B-45 Other Rheumatologic Dz - Complete

Front 1

What is Still's Disease? aka?

Back 1

Systemic Onset Juvenile Idiopathic Arthrits (soJIA)
aka Juvenile Rheumatoid Arthritis
aka Juvenile Chronic Arthritis

Front 2

What HLA Associations are there with Juvenile RA?

Back 2

DRB1*13, DQB1*0301, DRB1*0201

Front 3

Describe the pathogenesis of JRA?

Back 3

TNF-α and macrophage migration inhibitory factor (MIF) overproduced in active disease
interleukin (IL)-6 levels to parallel the fever spikes

Front 4

What are the three major types of JRA?

Back 4

Systemic Onset (Acute febrile systemic) - 20%
Polyarticular Onset JRA - 20%
Pauciarticular JRA – 60%

Front 5

In Systemic Onset JRA, are boys or girls more affected? RF? ANA?

Back 5

Boys = Girls
RF & ANA Negative

Front 6

Describe the exanthem seen in systemic JRA

Back 6

High episodic fevers >101F (38.9C) > 2wks
Exanthem present in up to 90%
Transient (<24hrs ), non-pruritic, erythematous to salmon pink macular/maculopapular lesions on trunk
May precede onset of joint manifestations x months or years
Koebnerizes, exacerbated by heat & pressure
(fever and rash occur at the same time)

Front 7

Describe Arthritis seen in systemic JRA

Back 7

Arthritis of knees, hips, ankles > hands
Normally symmetric
Bone/joint destruction

Front 8

Describe the extra-articular features of systemic JRA

Back 8

Extraarticular features usually self-limited
generalized lymphadenopathy, hepatosplenomegaly, serositis (pericarditis, pleuritis, peritonitis)

Front 9

What are some complications of systemic JRA?

Back 9

Complications: cardiac tamponade or severe vasculitis; both respond to steroids

Front 10

What defines POLYarticular onset JRA?

Back 10

presence of arthritis in 5 or more joints

Front 11

How do you divide POLYarticular onset JRA?

Back 11

RF positive
and
RF negative

Front 12

Describe RF positive Polyarticular onset JRA? c/w RF negative?

Back 12

RF+:
Girls w/ later onset (>age 8)
HLA-DR4+
Erosive arthritis (>50%) of symmetric small-joints
+ Rheumatoid nodules
Greater risk of poor functional outcome
Most closely resembles adult RA
RF - :
Rarely erosive arthritis

Front 13

How do you define Pauciarticular arthritis?

Back 13

Requires 4 or fewer joints in first 6 months

Front 14

HOw do you sub-divide pauci-articular arthritis?

Back 14

Early onset
vs.
Late onset

Front 15

Describe early onset pauciarticular arthritis versus late onset pauci articular arthritis

Back 15

Early onset:
Girls:boys 4:1
Very young (1-5 years)
Often ANA+
High risk of chronic eye inflammation - UVEITIS
Best overall articular outcome

Late onset:
Boys > girls
50% HLA-B27+
Tendonitis and large joint arthritis (shoulders, hips, knees, spine)

Front 16

What mutation is in Familial Mediterranean fever?

Back 16

Mutations in pyrin/marenostrin gene

Front 17

What mutation is in Hyper-IgD syndrome?

Back 17

Mutations in mevalonate kinase gene

Front 18

Describe the fever of Adult-onset Still's Disease

Back 18

*High spiking fevers -- prominent feature
*Occurs in late afternoon or evening & resolves within hours

Front 19

Describe the exanthem in AOSD? Demographic of AOSD?

Back 19

Bimodal 2nd & 4th decades
90% have exanthem
is an Asymptomatic salmon pink macules
favors the trunk & sites of pressure and Koebnerization

Front 20

How do you diagnoses AOSD?

Back 20

>5 criteria (including 2 major)
Major:
Fever >39C
Arthralgia > 2wks
Still's rash
Neutrophilic leukocytosis
Minor:
Sore Throat
LN or splenomegaly
Liver dysfunction
Negative RF & ANA

Front 21

Describe the distinctive arthritis in Adult Onset Still's Disease (AOSD)

Back 21

Carpal ankylosis is distinctive feature of the arthritis
Ankylosis in DIP/PIP joints resulting in boutonniere deformity
X-ray demonstrating non-erosive fusion of carpal bones
Distinctive feature of AOSD

Front 22

What are some other clinical features of AOSD?

Back 22

Other: sore throat, LAD, splenomegaly, pleuritis, pericarditis, abdom pain

Front 23

What is Relapsing Polychondritis?

Back 23

Inflammatory d/o affecting cartilaginous structures, suspected autoimmune origin
Can involve ears, nose, respiratory tract

Front 24

What % of relapsing polychondritis is assoc with other autoimmune disorders?

Back 24

25-30%
also has an assoc with myelodysplastic syndromes

Front 25

What abs are seen in relapsing polychondritis?

Back 25

IgG to Type II collagen

Front 26

What HLA is assoc with relasping polychondritis?

Back 26

HLA-DR4

Front 27

What is Matrillin-1?

