Seronegative: AS, PsA, ReA, IBD-associated Flashcards
1
Q
ASAS Criteria
A
Only apply if: >3 mo back pain + onset <45y
- Sacroilitis on imaging (definite radiographic by NY or active inflammation on MRI) plus 1 SpA feature
- OR
- HLAB27 + 2 SpA features
2
Q
New york classification criteria
A
Clinical criteria
- LBP and stiffness >3 mo (improves w/ exercise not rest)
- Limited L-spine ROM in lateral flexion (expect >10cm) and frontal planes (schober - expect increase of 10—>14cm)
- Limited chest expansion relative to normal values correlated with age + sex
Radiological criteria (based on X-ray pelvis AP)
- ≥ Gr II bilaterally or ≥ Gr III unilaterally
- Definite = 1 of each
3
Q
ASAS SpA features
A
- Inflamm back pain
- Arthritis
- Enthesitis (heel)
- Uveitis
- Dactylitis
- Psoriasis
- CD/UC
- NSAID response
- Fam Hx SpA
- HLAB27
- Elevated CRP
4
Q
IBP vs Mech LBP
-Age
- Onset
- Duration
- AM stiffness
- Nocturnal
- Effect of exercise vs rest
- Back mobility
- Alternating buttock pain
A
-Age: <40 vs any age
-Onset: insidious vs acute s/p injury
-Duration: >3mo vs <4wks
-AM stiffness: >60min vs <30min
-Nocturnal: Freq vs absent
-Effect of exercise vs rest:
-Back mobility: lost in all planes vs flexion abnormal
-Alternating buttock pain: present in early vs not present
5
Q
Px tests
- Good and Bad
A
Good:
-Occiput to wall, chest expansion (abN <2.5, N>5), Schober (at least 4.5cm)
-Bad: pelvic compression, Gaenslens, Patricks/FABER
6
Q
Sites of enthesitis
A
-Supraspinatous
-Patellae
-Clavicles
-Calcanei (achilles or plantar)
-Epicondyle - lateral, medial
-ASIS, PSIS
-Greater trochanter
-SI joints
-Ligamentous structures of intervertebral disks
-Manubriosternal joints
-Symphysis pubis
-Attachment in spinous process
7
Q
Peripheral joints of axSpA
A
-TMJ
-Cricoarytenoid
-Shoulders
-Sternoclavicular, sternocostal, manubriosternal, costovertebral,
-Hips, Symphysis pubis
8
Q
DDx costochondritis
A
-Tietze syndrome
-Infxn
-Spondyloarthropathy
-SAPHO
-Relapsing polychondritis
9
Q
Extraarticular manifestations AxSpa
A
-Skin
-Neuro
-Ocular
-Cardiac
-Pulmonary
-GI
-Renal
-Discitis or spondylodiscitis (Andersson lesions)
10
Q
Cardiac manifestations AxSpa
A
-Aortopathy: regurg, aortitis, root dilation
-Conduction abnormalities: AV block
-Diastolic dysfcn,
-Pericarditis,
-CAD
11
Q
Neuro manifestations AxSpa
A
-C1-C2 subluxation,
-Cauda equina from spinal arachnoiditis,
-Traumatic spinal fractures w myelopathy (C5-6, C6-7),
-Ossification of posterior longitudinal ligament with spinal stenosis
12
Q
Renal manifestations AxSpa
A
-2ndary amyloid
-IgA nephropathy
-chronic prostatitis
13
Q
Skin manifestations AxSpa
A
-Psoriasis,
-Erythema nodosum,
-Keratoderma blennorhagicum,
-Pyoderma gangrenosum
14
Q
Pulmonary manifestations AxSpa
A
-ILD
-Chest wall restriction
-Spontaneous PTX
-Sleep Apnea (Cspine disease compresses oropharyngeal airway and respiratory centres in medulla)
15
Q
C spine involvement in Ank Spond
A
-C1-C2 subluxation —> spinal stenosis
-Cervical ossification, facet ankylosis, fracture, kyphosis
16
Q
Ocular manifestations AxSpa
A
Acute anterior uveitis
Conjunctivitis
Cataracts
Glaucoma
17
Q
GI manifestations AxSpa
A
-Asymptomatic microscopic colitis
-Crohn’s like lesions in ileum and colon
18
Q
HLA B27 pathogenesis of Ank Spond
A
-Arthritogenic peptide: microbial peptides bind HLA B27 → CD8+ cytotoxic T cells
-Molecular mimicry: shared epitopes on infecting organisms and HLAB27 or other self peptides
-Homodimer formation: HLAB27 form stable homodimers without associated beta 2 microglobulin on cell surface → activate NK, T, and B cells via TLR
-Misfolding protein: HLA B27 misfolds –> unfolded protein stress response and autophagy –> IL23 activates Th17 cells
19
Q
XR view for SI joints
A
AP and ferguson view (AP w tube angled 25-40degrees cephalad)
20
Q
MRI order for AS
A
MRI pelvis w/ T1 sequence (for ankylosis, erosions, backfill, fatty metaplasia) and STIR sequence (for osteitis/inflam)
-Include semi coronal views
21
Q
**seroneg XR features pelvis **
A
Bilateral, symmetric sacroiliitis (lower ⅔)
-NY grading
– Gr 0: normal
– Gr 1: suspicious changes
– Gr 2: Sclerosis or minimal iliac erosion
– Gr 3: erosions, sclerosis, WIDENING, narrowing, partial ankylosis
– Gr 4: complete ankylosis/fusion
