Step Up - Connective Tissue and Joint Diseases Flashcards
1
Q
SLE types:
A
- Spontaneous SLE
- Discoid lupus - skin lesions WITHOUT systemic disease.
- Drug-induced lupus.
- ANA(-) lupus.
2
Q
ANA(-) lupus - Associated findings:
A
- Arthritis, Raynaud’s phenomenon, subacute cutaneous lupus.
- Serology - Anti-SS-A(+), ANA(-).
- Risk of NEONATAL lupus in infants of affected women.
3
Q
Neonatal lupus - Clinical findings:
A
- Skin lesions
- Cardiac abnormalities - AV block, transposition of the great vessels.
- Valvular and septal defects.
4
Q
Cutaneous clinical features - SLE:
A
- Butterfly rash (30%).
- Photosensitivity
- Discoid lesions.
- Oral/Nasopharyngeal ulcers
- Alopecia
- Raynaud’s (20%).
5
Q
Musculoskeletal clinical features - SLE:
A
- Joint pain (90%).
- Arthritis (inflammatory and symmetric, NOT EROSIVE as in RA).
- Arthralgia/myalgia with or without myositis.
6
Q
Cardiac clinical features of SLE:
A
- Pericarditis
- Endocarditis (Libman-Sacks is a serious complication).
- Myocarditis
7
Q
Pulmonary clinical features of SLE:
A
- Pleuritis (MC pulmonary finding).
- Pleural effusion.
- Pneumonitis (may lead to fibrosis).
- Pulmonary HTN (rare).
8
Q
Hematologic clinical features of SLE:
A
- Hemolytic anemia with anemia or reticulocytosis of chronic disease.
- Leukopenia
- Lymphopenia
- Thrombocytopenia
9
Q
Renal clinical features of SLE:
A
- Proteinuria >0.5g/day (may have nephrotic syndrome).
- Cellular casts.
- GN (may have hematuria).
- Azotemia
- Pyuria
- Uremia
- HTN
10
Q
Immunologic clinical features of SLE:
A
- Impaired immune response due to many factors, including autoantibodies to lymphocytes.
- Abnormal T cell function.
- Immunosuppressive medications.
11
Q
GI clinical features of SLE:
A
- Nausea/vomiting
- Dyspepsia
- Dysphagia
- PUD
12
Q
CNS features of SLE:
A
- Seizures
- Psychosis (may be subtle)
- Depression
- Headaches
- TIA
- CVA
13
Q
Other findings in SLE:
A
- Conjunctivitis
- Incr. incidence of Raynaud’s and
- Sjögren
14
Q
MC initial findings in SLE:
A
- Malar rash
- Joint pain
- Fatigue
15
Q
Conditions in which ANAs are elevated:
A
- SLE
- RA
- Scleroderma
- Sjögren
- Mixed connective tissue disease
- Polymyositis and dermatomyositis
- Drug-induced lupus
16
Q
Antibodies in SLE:
A
- Anti-ds DNA (40%).
- Anti-Sm (30%).
- Anti-ss DNA (70%).
- Anti-histone (70%) are present in 100% of cases of drug-induced lupus.
- Ro (SS-A) and La (SS-B) are found in 15-35%.
17
Q
SS-A (Ro) and SS-B (La) are associated with:
A
- Sjögren
- Subacute cutaneous SLE
- Neonatal lupus (with congenital heart block).
- Complement def (C2, C4).
- ANA(-) lupus.
18
Q
ANAs - Highly sensitive for:
A
SLE
19
Q
RF - Conditions:
A
- RA (70%).
2. Healthy population up to 3%.
20
Q
c-ANCA?
A
Wegener - Sensitive + Specific, can vary with disease activity.
21
Q
p-ANCA?
A
Polyarteritis nodosa - 70-80% sensitive for microscopic PAN, NOT specific.
22
Q
Lupus anticoagulant?
A
Antiphospholipid syndrome
23
Q
If CRP is >15?
A
Bacterial infection is likely present.
24
Q
Positive LE preparation:
A
ANAs bind to nuclei of damages cells, producing LE bodies.
25
False(+) for syphilis - usually in?
SLE
26
Complement levels in SLE:
Usually decreased.
27
Best long-term therapy for SLE:
Antimalarial agents such as hydroxychloroquine - for constitutional, cutaneous, and articular manifestations.
28
Cyclophosphamide for SLE:
For ACTIVE glomerulonephritis.
29
What should be monitored properly in SLE?
1. Renal disease, which produces the most significant morbidity.
2. HTN.
30
Best treatment for SLE patients with acute flare?
Steroids.
31
SLE - HLA associations:
1. HLA-DR2
| 2. HLA-DR3
32
Sjögren - HLA associations:
HLA-DR3
33
RA - HLA associations:
HLA-DR4
34
HLA-B27 associations:
1. Ankylosing spondylitis
2. Reiter
3. Psoriatic arthritis
35
SLE prognosis:
1. Most patients do NOT achieve normal life expectancy.
2. With proper treatment severe organ damage can be prevented and symptoms controlled in many cases.
3. MCCs of death are opportunistic infections and renal failure.
36
Scleroderma - Pathophysiology:
Cytokines stimulate fibroblasts, causing an abnormal amount of collagen deposition.
It is the HIGH AMOUNT of collagen that causes the problems associated with this disease (composition of the collagen is normal).
37
Drug-induced lupus - which systems do not have problem?
1. CNS
| 2. Kidneys
38
Commonly implicated drugs that cause lupus?
