Darrow Lectures Flashcards
criteria for SLE? TQ
B3O1R1N1 with D3ermA1titiS1
SOAP BRAIN MD
S- Serositis (pleuritis or pericarditis) - affects lungs and heart
O- Oral Ulcers (vagina, nose, alopecia)
A- Arthritis - with or without active synovitis. - Can get reversible swan neck deformities.
P- Photosensitivity
B - Blood Disorder (anemia, leukopenia, thrombocytopenia*)
R- Renal Disorder (proteinuria or cellular casts)
A- ANA
I - Immunologic Disorder (ds-DNA, or Sm, or APA, or FPSTS)
N- Neurologic Disorder (seizures or psychosis)
M- Malar Rash
D- Discoid Rash
** DDx requires 4 out of 11 criteria!!!
+ ANA : TQ
think SLE - more common in young women and nonwhites
in SLE see malar rash, anemia, leukopenia, thrombctyopenia, GN, CNS disease, splinter hemorrhages, synovitis, conjunctivitis, pleurisy, pleural effusion
systemic presentation of fever, anorexia, malaise, w/l
Anti-Jo- 1
polymositis/dermatomyositis
indicates worse chance of pulmonary fibrosis!
ANCA
Granulomatosis w/ polyangiitis (Wegeners granulomatosis)
anticentromere pattern
think CREST
peripheral rim anti-DNA
seen in SLE
where is alveolar hemorrhage seen?
think Lupus and Goodpasture’s syndromes
what are lung and heart involvements in SLE? TQ
Bronchopneumonia, pleural effusions, restrictive lung disease, alveolar hemorrhage*, coronary aneurysms, myocarditis, hypertension, CHF, and Libman-Sacks endocarditis**
an imp. drug to know in tx of SLE?
Hydroxychloroquine -
prevents flares, reduces congenital heart block, lowers diabetes risk, and reverses platelet activation by IgG antiphospholipid.
causes of splinter hemorrhages? TQ
- Nail trauma
- subacute bacterial endocarditis
- Antiphospholipid antibody syndrome – including lupus
- Hypereosinophilic syndrome
if found to have cardiac echo…. think Libman- Sacks vegetations
= (atypical verrucous vegetations) with
mitral regurgitation
= (Marantic or non-bacterial thrombotic
endocarditis)
Libman-Sacks endocarditis
a form of nonbacterial endocarditis that is seen in systemic lupus erythematosus. It is one of the most common cardiac manifestations of lupus
vegetations are small and formed from strands of fibrin, neutrophils, lymphocytes, and histiocytes. The mitral valve is typically affected, and the vegetations occur on the ventricular and atrial surface of the valve.
CAUSE MITRAL REGURG!
Which drugs can give drug induced lupus? TQ
Hydralazine Isoniazid Procainamide Methimazole Prophylthiouracil Etanercept
Will see no renal disease, no CNS disease, +anti-histone Abs
Slow acetylators: *if you inhibit DNA methylation in helper T cells, they lose requirement for antigen =auto-reactive.
(i.e. isoniazid)
which staining is seen in drug induced SLE? TQ
anti-histone “diffuse/homogenous” antibodies
Lupus and pregnancy: how do you tell she has a lupus flareup rather than preeclampsia? TQ
- should be screened for LA, antiphospholipid Ab, apolipoprotein H
- use aspirin to decrease risk of antiphospholipid Ab syndrome
SLE vs. preeclampsia:
- both have HTN, proteinuria, low platelets
- SLE has dsDNA, **low C3/C4
- preeclampsia: has abn LFT’s and high uric acid
most common Ab seen w/ annular lesion of SCSLE? what to worry about? TQ
AntiRO/SSA and AntiLa/SSB
- worry about heart block!!!!
Subcutaneous SLE:
- Spares knuckles and face
- scaling annular lesions
- Sun exposed areas
- Also seen in RA and SS
- Can be caused by HCTZ
** don’t want baby to get heart block **
neonatal lupus: TQ
** Affects children born of mothers with Anti – Ro (SSA) or La (SSB). **
Transient:
- rashes of SCSLE
- thrombocytopenia
- HA
- arthritis
- complete heart block **
hx: spontaneous abortions, TIA, DVT, see reticulated rash. LAbs show elevated INR and PTT, along with low platelet count? TQ
patient has lupus anticoagulant -> APS
causes APS (Anitphospholipid Syndrome)
APS = hypercoagulatbility w/ thomboses
- presents with thombocytopenia, but no other features of SLE
- may see DVT, PE, change in mental status, microangiopathic nephropathy
how to DDX APS? TQ
Antiphospholipid Antibody syndrome:
To diagnose need 1 clinical criteria plus 1 lab criteria 3 months apart.
