Term
| Systemic Lupus Erythematosus |
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Definition
• Autoimmunediseasethataffectsmultisystems
• 1.5millioncasesoflupus
• Prevalenceof17to48per100,000population
• Women>Men-9:1ratio
• 90%casesarewomen
• AfricanAmericans>Whites
• Onsetusuallybetweenagesof15and45years, but
• Can occur in childhood or later in life |
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Term
| Clinical Manifestations of SLE |
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Definition
• For the purpose of identifying patients in clinical studies, a person has SLE if 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation. (specificity 95%, sensitivity 75%)
• It is important to remember that a patient may have SLE and not have 4 criteria. |
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Term
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Definition
1. Butterfly rash
2. Discoid lupus
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Neurologic d/o 8. Hematologic d/o 9. Renal d/o
10.Immunologic: anti- DNA, anti-Sm, false pos STS
11.Anti-nuclear antibody |
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Term
| Cutaneous findings in SLE |
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Definition
• Most common rash is photosensitive, raised erythematous malar rash. 55-85% develop at some point in disease
• Discoid Lupus Erythematosus(DLE):15-30% circular, scaly hyperpimented lesions with erythematous rim, atrophic center—can be disfiguring
• Mouth/vaginal/nasalulcers
• Alopecia: may be diffuse or patchy. Occurs 50% |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
| Musculoskeletal SLE findings |
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Definition
• Polyarthritis, mild to disabling, occurs most frequently in hands, wrists, knees. Occurs 90%
• Joint deformities occur in only 10%
• Arthritis of SLE tends to be transitory
• If single joint has persistent pain, consider osteonecrosis (prevalence increased in SLE over general population, especially if on steroids.)
• Myositis with elevated CK and weakness rarely occurs |
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Term
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Definition
So these are some of the examples of the transient lupus arthritis. Here you can see tenosynovitis in the image on the left, almost looks like a sausage finger, but you see this fusiform swelling like that, which will resolve as the disease is treated. You can get various forms of arthritis. So this patient appears to have a little bit of swan necking going on in the middle picture.
And then lastly, as we discussed in the previous lectures about rheumatoid arthritis, rheumatoid arthritis gives you an ulnar deviation that's permanent. Now in lupus, you have what's called a Jaccoud-like arthropathy, which, due to tendinopathy, there is an ulnar deviation of your fingers, but this is not permanent. And with treatment and with decreasing of the tendinopathy tendinitis, the fingers will return back to their normal position. |
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Term
| Serositis - Pulmonary SLE |
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Definition
• Pleuritis with or without effusion - if case is mild, tx: NSAIDS
- if case is severe, tx: steroids
• Life-threatening manifestations: interstitial inflammation which can lead to fibrosis and intra-alveolar hemorrhage.
• Also pneumothorax and pulmonary HTN can occur |
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Term
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Definition
• Pericarditis: most common cardiac manifestation and usually responds to NSAIDs.
• Myocarditis(rare)and fibrinous endocarditis (Libman-Sacks) may occur. Steroids plus treatment for CHF/arrhythmia or embolic events.
• MI due to atherosclerosis can occur in<35y/o |
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Term
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Definition
• Cranial or peripheral neuropathy occurs in 10-15%, it is probably secondary to vasculitis in small arteries supplying nerves.
• Diffuse CNS dysfunction: memory and reasoning difficulty
• Headache: if excruciating, often indicate acute flare
• Seizures of any type
• Psychosis: must distinguish from steroid-induced psychosis
– Occurs in 1st weeks of treatment at doses ≥40mg prednisone and resolves after several days of reducing or stopping treatment
• TIA, Stroke: mostly increased among patients that are APLA positive
• 50-fold increase in risk of vascular events in women under 45 compared to healthy women
• Treatment for clotting event is long-term anticoagulation |
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Term
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Definition
• Anemia: usually Normochromic, normocytic
• Leukopenia: almost always consists of lymphopenia, not granulocytopenia
• Thrombocytopenia |
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Term
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Definition
Renal
• Nephritis: usually asymptomatic, so always check UA if patient has known or suspected SLE
• Occurs early in course of disease-if not present w/in 1 yr, probably will not occur.
