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Imaging, Labs and Misc

Research Questions related to SLE
  • SLE and Immunopathophysiology: Why CRP is increased in few patients and not in others, are they different immuno-pathophysiology i.e end-type vs phenotype? or additional disease process ongoing that we do not recognize fully?
  • SLE and trigger! SLE, not all patients have all ab, some ab confer worse prognosis? is there a different trigger in instances that leads 
  • Do they respond well?
  • Research topic: On patients with Lupus, folks with increased CRP and normal CRP, do they behave similarly on treatment? 
  • TNF inhibitors, presumed mechanisms for DILE is due to blockage of Th1 pathways, and may cause switch to TH2 pathways? What is the mechanism for Pracainamde, Hydralazine?
  • Why SLE, RA, SS cause Fibromyalgia, and not so much in others like SSc, Spondyloarthritis?
  • SLE grants? 

Dr. A. R
  • Path: Learn Immunology research and techniques now? When I do fellowship, if i could do here, then could use his lab space for research during those 6 months of lab?
    • First, invest to learn, then reward to work on own project?
  • One of the joined faculty with 60:40 clinic / research? Desh: It is great you are interested on bench research? If you invest on your time make sure you get a return as well? Unless you have a publication, you will not get grant? If you go by bench research, if you get lucky and experiements work, then you may get publication in 2-3 years? and then you will apply for grants? Where as if you start with clinical questions, get publications, and then build on to that to get a grant, you will find a lab space to work some where for sure, but funds to do experiment is vital? That way you will have explored the options of both clinical research and basic research? And, let time decide, sometime we may like what we do not know yet? 

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


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


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)

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.

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.

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.

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


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


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


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)


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


Palpable purpura; cutaneous nodules; ulcers; necrosis

Behçet syndrome

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


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


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


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


Table 4. Internal Organ Involvement in Rheumatologic Disease


Type of Involvement


Kawasaki disease

Coronary artery vasculitis

Systemic sclerosis

Arrhythmia; myocardial fibrosis


Pericarditis; valvular disease; myocarditis


Pericarditis; myocarditis

Rheumatic fever; antiphospholipid syndrome

Valvular disease


Aortic aneurysm/dissection; aortitis; large-vessel obstruction



Serositis; ILD; rheumatoid nodules

SLE; CTDs; Henoch-Schönlein purpura

Serositis; pneumonitis; pulmonary hemorrhage from vasculitis


Pulmonary hemorrhage; cavitary nodules

Diffuse cutaneous systemic sclerosis

ILD; pulmonary hypertension

Limited cutaneous systemic sclerosis

Pulmonary hypertension

Antiphospholipid syndrome

Pulmonary embolism


Hilar lymphadenopathy; ILD

Goodpasture syndrome

Pulmonary hemorrhage


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



Renal artery vasculitis; pseudoaneurysms

Antiphospholipid syndrome

Renal infarct; renal vein thrombosis

Sjögren syndrome

Acute interstitial nephritis/renal tubular acidosis

Goodpasture syndrome


Gastrointestinal System


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


Nervous System

SLE; CTDs; AAV; systemic vasculitis

Mononeuritis multiplex; peripheral neuropathy


CNS vasculitis

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

Autoantibodies in Rheumatologic Disease


Rheumatologic Disease




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: 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



SLE: 30% sensitivity, 99% specificity

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



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


15% sensitivity

Associated with CNS lupus and lupus hepatitis

Anti–Scl-70 (antitopoisomerase-1)


10%-30% sensitivity

Seen more often in patients with DcSSc who have pulmonary fibrosis



10%-30% sensitivity

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

c-ANCA (antiproteinase-3)


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

Correlation with disease activity is unclear

p-ANCA (antimyeloperoxidase)


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



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: 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



95% sensitivity; poor specificity

Also seen in primary SLE


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

Synovial Fluid Analysis




Crystal Induced










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