Lab criteria:
1. Anticardiolipin antibody (AcL)
- Lupus anti-coagulant (LA)
- Anti-β2 glycoprotein 1* (ApoH**) (anti-B1GP)
Clinical Criteria: CLOTS!!!!
- Spontaneous abortion
- Vascular thrombosis: TIA, CVA, thrombosis, DVT, PE, Budd-Chiari syndrome, infarction, MI, heart valve disease, adrenal infarction… etc.
needs to be 3 mos apart!!!
confirm w/ russel viper venom test
Abs in APS?
Lupus anticoagulant is the worst one and assoc. w/ thrombotic events in APS
if have all three Abs = worst disease!
tx for APS? TQ
***Hydroxychloroquine (retinal screening) = reduces thrombosis.
hx: pt. w/ hep C presents with rash (livedo reticularis = giraffe rash)
giraffe rash = Spasm of the deeper arterioles
due to: cryoglobulinemia
Progressive Systemic Sclerosis Syndrome??
A syndrome characterized by densely packed collagen and fibrosis :(could be d/t metabolic defect with increased collagen in EC matrix…)
- Raynaud’s syndrome.
- Cutaneous, subcutaneous calcification, pigmentation
and depigmentation, telangiectasias. - Cardiac: pericarditis, fibrosis, MI*, heart block, R-CHF.
- Pulmonary: restrictive lung disease with decreased CO diffusion, pulmonary hypertension.
- GI: GERD, sticking below the sternum, hypomotility with bacterial overgrowth, large mouth diverticulum.
- sticking below sternum, d/t
- Renal: “onion skinning” and hypertension.
NOTE CREST, is part of scleroderma (“limited scleroderma” )
how to ddx scleroderma? TQ
= Fibrosis and vasculopathy of the skin and visceral organs.
1 major or 3 minor criteria necessary:
Major:
1. symmetric thickening, tightening, and induration of the skin proximal to the metacarpophalangeal (or MTP) joints , ie. arms, trunk, etc.
Minor:
- sclerodactyly (swelling and flexion of fingers)
- digital pitting
- bibasilar pulmonary fibrosis
in full blown scleroderma will hear “tendon friction rubs” over the forearms and shins!
CREST
can ddx high probability of scleroderma w/ 3/5 CREST sx
= “limited scleroderma”
Calcinosis, Raynaud’s, Esophageal dysmotility, Scleroderma, telangiectasias
DDx of Raynauds? TQ
Raynauds = episodic ischemia of digits, ears or nose w/ triphasic color changes: pallor, cyanosis, rubor
** Primary RP: age < 30, symmetrical, normal SR, no nail bed capillary changes.
Secondary RP:
- CT disease, especially scleroderma with nail capillary changes and serological changes.
- Drugs & Toxins – bleomycin
- Structural arterial disease – atherosclerosis, emboli, migraine.
- Occupational –vibration/jackhammers.
- Hemorrheologic - PV, cryoglobulins, cold agglutinins.
- Other - thoraic outlet and carpal tunnel syndrome,
- Pheochromocytoma, hypothyroidism.
NOTE: need to know how to seperate primary from secondary b/c secondary raynauds is often the first sign of scleroderma!
what are visceral changes in scleroderma?
Risk of internal organ involvement strongly linked to extent & progression of skin thickening.
Involvement of internal organs, including heart, lungs, GI tract, and kidneys, accounts for increased morbidity and mortality.
- hypomotile bowels: bacterial overgrowth and atrophic tubules
- pulmonary fibrosis
- heart block
- diastolic dysfunction
- kidney involvement: HTN, this is what eventually kills a person
miracle drug that helps tx scleroderma?