1. Hydralazine
2. Procainamide
3. Isoniazid
4. Chlorpromazine
5. Methyldopa
6. Quinidine
39
Drug-induced lupus - Antibodies:
1. Anti-histone Ab are always present.
| 2. ABSENT anti-ds DNA and anti-Sm.
40
Lupus GN - Types:
```
MC finding (usually present at diagnosis).
Type I (5%) - Minimal lesions - renal failure is very rare.
Type II (20%) - Mesangial lupus GN - renal failure is rare.
Type III (25%) - Focal proliferative GN - renal failure is uncommon.
Type IV (40%) - Diffuse proliferative GN - renal failure is common.
Type V (10%) - Membranous GN - renal failure is uncommon.
```
41
Scleroderma - Target group:
Women - 35-50.
42
Types of scleroderma?
1. Diffuse (20%).
| 2. Limited (80%).
43
MC symptoms in scleroderma?
Raynaud's - usually appears before other findings.
44
Scleroderma - Cutaneous fibrosis:
1. Tightening of skin of the face and extremities - sclerodactyly refers to a claw-like appearance of the hand.
2. Can lead to contractures, disability, and disfigurement.
45
Scleroderma - GI involvement:
1. Occurs in most patients - both diffuse and limited.
2. Dysphagia/reflux (90%).
3. Delayed gastric emptying.
4. Constipation/Diarrhea.
5. Abdominal distention.
6. Pseudo-obstruction.
7. Prolonged reflux may lead to esophageal strictures.
46
Scleroderma - main difference between diffuse/limited?
Only diffuse has renal, lung, and heart involvement.
47
Scleroderma - MCC of death:
Pulmonary involvement - Interstitial fibrosis and/or pulm. HTN may be present.
48
Scleroderma - Cardiac involvement:
1. Pericardial effusions.
| 2. Myocardial involvement, that can lead to CHF, arrythmias.
49
Scleroderma - Renal involvement:
1. Renal crisis - rapid malignant HTN.
| 2. Occurs in patients with diffuse scleroderma - rare today.
50
Scleroderma - What predicts prognosis?
Degree of skin involvement. Diffuse scleroderma has a worse prognosis than limited scleroderma.
51
DDx of Raynaud's:
1. Primary - no other disorder exists.
2. Scleroderma
3. SLE
4. Mixed connective tissue disease.
5. Vasculitis (Buerger's disease).
6. Certain medications (beta-blockers, nicotine, bleomycin).
7. Disorders that disrupt blood flow or vessels, such as thromboangiitis obliterans.
52
Antiphospholipid antibody syndrome:
Hypercoagulable state that can be idiopathic or associated with SLE or other collagen vascular diseases such as scleroderma.
53
Antiphospholipid antibody syndrome - Typical findings:
1. Recurrent venous thrombosis - PE is a risk.
2. Recurrent arterial thrombosis.
3. Recurrent fetal loss (abortions).
4. Thrombocytopenia.
5. Livedo reticularis.
54
Antiphospholipid antibody syndrome - Lab:
1. Lupus anticoagulant
2. Anticardiolipin antibody
3. Prolonged PTT or PT is NOT corrected by adding normal plasma.
55
Antiphospholipid antibody syndrome - Treatment:
Long-term anticoagulation (INR 2.5-3.5).
56
Diffuse vs Limited scleroderma - Onset?
Diffuse --> Rapid onset - skin + other complications occur rapidly after onset of Raynaud's.
Limited --> Delayed onset - skin involvement occurs slowly after the onset of Raynaud's. Therefore the patient has a long history of Raynaud's before other symptoms begin.
57
Diffuse vs Limited scleroderma - Antibodies:
Diffuse --> Associated with ANAs but ABSENCE of anticentromere antibodies.
Limited --> Anticentromere antibody is found in most patients.
58
Diffuse vs limited scleroderma - Prognosis:
Diffuse --> Poorer prognosis - 10yr is 40-65%.
| Limited --> Better prognosis - Normal lifespan is expected in most cases, unless severe pulmonary HTN develops.
59
CREST syndrome:
```
Variant of limited scleroderma:
C --> Calcinosis of the digits.
R --> Raynaud's.
E --> Esophageal dysmotility.
S --> Sclerodactyly.
T --> Telangiectases - over the digits and under the nails.
```
60
Antibody for the diffuse scleroderma:
Antitopoisomerase I (antiscleroderma-70) Ab is very specific for the diffuse form.
61
Treatment of scleroderma:
1. No effective cure.
2. Treat symptoms --> NSAIDs for musculoskeletal pains, H2 blockers or PPIs for reflux.
3. Raynaud's --> Avoid cold and smoking - If severe, use CCBs.
4. Treat pulmonary and renal complications if present.
62
Is Sjögren a multiorgan disease?
YES:
1. Skin
2. Lung
3. Thyroid
4. Vessels
5. Liver
63
Percentage of scleroderma patients that also have Sjögren:
20%.
64
In patients with Sjögren search for occult?
Occult lymphoma - look for lymphadenopathy and HSM.
65
Primary vs Secondary Sjögren:
Primary is Sjögren alone.
| Secondary is Sjögren + RA/SS/SLE/Polymyositis.
66
Sjögren - MCC of death:
Patients have incr. risk for NHL. Malignancy is the MCC of death.
