Step Up - Connective Tissue and Joint Diseases Flashcards
SLE types:
- Spontaneous SLE
- Discoid lupus - skin lesions WITHOUT systemic disease.
- Drug-induced lupus.
- ANA(-) lupus.
ANA(-) lupus - Associated findings:
- Arthritis, Raynaud’s phenomenon, subacute cutaneous lupus.
- Serology - Anti-SS-A(+), ANA(-).
- Risk of NEONATAL lupus in infants of affected women.
Neonatal lupus - Clinical findings:
- Skin lesions
- Cardiac abnormalities - AV block, transposition of the great vessels.
- Valvular and septal defects.
Cutaneous clinical features - SLE:
- Butterfly rash (30%).
- Photosensitivity
- Discoid lesions.
- Oral/Nasopharyngeal ulcers
- Alopecia
- Raynaud’s (20%).
Musculoskeletal clinical features - SLE:
- Joint pain (90%).
- Arthritis (inflammatory and symmetric, NOT EROSIVE as in RA).
- Arthralgia/myalgia with or without myositis.
Cardiac clinical features of SLE:
- Pericarditis
- Endocarditis (Libman-Sacks is a serious complication).
- Myocarditis
Pulmonary clinical features of SLE:
- Pleuritis (MC pulmonary finding).
- Pleural effusion.
- Pneumonitis (may lead to fibrosis).
- Pulmonary HTN (rare).
Hematologic clinical features of SLE:
- Hemolytic anemia with anemia or reticulocytosis of chronic disease.
- Leukopenia
- Lymphopenia
- Thrombocytopenia
Renal clinical features of SLE:
- Proteinuria >0.5g/day (may have nephrotic syndrome).
- Cellular casts.
- GN (may have hematuria).
- Azotemia
- Pyuria
- Uremia
- HTN
Immunologic clinical features of SLE:
- Impaired immune response due to many factors, including autoantibodies to lymphocytes.
- Abnormal T cell function.
- Immunosuppressive medications.
GI clinical features of SLE:
- Nausea/vomiting
- Dyspepsia
- Dysphagia
- PUD
CNS features of SLE:
- Seizures
- Psychosis (may be subtle)
- Depression
- Headaches
- TIA
- CVA
Other findings in SLE:
- Conjunctivitis
- Incr. incidence of Raynaud’s and
- Sjögren
MC initial findings in SLE:
- Malar rash
- Joint pain
- Fatigue
Conditions in which ANAs are elevated:
- SLE
- RA
- Scleroderma
- Sjögren
- Mixed connective tissue disease
- Polymyositis and dermatomyositis
- Drug-induced lupus
Antibodies in SLE:
- 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%.
SS-A (Ro) and SS-B (La) are associated with:
- Sjögren
- Subacute cutaneous SLE
- Neonatal lupus (with congenital heart block).
- Complement def (C2, C4).
- ANA(-) lupus.
ANAs - Highly sensitive for:
SLE
RF - Conditions:
- RA (70%).
2. Healthy population up to 3%.
c-ANCA?
Wegener - Sensitive + Specific, can vary with disease activity.
p-ANCA?
Polyarteritis nodosa - 70-80% sensitive for microscopic PAN, NOT specific.
Lupus anticoagulant?
Antiphospholipid syndrome
If CRP is >15?
Bacterial infection is likely present.
Positive LE preparation:
ANAs bind to nuclei of damages cells, producing LE bodies.
False(+) for syphilis - usually in?
SLE
Complement levels in SLE:
Usually decreased.
Best long-term therapy for SLE:
Antimalarial agents such as hydroxychloroquine - for constitutional, cutaneous, and articular manifestations.
Cyclophosphamide for SLE:
For ACTIVE glomerulonephritis.
What should be monitored properly in SLE?
- Renal disease, which produces the most significant morbidity.
- HTN.
Best treatment for SLE patients with acute flare?
Steroids.
SLE - HLA associations:
- HLA-DR2
2. HLA-DR3
Sjögren - HLA associations:
HLA-DR3
RA - HLA associations:
HLA-DR4
HLA-B27 associations:
- Ankylosing spondylitis
- Reiter
- Psoriatic arthritis
SLE prognosis:
- Most patients do NOT achieve normal life expectancy.
- With proper treatment severe organ damage can be prevented and symptoms controlled in many cases.
- MCCs of death are opportunistic infections and renal failure.
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).
Drug-induced lupus - which systems do not have problem?
- CNS
2. Kidneys
Commonly implicated drugs that cause lupus?
- Hydralazine
- Procainamide
- Isoniazid
- Chlorpromazine
- Methyldopa
- Quinidine
Drug-induced lupus - Antibodies:
- Anti-histone Ab are always present.
