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JIA, Imaging, Labs and Misc




JIA Categories:
  • Systemic: Stills
  • PsA
  • ERA
  • Oligoarthritis 
    • Persistent
    • Extended 
  • Polyarthritis Seronegative
  • Polyarthritis Seropositive
  • Undifferentiated / Overlap

Radiography: MKSAP 18

  • Plain Xray can help assess and differentiate inflammatory arthritis, osteoarthritis, and crystal arthropathies. Plain Xray is limited in its ability to visualize soft tissues, and may not detect early or small erosive changes
  • CT provides multiple views and orientations from a single study but is more useful for bony abnormalities than for soft-tissue inflammation or fluid collections. CT is more sensitive for detecting bone erosions than plain radiographs or MRI
  • MRI is the most sensitive routine radiologic technique for detecting soft-tissue abnormalities, inflammation, and fluid collections but is less effective than CT in demonstrating bony abnormalities or erosions. MRI is sensitive for detecting early spine and sacroiliac joint inflammation and may be indicated for the evaluation of suspected spondyloarthritis if plain radiographs are negative.
  • USG can assess soft-tissue abnormalities, including synovitis, tendonitis, bursitis, and effusions; assess disease activity using Doppler; and assist with tendon or joint injections. However, it is operator dependent, and training/practice is needed to achieve competence.

Rheumatologic Disease

Radiographic Findings

Rheumatoid arthritis

Marginal Bony erosions; periarticular osteopenia; subluxations; soft-tissue swelling; MCP, PIP, and wrist involvement

Osteoarthritis

Asymmetric joint-space narrowing; osteophytes; subchondral sclerosis and cystic changes; degenerative disk disease with collapse of disks; degenerative joint disease with facet joint osteophytes; spondylolisthesis (anterior/posterior misalignment of the spine); kyphosis

Diffuse idiopathic skeletal hyperostosis

Calcification of the anterior longitudinal ligament; bridging horizontal syndesmophytes; usually seen in the thoracic spine and more prominent on the right side of the spine

Ankylosing spondylitis

Sacroiliitis; squaring of the vertebral bodies; bridging vertical syndesmophytes; shiny corners; ankylosis does not skip vertebrae

Psoriatic arthritis

Destructive arthritis with erosions and osteophytes; DIP involvement is common; pencil-in-cup deformity on hand radiograph; arthritis mutilans; syndesmophytes

Gout

Punched-out erosions with sclerotic borders and overhanging edges of cortical bones; periarticular soft-tissue swelling with calcifications in tophaceous deposits

Calcium pyrophosphate deposition

Chondrocalcinosis, most commonly of the knees, shoulders, wrists, pubic symphysis; osteoarthritis, including in locations atypical for primary osteoarthritis (MCPs, wrists, shoulders)


Gout: 
Punched-out lesions with overhanging edge of cortical bones. 
Ultrasounds can show unsuspected tophi or a double contour sign at cartilage surfaces, which is highly specific for urate deposits in joint
The ultrasound double contour sign, the identification of monosodium urate crystal deposition by dual-energy CT, and gout-related joint damage on radiography are all included in the new gout classification criteria.

CPPD
Cartilage calcification appears as a linear opacity below the surface of articular cartilage). It most commonly occurs in the knees, wrists (triangular fibrocartilage), pelvis (pubis symphysis), and metacarpophalangeal (MCP) joints, in descending order.

OA
Radiographic features of OA include asymmetric joint-space narrowing, subchondral sclerosis, osteophytes, and bone cysts; however, these changes may not be present in early disease.
 Even in established OA, symptoms may correlate poorly with imaging findings
Although MRI and ultrasonography can detect subtle OA changes at an earlier stage and are increasingly used in OA research, they are not needed for routine OA diagnosis. MRI may be indicated in the setting of symptoms suggestive of a concomitant mechanical disorder (joint catching, locking, instability), but incidental abnormalities such as meniscal tears are commonly seen on MRI in patients with OA and may prompt unnecessary surgical intervention.
Erosive OA: Diagnosis-defining central erosions (in contrast to marginal erosions seen in rheumatoid arthritis) with a “seagull” or “gull-wing” appearance in the finger joints; joint ankylosis (bony fusion) may also occur.

