Seronegative Arthritis

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    Seronegative Arthritis (common)

    • In the past was called "seronegative spondyloarthropathies"
    • Refers to the group of inflammatory diseases:
      • Ankylosing Spondylitis
      • Psoriatic Arthritis
      • IBD-Ass'd Arthritis
      • Reactive Arthritis (prev. called Reiter's syndrome)
    • Can overlap, and Shared Tendency --> Inflammation and calcification of enthesis (new bone formation in tendon insertion sites)
    • Risk Factors
      • Strong Genetic Predisposition (HLA-B27 is the strongest risk factor)
        • 95% of AnkSpond Patients are HLA-B27 positive (sub-Saharan Africa has low incidence)
        • 50% of Reactive Arthritis (possibly predicting worse outcomes). 
    • Must distinguish between axial & peripheral involvement (treatments can vary!)    
    • Consider in any patient with inflammatory back pain who is younger than 40yo
      • Definition of "Inflammatory Back Pain":

        • Age < 40yo
        • Insidious onset of back pain
        • Improvement with exercise
        • No improvement / worse with rest
        • Pain at night --> improves when get out of bed

         

      •  
    • Diagnosis:
      • ASAS - mnemonic
      • Diagnostic Criteria of Spondyloarthritis

        • Sacroiliitis revealed on imaging
          (MRI most sensitive, CT for bony disease)
        • At least one spondyloarthropathy feature (see below)

          OR

          (Considered "Pre-radiographic axial spondyloarthritis")
        • HLA-B27 Positive and
        • Two Additional spondyloarthropathy features (see below)

         

        Spondyloarthropathy features (ask all patients):

        • Inflammatory back pain
        • Arthritis
        • Enthesitis  (esp. check plantar, Achilles, elbow epicondyles)
          • Improvement with NSAIDs can help distinguish from fibromyalgia 
        • Dactylitis (sausage-like toes/fingers - due to tenosynovitis)
        • Uveitis
        • Psoriasis
        • Crohn's Disease
        • Ulcerative Colitis
        • Family History of Spondyloarthritis
        • Presence of HLA-B27
        • Elevated CRP
        • Good Response to NSAID

     

    • Laboratory:
      • RF and Anti-CCP are usually negative
      • CRP and ESR correlate with disease activity in SOME patients (especially those with peripheral disease)
        • Most have normal ESR/CRP
      • HIV testing (for reactive and PsA, especially with severe skin manifestations)
      • Stool Cultures + Urine samples (chlamydia)
      • IgA and IgM level elevation --> may give evidence of infection (i.e. Yersinia, Salmonella)
    • Imaging:
      • Single AP Pelvis Xray + Hips --> all patients with suspected SpA
        • Erosion at iliac portion of SI joints (earliest)
        • Irregularity of cortex (moderate)
        • Joint space obliterated - fused (severe/late)
        • Spine: Bridging Syndesmophytes -> flowing connections + squaring of vertebrae (instead of normal Hourglass shape)
      • MRI of SI joints (most sensitive)
        • Performed if dx of sacroiliitis is still suspected
        • Evaluate bone marrow edema (acute SI inflammation)
      • CT Scan
        • Can be performed, but MRI is considered best

     

    Ankylosing Spondylitis

    • Pathobiology/Introduction
      • The pathobiologic hallmark is that inflammation of the tendons and ligaments causes bone deposition.
      • The key is to decrease inflammation (NSAIDs for spinal involvement) to prevent bone deposition.
      • Inflammation typically involves spine and SI joints.
        • Any level of spine can be involved - can be patchy
    • Epidemiology
      • M:F ratio 3:1
      • Prevalence 0.2-1.4% (mechanical back pain is 80%)
      • Inflammatory back pain features in 20-25% of mechanical back pain. 
    • Classification
      • New York Criteria
      • Radiologic Criteria (Sacroilitis grade, bilat/unilat, etc..)
    • joints Asp.png

     