2. ABSENT anti-ds DNA and anti-Sm.
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.
Scleroderma - Target group:
Women - 35-50.
Types of scleroderma?
- Diffuse (20%).
2. Limited (80%).
MC symptoms in scleroderma?
Raynaud’s - usually appears before other findings.
Scleroderma - Cutaneous fibrosis:
- Tightening of skin of the face and extremities - sclerodactyly refers to a claw-like appearance of the hand.
- Can lead to contractures, disability, and disfigurement.
Scleroderma - GI involvement:
- Occurs in most patients - both diffuse and limited.
- Dysphagia/reflux (90%).
- Delayed gastric emptying.
- Constipation/Diarrhea.
- Abdominal distention.
- Pseudo-obstruction.
- Prolonged reflux may lead to esophageal strictures.
Scleroderma - main difference between diffuse/limited?
Only diffuse has renal, lung, and heart involvement.
Scleroderma - MCC of death:
Pulmonary involvement - Interstitial fibrosis and/or pulm. HTN may be present.
Scleroderma - Cardiac involvement:
- Pericardial effusions.
2. Myocardial involvement, that can lead to CHF, arrythmias.
Scleroderma - Renal involvement:
- Renal crisis - rapid malignant HTN.
2. Occurs in patients with diffuse scleroderma - rare today.
Scleroderma - What predicts prognosis?
Degree of skin involvement. Diffuse scleroderma has a worse prognosis than limited scleroderma.
DDx of Raynaud’s:
- Primary - no other disorder exists.
- Scleroderma
- SLE
- Mixed connective tissue disease.
- Vasculitis (Buerger’s disease).
- Certain medications (beta-blockers, nicotine, bleomycin).
- Disorders that disrupt blood flow or vessels, such as thromboangiitis obliterans.
Antiphospholipid antibody syndrome:
Hypercoagulable state that can be idiopathic or associated with SLE or other collagen vascular diseases such as scleroderma.
Antiphospholipid antibody syndrome - Typical findings:
- Recurrent venous thrombosis - PE is a risk.
- Recurrent arterial thrombosis.
- Recurrent fetal loss (abortions).
- Thrombocytopenia.
- Livedo reticularis.
Antiphospholipid antibody syndrome - Lab:
- Lupus anticoagulant
- Anticardiolipin antibody
- Prolonged PTT or PT is NOT corrected by adding normal plasma.
Antiphospholipid antibody syndrome - Treatment:
Long-term anticoagulation (INR 2.5-3.5).
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.
Diffuse vs Limited scleroderma - Antibodies:
Diffuse –> Associated with ANAs but ABSENCE of anticentromere antibodies.
Limited –> Anticentromere antibody is found in most patients.
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.
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.
Antibody for the diffuse scleroderma:
Antitopoisomerase I (antiscleroderma-70) Ab is very specific for the diffuse form.
Treatment of scleroderma:
- No effective cure.
- Treat symptoms –> NSAIDs for musculoskeletal pains, H2 blockers or PPIs for reflux.
- Raynaud’s –> Avoid cold and smoking - If severe, use CCBs.
- Treat pulmonary and renal complications if present.
Is Sjögren a multiorgan disease?
YES:
- Skin
- Lung
- Thyroid
- Vessels
- Liver
Percentage of scleroderma patients that also have Sjögren:
20%.
In patients with Sjögren search for occult?
Occult lymphoma - look for lymphadenopathy and HSM.
Primary vs Secondary Sjögren:
Primary is Sjögren alone.
Secondary is Sjögren + RA/SS/SLE/Polymyositis.
Sjögren - MCC of death:
Patients have incr. risk for NHL. Malignancy is the MCC of death.
Sjögren - Extraglandular features:
More common in primary disease:
- Chronic arthritis
- Interstitial nephritis
- Vasculitis
Diagnosis of Sjögren - Antibodies:
- ANAs (95%).
- RF (50-75%) - SECONDARY disease.
- Ro (SS-A) in 55%.
- La (SS-B) in 40%.
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.
Diagnosis of Sjögren - Salivary gland biopsy?
Lip or parotid - MOST accurate, BUT NOT needed for diagnosis.
Treatment of Sjögren:
- Pilocarpine or Cevimeline - enhance oral and ocular secretions.
- Artificial tears for dry eyes.
- Good oral hygiene.
- NSAIDs, steroids for arthralgias , arthritis.
- Secondary Sjögren –> Therapy for the connective tissue disease.
Patients with antibodies to Ro (SS-A) are at incr. risk of having a child with…?
Neonatal SLE - Congenital heart block.
