Rheumatology Flashcards
(134 cards)
1
Q
Skin manifestations of SLE
A
Acute cutaneous lupus erythematosus: malar or butterfly rash; erythema of cheeks and bridge of nose, +/- forehead & chin; spares nasolabial folds
Subacute cutaneous lupus erythematosus: photosensitive rash that occurs over the arms, neck, and face; may leave the skin with post-inflammatory changes (hyper- or hypo-pigmentation)
Discoid lupus erythematosus: most common chronic skin manifestation, isolated development of DLE usually does not mean the patient will develop SLE, most commonly face, neck, scalp, can cause scarring, atrophy, and permanent alopecia (as opposed to the other two above)
2
Q
MSK involvement of SLE
A
Joint involvement: very common, non-erosive, small & large joint, but can cause subluxation and deformities
Osteonecrosis of the hips: may be attributed to steroid use especially prednisone doses of >20/d, sometimes vasculitis
Myalgia: common, but myositis is fairly rare; SLE myositis resembles polymyositis clinically and histologically; antimalarials and steroids can also cause myopathies
Fibromyalgia: is fairly common, must be distinguished
3
Q
Kidney involvement in SLE
A
Lupus nephritis: occurs in about 70%, ass’d with anti-DS-DNA
Renal artery or vein thrombosis: in patients with APS or nephrotic syndrome
4
Q
Neuro involvement in SLE
A
Note: Almost any involvement can occur; estimated that 70% have a neuropsych condition
Most common: headache, cognitive dysfunction, mood disorder
Central involvement: aseptic meningitis, demyelination, chorea, myelopathy, HA, mood disorder
Peripheral involvement: guillan-barre, peripheral neuropathy, mononeuropathy, myasthenia, etc
5
Q
Indication for kidney biopsy in SLE
A
Increasing serum creatinine without explanation
Proteinuria >1000 mg/24 h
Proteinuria >500 mg/24 h with hematuria
Proteinuria >500 mg/24 h with cellular casts
6
Q
How often should you monitor kidney in SLE?
A
Minor abnormalities (protein < 500/24h, minimal blood, no casts): monitor q3mo’s
Casts or significant changes: “further evaluation” (ie biopsy?)
7
Q
Antibodies associated with SLE neuro disease?
A
Antineuronal
anti-NMDA receptor
antiribosomal P
antiphospholipid antibodies/lupus anticoagulant (APLA/LAC)
8
Q
Cardiovascular involvement in SLE
A
Pericarditis & myocarditis: can be dramatic with acute-onset heart failure, EF often depressed maybe to < 20%, a rapid response to steroids supports SLE as the cause
Leibman-Sacks (sterile endocarditis)
Ischemic heart disease: increased risk with severe disease or prednisone dose >20/d
9
Q
Pulmonary involvement in SLE
A
Pleuritis
Pleural effusion
Interstitial lung disease (actually rare in SLE)
Acute lupus pneumonitis (high mortality, tx = aggressive immunosuppression)
Diffuse alveolar hemorrhage (high mortality, tx = aggressive immunosuppression)
Shrinking lung syndrome (progressive lung volume loss; cause unknown; tx = agg immunosuppression)
10
Q
Heme involvement in SLE
A
Any cytopenia
Hemolytic anemia
Antiphospholipid antibodies/lupus anticoagulant
Evans syndrome: severe thrombocytopenia + hemolytic anemia
11
Q
GI involvement in SLE
A
GERD
Esophageal dysmotility
Sterile peritonitis
Mesenteric vasculitis (often with cutaneous vasculitis)
Mesenteric thrombosis (with APS)
12
Q
Relation of SLE to malignancy
A
Increased risk of NHL, esp DLBCL, and cervical cancer
13
Q
Clinical manifestations of RA
A
Joints: Multiple small joints of hands and feet, morning stiffness lasting at least 1 hour, DIP involvement is RARE, protracted onset (should be at least 6 weeks) +/- constitutional symptoms
Skin: Rheumatoid nodules, pyoderma gangrenosum, vasculitis (livedo reticularis & digital infarcts)
Eyes: Keratoconjunctivitis sicca, episcleritis, and vision-threatening inflammation (scleritis, uveitis, ulcerative keratitis, corneal filamentary keratitis
Pulmonary: Pleuritis, ILD (esp in smokers)
Cardiac: Pericarditis, rarely can develop restrictive cardiomyopathy not responsive to steroids
Other: Felty syndrome, mesangioproliferative GN, amyloidosis, alantoaxial subluxation, peripheral neuropathy
14
Q
Diagnosis of RA
A
Need >= 6 points needed for “definite RA”:
Joint involvement (1-5 points; more for small & many joints)
Serology (3 for high-positive, 1 for low)
Acute phase reactants (1 pt for either ESR or CRP)
Duration of joint symptoms (1pt for > 6 weeks)
15
Q
Diagnosis of SLE
A
Need 4/11 criteria:
Skin/mucosa (1 each) - rash (malar, discoid, or photosensitive), oral ulcers
Serosa (pleuritis or pericarditis)
Neuro disorder (seizures or psychosis)
Heme disorder (cytopenias/hemolytic anemia)
Kidney disorder (3+ protein, >500/24hr, cell casts)
Joint disorder (inflammatory polyarthritis)
Antibodies - 1 for ANA, 1 for other (dsDNA, a-Smith, APA)
16
Q
Antibodies in RA
A
RF is 70% sensitive (50% initially, 60-80% later in established disease)
Anti-CCP is ~95% specific
Seronegative in 20%
Seronegative RA more likely in men
17
Q
Antibodies in SLE
A
Antinuclear - 95% - Useful as an initial screening test
Anti–double-stranded DNA - 50% - Found in more severe disease, especially kidney disease; antibody levels commonly follow disease activity and are useful to monitor
Anti-Ro/SSA - 40% - Associated with photosensitive rashes, discoid lupus, and neonatal SLE, including congenital heart block; also common in Sjögren syndrome
Anti-U1-ribonucleoprotein - 35% - Associated with Raynaud phenomenon and esophageal dysmotility; also seen in MCTD
Anti-Smith - 25% - Specific for SLE; often associated with more severe disease
Anti-La/SSB - 15% - Common in Sjögren syndrome; less common in SLE and neonatal SLE
Antiribosomal P - 15% - Associated with CNS lupus and lupus hepatitis
18
Q
What antibody combo definitively rules out SLE?