Enthesopathy: Iliac crest, greater tuberosities of the humerus, ischial tuberosities, femoral trochanters, calcaneus, vertebral spinous processes
22
Q
**XR features Spine (and what causes it) **
A
Early: Romanus lesion / shiny corners
Moderate: Squaring of vertebral bodies
Late:
-Andersson lesions (inflamm destructive spondylodiscitis)
-Flowing syndesmophytes (ossification of annulus fibrosis)
-Bamboo spine (fusion of facet joints and calcification of spinal ligaments) → chalk stick fracture
-Dagger sign (supraspinous ligament calcification)
23
Q
SASSS stoke ankylosing spondylitis spine score
A
Anterior/posterior changes in L spine T12-S1
-Gr 0: normal
-1: erosion, sclerosion, squaring
-2: syndesmophytes (NONBRIDGING)
-3: ankylosis (bridging between upper and lower vertebrae)
24
Q
Romanus lesion
A
Enthesitis of annulus fibrosis @ corner of vertebrae
25
Ax Spa imaging monitoring
-Avoid MRI to confirm inactivity
-Against repeat XR at scheduled intervals
26
**MRI features AS**
-Bone marrow edema
-Bone erosions
-Fat infiltration (increased signal in bone marrow)
-Bone spur from vertebral endplate to adjacent vetebra
-Syndesmophytes
-Spondylodiscitis (Andersson lesion)
-Ankylosis across spine /SI joint
27
**Pathogenesis of AxSpA radiographic changes - erosions, syndesmophytes**
-Bone morphogenic proteins (BMP) and WNT cause calcification at SI joints and entheses
-TNFa stim BMP but downregulates WNT
-Enthesis T cells (CD3/4/8/IL23) respond to IL23 and release IL17 (cause inflamm) and IL22 (induce osteoblast bone formation)
28
**DDx SI Joint changes (AxSpa)**
-Inflamm: Spondyloarthropathy, Behcet, Gout
-Infxn: Staph, Psuedomonas, brucellosis, TB
-Cancer: Mets
-Traumatic: Fracture, OA/Degeneration, Osteitis condensans Ilii, Paraplegia
-Metabolic: HyperPTH, Paget
29
OCI XR/MRI findings
XR: dense sclerotic triangle only on iliac side (lower half of SIJ)
-MRI: Hypointense SI joint
30
OCI risk factors
-Multiparous women → stress on SI joint from loosened pelvic ligaments
-Obesity
31
**DISH radiographic findings**
-Flowing hyperostosis (bone formation) on right side of spine (contralateral to heart and aorta)
-Calcification of anterior longitudinal ligament of at least 4 contiguous vertebral bodies)
-Nonerosive enthesopathy (whiskering)
-Lateral XR: linear radiolucency between calcified anterior longitudinal ligament and anterior vertebral surface
32
**AS poor prognosis factors**
-EARLY hip involvement or syndesmophytes
-Extra-articular: uveitis, CV involvement, pulm fibrosis
-ESR >30 or persistent high CRP
-Poor NSAID response
33
**RF for poor TNFi response in ank spond**
Older
High BMI,
High BASFI
Low CRP
Low physician global
34
Causes of death
-CV disease
-Infxn
-Cancer
-Spinal fractures
35
**AxSpa Tx (and which are not effective)**
-NSAIDs (high dose x 2-4 weeks; continuous celecoxib decreased radiographic progression, ie disease modifies!)
-ASAS/EULAR 22: TNF = IL17i = JAKi (for radiologic SpA only NOT NR-SpA)
-**NO concurrent MTX with TNF (consider with infliximab)
-IA GC injxn (NOT for enthesopathy)
-Bisphosphonate, Ca/Vit D
-Not effective: abatacept, IL6i (toci/sarilumab), anti- IL23, Ritux, steroids (except in preg)
36
**How to measure biologic treatment efficacy**
Change in ASDAS >1.1 or BASDAI >2
*AFTER 12 weeks of tx
37
**IL17i (list 3-4) and how it works**
Ixekizumab = human IgG4 mab binds IL17A and prevents binding to IL17R
-Secukinumab = human IgG1 mab binds IL17A and prevents binding to IL17R
-Others: brodalumab, bimekizumab
38
**IL17 when to use and not use in ax-spa**
Preferred if psoriasis,
Avoid in IBD, can cause flare
39
**JAKi caution**
Infxn: Zoster, TB
Cardiac: DLPD, CVD, CAD, VTE
Cytopenias
Bowel perforation
Cancer
40
TNFi for uveitis or IBD
Monoclonal AB (not soluble R): Infliximab or Adalimumab
41
**Options if losing efficacy w/ antiTNF**
Change dose/interval
-Change to IL17i over different TNFi or adding DMARD if PRIMARY nonresponse (fails to induce)
-Change to different TNFi if SECONDARY nonresponse
42
**AxSpa Nonpharm**
-Daily exercise: stretch, chest expansion, swim
-Mattress: firm, supine, small neck support, sleep prone 15-30 min prev kyphosis
-No smoking
-Fall evaluationcounseling
43
**AxSpa Surgical Options**
-THA for severe pain, limited ROM
-Vertebral wedge osteotomy for severe kyphotic deformities (high risk, not recommended)
- Spinal fusion
- Spinal decompression