• Histologic classification by renal biopsy is useful to plan therapy |
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Term
| Histologic Classifications classes of SLE |
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Definition
• Class I is minimal mesangial glomerulonephritis which is histologically normal on light microscopy but with mesangial deposits on electron microscopy.
• Class II is based on a finding of mesangial proliferative lupus nephritis. This form typically responds completely to treatment with corticosteroids.
• Class III is focal proliferative nephritis and often successfully responds to treatment with high doses of corticosteroids.
• Class IV is diffuse proliferative nephritis. This form is mainly treated with corticosteroids and immunosuppressant drugs.
• Class V is membranous nephritis and is characterized by extreme edema and protein loss.
• Class VI Glomerulosclerosis |
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Term
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Definition
• Anti-dsDNA IgG: very specific, may correlate with disease activity
• Anti-Sm: specific, but only present in 25% of cases, does not correlate with activity
• APLA: not specific. Used to identify patients at increased risk for clots, thrombocytopenia and fetal loss |
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Term
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Definition
• ANA: positive in 95% of cases. Pretest probability affects interpretation. In PCP setting, 2% for SLE. In rheum: 30%
• LowPositive(1:160 or lower):SLE likelihood <2% (<26% for rheumatologists)
• HighPositive(1:320 or higher):SLE likelihood: 2-17% (32-81% for rheumatologists)
• SLE specific patterns: Rim and Homogenous |
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Term
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Definition
- Serum cr. and albumin - CBC w/ diff
- U/A
- ESR
- Complement levels
- Renal bx if warranted |
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Term
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Definition
• Treatment plans are based on patient age, sex, health, symptoms, and lifestyle
• Goals of treatment are to: -prevent flares
-treat flares when they occur
-minimize organ damage and complications |
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Term
| Conservative management for SLE |
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Definition
• For those w/out major organ involvement.
• NSAIDs: to control pain, swelling, and fever
• Caution w/ NSAIDS though. SLE pts are at increased risk for aseptic meningitis
• Antimalarials: Generally to treat fatigue joint pain, skin rashes, and inflammation of the lungs
• Commonly used: Hydroxycholorquine
• Used alone or in combination with other drugs |
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Term
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Definition
• Corticosteroids (Mainstay of SLE treatment)
• To rapidly suppress inflammation
• Usually start with high-dose IV pulse and convert to PO steroids with goal of tapering and converting to something else.
• Commonly used: prednisone, hydrocortisone, methylprednisolone, and dexamethasone |
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Term
| Immunosuppressives for SLE |
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Definition
• Primarily for CNS/renal involvement
• Mycophenolate mofetil (cellcept)
• Azathioprine (imuran): requires several months to be effective, effective in smaller percentage of patients
• MTX: for treatment of dermatitis and arthritis, not life- threatening disease
• Cyclosporine: used in steroid-resistant SLE, risk of nephrotoxicity
• Cyclophosphamide (cytoxan) Almost all trials performed on patients with nephritis |
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Term
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Definition
• Sjögren's syndrome(S.S) is a systemic, chronic, autoimmune, inflammatory disorder. Characterized by:
– Lymphocytic infiltrates in exocrine organs.
• Most individuals with Sjögren syndrome present with sicca symptoms.
– In addition, numerous extraglandular features may develop.
• Primary Sjögren syndrome occurs in the absence of
• another underlying rheumatic disorder
• Secondary Sjögren syndrome is associated with another underlying rheumatic disease |
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Term
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Definition
• The etiology is not well understood.
• Autoimmune disease with ongoing interaction between the innate
and acquired immune systems.
• There is presence of activated salivary gland epithelial cells
expressing major histocompatibility complex (MHC) class II
molecules.
• Association with the human leukocyte antigen(HLA)
• Some evidence indicates that the true association of Sjörgren
syndrome may be with HLA-DQA1.
• Possible disease triggers
– Viruses are viable candidates as environmental triggers, uncertain.