A
Negative ANA + negative Ro/SSA
19
Q
In SLE, what is more useful - ESR or CRP?
A
ESR; some patients with SLE do not produce CRP in flares; if they do then CRP can be used however
20
Q
Other than antibodies & ESR/CRP, what else should be measured in SLE?
A
Complements should also be assessed (most commonly, C3 and C4) because these levels are reduced during SLE activity
21
Q
What are the classic drugs causing drug-induced lupus?
A
procainamide
methyldopa
quinidine
hydralazine
22
Q
If a patient has a disease that looks similar to SLE but doesn’t meet full criteria, what would you call it?
A
Undifferentiated connective tissue disease
23
Q
Labs that need serial monitoring in SLE:
A
CBC
ESR
anti-dsDNA
C3/C4
UA
UCr/Pr
24
Q
Management of RA
A
DMARD monotherapy: low disease activity or moderate/high activity without poor prognostic features
DMARD combo therapy: Moderate or high activity with or without poor prognostic features
Biologics DMARDs: High activity with poor prognostic features Poor prognostic features: functional limitation, extra-articular disease, + RF or CCP, bony erosions
Non-biologics:
MTX is first choice, and the only one that can be used in combo with a biologic
Combo therapy can include HCQ +/- sulfasalazine
Leflunomide is an alternative if MTX is not a good option for one reason or another
Anti-TNF biologics:
anti-TNFs are the most commonly used (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol)
Improvement is seen in weeks, more efficacious when used with MTX
Other biologics (use after one or two anti-TNFs have failed):
Abatacept (stops APCs presenting to T-cells; for severe disease)
Rituximab (depletes B cells; for severe disease)
Tocalizumab (anti IL-6)
Tofacitinib (JAK/STAT small molecule)
25
General management of SLE
Hydroxychloroquine for everyone (improves survival)
Prednisone 20-60/d for most acute manifestations
Prednisone 1000/d for most severe & life-threatening conditions
Mycophenolate mofetil for active lupus nephritis (more in nephrology section); Mycophenolate mofetil may be at least as effective as cyclophosphamide for systemic lupus erythematosus but with fewer, and milder, side effects
IV cyclophosphamide followed by mycophenolate (maybe azathioprine) for very severe conditions
Belimumab if all the above fail (add-on therapy)
26
The main types of scleroderma, and the main differences between them
Diffuse cutaneous: distal + proximal thickening, more often involving organ fibrosis & ILD, Raynaud's usually accompanies onset of other symptoms
Limited cutaneous: Distal skin affected (face, neck, hands) without proximal (chest, abdomen, wrists up), typically no internal organ fibrosis however more likely to develop PAH, early Raynaud's, and CREST
Morphea: localized plaques on the trunk, not associated with systemic manifestations
Linesar scleroderma: streaks/lines of thickened skin, not associated with systemic manifestations
27
Antibodies in systemic sclerosis
Anticentromere: LcSSc + PAH
Anti-scl-70 (DNA topoisomerase-1): DcSSc, ILD
Anti-RNA polymerase III: DcSSc, kidney disease
Anti-U3-RNP: DcSSc, PAH, myositis
Anti-PM-Scl: Myositis, associated with overlap polymyositis
28
Systemic sclerosis management
No "DMARD"; manage complications
Steroids should be used cautiously as they may precipitate a renal crisis
Cyclophosphamide for severe/rapidly progressive lung disease
ACEIs for mild HTN or unexplained creatinine elevations (prevent scleroderma renal crisis)
29
Treatment of Raynaud's
avoid cold, avoid smoking
1st line: CCBs, anti-platelets, topical nitrates, aspiration
2nd line: PDE5i's (sildenafil/tadalafil)
30
Systemic sclerosis clinical manifestations
Pulmonary (common): ILD, PAH, aspiration
Cardiac : cardiac fibrosis (rare but deadly), conduction disease (fibrosis), CAD
GI: Pharynx, esophageal, GERD, anal sphincter incompetence
Renal: Scleroderma renal crisis
Misc: Raynaud's, Inflammatory arthritis, Peripheral neuropathy
31
Typical presentation & treatment of scleroderma renal crisis
acute kidney injury and severe hypertension, mild proteinuria, urinalysis with few cells or casts, microangiopathic hemolytic anemia, and thrombocytopenia. Some patients develop pulmonary edema and hypertensive encephalopathy. Occasionally, patients remain normotensive despite kidney dysfunction.
