Chap 44 Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
Rheumatic arthritis manifestations (articular and extra-articular)
Articular: symmetric & polyarticular joint involvement Early: joint pain & stiffness causing limitation of movement; wrists, MCP joints, PIP joints of fingers, interphalangeal joints of thumb and MTP joints most commonly affected; pain in ball of foot upon arising & widening of forefoot; pain turning door knobs, opening jars, buttoning clothes d/t swelling of wrists & hand joints Disease progression: involvement of ankles, knees, elbows shoulders, cervical spine; joint deformities d/t mechanical forces ulnar deviation of fingers; PIP & DIP swan-neck deformity; knee swelling with joint contractures, instability & genu valgus; Baker cyst; ankle involvement, MTP with subluxation, hallux valgus, hammertoe difficulty in ambulation Extra-articular: fatigue, weakness, anorexia, weight loss d/t systemic inflammation; rheumatic nodules over pressure points; vasculitis of small & medium-sized arteries with ischemia of nail folds & digital pulp, ulceration in lower extremities (malleolus), neuropathy; dryness of eyes, mouth, other mucous membranes, ocular manifestations; pulmonary fibrosis & pericarditis
Gout manifestations, diag, treatment
Clinical Manifestations: acute attack is monoarticular affecting the first metatarsophalangeal joint; other joints include tarsal joints, insteps, ankles, heels, knees, wrists, fingers elbows; begins at night precipitated by excessive exercise, certain medications or foods, alcohol or dieting; abrupt onset of pain with redness & swelling lasting for days/weeks; first attack called intercritical gout; deformities occur with recurrent attacks Diagnosis: monosodium urate crystals present in synovial fluid or in tissue sections of tophaceous deposits Treatment: termination & prevention of acute attacks, correction of hyperuricemia, inhibition of further precipitation of sodium rate, absorption of urate crystal deposits in tissues; initial treatment directed at acute inflammatory process with NSAIDs (indomethacin & ibuprofen); colchicine & intra-articular injection of corticosteroids; nonpharmacologic: between acute attacks—normalize uric acid levels with weight management, moderation in alcohol consumption & avoidance of purine-rich food; pharmacologic—allopurinol & uricosuric agents
Systemic sclerosis / Scleroderma def, cause, clinical manifestations, treatment
Definition: autoimmune disease of connective tissues that causes extensive fibrosis throughout the body; women between ages 35-50 yrs Cause: humoral & cellular immune system abnormalities; presence of microvascular disease with repeated cycles of endothelial damage followed by platelet activation and release of platelet factors causing fibrosis & ischemia; hallmark—fibroblast activation with excessive fibrosis; skin & organ involvement (lungs, GI, heart, kidneys) Clinical manifestations: limited cutaneous scleroderma with changes in skin of fingers, forearms, face; CREST syndrome; diffuse scleroderma severe, widespread, progressive skin involvement ---> stone facies, hair loss, teleangiectasis on face, buccal mucosa, chest, hands; Raynaud phenomenon; early system sclerosis with arthralgia and myalgia; dysphagia; malabsorption; dyspnea & respiratory failure; malignant hypertension & progressive renal insufficiency; pericarditis, heart block, myocardial fibrosis Treatment: symptomatic & supportive
Systemic lupus Erythematosus def, pathogenesis, genetic, hormonal, and environmental factors
Definition: chronic inflammatory disease that can affect any organ system, including the musculoskeletal system; disease of young women with peak between ages of 15-40 yrs Pathogenesis: formation of autoantibodies & immune complexes (type III hypersensitivity); defective elimination of self-reactive B cells with increase in production of antibodies that damage tissues or combine with corresponding antigens to form tissue-damaging immune complexes; autoantibodies include ANA that binds DNA; RNA, nuclear proteins & protein nuclear complexes (Sm); additional autoantibodies form against red cells, platelets, lymphocytes & plasma proteins Genetic factors: HLA-DQ loci in MHC class II molecules Hormonal factors: more prevalent in women Environmental triggers: UV light, chemicals (drugs—hydralazine & procainamide; hair dyes), some foods & infectious agents
Ankylosing spondylitis def, pathogenesis, clinical manifestations
