Seronegative: AS, PsA, ReA, IBD-associated Flashcards
ASAS Criteria
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
New york classification criteria
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
ASAS SpA features
- Inflamm back pain
- Arthritis
- Enthesitis (heel)
- Uveitis
- Dactylitis
- Psoriasis
- CD/UC
- NSAID response
- Fam Hx SpA
- HLAB27
- Elevated CRP
IBP vs Mech LBP
-Age
- Onset
- Duration
- AM stiffness
- Nocturnal
- Effect of exercise vs rest
- Back mobility
- Alternating buttock pain
-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
Px tests
- Good and Bad
Good:
-Occiput to wall, chest expansion (abN <2.5, N>5), Schober (at least 4.5cm)
-Bad: pelvic compression, Gaenslens, Patricks/FABER
Sites of enthesitis
-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
Peripheral joints of axSpA
-TMJ
-Cricoarytenoid
-Shoulders
-Sternoclavicular, sternocostal, manubriosternal, costovertebral,
-Hips, Symphysis pubis
DDx costochondritis
-Tietze syndrome
-Infxn
-Spondyloarthropathy
-SAPHO
-Relapsing polychondritis
Extraarticular manifestations AxSpa
-Skin
-Neuro
-Ocular
-Cardiac
-Pulmonary
-GI
-Renal
-Discitis or spondylodiscitis (Andersson lesions)
Cardiac manifestations AxSpa
-Aortopathy: regurg, aortitis, root dilation
-Conduction abnormalities: AV block
-Diastolic dysfcn,
-Pericarditis,
-CAD
Neuro manifestations AxSpa
-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
Renal manifestations AxSpa
-2ndary amyloid
-IgA nephropathy
-chronic prostatitis
Skin manifestations AxSpa
-Psoriasis,
-Erythema nodosum,
-Keratoderma blennorhagicum,
-Pyoderma gangrenosum
Pulmonary manifestations AxSpa
-ILD
-Chest wall restriction
-Spontaneous PTX
-Sleep Apnea (Cspine disease compresses oropharyngeal airway and respiratory centres in medulla)
C spine involvement in Ank Spond
-C1-C2 subluxation —> spinal stenosis
-Cervical ossification, facet ankylosis, fracture, kyphosis
Ocular manifestations AxSpa
Acute anterior uveitis
Conjunctivitis
Cataracts
Glaucoma
GI manifestations AxSpa
-Asymptomatic microscopic colitis
-Crohn’s like lesions in ileum and colon
HLA B27 pathogenesis of Ank Spond
-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
XR view for SI joints
AP and ferguson view (AP w tube angled 25-40degrees cephalad)
MRI order for AS
MRI pelvis w/ T1 sequence (for ankylosis, erosions, backfill, fatty metaplasia) and STIR sequence (for osteitis/inflam)
-Include semi coronal views
**seroneg XR features pelvis **
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
**XR features Spine (and what causes it) **
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)
SASSS stoke ankylosing spondylitis spine score
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)
Romanus lesion
Enthesitis of annulus fibrosis @ corner of vertebrae
Ax Spa imaging monitoring
-Avoid MRI to confirm inactivity
-Against repeat XR at scheduled intervals
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
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)
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
OCI XR/MRI findings
XR: dense sclerotic triangle only on iliac side (lower half of SIJ)
-MRI: Hypointense SI joint
OCI risk factors
-Multiparous women → stress on SI joint from loosened pelvic ligaments
-Obesity
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
AS poor prognosis factors
-EARLY hip involvement or syndesmophytes
-Extra-articular: uveitis, CV involvement, pulm fibrosis
-ESR >30or persistent high CRP
-Poor NSAID response
RF for poor TNFi response in ank spond
Older
High BMI,
High BASFI
Low CRP
Low physician global
Causes of death
-CV disease
-Infxn
-Cancer
-Spinal fractures
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)
How to measure biologic treatment efficacy
Change in ASDAS >1.1 or BASDAI >2
*AFTER 12 weeks of tx
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
IL17 when to use and not use in ax-spa
Preferred if psoriasis,
Avoid in IBD, can cause flare
JAKi caution
Infxn: Zoster, TB
Cardiac: DLPD, CVD, CAD, VTE
Cytopenias
Bowel perforation
Cancer
TNFi for uveitis or IBD
Monoclonal AB (not soluble R): Infliximab or Adalimumab
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
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
AxSpa Surgical Options
-THA for severe pain, limited ROM
-Vertebral wedge osteotomy for severe kyphotic deformities (high risk, not recommended)
- Spinal fusion
- Spinal decompression
AxSpa Meds if peripheral
-SFZ 1500BID > MTX
-NO LFN or apremilast
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
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
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
Extraarticular systems: ReA
-Constitutional: fever, weight loss
-Ocular:
-Cardiac (rare)
-GI
-GU /Renal
-Mucocutaneous
-Renal:
-MSK
-Other
Ocular manifestations ReA
-Sterile conjunctivitis,
-Anterior uveitis (acute/unilat)
Cardiac manifestations ReA
-Heart block,
-Aortitis,
-Aortic regurg,
-Pericarditis
GI manifestations ReA
-Colitis/ileitis (infectious and sterile)
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
Mucocutaneous manifestations ReA
-Painless oral ulcers,
-Hyperkeratotic nails,
-Erythema nodosum,
-Keratoderma blenorrhagicum (psoriasiform on soles, palms; waxy papular → hyperkeratotic scaly) - Chlamydia
- Livedo reticularis
Thrombophlebitis
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
ReA DDx
Infectious:
- Gonococcal arthritis
- Acute septic
- Syphilis
- Lyme
- Rheumatic fever
IA: PsA, RA, IBD arthritis
Autoimmune: Crystal, Behcet
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
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
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
Radiographic features ReA
Asymmetric erosive oligoarthritis lower > upper: MTP, SI joint
Dactylitis, Enthesitis
Periostitis, Ankylosis
ASYMMETRIC NONMARGINAL JUG HANDLE syndesmophytes
HLA B27 impact on ReA
-Disease severity
-Freq of exacerbations
-EAM: Aortitis, uveitis, spondylitis
Nonpharm ReA
-RICE - rest, ice, compress
-Exercise: light+ROMwhen inflam subsides (1-2wks) → active
-Avoid reinfection behaviour
**ReA: Extraarticular manifestations tx **
-Uveitis → optho, MTX, MMF, AZA, LEF, CNI, CYC, ADA, IFX, Sek, NO etanercept
-Keratoderma blenonorrhagicum → steroids and keratolytic agents
2 Biologics for IBD with uveitis
-Adalimumab
-Infliximab
-NO ETANERCEPTor IL17
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)
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)
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)