– Epstein-Barr virus(EBV), HTLV-1,human herpes virus 6(HHV-6),HIV.
– Hepatitis C virus (HCV), and cytomegalovirus (CMV) may have a role |
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Term
| Epidemiology of Sjogren's |
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Definition
• Second most common rheumatologic disorder, behind SLE.
• Affects 0.1-4% of the population.
• Between different ethnic groups, the disease occurs worldwide with similar prevalence.
• The female-to-male ratio of is 9:1. |
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Term
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Definition
• Carries a generally good prognosis.
• Morbidity is mainly associated with the gradually decreased function of exocrine organs.
• Patients with primary Sjögren syndrome have a normal life expectancy.
• Children born to mothers with antibodies against SSA/Ro are at an increased risk of neonatal lupus and congenital heart block. |
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Term
| Presentation of Sjogren's |
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Definition
• The first symptoms in primary Sjögren syndrome can be easily overlooked and overlapped.
• Xerophthalmia (dry eyes) and xerostomia (dry mouth) are the main clinical presentations in adults.
• Bilateral parotid swelling is the most common sign of onset in children.
• Extraglandular involvement in Sjögren syndrome falls into 2 general categories:
– Periepithelial infiltrative processes include interstitial nephritis, liver involvement, and bronchiolitis and generally follow a benign course.
– Extraepithelial extraglandular involvement is related to B-cell hyperreactivity, hypergammaglobulinemia, and immune complex formation and includes palpable purpura, glomerulonephritis |
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Term
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Definition
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Term
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Definition
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Term
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Definition
• No single test is sufficiently sensitive or specific in the diagnosis of Sjörgren syndrome.
• Laboratory test results may indicate the following:
– Elevated erythrocyte sedimentation rate (ESR)
– Anemia
– Hypergammaglobulinemia
– Presence of antinuclear antibodies, especially anti-Ro and anti- La
– Presence of anti–alpha-fodrin antibody (reliable diagnostic marker of juvenile Sjörgren syndrome)
– Creatinine clearance may be diminished in up to 50% of patients
– Schirmer test.
– Serum electrophoresis.
– Sialography and Scintigraph. |
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Term
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Definition
• No curative agents for exist.
• The treatment of the disorder is essentially symptomatic.
• In secondary Sjörgren syndrome, treatment is based on the accompanying disease and its
clinical features.
• Skin and vaginal dryness
– Patients should use skin creams, such as Eucerin, or skinlotions, such as Lubriderm
– Arthralgias and arthritis- Acetaminophen or nonsteroidal anti-inflammatory
drugs(NSAIDs).
• Dry Eyes:
– Artificial tears should be applied liberally.
– Topical steroids.
– Cyclosporine.
– Nutritional supplements.
• Dry mouth:
– Patients with dry mouth can liberally drink sips of water and take bottled water with them
on trips.
• Additional treatment considerations:
– In patients with major organ involvement, such as lymphocytic interstitial lung disease, consider therapy with steroids and immunosuppressive agents, such as cyclophosphamide. |
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Term
| Medications for Sjogren's |
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Definition
Dry Mouth:Salagen, Evoxac, Salivart, Biotene Oralbalance MOuth Moisturizing Gel, Moi-Stir Solution/Swabs
Dry eye: Lacxrisert, Restasis, GenTeal, Refresh Plus/Tears/Celluvisc/Thera Tears, Visine Tears, Murine tears, Refresh PM Ointment |
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Term
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Definition
CREST Syndrome, Scleroderma
So here actually are the pictures of the real life examples in order. So here, in the first picture, is an example of calcinosis and deposition of calcium within the skin. And we can see kind of forming these lumpy, bumpy areas, as well as these definitive, white bumps. Here, we see in this finger, the fourth and fifth fingers, an example of Raynaud's-- the finger turning white. But remember, the finger can turn blue, purple, and red. This is most likely an esophageal modified barium esophagram, which shows esophageal motility, probably a bolus of liquid or fluid in the food that's not passing properly. And that can be a sign of the esophageal dysmotility-- the food transport being delayed.