ACEI’s!!!
before this drug, renal disease used to be #1 killer in scleroderma
what Ab is associated with sclerodermal renal disease? TQ
Risk factors pointing to renal disease:
** anti-RNA Polymerase III** (“speckled ANA”) - goes along with onion skinning and renal failure
rapid skin progression
anemia
( May present as hypertension, encephalopathy, sudden decrease in GFR, RBC or protein in urine, grade 3 to 4 retinopathy, or even micoangiopathic hemolytic anemia. )
sclerodermal cardiac disease?
Often silent pericardial effusions, LV diastolic dysfunction, conduction abnormalities, arrhythmias, myocarditis, microvascular disease (with possible MI) and myocardial fibrosis.
What Ab is associated with scleroderma lung disease? TQ
Interstitial Lung Disease
**Anti-topoisomerase (Anti-SCL-70) = worsening lung disease
= leading cause of scleroderma death!
what lung disease and Ab seen more w/ CREST? TQ
higher incidence of pulmonary HTN
risk factors:
- telangiectasia
- *** + anticentromere ab
causes of dysphagia?
SAD CREaP
SAD = solid and liquids
- scleroderma, achalasia, diffuse esophageal spasm
CREaP =
Carcinoma
Ring(Schatski’s)*/webs**
Eosinophilic esophagitis
and
Peptic stricture
nephrogenic fibrosing dermopathy? TQ
looks like scleroderma
- caused by CT use of gadolinum
- no autoabs
- affects skin, mm, heart, kidneys
(lacks raynauds, sclerodactyly, nail capillary changes)
eosinophilic fascitis? TQ
scleroderma like syndrome
follows vigorous exercise - just see one area of fibrotic thickening of fascia d/t eosinophilia
assoc. w/ M protein
see “groove sign” - inflamm. and fibrosis in subcu tissues yield a “woody texture” of distal limbs
Plantar/Palmar Fascitis and Polyarthritis Syndrome
Paraneoplastic syndrome: adenocarcinomas and hematologic malignancies (MM, CML, Hodgkins)
- fibroblast proliferation d/t TGF-beta
- thickening of palmar fascia
- finger flexion contraction
three types of inflammatory mm. diseases? TQ
- Polymyositis – painless proximal muscle weakness (difficulty in arising from a chair, climbing stairs, or lifting arms above the head).
- Dermatomyositis – painless proximal muscle weakness with preceeding rash.
- Inclusion Body Myositis - asymmetric distal weakness, thigh atrophy, finger flexor weakness, dysphagia, and older men.
what do you need to ddx Dermato/Polymyositis: TQ
- Shoulder and hip weakness
- Elevated enzymes
- Positive EMG
- Myofiber degeneration with mononuclear infiltration
- Skin changes in DM (shawl sign, Gottron’s papules, heliotrope eyes, and nailfold capillary loops) - seen only in dermatomyositis
3/5 suggest DM/PM
4/5 define the diagnosis
pathogenesis of DM/PM
DM = B cells PM = CD8 T cells
DM: Autoimmune microangiopathy. Complement activation with MAC and lysis of endomysial capillaries, capillary necrosis, perivascular inflammation, muscle ischemia, and muscle fiber destruction. Infiltration of B cells, CD4 cells and upregulation of MHC 1 and adhesion molecules. = B cell disease
PM and IBM: Cytoxic CD8 T cells with perforin and macrophages invading myosites in endomysial areas. = T cell disease
characteristics of dermatomyositis?
Women:Men / 2:1. 40s and 50s.
Autoimmune HLA DR 3,5,7, DRW52.
Symmetrical proximal muscle weakness.
Difficulty climbing stairs or arising from chair.
Oropharyngeal (proximal) dysphagia. (b/c skeletal mm. is problem)
Facial erythema.
Shawl sign.
Heliotrope (purple rash around eyes)
Gottron’s patches (over nuckles)
Mechanic’s hands.
** may get puomonary/cardio involvement: ILD, CHF
Shawl Sign?? TQ
= erythematous rash on chest and shoulders/back
seen with DM but ALSO ASSOCIATED WITH ADCA!!!
woman should be screened for ADCA
anti-synthetase Ab (anti Jo-1) indicates? TQ
in DM/PM: indicates involvement of joints and lungs - may progress to pulmonary fibrosis
Anti-Jo-1/ Antisynthetase syndrome (ASS): TQ
present in 25% of people with PM/DM
fever, polyarthritis, RP, “mechanic’s hands”, DM rash, and pulmonary fibrosis/ILD (worse with Ro52).
labs seen in PM/DM?
muscle enzymes (CPK) increased, MRI shows edema in striated mm. Anti-Jo-1 Ab
DM with anti-p155/140?? TQ
associated with cancer with DM!!!
