Arthritis Overview and Classification

Arthritis I

• Arthritis is joint inflammation and swelling.
• Types include osteoarthritis, rheumatoid arthritis, and others.
• Diagnosis may involve arthrocentesis, the aspiration of synovial fluid.
• Arthrocentesis is used for diagnosis in some cases and can also be therapeutic for large effusions.

Arthritis Classification

• Non-inflammatory: Degenerative arthritis, usually due to osteoarthritis. Joint pain is without warmth or swelling. Low WBC in synovial fluid. May cause brief (<30 min) morning stiffness.

• Inflammatory: Warm, swollen joints. Elevated WBC in synovial fluid and prolonged (>30 min) morning stiffness.

• Normal white blood count (WBC) in synovial fluid is < 200 cells/mm³

• Osteoarthritis WBC is 200-2000 cells/mm³

• Inflammatory arthritis WBC is > 2000 cells/mm³

• Number of joints involved:

  • Monoarthritis: 1 joint
  • Oligoarthritis: 2-4 joints
  • Polyarthritis: >5 joints

Osteoarthritis

• Degeneration of synovial joints.
• Breakdown of hyaline cartilage.
• Cartilage provides a smooth surface for joint gliding.
• Hypertrophy of bone.
• "Bone sclerosis" of subchondral bone, formation of bone spurs (osteophytes).
• Joint space narrows.
• Minimal inflammation of synovial fluid.
• Non-inflammatory.

Osteoarthritis Clinical Features

• Insidious onset of joint pain (deep, dull ache).
• Pain worsened by activity, improved by rest.
• Morning stiffness lasting < 30 minutes.
• Restricted motion.
• Boney enlargement limits movement.

Osteoarthritis Clinical Features (cont'd)

• Affects weight-bearing joints most commonly (hips, knees).
• Can affect any joint.
• Cervical spine, lumbar spine, or mono/polyarticular disease
• May present as monoarticular symptoms.

Osteoarthritis Risk Factors

• Advanced age (80% over 55 years old).
• Obesity (especially in the knees).
• Trauma (major trauma or repeated microtrauma to the joint).

Osteoarthritis Diagnosis

• Clinical diagnosis.
• Supportive evidence from X-rays, including:
  • Joint space narrowing
  • Subchondral sclerosis
  • Osteophytes (bone spurs).
  • Subchondral cyst.
• Low WBC in synovial fluid.
• "Non-inflammatory arthritis"
• All blood tests normal.

Joint Space Narrowing, Subchondral Sclerosis, and Bone Spurs

• Joint space narrowing is a finding on X-ray.
• Subchondral sclerosis is thickening of the subchondral bone with increased collagen mineralization.
• Bone spurs (osteophytes) are bony growths at joint margins.

Subchondral Cysts

• Fluid-filled sacs.
• Synovial fluid accumulation due to bone cracks.

Knee Involvement (cont'd)

• Typically involves both knees.
• More weight-bearing on medial knee.
• Narrowing may be asymmetric on the medial side.

Hip Involvement (cont'd)

• Characterized by pain in the groin, buttock, or thigh.
• Examination reveals reduced range of motion.
• Clicks (crepitus) may be present.
• Usually unilateral.
• Often bilateral, differing from knee involvement.

Hand Involvement (cont'd)

• Distal interphalangeal (DIP) joints are spared in contrast to rheumatoid arthritis.
• Proximal interphalangeal (PIP) joints are not involved.
• First carpometacarpal (CMC) joint is also spared.

Nodal Osteoarthritis

• Occurs in patients with interphalangeal osteoarthritis of hands.
• Heberden's (DIP) and Bouchard's (PIP) nodes result.
• Over time, joints become less painful.
• Inflammatory signs subside (swellings).
• Common on index and middle fingers.

Rheumatoid Arthritis

• Autoimmune inflammation of synovium.
• Thin tissue layer lining joints/tendon sheaths.
• Secretes hyaluronic acid (lubricant).
• Systemic disease, complications outside joints.
• More common in women.
• Onset usually between 20 and 40 years.
• Disease flares and subsides.

Rheumatoid Arthritis Clinical Features

• Symmetric joint inflammation.
• Gradual onset.
• Pain, stiffness, and swelling.
• Classically, "morning stiffness" lasting >1 hour after rising.
• Improves with use.
• May have systemic symptoms (fever, fatigue, weight loss).

