continue Flashcards
polymyositis
inflammation and necrosis of skeletal muscle fibers is immune mediated (CD8)
what antibodies in PM
Anti-SRP antibodies
what muscles are affected in PM
Symmetric, proximal muscle weakness (shoulders, thighs)
• Difficulty climbing stairs, rising from a chair, lifting objects
• Neck flexor weakness (difficulty holding up head)
• No significant pain (unlike polymyalgia rheumatica)
extramuscular involvement in PM
• Dysphagia (pharyngeal muscle weakness) → Aspiration risk
• Interstitial lung disease (ILD) → Progressive dyspnea, cough
• Arthralgia (joint pain, but no erosions)
• Cardiac involvement (rare, arrhythmias, myocarditis)
what is dermatomyositis
proximal muscle weakness and distinctive skin rashes. It involves humoral (B-cell) immune attack on muscle capillaries and perimysial connective tissue, unlike polymyositis, which is cell-mediated (CD8+ T cells).
what antibodies are in DM
Anti-Mi2 antibodies
Characteristic skin changes in DM
Heliotrope Rash- Violaceous rash on upper eyelids, often with periorbital edema
Gottron’s Papules- Raised, scaly erythematous plaques over MCP & PIP joints (pathognomonic)
Gottron’s Sign- Macular erythema over elbows, knees, or malleoli
Shawl & V Sign - Photosensitive erythematous rash over shoulders & upper chest
Mechanic’s Hands- Hyperkeratosis & fissuring of fingers (associated with anti-Jo-1)
diagnosis of PM and DM
• Muscle biopsy, the definitive test. (inflammatory cell infiltration and necrosis of muscle cells)
• Serum muscle enzymes (creatine kinase, aminotransferase, aldolase) are elevated.
• Positive ANA in more than 75%
• Anti-JO antibodies (anti-tRNA synthetase) are positive (1:
most common, 2: more in DM)
what changes in EMG are found in PM
o Short duration, low amplitude polyphasic units on
voluntary activation.
o Increased spontaneous activity with fibrillations,
complex repetitive discharges, positive sharp waves.
connective tissue diseases
Marfan’s Syndrome
Ehlers-Danlos Syndrome
marfan syndrome mutation in what
autosomal dominant disorder associated with mutation in fibrillin 1 gene on chromosome 15.
clinical features of marfan syndrome
• Clinical Features:
o Collagen abnormalities: fragility of the skin and bruising o Skeletal abnormalities: tall stature, arm span greater than height, arachnodactyly, sternal depression, hypermobile joints, high arched palate.
o Other features: upward dislocation of the lens & cardiovascular complications (Ascending aortic aneurysm formation & valve incompetence)
ehlers danlos syndrome
• Definition: inherited defect of collagen -> fragility and hyperelasticity of the skin
• Clinical features: easy bruising, “paper thin” scars, hypermobility of the joints, and rarely the weak walls of the aorta and gut may rupture.
muscle disorders
Myalgia: muscle symptoms without increased serum CK levels.
Myositis: muscle symptoms + elevated CK levels, after excluding causes of high CK.
Myopathy: primary functional or structural impairment of skeletal muscle, which can be acquired or hereditary
fibromyalgia
• Chronic widespread pain (≥3 months) & ≥
response to pressure
• 9 times more common in females
• Pain in at least 11 out of 18 tender points
• Fatigue, sleep disturbances, cognitive depression, foggy
• Partially respond to exercise & Amitriptyline
Myofascial pain syndrome
• Unbearable pain from one point of body to next
• Deep aching muscle pain, joint stiffness, areas of tension (knot-like feeling)
• Sites: arms/ legs, neck & back, buttocks, + many referred trigger points
• Treatment: analgesia, antidepressants, muscle relaxants, physiotherapy, acupuncture
Polymyalgia rheumatica
• Periarticular pain (shoulder & hips)
• Bilateral aching & stiffness
• Morning stiffness > 1 hour
• Fatigue, loss of appetite, weight loss
• VERY HIGH ESR **
Osteoporosis is a progressive systemic skeletal disease characterized by:
- reduced bone mass
- micro-architectural deterioraton of bone tssue
- increased skeletal fragility
- The normal bone remodeling process consists of diferent phases:
- Actvaton phase: osteoclasts recruited to the surface of the bone.
- Resorpton phase: osteoclasts generate an acidic microenvironment between the cell and the surface of the bone, dissolving the mineral content of the bone.
- Reversal phase: osteoclasts undergo apoptosis and osteoblasts are recruited to the bone surface.