Mixed connective tissue disease:
Overlap syndrome:
Features similar to those of SLE, RA, SS, Polymyositis.
Mixed connective tissue disease - Features:
- Pulmonary involvement
- Esophageal dysfunction
- Polyarthritis
- Sclerodactyly
- Cutaneous manifestations
- Myopathy
- Raynaud’s
Key lab in mixed connective tissue disease?
Anti-U1-RNP antibody.
High ANA + RF may be present.
What is RA?
Chronic inflammatory autoimmune disease INVOLVING THE SYNOVIUM OF JOINTS.
The inflamed synovium can cause damage to cartilage and bone.
RA target group:
20-40 WOMEN 3:1.
RA etiology:
Uncertain –> By an infection or a series of infections (most likely viral), but genetic predisposition is essential.
RA is unlikely if:
- Joint distribution is NOT symmetric.
- DIP is involved.
- Constitutional symptoms (esp. morning stiffness) are absent.
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.
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.
RA - Cutaneous manifestations:
- Skin becomes thin and atrophic - bruises easily.
- Vasculitic changes/ulcerations involving fingers, nail folds.
- Subcutaneous rheumatoid nodules (elbows, sacrum, occiput) –> Pathognomonic for RA.
RA - Pulmonary symptoms:
- Pleural effusions - very common. Pleural fluid characteristically has very LOW GLUCOSE + LOW complement.
- Pulm. fibrosis.
- Pulm. infiltrates.
- Rheumatic nodules in lungs (similar to those on skin) - can cavitate or become infected.
RA - Cardiac symptoms:
- Rheumatic nodules - can lead to conduction disturbances (heart block and BBB).
- Pericarditis - in 40% of patients with RA.
- Pericardial effusion.
RA - Eyes symptoms:
- Scleritis
- Scleromalacia - may perforate, leading to blindness.
- Dry eyes (and dry mucous membranes in general) –> May develop Sjögren.
RA - Nervous system symptoms:
- Mononeuritic complex - infarction of nerve trunk.
2. Patient cannot move the arm or leg - implies systemic vasculitis, which is a bad sign.
Felty’s syndrome - Features:
- Triad of RA + Neutropenia + Splenomegaly.
- Also anemia, thrombocytopenia, lymphadenopathy.
- High RF + Extra-articular disease.
- Incr. susceptibility to infection.
- Usually occurs fairly LATE in the disease process.
RA - Blood:
- Anemia of chronic disease - mild, normocytic, normochromic.
- Thrombocytosis.
RA - Vasculitis symptoms:
- Microvascular vasculitis - can progress to mesenteric vasculitis, PAN, or other vascular syndromes.
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.
Percentage of RA patients with cervical spine involvement:
30-40%.
What has dramatically reduced the need for cervical spine surgery in RA patients?
DMARDs.
Poor prognostic indicators in RA:
- High RF
- Subcutaneous nodules
- Erosive arthritis
- Autoantibodies to RF.
Subcutaneous rheumatoid nodules - where to find?
- Over extensor surfaces, may also occur in visceral structures, eg. lungs, pleura, pericardium.
- Pathognomonic for RA.
- Nearly ALWAYS in seropositive patients - RF(+).
Is RF useful for following the RA patients?
NO - Does not change with disease activity.
Helpful ONLY in determining PROGNOSIS.
ACPA in RA diagnosis?
Sensitivity is 50% to 75%, specificity over 90%.
Diagnosis of RA - Criteria:
- Inflammatory arthritis of 3 or more joints - MCP, PIP, wrist, elbow, knee, ankle, MIP.
- Symptoms lasting at LEAST 6 WEEKS.
- UP CRP, ESR.
- RF(+) or ACPA(+).
- Radiographic changes consistent with RA - Erosions and periarticular decalcification.
Does synovial fluid analysis help in RA?
NON specific.
Juvenile RA:
- Begins before 18yrs of age.
- Extra-articular manifestations may predominate - Still’s disease.
- Or arthritis may predominate.
First line agents for RA:
Methotrexate - best initial DMARD.
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.
Methotrexate - Side effects:
- GI upset.
- Oral ulcers (stomatitis)
- Mild alopecia
- Bone marrow suppression
- Hepatocellular injury.
- Idiosyncratic interstitial pneumonitis –> Pulm. fibrosis.
In RA patients treated with methotrexate, what should be closely monitored?
Liver and renal function.
What should supplement RA treatment with methotrexate?
Folate.
Alternative to methotrexate treatment in RA?
Leflunomide - same efficacy as methotrexate.
Alternative first line agent, but not so effective as methotrexate?
Hydroxychloroquine
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.