DISH
Radiographic changes characteristic of DISH include confluent ossification of at least four contiguous vertebral levels, usually on the right side of the spine


RA

Plain radiography of the hands and/or feet is a standard imaging study for RA and can aid in diagnosis and assessing progression, although early radiographs may be normal. 

Radiographic changes include periarticular osteopenia, marginal erosions, and joint-space narrowing . 

Radiography of the cervical spine with flexion/extension views is appropriate if C1-C2 subluxation is suspected.

MRI and ultrasonography are more sensitive than plain radiography and may have utility in following disease, assessing risk of progression, and determining response to therapy. 

Ultrasonography is becoming a standard tool for detecting joint fluid, synovial tissue thickening, early erosions, and increased vascularity. 

MRI is used for measuring bone marrow edema, synovitis, and erosions; it is also specifically indicated if atlantoaxial involvement is suspected.


Additional References 
Imaging in rheumatology: reconciling radiology and rheumatology doi: 10.1007/s13244-013-0293-1

Dermatological description

Mechanics hand:  rough, cracked, scaly skin along the lateral aspects of the digits and palms with horizontal lines resembling the weathered hands of a laborer. Seen in Anti-synthetase syndrome in associated with PM or DM 
Gottron rash (Gottron papules and Gottron sign), erythematous to violaceous areas over the metacarpophalangeal and proximal interphalangeal joints seen in DM

Cutaneous Manifestations of Dermatomyositis MKSAP 18

Cutaneous Sign

Location

Clinical Appearance

Gottron rash (Gottron papules and Gottron sign)

Metacarpophalangeal and proximal interphalangeal joints; occasionally on distal interphalangeal joints, elbows, knees

Erythematous to violaceous papules; occasional scale; can ulcerate; atrophic scars may occur

Heliotrope rash

Eyelids

Subtle pink to deep purple or brown discoloration; may be associated with edema of eyelids or periorbital edema

V sign

V of neck

Erythematous to violaceous papules to patches

Shawl sign

Base of posterior neck to upper back

Erythematous to violaceous papules to patches

Fixed erythema

Malar area (may cross nasolabial folds); flanks of trunk

Erythematous to violaceous papules to patches

Nail area changes

Periungual area; cuticles

Periungual erythema; capillary dilatation and dropout; cuticular hypertrophy; cuticular infarcts

Mechanic's hands

Lateral aspects of digits and palms

Hyperkeratotic fissuring of the palmar and lateral surfaces of the fingers resembling the hands of a laborer




Dermatologic Manifestations of Rheumatologic Disease

Rheumatologic Disease

Dermatologic Manifestations

Systemic lupus erythematosus

Butterfly (malar) rash; photosensitive rash; discoid lupus erythematosus; subacute cutaneous lupus erythematosus; oral ulcerations (on the tongue/hard palate; usually painless); alopecia; lupus panniculitis (painful, indurated subcutaneous swelling with overlying erythema of the skin)

Dermatomyositis

Gottron papules (erythematous plaques on extensor surfaces of MCP and PIP joints); photodistributed poikiloderma, including shawl sign (over the back and shoulders) and V sign (over the posterior neck/back or neck/upper chest); heliotrope rash (violaceous rash on the upper eyelids); mechanic's hands (hyperkeratotic, fissured skin on the palmar and lateral aspects of fingers); nailfold capillary abnormalities; holster sign (poikilodermic rash along lateral thigh); can occur in the absence of myositis (amyopathic dermatomyositis)

Systemic sclerosis

Skin thickening and hardening; nailfold capillary changes

Vasculitis

Palpable purpura; cutaneous nodules; ulcers; necrosis

Behçet syndrome

Painful oral and genital ulcers; erythema nodosum; acne/folliculitis; pathergy (skin inflammation/ulceration from minor trauma)

