Connective tissue Diseases (Darrow) - SRS

Question 1

What are the 11 criteria for SLE?

Answer 1

B₃ O₁ R₁ N₁ with D₃ermA₁titiS₁

Blood

1. Hematologic disorder: pancytopenia
2. Immunologic Disorder: anti-ds-DNA, Sm, APA, FPSTS
3. ANA

Oral

4. Ulcers (vagina, nose, alopecia)

Renal

5. Renal disorder (proteinuria or cellular casts)

Neurologic

6. Seizures or psychosis

Dermatitis

7. Malar Rash
8. Discoid rash
9. Photosensitivity

Arthritis

10. Arthritis with or without active synovitis

Serositis

11. Serositis (pleuritis or pericarditis)

Question 2

Again, what are the 11 clinical criteria per rheum tutor?

Answer 2

1. Acute cutaneous lupus
2. chronic cutaneous lupus
3. oral/nasal ulcers
4. non-scarring alopecia
5. arthritis
6. serositis
7. renal
8. neurological
9. hemolytic anemia
10. leukopenia
11. thrombocytopenia

Question 3

What are the immunologic criteria for lupus?

Answer 3

1. ANA
2. Anti-DNA
3. Anti-Sm
4. Antiphospholipid antibodies
5. Low complement
6. Direct coombs test (not in the presence of hemolytic anemia

Question 4

What are the requirements for SLE diagnosis?

Answer 4

greater than or equal to 4 criteria with at least one clinical and one laboratory criteria.

Question 5

What are the ANA subtypes?

Answer 5

1. Ro/SSA, La/SSB
2. Sm
3. RNP/U1-RNP
4. Scl70/topoisomerase 1
5. Jo-1

Question 6

What is Scl70/topoisomerase 1 associated with?

Answer 6

Scleroderma

Question 7

What is the Sm ANA subtype associated with?

Answer 7

Lupus mostly

Question 8

What antibodies are associated with the IF pattern shown here? 6

Answer 8

​Speckled Pattern

1. anti-Sm - SLE
2. Anti-RNP
3. Anti-Ro - SS
4. Anti-La - SS
5. Anti-Jo-1 and Mi-2 PM/DM
6. Anti-Scl70

Question 9

What antibodies are associated with this IF pattern?

Answer 9

Centromere

1. anti-centromere - PSS (CREST)

Question 10

Lupus can produce mesangial, mesangial proliferative, focal proliferative, diffuse proliferative, membraneous, and sclerosing glomerulonephritis.

• What kind of casts can you find?
• What is the amount of proteinuria going to exceed?

Answer 10

• any type of casts, ie “telescoping urinary sediment”. (but red cells casts most common)
• Proteinuria of > 500 mg/24 hrs, or 3+ dipstick.

Question 11

CNS involvement in SLE may present with seizures, psychoses, neuropathies, strokes, and what condition that simulates UTI d/t fever and urinary retention?

Answer 11

Transverse myelitis

Question 12

Differentiate the impact of SLE and APS on the cerebrum.

Answer 12

SLE - Cerebral inflammation

APS - Cerebral Ischemia

Question 13

What are two specific cardiopulmonary involvements of SLE?

Answer 13

• alveolar hemorrhage
• Libman-sacks endocarditis

Question 14

What is CRP useful for in an SLE patient?

Answer 14

Differentiating between flare ups and infection.

CRP > 10mg/dL = 80% chance of infection

Question 15

Why is hydroxychloroquine so wonderful in treating SLE?

Answer 15

1. prevents flares
2. reduces congenital heart block
3. lowers diabetes risk
4. reverses platelet activation by IgG antiphospholipid

Question 17

Is hydroxychloroquine ok for the pregnant patient?

Answer 17

yes, it is great for preggos

Question 18

What are 5 causes of splinter hemorrhages?

Answer 18

1. Nail trauma
2. SBE
3. Antiphospholipid antibody syndrome
4. Hypereosinophilic syndrome
5. Libman Sacks endocarditis

Question 19

Before making a diagnosis of SLE in a random patient what must one exclude?

