Lecture 7: Connective Tissue Diseases Flashcards
1
Q
Homogenous/diffuse ANA staining patterns may be associated with what 3 underlying conditions?
A
- Drug-induced SLE**
- Sjogren’s syndrome
- SLE
2
Q
What does the centromere pattern of ANA staining refer to and what condition is it seen in?
A
- Presence of 30-60 uniform speckles distributed throughout the nucleus of resting cells
- Limited systemic sclerosis (CREST)
3
Q
A nucleolar pattern of ANA staining may be seen in which 2 conditions?
A
- Diffuse systemic sclerosis
- SLE
4
Q
What are 3 positive serology findings seen in SLE; which is most specific and correlates with disease activity?
A
- (+) ANA
- (+) anti-ds DNA –> correlates w/ disease activity; most specific
- (+) Sm (Smith)
5
Q
What will be seen with complement activity during active SLE?
A
↓ C3 or C4 due to ↑ consumption
6
Q
Anti-Phospholipid Antibody Syndrome (APS) arises in association with what?
A
- 1/3 of SLE pt’s (secondary APS)
- Can also be present w/o a dx of SLE (primary APS)
7
Q
Of the 3 types of antiphospholipid antibodies, what is the significance of Type One?
A
Causes biologic false-(+) tests for syphilis
8
Q
Of the 3 types of antiphospholipid antibodies, what is the significance of Type Two; how is it detected?
A
- Lupus anticoagulant
- Risk factor for venous and arterial thrombosis and miscarriage
- Causes prolongation of aPTT
- Presence is confrmed by an abnormal dilute Russell viper venom time (DRVVT)
9
Q
Of the 3 types of antiphospholipid antibodies, what is the significance of Type Three?
A
- Anti-cardiolipin antibodies
- Directed at a serum co-factor Beta2GPI
10
Q
Which 2 serology findings if positive correlates with lupus-like syndrome/drug-induced?
A
- (+) ANA
- (+) Anti-histone antibodies (95%)
11
Q
Neonatal lupus affects children born of mothers with which serum antibodies?
A
Anti Ro (SSA) or La (SSB) Abs
12
Q
Which complication may arise in children with neonatal lupus?
A
Permanent complete heart block
13
Q
What are 4 treatment strategies/drugs used for SLE?
A
- Avoid sun exposure, wear sunscreen
- NSAIDs
- Corticosteroids (topical or systemic)
- Hydroxychloroquine
14
Q
What is the hallmark finding of Scleroderma (systemic sclerosis)?
A
- Thickening and hardening of the skin
- Microangiopathy and fibrosis of the skin and visceral organs
15
Q
Which antibodies are specific to diffuse cutaneous scleroderma?
A
- (+) Anti-Scl 70 –> aka Anti-(DNA) topoisomerase I
- Anti-RNA polymerase III
16
Q
Which antibody is specific to the limited cutaneous type of scleroderma?
A
(+) Anti-centromere
17
Q
Which type of imaging may be appropriate for working up Scleroderma?
A
- CXR
- Barium swallow if indicated
- Hand x-rays may show distal tuft resorption and calcinosis
18
Q
Which manifestations of disease are more pronounced in the limited cutaneous type of Scleroderma?
A
- Vascular manifestations i.e., digital ischemia and progressive Pulmonary artery HTN
- Think is limited to pulmonary a.; while diffuse is all over and caused interstitial lung disease
19
Q
A patient with diffuse cutaneous systemic sclerosis (scleroderma) in renal crisis may have what lab finding?
A
Hemolytic anemia
20
Q
What is localized scleroderma and most often affects whom?
A
- Benign skin conditions; most often affects children
- Discreet areas of discolored skin induration; patches = morphea
21
Q
Deficiency of which nutrients is common in systemic sclerosis patients with GI involvement?
A
Fat + protein + B12 + vitamin D
22
Q
Which esophageal manifestations may be seen with systemic sclerosis?
A
Strictures, Barret esophagus –> ↑ risk of esophagal adenocarcinoma
23
Q
Which disease manifestations of the stomach may be seen in systemic sclerosis?
A
- Gastric Antral Vascular Ectasia (GAVE) aka Watermelon stomach
- Gastroparesis
24
Q
Which biliary disease manifestation may be seen with systemic sclerosis; what is the associated antibody?
A
Primary biliary cirrhosis –> anti-Mitochondrial Ab
25
What is the primary cause of morbidity and mortality in patients with systemic sclerosis?
**Pulmonary involvement**
26
What type of pulmonary involvement is seen in the diffuse type of systemic sclerosis and how is it diagnosed/confirmed?