ACE inhibitors significantly improve kidney survival and decrease mortality among patients with SRC. Treatment with an ACE inhibitor should be initiated promptly in SSc patients with even mild hypertension or otherwise unexplained elevations in serum creatinine levels.
The ACE inhibitor should be up-titrated until good control of blood pressure is achieved and continued even in the setting of kidney disease.
32
Chronic steroid use necessitates consideration of what?
Vitamin D supplementation (all patients on chronic steroids or frequent tapers)
Bisphosphonate therapy (if \>=5mg/d for \> 4 weeks)
33
Adalimumab
TNF-alpha inhibitor
RA
34
Etanercept
TNF-alpha inhibitor
RA
35
Certolizumab pegol
TNF-alpha inhibitor
RA
36
Golimumab
TNF-alpha inhibitor
RA
37
Infliximab
TNF-alpha inhibitor
RA
38
Abatacept
T-call costimulation (APCs/Tcells)
RA
39
Rituximab
CD20 blocker (B-cells)
RA and ANCA vasculitis
40
Tocilizumab
IL-6 receptor
RA, JIA, Castleman disease
41
Belimumab
BLyS/BAFF
SLE
42
Tofacitinib
JAK
RA
43
Ustekinumab
IL-12/IL-23
Psoriasis; psoriatic arthritis
44
Anakinra
IL-1β receptor
RA, AOSD, cryopyrin-associated syndromes
45
Rilonacept
IL-1
Cryopyrin-associated syndromes, refractory gout
46
Canakinumab
IL-1β
Cryopyrin-associated syndromes
47
Methotrexate
DHFR inhibition
RA, psoriatic arthritis, DM & PM, vasculitis
48
Hydroxychloroquine
Unknown
SLE, RA
49
Sulfasalazine
Antimetabolite - a pro-drug broken down into 5-amino salicylic acid (active metabolite in GIT) and sulfapyridine (exerts systemic action)
RA, SpA, IBD
50
Leflunomide
Blocks dihydroorotase, enzyme involved in pyrimidine biosynthesis, antiproliferative
RA
51
Azathioprine
Purine analogue; inhibits DNA synthesis
SLE; DM; PM; vasculitis; IBD
52
Cyclophosphamide
Alkylating agent; blocks DNA synthesis
Severe and life-threatening disease in SLE, DM, PM, and vasculitis
53
Mycophenolate mofetil
Inosine monophosphate inhibition; antiproliferative; mycophenolate is converted into the active metabolite, mycophenolic acid, which inhibits inosine monophosphate dehydrogenase (an enzyme in the purine synthetic pathway) and preferentially inhibits T- and B-lymphocytes
SLE (especially lupus nephritis); vasculitis; DM; PM
54
General monitoring of DMARDs
Thereafter: CBC, LCTs, serum creatinine every 3-6 months
55
Leflunomide monitoring
LCTs every 8-12 weeks, and leflunomide temporarily or permanently discontinued for significant elevations \>2 times normal
56
Hydroxychloroquine monitoring
Baseline/periodic ophthalmologic examinations approximately every 12 months to evaluate for hydroxychloroquine deposition, which rarely can lead to visual loss
57
Cyclophosphamide monitoring
Urinalysis every 4-8 weeks
58
Cyclosporine
Inhibits calcineurin (a transcription activating factor); preferentially targets T cells
SLE; psoriasis; RA
59
Apremilast
Inhibits phosphodiesterase 4
Psoriasis; psoriatic arthritis
60
Apremilast monitoring
Weight, neuropsychiatric effects
61
General management of DMARDs
Key Points
◾Infection risk is elevated with most biologic agents; therapy should be temporarily interrupted during any significant infection.
◾Tumor necrosis factor α inhibitors are usually the treatment of first choice for patients with rheumatoid or psoriatic arthritis after inadequate response to nonbiologic disease-modifying antirheumatic drugs.
◾Other biologic agents are typically started after failure of one or two tumor necrosis factor α inhibitors, although some are also approved as first-line therapies.
62
DMARDs and vaccines
Key Points
◾Whenever possible, patients should be brought up to date on vaccinations prior to starting immunosuppressive therapy.
◾Live attenuated vaccines are currently contraindicated for patients on biologic therapies; however, live attenuated vaccines may be administered approximately 4 weeks before starting biologic therapy.
◾Prior to initiating aggressive immunosuppressive therapy, screening for infections (tuberculosis, hepatitis B and C, HIV) is indicated; if needed, infection therapy must be started before initiating immunosuppressive therapy.
63
Rheum medications and pregnancy
Key Points
◾Methotrexate is highly teratogenic and abortifacient and must be discontinued at least 3 months prior to conception.
◾Hydroxychloroquine is relatively safe in pregnancy and should not be discontinued.
◾Leflunomide is extremely teratogenic and must not be used before/during pregnancy; if leflunomide is inadvertently administered, cholestyramine treatment is required to remove the drug from the body before pregnancy.
64
Radiographic findings of OA
Joint-space narrowing (articular cartilage loss)
Subchondral sclerosis
Marginal osteophyte formation
Subchondral cysts
65
Erosive OA
OA with radiographic erosions seen Manifests clinically as intermittent flares of swelling and redness Differentiated from inflammatory arthritis due to central erosions (RA & psoriatic arthritis show marginal erosions) You should also see collapse of subchondral bone
66
What is DISH?