Answer 19

Drug induced lupus

Question 20

What are the main drugs involved in triggering drug induced lupus?

Answer 20

1. Hydralazine
2. Isoniazid
3. Procainamide
4. Methimazole
5. Prophylthiouracil
6. Etanercept

Question 21

What is a shared characteristic of many patients who get drug induced lupus?

What are two components of SLE that are absent in drug induced lupus?

Answer 21

• Slow acetylators*
• No renal disease
• No CNS disease

Question 22

What antibodies are involved in drug induced lupus?

Answer 22

Anti-histone

Question 23

What tests must be done in a patient with possible lupus who wishes to become pregnant?

Answer 23

1. Lupus anticoagulant
2. Anticardiolipin antibody
3. anti-B2 glycoprotein (apolipoprotein H)
4. Antiphospholipid antibody
5. anti-RO
6. Anti-LA
7. nephrotic syndrome

Question 24

Why screen for the following in a SLE patient wishing to become pregnant?

1. Lupus anticoagulant
2. Anticardiolipin antibody
3. anti-B2 glycoprotein (apolipoprotein H)
4. Antiphospholipid antibody
5. anti-RO
6. Anti-LA

Answer 24

1. lupus anticoag, antiphospholipid, anticardiolipin, anti-B2 glycoprotein 1 d/t incresed odds of spontaneous abortion and to identify if patient has APS.
2. anti-RO and Anti-La d/t risk of heart block to the child

Question 25

An SLE patient becomes pregnant, their mycophenolate is stopped and she is started on Aza and HCQ. ASA is added. At 26 weeks, the patient’s BP jumps to 168/104, 5 gm proteinuria, with BUN of 35 and Cr of 2.1 mg/dL. Which of the following would indicate a lupus flare rather than pre-eclampsia? A.Proteinuria B.Hypertension C.High LFTs D.Low C3/C4 E.High uric acid

Answer 25

D.Low C3/C4

Question 26

What is the blood pressure like in SLE vs. preeclampsia?

Answer 26

SLE = HTN present Preeclampsia = HTN pregnant No difference, not helpful

Question 27

What is the urine protein like in SLE and Preeclampsia?

Answer 27

SLE = Proteinuria Preeclampsia = Proteinuria Again, no difference/not helpful

Question 28

What are the platelet levels like in SLE vs Preeclampsia?

Answer 28

SLE = Low Preeclampsia = low Again, no difference/not useful for discriminating

Question 29

What are the LFTs in SLE vs preeclampsia?

Answer 29

SLE = normal typically Preeclampsia: commonly abnormal Useful for differentiation

Question 30

What are the differences seen in serology between SLE and preeclampsia?

Answer 30

SLE = dsDNA and Low C3/C4 Preeclampsia = no findings

Question 31

What are the uric acid levels like in SLE vs preeclampsia?

Answer 31

1. SLE: normal 2. Preeclampsia: High

Question 32

Describe the following for each.... ## Footnote **_SLE Preeclampsia_** HTN: ____ \_\_\_\_\_ UA: ____ \_\_\_\_\_ Platelets: ____ \_\_\_\_\_ Abn LFTs: ____ \_\_\_\_\_ Serology: ____ \_\_\_\_\_ Uric acid: ____ \_\_\_\_\_

Answer 32

**_SLE Preeclampsia_** HTN: Yes Yes UA: proteinuria proteinuria Platelets: low low Abn LFTs: rare common Serology: dsDNA none low C3/C4 Uric acid: normal high

Question 33

What antibodies are common to subacute cutaneous SLE?

Answer 33

anti-ro anti-la

Question 34

What can be a permanent impact of neonatal lupus? What is the tx we use for neonatal lupus?

