1. Systemic sclerosis (scleroderma): Often associated with diffuse or limited forms, with accompanying features like skin thickening, telangiectasias, and organ involvement.

2. Systemic lupus erythematosus (SLE): Commonly seen in autoimmune connective tissue disorders, including lupus.

3. Mixed connective tissue disease (MCTD): Often characterized by features overlapping systemic sclerosis, lupus, and polymyositis.

4. Rheumatoid arthritis (RA): Can occur as part of vasculitis in RA or secondary to other autoimmune mechanisms.

5. Sjogren’s syndrome: An autoimmune condition that may involve Raynaud's as part of its systemic manifestations.

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune, multisystem inflammatory disease characterized by the production of autoantibodies and immune complex deposition leading to tissue damage.

1. UV radiation: Induces keratinocyte apoptosis, leading to increased nuclear antigen release.

2. Infections: May trigger autoimmunity through molecular mimicry.

3. Hormonal factors: Higher prevalence in females (estrogen enhances immune response).

cell begins apoptosis, formation of blebbing (nucleus condensing) sending singlas to macrophages to come & engulf. Phagocytosis will come and engulf.

In lupus, macrophages are taking too long or not consumed at all. The tiny fragmented pieces leak and spill into the body, causing the immune system to form anti-nuclear antibodies that attack antigens.

These immune system complexes can affect any part of the body.

1. Fatigue, fever, weight loss. (for lupus its actually pretty common)

2. Lymphadenopathy.

1. Malar rash (butterfly rash): Fixed erythema-sparing nasolabial folds.

2. Discoid rash: Erythematous patches with scarring.

3. Photosensitivity.

4. Oral or nasal ulcers.

1. Arthralgia and arthritis: Symmetrical, non-erosive (different from rheumatoid arthritis).

2. Myalgia and myositis.

1. Renal:

   • Lupus nephritis: Proteinuria, hematuria, or nephrotic syndrome. Classified into six histological classes (based on ISN/RPS).

   • May progress to chronic kidney disease (CKD).

2. Cardiovascular:

   • Pericarditis (most common cardiac manifestation).

   • Libman-Sacks endocarditis (sterile vegetations on heart valves).

   • Increased risk of atherosclerosis.

3. Pulmonary:

   • Pleuritis with pleuritic chest pain.

   • Interstitial lung disease.

   • Pulmonary hypertension.

4. Neurological:

   • Seizures, psychosis.

   • Peripheral neuropathy, cranial neuropathy.

   • Cognitive dysfunction.

5. Hematological:

   • Anemia of chronic disease, autoimmune hemolytic anemia.

   • Leukopenia, lymphopenia.

   • Thrombocytopenia.

6. Gastrointestinal:

   • Abdominal pain, nausea, vomiting.

   • Mesenteric vasculitis (rare).

1. Antinuclear antibody (ANA): Sensitive but not specific (present in >95% of SLE cases).

2. Anti-dsDNA antibodies: Specific, associated with lupus nephritis.

3. Anti-Smith (Anti-Sm) antibodies: Highly specific but less sensitive.

4. antiphospholipid antibodies

decreased C3, decreased C4

1. Elevated ESR (not CRP unless infection or concurrent inflammation).

2. High CRP suggests superimposed infection or inflammation.

General Measures:

• Sun protection.

• Smoking cessation (reduces flares and cardiovascular risk).

• Patient education regarding triggers.

Pharmacological Treatment:

• Hydroxychloroquine (HCQ): First-line for all patients unless contraindicated; reduces flares and improves survival.

• Corticosteroids: For acute flares or organ-threatening disease.

  • Dose tailored to severity (e.g., low-dose for skin/joint involvement, high-dose for nephritis or CNS lupus).

• Immunosuppressants:

  • Azathioprine: Maintenance therapy.

  • Mycophenolate mofetil (MMF): First-line for lupus nephritis.

  • Cyclophosphamide: Used for severe organ involvement (e.g., nephritis, CNS lupus).

• Biologics:

  • Belimumab: Anti-BLyS monoclonal antibody for refractory SLE.

• NSAIDs: Symptomatic relief for arthritis or serositis.

• Anticoagulation: For antiphospholipid syndrome (warfarin, heparin in pregnancy).

infections

early atherosclerosis

valvular heart diseasese

osteoporosis

fibroblast dysregulation cause a connective tissue proliferation resulting in skin thickening

and visceral organ damage

Limited cutaneous systemic sclerosis skin involvement distal to elbows and kness + Crest sydnrome

Diffuse cutaneous systemic sclerosis

• crest + organ involvement

• effects all of body

Fibroblast Activation:

• Excessive collagen production → fibrosis of skin and organs.