Diffuse Idiopathic Skeletal Hyperostosis Essentially similar to OA of the spine, however classified differently Osteophytes of the anterolateral spine (often thoracic) on XRs, "bridging" of the osteophytes, and preservation of the disk spaces Radiographically, DISH may be difficult to differentiate from ankylosing spondylitis GI/airway complications: Dysphagia Aspiration pneumonia Difficult intubation Spine complications: Unstable spinal fractures Spinal stenosis Myelopathy
The prevalence of DISH increases with age and is approximately 15% in patients over 50 years of age
67
Heberden & Bouchard nodes
Heberden = bony enlargement of DIP due to OA
Bouchard = bony enlargement of PIP due to OA
68
When are steroid joint injections particularly useful?
One or limited number of joints
Effusions
69
Criteria for diagnosis of fibromyalgia
High score on Widespread Pain Index (WPI) + Symptom Severity Scale (SSS)
WPI: self-reported pain for at least 3 months at 19 different body locations
SSS: severity of 3 symptoms: fatigue, waking unrefreshed, cognitive symptoms
ESR & CRP should be obtained and should usually be normal.
(The combination of a WPI of ≥7 plus an SSS of ≥5, or a WPI between 3 and 6 plus an SSS of ≥9, establishes a diagnosis of fibromyalgia for the purposes of study enrollment)
70
Treatment for fibromyalgia
Exercise
pregabalin
SNRIs duloxetine & milnacipran
71
Common features of spondyloarthropathies
inflammation of the axial skeleton, tendons, and entheses
tendon and enthesis calcification
association with HLA-B27
mucocutaneous, gastrointestinal, and ocular inflammation
72
Unexpecedly severe cases of reactive or psoriatic arthritis should prompt suspicion of what?
HIV infection (+HLAB27)
73
Presentation of ankylosing spondylitis
L-spine involvement that progresses upwards wtih time
Enthesitis (achilles?)
Psoriasis can coexist
Aortic valve disease; aortitis; conduction abnormalities; CAD
Restrictive lung disease from costovertebral rigidity; apical fibrosis (rare)
Falsely elevated bone mineral density from syndesmophytes; increased risk of spine fracture
Increased mortality (heart disease, cancer, infection)
74
Presentation of psoriatic arthritis
Joint pattern:
1. asymmetric lower extremity oligoarthritis
or
2. symmetric polyarthritis of the hand joints (including DIP)
Psoriasis usually but not always precedes arthritis
Dactylitis & onycholysis relatively common
Spondylitis may occur but is usually asymmetric and skips regions (compare to ankylosing spondylitis)
RF/anti-CCP usually (~90+%) but not always negative
Radiographs: marginal joint erosions and new bone formation
75
Presentation of IBD-associated inflammatory arthritis
Peripheral joint involvement may be:
oligoarticular (type 1)
or
polyarticular (type 2)
Only the oligoarticular peripheral arthritis parallels IBD activity
76
Presentation of reactive arthritis
Occurs after specific gastrointestinal or genitourinary infections
Asymmetric monoarthritis or oligoarthritis in the lower extremities is the most common presentation
Enthesopathy (including at the Achilles tendon insertion to the calcaneus), dactylitis, and sacroiliitis may occur
Occurs approximately 3 to 6 weeks after the infectious trigger
Generally self-limited but can progress to a chronic disease
GI pathogens: Yersinia, Salmonella, Shigella, Campylobacter, and, rarely, Escherichia coli and Clostridium difficile
GU pathogens: Chlamydia trachomatis, Ureaplasma urealyticum
77
Diagnostic evaluation of suspected spondyloarthritis
78
How to diagnose which sponyloarthropathy it is
79
Differentiation of DISH from ankylosing spondylitis on radiographs
the changes in ankylosing spondylitis are usually on both sides of the spine, whereas in DISH they are characteristically right sided
DISH is most commonly thoracic, whereas ankylosing spondylitis starts with sacroiliitis and lumbar arthritis and usually does not skip regions as it ascends
80
Management of spondyloarthritis
Exercise (especially for ankylosing spondylosis)
Steroid injections (especially if a few joints)
NSAIDs (it can be helpful to try a second NSAID if the first has produced an inadequate response)
For ankylosing spondylitis & psoriatic arthritis: go straight to anti-TNFs
For psoriatic arthritis: Ustekinumab has shown to be really good, can be used with MTX
For IBD-associated & reactive: try non-biologic DMARDs before anti-TNFs
In general, non-biologics do not help with axial disease
81
What is sjogren syndrome?
immune-mediated disease of unknown cause
manifests as infiltrative inflammation that damages exocrine glands, including:
major and minor salivary glands
lacrimal glands
less commonly, other exocrine glands such as the pancreas
82
Clinical manifestations of sjogren syndrome
sicca, or dryness, particularly of the:
eyes (keratoconjunctivitis sicca; result in corneal damage and visual impairment)
and
mouth (xerostomia; can result in dental caries)
Can have extra-glandular manifestations
Most common = fatigue and arthralgia
Can affect almost any organ it looks like
increased risk of lymphoma, with diffuse large B-cell and mucosa-associated lymphoid tissue (MALT) lymphomas being the most common
83
Schirmer test
Documenting reduced tear production (decreased wetting of tear test strips)
Used for diagnosis of Sjogren's & lacrimal gland dysfunction
84
Diagnosis of Sjogren's
Clinical presentation
Laboratory findings include positive autoimmune serologies (rheumatoid factor, antinuclear, anti-Ro/SSA, and anti-La/SSB antibodies)
Hypergammaglobulinemia
Anti-Ro/SSA and anti-La/SSB antibodies are characteristic for Sjögren syndrome
Gland biopsy (usually lip) is considered the gold standard
Other autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and autoimmune thyroiditis, are commonly associated with Sjögren syndrome.