Definition: chronic, systemic inflammatory disease of axial skeleton joints; progressing to stiffening of spine beginning in late adolescence or early adulthood; greater incidence in men Pathogenesis: HLA-B27 antigen suggesst hereditary link & increased susceptibility to infections or environmental triggers Clinical manifestations: enthesitis where tendons & ligaments attach to bones; begins with bilateral involvement of sacroiliac joints moving to smaller joints of posterior elements of spine with destruction of joints & posterior fusion of spine (anklyosis); persistent or intermittent back pain becoming worse with rest; LS pain with discomfort in buttocks & hips at times radiating to thigh; prolonged stiffness in AM relieved with hot shower & mild physical activity; loss of motion in spinal column, lumbar lordosis & kyphosis; other s/s include uveitis, weight loss, fever & fatigue; osteoporosis
Osteoporosis def and pathogenesis, clinical manifestations, prevention, diagnosis, treatment
Definition: decrease in bone density and strength in which both bone matrix and mineralization are decreased; most often associated with aging BMD >2.5 SD below mean for normal young white women (WHO) Pathogenesis: imbalance between bone resorption and formation so that bone resorption exceeds bone formation; peak bone mass—maximal amount of bone in a given person Clinical manifestations: vertebral compression fracture with dowager hump; fracture of hip (mainly >65 yrs), pelvis, humerus sudden in onset caused by fall, sudden movement, lifting, jumping, coughing Prevention and early detection: adequate calcium and vitamin D intake, weight-bearing exercises and weight lifting; screening per USPSTF guidelines Diagnosis: DEXA of spine and hip Treatment: Types of drugs—bisphosphonates, selective estrogen receptor modulators, calcitonin, recombinant parathyroid hormone Surgery—vertebroplasty and kyphoplasty
rickets def, manifestations, pathogenesis, treatment
Definition: failure or delay in calcification of cartilaginous growth plate in children whose epiphyses have not yet fused; widening & deformation of metaphyseal regions of long bones and delay in mineralization of trabecular, endosteal and periosteal bone surfaces Pathogenesis: changes in growing bones of children with overgrowth of epiphyseal cartilage due to inadequate provisional calcification and failure of cartilage cells to disintegrate Clinical manifestations: dependent on severity and duration of rachitis process and bone stresses Infancy nonmobile stages—skull enlarged, soft with delayed closure of fontanels; difficulty standing Ambulating child—deformities of spine, pelvis long bones; lumbar lordosis, bowing of legs, ends of long bones enlarged, stunted growth, protruding abdomen (rachitic pot belly) Treatment: Nutritional—balanced diet with sufficient calcium, phosphorus, vit D; sunlight exposure; premature infants—large amts supplemental vit D Vitamin D-dependent rickets—calcitriol (active form of vit D) Vitamin D-resistant rickets—oral phosphorus & calcitriol Prevent deformities, posture, positioning, bracing; surgical correction
osteomalacia def, causes, clinical manifestations, diagnosis, treatment
Definition: generalized bone condition of inadequate mineralization of bone related to vitamin D deficiency Causes: 1) insufficient calcium absorption from intestine either due to deficiency or resistance of action of vit D 2) phosphate deficiency caused by increased renal losses or decreased intestinal absorption Reduced skin synthesis, inadequate dietary intake, diminished intestinal absorption, inherited and acquired disorders of vit D metabolism and responsiveness (e.g., long-term use of anticonvulsant drugs) Renal rickets—chronic renal failure d/t inability of kidney to activate vit D and excrete phosphate accompanied by hyperparathyroidism Vit D-resistant rickets—inherited X-linked dominant gene causing primary hyperparathyroidism with increased calcium resorption from bone and hypophosphatemia affecting both children (rickets) and adults Clinical manifestations: bone pain, tenderness, fractures; severe cases present with muscle weakness; predisposes to pathological fractures in distal radius & proximal femur (delayed healing & poor retention of internal fixation devices) Diagnosis: identify osteomalacia and determine cause; x-ray studies (Looser zones), lab tests, bone scan, bone biopsy (nonspecific osteopenia with no improvement after treatment with exercise, vit D and calcium) Treatment: based on cause Nutritional—restore adequate amounts of calcium and vit D to diet; supplemental vit D (resistant rickets) Pancreatic insufficiency--replacement of pancreatic enzymes Renal tubular disorders—correct altered renal physiology Chronic liver disease and kidney failure—large doses of biologically active forms of vit D