67
Sjögren - Extraglandular features:
More common in primary disease:
1. Chronic arthritis
2. Interstitial nephritis
3. Vasculitis
68
Diagnosis of Sjögren - Antibodies:
1. ANAs (95%).
2. RF (50-75%) - SECONDARY disease.
3. Ro (SS-A) in 55%.
4. La (SS-B) in 40%.
69
Diagnosis of Sjögren - Schirmer test:
Filter paper inserted in eye to measure lacrimal gland output - degree of wetting in a specified time period - HIGH sensitivity + specificity.
70
Diagnosis of Sjögren - Salivary gland biopsy?
Lip or parotid - MOST accurate, BUT NOT needed for diagnosis.
71
Treatment of Sjögren:
1. Pilocarpine or Cevimeline - enhance oral and ocular secretions.
2. Artificial tears for dry eyes.
3. Good oral hygiene.
4. NSAIDs, steroids for arthralgias , arthritis.
5. Secondary Sjögren --> Therapy for the connective tissue disease.
72
Patients with antibodies to Ro (SS-A) are at incr. risk of having a child with...?
Neonatal SLE - Congenital heart block.
73
Mixed connective tissue disease:
Overlap syndrome:
| Features similar to those of SLE, RA, SS, Polymyositis.
74
Mixed connective tissue disease - Features:
1. Pulmonary involvement
2. Esophageal dysfunction
3. Polyarthritis
4. Sclerodactyly
5. Cutaneous manifestations
6. Myopathy
7. Raynaud's
75
Key lab in mixed connective tissue disease?
Anti-U1-RNP antibody.
| High ANA + RF may be present.
76
What is RA?
Chronic inflammatory autoimmune disease INVOLVING THE SYNOVIUM OF JOINTS.
The inflamed synovium can cause damage to cartilage and bone.
77
RA target group:
20-40 WOMEN 3:1.
78
RA etiology:
Uncertain --> By an infection or a series of infections (most likely viral), but genetic predisposition is essential.
79
RA is unlikely if:
1. Joint distribution is NOT symmetric.
2. DIP is involved.
3. Constitutional symptoms (esp. morning stiffness) are absent.
80
Why is early treatment with DMARDs critical in RA?
Much of the joint damage that ultimately leads to disability occurs early in the course of the disease.
81
Clinical course of RA - 4 CLASSES:
10% --> Acute attack, which subsides, and never attacks again.
20% --> Undulating course - exacerbations and remissions.
65% --> Periods of exacerbations and "remissions" - "remissions" are really improvements - patients ALWAYS symptomatic to some extent.
5% --> Severe, progressive course.
82
RA - Cutaneous manifestations:
1. Skin becomes thin and atrophic - bruises easily.
2. Vasculitic changes/ulcerations involving fingers, nail folds.
3. Subcutaneous rheumatoid nodules (elbows, sacrum, occiput) --> Pathognomonic for RA.
83
RA - Pulmonary symptoms:
1. Pleural effusions - very common. Pleural fluid characteristically has very LOW GLUCOSE + LOW complement.
2. Pulm. fibrosis.
3. Pulm. infiltrates.
4. Rheumatic nodules in lungs (similar to those on skin) - can cavitate or become infected.
84
RA - Cardiac symptoms:
1. Rheumatic nodules - can lead to conduction disturbances (heart block and BBB).
2. Pericarditis - in 40% of patients with RA.
3. Pericardial effusion.
85
RA - Eyes symptoms:
1. Scleritis
2. Scleromalacia - may perforate, leading to blindness.
3. Dry eyes (and dry mucous membranes in general) --> May develop Sjögren.
86
RA - Nervous system symptoms:
1. Mononeuritic complex - infarction of nerve trunk.
| 2. Patient cannot move the arm or leg - implies systemic vasculitis, which is a bad sign.
87
Felty's syndrome - Features:
1. Triad of RA + Neutropenia + Splenomegaly.
2. Also anemia, thrombocytopenia, lymphadenopathy.
3. High RF + Extra-articular disease.
4. Incr. susceptibility to infection.
5. Usually occurs fairly LATE in the disease process.
88
RA - Blood:
1. Anemia of chronic disease - mild, normocytic, normochromic.
2. Thrombocytosis.
89
RA - Vasculitis symptoms:
1. Microvascular vasculitis - can progress to mesenteric vasculitis, PAN, or other vascular syndromes.
90
RA - Cervical spine involvement:
Is common --> C1-C2 subluxation and instability, but is less common in the lower cervical spine.
--> Potentially, life-threatening complication of RA.
91
Percentage of RA patients with cervical spine involvement:
30-40%.
92
What has dramatically reduced the need for cervical spine surgery in RA patients?
DMARDs.
93
Poor prognostic indicators in RA:
1. High RF
2. Subcutaneous nodules
3. Erosive arthritis
4. Autoantibodies to RF.
94
Subcutaneous rheumatoid nodules - where to find?
1. Over extensor surfaces, may also occur in visceral structures, eg. lungs, pleura, pericardium.
2. Pathognomonic for RA.
3. Nearly ALWAYS in seropositive patients - RF(+).
95
Is RF useful for following the RA patients?
NO - Does not change with disease activity.
| Helpful ONLY in determining PROGNOSIS.
96
ACPA in RA diagnosis?
Sensitivity is 50% to 75%, specificity over 90%.
