Rheumatoid arthritis (RA): Pathogenesis and Joint diseases features
• RA affects 1% of population, women > men
• Characterized by poly-articular joint pain, swelling, and stiffness, most commonly affecting the small joints (wrists, metacarpal-phalangeals). Joint involvement is bilaterally symmetrical.
• Extra-articular manifestations are often seen.
• Plasma cells often produce characteristic antibodies -> Anti-Cyclic Citrullinated Peptide (aCCP), Rheumatoid Factor (RF) in serum
• Non-specific Acute-phase reactants are also produced -> High serum CRP. ESR
• Stimulation of nerve endings in subchondral bone & synovial membrane (NOT in cartilage) -> Symmetrical, poly-articular arthralgia (joint pain), especially in small joints.
• Rate of inflammatory fluid accumulation in synovial joint capsule exceeds rate of fluid drainage -> Palpable Joint effusion (Swelling notable on Xray)
• Synovial enlargement forms palpable lumps in the joint -> Enlarged, "boggy" joints, esp carpal, MCP, PIP joints
• Physical narrowing of joint space decr joint mobility -> Incr joint stiffness, Decr Range of movement
• As cartilage and subcondral bone is eroded, continued usage / pressure on joints can mal-align, sublux, or collapse joints -> Joint Deformities. i.e. Swan-neck Boutonniere's ulnar drift of fingers, radial wrist deviation, etc
• Systemic inflammation + other mechanisms -> Extra-articular signs
#RheumatoidArthritis #RA #pathophysiology #signs #symptoms #diagnosis
Rheumatoid Arthritis - Signs and Symptoms
• Ocular: Keratoconjunctivitis sicca, Episcleritis, Scleritis, Scleromalacia perforans
• Pulmonary: Parenchymal lung disease, Pleural disease, Airways disease, Complications of DMARDs
• Skin: Rheumatoid nodules, Vascular lesions
• Gastrointestinal: Esophagitis, gastritis and peptic ulcer disease, Hepatotoxicity from DMARDs
• Neurological: Entrapment neuropathy, Cervical myelopathy, Peripheral neuropathy, Mononeuritis multiplex
• Vascular: Rheumatoid vasculitis, Raynaud's, Atherosclerosis
• Cardiac: Coronary artery disease, Pericarditis
• Renal: Tubulo-interstitial nephritis, AA amyloid, Membranous glomerulonephritis
• Musculoskeletal: Joint, Tendon, Bursa, Muscle, Bone
• Hematological: Anemia, Thrombocytosis, Felty's syndrome
#Rheumatoid #Arthritis #RA #Signs #Symptoms #diagnosis #rheumatology
Psoriatic Arthritis: Pathogenesis and Clinical findings
In tendons and connective tissues:
• Enthesitis - Pain/tenderness over ligament insertion into bone
• Dactylitis - Inflammation of entire digit- soft tissue and joints are inflamed
In skin:
• Psoriatic plaques on skin, pitting, ridging, oil spots, onycholysis, discoloration and hyperkeratosis
In Joints:
1. Asymmetric oligoarthritis
2. Arthritis of DIP joints
3. Symmetric polyarthritis (like RA)
4. Axial involvement (unknown reason, probably due to "biomechanical", "innervation" & "vascularity")
5. Arthritis mutilans (aggressive & destructive)
• X-ray: Periostitis; syndesmophytes, erosions, pencil in cup deformities due to osteolysis (IP joints), ankylosois of IP joints
#PsoriaticArthritis #pathophysiology #diagnosis #signs #symptoms
Panic Disorder: Pathogenesis and clinical findings
Social Factors
• Parenting and infant attachment
• Childhood illness/abuse
• Prolonged stress or trauma
• Substance abuse
Biological Factors
• Dysregulation of autononomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis
• GABA abnormalities
Psychological Factors
• Strong belief/fear of physical or mental harm from bodily sensations
• Neurotic personality
Genetics ~30-40% heritability
>> Panic Disorder - Panic Attack most often in absence of external cue/trigger
Physical Symptoms
• Incr Heart rate, hyperventilation, sweating, trembling, nausea, dyspnea, chest pain, heart palpitations, diaphoresis
• Hyperventilation -> respiratory alkalosis
• Dizziness, lightheadedness, numbness, shortness of breath
Psychological Symptoms
• Uncontrollable fear about symptoms/losing control/dying
• Sense of altered reality