44
AxSpa Meds if peripheral
-SFZ 1500BID > MTX
-NO LFN or apremilast
45
**Pathogenesis ReA**
HLA pathogenesis:
-Arthritogenic peptide: HLAB27 bind microbial peptides (molecular mimicry) to activate CD8 cytotox T cells
-HLAB27 homodimer → activate NK, T/B cells
-HLAB27 misfolding → autophagy and IL17/23 activation
Gut microbiome:
-Microbiome is different in SpA and degrade gut mucosal barrier → microbes translocate to circulation --> stim IL17/23
46
**Infectious bugs causing ReA**
- GU
- GI
- Resp
- Viral
GU: chlamydia trachomatis
-GI: Salmonella, Shigella, Yersinia, Campylobacter > Cdiff, Giardia, E coli
-Resp: chlamydia PNA, GAS
-Viral: HIV
-Other rare: vibrio, H pylori, Kleb PNA, Stringy, Mycobacterium bovis
47
**Risk factors for chronic ReA / poor prognostic features**
-Male
-ESR>30
-Age of onset <16y
-Unresponsive to NSAIDs
-HLAB27+
-Family Hx SpA
-Hip involvement
-Dactylitis
-Lumbar spine stiffness
-Heel & foot involvement
-Chlamydia induced ReA
-Reinfection
-Chronic Gut inflammation
48
**Extraarticular systems: ReA**
-Constitutional: fever, weight loss
-Ocular:
-Cardiac (rare)
-GI
-GU /Renal
-Mucocutaneous
-Renal:
-MSK
-Other
49
**Ocular manifestations ReA**
-Sterile conjunctivitis,
-Anterior uveitis (acute/unilat)
50
**Cardiac manifestations ReA**
-Heart block,
-Aortitis,
-Aortic regurg,
-Pericarditis
51
**GI manifestations ReA**
-Colitis/ileitis (infectious and sterile)
52
**GU manifestations ReA**
Same as Ank Spond: IgA nephropathy, Renal amyloid, and prostatitis
+ inflammation of GU structures (urthreitis, hemorrhagic cystitis, salpingitis, vulvovaginitis)
**Circinate balanitis (painless serpiginous ulcer of glans penis) - Chlamydia**
53
**Mucocutaneous manifestations ReA**
-Painless oral ulcers,
-Hyperkeratotic nails,
-Erythema nodosum,
-**Keratoderma blenorrhagicum (psoriasiform on soles, palms; waxy papular → hyperkeratotic scaly) - Chlamydia**
- Livedo reticularis
Thrombophlebitis
54
MSK manifestations ReA
-Asymmetric oligo >poly (knees, ankles, feet > upper extremity) >1mo
-Axial: C/T/L spine, SI joints
-Enthesitis (plantar fascia, achilles, iliac spine/crest)
-Dactylitis (arthritis + enthesitis + tendinitis)
-Tenosynovitis
-Peritendinitis
-Bursitis
- Neuropathy
55
ReA DDx
Infectious:
- Gonococcal arthritis
- Acute septic
- Syphilis
- Lyme
- Rheumatic fever
IA: PsA, RA, IBD arthritis
Autoimmune: Crystal, Behcet
56
ReA vs Gonococcal
-Sex
-Age
-Migratory
-Joints
-Enthesitis
-Spondylitis
-Tenosynovitis
-Dactylitis
-Urethretitis
-Uveitis
-Oral ulcers
-Cutaneous lesions
-Cx positive
-HLA B27
-Cephalosporin responsive
-Sex: M>F vs F>M
-Age: 20-40 vs all
-Migratory: no vs yes
-Joints: lower limbs vs upper limbs and knees
-Enthesitis: yes vs no
-Spondylitis: yes vs no
-Tenosynovitis: yes for both
-Dactylitis: yes vs no
-Urethretitis: yes for both
-Uveitis: yes vs no
-Oral ulcers: yes vs no
-Cutaneous lesions: keratoderma and balanitis vs pustules
-Cx positive: No vs Yes in <50%
-HLA B27: Yes vs Same as general popln
-Cephalosporin responsive: No vs yes
57
ReA vs RA
-Sex, age
-Joints, Enthesitis, Spondylitis
-Ocular
-Lung disease:
-Urethritis
-Cutaneous lesions
-RF
-HLA
-Sex: M>F vs F>M
-Age: 20-40 vs all
-Joints: oligo large vs poly small
-Enthesitis: yes vs no
-Spondylitis: yes vs no
-Ocular: conjunctivitis/uveitis vs keratitis/scleromalacia/sicca/scleritis
-Lung disease: no vs yes
-Urethritis: Yes vs no
-Cutaneous lesions: keratoderma and balanitis vs SC nodules and vasculitis
-RF: neg vs pos
-HLA: B27 vs DR4
58
Synovial findings ReA
-Nonspecific inflammatory: WBC 2k-50k (acute=neuts, chronic= lymph/mono)
-Decreased viscosity, Normal glucose, Increased protein
**Reiter cells = large macrophages w/ engulfed lymph, PMN**
59
Radiographic features ReA
Asymmetric erosive oligoarthritis lower > upper: MTP, SI joint
Dactylitis, Enthesitis
Periostitis, Ankylosis
ASYMMETRIC NONMARGINAL JUG HANDLE syndesmophytes
60
HLA B27 impact on ReA
-Disease severity
-Freq of exacerbations
-EAM: Aortitis, uveitis, spondylitis
61
Nonpharm ReA
-RICE - rest, ice, compress
-Exercise: light+ROMwhen inflam subsides (1-2wks) → active
-Avoid reinfection behaviour
62
**ReA: Extraarticular manifestations tx **
-Uveitis → optho, MTX, MMF, AZA, LEF, CNI, CYC, ADA, IFX, Sek, NO etanercept
-Keratoderma blenonorrhagicum → steroids and keratolytic agents