Sarcoidosis

Erythema nodosum; infiltrated plaques; maculopapular and papular lesions; nodules; soft infiltrates of the nose (lupus pernio); on blanching with a glass slide, sarcoid skin lesions reveal “apple jelly” discoloration

Psoriatic arthritis

Plaque psoriasis typically on extensor surfaces, umbilicus, gluteal fold, scalp, and behind ears; pustular psoriasis on palms and soles; nail pitting; onychodystrophy

Reactive arthritis

Keratoderma blennorrhagicum (psoriasiform rash on soles, toes, palms); circinate balanitis (psoriasiform rash on penis)

Adult-onset Still disease

Evanescent, salmon-colored rash on trunk and proximal extremities

Rheumatic fever (secondary to streptococcal infection)

Erythema marginatum (annular pink to red nonpruritic rash with central clearing)

Lyme disease

Erythema chronicum migrans (slowly expanding, often annual lesion with central clearing)

  • MCP = metacarpophalangeal; PIP = proximal interphalangeal.

Table 3. Ocular Manifestations of Systemic Inflammatory Disease

Systemic Inflammatory Disease

Ocular Manifestations

Ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease (anterior chamber); sarcoidosis and Behçet syndrome (anterior and/or posterior chamber); granulomatosis with polyangiitis (posterior chamber)

Uveitis (inflammation of the anterior and/or posterior chamber and/or retina)

Rheumatoid arthritis; spondyloarthritis; systemic vasculitis

Episcleritis

Rheumatoid arthritis; relapsing polychondritis; inflammatory bowel disease; systemic vasculitis

Scleritis

Systemic vasculitis; antiphospholipid syndrome

Retinal ischemia

Sjögren syndrome

Dryness of the eyes (keratoconjunctivitis sicca)

Giant cell arteritis

Anterior/posterior ischemic optic neuropathy; central retinal artery occlusion; loss of vision

Sarcoidosis; granulomatosis with polyangiitis

Exophthalmos/retrobulbar inflammatory infiltrate

Reactive arthritis

Conjunctivitis



Table 4. Internal Organ Involvement in Rheumatologic Disease

Disease

Type of Involvement

Heart

Kawasaki disease

Coronary artery vasculitis

Systemic sclerosis

Arrhythmia; myocardial fibrosis

SLE

Pericarditis; valvular disease; myocarditis

RA

Pericarditis; myocarditis

Rheumatic fever; antiphospholipid syndrome

Valvular disease

GCA

Aortic aneurysm/dissection; aortitis; large-vessel obstruction

Lung

RA

Serositis; ILD; rheumatoid nodules

SLE; CTDs; Henoch-Schönlein purpura

Serositis; pneumonitis; pulmonary hemorrhage from vasculitis

AAV

Pulmonary hemorrhage; cavitary nodules

Diffuse cutaneous systemic sclerosis

ILD; pulmonary hypertension

Limited cutaneous systemic sclerosis

Pulmonary hypertension

Antiphospholipid syndrome

Pulmonary embolism

Sarcoidosis

Hilar lymphadenopathy; ILD

Goodpasture syndrome

Pulmonary hemorrhage

Kidney

SLE; CTDs; AAV; systemic vasculitis (except PAN)

