Connective tissue Diseases (Darrow) - SRS Flashcards
What are the 11 criteria for SLE?
B3 O1 R1 N1 with D3ermA1titiS1
Blood
- Hematologic disorder: pancytopenia
- Immunologic Disorder: anti-ds-DNA, Sm, APA, FPSTS
- ANA
Oral
- Ulcers (vagina, nose, alopecia)
Renal
- Renal disorder (proteinuria or cellular casts)
Neurologic
- Seizures or psychosis
Dermatitis
- Malar Rash
- Discoid rash
- Photosensitivity
Arthritis
- Arthritis with or without active synovitis
Serositis
- Serositis (pleuritis or pericarditis)
Again, what are the 11 clinical criteria per rheum tutor?
- Acute cutaneous lupus
- chronic cutaneous lupus
- oral/nasal ulcers
- non-scarring alopecia
- arthritis
- serositis
- renal
- neurological
- hemolytic anemia
- leukopenia
- thrombocytopenia
What are the immunologic criteria for lupus?
- ANA
- Anti-DNA
- Anti-Sm
- Antiphospholipid antibodies
- Low complement
- Direct coombs test (not in the presence of hemolytic anemia
What are the requirements for SLE diagnosis?
greater than or equal to 4 criteria with at least one clinical and one laboratory criteria.
What are the ANA subtypes?
- Ro/SSA, La/SSB
- Sm
- RNP/U1-RNP
- Scl70/topoisomerase 1
- Jo-1
What is Scl70/topoisomerase 1 associated with?
Scleroderma
What is the Sm ANA subtype associated with?
Lupus mostly
What antibodies are associated with the IF pattern shown here? 6
Speckled Pattern
- anti-Sm - SLE
- Anti-RNP
- Anti-Ro - SS
- Anti-La - SS
- Anti-Jo-1 and Mi-2 PM/DM
- Anti-Scl70
What antibodies are associated with this IF pattern?
Centromere
- anti-centromere - PSS (CREST)
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?
- any type of casts, ie “telescoping urinary sediment”. (but red cells casts most common)
- Proteinuria of > 500 mg/24 hrs, or 3+ dipstick.
CNS involvement in SLE may present with seizures, psychoses, neuropathies, strokes, and what condition that simulates UTI d/t fever and urinary retention?
Transverse myelitis
Differentiate the impact of SLE and APS on the cerebrum.
SLE - Cerebral inflammation
APS - Cerebral Ischemia
What are two specific cardiopulmonary involvements of SLE?
- alveolar hemorrhage
- Libman-sacks endocarditis
What is CRP useful for in an SLE patient?
Differentiating between flare ups and infection.
CRP > 10mg/dL = 80% chance of infection
Why is hydroxychloroquine so wonderful in treating SLE?
- prevents flares
- reduces congenital heart block
- lowers diabetes risk
- reverses platelet activation by IgG antiphospholipid
Is hydroxychloroquine ok for the pregnant patient?
yes, it is great for preggos
What are 5 causes of splinter hemorrhages?
- Nail trauma
- SBE
- Antiphospholipid antibody syndrome
- Hypereosinophilic syndrome
- Libman Sacks endocarditis
Before making a diagnosis of SLE in a random patient what must one exclude?
Drug induced lupus
What are the main drugs involved in triggering drug induced lupus?
- Hydralazine
- Isoniazid
- Procainamide
- Methimazole
- Prophylthiouracil
- Etanercept
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?
- Slow acetylators*
- No renal disease
- No CNS disease
What antibodies are involved in drug induced lupus?
Anti-histone
What tests must be done in a patient with possible lupus who wishes to become pregnant?
- Lupus anticoagulant
- Anticardiolipin antibody
- anti-B2 glycoprotein (apolipoprotein H)
- Antiphospholipid antibody
- anti-RO
- Anti-LA
- nephrotic syndrome
Why screen for the following in a SLE patient wishing to become pregnant?
- Lupus anticoagulant
- Anticardiolipin antibody
- anti-B2 glycoprotein (apolipoprotein H)
- Antiphospholipid antibody
- anti-RO
- Anti-LA
- lupus anticoag, antiphospholipid, anticardiolipin, anti-B2 glycoprotein 1 d/t incresed odds of spontaneous abortion and to identify if patient has APS.
- anti-RO and Anti-La d/t risk of heart block to the child
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
D.Low C3/C4
What is the blood pressure like in SLE vs. preeclampsia?
SLE = HTN present
Preeclampsia = HTN pregnant
No difference, not helpful
What is the urine protein like in SLE and Preeclampsia?
SLE = Proteinuria
Preeclampsia = Proteinuria
Again, no difference/not helpful
What are the platelet levels like in SLE vs Preeclampsia?
SLE = Low
Preeclampsia = low
Again, no difference/not useful for discriminating
What are the LFTs in SLE vs preeclampsia?