63
**2 Biologics for IBD with uveitis**
-Adalimumab
-Infliximab
-NO ETANERCEPT or IL17
64
Pharm ReA: Arthritis
Initial (<6mo)
-NSAIDs x2 weeks (CBC, Cr, LFT q2-3mo)
-IA GC
-PO GC (20mg/d → 30-60mg daily) - taper
-csDMARD (after fail 2 NSAID or pred >5mg x3mo)
Chronic (>6mo or resistant to initial)
-csDMARD: SFZ (2-3g/d) > MTX, LFN x3-4 mo (if respond, continue for 3-6mo after remission; otherwise switch)
-bDMARD (TNFi if fail above or enthesitis/dactylitis)
65
Pharm ReA: Abx
- Initial
-Chronic
-Prophylaxis
Initial:
-None if uncomplicated, unless old/immunocompromised or Cdiff:
- Azithro 1g or doxy100mg BID x7 for Chlamydia
Chronic chlamydia ReA:
-6mo: doxy 100mg BID + rifampin 300mg daily
Prophylactic if prev ReA and develops urethritis (azithro 1g) or diarrhea (campylo: azithro; vs + cipro if salmonella, shigella, yersinia)
66
Diagnostic criteria for undifferentiated peripheral spondyloarthropathy
ASIS:
-Peripheral arthritis (asymmetric lower) or enthesitis or dactylitis + one of (HLAb27, GI/GU infxn, psoriasis, IBD, MRI sacroillitis)
-OR
Peripheral arthritis (asymmetric lower) or enthesitis or dactylitis + 2 of following (arthritis, enthesitis, dactylitis, inflamm back pain, fam hx spondyloarthropathy)
67
Bowel diseases assocd w/ inflam arthritis
-IBD
-Microscopic colitis (lymphocytic or collagenous)
-Infectious gastroenteritis
-Whipple’s disease
-Celiac disease
-Bowel assoc’d dermatosis arthritis syndrome (BADAS)
68
Most common peripheral joints in CD/UC
Knees and ankles
69
Type 1 vs Type 2 arthritis in IBD
- Chronicity
- Erosions
- Joint distribution
- IBD activity
- Genetics
-Acute (resolve w/i 3-6mo) vs Chronic
-Nonerosive vs Erosive
-Pauci vs Polyarticular
-Parallels vs Independent of IBD activity
-HLAB27/B35, DR B1*0103 vs HLAB44
70
Extraintestinal manifestations IBD SpA
-Derm: Pyoderma gangrenosum, erythema nodosum, aphtous ulcers, granulomas
-Inflamm eye (acute anterior uveitis), vasculitis
-MSK: Periostitits (HPOA w clubbing), OP, AVN, enthesitis
-Psoas abscess or septic hip from fistula (CD)
-Amyloid
71
IBD Serologies
-ANCA (pANCA to lactoferrin NOT MPO)
-ASCA
72
IBD assocd SpA Tx (Peripheral vs Axial)
Peripheral:
- NSAID, Steroids,
- Mexalamine
- SFZ, MTX, AZA
- TNFi, Secukinumab, Ustekinumab
- Bowel resection for UC Type 1 only
Axial
- NSAIDs, steroids
- TNFi, Secukinumab, Ustekinumab
73
Pouchitis
-Cause
-Presentation & rheum dz
-Tx: 1st, 2nd, 3rd
-Inflamm of ilean pouch after UC colectomy
-Watery or bloody diarrhea;
Peripheral SpA (but NO axial SpA, RA, or thyroid disease as seen in lymphocytic/collagenous colitis)
-1st line: Flagyll and Cipro
-2nd line: Immunosuppression if abx resistant
-3rd line: surgical if treatment resistant
74
Microscopic colitis
-Presentation & rheum dz
-Tx
-Presentation: watery diarrhea +/- arthritis +/- autoimmune thyroiditis
-Tx: Budesonide +/- loperamide
75
**Link btwn BOWEL and AS pathogenesis **
- 5-10% AS pt develop IBD, up to 70% hv subclinical gut inflammation
-Overlapping genes: IL23-R, TYK2, JAK2, IL27
-IL23 production increased in terminal ileum of patients w/ AS --> IL17 secretion
-TH17 mediated inflamm (increased IL6/17a/23)
-Gut derived lymph/macrophages in circulation and synovial fluid
76
Celiac dz manifestations
-Symmetric nonerosive polyarthritis - large joints (knees, ankles > hips/shoulders)
-Gluten --> immune response on gut --> steatorrhea --> deficient Fe, B12 (cerebellar/periph neuropathy), Vit D (hyperPTH --> osteomalacia and metabolic bone dz )
-Dermatitis herpetiformis (→ gluten free +/- dapsone)
-Infertility
77
Celiac pathophys
-Gluten partially digested to peptide → deaminated by tissue transglutaminase increase immunogenecity
-Gliadin peptide presented to CD4 Tcells via HLA DQ2/8 → interferon gamma release, inflamm, gut perm, and villous atrophy
78
-Celiac dx
-IgA antibodies against tissue transglutaminase if NOT IgA deficient (while on gluten rich diet)
-Gold std: Jejunal biopsy shows villous atrophy
-DO NOT use antigliadin AB (not spec)
79
Bowel-associated dermatosis-arthritis syndrome (BADAS) presentation
-Constitutional - flu-like, fever, malaise, myalgia
-Arthritis - nonerosive, inflamm, oligoarticular (upper and lower, large and small), migratory
-Rash - maculopapular or vesiculopustular of trunk or upper extremity
80