- **Interstitial lung disease**
- Dx by **pulmonary function test (PFT)**
27
What type of pulmonary disease is seen in the limited type of systemic sclerosis and how is it diagnosed?
- **Pulmonary artery hypertension (PAH)**
- _**Right heart** catheter_ to confirm dx: mean pulm. artery pressure of **25 mmHg** or **greater**
28
There is an increased incidence of which lung malignancy in those with systemic sclerosis?
**Bronchoalveolar carcinoma**
29
Which MSK and endocrine are often seen with systemic sclerosis?
- **Carpal tunnel syndrome**
- **Hypothyroid** from **thyroid fibrosis**
30
Sjögren syndrome has strong association with what malignancy?
**B-cell Non-Hodgkin lymphoma**
31
What are the sicca sx's associated with Sjögren syndrome; increased risk for what complication?
- **Immune-mediated** destruction of **lacrimal** and **salivary glands**
- Dry eyes + mouth (xerostomia) + vaginal dryness + tracheobronchial dryness
- ↑ incidence of oral infections (**candida**) + **dental caries**
- **Parotid** or other major salivary gland enlargement
32
What type of biopsy is essential for the diagnosis of Sjögren syndrome; what is seen?
**Lip biopsy** --\> reveals characteristic lymphoid foci in accessory salivary glands
33
What serological findings are characteristic of Sjögren syndrome?
- **Hypergammaglobulinemia**
- **(+) Anti SSA/Ro**
- **(+) Anti SSB/La** = _never_ present without **Ro**
34
Which type of medicated drops may help the dry eye sx's of Sjögren syndrome?
**Cyclosporine** drops
35
Which 2 medications may help the sicca manifestations of Sjögren syndrome?
**Pilocarpine** _and_ **Cevimeline**
36
Inflammatory myopathies are associated with what muscle sx's?
- **Myalgias**
- **_Symmetric_** bilateral **proximal** muscle **_weakness_**
- Difficulty rising from a chair or bathtub or climbing stairs
37
What is the characteristic biopsy finding of Dermatomyositis?
**Perimysial** and **peri**vascular inflammation, **_perifascicular atrophy_**
38
What are the most common malignancies associated with Dermatomyositis?
- **Ovarian**: check transvaginal US, CT abd/pelvis, CA-125
- **Lung**
- **Pancreatic**
- **Stomach**
- **Colorectal**
- **NHL**
39
Which serology findings will be positive in Polymyositis?
- **_Elevated_ serum CK**
- **Anti-Jo-1**
40
What are the steps to tx of the inflammatory myopathies, DM and PM?
- **Step 1:** Glucocorticoids (3-4 wks, then tapered very gradually)
- **Step 2:** Approximately 75% of pt's require additional therapy with other immunosuppressive drugs
- **Step 3:** IV immunoglobulin
- **Step 4:** a trial of one of the following: **rituximab**, **cyclosporine**, cyclophosphamide, or **tacrolimus**
41
Which sex and ethnicity are most often affected by Inclusion Body Myositis (IBM)?
**Males** \> **F**; more often **Caucasians**
42
What are characteristic sign/sx's of Inclusion Body Myositis (IBM); what are the serum CK levels like?
- **Finger flexion** or **quadriceps weakness**
- **CK** is **_mild**_ or _**normal_**
43
What is the characteristic finding on muscle biopsy in Inclusion Body Myositis (IBM); which autoantibodies may be present?
- **Endomysial** inflammation, **_rimmed vacuoles_**, invasion of non-necrotic muscle fibers
- **Anti-cN1A autoantibodies**
44
What are the characteristic gross vascular lesions of Takayasu Arteritis; what is seen histologically?
- **Long smooth tapered stenosis**
- **Granuloma** w/ some **giant cells**, fibrosis in chronic stages
45
What are some of the complications of Takayasu Arteritis?
- **50%** have **pulmonary involvement**
- **Retinopathy**, **Renal artery stenosis**, **Aortic dilations**, **Aortic regurgitation**, **Aneurysm**, and **Aortic rupture**
46
How is diagnosis of Takayasu Arteritis made; what is the tx?
- **Dx:** **MRI** _or_ **CT angiography**
- **Tx:** Glucocorticoids
47
What is a characteristic fundoscopic finding in pt with Takayasu Arteritis?
**Copper-wiring**
48
What is the triad of Behcet Syndrome?
- **Recurrent mouth ulcers**
- **Genital ulcers**
- **Eye inflammation** **(uveitis****)**
49
What is Pathergy seen in the setting of Behcet Syndrome?
Pustules at site of sterile needle pricks
50
Which HLA is Behcet Syndrome associated with?
**HLA-B51**
51
What are 2 vessel complication which may arise in the setting of Behcet Syndrome?