Rheumatoid Arthritis Clinical Features (cont'd)

• Most often involves wrists and hands
• Often tender to touch(MCP and PIP joints are involved).
• Distal interphalangeal (DIP) joints are spared.
• Lumbar spine usually spared.
• Contrasts with osteoarthritis.
• Characteristic deformities:
  • Ulnar deviation (arms)
  • Swelling of MCP joints (hands)
  • Swan-neck deformity (hands)
  • Flexed DIP joints(hands)

Rheumatoid Arthritis Clinical Features (cont'd)

• Axial spine spared expect cervical region
• "Atlantoaxial joint" involved in longstanding disease
• Neck pain and stiffness
• Cervical subluxation is possible
• May require surgical treatment, monitored by DMARD therapy
• Risk of neurologic injury during intubation, cervical spine X-ray advised pre-surgery.

Baker's Cyst (popliteal cyst)

• Swelling of the gastrocnemius-semimembranosus bursa
• Synovium-lined sac at back of the knee, continuous with the joint space.
• Common in patients with OA or RA.
• Often asymptomatic.
• Rupture: symptoms similar to deep vein thrombosis (DVT).
• Symptoms include posterior knee pain, swelling, and ecchymosis.

Rheumatoid Arthritis Extraarticular Features

• Serositis (inflammation of serosal surfaces): pleuritis, pericarditis.
• Parenchymal lung disease (Interstitial fibrosis, pulmonary nodules).
• Carpal tunnel syndrome.
• Anemia of chronic disease.
• Palpable nodules (20-35% patients), pathognomonic for RA, commonly on elbows.

Rheumatoid Arthritis Extraarticular Features (cont'd)

• Episcleritis and scleritis (red eye inflammation).
• Eye pain.
• Discharge from the eye.
• Sjogren's syndrome (common in RA patients)

Rheumatoid Arthritis Osteoporosis

• Accelerated by RA.
• Worsened by steroid treatment.
• 30% increased risk of major fracture.
• 40% increased risk of hip fracture.

Rheumatoid Arthritis Diagnosis

• Inflammatory arthritis of 3 or more joints lasting > 6 weeks.
• Rheumatoid factor (RF) is present in 70-80% of patients but is not specific
• Antibodies to citrullinated peptides (ACPA) are more specific.
• Elevated acute phase reactants (CRP or ESR).

Rheumatoid Arthritis Treatment

• Traditional Disease-Modifying Antirheumatic Drugs (DMARDs)
• Protect joints from destruction, reduce disease progression.
• Slow onset of effect, usually delivered orally
• Bridging therapy if needed until DMARD effectiveness.
• NSAIDS for pain (drug of choice).
• Corticosteroids are temporarily used for symptom flares.

DMARDs (Disease Modifying Antirheumatic Drugs)

• Methotrexate
  • Best initial DMARD, may cause bone marrow suppression, hepatitis, stomatitis.
  • Monitor CBC, LFTs with creatinine.
• Hydroxychloroquine
• Sulfasalazine
• Leflunomide

Biologics

• Antibody-based treatments (infusions/injections).
• Used when methotrexate fails to control disease.
• Examples:
  • Anti-TNF alpha therapy (etanercept, infliximab).
  • Non-TNF biologics (abatacept, rituximab, tofacitinib).
• Pre-treatment screening for latent TB, hepatitis B, and C.

Rheumatoid Arthritis Long-Term Complications

• Increased risk of coronary disease (leading cause of mortality).
• Secondary (AA) amyloidosis

Felty Syndrome

• Syndrome of splenomegaly and neutropenia in RA.
• Low WBC (blood tests).
• Increased risk for bacterial infection.
• Abdominal pain from enlarged spleen.
• Classically occurs years after onset of RA.
• Usually occurs in patients with severe RA.
• Joint deformity.
• Extraarticular disease.
• Improves with RA therapy.

Septic Arthritis

• Joint infection.
• Multiple acquisition mechanisms:
  • Hematogenous spread.
  • Contagious spread (osteomyelitis).
  • Direct inoculation (trauma, surgery).
• Usually mono-bacterial.
• Most common cause: Staph aureus (including MRSA).
• Also, streptococci and gram-negative rods.

Septic Arthritis Clinical Features

• Acute onset of arthritis symptoms.
• Usually monoarthritis (single, swollen, painful joint).
• Knee most common, less often wrists, ankles, or hips.
• Fever.

Septic Arthritis Risk Factors

• Pre-existing joint disease (rheumatoid arthritis, osteoarthritis, gout).
• IV drug use.
• Immunosuppression (including diabetes).