Which Ab is connected with mixed connective tissue diseaes? TQ
Anti-U1-RNP
Clinical features: overlap with SLE, scleroderma and myositis
- RP (Raynaud’s phenomenon)
- No renal or CNS disease*
- More severe arthritis (+RF) and non-fibrosis pulmonary hypertension
can’t get pt off respirator, in shock, have flaccid distal and proximal mm. weakness just like dermatomyositis, also have decreased pain and temp and absent DTRs…
critical illness myopathy neuropathy
anti-Ro and La, along with dry eyes and mouth?
Sjogren’s syndrome
immuno/path behind sjogrens? TQ
this syndrome is d/t CD4 T cells!!!! - have infiltrated the salivary glands (stimulate formation of Abs)
CD4+ helper T cells have infiltrated the glands, causing them to enlarge, there are so many of them, they are helping formation of B cell stimulation: AntiRo and AntiLA
So…
- periepithelial attack of CD4 cells –>
- interstitial nephritis, interstitial pneumonia, lung and liver disease
= pneumonia and renal failure - extraepithelial sjogrens: B cells go crazy –> produce cryoglobulins
- cyoglobinulinemia, glomerulonerphritis,
= vasculitis, peripheral neuropathy, red cell casts
relapsing polychondritis: TQ
IgG4 related disease where there is immune mediated attack of cartilage
= a multi-systemic condition characterized by inflammation and deterioration of cartilage
- polyarthritis
- auricular and nasan cohondritis
- tracheal condritis
- CV problems
ex: in pt. see that eyes, ears and trachea are being attacked, trachea begins to collapse
how to ddx IgG4 related disease? TQ
Minor criteria:
- Non-obliverative phlebitis
- Mild eosinophilic infiltrate
Major Criteria (biopsy): - Lymphoplasmacytic infiltrate with - IgG4 + plasma cells - Storiform fibrosis - Obliterative phlebitis - inflammation in the wall of a vein so extensive that the lumen is obstructed!
ex. relapsing polychondritis
migratory arthritis, fever, diarrhea, abdominal pain, weightloss…. ddx? TQ
whipple’s disease
- rare, systemic infectious disease caused by the bacterium Tropheryma whipplei.
- primarily causes malabsorption, but can also cause joint pain and arthritis
Two stages:
Prodromal – migratory arthritis.
Steady state – diarrhea and weight loss.
Cause: Tropheryma whipplei infiltrates macrophages, intestional villi (malabsorption), organs (liver, spleen, heart valves), CNS, and synovium.
** results in hyperpigmentation d/t malabsorption –> niacin deficiency (one of the three d’s of pelagra: diabetes, dermatitis, dementia)
Duodenal biopsy - PAS + macrophages
what do seronegative spondyloarthropathies have in common? TQ
Male preponderance
Onset before age 40. (young males)
Inflammatory arthritis of spine and SI joints.
HLA-B27 +
RF -, CCP -, ANA -
NOTE: HLAB27 interacts with CD8 cells and activates cytotoxic T cells and NK cells
NOTE: TH17 is also involved in tissue inflammation– has to do with enthesis
what causes enthesis? TQ
TH17 cells release of IL17 and IL23 –>osteoproliferation, inflamation and bone loss
TH17 cells are very active in AS and spodyloarthrtides
features of ankylosing spondylitis? TQ
HLA B27 positive
- ‘Bamboo spine’ – brittle, rigid
- Sacroiliac inflammation/pain
- Increased kyphosis
- Fatigue (systemic symptom)
- Ocular inflammation, uveitis
- Reduced rib expansion - reduced inhalation
- Weight loss (systemic sym.)