97
Diagnosis of RA - Criteria:
1. Inflammatory arthritis of 3 or more joints - MCP, PIP, wrist, elbow, knee, ankle, MIP.
2. Symptoms lasting at LEAST 6 WEEKS.
3. UP CRP, ESR.
4. RF(+) or ACPA(+).
5. Radiographic changes consistent with RA - Erosions and periarticular decalcification.
98
Does synovial fluid analysis help in RA?
NON specific.
99
Juvenile RA:
1. Begins before 18yrs of age.
2. Extra-articular manifestations may predominate - Still's disease.
3. Or arthritis may predominate.
100
First line agents for RA:
Methotrexate - best initial DMARD.
101
Methotrexate in RA - When do we see improvement?
In 4-6 weeks. Nearly 80% of treated patients will experience moderate-to-excellent symptomatic benefit from treatment - remission is RARE.
102
Methotrexate - Side effects:
1. GI upset.
2. Oral ulcers (stomatitis)
3. Mild alopecia
4. Bone marrow suppression
5. Hepatocellular injury.
6. Idiosyncratic interstitial pneumonitis --> Pulm. fibrosis.
103
In RA patients treated with methotrexate, what should be closely monitored?
Liver and renal function.
104
What should supplement RA treatment with methotrexate?
Folate.
105
Alternative to methotrexate treatment in RA?
Leflunomide - same efficacy as methotrexate.
106
Alternative first line agent, but not so effective as methotrexate?
Hydroxychloroquine
107
Hydroxychloroquine therapy in RA requires what control?
Eye examination every 6 months because of the risk of visual loss due to retinopathy - although quite rare.
108
When do we use anti-TNF agents (etanercept, infliximab)?
If methotrexate does not fully control the disease.
109
What is gout?
Inflammatory monoarthritis caused by crystallization of monosodium urate in joints.
110
Hallmark of gout:
Hyperuricemia
111
Gout - Target group:
Men over 30 (90%). Women NOT affected until after menopause.
112
Pathogenesis of gout:
1. Incr. production of urate.
| 2. Decr. excretion of urate (90% of cases).
113
Incr. production of urate - etiology:
1. Hypoxanthine-guanine phosphoribosyltransferase deficiency - Lesch-Nyhan syndrome.
2. Phosphoribosyl pyrophosphate synthetase overactivity.
3. Incr. cell turnover.
114
Decr. excretion of urate - etiology:
1. Renal disease
2. NSAIDs
3. Diuretics
4. Acidosis
115
Inflammatory cells in gout?
PMNs play a key role --> IgGs coat monosodium urate crystals, which are phagocytized by PMNs --> release of inflammatory mediators + proteolytic enzymes from the PMNs --> Inflammation.
116
Gout - Common sites of involvement:
1. 1st MTP.
2. Midfoot
3. Ankle
4. Knee
117
4 stages of gout:
1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
3. Intercritical gout
4. Chronic tophaceous gout
118
Asymptomatic hyperuricemia - Features:
1. Incr. serum urate in the absence of clinical findings of gout, may be present without symptoms for 10-20yrs.
2. Should NOT be treated because OVER 95% remain asymptomatic.
119
Acute gouty arthritis - Peak age?
Onset is 40-60 yrs of age for men.
120
Acute gouty arthritis - initial attack?
Usually involves one joint of the lower extremity.
1. Sudden onset of exquisite pain - the patient may be unable to tolerate a bed sheet on affected joint. Pain often WAKES PATIENT FROM SLEEP.
2. Most often affects the big toe - the 1st metatarsophalangeal joint (podagra). Other common joints affected are the ankles and knees.
121
What is the intercritical gout?
Asymptomatic period after the initial attack. The patient may not have another attack for years.
122
Intercritical gout - Percentage of recurrence within 1 yr?
60%. Fewer than 10% NEVER have another attack of gout.
123
Percentage of likelihood of a 2nd attack within the first 2 years?
75%.
124
Chronic tophaceous gout - When?
In people who have had poorly controlled gout for more than 10-20yrs.
125
Tophi:
1. Aggregations of urate crystals surrounded by giant cells in an inflammatory reaction.
2. Seen only after several attacks of acute gout.
3. Noted after an average of 10yrs following the initial attack.
126
Common locations of tophi:
1. Extensor surface of forearms
2. Elbows
3. Knees
4. Achilles tendon
5. Pinna of the external ear
127
Precipitants of an acute gouty attack:
1. Decr. in temperature.
2. Dehydration.
3. Stress (emotional or physical).
4. Excessive alcohol intake.
5. Starvation
128
If untreated, how long does an acute gouty attack last?
7 to 10 days and then resolves.
| Severe episodes may last longer.
129
Gout - Only way to make definitive diagnosis:
Joint aspiration and synovial fluid analysis (under a polarizing microscope) is the only way to make a definitive diagnosis.
130
Gout crystals:
Needle-shaped and NEGATIVELY birefringent urate crystals appear in synovial fluid.
131
Gout diagnosis - Is serum urate helpful?
Not helpful in diagnosis because it can be normal even during an acute gouty attack.
132
Gout diagnosis - Radiographs:
Reveal punched-out erosions with an overhanging rim of cortical bone.
133
Gout diagnosis - Why should a gram stain and a culture of the synovial fluid be done?
To rule out septic arthritis - which is the most worrisome diagnosis on the differential list.
134
Complications of gout:
1. Nephrolithiasis - risk is small (<15% of patients.
135
Treatment of gout:
In ALL stages, avoid secondary causes of hyperuricemia.