Septic Arthritis in Infants

• Usually hip or knee joint involved.
• Symptoms include fever, irritability, poor feeding, swollen, red, and warm joint, and tenderness to palpation.

Septic Arthritis Diagnosis and Treatment

• Blood cultures and synovial fluid analysis (crucial before antibiotics).
• Synovial WBC usually 50,000 to 150,000 cells/microL; mostly neutrophils.
• Purulent fluid.
• Joint drainage, similar to abscess management.
• Serial aspiration of easily accessible joints (knee).
• Arthroscopy or arthrotomy.
• Antibiotics (tailored to culture results if possible).

Septic Arthritis Antibiotics

• Gram-positive cocci: vancomycin
• Gram-negative bacilli: usually cephalosporins
• Ceftriaxone
• Ceftazidime (if concern for pseudomonas)

Acute Monoarthritis

• Arthrocentesis is necessary for diagnosis.
• WBC < 2,000: non-inflammatory
• 2,000-100,000 WBC: inflammatory
• WBC > 100,000 WBC: septic (blood, fat).
• Crystal types may be present (gout, pseudogout, septic, RA).
• Additional causes.

Lyme Arthritis

• Occurs in endemic areas (Northeast US).
• Suspected in patients with possible exposure.
• Endemic areas (prior tick bite, hiking, or camping).
• Arthrocentesis: inflammatory findings.
• Negative gram stain and culture.
• Diagnosis: Lyme serology.
• Treatment: doxycycline, amoxicillin, or ceftriaxone.

Seronegative Spondyloarthritis

• Disorders share common features:
  • Spondylo = Spine
  • Arthritis: Joint inflammation
  • Seronegative: Negative rheumatoid factor.
• Disorders with common features:
  • Ankylosing spondylitis
  • Psoriatic arthritis
  • Inflammatory bowel disease
  • Reactive arthritis

Parvovirus B19

• Erythema infectiosum (childhood).
• In adults, arthralgia or arthritis is possible, acute symmetric polyarthritis.
• Skin lesions (small joints, especially hands/wrists).
• Diagnosis: clinical + anti-parvovirus IgM.

Juvenile Idiopathic Arthritis

• Group of inflammatory disorders.

• Occurs in children <16 years.

• All involve arthritis of >1 joint for ≥ six weeks.

• Diagnosed clinically.

• Treatment: NSAIDs, steroids, or DMARDs.

• Major subtypes:

  • Oligoarticular
  • Polyarticular
  • Systemic

Juvenile Idiopathic Arthritis Oligoarticular Subtype

• Fewer than 5 joints affected in children ages 2-3 years.
• Females>males
• Common in toddlers, causing limp/swollen joint.
• Usually negative RF.
• Uveitis (eye inflammation) is a complication (20-25% children).

Juvenile Idiopathic Arthritis Polyarticular Subtype

• Similar to oligoarticular but involves >5 joints.
• Two peaks of incidence: 2-5 years and 10-14 years.
• Females>males
• Uveitis is a less common complication.

Juvenile Idiopathic Arthritis Systemic Subtype

• Previously called Still's disease.

• 1 joint involvement occurring in children of any age.

• High "quotidian fever" (one high spike per day; normal temp rest of day).
• Rash (Evanescent: comes/goes).
• Rash usually pink and macular.
• Hepatosplenomegaly (enlarged liver and spleen).
• Lymphadenopathy (enlarged lymph nodes).

Juvenile Idiopathic Arthritis Systemic Subtype (cont'd)

• Increased WBC
• Elevated platelets
• Elevated ESR
• ANA and RF usually negative.

Adult Still's Disease

• Similar to systemic juvenile idiopathic arthritis.
• Occurs in adults.
• Polyarthritis.
• Quotidian fever
• Rash
• ANA and RF usually negative.
• Diagnosed by exclusion.

Transient Synovitis

• Benign, self-limited condition.
• Acute inflammation of synovium, commonly in hip of children.
• Usually proceeds a viral infection (upper respiratory or diarrhea).
• Child usually appears well-appearing
• Low-grade fever may occur
• Low blood counts (WBC, ESR, and CRP).
• NSAIDS for treatment.

Gout

• Deposition of monosodium urate crystals in joints.
• Urate is the form of uric acid after loss of a proton (H+).
• Triggers inflammatory response.
• Recurrent acute arthritis attacks.
• Severe joint pain, redness, swelling, and warmth.

