SBRC

RHEUMATOLO
GY
SPRING 2024

CLAUDE-BERNARD ILIOU,
MD
 OVERVIEW & EPIDEMIOLOGY

 Musculoskeletal complaints account for > 350 million outpatient visits per year

 33% of the US population is affected by arthritis and other joint disorders

 Most important of the diagnoses that require prompt diagnosis and attention: septic arthritis, acute crystal-induced arthritis
and fractures
 Identification of the pathological process:
 Articular vs. nonarticular
 Inflammatory vs. noninflammatory
 Drug-induced vs. trauma vs. autoimmune
 CLASSIFICATIONS

 Osteoarthritis Immune–Mediated Arthritis: Arthropathies associated with systemic diseases:

 Rheumatoid Arthritis  Psoriatic Arthritis  Familial Mediterranean Fever
 Septic Arthritis  Ankylosing Spondylitis  Hemochromatosis
 Reactive Arthritis  Behcet’s Syndrome  Sarcoidosis
Crystal Associated Arthropathies:  Systemic Lupus Erythematosus  Celiac Sprue
 Gout  Sjogren’s Syndrome  Polymyositis/Dermatomyositis
 Pseudogout  Systemic Sclerosis (CREST)  Mixed Connective Tissue Disease
 Eosinophilic Fasciitis  Polymyalgia Rheumatica
 Juvenile Idiopathic Arthritis
 Lyme Disease
 Non-Celiac Gluten Sensitivity
 Relapsing Polychondritis
 OSTEOARTHRITIS

 Most common type of arthritis with high prevalence in elderly

 Osteoarthritis is mono-articular or oligo-articular

 Risk factors include: Obesity, trauma, nutritional factors, age

 NSAIDs are mainstay of therapy

 CRYSTAL-ASSOCIATED ARTHROPATHY

 Monosodium urate (Gout)

 Calcium Pyrophosphate (Pseudogout)

 Calcium Apatite (Dystrophic Calcification)

 Calcium Oxalate
 GOUT
Can be acute or chronic peripheral joint inflammation caused by deposition of monosodium urate crystals
This is associates with elevated plasma uric acid levels (> 7 mg/dL)
Formation of needle-shaped crystals in and around joints and tendons with a predilection for cooler joints (urate solubility)
Urate can also precipitate readily in acidic pH such as occurs in urine
Predisposing factors: diuretic therapy, increased purine synthesis, deficiency of HGPRT or overactivity of PRP synthetase,
purine-rich foods, alcohol (which induces nucleotide catabolism and lactate production blocking renal urate secretion)
Diagnosis: Negatively birefringent needle-shaped crystals
Treatment: Acute gout can be initially treated with colchicine and NSAIDs
Chronic gout can be treated with Allopurinol, Febuxostat, Sulfinpyrazone and Probenicid
 PSEUDOGOUT

 Arthritis caused by deposition of Calcium Pyrophosphate Dihydrate crystals

 Crystals are weakly positively birefringent with polarized light

 May present as monoarticular or polyarticular , 4-7% of adult population, F ≥ M

 Chondrocalcinosis can be seen on X-Ray, CT or other imaging

 Risk factors: age (>60), amyloidosis, myxedema, hyperparathyroidism, gout, hemochromatosis.

 Treatment: Colchicine, NSAIDs

 CRYSTAL-ASSOCIATED ARTHROPATHY

 Calcium Apatite (Dystrophic Calcification)

 Dystrophic calcifications occurs in the absence o f a mineral imbalance. Rather it occurs in

previously damaged tissue in normal serum calcium levels.
 Dystrophic calcifications Are most often seen in caseous or fat necrosis, atherosclerosis,
damaged heart valves, granulomas, meningiomas or psammoma bodies
 Phosphate is released from the damaged tissue by the action of phosphatases

 Calcium phosphate appears basophilic in hematoxylin-eosin stain

 Calcifications will involve various tissues causing tendinitis, synovitis, arthritis

Calcinosis cutis
 CRYSTAL-ASSOCIATED ARTHROPATHY
 Calcium Oxalate (kidney stones)

 Most commonly associated with urine pH between 6.0 amd 7.0

 Most common type of kidney stone (65%), and most common type of calcium stone (80%)