    • Involvement:
      • Articular:  (usually oligoarthritis)
        • Hips
      • Extra-Articular: 
        • Cardiac: Aortic Valve Disease, Aortitis, premature CAD
        • Resp: Restrictive Lung Disease (CVA rigidity), Apical fibrosis
    • Terms:
      • "Nonradiographic axial spondyloarthritis" - axial SpA without radiographic changes of AS on plain Xrays (MRI usually shows changes)
    • Symptoms:
      • Typically presents in early adulthood
      • Progressive inflammatory back pain (worse in AM, improves with movement/exercise)
        • Pain/Stiffness in Back (usually localized to low back, buttocks, post-thighs).
        • Inflammation with time goes up spine producing stooped posture + limited ROM of spine+chest.
        • Rigidity increases risk of Fracture (causing myelopathy/radiculopathy)
      • Other Symptoms
        • Olygoarthritis (usually hip involvement)
        • Dactylitis
        • etc. 
    • Physical Exam:
      • Vital Signs (RR elevated if resp involvement)
      • Inspection (Extra-articular features)
        • Dactylitis
        • Nail changes (onycholysis, pitting, oil drops)
        • Joints for swelling
        • Skin for rashes/psoriasis? (suggest alt dx)
      • Examine all joints (passive/active ROM)
      •  
      • Inflammatory Spine Exam
        • Gait - Trendelenburg gait if hip pathology, 
        • Spine tenderness/ SI joint tenderness
        • Spine ROM (flexion/extension, lateral flexion, rotation) - can measure against wall. 
        • Chest Expansion
          • Tape measure around chest, take deep breath (full insp – rest)
        • Schober’s Test (ank. Spond., seronegative)
          • Mark midline 5cm below PSIS and 10cm above, ask to flex and measure length (5cm incr or more is normal)
        • Occiput to Wall
        • SI Joints:
          • FABER/Patrick's Test
            • Flexion-Abduction-External Rotation
            • Pain on ipsilateral buttock
          • Gaenslen's Maneuver
            • Flexion and extension of contralateral hips 
            • Stresses SI joints
      • Extra-Articular Manifestations
        • Enthesitis (tenderness of insertion of tendons)
          • Check plantar, achilles, and lateral elbow epicondyles
        • Head & Neck - Anterior Uveitis (unilateral)
        • Cardiac (AR? Aortic root dilation, aortitis)
        • Respiratory -upper lobe crackles? (apical fibrosis?), decreased chest expansion
        • Neurologic - cord or root signs (if cord or root compromized)
    • Diagnosis
      • History findings (inflammatory back pain)
      • Physical (arthritis/enthesitis)
      • Labs:
        • Normocytic anemia, ESR/CRP elevated
        • HLA-B27 (if high suspicion of AS)
          • (4-14% of all pop'n will have positive)
          • 95% of ASp patients will have HLA-B27 positive
      • Imaging
        • Starts at SI joints
        • SI Joints (X-rays or MRI more sensitive)
          • Inflammation
          • Erosions
          • Fusing of joints
        • Spine: (ascends up spine)
          • Squaring of vertebral bodies (instead of healthy hour-glass)
          • Enthesophytes - vertical bridging syndesmophytes (not horizontal like in OA) following ligaments
          • NOTE:
            • DISH - Diffuse idiopathic skeletal ostosis (usually asymptomatic) - see calcification of ant. longitudinal ligament + horizontal syndesmophytes (starts thoracic spine). 
        • Only do MRI of SI joints if suspect on Xray (X-ray first)
        • Initially lateral spine view shows loss of posterior concavity
    • Disease Severity Index
      • BATH (Ankolysing spondylitis disease activity index)
    • Treatment:
      • Hallmarks: NSAIDs and Physiotherapy
      • Anti-TNF therapy for axial disease (methotrexate does not help spine) if no response to NSAIDs
        • Unclear if TNF-inhibitors are disease modifying (but control symptoms)    
      • Non-Pharmacologic
        • Physical Therapy --> Improves physical function, wellbeing
      • Pharmacologic
        • Axial Disease
          • 1st Line: NSAIDs
            • 80% of pts respond to anti-inflammatory regular doses.
            • No data on type of NSAID to be used, but if no response after 2 weeks => switch.
          • Anti-TNF (does not respond to DMARDs)
            • Considered 2nd line to NSAIDs
            • For peripheral and axial involvement. (not first line due to cost and safety).
            • Only advised if NSAIDs are ineffective or not tolerated.
        • Peripheral Joint Disease
          • NSAIDs
          • IA steroids
          • Non-Biologic DMARDs (Methotrexate, Sulfasalazine)
            • Used for peripheral arthritis (not effective in axial spondyloarthritis).
    • NOTES:
      • methotrexate does not work (except maybe extra-axial involvement)
      • steroids do not work
      • no role for opioids
    • Reference:
      • Song IH, Poddubnyy DA, Rudwaleit M, Sieper J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal anti-inflammatory drugs. Arthritis Rheum. 2008;58(4):929-938. PMID: 18383378
      • NEJM Knowledge+ Question
      • MKSAP 16 audio lectures

     

    Psoriatic Arthritis

    • 3-10% of pts with psoriasis. (precedes psoriasis in 15%)
    • Patterns of PsA

      joints PsA.png

      • Axial / Spondylitis 
      • Asymmetric 
      • DIP involvement
    • Criteria:
      • CASPAR Criteria (2006)
      • RF-, Dactylitis, psoriasis (current/ FMhx)

     

