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Mechanisms of Disease - - Rheumatology


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This disease is the most common form of arthritis. It occurs more frequently with aging but is not considered "normal"
What is the pathology of osteoarthritis?
Irregularity of cartilidge, ulceration and loss of cart., bone-on-bone contact
What is the pathology of OA?
fibrillation of cartilidge,
Not inflammatory!!
What is the pathology of OA?
decreased glycosaminoglycan, including less chondroitin sulfate, keratin sulfate, and hyaluronic acid.
increased MMP activity
OA is a disease of the _______ of the joints
hyaline cartilidge
What is the initiating event in OA?
mechanical stress
As OA progresses, crystals of ____________ are shed into the joint fluid.
calcium phosphate
What are the clinical features of OA?
-pain and stiffness of joint
-morning stiffness, gelling
-radicular symptoms in limbs due to impinging osteophytes
What is noted on Physical Exam with OA?
Tenderness and bony enlargement of joints, especially at DIP and PIP joints.
-Crepitus, locking, varus deformity in knees
What are the Radiologic Features of OA?
Assymetric joint space narrowing, subchondral bone sclerosis, s.c. bone cysts, osteophytes
What are the Labs you would order when suspecting OA?
WBC of synovial fluid (<200)
RF and esr to rule out other, more serious arthritides, however take results with caution
What is the treatment for OA?
exercise, weight loss, heat, massage, OT, PT
Drugs: APAP, NSAIDS, capsaicin cream, chond. sulf./glucosamine, steroid inj, hyaluronic acid inj.
A metabolic disease characterized by hyperuricemia and has musculoskelatal consequences
What are risks for hyperuricemia?
usually men over 40
alcohol, obesity, renal dysfunction
What are the causes of and what is the most common cause of hyperuricemia
Overproduction of u.a. and underexcretion of u.a., or a combination. Underexcretion is the cause in 90% of pts.
What happens when there is a high plasma concentration of urate?
monosodium urate crystals tend to precipitate out of solution, especially in cooler, peripheral joints
What joints are most affected by gout?
ankles, toes, hands, soft tissue of ear.
What is the clinical presentation of Acute Gout?
Very abrupt, affects only one joint, usually overnight, extremely painful, resolves in days to weeks despite presence of crystals.
What factors precipitate an acute gout attack?
start of u.a. lowering tx.
start of diuretic
surgury/trauma, illness, stroke, MI, alcohol binges
How do you diagnose gout?
abrupt onset of mono or oligoarthitis of L.E.
aspiration of joint fluid shows needle shaped negatively birefringement crystals
What are the treatments for Acute Gout?
NSAIDS: Indocin, Advil, naproxen (high doses) NO ASA
Colchicine:0.5mg/hr until relief or GI sx.
Steroids if can't use either of above
What does colchicine do for gout?
1. decreases neutrophil emigration into synovial space
2. blocks release of chemicals that are chemotactic for neutros and monocytes
What is the treatment for recurrent gout attacks? (and prophylaxis)
lose weight, stop alcohol, avoid dehydration, avoid diuretics, keep serum u.a. below 5 mg/dl using probenicid or allopurinol
What happens in pseudogout?
similar to regular gout, however, instead of monosodium urate crystals, calcium pyrophosphate crystals are formed.
What causes pseudogout?
trauma, surgery, illness, aging
What are the most common joints affected by pseudogout?
knee and wrist joints are most affected.
How to diagnose pseudogout?
abrupt mono or oligoarthritis, but serum u.a. is not elavated, and c.p. crystals are found in joint fluid.(positively birefringent)
How to treat pseudogout?
NSAIDS, colchicine, intra-articular steroids
What is the most typical skin lesion of psoriatic arthritis
well demarcated pink to salmon plaques with loose silver/white scales, usually on scalp or extensor surfaces of elbows and knees
What is the pathophys. of psoriasis?
inc'd epidermal cell turnover --> acanthosis
What else do you see in psoriasis besides lesions?
nail changes (discoloration, pitting)
Auspitz sign
Koebner phenomenon
Multiple small bleeding points when scrape gently or lift scales
Auspitz sign
Psoriatic lesion at the sight of minor skin trauma
Koebner phenomenon
A seronegative spondyloarthropathy, may even be reactive arthritis
Psoriatic Arthritis
What are the clinical features of P.A.