Gout def, pathogenesis
Definition: group of diseases known as gout syndrome including gouty arthritis with recurrent attacks of severe articular & periarticular inflammation, tophi, & gouty nephropathy or renal impairment & uric acid kidney stones; primary gout—cause is unknown characterized by hyperuricemia & gout; secondary gout—due to rapid tumor cell lysis during treatment for lymphoma or leukemia or from chronic kidney disease Pathogenesis: elevated serum uric acid levels; primary gout—enzyme defect resulting in overproduction of uric acid, inadequate elimination of uric acid by kidney or combination of both; attack occurs when monosodium urate crystals precipitate into the joint & initiate an inflammatory response; crystals are chemotactic to leukocytes & activate complement; inflammation causes destruction of cartilage & subchondral bone; repeated attacks of acute arthritis lead to chronic arthritis & formation of large, hard nodules (tophi)
Rheumatoid arthritis def, cause, pathogenesis
Definition: irreversible, chronic autoimmune systemic disease with peak incidence between 40-50 yrs Cause: genetic predisposition with joint inflammation immunologically mediated; MHC alleles of HLA types, specifically HLA DR alleles sharing sequence of amino acids in antigen-binding site of DR molecule Pathogenesis: aberrant immune response leading to synovial inflammation & destruction of joint architecture d/t activation of CD4+ helper T cells, local release of inflammatory mediators and cytokines that destroy joint and form antibodies directed against joint-specific and systemic autoantigens (RF that reacts with fragment of IgG forming immune complexes; anti-CCP antibodies); inflammatory process with destructive vascular granulation tissue called pannus extend from synovium to involve a region of unprotected bone at junction between cartilage and subchondral bone; pannus inflammatory cells destroy joint cartilage and bone with reduced joint motion and ankylosis; joint instability, muscle atrophy, stretching of ligaments & involvement of tendons & muscles
Juvenile idiopathic arthritis (JIA) def, clinical manifestations, types, treatment
Definition: most common form of childhood arthritis; characterized by synovitis and can influence epiphyseal growth by stimulating growth of affected side Clinical manifestations: morning stiffness & gelling; easy fatigability; joint swelling; joints warm, resist full ROM, pain with motion Types: 1) oligoarticular or pauciarticular arthritis (affects 4 or fewer joints of lower extremities)—mild joint symptoms; chronic eye inflammation; 2) polyarthritis (affects 5 or more both large & small joints)—similar to adult form; fatigue, low grade fever, weight loss, malaise, anemia, stunted growth, slight organomegaly & lymphadenopathy; 3) systemic-onset disease—arthritis & hepatosplenomegaly, lymphadenopathy, serositis (e.g., pericardial effusion) with daily intermittent high fever; transient, salmon-colored macular rash; systemic symptoms subside in 6-12 mos Treatment: NSAIDs, polyarticular or systemic requires glucocorticoids for overwhelming inflammation; nutrition & monitoring growth & development
Psoriatic arthritis def, pathogenesis, types, clinical manifestations, treatment
Definition: seronegative inflammatory arthropathy that may accompany psoriasis Pathogenesis: unknown; environmental factors include infectious agents & physical trauma; T-cell-mediated immune response in skin & joints Types: 1) oligoarticular form affecting 4 or less joints 2) spondylitis with scaroiliitis & spinal involvement 3) polyarticular or symmetric (resembling RA) 4) distal interphalangeal joint involvement 5) arthritis mutilans Clinical manifestations: dependent on type: inflammatory joint involvement with swelling & stiffness; may present with deformity & joint damage; asymmetric sacroiliac involvement; dactylitis DIP joint disease Treatment: similar to treatment of RA; suppression of psoriasis to control arthritis; biologic response modifiers
Osteoarthritis def, pathogenesis, manifestations