136
How to avoid secondary causes of hyperuricemia:
1. Avoid medications that incr. urate levels (thiazides, loops).
2. Obesity
3. Reduce alcohol.
4. Reduce dietary purine intake. Limit intake of seafood/red meat.
137
Treatment of acute gout:
1. Bed rest is important.
2. NSAIDs.
3. Colchicine.
4. Corticosteroids.
138
What should be avoided in acute gout?
1. Aspirin - can aggravate the problem.
| 2. Acetaminophen - has no anti-inflammatory properties.
139
Acute gout - Treatment of choice:
NSAIDs - Indomethacin is usually used, but other NSAIDs are effective.
140
Problems with colchicine:
Effective but less favored because 80% of treated --> significant nausea/vomiting, abdominal cramps, and severe diarrhea.
Compliance tends to be low due to these side effects.
141
Colchicine - where is it contraindicated?
In renal insufficiency and cytopenia.
142
When do we give corticosteroids in acute gout?
```
Oral prednisone (7-10d course) if patient does NOT respond to or cannot tolerate NSAIDs and colchicine.
--> Intra-articular corticosteroid injections (if only one joint is involved) - dramatic relief of symptoms.
```
143
Pseudogout:
Calcium PYROPHOSPHATE crystals deposit in joints --> inflammation.
144
Pseudogout - Risk factors:
1. Deposition increases with age + with OA of the joints --> Common in elderly.
2. Other conditions that may increase crystal deposition --> Hemochromatosis/Hyperparathyroidism/Hypothyroidism/Bartter's syndrome.
145
Pseudogout - MC joints affected:
1. Knees
| 2. Wrists
146
Pseudogout - presentation:
1. Classically monoarticular, but can also be polyarticular as well.
2. Presentation similar to gout, but typically occurs in larger joints (knee).
147
Pseudogout - Diagnosis:
Joint aspirate is required for definitive diagnosis - weakly positively birefringent, rod-shaped and rhomboidal crystals in synovial fluid (calcium pyrophosphate crystals).
148
Pseudogout - Radiographs:
Chondrocalcinosis - cartilage calcification.
149
Pseudogout - Treatment:
1. Treat the underlying disorder (if identified).
2. Symptomatic management like gout (NSAIDs, colchicine, intra-articular steroid injections).
3. Total joint replacement is appropriate if symptoms are debilitating.
150
Difference between polymyositis and dermatomyositis:
Polymyositis - term is used when the condition does not involve the skin (usually occurs in adults).
Dermatomyositis - Polymyositis associated with a characteristic skin rash.
151
Idiopathic inflammatory myopathies - Classification:
1. Polymyositis
2. Dermatomyositis
3. Childhood onset dermatomyositis - subcutaneous calcifications.
4. Myositis associated with collagen vascular disease.
5. Myositis associated with malignancy.
6. Inclusion body myositis
152
Inclusion body myositis - "Oddball" because?
1. Affects male patients more than female.
2. Absence of autoantibodies.
3. Distal muscle involvement.
4. Relatively low CK.
153
Inclusion body myositis - Prognosis:
Poor.
154
Diagnostic criteria in polymyositis:
1. Symmetrical proximal muscle involvement.
2. Elevation in serum CPK.
3. EMG findings of a myopathy.
4. Biopsy evidence of myositis.
5. Characteristic rash of dermatomyositis.
155
Idiopathic inflammatory myopathies - Etiology:
Hypothesis --> Genetically susceptible individual plus an environmental trigger leads to immune activation, which results in chronic inflammation.
156
Pathologic changes in muscle - Polymyositis/Dermatomyositis:
Dermatomyositis --> Humoral immune mechanisms.
| Polymyositis + inclusion body myositis --> Cell mediated process.
157
Features common to both polymyositis and dermatomyositis:
1. Symmetrical proximal muscle weakness that develops subacutely over weeks or several months.
2. Myalgia in 33%.
3. Dysphagia in up to 30% - esophageal muscles.
158
Features unique to dermatomyositis:
1. Heliotrope rash (butterfly).
2. Gottron's papules --> over the knuckles (MCP, PIP, DIP).
3. V sign - rash on the face, neck, and anterior chest.
4. Shawl sign - rash on shoulders, upper back, elbows, and knees.
5. Periungual erythema and telangiectases.
6. Subcutaneous calcifications in children - can be extremely painful.
159
Associated findings in BOTH polymyositis and dermatomyositis:
1. Arthralgias (common).
2. CHF and conduction defects (rare).
3. Interstitial lung disease (in minority of patients).
160
Associated findings in dermatomyositis ONLY:
1. Vasculitis of the GI, kidneys, lungs, eyes (more common in children).
2. Incr. incidence of malignancy in older adults (lung, breast, ovary, GI, myeloproliferative disorders).
3. Make an effort to uncover OCCULT MALIGNANCY. Dermatomyositis associated with malignancy often remits once the tumor is removed!!!
161
Idiopathic inflammatory myopathies - Diagnosis - Lab CK:
Significantly elevated - corresponds to the degree of muscle necrosis, so one can monitor the disease severity.
162
Idiopathic inflammatory myopathies - Other lab results:
Elevated:
| LDH, aldolase, AST, ALT.
163
Idiopathic inflammatory myopathies - ANA:
In over 50%.
164
Idiopathic inflammatory myopathies - Antibodies:
Antisynthetase antibodies (anti-Jo-1 antibodies) - abrupt onset of fever, cracked hands, Raynaud's, interstitial lung disease, arthritis - does NOT respond well to therapy.