- Formaton phase: osteoblasts then deposit collagen; this is mineralized to form new bone.
what is osteoclasts job
Osteoclasts dissolve old and damaged bone tssue so it can be replaced with new, healthier cells created by osteoblasts.,
Osteoclasts are the cells that degrade bone to initate normal bone remodeling and mediate bone loss in pathologic conditons by increasing their resorptve actvity
osteoblast job
Osteoblast:form new bones and add growth to existng bone tssue
what risk factors are from BMD dependent
1) Female sex/ hypogonadism Post menopausal osteoporosis: Estrogens stimulate osteoblast and inhibit osteoclast. The decreased estrogen level following menopause lead to increased bone resorpton
2) Immobilizaton
3) Chronic liver/ renal disease, COPD
4) GI disease , low dietary calcium intake, vitamin D defciency Endocrine ( cushing’s, hyperthyroidism , hyperparathyroidism )
5) Drugs ( heparin, antconvulsant, cyclosporin ) Most commonly due to systemic long term therapy with cortcosteroid
6) Others( diabetes, multple myeloma)
7) Caucasian/ Asian
risk factors that are BMD independent
1) Increasing age ( gradual loss of bone mass as patent age especially > 70 years)
2) Previous fragility fracture, family history, history of hip fracture Low BMI
3)Smoking and alcohol
4)Steroid therapy
5)Increased risk of falls
6)High bone turnover
7) Rheumatoid arthrits
Fragility fractures ( typically following minor trauma ) , which typically occur at 4 sitesin osteoporosis:
- Thoracic vertebrae (may lead to kyphosis and loss of height)
- Lumbar vertebrae
- Proximal femur
- Distal radius (Colles fracture)
diagnosis of osteoporosis
o Clinically by presence of fragility fracture
o BMD measured by DEXA (gold standard in measurement of bone density) of the lumbar spine
and proximal femur ( DEXA : dual energy X-ray absorptometry)
The WHO has established the following diagnostc guidelines for DEXA scan osteoporosis
• T-score + 2.5 to -1.0 is normal
• T score between -1.0 and -2.5 is osteopenia
• T-score -2.5 or below is osteoporosis
tx of osteo pharmacokogical
-Oral bisphosphonates (alendronate and risedronate) are frst-line therapy.
-Denosumab is human monoclonal antbody to RANKL ( osteoclast diferentaton factor) given as single injecton every 6 months. It is an ant-resorptve agent which increases BMD and reduces fractures.
-Selectve estrogen receptor modulators (SERM), such as Raloxifene, actvate estrogen receptors on
bones while having no efect on endometrium
when is estrogen therapy used for tx of osteoporosis
Estrogen therapy (HRT) is reserved for early post-menopausal women with perimenopausal
symptoms because of the risk factors on breast ca and CVS risk. ( inhibit bone remodeling)
if the patent has osteopenia + fracture risk factors, she can be started on
bisphosphonates or Raloxifene to reduce her risk. ( osteopenia: decreased bone strength but less severe than
osteoporosis)
osteomalacia
- clinical manifestatons of profound Vitamin D defciency following epiphyseal closure in adults.
- disorder of bone mineralizaton. In osteomalacia, remodeling of preexistng bone is defectve
- can afect individuals of any age, whereas rickets can only occur in children
- Caused by insufcient calcium , phosphate depleton, and/or direct inhibiton of bone mineralizaton, the most common cause is vitamin D defciency
investigations of osteomalacia
- Serum 25-hydroxyvitamin D3 is low
- Alkaline phosphatase is high
- PTH is high
pagets disease of the bone
a disorder of bone remodeling in which there is increased osteoclastc bone resorption followed by formation of weaker new bone, increasing the local bone blood flow and fibrous tissue
pagets disease main problem in what
bone remodeling
clinical features of pagets disease
o Most common sites are the pelvis, femur, lumbar spine, skull, tbia.
o Pain in the bone or nearby joint
o Deformites: enlargement of the skull, bowing of the tbia.
o Complicatons: nerve compression (deafness, paraparesis), pathological fractures, high output cardiac failure (due to increased bone blood fow), osteogenic sarcoma.
investigations of pagets
o Raised serum alkaline phosphatase concentraton (>1000 U/L) with a normal calcium & phosphate.
o Raised urinary hydroxyproline excreton (used as marker of disease actvity)
o X-rays: localized bony enlargement and distorton, sclerotc changes, and osteolytc areas.
osteomalacia present with soft bones what is the reasonn
bcz of low vit d so no calcium so high PTH will compensate and will absorb calcium from bones and release in blood stream
vasculitis
inflammation of the blood vessel walls. It can be seen
in many diseases including SLE, RA, polymyositis & some allergic drug reactions.
• They are all associated with anemia and a raised ESR, as well as fever, malaise, fatigue, weight loss, and arthralgia/myalgia
• Classification is based on the size of the vessels affected
LARGE CELL VASCULITIS(aorta & its major branches)
giant cell arterities
and takayasu arterities
giant cell arterities
-affects the carotid artery and branches of it temporal facial ophthalmic leads to vison loss hurts when eating jaw
- lab shows v high ESR
- temporal artery biopsy performed if giant cell arterities is suspected
takayasu arterities
• Epidemiology: rare except in Japan.