- Possible atlantoaxial subluxation
- Pulmonary fibrosis in upper lobes! **
- Aortic insufficiency**
- see “chronic LBP” in young adult, worse in morning, insidious onset
- SI abnormalities on Xray
- iritis, aortic insufficiency
- elevated ESR, negative RF and CCP
** Schober’s test:
draw line across iliac crest, draw line 10 cm above, when pt. bends over the line should grow to be 15-17 cm above if they are normal
MRI may show whole body edema and enthesitis at sites prior to recognizable changes on xray
characteristic lesions seen on xray with AS? TQ
Anderson lesion: simulates diskitis
syndesmophyte = bamboo spine - leads to fusion of vertebra
“shiny corner sign” = reactive sclerosis
DISH syndrome differentiated from AS? TQ
in DISH : No involvement of SI joints and syndesmophytes are more anterior and thicker.
(lateral bamboo spine seen in AS)
Psoriatic arthritis: TQ
manifestations :
- unilateral sacroiliitis = low back pain
- “pencil in cup deformity” = swollen and painful finger
- dactylitis = sausage fingers
- psoriatic skin rash
- enthesitis = heel pain
** d/t TH17 cells causing inflammation
essentials for ddx:
- psoriasis: precedes arthritis in 80% - search for it!
- Arthritis usually asymmetric with sausage appearance of fingers & toes (dactylitis).
- Unilateral sacroilitis.
- X-ray findings: osteolysis; pencil-in-cup deformity
- May be associated with uveitis, pleuritis, aortitis, etc.
5 types of psoriatic arthritis? TQ
- Oligoarthritis** most common
- SI
- Asymmetrical polyarthritis
- DIP
- Opera glass = “arthritis mutilans” = “pencil cup deformity” (worst kind!)
what else can give a picture that looks like psoriatic arthritis? TQ
HIV
what are the bacteria that can cause reactive arthritis? TQ
(S3YC3)
Veneral:
Chlamydia trichomatis
Ureaplasma urealyticum (men)
Enteric: Shigella flexneri Salmonella species Yersinia enterocolitica Yersinia pseudotuberculosis Campylobacter jejuni Clostridium difficile
Miscellaneous:
Streptococcus
NOTE: HIV may cause this as well!!!
reactive arthritis?
“can’t see, can’t pee, can’t climb a tree” = Reiter’s syndrome
= Seronegative asymmetric arthritis that follows urethritis, cervicitis or infectious diarrhea!
Associated with:
- Enthesopathy - “Lover’s heels”.
- Inflammatory eye disease.
- Palmar pustulosis.
- Circinate balanitis.
- Keratoderma blenorrhagicum.
- Oral ulcers (painless unlike Behcets).
- Sacroiliitis in 20%.
Essentials for DDx:
- HLA B27 + (50-80%)
- Large joint oligoarthritis or sacroiliitis, Uveitis, conjunctivitis, Urethritis, Mouth ulcers.
- follow GI or GU infection
inflammatory bowel disease and arthritis??? Two types? TQ
- especially Crohn’s disease!!!
- Peripheral nondeforming asymmetric oligoarthritis
- parallels bowel disease.
- Usually acquired after bowel disease is apparent.
- corresponds to the status of the IBD - Bilateral and symmetrical sacroiliitis as in AS – 50% are HLA-B27+.
- Acts independently of the IBD.
what arthritis will people with hemophilia get? TQ
hemarthrosis!
Recurrent hemorrhage:
- Knees, ankles and elbows.
- Synovial hypertrophy.
- Persistent “boggy” synovitis.
- Cartilage erosion.
- Fibrosis and ankylosis.
Septic Arthritis: TQ
- Monoarthritis is septic arthritis until proven otherwise!
- The more joints involved the less likely septic arthritis, except for RA, group B strep, or endocarditis!
- 15% of patients with septic arthritis present with multiple joint involvement. - Persons on anti-TNF therapy are twice as susceptible to septic arthritis.
Most common: Staph aureus, MRSA, Strep
–> in drug users see: pseudomonas, HIV, salmonella, E. coli
Essentials of DDx:
- Sudden onset of acute arthritis, usually monoarticular, most often in large weight – bearing joints.
- Previous joint damage or intravenous drug abuse common risk factors.
- Infection with causative organisms commonly found elsewhere in the body.
- Joint effusions are usually large, with WBC commonly > 50,000/cmm.
Diagnostic approach?