Acute Gouty Arthritis

• Hyperuricemia + genes + cool temperatures.
• Usually monoarthritis, base of great toe (podagra) is most common location, or knee.
• 1st metatarsophalangeal joint, often seen in obese males
• High association with hypertension
• Common in obese males.

Gout Clinical Course

• Gout flares: acute arthritis, usually monoarticular
• Often associated with a trigger
• Intercritical period
• Tophaceous gout.

Chronic Tophaceous Gout

• Tophi: urate collections in connective tissue (ears, tendons, bursa).

• Slowly enlarging, hard masses.

• Usually not painful.

• May result from prolonged or severe hyperuricemia with bone erosion.

• May be confused with rheumatoid arthritis nodules.

• History of gout and concurrent monoarthritis attacks.

Urate Nephropathy

• Consequence of prolonged or severe hyperuricemia.
• Uric acid crystals in urine
• Uric acid kidney stones
• Chronic renal failure.

Gout Triggers

• Increased serum uric acid levels.
• Overproduction of uric acid.
• Decreased excretion by the kidneys.
• Rare genetic enzyme defects.
• Excess purines.
• Purine sources (red meat, seafood).
• Trauma/surgery (tissue breakdown).
• Other triggers: myeloproliferative disorders, other issues causing high cell turnover, or diuretic use.
• Alcohol ingestion triggers lactic acid production; lactic acid increases renal urate reabsorption.
• Certain medications, such as diuretics, can also be triggers, as they lower urine volume and increase the levels of metabolic waste product in the body.

Gout Diagnosis (Arthrocentesis)

• Sampling synovial fluid.
• WBC typically between 20,000 and 50,000.
• Polarization light microscopy: needle-shaped, negative birefringent crystals.
• X-rays may show evidence of joint destruction, particularly in advanced, chronic disease.

Hyperuricemia

• All patients with gout have some degree of hyperuricemia, but most hyperuricemic patients never have gout.

• Normal or low serum urate levels are possible during gout flares (cytokine effects).

• Testing serum urate may not aid early in diagnosis, best testing performed 2 weeks+ after a flair.

Gout Treatment (Acute Attacks)

• Oral glucocorticoids (prednisone or prednisolone), avoid in individuals with infections/post-op/brittle diabetes.
• NSAIDs (high-dose potent NSAIDs; naproxen/indomethacin); avoid in those with bleeding risk, CKD, or peptic ulcer.
• Colchicine; a white blood cell inhibitor, alternative to steroids/NSAIDS.
• Glucocorticoid intraarticular joint injections are helpful if the gout flair is in one or two joints.
• Aspirin not used to treat acute gout flares; used to inhibit urate excretion if needed (lower dose daily).

Gout Treatment (Prevention of Acute Attacks)

• Lifestyle modifications: weight loss, exercise, reduced animal/seafood intake, limited alcohol.

• Indications: frequent or disabling flares, tophi or structural joint damage, renal insufficiency (CrCl < 60).

• Allopurinol, Febuxostat: Xanthine oxidase inhibitors to reduce uric acid production and promote excretion. Monitor urate levels, be mindful of possible side effects (rash, leukopenia/thrombocytopenia, or diarrhea).

• Probenecid: Uricosuric drug, promotes urate excretion.

• Pegloticase: Recombinant form of uricase; intravenous drug given as an infusion every 2 weeks; helpful for severe, refractory gout.

• Rasburicase: Recombinant uricase; used in tumor lysis syndrome.

Lesch-Nyhan Syndrome

• X-linked enzyme defect (hypoxanthine-guanine phosphoribosyltransferase).
• Results in increased uric acid and "juvenile gout" as well as neurologic impairment (including hypotonia, chorea, and self-mutilating behavior).
• Male children's classic presentation.

Von Gierke's Disease (Glycogen Storage Disease Type I)

• Glucose-6-phosphatase deficiency.
• Infants usually diagnosed between ages 2-6 months with severe hypoglycemia between meals and a risk of seizures.
• Associated with lactic acidosis, causing urate reabsorption and gout attack risk.

Calcium Pyrophosphate Deposition Disease (CPPD)

• "Pseudogout," deposition of calcium pyrophosphate in joints.
• Common in older patients (72 years old, average).
• Often found in patients with hemochromatosis.
• May affect any joint but commonly affects knee..
• Associated with hypercalcemia and hyperparathyroidism.