85
Treatment of Sjogren's
Topical/symptomatic (artifical tears, lubrication)
NSAIDs and steroids
Non-biologic DMARDs
86
Definition of MCTD
Mixed connective tissue disease
Overlap syndrome that includes features of:
SLE
SSc
And/or polymyositis
In the presence of:
anti-U1-ribonucleoprotein (RNP) antibodies
87
Diagnosis of MCTD
Numerous clinical manifestations; any features of SLE, SSc, or PM
Very high ANA titer (≥1:1200) in a speckled pattern
Positive anti-U1-RNP antibodies; presence of anti-Smith or anti–double-stranded DNA antibodies should suggest SLE rather than MCTD
88
Pathophysiology of gout
Purines are created by cell turnover, are converted to xanthine/hypoxanthine, then converted by xanthine oxidase to uric acid
In purine overproduction, overconsumption, or under-excretion, macrphages eat the crystals and release cytokines causing neutrophil infiltration and an inflammatory cascade
89
Synovial fluid analysis of crystal arthropathy
monosodium urate crystals are needle shaped and negatively birefringent
CPP crystals are rhomboid shaped and positively birefringent
gout fluid is typically inflammatory (2000/µL to \>100,000/µL [2.0-100 × 109/L], neutrophil predominance of ≥50%)
Whereas extracellular crystals confirm a chronic gout diagnosis, crystals within neutrophils define active, gout-induced inflammation
Gram stain and cultures must be obtained to exclude infection. Acute gout and joint infection occasionally coexist.
90
Raiographic findings of gout
Normal in acute/short-duration gout
In long-standing uncontrolled disease:
punched-out lesions
often with overhanging edges where the bones have been eaten away by tophaceous deposits
91
Treatment of acute gouty arthritis
Colchicine
NSAIDs
Steroids
Intra-articular steroids are very effective
Patients already taking urate-lowering therapy should continue at the same dose throughout a flare because changes in serum urate can exacerbate attacks
92
Foods that elevated purine levels
Meat
Beer
High-fructose (cokes, processed foods)
93
Urate lowering therapy in gout
ACR vs EULAR
Urate-lowering therapy
Flare prophylaxis
---------------------
ACR: "treat to avoid symptoms"
EULAR: "treat to target"
\< 6.0 wtihout tophi
\< 5.0 wtih tophi
Both the ACR and EULAR recommend urate-lowering therapy for patients with gout plus any of the following: (1) ≥stage 2 CKD; (2) ≥2 acute attacks per year; (3) one or more tophi; or (4) uric acid nephrolithiasis.
----------------
1st line = usually allopurinol, febuxostat is a more expensive but maybe more efficacious option
2nd line = probenecid (however may increase risk of renal stones and doesn't work as well in CKD)
3rd line = the potent intravenous agent pegloticase is a treatment option; provides uricase activity, converting uric acid to allantoin
---------------------
Start flare prophylaxis when starting urate-lowering therapy (colchicine & NSAIDs preferred, steroids 2nd line)
ACR currently recommends that prophylaxis should be continued for the greater of the following: 6 months; 3 months after achieving the target serum urate level for a patient without tophi; or 6 months after achieving the target serum urate level where there has been resolution of tophi
94
The four clinical presentations of CPPD & their treatments
Calcium Pyro-Phosphate Deposition
1. cartilage calcification (also known as chondrocalcinosis)
tx = no specific tx
2. acute CPP crystal arthritis (also known as pseudogout)
tx = NSAIDs, colchicine, steroids
3. chronic CPP crystal inflammatory arthritis (“pseudo-rheumatoid arthritis”)
tx = NSAIDs, colchicine, steroids, MTX, HCQ
4. osteoarthritis with CPPD (accelerated osteoarthritis findings in joints not commonly involved with simple osteoarthritis)
tx = as regular OA
95
The diseases associated with CPPD are:
hyperparathyroidism
hemochromatosis
hypomagnesemia
hypothyroidism
previous joint injury
96
What is "Basic Calcium Phosphate Deposition"
common cause of cartilage calcification and may be radiographically indistinguishable from CPPD
Unlike CPP crystals, BCP crystals also commonly deposit in periarticular tendons, bursae, and other soft tissues
Patients are often asymptomatic, but BCP crystals can cause destructive arthropathy
BCP crystals also can stimulate inflammation via pathways similar to monosodium urate and CPP crystals
Diagnosis of BCP deposition is made clinically or by joint aspiration
Synovial fluid is characteristically noninflammatory (\<2000/µL)
BCP crystals are not visible on polarized microscopy
Treatment for symptomatic BCP deposition includes NSAIDs, joint aspiration and tidal lavage, and intra-articular glucocorticoid injection
97
Synovial fluid analysis of infectious arthritis
leukocyte count is markedly increased (usually \>50,000/µL [50 × 109/L] with neutrophil predominance)
sensitivity of cultures are only 80% and may be negative due to precefing antibiotics, so clinical assessment ultimately guides treatment
98
Presentation of gonooccal arthritis
Actually has two main presentations:
1. Grossly purulent mono- or oligoarthritis
2. Dissemminated infection with rash, constitutional symptoms, and polyarthralgia, and tenosynovitis of the hand and feet; leukocyte counts are lower (\<25k)
99
Presentation of Lyme arthritis