Glomerulonephritis

PAN

Renal artery vasculitis; pseudoaneurysms

Antiphospholipid syndrome

Renal infarct; renal vein thrombosis

Sjögren syndrome

Acute interstitial nephritis/renal tubular acidosis

Goodpasture syndrome

Glomerulonephritis

Gastrointestinal System

PAN

Mesenteric vasculitis

Henoch-Schönlein purpura

Intestinal vasculitis and ulcerations

Diffuse and limited cutaneous systemic sclerosis

Esophageal and small bowel hypomotility

Behçet syndrome

Mucosal ulcerations

Familial Mediterranean fever

Peritonitis

Nervous System

SLE; CTDs; AAV; systemic vasculitis

Mononeuritis multiplex; peripheral neuropathy

PACNS

CNS vasculitis


ESR
ESR is dictated by characteristics of the erythrocytes themselves and by the presence of specific plasma proteins that alter the normal repulsive forces between erythrocytes and influence their ability to aggregate, form rouleaux, and sediment more quickly. These plasma proteins include acute phase reactants (such as fibrinogen) produced by the liver in response to proinflammatory cytokines occurring in rheumatologic disease, infection, and malignancy that neutralize these negative surface charges and increase ESR. Noninflammatory conditions causing elevated fibrinogen, including kidney disease, diabetes, pregnancy, and obesity, can also result in an elevated ESR. Normal aging can also cause an elevated ESR; for this female patient, an equation to find the estimate of the maximal expected ESR is (age in years + 10)/2, resulting in 42 mm/h
Ref:MKSAP


Autoantibodies in Rheumatologic Disease

Autoantibody

Rheumatologic Disease

Sensitivity/Specificity

Comments

ANA

SLE; also SSc, Sjögren, MCTD

SLE: >95% sensitivity, poor specificity; indirect IFA is the most appropriate methodology

Does not correlate with disease activity

Anti–double-stranded DNA

SLE

SLE: 50%-60% sensitivity, >95% specificity; Crithidia IFA or Farr assays more specific than ELISA

Found in more severe disease, especially kidney disease; antibody levels commonly follow disease activity and are useful to monitor

Anti-Smith

SLE

SLE: 30% sensitivity, 99% specificity

Most specific test for SLE; does not correlate with disease activity

Anti-U1-RNP

MCTD; SLE

High sensitivity for MCTD

High titer seen in MCTD (>1:10,000); does not correlate with disease activity

Anti-Ro/SSA; anti-La/SSB

Sjögren; SLE; RA; SSc

Sjögren: 70% sensitivity; SLE: 20% sensitivity

Sicca symptoms; in SLE, associated with photosensitive rash; offspring of mothers who are positive for anti-Ro/SSA or anti-La/SSB are at increased risk for neonatal lupus erythematosus (rash and congenital heart block)

Antiribosomal P

SLE

15% sensitivity

Associated with CNS lupus and lupus hepatitis

Anti–Scl-70 (antitopoisomerase-1)

DcSSc

10%-30% sensitivity

Seen more often in patients with DcSSc who have pulmonary fibrosis

Anticentromere

LcSSc (CREST)

10%-30% sensitivity

Patients with LcSSc with this antibody are more likely to develop pulmonary arterial hypertension

c-ANCA (antiproteinase-3)

GPA

90% sensitivity when disease is active; high specificity in classic presentations

Correlation with disease activity is unclear

p-ANCA (antimyeloperoxidase)

MPA; EGPA

MPA: 80% sensitivity; EGPA: 60% sensitivity; less specific than c-ANCA

Atypical p-ANCA (antimyeloperoxidase negative) can be seen in inflammatory bowel disease and with positive ANA

Anti–Jo-1

Polymyositis

20%-30% sensitivity

Associated with antisynthetase syndrome, including lung inflammation

Rheumatoid factor

RA; Sjögren; cryoglobulinemia

RA: 70% sensitivity; limited specificity, especially in patients without a classic disease presentation

RF is common in multiple other diseases (e.g., hepatitis C, endocarditis, SLE); 30% with RA are RF negative but may become positive later in RA course

Anti–cyclic citrullinated peptide

RA

RA: 70% sensitivity; 95% specificity

Can be positive in RF-negative RA patients; often present before RF becomes positive; associated with erosions; predicts disease progression in undifferentiated arthritis