Experiential Avoidance
• Avoidance of situations that reproduce bodily sensations similar to panic attacks (exercise, caffeine, alcohol, saunas)
Safety Behaviours
• I.e. carrying anti-anxiety medication, locating the nearest hospital (to sense of security in the event of a panic attack)
Anticipatory Anxiety
• Intrusive thoughts and worries about where/when a panic attack will occur and the consequences (embarrassment, discomfort)
#PanicDisorder #Anxiety #BehavioralDisorder #Pathophysiology #diagnosis #symptoms #signs #psychiatry
Sjogren's Syndrome Overview
Epidemiology:
• F > M: 9:1
• 5-6th Decades (can be any age)
Autoimmune exocrinopathy multisystemic disease affecting salivary and lacrimal glands:
• Focal lymphocytic sialadenitis
• Keratoconjunctivitis sicca
• Xerostomia
• Symmetric parotid swelling
• Lacrimal swelling
• Skin dryness
• Vaginal dryness
• Primary form: not associated with other diseases
• Secondary form: overlaps with RA, SLE
• Mikulicz syndrome: Prominent parotid and lacrimal glandular enlargement
Sjogren's Syndrome Diagnosis:
• Dry eyes
• Salivary hypofunction
• Antibodies: Anti-Ro/SSA & Anti-La/SSB ab
• Lip (minor salivary gland) biopsy
• Ocular examination
Labs:
• Antibodies:
• Anti-Ro/SSA ab (specific in primary)
• Anti-La/SSB ab
• RF
• Antinuclear antibodies ≥ 1:320
• Cytopenia: 2%
• Hypocomplementemia
• Can cause TYPE IV RTA, TYPE I RTA
Diagnosis:
• LIP (minor salivary gland) biopsy
• Histo: aggregate foci (>50 cells/aggregate) of CD4 T cells, B cells, and plasma cells around salivary ducts
Clinical Features:
HEENT:
• Keratoconjunctivitis sicca
• Xerostomia
• Dental caries
• Parotid swelling
CNS Involvement:
• Central nervous system (CNS): demyelinating disease, myelopathy, cranial nerve neuropathy
• Peripheral nervous system: small-fiber neuropathy, mononeuritis multiplex, peripheral neuropathy, transverse myelitis
• 8%-27% for CNS and peripheral
Thyroid Disease:
• 10%-15%
Pulmonary
• Interstitial Pneumonitis (LIP, UIP, NSIP):
• Lymphocytic interstitial pneumonia
• Usual interstitial pneumonia
• Tracheobronchial disease
• Xerotrachea
• NSIP: Pleural thickening or effusion, INC risk PE, Pulmonary amyloidosis, PAH
Skin:
• Dry skin (xerosis)
• Cutaneous vasculitis: 10%-16%
Liver:
• Autoimmune hepatitis, primary biliary cirrhosis: 3%-20%
Renal:
• Interstitial nephritis
• Distal (Type I) renal tubular acidosis
• NAGMA
• Glomerulonephritis: 5%-6%
• Membranoproliferative GN
• Nephrogenic DI
Hematologic:
• Lymphoma, Cytopenia: 2%
Systemic Vasculitis:
• 7%, Cryoglobulinemia (4%-12%), Raynaud phenomenon (16%)
MSK:
• Arthralgia and Arthritis
Malignancy Risk:
• Non-Hodgkins lymphoma
• B cell lymphoma
• Large B cell lymphoma
• MALT Lymphoma
• Lung Adenocarcinoma
Treatment:
• Symptomatic: artificial tears/artificial saliva/mouth lubricants
• Pharmacologic:
• Severe oral dryness: muscarinic agonists
• Active extraglandular autoimmune disease: Glucocorticoids
• Immunomodulatory/Biologic: 2nd or 3rd line
#Sjogrens #Syndrome #Rheumatology #Diagnosis #Management
Sweet Syndrome
Acute febrile neutrophilic dermatosis (Sweets Syndrome) is a skin condition characterized by fever and inflamed or blistered skin and mucosal lesions. Neutrophilic dermatoses are autoinflammatory conditions that can be associated with systemic disease.
Rare Disorder:
- Fever + sudden onset of a rash
- Rash: multiple tender, red or bluish-red bumps or lesions.
- Occurs on the arms, legs, trunk, face or neck.
Other areas:
- Musculoskeletal system such as inflammation of the joints (arthritis)
- The eyes such as inflammation of the conjunctiva or the membrane that lines the eyes (conjunctivitis)
- Internal organs
Most common extra cutaneous involvement:
Eyes
- Conjunctivitis
- Episcleritis
Signs and Symptoms:
- Fever
- Fatigue
- Headaches
- A general feeling of ill health (malaise)
- Muscle pain (myalgia)
- Inflammation and pain of the joints (arthritis and arthralgia)
- Fever can precede the development of skin symptoms by days or weeks.