165
Idiopathic inflammatory myopathies - Antisignal recognition particle:
1. Cardiac manifestations (common).
| 2. Worst prognosis of ALL subsets.
166
Idiopathic inflammatory myopathies - Anti-Mi-2 antibodies:
Better prognosis.
167
Idiopathic inflammatory myopathies - EMG:
Abnormal in 90% of patients.
168
Idiopathic inflammatory myopathies - Muscle biopsy:
1. Shows inflammation and muscle fiber fibrosis in ALL THREE.
2. Dermatomyositis - Perivascular + Perimysial.
3. Polymyositis + Inclusion body myositis - Endomysial.
169
Idiopathic inflammatory myopathies - Treatment:
1. Corticosteroids - initial treatment.
2. Immunosuppression - methotrexate, cyclophosphamide, chlorambucil.
3. Physical therapy.
170
Important point about corticosteroids in idiopathic inflammatory myopathies treatment:
Continue until symptoms improve, and then taper very slowly (up to 2 years may be necessary).
171
Inclusion body myositis - more common in men or women?
Men (eldelry).
172
Why is diagnosis of inclusion body myositis often delayed?
Insidious onset of slowly progressive proximal + distal weakness, often leads to delay in diagnosis.
173
Inclusion body myositis - Early weakness + atrophy of?
1. Quadriceps
2. Forearm flexors
3. Tibialis anterior muscles.
ASYMMETRICAL INVOLVEMENT.
174
Inclusion body myositis - Deep tendon reflexes:
Loss of deep tendon reflexes - Nerves are NOT involved in polymyositis and dermatomyositis.
175
Lab in inclusion body myositis:
Slight elevation of CK (relatively low).
176
Inclusion body myositis - response to therapy:
Poor response to therapy.
177
Polymyalgia rheumatica - Target:
Usually in elderly patients (rare before 50). Mean age of onset is 70.
More common in WOMEN.
178
Polymyalgia rheumatica - Etiology:
Unknown - autoimmune may be responsible - Possible link with HLA-DR4.
179
Polymyalgia rheumatica - Course:
Self-limited disease - duration of 1-2yrs.
180
Relationship of polymyalgia rheumatica with temporal arteritis:
About 10% of PR develop temporal arteritis.
| Whereas up to 40-50% of TA have co-existing polymyalgia rheumatica.
181
Polymyalgia rheumatica - Clinical features:
1. Hip and shoulder muscle pain - BILATERAL.
2. Constitutional symptoms.
3. Joint swelling.
4. Signs and symptoms of temporal arteritis.
182
Polymyalgia rheumatica - Diagnosis:
1. A clinical diagnosis.
2. ESR is usually elevated and aids in diagnosis. Almost always >50, frequently >100 --> Correlates with disease activity.
183
Polymyalgia rheumatica - treatment:
Corticosteroids
184
PR - response to corticosteroids:
Usually within 1-7days. Not curative, but are effective in suppressing inflammation until the disease resolves itself.
185
PR - Corticosteroids - when to begin to taper slowly?
After 4-6wks.
186
Fibromyalgia - Target:
Adult women account for 80-90% of cases.
187
Fibromyalgia - Course:
Chronic NON progressive course with waxing and waning in severity - many patients improve with time.
188
Fibromyalgia - Key to diagnosis:
Multiple trigger points - points that are tender to palpation.
Symmetrical.
18 characteristic locations have been identified - occiput, neck, shoulder, ribs, elbows, buttocks, and knees.
189
Fibromyalgia - Etiology:
Unknown - somatization is not a proven cause.
190
Fibromyalgia - Clinical features:
1. Stiffness, body aches (musculoskeletal), fatigue.
2. Pain is constant, worse in the morning.
3. Rest, warmth, and mild exercise improve the pain.
4. Sleep patterns are disrupted, and sleep is unrefreshing.
5. Anxiety and depression are common.
191
Fibromyalgia - Diagnostic criteria:
1. Widespread pain including axial pain for at least 3 months.
2. Pain in at least 11/18 possible tender point sites.
192
Fibromyalgia - Before confirming the diagnosis, what should be ruled out first?
1. Myofascial syndromes.
2. Rheumatoid disease.
3. Polymyalgia rheumatica.
4. Ankylosing spondylitis.
5. Spondyloarthropathy.
6. Chronic fatigue syndrome.
7. Lyme.
8. Hypothyroidism.
9. Polymyositis.
10. Depression.
11. Somatization disorder.
12. Hypertrophic osteoarthropathy.
193
Fibromyalgia - Treatment:
1. Advise patient to stay active and productive.
2. Medications are generally NOT effective.
3. SSRIs and TCAs have shown some effect and may be beneficial. Avoid narcotics.
4. Cognitive-behavioral therapy, exercise, consider psychiatric evaluation.
194
Ankylosing spondylitis - More common in men or women?
3x more common in MEN.
195
Ankylosing spondylitis - Look for history of:
1. Ank. Spondylitis
2. IBD
3. Psoriasis
196
Ank. Spondylitis - Prerequisite for making the diagnosis:
Bilateral sacroiliitis.
197
Ank. spondylitis - course:
1. Highly variable - acute exacerbations are common.
2. Life expectancy is usually normal.
3. The first 10yrs of the disease can give an indication of long term severity.
198
Low back pain and stiffness in ank. spondylitis:
Worse in the morning and better as the day progresses.
| Improve with exercise and a hot shower and worsen with rest or inactivity.