         Involvement

    • Classically DIP points (unlike RA)
      • Often pencil-in-cup deformity at PIP joints. 
    • VERY HETEROGENEOUS --> 5 patterns of joint involvement
      • DIP and nail changes.
      • Asymmetric oligoarthritis (most common - 70%) <5 joints
      • Symmetric polyarthritis (similar to RA)
      • Arthritis Mutilans (5%) (extensive osteolysis of digits with striking deformity)
      • Sacroiliitis and spondylitis (usually older, male)
    • Other findings:
      • Dactylitis
      • Tenosynovitis (hands)
      • Enthesitis
    • Extra-articular/skin manifestations:
      • Optho: Conjunctivitis, Iritis (anterior uveitis)
      • CV/Resp: AR murmur, apical lung fibrosis
      • Neuro: Cauda Equina
      • Radiologic:
        • Floating syndesmophytes
        • Pencil-in-cup appearance of IP joints.
        • Osteolysis
        • Periostitis
    • Dermatologic:
      • Psoriasis: Well-demarcated erythematous plaques
        • Look at inter-gluteal fold, scalp behind ear
      • Nail changes:
        • Pitting
        • transverse/longitudinal ridging, subungual hyperkeratosis,
        • Onycholysis  (exclude fungal)
        • O il drops. 
      • onycholysisOilDrops.jpg    SubUngualHyperkeratosis.jpg
      • (Onycholysis+oil drops on R, and subungual hyperkeratosis on L)
    • Laboratory Findings
      • No autoantibodies that are specific for PsA
        • ANA positive 1:40 in 50%, and ≥1:80 in 14%
        • RF positive in 10%, Anti-CCP in 5-10%
        • dsDNA antibodies can appear after exposure to TNF inhibitors
        • HLA-B27 positive
    • Imaging Studies:
      • Erosions
      • Osteophytes (bone destruction/creation - absent in RA)
      • Pencil-in-Cup Deformity (prox phalanx eroded into pencil, and distal phalanx is cup)
      • Arthritis Mutilans (erosions aggressive - entire phalanx eroded)

     

         Treatments

    • EROSIVE arthritis (like RA), treat EARLY
      • It is said that erosive nature is more aggressive than RA.
    • Skin:
      • Dovobet (50mcg/g & 0.5mg/g) - Vitamin D & betamethasone ointment.
      • Treat skin lesions (steroid cream, salicylic and/or retinoic acid, tar, UV light)
      • Vitamin D analogues are useful.
    • Joints:
      • NSAIDs for mild arthritis (not effective for skin, can worsen skin involvement)
      • Often first line: **Methotrexate**
        • Improves skin symptoms too.
      • Notes:
        • AVOID steroids  (worsen skin symptoms, and not very effective).
        • Rituximab - only one case report, do not use.
    • Ref:
      • Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665-2673.PMID: 16871531
      • MKSAP 16 audio lectures

    Reactive Arthritis

    • Post-infectious aseptic arthritis, formerly called Reiter's Syndrome
    • Incidence 30 in 100,000 pts.
    • 1-4w after infection (usually GI)
    • R/O HIV
    • Classic triad (1/3 have)
      • Arthritis
      • Urethritis
      • Conjunctivitis
    • Classic Pathogens:   (GI and GU tract)  - but can be asymptomatic infection
      • Chlamydia
      • Yersinia
      • Salmonella
      • Shigella
      • Campylobacter
      • Less common: C.difficile & Chlamydophila pneumoniae
    • Clinical Presentation
      • Oligoarticular Arthritis develops several days to weeks after infection
    • Involvement
      • Axial:
        • SI joint involvement can be seen, full spinal involvement is less common
    • Management:
      • Self-limited, treat underlying infection
        • Symptoms last 3-6mo
        • No joint destruction
        • NSAIDs for symptoms (can try various)
        • If pain persists:
          • Intra-articular steroids
      • If symptoms persist >6mo, use DMARD (methotrexate)
      • 30-40% become chronic/recurrent (typically HLA-B27 positive)
        • Can develop features of PsA, IBD-assd arthritis, AnkSpond
    • Source: MKSAP 16 audio lectures

     

    IBD-Associated Arthritis

    • 50% of IBD patients will get MSK symptoms (but arthritis is uncommon)
    • Clinical Features:
      • Axial: Spine disease can be asymptomatic or mimic AnkSpond
        • 20% have axial involvement (mostly men)
        • Radiographic sacroiliitis and spondyloarthritis (+/- inflammatory back pain)
        • Axial disease does NOT parallel 
      • Peripheral Joints: Oligoarthritis of lower extremities
        • Can be acute or chronic
        • Pauci-articular distribution
        • Knee (acute) - correlates with IBD activity
        • MCP joints (chronic) - correlates less. 
      • Other:
        • Enthesitis (10%)
    • NOTE: HIGH risk of septic arthritis (immunosuppressive treatment) + baseline disease
    • Management
      • Resolves without intervention
      • No joint destruction
    • Source: MKSAP 16 audio lectures
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