Antihistone

DILE

95% sensitivity; poor specificity

Also seen in primary SLE

Cryoglobulins

Vasculitis; hepatitis C; myeloma; SLE; RA

Type II or III cryoglobulins seen in cryoglobulinemic vasculitis

May be present in connective tissue diseases in the absence of vasculitis




ACPA
ELISA : arginine residues are replaced by citrulline in a mixture of CCP, increasing the sensitivity of the assay for ACPA.
69 % sensitivity, 96 % specificity for RA
Other situation when test is positive 
  • SLE : 17 % of 335 patients
  • SS - 10 % of 155 patients 
  •         Best to label as SLE-RA, SS-RA 
  • PsA - 8-16 % esp in the erosive form 
  • Active TB  32-35 % (unmodified Arginine is detected in place of citrulline)
  • Not seen with Hep C (unlike RF)
  • AATD (Alpha-1 antitrypsin deficiency) - 3-5 % 




Synovial Fluid Analysis

Normal

Noninflammatory

Inflammatory

Crystal Induced

Infectious

Hemorrhagic

Appearance

Clear/yellow/transparent

Clear/yellow/transparent

Yellow/white/translucent/opaque

Yellow/white/translucent/opaque

Yellow/white/opaque

Red/opaque

Leukocyte count

<200/µL (0.2 × 109/L)

200-2000/µL (0.2-2.0 × 109/L)

2000-20,000/µL (2.0-20 × 109/L) (may be higher)

10,000-50,000/µL (10-50 × 109/L) (may be higher)

>50,000/µL (50 × 109/L) (may be lower)

Other studies

Negative Gram stain; negative culture

Negative Gram stain; negative culture

Negative Gram stain; negative culture

Negative Gram stain; positive crystalsa

Positive Gram stainb; positive culturec

Negative Gram stain; negative culture

  • aCrystal description: Urate crystals are needle shaped and bright. Viewed under polarized light, they are negatively birefringent; they appear yellow when parallel to the axis of the polarized field and blue when perpendicular to the axis. Calcium pyrophosphate crystals are rhomboid, pale, and weakly (not as vividly) positively birefringent; they appear blue when parallel to the axis and yellow when perpendicular.

Misc (Need more references)
  • Inflammatory Osetoarthritis
    • Mostly in Middle aged women
    • PIP and DIP mostly involved
  • DISH
  • Late Onset Spondyloarthopathy
    • Differentiated from PMR by the presence of enthesitis, dactylics, anterior uveitis, Sacrolieitis on imaging, or HLA - B27
  • Remitting Seronegative Symmetric Synovitis with pitting edema syndrome (RS3PE Syndrome)
    • Extensor muscle Senovititis is very prominent compared to the flexor muslce synovitis
    • May respond to low dose steroids
    • Could progress to RA 
  • Inflammatory Myopathy
Systemic Disease with Arthritis as a symptom
  • GI Diseases
    • Autoimmune hepatitis 
    • Primary biliary cirrhosis 
    • Pancreatitis-arthritis syndrome 
    • Whipple’s disease
    • Gluten-sensitive enteropathy
    • Inflammatory bowel disease 
    • Hepatitis B/hepatitis C
    • Intestinal bypass arthritis
  • Hematological Diseases
    • Hemophilia 
    • Hemoglobinopathies 
    • Hypogammaglobulinemia 
    • Plasma cell dyscrasias
  • Endocrinal Diseaseas
    • Diabetes mellitus 
    • Thyroid disorders 
    • Parathyroid disorders 
    • Acromegaly 
    • Hyperlipoproteinemia 
    • Paget’s disease
  • Malignant Disorders
    • Hypertrophic osteoarthropathy 
    • Leukemia and lymphoma 
    • Carcinomatous polyarthritis 
    • Palmar fasciitis and arthritis 
  • Misc
    • Hemochromatosis
    • Multicentric reticulohistiocytosis Sarcoidosis
    • Alkaptonuria
    • Fabry’s disease
    • Relapsing polychondritis
    • Cystic fibrosis
    • Pigmented villonodular synovitis 
    • Systemic infections
Temporomandibular Disorders
Further reading 