- do gram stain and cell count of synovial fluid
- imaging is with MRI
** NOTE: can be caused by TB and HIV as well
Class I synovial fluid? TQ
noninflammatory = Osteoarthritis
- clear/yellow
- high viscosity
- WBC <25 %
Class II synovial fluid? TQ
inflammatory = RA and Gour
- opaque (can’t see through)
- low viscosity
- WBC 2-75,000
- > 50% PMNs
- positive for crystals
Class III synovial fluid? TQ
purulent = infectious
- opaque/green
- low viscosity
- > 100,000 WBCs**
- > 75% PMNs **
red synovial fluid?
think hemorrhagic arthritis
gonococcal arthritis? what to check for? TQ
sx: migratory polyarthralgia, meningitis, pericarditis, pustules
Disseminated gonococcal infection (DGI) – Arthritis/Dermatitis syndrome:
- Oligoarthritis form (usually preceeded by migratory polyarthritis).
- Tenosynovitis form.
- Rash –pustules especially palms and sole.
- Fever.
- May also get osteomyelitis
risk factors: C5-9 deficiencies
*** what should you check them for??? complement deficiency
viral arthritis? TQ
presentation: usually migratory, little fever, maybe a diffuse/vague rash
- arthralgia may be present in wrists, hands, knees, often symmetric
- Hep C may look likeRA d/t cryoglobulins
Causes:
Parvo B19
HIV
Hepatitis B & C
EBV
Adeno and coxsackie
Rubella
Mumps
dry eyes, dry mouth, intermittent SEVERE joint pains, myalgias, rash on hands and feet? TQ
= HIV
HIV LOOKS LIKE SJOGREN SYNDROME – HIV infects CD4 T cells, leaving lots of CD8 T cells – CD8 cells invade the parotid glands, lacrimal glands, SEVERE joint pains
know that SEVERE joint pain = HIV
CD8 T cells can infiltrate any organ causing:
- Sjogrens and Bell’s palsy.
- Myositis
- Reactive arthritis - SEVERE!!!
- Peripheral neuropathy –
- Hepatitis
- Interstitial nephritis
- Pneumonia
- Psoriasis
Side note, not sure if on test….
- HAART begun, develops lymphadenopathy, dyspnea and cough, symmetric ankle periarthritis, hepatosplenomegaly, and rash = Sarcoidosis
d/t Immune Reconstitution Inflammatory Syndrome(IRIS)
- The immune system begins to recover, but then responds to a previously acquired
opportunistic infection with an overwhelming inflammatory response that paradoxically
makes the symptoms of infection worse. Usually relates to tuberculosis and cryptococcal
meningitis.
Lyme disease? Three stages? TQ
Stage I: Flu syndrome with rash (ECM)
Stage II: Dissemination: heart, joints, nerves and skin (heart block, Bell’s palsy, migratory arthralgias, ECM)
Stage III: Late: joints (oligoarthitis), CNS (encephalitis/memory loss, sleep disturbances), and PNS (neuropathies/paresthesias)
** Bell’s palsy and heart block are two most important!!
caused by ioxides scapularis tick = borrelia burgdorferi
ddx? + ELISA test, use Western blot for confirmation
KNOW THIS! TQ: How do you treat lupus?
Lupus Arthritis and dermatitits:
NSAIDs, corticosteroids, Hydroxychloroquine, MTX
If you get a flare up of SLE and they are chronically on azathioprine, what do you tx it with? Give them a blast of corticosteroids !!!
whats the pathogenesis/characteristics of Vasculidities? Large, Medium, small?
KNOW THIS.
Characteristics: - Deposition of circulating immune complexes. - Activation of complement. - Damage to vessel walls. - Necrosis & thrombosis. (constitutional sx: fever, w/l, malaise)
** when see PALPABLE PURPURA, think VASCULITIS!!!
LARGE: (Takayasu’s and Giant Cell)
- limb claudication
- asymmetric BP
- absence of pulses
- bruits
- aortic dilation
MEDIUM: (Polyarteritis Nodosa, Kawasaki)
- cutaneous nodules
- ulcers
- arthritis
- livedo reticularis
- gangrene of digits
- mononeuritis multiplex
- microaneurysms
SMALL:
- purpura
- urticaria
- glomerulonephritis
- alveolar hemorrhage
- arthritis
- cutaneous extra-vascular necrotizing granulomas
- splinter hemorrhages
- uveitis/scleritis
Small vasculitidies:
- ANCA associated:
- microscopic polyangitis
- granulomatosis w/ polyangiitis
- eosinophilic granulomatosis w/ polyangiitis (Churg-strauss) - Immune complex associated:
- Anti-GBM (Goodpastures)
- IgA vasculitis (HSP)
- cryoglobulinemia
variable vessel vasculitis?