SLE = normal typically
Preeclampsia: commonly abnormal
Useful for differentiation
What are the differences seen in serology between SLE and preeclampsia?
SLE = dsDNA and Low C3/C4
Preeclampsia = no findings
What are the uric acid levels like in SLE vs preeclampsia?
- SLE: normal
- Preeclampsia: High
Describe the following for each….
SLE Preeclampsia
HTN: ____ _____
UA: ____ _____
Platelets: ____ _____
Abn LFTs: ____ _____
Serology: ____ _____
Uric acid: ____ _____
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
What antibodies are common to subacute cutaneous SLE?
anti-ro
anti-la
What can be a permanent impact of neonatal lupus?
What is the tx we use for neonatal lupus?
Complete heart block
HCQ
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
E. Anticardiolipin antibody - since there is no history of SLE in the patient’s background.
What are the causes of secondary antiphospholipid antibody syndrome?
CTD’s (SLE especially)
Malignancy
Infections (HIV)
Drugs: phenytoin, chlorpromazine
What is a somewhat unique feature of antiphospholipid antibody syndrome?
Clots both in the venous AND arterial systems
What are the lab criteria for antiphospholipid antibody syndrome?
TQ
- Anticardiolipin antibody
- Lupus anti-coagulant
- Anti-β2 glycoprotein 1* (Apo H**; FPSTS)
What are the clinical criteria for Antiphospholipid antibody syndrome?
- spontaneous abortion
- vascular thrombosis
What antibody has the best correlation with thrombotic events in APS?
What drugs can induce this antibody formation?
LA
Anticoagulants (heparin, etc)
What test is used to confirm antiphospholipid antibody syndrome?
Russel Viper Venom Test
What lab and clinical criteria are needed for dxing antiphospholipid antibody syndrome?
TQ
To diagnose need 1 clinical criteria plus 1 lab criteria 3 months apart.
What are the key components of treatment of APS?
- Anticoagulation
- Steroids
- Hydroxychloroquine
- Statins
- B cell inhibitors
- Complement inhibitors
What is an ADR to watch for with hydroxychloroquine?
Retinitis
If you hear a patient has cryoglobulinemia what does that make you think of?
Hep C
Sjogren
What are the main causes of livedo reticularis of the obstructive variety?
1. Cryoglobulins, cold agglutinins.
2. Antiphospholipid syndrome.
- DIC, TTP.
- Hypercalcemia.
- Polycythaemia rubra vera or thrombocythaemia.
- Infections – Parvo B19, syphilis.
- Arteriosclerosis (cholesterol emboli) and homocystinuria.
What vasculitises cause livedo reticularis?
RA
SLE
DM
PSS
PAN
What are the “characteristics” for scleroderma?
TQ
1.Raynaud’s syndrome.
2.Cutaneous, subcutaneous calcification, pigmentation
and depigmentation, telangiectasias.
- Cardiac: pericarditis, fibrosis, MI*, heart block, R-CHF.
- Pulmonary: restrictive lung disease with decreased CO diffusion, pulmonary hypertension.
- GI: GERD, sticking below the sternum, hypomotility with bacterial overgrowth, large mouth diverticulum.
- Renal: “onion skinning” and hypertension.
What is the main component of the pathogenesis of PSS?
Excess collagen deposition d/t overproduction of TGF-B
What are some causes of PSS (Scleroderma)?
- Fibroblast metabolic defect with increased collagen in the extracellular matrix.
- Endothelial dysfunction and apoptosis with subsequent obliteration.
- Autoimmunity (HLA-DPB1, HLA-DPB2).
- Silica, solvents.
- Paraneoplastic.
The diagnosis of scleroderma requires how many major/minor criteria?
1 major
or
2/3 minor
What are the major criteria in scleroderma?
TQ
Symmetric thickening, tightening and induration of the skin proximal to the MTP/MCP joints. e.g. arms, trunk etc
What are the three minor criteria for scleroderma?
TQ
- sclerodactyly
- digital pitting
- bibasilar pulmonary fibrosis
You can diagnose a high probabilit of scleroderma with 3/5 features of CREST syndrome. Or what three things?
- RP
- nail fold changes
- Scleroderma specific antibody.
What are the components of CREST?
- Calcinosis
- Raynauds Phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
What are the key skin findings in PSS? 5 bold items and more
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.
What are the key differentiating features between primary and secondary RP?
TQ
Primary WILL NOT have nail bed capillary changes
Normal SR (sed rate?)
Age will be Under 30
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?
Digital ulcers: anti-topoisomerase
Finger Loss: anti-centromere
What are the secondary causes of RP? 5 bold categories
- CT disease, especially scleroderma with nail capillary changes and serological changes.
- Drugs & Toxins – ergotamine, sumatriptan, bleomycin*, vinblastine, caffeine, nicotine.
- Structural arterial disease – atherosclerosis, emboli, migraine.