CPPD Major Clinical Manifestations

• Asymptomatic
• Acute arthritis (similar to gout).
• Chronic joint disease (similar to OA).
• Chondrocalcinosis (calcification of cartilage)

Pseudo-gout

• Commonly involves the knee (50% cases).
• Acute attack of inflammatory arthritis.
• Symptoms resemble gout (pain, redness, warmth, swelling). Mechanism includes trauma, surgery, or medical illness that trigger an acute flair.
• Frequently post-parathyroidectomy.

Pseudo-gout Polarized Light Microscopy

• Rhomboid crystals.
• Positively birefringent.
• Blue color when parallel to the light.

Chronic Joint Disease (CPPD)

• Pseudo-osteoarthritis is the term assigned to progressive joint degeneration, present in ~50% of CPPD patients.
• Progressive cartilage deterioration.
• Bony enlargement and tenderness similar to osteoarthritis.

CPPD Treatment

• Acute pseudogout attack: intraarticular glucocorticoid injection, NSAIDS, Colchicine.
• Chronic joint disease: Treatment similar to osteoarthritis.
• Prophylaxis (for pseudogout): Colchicine.

Systemic Lupus Erythematosus (SLE)

• Autoimmune disease.
• Antibody-antigen complexes circulate in plasma, causing type-III hypersensitivity.
• Deposits occur in many tissues.
• Most patients (90%) are women.
• Onset typically occurs between ages 15 and 45.

SLE Clinical Features

• Flares and remissions are common.
• Fever, weight loss, fatigue, and lymphadenopathy.
• Malar rash ("butterfly" rash), commonly occurring in sun-exposed areas.
• Discoid skin lesions
• Circular skin patches, typically on the forearm.
• Raynaud phenomenon: white/blue fingertips on exposure to cold, vasospasm of arteries, and possible fingertip ulcers.

SLE Clinical Features (cont'd)

• Symptoms: polyarthritis (monarthritis unusual), symmetric, and migratory symptoms that come/go over 24 hours.
• Mild morning stiffness (< RA timeframe).
• Pain is disproportionate to findings on objective examination Mild swelling, minimal X-ray abnormalities
• Oral or nasal ulcers
• Serositis: inflammation of the pleura (pain with inspiration), pericarditis (inflammation of the pericardium).
• "Penias": anemia, thrombocytopenia, leukopenia (low blood counts), antibody deposition.
• Immune system dysfunction, increased infection risk
• Lupus cerebritis (CNS involvement): cognitive dysfunction, confusion, memory loss, stroke or seizures.
• Lupus nephropathy: Nephritic or nephrotic syndrome (or both), common cause of death in SLE.

SLE Laboratory Findings (cont'd)

• Anti-double-stranded DNA (anti-dsDNA): specific for SLE, increased with disease activity, commonly seen in renal involvement.
• Anti-Smith (anti-Sm): specific for SLE.
• Other diagnostic panels: Extractable Nuclear Antigens (ENA) panel, also other antibody tests for phospholipd disease.

SLE Diagnosis

• Need 4 of 11 ACR criteria or 4 of 17 SLICC criteria to establish SLE.

SLE Treatment

• Avoid sunlight exposure and wear sunscreen (many patients are photosensitive).
• Wear sun protection.
• Pregnancy counseling as SLE can worsen the condition.
• Hydroxychloroquine is a first-line anti-malarial medication with immunosuppressant properties.
• Avoid eye-related complication risk, routine eye exams required.
• Glucocorticoids are added to hydroxychloroquine if a more severe form is suspected (e.g. oral prednisone, intravenous methylprednisolone), and other immunosuppressants.

Avascular Necrosis

• Osteonecrosis, bone collapse.
• Common femoral head affected.
• Interruption of blood flow (infarct); demineralization/bone thinning
• Associated with glucocorticoid use and SLE and also occurs in sickle cell disease.
• Pain in groin/thigh or buttock usually present, Reduced range of motion, X-rays or MRI are necessary for diagnosis. Often requires surgical intervention

Drug-Induced Lupus

• Lupus-like syndrome after a drug
• Classic culprit drugs are isoniazid, hydralazine, and procainamide
• Common symptom: rash.
• Other possible symptoms: arthritis, anemia/low blood cell counts, positive ANAs
• Renal involvement, or CNS involvement is rare.
• Key features include anti-histone antibodies .
• Resolution of symptoms following discontinuation of drug.