Definition: slowly destructive disorder of articular cartilage presenting as primary disease or secondary related to congenital or acquired defects affecting distribution of joint stress Pathogenesis: multifactorial with genetic and environment risk factors (primarily age); significant changes in composition & mechanical properties of cartilage caused by chondrocyte injury & release of cytokines that stimulate production & release of proteases ---> destructive to joint structures interfering with cartilage synthesis & repair; imbalances between proteases & inhibitors cause disease progression Clinical manifestations: typically affected joints include hips, knees, lumbar & cervical vertebrae, proximal & distal joints of hand; aching joint pain worsening with use or activity & relieved by rest; gelling—difficulty initiating joint movement after inactivity; later stages—night pain; audible crepitus & joint locking with movement; limitations of joint motion & joint instability; joint enlargement & synovitis
SLE diag, treatment
Diagnosis: H&P, laboratory—immunofluorescence for ANA; antibodies to double-stranded DNA; complete blood count Treatment: management of acute and chronic symptomatology to prevent loss of organ function, reduce exacerbations, minimize disability with disease progression, prevent complications of medication therapy Photosensitivity—protect against sun exposure; topical corticosteroid to skin lesion Joint symptoms—rest and NSAIDs Medications: hydoxychloroquine to treat lupus rashes or musculoskeletal manifestations; corticosteroids for renal or CNS disorders; immunosuppressive drugs when corticosteroids fail
Osteoarthritis diag, treatment
Diagnosis: H&P, x-ray studies, laboratory findings Treatment: Physical rehabilitative—improving supporting structures of joint & strengthening opposing muscle groups; balance of rest & exercise, splinting to protect & rest joint, heat & cold for pain & muscle spasm relief, adjusting ADLs; weight reduction; use of cane or walker for hips & knees involvement; Nutritional supplements—glucosamine & chondroitin (no rigorous testing to support efficacy); Oral medications: NSAIDs, acetaminophen; Intra-articular corticosteroid injections when other measures fail & in presence of joint effusion; visocsupplementation with hyaluronate; Topical: capsaicin Surgery: severe pain with reduced joint function; arthroscopic lavage & debridement, osteotomies, decompression of spinal roots, joint replacement, arthrodesis
Akylosoing spondylitis diag, treatment
Diagnosis: H&P, x-ray; lab—elevated ESR, mild normocytic, normochromic anemia; HLA typing is diagnostic Treatment: control pain & maintain mobility by suppressing inflammation; proper posture & positioning; supine sleeping position with firm mattress; therapeutic exercises to maintain motion, muscle strengthening exercise; heat applications before exercise; weight management; maintain pulmonary function with deep-breathing exercises & smoking cessation Medication: NSAIDs, DMARDs (second-line therapy—unproven efficacy),
Rheumatic arthritis diagnosis and treatment
Diagnosis: H&P; see Chart 44-2—presence of 4 to make diagnosis; Lab--RF & anti-CCP antibodies with correlation to disease severity and activity; synovial fluid analysis Treatment: reduce pain, minimize stiffness & swelling, maintain mobility, informed healthcare consumer Rest to reduce joint stress & relieve pain Therapeutic exercises to maintain joint motion & muscle strength Education re: proper posture, positioning, body mechanics, supportive shoes & principles of joint protection & work simplification, proper use of heat & cold Medications: salicylates, NSAIDs, Cox-2 inhibitors, disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologic agents
SLE disease course, manifestations
Disease course: acute or insidious onset; characterized by exacerbations & remissions Clinical manifestations: dependent on site Musculoskeletal: arthralgias/arthritis w/ hand deformities & loss of function Skin: acute skin lesions with butterfly rash on nose & cheeks, fingertip lesions--periungual erythema, nail fold infarcts, splinter hemorrhages; hair loss; sun sensitivity Renal: glomerulonephritis or interstitial nephritis with nephrotic syndrome Pulmonary: pleural effusions or pleuritis Cardiac: pericarditis, myocarditis, congenital heart block, hypertension, ischemic heart disease Hemotologic: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia CNS: acute vasculitis strokes (ischemic or hemorrhagic)
Rickets types (nutritional, vit. D dependent, vit. D resistant)
Nutritional—inadequate sunlight exposure or inadequate intake of vit D, calcium, or phosphate; risk factor—solely breast fed & dark-skinned infant or limited sunlight exposure Vitamin D-dependent rickets—abnormalities in gene coding for enzyme that converts inactive vit D to active form or autosomal disorder caused by mutations of vitamin D receptor Vitamin D-resistant rickets—hypophosphatemia or decrease in serum phosphate levels most often caused by mutations of the phosphate-regulating gene on X chromosome causing renal wasting of phosphate at proximal tubules of kidney