Although arthralgia is common in early Lyme disease, Lyme arthritis generally refers to frank inflammation of the joints as a manifestation of late Lyme disease
Impressively large effusions, most often a knee monoarthritis with prominent stiffness but relatively little pain
Diagnosis is made by serologic testing (Borrelia burgdorferi)
Joint aspiration demonstrates a moderately inflammatory synovial fluid (leukocyte count typically 20,000-25,000/µL [20-25 × 109/L], neutrophil predominant)
100
MTB arthritis
| (mycobacterium tuberculosis)
most commonly presents as spondylitis (Pott disease) or vertebral osteomyelitis
chronic, indolent course, often without constitutional symptoms
monoarticular, often involving the hip or knee
Synovial fluid analysis usually suggests a nonspecific inflammatory process
101
Mycobacterium marinum infections
typically begin as red or violaceous plaques, nodules, or abscesses in the skin, and may spread locally to involve the hand joints
102
Viral infections causing arthritis
HBV:
symmetric polyarthritis, especially of hands & knees, often with rash
HCV:
chronic arthirits, numerous presentations
Parvo B19:
usually gotten from an infected child, symmetric arthritis with swelling of small joints (hands & feet, wrists & knees), lasting weeks to months, dx = IgM (not IgG)
Rubella:
Small joint polyarthritis
Associated with rash, fever, and lymphadenopathy
Resolves in ~2 weeks
dx = IgM
Can occur in response to the vaccine
Chikungunya:
From asia & africa, mosquito virus
fever, rash, myalgia, thrombocytopenia and/or leukopenia
Self-limited polyarthritis/tenosynovitis but lasting up to 6 months
IgM
103
Early vs delayed vs late prosthetic joint infections
Early is \< 3 months
Acute pain and swelling
Acquired during prosthesis implantation
Delayed is \< 12 months
Prolonged joint pain, often without fever
Acquired during prosthesis implantation
Late is \> 12 months
Acute pain and swelling
De novo from hemtogenous seeding
104
Describe the three idiopathic inflammatory myopathies and their proposed pathophysiologies
PM (polymyositis) is a CD8-positive T-cell–mediated immune disease with direct myocyte injury
DM (dermatomyositis) is considered an immune complex disease with vascular inflammation in muscle and subsequent muscle damage
IBM (inclusion body myositis) is most likely a myodegenerative disorder with vacuolar inclusions and a related T-cell response
105
What is antisynthetase syndrome?
Seen in DM and PM
Defined by the presence of autoantibodies to aminoacyl-transfer (t)RNA synthetase enzymes (such as anti–Jo-1), plus two of the following clinical features:
inflammatory myositis
interstitial lung disease
Raynaud phenomenon
nonerosive inflammatory arthritis
"mechanic's hands"
106
Muscle involvement in the idiopathic inflammatory myositis syndromes
Symmetric painless proximal weakness of the arms and legs is the classic feature of DM and PM:
difficulty combing hair, rising from a chair, and climbing stairs (classic triad of hair, chair, stair)
difficulty with routine activities
muscle weakness in IBM characteristically affects both distal and proximal muscles
Onset is insidious and slowly progressive, often over years
107
Cutaneous involvement in dermatomyositis
Gottron sign/papules:
symmetric erythematous/violaceous macules, patches, or papules located on the extensor surfaces of the metacarpophalangeal joints
heliotrope rash:
edematous lilac discoloration of periorbital tissue
photodistributed rashes:
shawl sign (upper back)
V sign (neck/upper chest)
Poikiloderma:
mottled pigmentation, epidermal atrophy, and telangiectasia in both sun-exposed and unexposed areas
Gottron sign/papules and heliotrope rash are considered pathognomonic for DM
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Amyopathic dermatomyosits
classic cutaneous findings of dermatomyositis occurring in the absence of muscle involvement
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Main cardiopulmonary involvement in PM/DM
ILD:
Often associated with antisynthetase antibodies, including anti–Jo-1
Poor prognostic finding
Routine screening for ILD with imaging such as chest radiography or CT is appropriate in asymptomatic patients in the presence of antisynthetase antibodies
Diaphragm muscle weakness
resulting in shortness of breath and, occasionally, respiratory failure
Pharyngeal muscle involvement
aspiration pneumonia
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How to differentiate PM/DM from IBM
DM/PM:
Female, younger, ass'n with cancer
Proximal only
CK/aldolase \> 10x ULN
Acute/subacut onset & rapidly progressive
Responds to therapy
IBM:
Male, older (\>50), familial ass'n
Proximal + distal
CK \< 10x ULN
Insidious onset & slowly progressive ( large impact on daily activities but little impact on overall survival)
Does not respond to therapy
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Antibodies in idopathic inflammatory myositis
DM/PM:
ANA (80%)
Myositis-specific autoantibodies (MSA): checked 1st
anti–Jo-1
antibodies to signal recognition particle (SRP)
antibodies to Mi-2
Myositis-associated autoantibodies (MAA): checked 2nd
anti-PM-Scl
anti-Ku
anti-Ro/SSA
anti-La/SSB
anti-U1-ribonucleoprotein (RNP) antibodies
Positive anti-U1-RNP antibodies suggest an overlap syndrome with mixed connective tissue disease.