Bowel assocd dermatosis arthritis syndrome (BADAS) Pathogenesis & DDx
Bacterial overgrowth of blind bowel loop → antigenic stimulation + immune complex formation depositing in skin/joints
DDx:
-Intestinal peristalsis: bypass, resection, scleroderma
81
BADAS Tx
NSAIDs, steroids, antibiotics
Surgical reanastomosis of blind loop eliminates symptoms
82
Pancreatic dz assoc’d w/ rheum syndromes
Pancreatitis, pancreatic cancer, pancreatic insuff
83
Pancreatic, panniculitis, and polyarthritis (PPP) syndrome pathogenesis
Pancreatitis/cancer → damage and release of trypsin/lipase/amylase
84
Pancreatic, panniculitis, and polyarthritis (PPP) syndrome presentation
PANCREAS
-P - Pancreatitis
-A - arthritis/arthralgias - ankles, feet; noninflamm synovial fluid, creamy from lipid, stain w/ sudan black or oil red
-N - nodules (tender, red, extremities) with lobular panniculitis w/ fat necrosis (not septal as in EN). Fasciitis from subcut fat necrosis
-C - cancer > pancreatitis
-R - radiographic osteolytic lesions from BM necrosis
-E - Eosinophilia (Schmidt’s triad = eos + nodule + arthritis)
-A - amylase/lipase/trypsin elevated → fat necrosis in skin, synovium, and bone marrow
-S - serositis (pleuropericarditis) + fever
85
Autoimmune hepatitis Type 1 vs Type 2
-AB
-Overlaps with which autoimmune conditions
-Type 1 (95%): ANA, antiDNA, AMA, pANCA, anti-smooth, anti-F-actin, Anti-SLA/LP, hypergammaglobulinemia
-T1DM, autoimmune thyroid, IBD, celiac, psoriasis, rarely RA, SS, SLE MCTD, SS
-Type 2 (5%) - anti LKM and anti-liver cytosol AB.
-T1DM, vitiligo, autoimmune thyroid
86
Conditions assocd w/ PBC
-Arthritis, Sicca (Secondary Sjogrens),
-Raynaud (Limited SSc, SLE, PM)
-Autoimmune thyroiditis
-Celiac, IBD
-Pernicious anemia
-Osteomalacia and OP (Vit D malabsorption and RTA)
-HPOA
87
Dose adjustment for severe hepatobiliary
See Rheum secrets
88
**CASPAR classification of PsA**
Entry criteria = inflamm arthritis + 3 of the following:
-Current (2 pts) OR past OR Fam Hx of Psoriasis
-Psoriatic nail dystrophy
-Neg RF
-Dactylitis (current OR past)
-XR findings: juxtaarticular new bone formation
89
PsA subtypes/patterns & assoc’d features
1. Asymmetric oligoarthritis - dactylitis
2. Predominant DIP - nail changes
3. Arthritis mutilans - osteolysis and telescoping of digits
4. RA like - wrist fusion
5. Isolated Axial involvement - asymmetric SI-itis, jughandle like syndesmophytes
90
Sacroiliitis in PsA, ReA, IBD, AS
-PsA: asymmetric sacroiliitis. large nonmarginal, jug handle like syndesmopytes
-ReA: asymmetric
-IBD: symmetric
-AS: symmetric sacroiliitis. Thin marginal symmetric syndesmophyhtes
91
PsA features (less likely in RA)
-Asymmetric, oligoarticular
-No RF
-Nail pitting/dystrophy
-DIP involvement w/o OA
-Dactylitis
-Enthesitis
-Fam Hx psoriasis/PsA
-Sacroiliits, syndesmophytes
-Lack of periarticular osteopenia
92
**Types of psoriasis**
(Vulgar, guttaral, flex, palm, nail, erythedermic)
-Guttate - pink/red scaly raindrops
-Vulgaris - MC; demarcated, thickened, silver scales
-Flexural/Inverse psoriasis - body folds/genitals
-Palmoplantar - palms/soles, fissures, cracks, pustulosis
-Nail psoriasis - pitting, onycholysis, yellowing, ridging
-Erythrodermic - redness with scaling ; triggered by infxn, low Ca, prednisone withdrawal, antimalarials, EtOH
93
**Diseases assoc’d w/ psoriasis**
-Seroneg: ReA, inflamm arthritis, uveitis
-GI: Celiac’s, IBD
-Metabolic syndrome: DLPD, HTN, T2DM, obesity, CAD, ACS, stroke, NAFLD
-Ca - cutaneous Tcell lymphoma
-Psych: Depression, anxiety, fibro
94
PsA Nail findings
-Pitting,
-Onycholysis,
-Oil spot sign
-Hyperkeratosis
-Nail crumbling
-Yellowing
-Transverse ridging
95
PsA Eye findings
-Anterior uveitis,
-Conjunctivitis
96
Other PsA findings
-Oral ulcers
-Urethritis
-Colitis
-Aortic arch dilatation → aortic insuff
97
** PsA Pathogenesis **
-Genetic predisposition w/ exposure to environmental DAMPs/PAMPs --> IL1, 6, 17, 23, TNFa release --> dermal hyperplasia, synovitis, enthesitis
-IL17 --> promotes synovial fibroblast, chondrocyte, and OC activation
-IL22 phosphorylates STAT3 in OB -> bone formation. and induces hyperkeratosis
- IL23 causes more inflammation via IL17, TNFa, IFNg
- TNFa activates keratinocytes → psoriasis
98
PsA Imaging findings
-Asymmetric distrib, incl SI
-DIPs
-Eccentric erosions
-Periostitis
-Bony ankylosis
-LACK of periarticular osteopenia