Oligoarthritis, arthritis mutilans (causes resorption and telescoping of distal phalanx.
What is the extra-articular involvement of P.A.?
psoriatic skin lesions, nail changes, dactylitis, enthesopathy
What are the radiologic features of P.A.?
marginal erosions of phalanges plus bone proliferation, "pencil in cup deformity", acroosteolysis, joint space loss, esp. interphalangeal
What is the treatment for psoriasis and P.A.?
Skin: topical steroids, coal tar preps, Vit. A&D derivatives, PUVA, Rheumatrex
Arthritis: NSAIDS, steroid inj., DMARDS
Both: Enbrel (etanercept)
What is the arthritis that occurs after the triad of Gastroenteritis, Urethritis, and Conjunctivitis?
Reiter's syndrome
What are the sero-negative spondyloarthropathies?
OA, Septic Arthritis, Lyme disease, Reactive Arthritis, Psoriatic Arthritis, Gout
What is the time line for Reiter's syndrome?
1)Gastroenteritis or V.D.
2)Nongonococcal urethritis w/ C. Trachomatis
4)Articular manifestation (after others have subsided, 1-3 weeks after g.e. resolved.
What are the Articular Manifestations of Reiter's Syndrome?
"sausage digits"
asymmetric oligoarthritis, Enthesopathy (heel most freq)
Circinate balanitis
kertodermal blennorrhagica
What lab studies/results can be done to Dx. Reiter's?
increased esr and CRP
Synovial Fluid: turbid, high WBC, low viscosity, normal glucose
When to consider reactive arthritis?
asym oligoarthritis in young person, extra-articular manifestations, h/o prior infection
What is the treatment for Reiter's syndrome?
NSAIDs, exercise, rarely steroids, DMARDs
Inflammatory arthritis linked to bites by ixodes.
Lyme disease
Whate is the pathogen for Lyme disease?
the spirochete Borrelia burgdorferi (and other Borrelia)
What are the clinical features of Lyme disease?
Occurs most often in summer and fall, Rash: erythema migrans, within 1 month of bite, anular, red, Fatigue, fever, h/a, arthralgias
What are some complications of untreated lyme disease?
Arthritis, headaches, nuchal rigidity, bilateral bell's palsy, cardiac symptoms
What are the lab studies done for Lyme disease?
Serum IgM response 3-4 weeks after bite, gradually replaced by IgG, both detected by ELISA
increase in WBC, esr, neutros in joint fluid, increased CSF protein
What is the treatment for Lyme disease?
prevent with Tick repellants
-Abx: p.o. doxycycline, or amox, or iv Rocephin if cardiac/meningitis symptoms
What is the most feared possibility when someone presents with a red, hot, swollen, painful joint
Septic Arthritis
What occurs with a Bacterial Joint Infection (SA)?
Hydrolytic enzymes irreversibly destroy cartilidge and may result in sepsis and death.
How does bacteria gain access to the joint?
Through the bloodstream, prosthetic joint, joint injection, joint penetrating injury, contiguous osteomyelitis.
What is the most common bacteria to cause SA in teens and adults?
Neisseria gonorrhea
What Lab studies confirm SA?
Blood culture + in 50%
Synovial Fluid dec. glucose, inc. protein and lactate, wbc > 10,000, with 90% neutros
What does normal synovial fluid look like?
Clear and straw colored, very viscous due to H.A.
prot 2g/dl, gluc 10mg/dl less than serum value, wbc <200
What is the Treatment for S.A.?
Treat Early w/ abx. Therefore you may have to treat before confirmatory labs. most common is rocephin, or nafcillin + gentamicin, IV
What is Paget's Disease?
episode of intense osteoclastic activity and hypervascularity, followed by intense abnormal osteoblastic activity
Repeated cycles results in excessive, abnormal, unstable bone.