No Abs for IBM
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Ddx of idiopathic inflammatory myopathies
hereditary diseases
infection
endocrine
drug-induced myopathies (colchicine, hydroxychloroquine, steroids)
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Treatment of idiopathic inflammatory myopathies
Steroids are the mainstay of therapy
Immunosuppressive therapy with methotrexate or azathioprine is used for glucocorticoid-resistant disease or ILD
mycophenolate mofetil and leflunomide
IVIG is recommended as an alternative treatment for DM
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Giant cell arteritis:
1. Clinical findings
2. Affected arteries
3. Management
1. Clinical findings:
headache
jaw claudication
amaurosis fugax & blindness
decreased pulses and hand or forearm ischemia
aortic aneurysm and aortic dissection
elevated ESR
age \> 50
2. Affected arteries:
external carotids
temporal arteries (hence the alternative designation temporal arteritis)
ciliary and ophthalmic arteries
subclavian and brachial arteries can be affected
3. Management:
Treat with steroids empirically, total of 6-18 months
Biopsy may miss the affected area anyways (not super sensitive)
Still can interpret biopsy even after up to 2 weeks after treatment initiation
ESR can serve as a marker of disease activity
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Polymyalgia Rheumatica
1. Diagnosis
2. Treatment
1. Diagnosis:
clinical diagnosis based on the characteristic symptoms in a patient older than 50 years
pain & stiffness in the shoulder, neck, and hips
inability to comb hair or rise from a chair unassisted
creatine kinase and aldolase are generally normal
elevated ESR
2. Treatment:
low-dose prednisone, good response (but often relapses wtih steroid discontinuation so may be on steroids for a long time)
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Takayasu Arteritis
1. Affected arteries
2. Clinical findings
3. Management
1. Affected arteries:
aorta (any part) and its major branches.
2. Clinical findings:
young women, typical age at onset between 15 and 25 years
fever, fatigue, malaise, weight loss, arthralgia and myalgia often precede the onset
narrowings & dilations of large arteries
diminished or absent pulses often accompanied by bruits
asymmetric BP measurements
hypertension (aortic coarctation)
AR (aortic root aneurysm/dilation)
3. Management:
High-dose prednisone (1mg/kg/d) then taper
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Polyarteritis Nodosa
1. Vessels involved
2. Clinical findings
3. Management
1. Vessels involved:
Aneurysms and microaneurysms of medium & small arteries
kidneys, gastrointestinal tract (especially the mesenteric artery and small intestine), peripheral nervous system, and skin
Coronary arteries can also be affected
2. Clinical findings:
fatigue, malaise, fever, myalgia, arthralgia
hypertension (renal artery involvement; not GN)
abdominal angina (mesenteric artery invovlement) & bowel infarction
mononeuritis multiplex (peripheral nervous system invovlement)
skin involvement (livedo reticularis, purpura, and painful subcutaneous nodules)
hepatitis B association (30%)
3. Management:
Can have a poor prognosis
Treatment is aggressive, including high-dose prednisone and cyclophosphamide
Patients with hepatitis B should receive plasma exchange and antiviral therapy whenever feasible
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PACNS
"Primary Angiitis of the Central Nervous System"
Necrotizing granulomatous vasculitis limited to the vessels of the CNS
Recurrent headaches with progressive encephalopathy
Can also see strokes, seizures, and visual field deficits
Difinitive test is brain biopsy showing granulomatous vasculitis
Management is aggressive and includes high-dose glucocorticoids and daily oral cyclophosphamide
But generally is unstoppable and leads to cognitive decline, dementia, and death
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Granulomatosis with polyangiitis
1. Clinical findings
2. Management
1. Clinical findings:
"C-disease"
upper respiratory tract (including sinuses and ears), lungs, and kidneys
c-ANCA pattern and anti-PR3 antibody positivity
2. Management:
Treatment can be started with c-ANCA and clear presentation
Biopsy may be helpful
Kidney biopsies will generally not show granulomas however so may mkae it difficult to distinguish from other ANCA diseases
Glucocorticoids alone are insufficient to control GPA:
Treatment includes high-dose glucocorticoids plus cyclophosphamide or rituximab
Followed by maintenance therapy with methotrexate, azathioprine, mycophenolate mofetil or rituximab for at least 24 months
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Microscopic polyangiitis
1. Clinical findings
2. Management
1. Clinical findings
kidneys & lungs
kidneys = almost 100%, and as in GPA, the lesions are those of necrotizing glomerulonephritis; immune deposits are sparse or absent
lungs = non-granulomatous alveolar infiltrates, may have DAH which can be fatal
p-ANCA and anti-MPO antibodies
2. Management:
high-dose glucocorticoids plus either cyclophosphamide or rituximab
followed by maintenance therapy with methotrexate, azathioprine, or mycophenolate mofetil.