Behcet’s Disease
Single Organ Vasculitis?
- Cutaneous Leukocytoclastic Angiitis (just skin)
- Primary CNS Vasculitis (“string of beads”) –
just involves CNS
Takayasu Arteritis: TQ
Large Vessel vasculitis
- oriental, young female
“pulseless disease”
Early inflammatory phase:
- fever, malaise, w/l
Late occlusive phase:
- decreased brachial artery
- BP difference >10 b/w arms
- Bruits over subclavian or aorta- Claudication of extremities.
Arteriogram- dilation, aneurysm or narrowing in aorta or main branches, including celiac and mesentaries.
- fibrous thickening of aorta
Giant Cell Arteritis? TQ
“temporal” arteritis
- elderly male
- pain and stiffness in shoulders/hips
- problems chewing
- tenderness in external carotid (temporal artery)
- cephalgia: new onset of h/a
- VERY elevated SR
- aortic aneurysms, stenosis of arch vessels
- PMR: proximal pain and stiffness, NO weakness (shoulders/hips)
- fever of undetermined origin!
- Polymyalgia Rheumatica **
- pain in proximal musculature: shoulders and legs/hips
common complaints:
- pain in legs/shoulders
- “tension headaches”
- jaw gets tired chewing
Polyarteritis Nodosa: TQ
medium sized vasculitis
Presentation:
- fever and w/l
- rapidly accelerated HTN
- Livedo reticularis!! skin ulcers, nodules
- can involve heart and brain (not lungs)
- abdominal pain: mesenteric vessel occlusion, renal problems
- ** testicular pain/tenderness
- ** multineuritis multiplex: can see wrist and foot drop
used to be associated with Hep B
wrist and foot drop?
think medium sized vasculitis!
Kawasaki’s Disease: TQ
medium vessel vasculitis
- seen in children, must have fever!
Clinical findings: CREAM
- mucus membranes “strawberry tongue”
- conjunctivitis
- rash
- erythema on palms and soles
- adenopathy
associated smoking and vasculitis with?
Thromboangitis obliterans = Buerger’s disease
- segmental, thrombosing, acute and chronic inflammation of medium and small arteries (tibial and radial aa.) – extends into vv. and nn. of extremities
- ofen leads to vascular insuff. in extremities
- CIGARETTE SMOKING
- ulceration in toes, feet, fingers, gangrene
urticarial vasculitis: TQ
small vessel vasculitis
- urticaria for >24 hours
- most commonly associated with C’ consumption and lupus!
ex: pt. presents with wheals for 48 hours, has had worsening arthritis in wrists and complement levels are low
case: 18 year old patient on no medications and with a preceding viral prodrome presents with fever, palpable skin lesions on his legs, arthralgias, hematuria, abdominal pain and GI bleeding. What is the immunoglobulin involved?
IgA - not sure if on test
IgA activates complement via the alternative complement pathway.
= HSP
Henoch-Schoenlein Purpura: TQ
small vessel vasculitis
“palpable purpura!!”
- Arthritis (60-85%)
- Nephropathy (10-50%): RBC casts — hematuria
- GI (85%) abdominal pain w bleeding
- IgA immune complexes**
mixed crygobulinemia: TQ
small vessel vasculitis
** associated with Hep C and Sjogrens!!!! ***
- Cold agglutinins! made of RF and IgG/IgM
- see low C4 levels
Clinical Findings:
- *** cold induced urticaria
- peripheral neuropathy (foot drop)
- hematuria, arthralgias, raynaud, digital gangrene
- nephritis: red cell casts
what are three ANCA associated vasculitis?
considered “pauci-immune” few immune complexes in these diseases!
- these affected all sizes of vessels!
Granulomatosis with Polyangiitis - (Wegener’s Granulomatosis)
Microscopic polyangiitis (no granulomas)
Eosinophilic Granulomatosis with Polyangiitis – (Churg-Strauss Disease) – Can be classified under the eosinophilic diseases with preceeding asthma and atopy, rather than ANCA associated.