Monostotic Paget's
only one bone is involved in this Paget's disease
polystotic Paget's
more than one bone is affected in this Paget's. (most common)
What is a pathognomic sign of Paget's disease?
woven bone, in a mosaic pattern. It lacks the normal lamellar structure.
What are the laboratory findings in Paget's disease?
normal serum Ca and Ph, serum alk phos elavated during osteoblastic phase, urine Ca elevated during osteolytic, urine hydroxyproline elevated in active disease
What are complications from Paget's disease? (hypervascularity)
Inc'd Cardiac output
Possible CHF
ischemic neuro events due to "steal phenomena"
What are complications from Paget's disease?
(Vertebral Crush fractures)
back pain and radiculopathy
What are complications from Paget's disease?
(Skull growth)
narrowed cranial nerve foramina --> cranial nerve entrapment --> headache, visual disturbances, deafness
What is the treatment for Paget's disease?
Bisphosphonates, started when alk phos is high
eg: Aredia, actonel, Didronel, Fosamax
What is Polymyalgia Rheumatica?
It is NOT autoimmune . . .
It IS dominated by myalgia of proximal muscle groups, but there is no permanent weakness or degeneration
Who is most commonly affected by polymyalgia rheumatica?
white women over 50
What are the most common clinical features of P.R.?
slow onset, systemic fever, wt. loss, malaise
proximal muscle weakness: stairs, chairs, and pillows
morning symptoms and gelling
What other, dangerous condition can develop with P.R.?
Temporal Arteritis, which can lead to blindness
What labs may indicate P.R.?
increased esr (50-100 mm/hr)
What is the treatment for P.R.?
Without temporal arteritis, use low dose steroids, monitor esr every few weeks.
With Temporal arteritis, High dose steroids immediately
What characterizes scleroderma?
fibrotic and degenerative skin changes
What does CREST syndrome stand for and what disease is seen with it?
R-aynaud's phenomenon
E-sophogeal dysmotility
What is the ab seen in limited scleroderma?
Anti-centromere ab
(also sometimes ANA and RF)
What is diffuse scleroderma?
Fibrotic and vascular changes affect not only hands, esophogus and face, but now intensify and cause problems in other systems.
AKA systemic sclerosis
What ab is seen in diffuse scleroderma?
SCL-70 Ab
What is treatment for scleroderma?
No cure, steroids do not help, treat symptoms as they come.
What is Sjogren's Syndrome?
autoimmune inflammatory disorder characterized by salivary and lacrimal gland dysfunction
Xerophthamia or keratoconjunctivitis sicca
dry eyes
What ab's are seen in Sjogren's syndrome?
anti-SS-A (anti-Ro)
anti-SS-B (anti-La)
What tests are done to diagnose Sjogren's?
Schirmer's Test, Rose Bengal, Whole Saliva Sialometry
definitive: Salivary Gland biopsy
What is the treatment for Sjogren's?
avoid anticholinergics
use eye drops, saliva stimulants, lubricants, steroids, DMARDs
This is the prototype of autoimmune diseases and is characterized by productions of ab's to components of cell nucleus
Systemic Lupus Erythematosus
What signs/symptoms dominate SLE?
Severe Fatigue, Arthralgias, some permutation of its many systemic effects, many of which are vasculitic
What is the immunopathology of SLE?
rampant production of auto-ab's to a variety of self ag's
Hyperglobulinemia, heightened immune responses
What ab tests can be done for lupus?
Generic ANA, anti-dsDNA,
What are general clinical features of SLE?
fever, weight loss, overwhelming fatigue
What are the skin features of SLE?
malar rash, erythema, photosensitivity, discoid lesions, alopecia, mucous membrane lesions, raynaud's phenomenon
What are the musculoskelatal features of SLE?
arthralgias, arthritis, myalgias, fibromyalgia
What are the renal features of SLE?
glomerulonephritis, nephrotic syndrome, renal failure
proteinuria, hematuria, pyuria, urinary casts, azotemia
What are the neuropsychiatric features of SLE?