Here, the fingers that are curling in, the skin is very shiny, very tight, again, you can see the shininess of the finger. You could very clearly see that there's no ridges or folds left in his knuckles. Basically, the skin is drawn back as far as possible. And if you try to lift the skin above, it would be impossible. You would not be able to grasp the skin as I'm able to grasp easily the skin above my PIP and MCP, less so the DIP. You would not be able to do that in a patient having sclerodactyly. The final example here we see in the hands is an example of telangiectasia of the finger. |
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Term
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Definition
Calcinosis on x-ray, Scleroderma
So how does calcinosis appear on X-ray? So, although rare and not frequently seen, this is a good x-ray that can be appear on an exam setting, for example, because it's so peculiar and so unique. And you see the kind of deposition of the calcium at the fingertip beyond the DIP. And again, you see it here in the carpel bones. You see it here in the metacarpal bones. You see it here in the proximal interphalangeal bones. And you see here in the distal interphalangeal bones. |
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Term
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Definition
| Remember this in a testing setting. Diffuse scleroderma is a more rapid process often with the onset of skin thickening within a year of the Raynaud's. Skin involvement is proximal to the elbows and knees, meaning up from the knees, and often can involve the trunk. Capillaroscopy reveals dropout with capillary dilatation and dropout. There is early organ involvement in diffuse scleroderma, often manifesting as renal disease. Unfortunately, interstitial lung disease, which can be quite debilitating, leading to loss of pulmonary function. These patients need to be screened with yearly pulmonary function testing, which can monitor their restrictive lung disease. |
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Term
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Definition
• MoreRapidProcess
-Often with onset of skin thickening within a year of Raynaud’s symptoms
• Skin involvement proximal to elbows and knees
- Often can involve the trunk
• Capillaroscopy reveals dropout
- With capillary dilatation and dropout.
• Early organ involvement
- Renal, interstitial lung disease, myocardial, diffuse gastrointestinal – often within the first 3 years.
• Antibodies
- Anti-Scl-70, anti-RNA Polymerase III. |
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Term
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Definition
| So here are more examples of manifestations of diffuse scleroderma, again, rehashing Raynaud's, rehashing sclerodactyly but now showing some truncal involvement. |
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Term
| Organs Involved in Scleroderma |
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Definition
• Skin
• Musculoskeletal
• Pulmonary
• Renal
• Gastrointestinal
• Cardiac |
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Term
| Skin Involvement in Scleroderma |
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Definition
- Early stages:
• Perivascular infiltrate which are primarily T cells.
• Skin swelling which eventually becomes skin thickening. • Involves the hands and/or feet (distal).
- Late Stages:
• Finger-like projections of collagen extend from the dermis to the subcutaneous tissue to anchor skin deeper.
• Skin becomes firm, thick and tight.
• Skin thickening moves proximally.
• Fibroblasts and collagen deposition.
• Hair and wrinkles overlying area of skin thickening disappears.
- May regress on its own over years
• reverse pattern (ie, starting with regression of skin thickening in the trunk, then proximal extremities, then more distal).
- Digital Ulcers:
• on extensor surface of PIP’s and elbows; may become secondarily infected.
- Digital ischemia:
• with pits in the distal aspect of the digits related to prolonged Raynaud’s.
- Thinning of the lips, beak-like nose. |
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Term
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Definition
| Again, here you see the beak-like nose in the patient on the left. You're going to see the thinning of the lips and the small oral aperture and the beak-like nose. Here are examples of ulcerations and digital tip ulcerations, which are starting just as a digital tip here, which I circled, but then progressing to necrosis. Now if it gets to a certain point, like for example here, this may need to be amputated because there's no recovering from that. That's critical ischemia. |
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Term
| Musculoskeletal Scleroderma findings |
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Definition
• Arthritis
- in > 50% with swelling, stiffness, and pain in the joints of the hands.