-Whittling of phalanges → pencil in cup
-Osteolysis (arthritis mutilans)
-Erosion of terminal tufts (acroosteolysis)
-Polyarticular unidigit (MCP, PIP, DIP involved in same finger)
-Erosions at entheseal sites
-US/MRI: enthesitis, dactylitis
99
**PsA Tx **
-NSAIDs,
-IA steroids
If PASI>10 or 3+ joints involved:
-MTX, LFN, SSZ
-Anti TNF +/- MTX
-IL12/23: Ustekinumab
- IL17: (PsA & psoriasis)
-PDE4i: Apremilast aka Otezla (PsA & psoriasis) - if mild and not for bDMARD or JAK
-CTLA4 Ig: Abatacept (PsA> psoriasis)
-JAKi: Tofacitinib/Upa/Figotinib
100
**Types of paradoxical PsO**
-Palmoplantar
-Plaque/Vulgaris
-Guttate
-Nail/scalp
101
**MC TNFi causing paradoxical PsO**
Adalimumab
102
**why does PsO flare w/ TNFi start**
-PsO is CD4 T cell mediated driven by TNF
-With TNFi, no TNF --> IFN driven immune process instead and overexpression of Type 1 IFNa --> paradoxical psoriasis
103
**Treating paradoxical PsO w/ TNFi**
-Mild: add topical GC, phototherapy,
-Add systemic tx: MTX, cyclosporin, acitretin
-Change to different biologic: Il12/23,
104
**PsA and PsO tx that don’t work in RA**
-IL12/23 - ustekinumab
-IL17 - secukinumab/ ixekizumab
-IL23 - guselkumab
105
**Order of PsA Tx - PERIPHERAL **
USE ALL
csDMARDs
TNFi = IL-17 = JAKi = IL-12/23 >
IL23 = PDE4i >
CTLA4 (if DMARD inadequate)
106
**Order of PsA Tx - AXIAL **
NSAID >
anti-TNF = IL17 = JAKi >
No recommendation, insuff evidnece: IL-12/23, IL-23
Recommend AGAINST PDE4i and csDMARDs
No CTLA4 listed on GRAPPA
107
**Order of PsA Tx - enthesitis or dactylitis **
USE ALL but only MTX for csDMARD
-TNFi, IL12/23, IL23, IL17, JAKi, PDE4 inhibitors > Methotrexate > NSAIDs, local GC injections, CTLA4 Ig
108
**Order of PsA Tx - skin **
USE ALL, except CTLA4
-Limited BSA = Topical agents
-Refractory local or widespread: Phototherapy, MTX, Cyclosporine, PDE4i, JAKi, IL17 (including brodalumab aka Siliq), IL12/23, IL-23 (including risankizumab aka skyrizi), TNFi
> Acitretin
109
**Order of PsA Tx - nails **
TNFi, IL-17, IL-23/23, IL-23, PDE4i >
Topicals (calcipotriol, topical GC, tacrolimus, cyclosporin, intralesional GC, pulsed dye laser), cyclosporine, MTX, acitretin, JAKi,
No CTLA4 listed on GRAPPA
110
**IBD assocd arthritis Tx**
IBD: TNFi (not etanercept), IL-12/23 > JAKi, IL-23, MTX. Avoid IL-17 (exacerbate CD)
111
**uveitis Tx**
TNFi (Humira, Remicade; NOT etanercept),
MTX or cyclosporin (conditional recom)
112
**Ustekinumab (stelara) MoA** and role of each cytokine
Monoclonal AB binds p40 subunit in IL12 and IL23 preventing cytokine binding to R
-IL23 involved in differentiation of naive T cells to Th17
-IL12 involved in Th1 response
113
**How does TNF cause rheum manifestations*
-Trigger prostaglandin and proinflammatory cytokine production, recruiting neutrophils
-Upregulates RANKL (osteoclastogenesis)
-Induces Dkk1 (OB inhibitor)
114
TNF types and differences
- Monoclonals - Infliximab (chimeric), Adalimumab (human IgG1 kappa mab), Golimumab (human IgG1 kappa mab), Certolizumab pegol (Fab fragment of recombinant humanized mab, fused to PEG moiety)
- Etanercept is Soluble TNF receptor that binds soluble TNF alpha and TNF beta
115
**IL17i - list 4 and their MoA**
- Secukinumab - humanized IgG1 kappa mab, binds IL17A to prevent interaction w/ R
- Ixekuzumab - humanized IgG4 mab, binds IL17A to prevent interaction w/ R
- Bimekizumab - binds IL17A/F - ongoing trials, not included in guidelines yet
- Brodalumab - binds IL17R - mostly Derm who uses this
116
**Apremilast MoA**
PDE4 inhibitor → higher intracellular cAMP in T cells and mononuclear cells → less pro-inflammatory cytokines (TNFa, IL12/23, IFNgamma, diNO synthase) and increases anti-inflammatory cytokines (eg IL10)
117
**Abatacept MoA**
Selective costimulation modulator - inhibits “signal 2” of T cell activation by binding to CD80/86 (on APCs) and preventing its interaction with CD28 (on T cells
118
**Tofa/Bari/Up/Figlotinib MoA & Risks**
JAK - intracellular prot for signal transduction, recruits STAT TF that translocate to nucleus to form inflammatory mediators
-Tofa = JAK 3 > JAK 1 > JAK 2
-Bari = JAK 1 and JAK 2
-Upa = JAK 1
-Figlotinib = JAK 1 (not in Canada)
-Deucravacitinib = TYK2
-Risks: CVD, VTE, VZV
119
How to treat PsA with active infection
-Hold TNFi
-Lowest infxn risk biologics in PsA