Anti-PR3
C-ANCA = granulomatosis with polyangitis
Anti-MPO
P-ANCA = microscopic polyangitis and Churg-Strauss disease
what are ANCA’s? TQ
** neutrophilic disease!!!
ANCA = anti-neutrophil cytoplasmic abs
C-ANCA, AntiPR3 = granulomatosis w/ polyangitis
P-ANCA, Anti-MPO = microscopic polyangitis, churg strauss disease
ANCAs are associated with pauci-immune systemic necrotizing small vessel vasculitis.
ANCAs activate neutrophils to damage vessel walls with ultimate vasculitis and necrosis.
ANCA induced neutrophil activation releases factors stimulating the alternate complement pathway, which in turn draws in more neutrophils, creating a continuous loop.
A granulomatous reaction to extravascular necrosis may occur from extravascular neutrophils interacting with interstitial ANCAs.
microscopic polyangiitis: TQ
P-ANCA positive, Anti-MPO
- see palpable skin lesions
- NO gramulomatous necrotizing vasculitis of aterioles, capillaries and venules
Presentation: hematuria, hemoptysis (NO upper resp. tract)
- diffuse alveolar hemorrhage and glomerulonephritis
- palpable purpura
only see lung and renal involvement!!!! NO granulomas!!!
granulomatosis w/ polyangitis: TQ
“Wegener’s”
+ C-ANCA, Anti-PR3
** has upper respiratory, lung and kidney involvment – along with granulomas!
presentation:
- Nasal, Otic, Ocular, or Oral Inflammation.
- Abnormal chest X-ray (nodules, fixed infiltrates, cavities –cough,
dyspnea, stridor, and or hemoptysis.
- Rapidly progressive glomerulonephritis!!! yikes.
- Oligoarthritis, neuropathy, uveitis
** death occurs from renal failure
which four diseases have pulmonary renal syndromes?
- goodpasture = anti-GBM Abs to type IV Collagen
- SLE
- Microscopic polyangitis: P- ANCA
- granulomatosis w/ polyangitis: C-ANCA
Eosinophilic Granulomatosis with Polyangiitis: TQ
= Churg-Strauss syndrome
** ddx is based on presence of eosinophils
presentation:
- Asthma
- Eosinophilia (> 10% of WBC).
- Mono or polyneuropathy.
- Transitory pulmonary infiltrates.
- Paranasal sinus abnormalities.
* * Biopsy with extravascular eosinophils.
Behcet’s Disease: TQ… whats the triad?
Multi-vessel disorder = “variable vessel vasculitis”
Presentation: eyes, mouth, genital skin
- middle easter/asian
- painful apthous oral lesions
- genital ulcerations
- uveitis/occular involvment
- skin lesions
Other systemic involvement:
- arthritis
- CNS involvement
- phlebitis
** pathergy phenomenon: have a pustule formation where there was previous needle stick
familial mediterranean fever: TQ
= “ fever syndrome”
Sx:
- ** periodic fever, thats recurrent
- hot ankle rash
- arthritis, pleuritis, peritonitis
cause:
- lack of “pyrin” gene: a neutrophil protein that keeps them from mobbing spaces, results in excess amount of IL-1 stimulation
- pyrin normally inactivates IL8 and C5A
tx: colchicine - prevents deadly secondary amyloidosis
what are two single organ vasculitis?
Primary Angiitis of the CNS (May be RCVS, or “string of beads” related, or true cerebral vasculitis, or amyloid angiopathy)
Cutaneous Leukocytoclastic Vasculitis (skin) – only present w/ palpable purpura!!
primary angiitis of CNS? TQ
only CNS complaints:
- see “string of beads” on angiogram
sx:
- TIA, h/a, altered mental status, ataxia, slowed speech, etc.
- NO constitutional sx
cutaneous Leukocytoclastic vasculitis? TQ
- drug reaction **
- think antibiotics, aspirin, etc.
Inflammation & fibrinoid necrosis of vessel walls & cellular debris in tissue of the skin.
Pathology indistinguishable from HSP, MPA, etc.
***Only Clinical sign is “palpable purpura”.