Recent Publications in Rheumatology




Learning Rheumatology
  • Understanding Mechanism of Action: 
    • 1. Name 2 rheumatological medications that are contraindicated or used with caution in patients on Azathioprine, and Why so?
      • Allopurinol, and 
    • Why does Rituximab work in RA?
      • B-cell activation occurs in RA. Of note, it is T-cell dependent. 
  • Understanding Pathogenesis
    • How do you differentiate SLE flare up vs Infections in patients with SLE? Why so?
      • CRP normal in flare up, elevated in Infections
      • CRP is high in RA as Th1 pathway is involved. 
    • How do you differentiate between Type I, Type II, Type III cryoglobunimia? 
      • Type I: M component present (Monocolnal Ig G or IgM); RF - (no Polyclonal Ig G)
      • Type II: M component present (Monoclonal Ig G or Ig M) RF + (as polyclonal Ig G is also present along with M protein)
      • Type III:M component absent (Polyclonal Ig G) RF + (Polyclonal Ig G)
    • How does RA and Gout cause erosions, but SLE does not?
      • Needs to verify but my conceptual answer is: Inflammatory mediators in Gout and RA activate degrading enzymes that cause joint erosions, but such enzymes are not activated in SLE!
        • SLE:
          • BLyS, IL -6, IL -1, TNF - alpha (please note these cytokines are also seen in RA and Gout) are involved in inflammatory process and tissue injury in a patient with SLE. 
            • But, this is not a Th1 mediated response (hence, CRP is normal). Does Th1 and Th2 pathway both lead to activation of same cytokines IL-1,6, TNF alpha. If then, why should CRP be normal in one, increased in other. 
        • RA
        • Gout:
          • 3 Pathway ends in recruitment of inflammatory cell
            • 1 and 2. IL 1 - B Mediated 
              • 1. Activates TNF alpha, IL-6, IL-8
              • 2. IL-1 receptor activation in synovial cells, that produce more chemokines.  
            • 3 (IL- B independet)
              • Monosodium urate activates C5-C9 directly that intern generates more TNF -Alpha, IL-6, IL-8
          • Needs verification: Does these cells activation eventually leads to activation of enzymes that are activated in RA or Not? 
          • Figure 1. Mechanisms of Inflammation in Gout. NEJM 2011
    • How is the pathogenesis of Scleroderma different than RA, and Gout?
      • In RA and Gout (either auto-antigen, or monosodium urate) leads to activation of inflammatory cells and enzymes. 
      • In Scleroderma, on the other hand, early microvascular damage, mononuclear-cell infiltrates, and slowly developing fibrosis is the main disease process. 
    • Which Immune axis pathway is blocked by Steroids in PMR / GCA? 
      • There are two major immune response network in PMR-GCR.
        • 1. IL-12 - Th1 - IFN-Y axis
          • The cells leading to this axis activation is not seen in temporal artery biopsy of a patient with PMR alone. This axis is however seen in a patient with GCA along with IL -6 - IL 17/ IL 21 axis. 
        • 2. IL -6 - Th17 - IL 17, Il- 21 axis
        • The latter, but nor former axis is effectively suppressed by steroids
        • These pathway leads to proteolytic enzyme activation and growth promoting factors (VEGF, PDGF). The action of proteolytic enzyme, and growth promoting factors promotes arterial wall remodeling  
        • IL -6 is a major stimulant of CRP production. Hence, it is elevated in GCA/PMR. Hence, CRP acts as a surrogate marker of IL-6 level. 
    • What is the cytokine mostly involved in CRP production. 
    • What are the final main mediators of inflammation in RA, JRA, AOSD?
      • RA: TNF -alpha, IL-6
      • JRA, AOSD: IL-1
    • How to differentiate classic complement pathway activation vs alternate pathway?
      • Classic Pathway: Decrease C4, Decreased C3
      • Alternate Pathway: Normal C4, Decreased C4
    • Why are opiates relatively ineffective in Fibromyalgia?
      • Due to hyperactive endogenous opoiod system. Low dose Naloxone hence may work. 
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