CNS problems, cranial and peripheral neuropathies, headaches, seizures, chorea, cva's, organic brain syndrome
What are the serous membrane features of SLE?
pleurisy, pericarditis
What are the GI features of SLE?
abd. pain, nausea, vomitting, anorexia, peritonitis, pancreatitis, IBD, mesenteric vasculitis
What are the Cardiac features of SLE?
pericarditis, myocarditis, endocarditis, coronary vasculitis, atherosclerosis
What are the Vascular features of SLE?
acute necrotizing vasculitis
What are the reticuloendothelial features of SLE?
splenomegaly, lymphadenopathy
What are the hematologic features of SLE?
increased esr, cytopenia
What is the clinical course for SLE?
usually relapsing/remitting, some can go down hill to death within months, 70% survival rate after 10 years.
What is the treatment for SLE?
avoid sun, NSAID's and steriods, DMARDS
What is the Systemic Inflammatory disease that is dominated by joint destruction?
Rheumatoid Arthritis (RA)
What is it that develops in joints in RA?
progressive synovitis
What are the commonly affected joints in RA?
MCP, PIP, carpal bones and wrist, knees and MTP joints
What is the pathology in RA?
Early: injury to the synovial microvasculature, accompanied by hyperplasia of Type A and B synoviocytes, synovial congestion and edema, fibrin leakage, early T cell emigration into synovial joints, hypertrophic synovium, which grows over joints and develops a pannus, which destroys cartilage.
What is a pannus?
The hypertrophic synovium which grows medially and progressively covers one or both articular cartilage surfarces. As it grows, it invades and destroys the cartilage and subchondral bone.
What are Rheumatoid Factors?
They are antibodies to the Fc portion of the IgG in the serum and synovial fluid.
Is RF specific to RA?
No, it is also seen in some normal people, and it is not seen in all people with RA. However, it is associated with severe RA and extra-articular manifestations are usually only seen in RF positive patients.
What is essential for the Dx of RA?
doc. of inflammatory synovitis (synovial fluid leukocytes) and typical erosions on X-Ray
What are the laboratory features of RA?
-RF in 80%
-increased esr and CRP
-anemia of chronic disease
What are the clinical manifestions of RA?
synovial hypertrophy and pannus may cause peripheral nerve entrapment in selected joints.
Is morning stiffness seen in RA?
Morning stiffness is generally greater than 2 hours
What are the cervical features of RA?
neck stiffness throughout ROM
What are the upper extremity manifestations of RA?
loss of ROM in shoulder, ulnar nerve entrapment, MCP and PIP joint involvement, nodules on finger tendons, "swan neck", boutonniere, opera glass hands, carpal tunnel syndrome, Guyons canal syndrome
What are the lower extremity manifestations of RA?
Hip pain, Baker's cyst at knee, tarsal tunnel syndrome, MTP subluxations.
What are the skin manifestations of RA?
Rheumatoid nodules in skin, bursae, tendons, and pressure points
What is the ocular manifestation of RA?
Keratoconjunctivitis sicca (dry eyes)
What are the respiratory manifestations of RA?
Interstitial fibrosis, pleurisy/pleural effusion
What are the cardiac manifestions of RA?
pericardial effusion, restrictive pericarditis, with signs of R heart failure
What is the Treatment of RA?
NSAID's, corticosteroids (both injected into joints and short-term p.o.),
and DMARD's.
What is the difference between polymyositis and dermatomyositis?
PM is an inflammatory disease of muscle, and DM is PM with dermatologic manifestations as well.
What are the four main clinical features of PM and DM? (and one more for DM alone)
1. proximal muscle weakness
2. inc'd muscle enzymes
3. electromyographic evidence
4. Biopsy evidence of muscle inflammation
5. (DM only) skin rash
What is the onset of PM and DM?
slow onset over 3-6 months without a precipitating event
What is the proximal muscle weakness seen in PM and DM?