• Carpal Tunnel Syndrome. • Contractures
• Polymyositis |
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Term
| Pulmonary Scleroderma findings |
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Definition
• Leading cause of death
• Symptoms:
- Exertional dyspnea
• Types of lung Involvement:
- Interstitial lung disease.
- Isolated pulmonary hypertension. |
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Term
| Interstitial Lung Disease Scleroderma findings |
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Definition
• Inflammatory phase
• with ground glass opacities and linear infiltrates • lower 2/3 of the lung fields on CT scan.
• Fibrosis:
• Late phase with honeycombing.
• Diagnosis
– Pulmonary function tests
• restrictive pattern with low FVC, low residual volume, low DLCO.
– High Resolution CT Scan
– BAL: often not required
– Lung biopsy: often not required
• ILD is most commonly associated with diffuse scleroderma. • Anti-Scl-70 |
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Term
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Definition
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Term
| Primary Pulmonary Hypertension in Scleroderma |
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Definition
- Symptoms:
• Exertional dyspnea
- Frequency
• 10-15% of patients with systemic sclerosis
- Definition:
• Mean PA blood pressure >25mmHg at rest or >30mmHg with exercise on right heart catheterization.
• Estimated systolic pulmonary artery pressure of >35mmHg on Echocardiogram
- Pathogenesis
• Intimal fibrosis and medial hypertrophy of the pulmonary arterioles and arteries. |
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Term
| Other Pulmonary Associations with Scleroderma |
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Definition
• Pneumonia:
- Due to aspiration secondary to GERD
• Increased incidenece of: – Alveolar carcinoma
– Bronchogenic carcinoma |
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Term
| Renal Manifestations of Systemic Sclerosis |
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Definition
• SclerodermaRenalCrisis
• Abruptly developing severe hypertension
– RiseinSBPby>30mmHg,DBPby>20mmHg
• One of the following:
– Increase in serum creatinine by 50% over baseline or creatinine > 120% of upper limit.
– Proteinuria > 2+ by dipstick.
– Hematuria > 2+ by dipstick or > 10 RBC/HPF
– Thrombocytopenia < 100
– Hemolysis (schisctocytes, low platelets, increased reticulocyte count).
• Can cause headache, encephalopathy, seizures, LV failure.
• 90% with blood pressure > 150/90.
• Can occur also with lower blood pressures < 140/90 and this confers worse prognosis. |
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Term
| Renal Crisis in Scleroderma risk factors |
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Definition
• Rapidly progressive skin thickening within the first 2-3 years.
• Steroid use (prednisone > 15 mg)
• Anti-polymerase III Ab.
• Pericardial Effusion. |
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Term
| treatment for scleroderma renal crisis |
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Definition
• Medical Emergency: generally with admission.
• Initiation of ACE inhibitors such as captopril; lifelong treatment with ACE inhibitors.
• Dose escalation of captopril.
• ACE-inhibitors do not prevent SRC |
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Term
| Renal Crisis - Prognosis for scleroderma |
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Definition
• Improved overall with ACE-inhibitors.
• Even with ACE-inhibitors 20-50% will progress to ESRD.
• Among patients who required dialysis during the acute phase, an appreciable proportion (40-50%) will be able to discontinue dialysis. |
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Term
| Gastrointestinal Manifestations for scleroderma |
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Definition
- Esophageal dysmotility: in up to 90%.
• Pathophysiology:
– reduced tone of gastroesophageal sphincter and distal dilatation of the esophagus.
– Lamina propia and submucosal tissue with Inflammatory changes and increased collagen on pathology.
• Symptoms
– Dysphagia, GERD; many asymptomatic.
• Diagnosis:
– Esophageal manometry, Esophagram, CT scan.
• Treatment
– Proton Pump Inhibitors
– Elevation of head of the bed.
• Complications:
– Barret’s Esophagus
- Gastric Involvement:
• Symptoms: Early satiety.
• Diagnosis: Nuclear Gastric Emptying Test.
• Treatment: promotility agents
• Watermelon Stomach: dilated vessel which can cause bleeding.
- Small Intestinal involvement
• Symptoms: distension, pain, bloating, steatorrhea
• Nutritional deficiencies secondary to bacterial overgrowth.