Answer 34

Complete heart block HCQ

Question 35

A 50 y/o woman presents with a massive PE. History is positive for two spontaneous abortions and a TIA. Her father died of a stroke at age 48. During recovery she develops a DVT in the left arm. The legs are shown and the ankles show hemosiderin deposits. Labs are normal except for an INR of 2.4 and PTT of 65 seconds (N = 25 - 35 seconds) and a low platelet count. This patient has which condition? A.Prothrombin gene mutation B.Factor V leiden mnutation C.Antithrombin III deficiency D.Lupus anticoagulant E.Anticardiolipin antibody

Answer 35

E. Anticardiolipin antibody - since there is no history of SLE in the patient's background.

Question 36

What are the causes of secondary antiphospholipid antibody syndrome?

Answer 36

CTD's (SLE especially) Malignancy Infections (HIV) Drugs: phenytoin, chlorpromazine

Question 37

What is a somewhat unique feature of antiphospholipid antibody syndrome?

Answer 37

Clots both in the venous AND arterial systems

Question 38

What are the lab criteria for antiphospholipid antibody syndrome? ## Footnote **TQ**

Answer 38

1. Anticardiolipin antibody 2. Lupus anti-coagulant 3. Anti-β2 glycoprotein 1\* (Apo H\*\*; FPSTS)

Question 39

What are the clinical criteria for Antiphospholipid antibody syndrome?

Answer 39

1. spontaneous abortion 2. vascular thrombosis

Question 40

What antibody has the best correlation with thrombotic events in APS? What drugs can induce this antibody formation?

Answer 40

LA Anticoagulants (heparin, etc)

Question 41

What test is used to confirm antiphospholipid antibody syndrome?

Answer 41

Russel Viper Venom Test

Question 42

What lab and clinical criteria are needed for dxing antiphospholipid antibody syndrome? TQ

Answer 42

To diagnose need **1 clinical criteria plus 1 lab criteria 3 months apart.**

Question 43

What are the key components of treatment of APS?

Answer 43

1. Anticoagulation 2. Steroids 3. Hydroxychloroquine 4. Statins 5. B cell inhibitors 6. Complement inhibitors

Question 44

What is an ADR to watch for with hydroxychloroquine?

Answer 44

Retinitis

Question 45

If you hear a patient has cryoglobulinemia what does that make you think of?

Answer 45

Hep C Sjogren

Question 46

What are the main causes of livedo reticularis of the obstructive variety?

Answer 46

**1. Cryoglobulins, cold agglutinins.** **2. Antiphospholipid syndrome.** 3. DIC, TTP. 4. Hypercalcemia. 5. Polycythaemia rubra vera or thrombocythaemia. 6. Infections – Parvo B19, syphilis. 7. Arteriosclerosis (**cholesterol emboli**) and homocystinuria.

Question 47

What vasculitises cause livedo reticularis?

Answer 47

RA **SLE** DM PSS **PAN**

Question 48

What are the "*characteristics"* for scleroderma? TQ

Answer 48

**1.Raynaud’s syndrome.** 2.Cutaneous, subcutaneous calcification, pigmentation and depigmentation, telangiectasias. 3. Cardiac: pericarditis, fibrosis, MI\*, heart block, R-CHF. 4. Pulmonary: restrictive lung disease with decreased CO diffusion, pulmonary hypertension. 5. GI: GERD, **sticking below the sternum, hypomotility with bacterial overgrowth**, large mouth diverticulum. 6. Renal: “**onion skinning**” and hypertension.

Question 49

What is the main component of the pathogenesis of PSS?

Answer 49

Excess collagen deposition d/t overproduction of TGF-B

Question 50

What are some causes of PSS (Scleroderma)?

Answer 50

1. **Fibroblast metabolic defect** with **increased collagen** in the extracellular matrix. 2. Endothelial dysfunction and apoptosis with subsequent obliteration. 3. **Autoimmunity** (HLA-DPB1, HLA-DPB2). 4. **Silica**, solvents. 5. Paraneoplastic.

Question 51

The diagnosis of scleroderma requires how many major/minor criteria?

Answer 51

1 major or 2/3 minor

Question 52

What are the major criteria in scleroderma? TQ

Answer 52

Symmetric thickening, tightening and induration of the skin proximal to the MTP/MCP joints. e.g. arms, trunk etc

Question 53

What are the three minor criteria for scleroderma? TQ

Answer 53

1. sclerodactyly 2. digital pitting 3. bibasilar pulmonary fibrosis

Question 54

You can diagnose a high probabilit of scleroderma with 3/5 features of CREST syndrome. Or what three things?