- Occupational –vibration.
- Hemorrheologic - PV, cryoglobulins, cold agglutinins.
- Other - thoraic outlet and carpal tunnel syndrome,
- Pheochromocytoma, hypothyroidism.
What are the skin and muscle changes in scleroderma?
Hyperpigmented fibrotic skin (no mucun deposition, or papules).
Tendon friction rubs, joint stiffness (with inflammation), and restricted ROM.
What GI stuff happens in scleroderma?
Gastric antral vascular ectasia (GAVE)
hypomotile bowels
If a patient with scleroderma has renal involvement what antibody will they have?
Anti-RNA polymerase III
What are the three risk factors for renal involvement in scleroderma?
- rapid skin progression
- anemia
- anti-RNA polymerase III
What are the components of scleroderma cardiac disease?
Works like an infiltrative cardiomyopathy
- R/L BBB
- Diastolic heart failure (preserved ejection fraction)
- Myocardial Fibrosis
What do all collagen vascular diseases have in common regarding the lungs?
All can cause Iterstitial lung disease (ILD)
What would tell you a patient has ILD caused by scleroderma specifically?
Anti-SCL-70 antibodies/antitopoisomerase 1
What is the leading cause of scleroderma death?
Interstitial lung disease
In addition to the ILD, what other lung problem can happen?
Why does it arise?
Pulmonary Hypertension - can arise independent of ILD d/t vascular thickening
What risk factors would predispose a scleroderma patient to developing pulmonary htn?
- telangectasia.
- late age at onset.
- decreasing diffusion capacity.
- elevated N-terminal pro-BNP.
5. anti-centromere antibody, and anti-B23.
What are the impacts of scleroderma on the GI system?
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- Dysphagia
- Bacterial overgrowth
- Intestional pseudoobstruction
- Gastric antral vascular ectasia
Where is scleroderma not seen in CREST?
Proximally
CREST has a lower incidence of internal organ dysfunction, with what noteable exceptions? 2
- Higher incidence of pulmonary HTN with +anticentromere antibody
- PBC common also
What does eosinophilic fasciitis typically follow?
What do you see?
TQ
Vigorous exercise
See sparing of the hands, with eosiniphilia and fascial thickening
What body parts does scleredema hit?
Prominent involvement of neck, shoulders, upper arms (hands spared)
What are the findings in sleredema (of Buschke)?
TQ
Mucin in the dermis
Woody induration of back
What are two things associated with Scleredema?
Diabetes
May follow acute URI
What is seen in scleromyxedema?
PApular mucinosis with skin papules and fibrosis.
What is scleromyxedema d/t?
Will you see raynauds phenomenon?
Gammopathy - skin lickenoid and thickened but not tethered.
May see raynaud’s
What do eosinophilic fasciitis, scleredema and scleromyxedema all have in common?
M proteins
Given that M protein is associated with eosinophilic fasciitis, scleredema and scleromyxedema, what is one type of patient likely to get these diseases?
Multiple myeloma patient
What is shown here?
Groove sign, associated with eosinophilic fasciitis
What is plantar faschitis and polyarthritis syndrome caused by?
TQ
Paraneoplastic syndrome d/t adenocarcinoma and hematologic malignancies (MM, CML, Hodgkins)
What are the characteristics of Plantar Fasciitis and polyarthritis syndrome?
- Fibroblast proliferation due to TGF-beta
- 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
What are the criteria for dermato/polymyositis?
TQ
- Shoulder and hip weakness
- Elevated enzymes
- Positive EMG
- Myofiber degeneration with mononuclear infiltration
- Skin changes in DM (shawl sign, Gottron’s papules, heliotrope eyes, and nailfold capillary loops).
Of the criterion for dermato/polymyositis, how many out of how many criteria are needed to “suggest” or straight up diagnose dermato/polymyositis?
3/5 suggest DM/PM
4/5 define the diagnosis
What cells are responsible for the dmg in dermatomyositis?
B cells and CD4 celld
What cells are associated with polymyositis?
CD8
macrophages
What are the hallmark signs of dermatomyositis?
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.
If dermatomyositis is causing ILD, what antibodies will be present?
Anti-Jo1
Antisynthetase
What are the clinical features for MCTD?
TQ
- RP
- No renal or CNS disease*
- More severe arthritis (+RF) and non-fibrosis pulmonary hypertension (HLA-DRB1)
- Anti-U1-RNP with 70 Kd protein abs
If a patient seems dead with…
absent DTRs
absent sensation
Flaccid distal and proximal muscle groups
Then what should you think?
Critical illness myopathy/polyneuropathy
What are the three main presentations of relapsing polychondritis?
What is it d/t?
TQ
Stridor, boxer ears, conjunctivitis
D/t autoimmune attack on type II collagen
What must you know about IgG4 related disease?
Involves obliterative phlebitis blocking blood vessels