-also see tenderness, myalgia, arthralgia
-large muscles of neck limb and trunk (stairs, chairs, pillows), dysphonia
What are the serum muscle enzymes seen in PM and DM?
increased CPK-MM, aldolase, ALT, AST, LDH
also inc'd esr, positive hemoglobinuria, though really myoglobinuria (rhabdomyolysis)
What electrical evidence is seen in PM and DM?
the electromyogram will show abn. which indicate muscle disease.
What will the muscle biopsy show in PM and DM?
muscle fibers in various stages of vacuolization and necrosis, destroyed fibers replaced by fibrous connective tissue and fat.
What is the immunopathology of PM and DM?
cytotoxic T cells and macros surround non-necrotic muscle fibers
What ANA is specific for PM and DM?
anti-JO-1 abs
In Dermatomyositis, what may precede the muscle weakness by up to a year?
skin rash
What is Gottron's sign?
erythematous or violaceous atropohic macules and plaques overlying the dorsal IP joints and sparing IP spaces.
-may also occur on elbows, patellae, or medial malleoli
(pathognomic for DM)
What is a heliotrope rash?
-seen in DM
-violaceous eruption of both eyelids and periorbital skin, with periorbital edema
What is a Shawl Sign?
-seen in DM
-poikilodermatous macules in a shawl distribution, over shoulders, arms, and upper back. (pigmented and atrophic changes in skin)
What is a V Sign
-seen in DM
-same as shawl sign, but over forehead, face, anterior neck and upper chest.
What is Mechanics Hands?
-seen in DM
-darkened lines on the lateral and palmar aspects of fingers, hands appear fissured, scaly, and hyperpigmented
What are periungual telanectasias?
dilated vessels of skin surrounding fingernails.
What are the treatments for PM and DM?
steroids like predinisone or methylprednisone, dc'd when cpk is nl
DMARD's methotrexate or azathioprine if no improvement on steroids.
Fibromyalgia Syndrome
-soft tissue rheumatism
-no organic pathology
-real pain at muscle and tendon insertions
-disordered, non-refreshing sleep
What are the clinical features of Fibromyalgia?
widespread pain, concentrated on muscles and tendons of axial area, also arms and legs
-extreme fatigue
-morning stiffness
What are associated sx. with Fibromyalgia?
tension headaches, IBS, sicca syndrome, urinary frequency and urgency, sensation of swollen hands without objective swelling
What is the epidemiology of Fibromyalgia?
typical middle age onset, mostly women.
What is the pathophys. of Fibromyalgia?
-unknown, but maybe CNS related
-inc'd substance P, decreased blood flow to thalamus and caudate nucleus, nonrestorative sleep
-may be precipitated by illness or trauma
How to Diagnose Fibromyalgia?
No diagnostic labs, test 18 trigger points
-a diagnosis of exclusion
What is the treatment for fibromyalgia?
-steroids do not work,NSAID's not much help
-exercise, muscle relaxants, tricyclic antidepressants(elavil), SSRI's (prozac)
What is Osteoporosis?
Most common metabolic bone disease, causes pathalogic fractures due to dec'd bone mass.
What bones are usually affected with Osteoporosis?
Vertebrae, pelvis, femur, distal radius
What are the signs and symptoms of Osteoporosis?
osteopenia on x-ray, pathologic fractures, back pain due to crush fractures, bone fragments impinging on spinal cord or dorsal root (radiculopathy)
What is localized Osteoporosis?
only affects one bone, typically due to disuse
What is Primary Osteoporosis?
Postmenopausal OP, senile OP
-most frequently affects white women
What is Secondary Osteoporosis?
OP due to various causes:
-eg: hyperparathyroidism, cushing's syndrome, multiple myeloma, malnutrition, malabsorption, Vit. C or D def., alcohol, long term steroids, immobilation long term
Where is bone loss most dramatic?
The parts of the skeleton containing abundant trabiculae
When does bone mass peak?
It increases steadily throughout childhood and peaks in young adulthood. Bone mass in later life depends on childhood factors such as nutrition and exercise.