199
Enthesitis in ank. spondylitis:
Inflammation at tendinous insertions into bone (Achilles tendon and supraspinatus tendon).
200
MC extra-articular involvement:
Eye involvement - acute anterior uveitis or iridocyclitis.
201
Ank. spondylitis - Diagnosis:
1. Imaging studies of lumbar spine and pelvis (plain film, CT, MRI) --> sacroiliitis - Sclerotic changes in the sacroiliac area.
2. Eventually the vertebral columns fuse, producing "bamboo" spine.
202
Ank. spondylitis - HLA-B27 is necessary for diagnosis?
No - Present in 8% of general population.
203
Major complications of ank.spondylitis:
1. Restrictive lung disease.
2. Cauda equina syndrome.
3. Spine fracture with spinal cord injury.
4. Osteoporosis.
5. Spondylodiscitis.
204
Ank. spondylitis - Treatment:
1. NSAIDs (indomethacin) for symptomatic relief.
2. Anti-TNF (etanercept, infliximab).
3. Physical therapy - maintaining good posture.
205
Seronegative spondyloarthropathies :
1. AS
2. Reactive arthritis (and Reiter's).
3. Psoriatic arthritis.
4. Arthropathy of IBD.
5. Undifferentiated spondyloarthropathies.
206
Seronegative spondyloarthropathies have the following in common:
1. RF (-).
2. Strong association with HLA-B27.
3. Oligoarthritis (asymmetrical).
4. Enthesitis - infl. at sites of insertion of fascia, ligament, or tendon to bone.
5. Infl. arthritis - axial and sacroiliac joints.
6. Extra-auricular features - eyes, skin, GUT.
7. Familial predisposition.
207
Causes of joint pain - POLYarticular :
1. RA
2. SLE
3. Viral arthritis
4. Reiter's
5. Rheumatic fever
6. Lyme
7. Gonococcal arthritis
8. Drug-induced
208
Causes of joint pain - MONOarticular joint pain:
1. Osteoarthritis
2. Gout
3. Pseudogout
4. Trauma
5. Septic arthritis
6. Hemarthrosis
209
Reactive arthritis - General presentation:
1. Asymmetric infl. OLIGOarthritis of LOWER extremities (upper are less common).
2. Preceded by an infectious process that is remote from the site of arthritis (1-4wks prior).
3. Mostly in HLA-B27 individuals.
210
Reiter's:
An example of reactive arthritis, but most patients do NOT have the classical findings of Reiter's, so the term reactive arthritis is now used.
211
Organisms associated with reactive arthritis:
1. Salmonella
2. Shigella
3. Campylobacter
4. Chlamydia
5. Yersinia
212
Reactive arthritis is a clinical diagnosis?
YES - If any patient presents with acute asymmetric arthritis progressing sequentially from one joint to another, reactive arthritis should be in the DDX.
213
Reiter's syndrome - Classic triad:
1. Arthritis
2. Urethritis
3. Ocular inflammation (conjunctivitis or anterior uveitis).
Can't see, can't pee, can't climb a tree.
214
When do we use the term "undifferentiated spondyloarthropathy"?
When a patient has features of reactive arthritis but there is no evidence of previous infection (in the GI or GUT) + THE CLASSIC FINDINGS OF REITER'S are ABSENT.
215
Diagnosis of reactive arthritis:
Send synovial fluid for analysis - to rule out infection or crystals.
216
Reactive arthritis - Treatment:
1. NSAIDs are 1st line therapy.
2. If no response, try sulfasalazine + immunosuppressive agents such as azathioprine.
3. Antibiotic use is controversial - usually NOT given.
217
Psoriatic arthritis - target:
<10% of patients with psoriasis.
218
Psoriatic arthritis - Onset:
Typically gradual in onset - Patients usually have skin disease for months to yrs before arthritis develops.
219
Psoriatic arthritis - Sites:
Usually asymmetric and POLYarticular.
| UPPER EXTREMITIES most often involved, smaller joints more common than large joints.
220
Psoriatic arthritis - Treatment:
Initial treatment is NSAIDs, but persistent arthritis may require drugs used to treat RA.
221
Giant cell arteritis - General features:
1. Unknown cause.
| 2. >50 woman.
222
Giant cell arteritis - incr. risk for:
1. Aortic aneurysm
| 2. Aortic dissection
223
Giant cell arteritis - Clinical features:
1. Constitutional symptoms.
2. Headaches - may be severe.
3. Visual impairment (25-50%).
4. Jaw claudication.
5. Absent temporal pulse + tenderness over temporal artery.
224
40% of giant cell arteritis patients also have?
Polymyalgia rheumatica
225
Giant cell arteritis - Diagnosis:
1. ESR up.
| 2. Biopsy of the temporal artery has a sensitivity of 90%. A single negative biopsy does NOT exclude diagnosis.
226
Keys to diagnosing temporal arteritis:
1. Age >50.
2. New headache.
3. Tender/palpable temporal artery.
4. High ESR.
5. Jaw claudication.
227
If temporal arteritis is suspected, what should be done?
Begin prednisone and order a temporal artery biopsy.
228
Takayasu's arteritis - General features:
1. Young Asian women.
2. Vasculitis of the aortic arch and its major branches - potentially leading to stenosis or narrowing of vessels.
3. Diagnosed by arteriogram.
229
Takayasu's arteritis - clinical features:
1. Constitutional symptoms.
2. Pain and tenderness over involved vessels.
3. Absent pulses in carotid, radial, or ulnar arteries.
4. Signs and symptoms of ischemia.
230
Severe complications in Takayasu:
1. Limb ischemia
2. Aortic aneurysms
3. Aortic regurgitation
4. Stroke
5. Secondary HTN.
Main PROGNOSTIC predictor is the presence or absence of these complications.