 Treatment: Strategies depend on underlying cause:

 Dehydration – inrease fluid intake
 Hyperoxaluria – avoid certain types of foods high in oxalate
 Hyperuricosuria – Insulin resistance
 Hypercalcuria – Thiazide diuretics
 Alikilinize the urine
 SEPTIC ARTHRITIS

 There is a wide variety of organisms causing septic arthritis. Most common:

 S. aureus, S. pneumoniae, N. gonorrheae and candida causing acute monoarticular arthropathy
 M. tuberculosis, B. burgdorferi, T. pallidum, S. schenkii, C. immitis, B. dematitidis, Nocardia causing chronic monoarticular arthropathy
 N. meningitidis, N. gonorrhea, M. pneumoniae, candida and some viruses causing polyarticular arthopathies
 REACTIVE ARTHRITIS
 Also known as Reiter’s Syndrome (especially when associated with Chlamydial infection)

 Caused by cross-reactivity between antigens of pathogenic organisms and synovial antigens

 Reactive Arthritis is often accompanied by conjunctivitis, uveitis, and urethritis (males) or cervicitis (females)

 Other manifestations of cross-reactivity can include: psoriasis, circinate balanitis, enthesitis and keratoderma
blennorrhagicum
 This is classified as an RF-seronegative, HLA_B27-linked arthritis

 Common triggers include: Chlamydia trachomatis, Salmonella, Shigella, Campylobacter, and Group A Strep

 Typical epidemiology: Ages 20-40, M>F , Caucasians>African-Americans

 Starts 1-3 weeks after infection

 Treatment occurs after eradicating the offending organism and decrease in immune response

 Typically resolves in 6 weeks to 6 months

 Complications: IgA Nephropathy, Ankylosing Spondylitis, Aortitis, etc.

 PSORIATIC ARTHRITIS

 Long-term inflammatory arthritis induced by autoimmune psoriasis.

 Seronegative spondyloarthropathy, asymmetric oligoarthritis

 Sausage-like digits and toes (dactylitis), thickened nails, pitting, red, scaly plaques on
extensor surfaces, sacroiliitis, spondylitis, enthesitis and plantar fasciitis
 50% have HLA-B27 genotype

 Treatment: NSAIDs, Methotrexate, Corticosteroids, Leflunomide, Cyclosporine,

Azathioprine, TNF-α inhibitors, Jak/Stat inhibitor, IL-12/IL23/IL-17a inhibitors,
Apremilast (PDEI-4 inhibitor)
 ANKYLOSING SPONDYLITIS

 Aka Marie-Strümpell Disease

 Seronegative spondyloarthropathy

 Rheumatic disorder characterized by inflammation of the axial skeleton and large joints

 Presents 20–30-year-olds, loss of spinal mobility, back pain, and non-articular symptoms:
anterior uveitis, aortic regurgitation, arrhythmias, aortitis, pericarditis, pulmonary fibrosis
 Diagnosis: Bamboo spine seen on X-ray, Mildly elevated ESR, CRP, Ig

 Risk factors: M>>F (3:1), Increased prevalence in HLA-B27 (20%), familial inheritance

 Treatment: NSAIDs, DMARDs (Methotrexate, Sulfasalazine, TNF-α inhibitors)

 RHEUMATOID ARTHRITIS

 Autoimmune disease characterized by symmetric inflammation and destruction of

small articular and periarticular surfaces with systemic involvement
 Associated with HLA-DR1/DR4 haplotypes

 Epidemiology: 1% of population, 4th-5th decades, F >> M (3:1)

 Presentation: Rheumatoid nodules, inflammation of MCP, MTP and proximal

interphalangeal joints
 Labs: ↑ ESR, ↑ IgG, ↑ CCP, 80% RF, > 90% CCP

 Treatment: NSAIDs, Corticosteroids, Hydroxychloroquine, Sulfasalazine,

Cyclosporine, Methotrexate, Azathioprine
 BEHCET’S SYNDROME

 A multisystem inflammatory chronic disorder that affects adults. M > F (2:1)