Mixed Connective Tissue Disease (MCTD)

• Overlap syndrome of SLE, scleroderma, and polymyositis
• Often with Raynaud's phenomenon.
• Arthritis.
• Myalgias
• Pulmonary disease (ILD, PH).
• Absence of renal disease.
• Hallmark: anti-U1 ribonucleoprotein (RNP)
• Treatment: glucocorticoids.

Scleroderma (Systemic Sclerosis)

• Autoimmune disorder.
• Fibroblast activation → excess collagen deposition causing stiff, hardened tissue.
• Skin (and other organ systems) involved.
• Most common in women, peak onset 30-50 years old.
• Clinical subtypes:
  • Diffuse: diffuse skin thickening.
  • Limited (CREST): Skin changes restricted to hands and extremities, with less involvement of other systems.

Scleroderma (Diffuse Form)

• Diffuse skin thickening
• Face:
  • Lip thinning and retraction
• Hands:
  • Fibrosis
  • Puffy fingers, hard to bend
  • Shiny skin and can't pinch
  • Loss of wrinkles
  • Hands like claws These characteristics are also present in the limited form.

Scleroderma (Diffuse Form) Clinical Features (cont'd)

• Raynaud's phenomenon.
• Common initial sign, frequently followed by visceral involvement within 1 year(GI tract-dysmotility, heartburn, renal disease- renal failure, heart-pericarditis/myocarditis, conduction disease, and joints/muscles- arthralgia/myalgias).

Scleroderma (Diffuse Form) Pulmonary Hypertension

• Can progress to right heart failure.
• Elevated jugular veins
• Pitting edema.
• Echocardiography for monitoring is frequently utilized.

Scleroderma Diffuse Renal Crisis

• Life-threatening condition, diffuse scleroderma complication.
• Characterized by acute onset of oliguric renal failure and marked hypertension.
• May present with microangiopathic hemolytic anemia (MAHA), such as schistocytes and thrombocytopenia.
• ACE inhibitors such as captopril are commonly used in treatment, even if creatinine is elevated.

Scleroderma (Limited/CREST Form)

• Skin sclerosis is limited to hands/ extremities, sometimes involving the distal forearm, face, and neck.
• Trunk and proximal extremities are spared
• Classic Features:
• Calcinosis.
• Raynaud's phenomenon.
• Esophageal dysmotility (difficulty swallowing). Sclerodactyly (thickening of the skin on the hands and fingers).
• Telangiectasias (dilated capillaries resulting in visible, red, or purple spots).

Sjogren's Syndrome

• Autoimmune disorder.
• Destruction of salivary and lacrimal glands.
• Clinical features: dry eyes (keratoconjunctivitis sicca, presents as feeling of dirt/debris in the eyes), dry mouth (xerostomia - difficulty chewing dry foods), dysphagia (difficulty swallowing), cavities, bad breath, and/or vulvovaginal dryness/pruritis/dyspareunia.

Sjogren's Syndrome Xerosis

• Dry, scaly skin.
• Often found on the lower extremities and axilla.
• Other symptoms: arthralgias or arthritis, Raynaud's phenomenon, and others.

Sjogren's Syndrome Demographics

• More common in women.
• Onset is usually in the 40s.
• Age-related sicca syndrome is frequently confused with Sjogren's.
• Occurs in elderly patients
• Dry mouth and eyes
• Antibody tests and/or biopsy are usually not needed or normal

Sjogren's Syndrome Classification

• May be primary disorder.
• Often secondary to other conditions (rheumatoid arthritis, SLE, primary biliary cirrhosis).

Sjogren's Syndrome Diagnosis

• No single diagnostic test.
• Usually a combination of features, antibody tests, eye and salivary gland testing, and/or a lip biopsy.

Sjogren's Syndrome Antibodies

• ANA and RF are often positive.
• Anti-Ro/SSA (SS-A) antibodies (also called Ro antigen).
• Anti-La/SSB (SS-B) antibodies (also called La antigen).
• Antibodies alone are not sufficient for diagnosis
• Need objective validation of glandular dysfunction

Sjogren's Syndrome Diagnostic Tests

• Schirmer test (tests reflex tear production, where filter paper is near lower eyelid while closing eyes)
• Labial salivary gland biopsy (lips, detects lymphocytic sialadenitis and lymphocytes in glandular tissue).

Sjogren's Syndrome Diagnostic Tests (cont'd)

• Salivary gland scintigraphy (nuclear test, measures low uptake of radionuclide, saliva production).
• Patient measures and weighs saliva collected over 15 minutes.