- Papules are solid, raised lesions; nodules are slightly larger and may extend deeper into the skin.
- Sudden onset of tender or painful bumps (nodules or papules) on the arms, legs, face or neck.
- They may also occur on the thighs and trunk.
Causes:
- Idiopathic Sweet syndrome - this is also known as classical Sweet syndrome.
- Underlying cancer (malignancy), lymphoma, breast CA
- Hematologic cancer such as certain types of leukemia
- Cancers of the genitourinary and gastrointestinal tracts.
- Drug induced: GCSF stimulating factor
- Upper respiratory infection, gastrointestinal infection, or influenza-like illness can precede skin lesions by one to three weeks.
DDX:
- Pyoderma gangrenosum
- Erythema multiforme
- Dermatomyositis
- CANDLE syndrome
- Allergic contact dermatitis
- Cellulitis
- Erythema nodosum
- Acral erythema
- Bacterial sepsis
- Neutrophilic rheumatoid arthritis
- Panniculitis
- Leukemia cutis
- Leukocytoclastic vasculitis
- Schnitzler’s syndrome
- Lupus
- Leukemia cutis
Diagnosis:
- Biopsy
- Microscopic examination of small samples of skin tissue may reveal the infiltrate of neutrophils in the dermis.
- CBC may also show neutrophils in the blood (neutrophilia).
Treatment:
- Systemic corticosteroids
#Sweet #Syndrome #diagnosis #dermatology #oncology
Sarcoidosis - Diagnosis and Management Summary
Epidemiology
1) High incidence in Scandinavian countries (11-24 cases per 100,000 individuals per year) and among African Americans (18-71 cases per 100,000 individuals per year)
2) Lowest in Asian countries (1 case per 100,000 individuals per year)
3) Sex: female > male (2:1)
4) Average age onset: 40-55; f 50-60y (hormonal changes around menopause) and m 30-50y
5) Global mortality: 9-14 cases per 1,000 person-years and 5-year survival is 93-95%
Pathophysiology:
1) T-cell dysfunction and increased B-cell activity → local immune hyperactivity and inflammation
2) Formation of non-caseating granulomas within the lungs and the lymphatic system
3) Fibrosis and damage of organs and tissue: Epithelioid cells → cytokines to fibroblasts → fibrosis.
4) Calcium dysregulation: activated macrophages produce 1-alpha hydroxylase → ↑ 1,25 hydroxyvitamin D (hypervitaminosis D) hyperphosphatemia, hypercalcemia, and possibly renal failure
Clinical Features:
• Many symptoms are not caused by granulomas in a specific location but result from their release of mediators such as hypercalcaemia (~10% of patients) and/or hypercalcuria (~40%); fatigue(→ post-sarcoidosis fatigue syndrome). 30-50% patients have no symptoms at the time of diagnosis (e.g. incidental CXR finding).
• Natural history: Self-limiting, chronic but stable or chronic and progressive
Acute sarcoidosis (1/3 of cases): 50% remits spontaneously within approx. 2 years and many others 5 years; remission less likely after 5 years. Progression to chronic sarcoidosis is rare.
1. General: fever, malaise, lack of appetite, weight loss
2. Pulmonary: dyspnea, cough, chest pain
3. Extrapulmonary: ankle arthritis, anterioruveitis, erythema nodosum
4. Otherinitial presentations: epileptic seizure, cranial neuropathy or cardiac arrest
Chronic sarcoidosis (2/3 of cases): rarely preceded by acute sarcoidosis
Pulmonary and extrapulmonary (peripheral lymph nodes: 13-15%, skin (16-32%): lupus pernio, papules, nodules; anterior/posterior MSK, heart (2-5%), liver (pain/abnormal LFT): 12-20%, spleen (pain): 5-10%, nervous system (Conductance disturbances, arrhythmias, dyspnoea, fatigue (for example, cardiomyopathy) and syncope): 2-5% Specific sarcoidosis syndromes: (distinct symptoms)
• Löfgren syndrome: ACUTE, fever, migratory polyarthritis(symmetrical, ankles), erythema nodosum (extensor surface of legs), bilateral hilarlymphadenopathy
• Heerfordt syndrome: Chronicclinical presentation with fever, parotitis, uveitis (iridocyclitis) and facial palsy.
Dr. Jorge Cortés @Jcortesizaguirr
#Sarcoidosis #Diagnosis #Management #Signs #Symptoms