 Risk factors: Common in the Middle East, HLA-B51, onset in 20-40-year-olds

 Presents with painful oral ulcers, penile or vaginal ulcers, iridocyclitis, choroiditis, uveitis, hypopyon, various skin
lesions (papules, pustules, vesicles, folliculitis), symmetrical large-joint arthritis, migratory thrombophlebitis, CNS
involvement in the form of meningoencephalitis or intracerebral hypertension, GI manifestations, and sometimes focal
glomerulonephritis
 Treatment: Corticosteroids, immunosuppressants such as TNF-α inhibitors,
 SYSTEMIC LUPUS ERYTHEMATOSUS
 A chronic inflammatory connective tissue autoimmune disorder affecting skin, joints,
kidneys, and blood vessels
 90% of cases occur in young women; 90% of patients suffer articular symptoms

 Presentations include malar rash, photosensitivity, polyarthropathy, pleurisy,

pericarditis, glomerulonephritis, hematological and CNS abnormalities
 Diagnosis: +ANA, anti-SM or anti-dsDNA Ab, antiphospholipid Ab, clinical findings,
leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia, +VDRL
 Drug-induced Lupus Erythematosus has + anti-histone Ab

 Treatment: Corticosteroids, Hydroxychloroquine, immunosuppressive therapy, long-

term anticoagulation for antiphospholipid antibodies
 DMARDs: Azathioprine, Methotrexate, Cyclosporin, Rituximab, Mycophenolate
 SJOGREN’S SYNDROME
 A chronic, systemic autoimmune disease characterized by dry eyes (kerato-conjunctivitis
sicca), dry mouth (xerostomia), dry mucous membranes, often associated with Rheumatoid
Arthritis and other autoimmune diseases.
 Pathogenesis is lymphocytic infiltration and subsequent fibrosis of various glands
associated with HLA-DR3, DRW52, HLA-B8, HLA-DQA1 and HLA-DQB1
 2 Forms: Primary (Sicca Syndrome) and Secondary (presents with other autoimmune
diseases (mostly RA)
 Extraglandular disease in 33%: synovitis, pulmonary fibrosis, peripheral neuropathy

 Epidemiology: Mostly in women (9:1) 50-60’s. 15% increased risk of lymphoma

 Lab: ↑ ESR, ↑ anti-Ro/SSA, ↑ Anti-LA/SSB, ↑ Anti-RNP

 Treatment: Supportive
 SYSTEMIC SCLEROSIS
 Aka Scleroderma or CREST syndrome

 Autoimmune disease, causing chronic inflammation leading to damage to vessels, fibrosis, and
organ involvement
 CREST: Calcinosis, Raynaud’s phenomena, Esophageal dysmotility, Sclerodactyly and
Telangiectasia
 Diffuse scleroderma involving GIT, MSK, Lungs, Heart, Kidneys

 Lab: Anti-DNA Topoisomerase (Anti-Scl-70), Anti-centromeric Abs (90%) +ANA (>90%),

+RF (33%)
 Epidemiology: F >> M (4:1); 30’s-50’s

 Treatment: NSAIDs, Corticosteroids, Immunosuppressants, CCB, PDEI type V, ACEI,

penicillamine
 EOSINOPHILIC FASCIITIS

 Autoimmune Disorder causing symmetric inflammation of proximal

extremities and occurring mostly in men
 Lab: Eosinophilia, ESR, Polyclonal IgG Hypergammopathy,

 Treatment: Prednisone or Hydroxychloroquine

 JUVENILE IDIOPATHIC ARTHRITIS
 The most common chronic rheumatic disease of childhood

 Onset begins before 16 years of age

 Autoimmune inflammatory condition & subtypes recognized:

 Oligoarticular, Polyarticular (RF+ and RF-), Systemic Onset, Psoriatic and Enthesis-Related Arthritis

 Presents as oligoarthritis of small joints, although sometime large joints may be involved, iridocyclitis is common, and
other symptoms are associated with various subtypes (see table)

Oligoarticular RF - Polyarticular RF+ Polyarticular Systemic Psoriatic Enthesis-Related

% of cases 50-60 20-30 5-10 10-20 5-10 15

Gender F:M 4:1 4:1 9:1 1:1 3:2 1:9

Peak onset 2-3 2-3 12-15 8-10 12-15

Joints Asymmetric Large Mixed Small & Large Symmetric Small &
Large
Symmetric Asymmetric small &
Large
Asymmetric Large