CREST

telengectasia

has more vigorous form of Rayndaud phenomonon

skin hyperpigementation & depigmentation “salt and pepper”

Nailfold capillary changes.

1. Musculoskeletal:

   • Arthralgia, contractures.

   • Osteoarthritis in advanced cases.

2. GI Tract:

   • Dysphagia (esophageal dysmotility, strictures).

   • Reflux, malabsorption.

3. Lungs:

   • Interstitial lung disease (ILD).

   • Pulmonary arterial hypertension (PAH).

4. Heart:

   • Myocardial fibrosis, arrhythmias.

5. Renal:

   • Scleroderma renal crisis (hypertension, renal failure).

1. Limited cutaneous SSc:

   • Anti-centromere antibodies (ACA): Associated with CREST

2. Diffuse cutaneous SSc:

   • Anti-Scl-70 (topoisomerase I): Associated with ILD.

   • Anti-RNA polymerase III: Associated with renal crisis.

1. Blood Tests:

   • Positive ANA (~95% cases).

   • Specific antibodies: Anti-Scl-70, anti-centromere, anti-RNA polymerase III.

2. Imaging:

   • Chest CT: Interstitial lung disease.

   • Echocardiogram: Pulmonary hypertension.

3. Pulmonary Function Tests:

   • Reduced diffusion capacity in ILD or PAH.

4. Nailfold Capillaroscopy:

   • Capillary dropout and dilatation in Raynaud's phenomenon.

5. Skin Biopsy:

   • Confirms fibrosis but rarely needed for diagnosis.

fibrosis

vasculopathy

inflammation

1. general:

   • No definitive cure; treatment is symptom-based and organ-specific.

2. Raynaud’s:

   • Calcium channel blockers (nifedipine), vasodilators (sildenafil, prostacyclin analogs). & PDE5

3. Pulmonary:

   • ILD: Mycophenolate mofetil, cyclophosphamide.

   • PAH: Endothelin receptor antagonists (bosentan), PDE-5 inhibitors (sildenafil).

4. Renal:

   • ACE inhibitors (first-line for renal crisis).

5. GI:

   • Proton pump inhibitors (PPI) for GERD.

6. Immunosuppression:

   • Methotrexate, rituximab in severe disease.

7. Emerging Therapies:

   • Autologous hematopoietic stem cell transplantation (for severe cases).

1. Immune Dysfunction: Autoantibodies (anti-SSA/Ro and anti-SSB/La) attack exocrine glands.

2. Glandular Dysfunction: Lymphocytic infiltration damages glands, reducing secretions.

3. Systemic Involvement: Immune-mediated damage to lungs, kidneys, and nervous system.

1. Exocrine Gland Involvement:

   • Dry Eyes: Burning, gritty sensation, photophobia.

   • Dry Mouth: Difficulty swallowing, dental caries, salivary gland swelling.

2. Systemic Symptoms:

   • Fatigue, arthralgia, myalgia.

   • Respiratory: Dry cough, interstitial lung disease.

   • Renal: Interstitial nephritis, renal tubular acidosis.

   • Neurologic: Peripheral neuropathy.

lymphoma (MALT)

• Clinical Symptoms: Dry eyes and dry mouth for >3 months.

• Ocular Tests:

  • Schirmer test (<5 mm in 5 minutes).

  • Fluorescein staining (corneal damage).

• Oral Tests:

  • Salivary flow rate.

  • Salivary gland biopsy (focal lymphocytic sialadenitis).

• Laboratory:

  • Autoantibodies: Anti-SSA/Ro, anti-SSB/La, ANA, RF.

  • Elevated ESR, hypergammaglobulinemia.

1. Sarcoidosis.

2. Amyloidosis.

3. Viral infections (HIV, hepatitis C).

4. Autoimmune diseases (RA, SLE).

1. ymptomatic Treatment:

   • Dry Eyes: Artificial tears, cyclosporine drops.

   • Dry Mouth: Frequent water sipping, pilocarpine, cevimeline.

2. Systemic Therapy:

   • NSAIDs for mild symptoms.

   • Hydroxychloroquine, methotrexate for systemic involvement.