Back 27

a cartilage matrix protein in auricular, septal, tracheal and sternal cartilage
- may also play role in humoral immune response

Front 28

Levels of what correlate with Dz severity in relapsing polychondritis?

Back 28

elevated ESR, CRP, Urinary type II collagen epitope

Front 29

What other organ systems are involved in relapsing polychondritis?

Back 29

Nasal chondritis in 70%
- Rhinitis with crusting/bleeding
- Saddle nose deformity can occur even w/ minimal inflammation

Arthritis in 80%
-- Sternoclavicular, costochondral, sternomanubrial joints
-- Complications: rib or clavicle dislocation, flail chest

Ocular inflammation involving any part of the eye in 65%
- Conjunctivitis, scleritis, iritis, globe perforation

Respiratory tract involvement is most serious complication
- Cough, hoarseness, choking, dyspnea, wheezing, tenderness to palpation of trachea
- Complications: airway obstruction/collapse, secondary pulmonary infections

Renal involvement confers worse survival

Dermatologic manifestations in 36%
- aphthosis, palpable purpura, livedo reticularis, Sweet’s, EED

Other features
hearing loss, cardiac valvular damage, cranial nerve palsies

Front 30

What is MAGIC syndrome?

Back 30

Mouth And Genital ulcers and Inflamed Cartilage
-- an overlap b/tw RP and Behcet's disease

Front 31

Describe the Histology of Relapsing Polychondritis

Back 31

Perichondrial inflammation
PMNs, lymphs (CD4>CD8), plasma cells
Degeneration of cartilage (chondrolysis) w/ vacuolization & decreased basophilia
Perichondrial fibrosis in older lesions
DIF → lupus-like continuous granular band of immunoglobulin and complement in perichondrium (NON-SPECIFIC)

Front 32

How do you Diagnose Relapsing polychondritis?

Back 32

Presence of greater than or equal to 3 of the following:
1. Bilateral auricular chondritis
2. Nonerosive inflammatory polyarthritis
3. Nasal chondritis
4. Ocular inflammation: conjunctivitis, keratits, scleritis/episcleritis, uveitis
5. Respiratory tract chondritis
6. Cochlear or vestibular dysfunction: neurosensory hearing loss, tinnitus, vertigo

Front 33

what is aka as Sicca Syndrome?

Back 33

Sjogren's syndrome

Front 34

What is the Classic Triad in Sjogren's syndrome?

Back 34

1. Keratoconjunctivitis sicca
2. Xerostomia
3. Arthritis

Front 35

When does Sjogren's present?

Back 35

Presents in 4th-5th decades; F:M 9:1
Primary d/o or in assoc with other autoimmune dz
Autoimmune phenomenon directed towards salivary glands

Front 36

What HLA types are assoc with Sicca syndrome?

Back 36

HLA-B8, -DR3, -DQ2, -DRw52a

Front 37

What is the DDx for elevated anti-Ro (SSA)?

Back 37

MN: RHOSSAN
RA
Hypocomplement
Oriental
SCLE
Sjogren
Aged
Neonatal lupus

Front 38

What are Ro and La?

Back 38

members of the Aquaporin family of water channels in duct and secretory cells targeted by Th1 T-cell response

Front 39

What are auto-abs to Ro called? to La?

Back 39

Ro = Anti-SSA (30-95% in Sjogrens)
La = Anti-SSB (15-60% in Sjogrens)

Front 40

What other auto-abs are seen in Sjogren's? and, what other lab abnmls are seen?

Back 40

Anti-fodrin IgA and IgG (a component of cell membrane cytoskeleton)
RF+
elevated ESR and CRP
elevated titers of IgG, IgA, and IgM

Front 41

Patient's w/ Sjogren's syndrome is prone to what type of malignancy?

Back 41

Marginal zone (non-Hodgkin's) B-cell lymphomas of the salivary glands
Pathogenesis related to increased levels of bcl-2 and bcl-x in lymphocytes infiltrating salivary glands (anti-apoptotic genes)

Front 42

Describe symptoms of Sjogren's Syndrome

Back 42

Most prominent feature is DRY MUCOUS MEMBRANES

Xerophthalmia
Foreign body sensation, photophobia, blurred vision, absence of tears

Xerostomia
Dry, sore, burning mouth & lips, perleche, dental caries, thrush

Vaginal xerosis
Dryness, burning, dyspareunia
Complicated by Candida & bacterial overgrowth

Front 43

What is the Schirmer test?

Back 43

Schirmer test: Paper wick folded over lower eyelid for 5 minutes; lacrimal gland dysfunction if tear film migrates <5mm

Front 44

What is at increased risk if vasculitis is seen in Sjogren's?

Back 44

increased risk of systemic involvment

Front 45

Describe the skin manifestations of Sjogren's syndrome

Back 45

Skin manifestations:

Xerosis w/ prominent pruritis (most common)

Annular erythema
- Subset of Asian pts w/ erythematous, indurated annular dermal plaques of face

Lymphocytic vasculitis mimicking pigmented purpura

Cryoglobulinemia Types II & III
- r/o B-cell lymphoma if Type II

Urticarial vasculitis, digital ulcers

Front 46

What are some Extra-glandular manifestations seen in Sjogren's?