Sjogren's Syndrome Treatment

• Behavioral modification (oral hygiene, artificial tears, hydration).
• Avoidance of substances that have desiccating effects (coffee, smoking).
• Secretagogues, such as pilocarpine and cevimeline (muscarinic agonists) are good treatment options.
• In severe cases, glucocorticoids and/or immunosuppressants may be used.

Sjogren's Syndrome B Cell Lymphoma

• Risk of B cell lymphoma in patients with Sjogren's is 5-10%
• Non-Hodgkin's B-cell lymphoma.
• Usually marginal zone lymphoma.
• Presentation as a persistent, unilateral swollen gland.

Neonatal Lupus

• Maternal antibodies (Ro/SSA or La/SSB) cross the placenta.
• Occurring in mothers with SLE or Sjogren's syndrome, as well as in those without a definitive diagnosis, yet exhibiting related antibodies.
• Mostly involves skin and heart
• Usually diagnosed at birth or within first few weeks, and often resolves over months (and rarely longer)

Neonatal Lupus Clinical Features

• Rash: multiple red circular lesions on the face, scalp; usually resolves over months.
• Congenital Complete Heart Block: fetal bradycardia (<110 bpm) during pregnancy followed by Bradycardia at birth. Pacemaker placement may be required.

Vasculitis

• Rare autoimmune disorders.
• Inflammation of blood vessels
• Typical symptoms of inflammation (fever, myalgias, arthralgias, fatigue).
• Organ-specific symptoms may also be present as inflammation of the vessel lumens narrows or occludes.

Purpura

• Red-purple skin lesions, extravasation (leakage) of blood into skin).
• Does not blanch when pressed
• Occurs in vasculitis
• Raised
• Can include temporal arteritis, Takayasu's arteritis, and other diseases.

Temporal Arteritis (Giant Cell Arteritis)

• Inflammation of the temporal artery system of the head and neck
• Symptoms include: fever, fatigue, weight loss; Painful jaw claudication (pain on chewing), vision loss, ophthalmic artery occlusion (transient or permanent blindness); may lead to aortic aneurysm.

Temporal Arteritis Epidemiology

• More common in women.
• Almost all patients over 50 years old.
• Key clinical clue is high ESR (erythrocyte sedimentation rate).

Temporal Arteritis Diagnosis and Treatment

• Diagnosis using temporal artery biopsy (removal of segment of superficial temporal artery).
• Granulomas are present in temporal arteritis.
• Treat with high-dose glucocorticoids (steroids).
• Rapid treatment is required.
• Avoid delay if high suspicion.
• ESR should fall with therapy.

Takayasu's Arteritis

• Granulomatous thickening of the aortic arch and branches
• Up to 90% of cases occur in women, affecting young adults ages 20-40.
• Often presents similar features of temporal arteritis
• Differentiates based on age of onset (< 50 yrs).
• Prevalence is greater in Asia, but found worldwide.
• Granulomatous inflammation of large vessels, presenting with features that may include: fever, fatigue, weight loss, high ESR/CRP, narrowing of the aorta or any one of its branches.
• "Pulseless disease," with weak carotid pulses, BP differences between arms/legs, and/or bruits over arteries.
• Vision loss frequently included in symptoms.
• Angiography frequently indicated as well as a vascular stent placement; initially treated with high-dose glucocorticoids.

Kawasaki Disease

• Primarily affects children aged 1-5.
• Features are: elevated ESR/CRP, leukocytosis and thrombocytosis; classic involvement (skin, lips, tongue, diffuse, red rash, palms/soles later desquamates), changes in lips/oral mucosa (“strawberry tongue”), feared complication (coronary aneurysms), possible lymphocytic myocarditis, and risk for coronary artery rupture/myocardial infarction.

Kawasaki Disease Clinical Criteria (cont'd)

• Fever (≥5 days) plus 4-5 additional findings: bilateral conjunctivitis, cervical lymphadenopathy, mucositis (erythema of lips and pharynx, strawberry tongue), extremity changes, and rash.
• Treatment includes intravenous immune globulin (IVIG) plus aspirin (to reduce risk of coronary aneurysms in children; risk of Reye syndrome is a consideration).

Scarlet Fever

• Diffuse, red rash following strep throat infection or skin infection: often preceded by a sore throat, many small papules (sandpaper skin texture), classic finding is strawberry tongue, and skin eventually desquamates (peels).

Reye's Syndrome

• Liver failure and encephalopathy characterized by vomiting, confusion, seizures, coma, followed by a viral illness
• Associated with aspirin use in kids (generally; an exception is Kawasaki disease).

