JIA Categories: - Systemic: Stills
- PsA
- ERA
- Oligoarthritis
- 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 |
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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
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 |
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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 |
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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 |
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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 |
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Heart |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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?
- 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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