• Pathophysiology: Vasculitis involving the aortic arch and other major arteries
• Symptoms: Hypertension, absent peripheral pulses, strokes and cardiac failure.
• Treatment: corticosteroids.
medium cell vasculitis includes
Polyarteritis nodosa (PAN):
Kawasaki disease (affects children <5 years)
Polyarteritis nodosa (PAN):
Predominantly affects middle-aged men
• Associated with chronic hep B and C (esp. hepatitis B)
• Due to immune complex deposition & necrotizing arteritis associated with
microaneurysms, thrombosis, and infarction.
• Spares the lungs
PAN present with what symptoms in what arteries if affected
1- Renal arteries -htn
2- mesentric arteries - GI pain and bleed
3- coronary arteries - brain symptoms
4- skin arteries- skin lesions
what does angiograohy show in PAN
beading appearance
what is kawasaki disease
middle vasculitis affects coronary arteries in children
small cell vasculitis include +ve and -ve anca
+ve ANCA :
1) microscopic polyangitis -P anca
2) wegner granulomatosis - C anca
3) churg strauss syndrome -p anca
wegner granulomatosis
affects middle aged male
1. Upper respiratory tract involvement (90%) → Sinusitis, nasal crusting, saddle-nose deformity
2. Lower respiratory tract involvement (80%) → Pulmonary nodules, hemoptysis
3. Renal involvement (75%) → Rapidly progressive glomerulonephritis (RPGN)
Leads to granuloma formation in affected organs (lungs, kidneys, sinuses)
churg strauss syndrome
affects small vessels
P-ANCA
1. Eosinophilia (>10%)
2. Asthma & allergic rhinitis (hallmark feature)
3. Necrotizing granulomas
4. Multisystem involvement (lungs, skin, nerves, heart, kidneys, GI)
microscopic polyangitis
same as wegner granulamatosis but the main diff is
1) does not affect nasopharynx ( only kidney and lungs)
2)no granulomas
3) p-ANCA
ANCA -ve
Henoch–Schoenlein purpura
Cryoglobulinemia %
Henoch–Schoenlein purpura
IgA-mediated small-vessel vasculitis, usually post-infectious
• Classic tetrad: Palpable purpura + Arthritis + GI symptoms + Renal involvement
• Diagnosis is clinical but can be confirmed by IgA deposition on biopsy
• Self-limiting in most cases, but severe renal or GI involvement may require steroids
what is cryoglobulins
is a disorder caused by abnormal immunoglobulins (cryoglobulins) that precipitate in cold temperatures and deposit in small- to medium-sized blood vessels, leading to vasculitis and end-organ damage.
there are 3 types of cryoglobukins
Type I= Monoclonal IgM or IgG, Hematologic malignancies (Waldenström’s, multiple myeloma)
Type II & III (Mixed Cryoglobulinemia) → Most common (90%) and strongly associated with chronic Hepatitis C virus (HCV) infection.
Classic Triad of Cryoglobulinemic Vasculitis (Especially in Type II & III)
- Palpable purpura (leukocytoclastic vasculitis)
- Arthralgia/arthritis (non-deforming, migratory)
- Weakness (fatigue, myalgia)
bechets disease
a rare disease that causes chronic infammaton, or swelling, in the body’s blood vessels. Behcet’s disease can afect many parts of the body, including the brain and spinal cord. Neurological complicatons may include: Stroke.
common triad of symotoms in bechets
- Recurrent oral ulcers (aphthous stomatitis)
• Painful, shallow ulcers with erythematous halos, commonly on the buccal mucosa or tongue.
• Seen in almost all cases and often the first sign. - Genital ulcers
• Painful, recurrent ulcers in the genital region (penis, vulva, scrotum). They are usually larger and deeper than oral ulcers and leave scars upon healing.
• Common in both men and women. - Uveitis
• Inflammation of the uveal tract (iris, ciliary body, choroid) leading to iritis or retinal vasculitis.
• Can cause pain, photophobia, blurred vision, and potential blindness if untreated.
cause of bechets
Immune-mediated: Behçet’s disease is thought to involve a combination of genetic predisposition (particularly HLA-B51) and environmental triggers, such as infections, which lead to immune dysregulation.
Diagnosis is clinical and requires the presence of oral ulceraton and any two of the following:
o Genital ulcers
o Eye lesions (uveits, retnal vascular lesions)
o Skin lesions (erythema nodosum, papulopustular lesions) o Or a positve skin pathergy test (skin injury, e.g. Needle prick, leads to pustule formaton within 48 hours).