-Peripheral: apremilast, abatacept, anti IL17, anti-IL 12/23, JAKi
-Axial: Nsaids > IL17 > JAK > TNF
120
PsA Poor prognostic factors
-Younger age of onset
-Female
-Polyarticular disease w multiple swollen joints
-High ESR/CRP
-Extra articular manifestations
-Structural damage
121
Other Derm conditions assoc’d w/ seroneg arthritis
-Palmoplantar pustulosis
-Acne conglobata
-Acne fulminans
-Psoriatic onchyopachydermoperiostitis
-Hidradenitis suppurativa
-*typically anterior chest wall, sternoclavicular, sternocostal joint pain
122
** Sapho manifestations**
Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis
-Synovitis: oligo asymmetric (Large>small joint), axial (**sternal**), and SI joints (unilateral)
-Acne: cystic acne, acne fulminans
-Pustulosis: pustular psoriasis, palmoplantar pustulosis, hidradenitis suppurativa
-Hyperostosis: costochondritis, sternocostoclavicular hyperostosis
-Osteitis: symphysis pubis, sacroiliiitis, spondylodiscitis, anterior chest wall and vertebral sclerosis
123
SAPHO etiology
-Infection: Cutibacterium, S Aureus, H flu
-HLAB27
124
** SAPHO Tx **
-NSAIDs
- Colchicine
- Pred
- DMARDs: SSZ, Colchicine
- TNFi
-Tetracycline abx for acne (doxy, minocycline)
- Oral retinoids
Others:
-Bisphosphonates for bone/ osteoarticular manifestations
-IL1, 12/23, 17
125
CRMO manifestations
Chronic, sterile, inflammatory, multifocal disease of metaphysis of long bones in children/adolescents
126
** Difference between Reiter and ReA**
Reiter is triad: conjunctivitis, nongonococcal urethritis, and arthritis
2/3 of ReA do not have all 3 features of triad
127
** Psoriasis treatment approved for PsO but NOT PsA**
L-23 Risankizumab (Skyrizi) is approved for skin psoriasis but not PsA
IL-17 Brodalumab (Siliq) is approved for skin psoriasis but not PsA
128
** Spondyloarthropathy during pregnancy and postpartum**
In preg: 1/3 improve, 1/3 worsen
Postpartum: 2/3 worsen
129
** Spondyloarthropathy fx on fertility and pregnancy**
Fertility: unaffected
Pregnancy: increased risk C section, preterm birth, and small for GA
130
** Genes associated with Ank Spond**
HLAB27
ERAP1 - trims peptides for loading in MHC molecules. Mutated + dysregulates processing --> misfolded proteins
IL23R
131
** Unilateral causes of sacroiliitis**
Cancer
Infection: TB, Brucellosis, Pyogenic septic arthritis
Paraplegia
SAPHO
132
** Bilateral ASYMMETRIC sacroliitiis**
PsA, ReA
Gout, Behcet
OA
Relapsing polychondritis
133
** Bilateral SYMMETRIC sacroiliitis**
IBD + IBD assoc'd arthritis
Ank Spond
RA
Multicentric reticulohistiocytosis
Whipple disease
134
** Components of uveal tract**
Anterior uvea: iris and ciliary body
Posterior uvea: choroid
135
** Diseases associated with uveitis and HLA molecule associated **
Seroneg SpA HLA-B27
Behcet: HLA-B51
VKH: HLA DRB1
TINU: HLA DRB1
Birdshot retinochoroidopathy: HLA-A29
Pars planitis: HLA DR2
136
** Uveitis Tx**
Prednisolone acetate 1% (for anterior)
Periocular or intravitreal corticosteroids (severe/posterior)
GC 1mg/kg/d
MTX 25mg weekly
LFN, AZA, MMF, CYC, Ritux
ADA 80mg wk 1, 40mg wk 2 and q2weeks
137
** Pathophysiology of syndesmophytes**
2 pathways:
- PGE2 stimulates OB
- Bone morphogenic protein (BMP) = cytokines of TGFb family involved in bone formation
- WNT pathway (important in osteoblastic bone formation). Inhibitors like DKK1 (Dickkopf related protein) and sclerostin lower in AS
138
** Evidence that inflammation of spine causes ankylosis**
Enthesis resident T cells (CD3,4,8, IL23) respond to IL23 and cause IL17 release (inflammation) and IL22 (induce osteoblast mediated bone formation
139
** DISH features that differentiate it from AS**
OLDER age of presentation (>50, obese, DM)
NO HLAB27 or family history
NONinflammatory back pain
NO sacroiliitis, facet joint ankylosis, erosions
NO extraarticular features (uveitis, IBD, PsO, enthesitis)
PRESERVED disk height
LACK of degenerative changes in vertebral segments involved
Ossification of anterior longitudinal ligament connecting at least 4 vertebral bodies
NONmarginal syndesmophytes
140
** DISH Treatment**
NSAID
PT
Bracing
Bisphosphonate
Surgery
141
** Anterior Uveitis DDX**
HLAB27 POSITIVE SpA
Sarcoid
Behcet
HSV
Syphilis
TB
Lyme, VZV, EBV, CMV
142
** Posterior uveitis DDX**
HLAB27 NEGATIVE w/ PsA and Enteropathic
Sarcoid
Bechet
HSV
Syphilis
TB
VKH (birdshot retinochoroidopathy)
