x!!!
- Autoimmunity in 20%
- AIHA, Pernicious, ITP
- AI thyroiditis
- Rheum- RA, vitiligo, Polymyositis
What are the investigations you would order to make a diagnosis of CVID?
What is the MANAGEMENT of CVID?
Firstly need to exclude any other causes of hypogammaglobulinaemia: Drugs (CMZ, Valproate, SZP, CAPTOPRIL) NSAIDS --> low IgA Myeloma Lymphoma Nephrotic syndrome GI protein loss
Investigations:
- Immunoglobulin levels = hypogammaglobulinaemia
- B Cell count = low or normal
- EPG/IEPG and Serum free light chains — to exclude myeloma (as myeloma may mimic hypogammaglobulinaemia)
Management:
- IVIG MONTHLY (SC, dosage 0.4g/kg)
- CHRONIC BACTRIM (Sulfamethoxazole plus trimethoprim = sulfonamide plus DHFR inhibitor = ANTIFOLATE agents) or chronic Amoxicillin
- Yearly flu vaccine
- avoid live vaccines
What is the function of CD40 ligand?
What is the condition defined by CD40 Ligand deficiency?
CD40 ligand deficiency = Hyper IgM Syndrome!!!
CD40 LIGAND is expressed on T cells.
CD40 RECEPTOR is expressed on B cells
–> Important in B and T cell INTERACTION
In Hyper IgM Syndrome,
a deficiency in T Cell CD40 ligand –> Results in failure of B and T cells to “talk” –> No isotope switching –> NO PLASMA CELLS, NO MEMORY B CELLS
–> Results in HYPER/ HIGH (or normal) IgM but verrrry LOW IgA/G/E.
–> Results in impaired response to T cell infections
(Recurrent bacterial infections, candidiasis, PJP)
Diagnosis:
Flow cytometry
Mx:
IVIG
Chronic BACTRIM
G-CSF a
How does IgA deficiency present and what is the management?
IgA def is common - 1 in 700. Due to a dysregulation in Ig class switching. Associated with IgG deficiency. IgM PROTECTS patient from infections.
May present with: Coeliac disease (tTG is an IgA) Sinopulmonary infections and giardiasis Atopy Autoimmune diseases - Haem & Rheum
Management:
Give Antibiotics when needed only.
(Not for IVIG)
If patient ever requires transfusion, needs IgA deficient blood.
What causes X-linked (Bruton’s) Agammaglobulinaemia and how does it present?
Early onset < 6 months Caused by an absence or mutation of "BTK" tyrosine kinase --> No B cell development --> NO antibodies --> No lymphoid tissues Positive family history in 50%
Clinical features as per CVID but also CHRONIC ECHOVIRUS MENINGIENCEOHALITIS
Investigations:
**Genetic analysis for BTK gene
B Cell count = 0
Mx: (as per CVID)
IVIG monthly
chronic Bactrim or Amoxycillin
Flu vaccine, avoid live vaccines
Lack of T cells. How do these patients present?
= Infections of INTRACELLULAR organisms
Fungi - Candidiasis, Pneumocystis
Viruses - CMV, VZV, HSV, Protozoa, Listeria
Mycoplasma - MAC, M.Tub