Systemic Uveitis (20%) Uveitis Rheumatoid Nodules Fever, rash, LN,

Hepatosplenomegaly
Psoriasis, Uveitis (10%) Uveitis (20%), IBD,
Enthesitis, Aortitis
 RELAPSING POLYCHONDRITIS

 Episodic, repetitive, inflammatory disease affecting the cartilage and connective tissue

 Frequent association with Rheumatoid Arthritis, Systemic Vasculitis, SLE and other autoimmune diseases M = F

 Presents as an acute, inflammation of the cartilage of the external ears, joints, nose, and other connective tissues

 Eye manifestations can include: conjunctivitis, uveitis, scleritis, iritis, or chorioretinitis

 Can involve trachea, larynx, bronchi, cardiac valves and vessels

 Treatment: NSAIDs, Corticosteroids, Methotrexate, and other immunosuppressive medications.

 POLYMYOSITIS/DERMATOMYOSITIS
 Systemic Connective Tissue Disease characterized by inflammation and degenerative changes in
muscles (and skin), leading to progressive weakness and muscle atrophy. Muscle changes are primarily
seen in limb girdles.
 Classifications: Primary Idiopathic Polymyositis, Dermatomyositis, Juvenile Polymyositis,
Sclerodermatomyositis
 Pathophysiology: Autoimmune disease with elevated inflammation markers (ESR, AST/ALT, CPK,
Aldolase), vascular deposition of Ig and C3 complexes, lymphocytic infiltration of the dermis and
muscles, anti-thymocyte Ab (60%) [pm-1 OR Jo-1]
 Presentation: Hallmark is proximal muscle weakness, F > M (2:1); Occurs in adults 40-60 y.o. or
children (5-15 y.o.) Polyarthralgia is manifests as joint swelling, effusions, may be accompanied by
Raynaud’s phenomenon
 An associated malignancy can be found in 15% of males > females

 Characteristic EMG findings such as spontaneous fibrillations, polyphasic potentials, biopsy shows
necrosis
 Treatment: Corticosteroids, immunosuppressive therapy
 MIXED CONNECTIVE TISSUE DISEASE

 Rheumatic disease containing overlapping characteristics of SLE,

Rheumatoid Arthritis, Scleroderma, Polymyositis or Dermatomyositis
 Presentation: Raynaud’s phenomenon, polyarthralgias (>90%),
inflammatory proximal myopathies, dactylitis, pulmonary disease [PAH]
(80%), esophageal dysmotility (> 50%) and chronic fatigue.
 Peak incidence is adolescence into adulthood (11-40’s) F > M (8:1)

 Lab: very high titers of ANA (speckled pattern) and anti-RNP Ab (U1),
+RF, ↑ ESR, ↑ CPK and ↑ Aldolase, CCP (>50%).
 Treatment: Corticosteroids and immunosuppressive therapy
 FIBROMYLAGIA

 Aka Myofascial Pain Syndrome or Fibro(myo)sitis

 Non-articular pain syndromes characterized by tenderness, stiffness, and diffuse achiness

 Fibromyalgia has a predilection for neck, back, occiput, and thighs, occurring more frequently in females 2:1

 Associated findings include difficulty sleeping (or non-rested sleep), parasthesias, depression, or anxiety

 Pain may be in response to minor trauma or exercise, coldness or dampness

 Treatment: Pregabalin, SNRI, TCAs, and SSRIs have been useful. NSAIDs or Corticosteroids have also been used.
 POLYMYALGIA RHEUMATICA

 Severe pain and stiffness in the proximal muscles

 Mostly occurs in > 60 y.o., F>M is 2:1

 Associated with Temporal Arteritis (Giant Cell Arteritis)

 Presents as acute or subacute pain in hips, shoulders, neck stiffness, malaise, fever, without muscle weakness.

 Labs: ↑↑ ESR (>60 mm/hr), ↑ CRP (>0.7 mg/dL)

 Treatment: Prednisone
 RELATIVE FREQUENCIES

Fibromyalgia = Gout > Ankylosing Spondylitis > Psoriatic Arthritis > Pseudogout > Sjogren’s > RA > SLE >
Polymyalgia Rheumatica > Systemic Sclerosis > PM/DM > MCTD > Relapsing Polychondritis