Toxo
143
** Panuveitis DDX**
Sarcoid
Bechet
HSV
TB
Toxo
144
** Osteoporosis risk factors in Ank Spond**
Demographic: female, older, low BMI, family hx #, post menopausal status
Disease: duration, inflammation, prednisone use, BASMI
145
** Erythema nodosum DDX**
Idiopathic
Infection: TB, leprosy, mono, HBV, HCV, HIV, parvo, EBV, histo, blasto
Inflamm: ReA, Behcet, IBD, Sarcoid, Whipple
Cancer: Lymphoma, Leukemia
Drugs: Penicillin, sulfonamide, OCP, TNFi
Pregnancy
146
** Is PsA as disabliing as RA? **
Joint damage worse in RA for same disease duration
Function/quality of life same for both
147
** DIP Erosive arthritis DDX**
Erosive OA
PsA
Septic arthritis
Malignancy
Gout
**Multicentric reticulohistiocytosis (~to RA but DIP destruction and arthritis mutilans; GC has little effect)**
148
** Frequency of B27 in general population?
Frequency of B27 in pt with AS?
Chance of son developing AS?**
6-9% in general population
90% of patients with AS
50% chance passing it to son, 2-6% of developing AS but increases to 15-20% if family has AS
149
** Diseases assoc'd w/ DISH **
DM
Obesity
HTN
CVD
DLPD
Gout
150
** Vertebral bony sclerosis DDX**
Osteomyelitis: staph, TB
Malignancy (osteoblastic): lymphoma, prostate mets, sarcoma, chondroma
Paget's
Fracture (reactive sclerosis)
Hemangioma
Degenerative endplate changes
SAPHO
Sarcoid
151
** Clinical and/or XR manifestations of enthesitis**
Clinical: pain, swelling, warmth
XR: Erosions, enthesophyte (bone spur)
152
** Osteophyte vs Syndesmophyte:
- Location**
Osteophyte:
- Starts at vertebral end plate;
- C/L spine
vs
Syndesmophyte:
- Starts at vertebral corners (enthesis);
- Lower T, L spine
153
** Osteophyte vs Syndesmophyte:
- Orientation**
Osteophyte: HORIZONTAL bony extension of vertebral endplate (ie PART of vertebral body w/ contiguous medulla and cortex)
vs
Syndesmophyte: VERTICAL ossification bridging 2 vertebral bodies (NO cortex or medulla)
154
** Osteophyte vs Syndesmophyte:
- Pathogenesis**
Osteophyte:
- Endochondral ossification
- Disk degeneration --> decreased buffering between bony surfaces, endplate sclerosis, and osteoophytes
Syndesmophyte:
- Ossification of annulus fibrosis (sharpey fibers),
- Gut biome releases IL23 --> IL17 inflammation and IL22 OB mediated bone formation;
-Role of WNT and BMP at entheses
155
** Dactylitis pathogenesis and DDX**
Flexor tenosynovitis +
Synovitis +
Circumferential soft tissue swelling +
Bone edema
DDx: PsA, SpA, TB, Syphilis, GOUT, SARCOID, hemoglobinopathy, sickle cell, idiopathic
156
** PASI score - 4 elements**
Psoriasis Area Severity Index (for head, trunk, arms, legs) - none, slight, mod, severe, v severe
Erythema
Induration
Desquamation/scaling
% covered (palm w/o fingers is 1% BSA)
157
** Proinflammatory cytokines in AS**
TNF, IFNg, IL17, IL23, IL1
158
DDX for arthritis, oral ulcers, uveitis
Behcet, Sarcoid, RPC
ReA, Ank Spond, IBD assoc'd arthritis
Syphilis, HIV
SAPHO
SLE, GPA
159
** Red flag features back pain**
Inflammatory features
Nocturnal pain
Alternating buttock pain
Response to NSAIDs
History of cancer
GC use
Constitutional sx
IVDU
Cauda equina sx
160
** What are Waddell's sign**
Signs of inorganic pain, 3+ of following is positive:
- Superficial and diffuse non-anatomic tenderness
- Pain with simulated movements (axial loading, acetabular rotation)
- No pain when distracted (sitting straight leg raise)
- Regional sensory changes or weakness not following neuroanatomy
- Overreaction to testing
161
** Risk factor for developing axial disease in PsA**
HLAB27
High ESR
Radiographically damaged joints
Nail dystrophy
Periostitis
Male
162
ASDAS components
Back pain (BASDAI q2)
Periph Pain/swelling (BASDAI q3)
AMS (BASDAI q6)
Pt global
CRP
ESR
163
High disease activity in Ank Spond
ASDAS ≥ 2.1 or BASDAI ≥ 4
164
Tapering bDMARD in Ank Spond
Only if ASDAS inactive disease or low disease activity x6months
Can taper TNFi and IL17 but no data on IL17
165
Reiter Cells DDX
Seroneg: IBD assoc’d, PsA,
Crystal arthritis
Septic arthritis, Lyme
JIA