Paget disease def, cause, clinical manifestations, diagnosis, treatment
Osteitis Deformans Definition: focal areas of excessive osteoclast-mediated bone reabsorption preceding disorganized osteoblast-mediated bone repair begins in mid-adulthood and more common with aging Cause: mutations in genes encoding proteins in RANK signaling pathways; potential cause by paramyxovirus acting as trigger in genetically pre-disposed Pathogenesis: onset of furious osteoclastic bone resorption followed by period of hectic bone formation with increased numbers of osteoblasts depositing bone in chaotic fashion with poor quality, disorganized new bone resulting in bowing and fractures in focal areas; bone marrow adjacent to bone-forming surface replaced by loose connective tissue containing osteoprogenitor cells and numerous blood vessels; lesions can be solitary or multiple localizing to skull, spine, pelvis, proximal femur and tibia; lesions have increased vascularity and bone marrow fibrosis forming mosaic-like pattern caused by areas of density outlined by heavy blue lines (cement lines) Clinical manifestations: dependent on site: affecting skull causing headaches, intermittent tinnitus, vertigo, hearing loss; vertebrae enlarge, weaken & collapse ---> nerve compression & kyphosis; weight-bearing causing bowing of femur and tibia; softening of femoral neck coxa vara causing waddling gait and secondary osteoarthritis; mild to moderate deep aching pain late in disease persisting through day and worsening at night; extensive disease with increased blood flow to bones and subcutaneous tissue causing high-output heart failure or exacerbation of cardiac disease; risk factor for sarcoma of femur, pelvis, humerus Diagnosis: bone deformities and x-ray; increased serum alkaline phosphatase and urinary hydroxyproline; bone scan Treatment: NSAIDs & other anti-inflammatory drugs for pain; bisphosphonates and calcitonin; adequate vit D and calcium
Juvenile spondyloarthropathies
ankylosing spondylitis, reactive arthritis, psoriatic arthritis & spondyloarthropathies associated with ulcerative colitis & regional enteritis; manifesting in peripheral joints; spondyloarthropathies more common in boys with positive family history—HLA-B27 typing for diagnosis; TX: physical therapy—exercises to maintain ROM of back, thorax & affected joints, education, growth & developmental monitoring; custom-fitted shoes for painful entheses of feet; medication—salicylates or NSAIDs; methotrexate if unresponsive
Osteopenia def and cause
common to all metabolic bone disease characterized by reduction in bone mineral density greater than expected for age, race, gender occurring because of decrease in bone formation, inadequate bone mineralization, excessive bone deossification Cause: osteoporosis, osteomalacia, malignancies (multiple myeloma), endocrine disorders (hyperparathyroidism, hyperthyroidism)
Metabolic bone disease def
disorder of bone metabolism resulting in structural effect on skeletal ---> bone density and diminished bone strength
vertebral fractures
disorders of cancellous bone
fractures of long bones
disorders of cortical bone or reduced mass
secondary osteoporosis
endocrine disorders, malabsorption disorders, malignancies, alcoholism, medications (aluminum containing antacids, antiretroviral therapy, corticosteroid therapy)
postmenopausal hormone deficiency
estrogen deficiency postmenopause with bone mass loss greatest during early menopause; cytokines stimulate osteoclast recruitment and activity by increasing levels of RANK ligand (RANKL), while diminishing expression of osteoprotegerin (OPG); compensatory osteoblastic activity and new bone formation does not keep pace with bone loss
Juvenile dermatomyositis (JDMS)
inflammatory myopathy involving skin & muscle associated with characteristic rash; average age of onset 7 yrs; history of infection in 3 mos preceding disease onset; symmetric proximal muscle weakness, elevated muscle enzymes; vasculitis & EMG changes; periorbital edema, erythema & eyelid telangiectasia; calcifications on pressure points or sites of previous trauma most debilitating symptom; Tx: corticosteroid therapy; immunosuppressants for refractory disease
age-related changes
osteoblasts have reduced replicative and biosynthetic potential; growth factors stimulating osteoblastic activity lose potential over time with decreased ability to make bone; reduced physical activity
female athlete triad
poor nutrition intense training, decrease in fat-muscle ratio