Is bone loss age-related?
Yes, osteoblastic activity begins to decrease around age 20.
What are complications of osteoporosis?
vertebral fx -- radiculopathy
other fx -- immobilization --more bone loss, pneumonia, DVT, PE
What are the Lab findings in Osteoporosis?
in primary OP, serum tests are all normal
-DEXA scan shows decreased bone density, osteopenia seen on XRAYs
How can one try to prevent osteoporosis?
Stay active, weight-bearing exercise, drink milk, eat yogurt (at least 2 gms of Ca/day)
What are the treatments for Osteoporosis?
HRT-has risks, but works well for post/peri-menopause
EVISTA-hormone, but has less risks, not as much help
Bisphosphonates - very popular, inhibits osteoclasts
Miacalcin-Nasal spray, also has analgesic effect
A chronic granulomatous disease
a distinct type of localized, nodular chronic inflammation
What is the first thing that happens at a site of chronic inflammation on its way to becoming a granuloma?
-macros arrive and become "angry"
-they morph into squamous cells that form a tightly stacked and packed center of the granuloma
What is the second thing that happens during granuloma formation?
Lymphos arrive and squirt cytokines on the macros, keeping them angry.
-Some macros fuse will 20 other ones and form a mulitnucleated Giant cell, which compose part of the center of the granuloma
What is the third thing that happens during granuloma formation?
the lymphos form the collar of the granuloma, attracting monocytes, more macros, and fibroblasts, all forming the collar. The fibroblasts wall off the center with an organized scar layer.
Non-caseating granuloma
The type of granuloma formed in sarcoidosis
--does not have the white, cheesy consistency of caseating granuloma (Tb)
Where are the granuloma's in sarcoidosis widely distributed?
lungs, lymph nodes, and liver
Who is generally affected with Sarcoidosis?
20-40 y/o, african americans and northern european whites
In sarcoidosis, there is generally depressed ________ immunity and hightened _______ immunity.
Cellular -lymphopenia

Humoral - autoantibody production (25% RF or ANA +)
What are the constitutional clinial features of Sarcoidosis?
fever, weight loss, malaise
What are the skin clinical features of Sarcoidosis?
Erythema nodosum - acute, good prognosis
Lupus pernio - chronic, poor prognosis
What are the lymph clinical features of Sarcoidosis?
peripheral lymphadenopathy, nontender,
cervical, and often axillary, epitrochlear and inguinal nodes
What are the pulmonary clinical features of Sarcoidosis?
interstitial disease, hemoptysis, bilateral hilar and mediastinal lymphadenopathy
What are the musculoskeletal clinical features of Sarcoidosis?
myalgia, arthritis
What are the hepatic clinical features of Sarcoidosis?
mild increase in ALT and AST associated with hepatic granulomas.
What tests help to diagnose Sarcoidosis?
transbronchial lung biopsy
ACE levels (double NL)
hypercalcemia, hypercalciuria, Kveim-Siltzbach test
Kveim-Siltzbach test
heat treated suspension of sarcoidosis is injected intradermally. Biopsy 4-6 weeks later shows granulomatous reaction in 75% of those with Sarcoid
What is the treatment for Sarcoidosis?
No tx for asx. hilar adenopathy, colchicine for arthritis, steroids p.o. for hypercalcemia or severe sarcoid of other organs. (Risk of osteoporosis)
DMARD's can be used in chronic disease
What is the prognosis of sarcoidosis?
most remit and do well, some develop pulmonary disability, even less progress to death.
The antibodies tested for in SLE
generic ANA's
The antibodies tested for in Systemic Sclerosis (diffuse scleroderma)
generic ANA's
-SCL-70 ab
The antibodies tested for in limited scleroderma
generic ANA's
Anticentromere ab
(limited, only got to centromere)
The antibodies tested for in Sjogren's syndrome
SS-A (anti-Ro)
SS-B (anti-La)
The antibodies tested for in polymyositis
Jo-1 ab
(po - - > jo)

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