» Vitamin B6/B12/folate/25-OH Vit D, low albumin
• Diagnosis:
– Glucose hydrogen breath test
– Low D-xylose absorption test
– Small bowel aspiration (only if resistance to rotating antibiotics)
• Treatment: Rotating antibiotics, Reglan, Erythromycin |
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Term
| Cardiac Manifestations for scleroderma |
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Definition
• Forms of cardiac involvement
• Pericardial Effusion
– symptomatic pericarditis in 20%
• Microvascular CAD:
– recurrent vasospasm of coronary arteries
– Necrosis
– patchy myocardial fibrosis; leads to diastolic > systolic dysfunction.
• Myocarditis
– Inflammation which leads to fibrosis
• Arrhythmias and conduction abnormalities – Fibrosis of cardiac conduction system.
– AV conduction defects and arrhythmias. |
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Term
| Scleroderma autoantibodies |
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Definition
if a patient comes into to you with ANA and a speckled pattern, and the antigen that comes up with Scl-70, you don't necessarily know that they have scleroderma. But if you establish a diagnosis of scleroderma, you may then know that patients with Scl-70 have a higher chance of developing lung fibrosis. So pay closer attention to their lungs and maybe screen their lungs with the appropriate imaging to check for these things.
If a patient has RNA Pol III, you know that they have a higher risk of scleroderma renal crisis. So this patient, you may try to avoid high dose steroids, or you may do urinalysis more frequently or check the renal function and creatinine to make sure that they are not developing scleroderma renal crisis. But also the RNA Pol III is associated with pulmonary hypertension. So these patients need to be thought about to be screened with echoes or right heart caths, if severe.
The centromere pattern is seen in limited scleroderma or CREST syndrome, also frequently associated with pulmonary hypertension and esophageal dysmotility. So it can help guide how you think your patients disease course is going to be and what type of manifestations they may develop, if they don't already have them. Another important one to identify is the anti-Th/To, which appears in the ANA as a nucleolar pattern and has been associated with pulmonary hypertension, lung fibrosis, and small bowel. |
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Term
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Definition
• Depends on clinical manifestations
- Aggressive disease versus stable disease
• Reversible inflammation vs Vasoconstriction.
• Organ Involvement
- Treatment is directed at organ involved. |
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Term
| Raynaud’s treatment for scleroderma |
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Definition
• Calcium Channel Blockers: nifedipine
• Nitroglycerin patches
• Sildenafil (Viagra) (but not in combination with nitroglycerine) –usually for refractory Raynaud’s.
• Parental vasodilators (iloprost) – for severe disease with impending digital ischemia. |
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Term
| Gastrointestinal Involvement treatment for scleroderma |
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Definition
- GERD
• Proton pump inhibitor.
- Delayed Gastric Emptying and peristalis
disorders
• Supportive
• Promotilants are sometimes used. |
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Term
| Pulmonary Involvement treatment for scleroderma |
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Definition
- Interstitial Lung Disease: with active inflammation
• Mycophenolate
• Azithioprine
• Cytoxan - IV
• plus lower dose of steroids if RNA Poly III neg (ie 10 mg daily); avoid steroids if RNA Poly III positive.
- Pulmonary Hypertension
• Vasodilators: bosentan, sildenafil, epoprostenol, treprostinil, iloprost.
• Lung Heart Transplant |
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Term
| Myositis scleroderma treatment |
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Definition
- Polymyositis overlap or MCTD
• Similarly to myositis alone with methotrexate, azathioprine in combination of low dose steroids.
• Tend to keep prednisone dose at around 10 mg or less to avoid risk of renal crisis. |
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Term
| Cardiac Involvement for scleroderma |
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Definition
- Pericarditis:
• NSAIDs
• Drainage of effusion if tamponade
- Myocarditis with elevated CK-MB &
troponin
• If CAD is excluded, MRI and biopsy confirms, then treatment would generally be with low dose prednisone (10 mg/day) and cytoxan; nifedipine may also be helpful. |
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