121
Eosinophilic Granulomatosis with Polyangiitis
1. Clinical findings:
history of atopy, including allergic rhinitis, nasal polyps, or asthma
Hypereosinophilia = both the peripheral blood and involved tissues; diagnosis of EGPA should be revisited in the absence of eosinophils
Lung disease = infiltrates and capillaritis
Peripheral nerve disease = mono- or polyneuropathy or mononeuritis multiplex
Kidney disease = less common than in other ANCA diseases
typically p-ANCA/anti-MPO pattern however may be ANC negative
2. Management:
mild or limited disease = glucocorticoid treatment alone may therefore be sufficient
severe disease = glucocorticoids plus cyclophosphamide is preferred, followed by maintenance therapy with a less toxic immunosuppressive agent
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Small vessel vasculidities: ANCA vs immune complex
ANCA = c- vs p-, "pauci-immune"
GPA
MPA
EGPA
Immune-complex = "leukocytoclastic vasculitis"
Cryoglobulinemic Vasculitis
Henoch-Schönlein Purpura
Hypersensitivity Vasculitis
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Cryoglobulinemic Vasculitis
1. Clinical findings
2. Associations
3. Management
1. Clinical findings:
precipitating in vitro at temperatures below normal body temperature
palpable purpura + other organ (usually glomerulonephritis + peripheral nerves, sometimes other organs)
cold-related precipitation, vascular ischemia, and infarction of the fingertips, ear helices, and tip of the nose
2. Associations:
Hematologic malignancy = monoclonal IgM
HCV = Polyclonal IgG + monoclonal IgM + RF
Autoimmune disease (SLE/RA) = Polyclonal IgG + polyclonal IgM + RF
3. Management:
Mild disease = treat underlying cause
Severe disease = steroids, cyclophosphamide/rituximab, plasmapharesis
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Henoch-Schönlein Purpura
1. Clinical features:
IgA depositions
Palpable purpura (palms and soles)
Abdominal pain wtih GI ischemia & bleeding
Glomerulonephritis (IgA nephropathy)
2. Management:
Steroids
125
Hypersensitivity Vasculitis
1. Clinical findings
Response to known or unknown antigen (ie drug or infection)
Immune-complex disease, usually not IgA
Palpable purpura and other rashes
Other organs are usually spared
2. Management:
If mild/moderate = remove offending antigen and rash should resolve within weeks
If severe = steroids
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Behçet Syndrome
a form of vasculitis that affects small to large arterial vessels and can affect veins as well
Diagnosis:
Recurrent painful ulcertain of mouth or tongue
+
One other manifestation:
Eye involvement (distinctive lesion is Hypopyon; a layered collection of pus in the anterior chamber)
Skin involvement (Erythema nodosum, acneiform lesions especially of the thighs or trunk)
Pathergy test (transient subcutaneous insertion of a sterile, large-bore needle under the skin results in the development of a pustule at the site 24-48 hours later)
Genetics:
HLA-B51
Other manifestions:
pulmonary artery, aorta, and/or femoral artery inflammation (3%-12% of patients). Aneurysms and stenosis can occu
headaches, stroke, pyramidal signs, behavioral changes, or, rarely, dural sinus thrombosis
Gastrointestinal involvement may be hard to distinguish from inflammatory bowel disease but ulceration typically involves the ileum rather than the rectal or perianal regions and does not lead to fistula formation
Treatment:
Low-dose prednisone or colchicine is used for oral/genital ulcers
high-dose prednisone and immunomodulating agents such as azathioprine are used for more severe disease
Tumor necrosis factor (TNF)-α inhibitors, interferon alfa, and anti-interleukin (IL)-1β therapy have been used in recalcitrant or severe cases.
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Relapsing Polychondritis
autoimmune response to type II collagen
Need 3/6 of the next two categories:
Chondritis of:
Ears (helix, not lobes) (recurrent)
Nose ("saddle nose" deformity)
Larynx or trachea (airway stenosis)
Also:
Nonerosive inflammtaory polyarthiritis
Eye inflammation
Chochlear/vestibular dysfunction
Associations:
Age 60s70s --\> look for MDS
Large vessel vasculitis
Other autoimmune diseases
Treatment:
Low dose prednisone for mild disease
High dose prednisone for life-threatening disease
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Adult-onset Still Disease
high spiking fevers
a salmon-colored rash
arthritis
high neutrophil counts
macrophage hyperactivation
can have severe and life-threatening dysfunction of almost any organ
diagnosis of exclusion (exclude infection, malignancy, other rheum disease)
ferritin is generally very high
NSAIDs and/or prednisone
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Familial Mediteranean Fever
MEFV1 gene
Attacks every 1-3 days:
Polyserositis
Arthritis
Erysipeloid rash around ankles
Elevation of acute-phase reactants
AA amyloidosis is a potential long-term consequence
Treatment = colchicine, chronic daily treatment
130
Löfgren syndrome
specific syndrome of sarcoidosis
younger adults
acute "arthritis"
(actually a nondestructive periarthritis of the soft tissue, entheses, and tenosynovium)
bilateral hilar lymphadenopathy
erythema nodosum
131
Genes associated with the true connective tissue diseases
Marfans
Ehlers-Danlos
Osteogenesis Imperfecta
Marfans
fibrillin 1 (FBN1)
Ehlers-Danlos
collagen-related genes (COL)
or the procollagen lysyl hydroxylase(PLOD)
Osteogenesis Imperfecta
COl genes (type I collagen)
132
Osteogenesis imperfects
Blue sclera
Broken bones
Bisphosphonates
COL gene (collagen type I)
133
Marfans vs Ehlers-Danlos
Marfans:
tall
arachnodactyly
anterior thoracic deformity
spinal curvature
sking & ocular involvement
aortopathy & MVP common
Echo at the time of diagnosis & at 6 months, then yearly if stable
Threshold is 5.0 usually
E-D:
joint hypermobility
stretchy skin
atrophic scars
velvety skin
"periodic" echo to assess root size
134
IgG-4 related disease
abundant IgG4-producing plasma cells
Almost any organ can be involved; lymph nodes are frequently affected
Diagnosis is made by tissue biopsy and the demonstration of a characteristic histology
(lymphs & plasmas with IgG-4 and no neutrophils/granulomas)
\*\*\* Serum levels are not always elevated!!! \*\*\*\*
Treatment = steroids