Answer 54

1. RP 2. nail fold changes 3. Scleroderma specific antibody.

Question 55

What are the components of CREST?

Answer 55

1. Calcinosis 2. Raynauds Phenomenon 3. Esophageal dysmotility 4. Sclerodactyly 5. Telangiectasia

Question 56

What are the key skin findings in PSS? 5 bold items and more

Answer 56

**Raynauds phenomenon - often the first sign.** Early **nonpitting edema** of the skin with erythema and itching. Later hair and subcutaneous fat loss with tightening & thickening of skin (scleroderma/sclerodactyly). **Subcutaneous calcification.** **Finger tip ulceration.** **Telangiectasia.** Pigmentation. Depigmentation. Nailfold changes.

Question 57

What are the key differentiating features between primary and secondary RP? TQ

Answer 57

Primary WILL NOT have nail bed capillary changes Normal SR (sed rate?) Age will be Under 30

Question 58

RP is mostly women, involving episodic ischemia of digits nose and ears with triphasis color change. Precipitated by cold, rxs, emotional stress and can be painful. What antibody are digital ulcers associated with? What antibody is finger loss associated?

Answer 58

Digital ulcers: anti-topoisomerase Finger Loss: anti-centromere

Question 59

What are the secondary causes of RP? 5 bold categories

Answer 59

1. **CT disease**, especially scleroderma with nail capillary changes and serological changes. 2. **Drugs & Toxins** – ergotamine, sumatriptan, bleomycin\*, vinblastine, caffeine, nicotine. 3. **Structural arterial disease** – atherosclerosis, emboli, migraine. 4. **Occupational** –vibration. 5. **Hemorrheologic** - PV, cryoglobulins, cold agglutinins. 6. Other - thoraic outlet and carpal tunnel syndrome, 7. Pheochromocytoma, hypothyroidism.

Question 60

What are the skin and muscle changes in scleroderma?

Answer 60

Hyperpigmented fibrotic skin (no mucun deposition, or papules). Tendon friction rubs, joint stiffness (with inflammation), and restricted ROM.

Question 61

What GI stuff happens in scleroderma?

Answer 61

Gastric antral vascular ectasia (GAVE) hypomotile bowels

Question 62

If a patient with scleroderma has renal involvement what antibody will they have?

Answer 62

Anti-RNA polymerase III

Question 63

What are the three risk factors for renal involvement in scleroderma?

Answer 63

1. rapid skin progression 2. anemia 3. anti-RNA polymerase III

Question 64

What are the components of scleroderma cardiac disease?

Answer 64

Works like an infiltrative cardiomyopathy ## Footnote - R/L BBB - Diastolic heart failure (preserved ejection fraction) - Myocardial Fibrosis

Question 65

What do all collagen vascular diseases have in common regarding the lungs?

Answer 65

All can cause Iterstitial lung disease (ILD)

Question 66

What would tell you a patient has ILD caused by scleroderma specifically?

Answer 66

Anti-SCL-70 antibodies/antitopoisomerase 1

Question 67

What is the leading cause of scleroderma death?

Answer 67

Interstitial lung disease

Question 68

In addition to the ILD, what other lung problem can happen? Why does it arise?

Answer 68

Pulmonary Hypertension - can arise independent of ILD d/t vascular thickening

Question 69

What risk factors would predispose a scleroderma patient to developing pulmonary htn?

Answer 69

1. **telangectasia**. 2. late age at onset. 3. decreasing diffusion capacity. 4. elevated N-terminal pro-BNP. **5. anti-centromere antibody, and anti-B23.**

Question 70

What are the impacts of scleroderma on the GI system? hgdhjtgfhjb

Answer 70

1. Dysphagia 2. Bacterial overgrowth 3. Intestional pseudoobstruction 4. Gastric antral vascular ectasia

Question 71

Where is scleroderma not seen in CREST?