Buerger's Disease (Thromboangiitis Obliterans)

• Inflammation of small or medium arteries and veins in extremities, formation of inflammatory occlusive thrombi, and more common in younger patients (<45) with tobacco use.
• Poor blood flow to hands/feet; Raynaud's phenomenon, superficial thrombophlebitis, gangrene/autoamputation of digits.

Buerger's Disease Diagnosis and Treatment

• Often a clinical diagnosis with patient age < 45 years, and history of tobacco use, distal extremity ischemia

• Positive exclusion of other causes including negative ANA testing

• Angiography sometimes employed.

• Treatment includes smoking cessation, calcium channel blockers (e.g., nifedipine), and/or intravenous iloprost (prostaglandin).

Polyarteritis Nodosa (PAN)

• Inflammation of medium-sized vessels.
• Clinical features involve multiple vascular beds, often with hypertension, renal insufficiency, abdominal pain/bloody diarrhea, motor or sensory nerve deficits, skin nodules, or purpura.

Polyarteritis Nodosa (PAN) cont'd

• Often suspected based on clinical findings, such as systemic symptoms, high ESR/CRP, and negative test results for other conditions (e.g., ANCA).
• Angiogram analysis, particularly to visualize kidney, liver, and mesenteric arteries (rosary sign); a biopsy of affected organs may reveal transmural inflammation with fibrinoid necrosis.

IgA Vasculitis (Henoch-Schönlein Purpura)

• Antibody deposition in tissues/vessels.
• Usually affected children..
• Commonly follows an upper respiratory syndrome.
• Associated with IgA vasculitis.
• Palpable purpura on legs and buttocks; abdominal pain and gastrointestinal bleeding; arthralgias and hematuria with no casts or protein, frequently encountered in children.

IgA Vasculitis Diagnosis and Treatment

• Clinical diagnosis based on classic findings
• Skin or renal biopsy to detect
  • Leukocytoclastic vasculitis
  • IgA deposition
• Supportive care (fluids, NSAIDs), monitor BUN/Cr
• Feared complication is renal failure in severe cases, treating severe cases with glucocorticoids

ANCA-associated Vasculitis Syndromes

• Group of disorders characterized by anti-neutrophil cytoplasmic antibodies (ANCAs).
• Different ANCA types (c-ANCA, p-ANCA).
• All have involvement of pulmonary and renal tissues.

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• Vasculitis with allergic features.
• Classic symptoms include asthma and eosinophilia
• Asthma with lung opacities on imaging, eosinophils >10% of total leukocytes, skin lesions (palpable purpura), and GI involvement (abdominal pain or bleeding).

Eosinophilic Granulomatosis with Polyangiitis (EGPA) cont'd

• Positive p-ANCA in 50% cases and elevated ESR/CRP
• Biopsy of involved site will show eosinophils.

Granulomatosis with Polyangiitis (GPA)

• Sinusitis, hemoptysis, or otitis media.
• Upper and lower airway disease.
• Glomerulonephritis (kidney involvement).
• Other symptoms: purpura, granulomas on biopsy, and positive C-ANCA.

Microscopic Polyangiitis

• Similar to GPA (without the presence of sinusitis, upper respiratory disease, granulomas, and C-ANCA).
• Characterized by: hemoptysis, glomerulonephritis, purpura, p-ANCA instead of c-anca, absence of granulomas during biopsy.

Goodpasture's Syndrome

• Autoimmune disease with anti-GBM antibodies, attacking type IV collagen found in glomeruli and alveoli.
• Hemoptysis and nephritic syndrome are frequent symptoms.
• Clinical features can mimic GPA or ANCA disease (negative ANCA).
• Diagnosis includes biopsy for linear IF antibody staining for IgG/C3.

Pulmonary-Renal Syndromes Summary

• Group of disorders.
• Disorders often involve higher-level organs affected in the case of ANCA
• Churg Strauss, Wegener's, microscopic polyangiitis, Goodpasture's syndromes as examples.

Spondyloarthritis

• Family of autoimmune disorders characterized by joint inflammation.
• Seronegative disorders, often without rheumatoid factor or other related antibodies
• Includes:
  • Anky

This quiz covers the essential aspects of arthritis, including its inflammation types, classification, and diagnostic methods such as arthrocentesis. Test your knowledge on the differences between non-inflammatory and inflammatory arthritis, as well as the specifics of osteoarthritis and joint involvement. Perfect for medical students and healthcare professionals.