   • Corticosteroids for vasculitis.

3. Preventive Measures:

   • Regular dental care to prevent caries.

   • fluroide as prophylactic measure

in association with Sjogren syndrome

• xerostomia

• xeropthalmia

• parotid gland enlargement

• dysparuria

labial salivary gland biopsy

anti-SSA- Ro antibody

anti-SSB- La antibody

against acetylcholine receptor

if mouth dry —> pilocarpine

if only dry eyes and mouth —> secretagogue

constitutional symptoms:

• DMARS or glucocorticoids

• cyclophosphamide

• 
  

RA is a chronic autoimmune disease characterized by persistent synovial inflammation, leading to joint destruction, systemic manifestations, and extra-articular involvement.

1. Autoimmune Trigger: Loss of tolerance leads to T-cell activation against self-antigens.

2. Inflammation:

   • Infiltration of T-cells, B-cells, and macrophages into synovium.

   • Cytokines: TNF-α, IL-1, and IL-6 mediate inflammation.

3. Pannus Formation: Hyperplastic synovial tissue destroys cartilage and bone.

4. Systemic Effects: Release of inflammatory mediators into circulation causes systemic manifestations.

1. Joint Symptoms:

   • Symmetrical polyarthritis.

   • Affects small joints: MCP, PIP, wrists, MTP (sparing DIP joints).

   • Morning stiffness >1 hour, improves with use.

   • Bakers cysts

2. Systemic Symptoms: Fatigue, fever, weight loss.

3. Extra-articular Symptoms: Rheumatoid nodules, vasculitis, lung involvement, and ocular inflammation (scleritis).

1. Small joints: MCP, PIP, wrist.

2. Feet: MTP joints.

3. Large joints in advanced disease: Knees, elbows, shoulders.

4. Cervical spine: Atlantoaxial subluxation in severe cases.

1. Skin: Rheumatoid nodules.

2. Lungs: Interstitial lung disease, pleuritis, nodules.

3. Heart: Pericarditis, increased risk of CAD.

4. Eyes: Scleritis, episcleritis.

5. Vasculitis: Small vessel vasculitis, digital ischemia.

6. Hematologic: Anemia of chronic disease, Felty syndrome (RA + splenomegaly + neutropenia).

1. Serology: RF and Anti-CCP antibodies. '

   • might be present, might be absent

   • if anti CCP present, more aggressive

2. Acute Phase Reactants: ESR, CRP elevation.

3. Duration of Symptoms: >6 weeks.

1. X-rays: Joint space narrowing, periarticular osteopenia, erosions.

2. Ultrasound/MRI: Early detection of synovitis, bone edema.

1. Disease-Modifying Antirheumatic Drugs (DMARDs):

   • Methotrexate (first-line).

   • Leflunomide, sulfasalazine, hydroxychloroquine.

2. Biologics:

   • TNF inhibitors: Infliximab, etanercept.

   • Non-TNF agents: Rituximab, abatacept. (this is biologic, used as last resort)

3. Janus Kinase (JAK) Inhibitors: Tofacitinib.

4. Glucocorticoids: For short-term control during flares.

5. NSAIDs: Symptom relief, adjunct therapy.

joint replacement in severe cases

1. Joint destruction and deformities (e.g., ulnar deviation, swan-neck deformity).

2. Atlantoaxial subluxation.

3. Increased risk of osteoporosis and fractures.

4. Cardiovascular disease.

5. Infections due to immunosuppressive therapy.

1. RA: Autoimmune, inflammatory, symmetric polyarthritis, affects MCP/PIP, morning stiffness >1 hour.

2. OA: Degenerative, non-inflammatory, asymmetric, affects DIP/weight-bearing joints, stiffness <30 minutes.

• smoking

• stress

• high caffeine consumption

PANNUS

layer of vascular fibrous tissue, grow so largley to damage bones and cartilage. space between joints will dissapear

MCP

PIP

MPT

• ulnar deviation

• swan neck deformity

• boutonnniere deformity

• carpal tunnel syndrome

• hammer life foot

• acetbular protusion

• baker cyst

• tempormandibular joint

• rheumatoid nodules

• dry eyes —> secondary sjogren

• kidney, lung and cardiovascular involvment

• osteopenia —> osteoporosis

• vasculitis

DAS 28 (all joints except hip and feet)

• physiotherapy

• local cold therapy

• exercises

  • range of motion

  • conditioning

  • strenthenign exercises