Answer 71

Proximally

Question 72

CREST has a lower incidence of internal organ dysfunction, with what noteable exceptions? 2

Answer 72

* **Higher incidence of pulmonary HTN with +anticentromere antibody** * **PBC common also**

Question 73

What does eosinophilic fasciitis typically follow? What do you see? TQ

Answer 73

Vigorous exercise See sparing of the hands, with eosiniphilia and fascial thickening

Question 74

What body parts does scleredema hit?

Answer 74

Prominent involvement of neck, shoulders, upper arms (hands spared)

Question 75

What are the findings in sleredema (of Buschke)? TQ

Answer 75

Mucin in the dermis Woody induration of back

Question 76

What are two things associated with Scleredema?

Answer 76

Diabetes May follow acute URI

Question 77

What is seen in scleromyxedema?

Answer 77

PApular mucinosis with skin papules and fibrosis.

Question 78

What is scleromyxedema d/t? Will you see raynauds phenomenon?

Answer 78

Gammopathy - skin lickenoid and thickened but not tethered. May see raynaud's

Question 79

What do eosinophilic fasciitis, scleredema and scleromyxedema all have in common?

Answer 79

M proteins

Question 80

Given that M protein is associated with eosinophilic fasciitis, scleredema and scleromyxedema, what is one type of patient likely to get these diseases?

Answer 80

Multiple myeloma patient

Question 81

What is shown here?

Answer 81

Groove sign, associated with eosinophilic fasciitis

Question 82

What is plantar faschitis and polyarthritis syndrome caused by? TQ

Answer 82

Paraneoplastic syndrome d/t adenocarcinoma and hematologic malignancies (MM, CML, Hodgkins)

Question 83

What are the characteristics of Plantar Fasciitis and polyarthritis syndrome?

Answer 83

1. Fibroblast proliferation due to **TGF-beta** 2. Pain, stiffness, and swelling of the DIP and PIP joints **3.Thickening of the palmar fascia** **4.Finger flexion contractures** 5.ANA negative **6.No RP**

Question 84

What are the criteria for dermato/polymyositis? TQ

Answer 84

1. Shoulder and hip weakness 2. Elevated enzymes 3. Positive EMG 4. Myofiber degeneration with mononuclear infiltration 5. Skin changes in DM (shawl sign, Gottron’s papules, heliotrope eyes, and nailfold capillary loops).

Question 85

Of the criterion for dermato/polymyositis, how many out of how many criteria are needed to "suggest" or straight up diagnose dermato/polymyositis?

Answer 85

3/5 suggest DM/PM 4/5 define the diagnosis

Question 86

What cells are responsible for the dmg in dermatomyositis?

Answer 86

B cells and CD4 celld

Question 87

What cells are associated with polymyositis?

Answer 87

CD8 macrophages

Question 88

What are the hallmark signs of dermatomyositis?

Answer 88

Symmetrical proximal muscle weakness. Difficulty climbing stairs or arising from chair. Oropharyngeal (proximal) dysphagia. Facial erythema. Shawl sign. Heliotrope. Gottron’s patches. Mechanic’s hands.

Question 89

If dermatomyositis is causing ILD, what antibodies will be present?

Answer 89

Anti-Jo1 Antisynthetase

Question 90

What are the clinical features for MCTD? TQ

Answer 90

1. RP 2. No renal or CNS disease\* 3. More severe arthritis (+RF) and non-fibrosis pulmonary hypertension (HLA-DRB1) 4. Anti-U1-RNP with 70 Kd protein abs

Question 91

If a patient seems dead with... absent DTRs absent sensation Flaccid distal and proximal muscle groups Then what should you think?

Answer 91

Critical illness myopathy/polyneuropathy

Question 92

What are the three main presentations of relapsing polychondritis? What is it d/t? TQ

Answer 92

Stridor, boxer ears, conjunctivitis D/t autoimmune attack on type II collagen

Question 93

What must you know about IgG4 related disease?

Answer 93

Involves obliterative phlebitis blocking blood vessels