- **Large vessel** = **aneurysms**
- **Venous impairment** ---\> **DVT**
52
Polyarteritis nodosa may be associated with what infectious agent?
**HBV**
53
Which neurological manifestations may be seen in the setting of Polyarterisitis Nodosa?
- **Peripheral nerve**: 80% have _vasculitis_ nephropathy
- Mononeuritis multiplex: **foot drop**
54
Which organ system is characteristically spared in Polyarteritis Nodosa?
**Lungs**
55
How is diagnosis of Polyarteritis made; what is seen?
- **Bx**: infiltration and destruction of blood vessels by inflammatory cells --\> **_fibrinoid necrosis_**, NO granulomas
- **Angiogram**: microaneurysms
56
If patient with Polyarteritis Nodosa is ANCA negative, what should you check for?
**HBsAg** and **HBeAg**
57
Which serum marker is positive in granulomatosis with Polyangiitis (Wegener's)?
**C-ANCA** aka **PR3-ANCA**
58
What are the 3 hallmarks of granulomatosis with Polyangiitis (Wegener's)?
- **_Granulomatous_** inflammation
- **Necrotizing vasculitis**
- **Segmental glomerulonephritis** (hematuria/RBC/proteinuria)
59
What are the upper and lower respiratory tract manifestations which may be seen in setting of granulomatosis with Polyangiitis (Wegener's); what may be seen on CXR?
- **90%** have nasal involvement: **saddle nose**, crusting, bleeding, obstruction
- **Lung**: Asx nodule --\> alveolar hemorrhage
- **CXR:** infiltrate/nodules/**cavitary lesions**
60
Which serum marker is positive in some cases of eosinophilic granulomatosis with Polyangiitis (Churg-Strauss)?
**MPO-ANCA** aka **P-ANCA**
61
What is the hallmark of eosinophilic granulomatosis with Polyangiitis (Churg-Strauss)?
**Asthma** + **Eosinophilia** --\> **Vasculitis**
62
What is the characteristic finding on angiography of Thromboangiitis Obliterans (aka Buerger Disease)?
**"Corkscrew" appearance**
63
Which finding on nailfold capillaroscopy is characteristic of secondary raynaud's?
**Distorted** with **widened** and **irregular looop**, dilated lumen and areas of vascular **"dropout"**
64
Which arteries most often affected in Giant Cell Arteritis (aka Temporal arteritis)?
- **Cranial arteries** (temporal/facial/opthalmic)
- **Aortic arch**
65
Which HLA is associated with Giant Cell Arteritis (aka Temporal arteritis)?
**HLA-DR4**
66
What are the signs/sx's and characteristic lab findings of Giant Cell Arteritis (aka Temporal arteritis)?
- **HA** + **jaw claudication** + **_PMR_** + **visual abnormalitis** (amaurosis fugax or diplopia)
- ↑↑ **ESR** (\>50 mm/h)
67
What is the gold standard for diagnosis of Giant Cell Arteritis (aka Temporal Arteritis); what is seen?
- **Temporal artery bx**: need a **1.0 cm** segment
- **Segmental granulomatous vasculitis** w/ **_multinucleated giant cells_**
68
What is an important thing to remember about the tx of Giant Cell Arteritis (aka Temporal Arteritis)?
Start **corticosteroids** (before biopsy!) --\> dramatic improvement
69
What are the signs/sx's of Polymyalgia Rheumatica and what is it associated with?
- **_Proximal_** severe _symmetrical_ morning and daylong **stiffness**, **soreness**, and **pain** in shoulder, neck, and pelvic girdles
- "Feelings" of weakness as a result of **pain** (as opposed to PM), no true weakness
- Associated with **Giant Cell Arteritis (aka Temporal Arteritis)**
70
What is seen on muscle biopsy and in the serum of patient with Polymyalgia Rheumatica?
- **_NO_** inflammation on muscle bx
- **Muscle enzymes** and **EMG** = **normal**
- ↑↑↑ **ESR** and **CRP**
71
What are the cardiopulmonary complications which may arise in SLE?
- Pleuritis + pericarditis + myocarditis + endocarditis
- Pt's also at ↑ risk of **MI** usually due to **accelerared atherosclerosis**
72
Which complication may arise in the eye associated with SLE/APS?
**Retinopathy**: cotton wool spots
73
Which antibody is seen in cases of polymyositis w/ pneumonitis + arthritis?
**Anti-Jo-1**
74
Henoch-Schonlein Purpura is associated with what underlying signs/sx's?
- **Palpable purpura**: _NO_ thrombocytopenia
- **Arthritis**
- **Abdominal pain**
- **Glomerulonephritis**