231
Takayasu arteritis - Treatment:
1. Steroids may relieve symptoms.
2. Treat HTN.
3. Surgery or angioplasty may be required to recannulate stenosed vessels. Sometimes bypass grafting.
232
Suspect Takayasu in a young woman with:
1. Decr./absent peripheral pulsies.
2. Discrepancies of BP (arm vs leg).
3. Arterial bruits.
233
Churg-Strauss - General:
Vasculitis involving:
1. Respiratory
2. Heart
3. GI
4. Skin
5. Renal
6. Neurologic
234
Churg-Strauss - Clinical features:
1. Constitutional findings.
2. Prominent respiratory tract findings - asthma, dyspnea.
3. Skin lesions --> subcutaneous lesions, palpable purpura.
235
Churg-Strauss - diagnosis:
1. Made by biopsy of lung or skin tissue - prominence of EOSINOPHILS.
2. p-ANCA
236
Churg-Strauss - prognosis:
5-yr survival of 25%. With steroids --> 50%.
| Death due to cardiac/respiratory complications.
237
Wegener granulomatosis - Clinical features:
1. Upper respiratory symptoms - sinusitis, purulent or bloody nasal discharge.
2. Oral ulcers (may be painful).
3. Pulmonary symptoms - couch, hemoptysis, dyspnea.
4. Renal involvement - GN - may have rapidly progressing renal failure.
5. Eye - conjunctivitis, scleritis.
238
Wegener - Musculoskeletal:
Myalgias + arthralgias.
239
Wegener - Trachea involvement:
Tracheal stenosis.
240
Wegener - Patients die from?
Renal disease.
241
Wegener - Diagnosis:
1. Chest radiograph is ABnormal (nodules or infiltrates).
2. Anemia, hematuria.
3. c-ANCA (90% of patients).
242
Wegener - What does confirm the diagnosis?
Open lung biopsy.
243
Wegener prognosis:
Poor - most patients die within 1 yr after the diagnosis.
244
Wegener treatment:
Cyclophosphamide + corticosteroids can induce remissions in many patients, but a relapse may occur at any time.
245
Wegener with ESRD:
Consider renal transplantation.
246
Polyarteritis nodosa (PAN) - General:
Vasculitis of medium-sized vessels involving the nervous system and GIT. Spares the LUNG.
247
PAN - Associations:
1. Hep B
2. HIV
3. Drug reactions
248
PAN - Pathophysiology:
PMN invasion of all layers and fibrinoid necrosis + resulting intimal proliferation lead to reduced luminal area, which results in ischemia, infarction, and aneurysms.
249
PAN - Clinical features - Early symptoms:
1. Fever
2. Weakness
3. Weight loss
4. Myalgias/Arthralgias
5. Abdominal pain - Bowel angina.
250
PAN - Other findings:
1. HTN
2. Mononeuritic multiplex
3. Livedo reticularis
251
PAN - Diagnosis:
1. Biopsy of involved tissue or mesenteric angiography.
2. ESR up, p-ANCA may be present.
3. Test for fecal occult blood.
252
PAN - Prognosis:
Poor, but is improved to a limited extent with treatment.
253
PAN - Treatment:
Corticosteroids. If severe, add cyclophosphamide.
254
Behcet's syndrome - what is it?
Autoimmune, multisystem, vasculitic disease - unknown cause.
255
Behcet - Clinical features:
1. Recurrent oral and genital ulcerations (usually painful).
2. Arthritis - knees and ankles most common.
3. Eye involvement - Uveitis, optic neuritis, iritis, conjunctivitis.
4. CNS - Meningoencephalitis, intracranial HTN.
5. Fever and weight loss.
256
Behcet - Diagnosis:
It is made by biopsy of involved tissue (lab tests are NOT helpful).
257
Behcet - Treatment:
Steroids - which are helpful.
258
Buerger's - Target:
Young men who smoke cigarettes.
259
Buerger's disease - Pathogenesis:
Acute inflammation of small- and medium-sized arteries and veins, affecting arms and legs.
260
Buerger's - complication:
Gangrene
261
Buerger's - Clinical features:
1. Ischemic claudication.
2. Cold, cyanotic, painful distal extremities.
3. Paresthesias of distal extremities.
4. Ulcerations of digits.
262
Buerger's - Mandatory to reduce progression?
Smoking cessation.
263
Hypersensitivity vasculitis - What is it?
Small-vessel vasculitis that is a hypersensitivity reaction in response to a drug (penicillin, sulfa drugs), infection, or other stimulus.
264
Hypersensitivity vasculitis - What is predominantly involved?
Skin - palpable purpura, macules, or vesicles (common on lower extremities) can occur. Lesions can be painful.
265
Hypersen. vasculitis - Diagnosis:
By biopsy of tissue.
266
Hypersen. vasculitis - prognosis:
Very good - spontaneous remissions are common.
267
Hypersen. vasculitis - Treatment?
Withdrawal of the offending agent and steroids are the treatments of choice.
268
In general, what does the pathophysiology of SLE involve?
1. Autoantibody production.
2. Deposition of immune complexes.
3. Complement activation.
4. Accompanying tissue destruction/vasculitis.