Back 46

Extra-glandular manifestations:
Fatigue
Arthritis
(polyarticular, chronic & progressive affecting knees & ankles)
Renal
(Interstitial nephritis, tubular dysfunction)
Pulmonary
(interstitial pneumonitis on X-ray)
CNS/PNS involvement (vasculitis)
- Immune mediated hearing loss & peripheral neuropathy
- short-term memory loss, depression
Extranodal lymphomas/pseudolymphomas

Front 47

What is the gold standard for diagnosing Sjogren's?

Back 47

Minor Salivary gland biopsy. LCCV can be seen at post-capillary venule; lymphocytic infiltrate of exocrine glands --> >50 lymphs/4mm2 (both T and B cells)

Front 48

What are the clinical features seen in Mixed Connective Tissue Disease?

Back 48

Raynaud’s phenomenon
Sausage digits (75%)
Sclerodermoid &
poikilodermatous areas
Photosensitivity
Polyarthritis (85%)
- Jaccoud’s arthropathy due to periarticular involvement & ligamentous laxity
Esophageal dysmotility (75%)
Pulmonary hypertension
- abnormal PFTs in 85%

Front 49

Compared to SLE, what dz are more or less involved in MCTD?

Back 49

MCTD has a decreased rate of renal/CNS disease, but increased rate of pulmonary disease than in SLE

Front 50

What autoab is found in MCTD?

Back 50

Anti-U1RNP
(also seen in SLE, SSc & Polymyositis)
Of note: Anti-TS1-RNA antibodies seen in subpopulation w/ predominance of lupus-like features

Front 51

What is U1RNP and which portion is usually the target of autoab?

Back 51

U1RNP is 3 polypeptides that associate with U1RNA
Most ab are against U1 small nuclear riboprotein (snRNP) or U1-70K protein

Front 52

Describe DIF of MCTD

Back 52

Granular epidermal nuclear IgG deposition

Front 53

What ratio of CD4/CD8 is seen in MCTD?

Back 53

increased CD4/CD8 (more CD4 T-lymphocytes than in PM or DM pts)

Front 54

Describe Histology of MCTD

Back 54

Early = proliferative vasculopathy of small and medium vessels
Late = dermal fibrosis and interface dermatitis
(similar to LE or DM)

Front 55

What are some factors in the development of Rheumatoid arthritis?

Back 55

HLA-DR1 & DR4
Infectious agents (EBV, E. Coli) with molecular mimicry of HLA-DR-Dw4
Gain of function polymorphism in PTPN22 gene (Neg regulator of T-cell activation)

Front 56

What % of pt's with RA have Rheumatoid Nodules?

Back 56

20%
Assoc with moderate to high RF titers

Front 57

What is rheumatoid nodulosis?

Back 57

Increased number of nodules in pts treated with MTX

Front 58

Which RA pt's get rheumatoid vasculitis?

Back 58

- Pts with long standing joint dz (a late complication and hih mortality)
- Very high RF levels
- Affects small (palpable purpura & scleritis), medium (ulcers, nodules, livedo reticularis, digital infarcts) to large vessels
-- shows neutrophilic destruction of vessel wall & fibrinoid necrosis (similar to PAN w/ medium vessel involvement)

Front 59

What other problems are found when medium vessels are involved in rheumatoid vasculitis?

Back 59

-- 40% w/ peripheral neuropathy (ex., mononeuritis multiplex)
-- rheumatoid papules (lesions of hands showing vasculitis and palisading granuloma)

Front 60

What are three signs of mononeuritis multiplex?

Back 60

1. Asymmetry
2. Asynchrony
3. Predilection for distal nerves

Front 61

What are Bywater's lesions?

Back 61

Purpuric papules affecting the digital pulp
(LCCV histo, but NOT assoc with systemic vasculitis)

Front 62

Name the Ulcerative Diseases associated with Rheumatoid Arthritis

Back 62

Rheumatoid vasculitis involving medium-sized vessels
Felty's syndrome
Pyoderma Gangrenosum
Palisading neutrophilic and granulomatous dermatosis (superficial ulcerating rheumatoid necrobiosis)
Antiphospholipid syndrome

Front 63

Three things that compose Felty's Syndrome?

Back 63

1. Granulocytopenia
2. Splenomegaly
3. Therapy-resistant leg ulcers

Front 64

What subset of RA pts get Felty's syndrome? How is it treated?

Back 64

UNCOMMON but severe dz in seropositive RA
Treated with G-CSF and/or splenectomy

Front 65

What subset of pts get rheumatoid neutrophilic dermatoses?

Back 65

Pts with seropositive RA

Front 66

What are the Rheumatoid Neutrophilic Dermatoses?

Back 66

Pyoderma gangrenosum
Sweet's syndrome
Rheumatoid Neutrophilic dermatitis

Front 67

What are the two major clinicopathologic patterns of Interstitial Granulomatous Dermatitis?

Back 67

1. Palisaded Neutrophilic and Granulomatous Dermatitis (PNGD)
2. Interstitial Granulomatous Dermatitis (ICD) with Arthritis