Diseases of joints
description
Transcript of Diseases of joints
JOINT PATHOLOGY
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Modeling/RE-modeling
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CELLS of BONE• OSTEOPROGENITOR (“STEM”)(TGFβ)• OSTEOBLASTS (surface of spicule)• OSTEOCYTES (completely within spicule)
• OSTEOCLASTS (macrophage lineage)
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Proteins (organic) of BONE• Type 1 collagen (90%)• Cell adhesion proteins• Calcium-binding proteins• Proteins involved in mineralization • Enzymes• Growth factors
– GF-1, TGF-β, PDGF
• Cytokines– Prostaglandins, IL-1, IL-6, RANKL
• Proteins Concentrated from Serum– β2 –microglobulinAlbumin– IGF, insulin-like growth factor– TGF, transforming growth factor– PDGF, platelet-derived growth factor– IL, interleukin– RANKL, RANK ligand
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Minerals (INorganic) of BONE
HYDROXY-APATITE
Ca5(PO4)3(OH) Ca10(PO4)6(OH)2
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ADJECTIVES of BONE
• Compact• Spongy• Cancellous• Membranous• Dense• Cortical• Endosteal• Woven• Lamellar• Spicular
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Woven vs Lamellar
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-BLASTS/-CLASTS
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BONE DISEASES• 1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS IN NUCLEAR PROTEINS AND
TRANSCRIPTION FACTORS, polydactyly, syndactyly, absence of a bone• 2) DISEASES CAUSED BY DEFECTS IN HORMONES AND SIGNAL TRANSDUCTION
MECHANISMS, achondroplasia, thanatophoria• 3) DISEASES ASSOCIATED WITH DEFECTS IN EXTRACELLULAR STRUCTURAL PROTEINS
– Type 1 Collagen Diseases (Osteogenesis Imperfecta)– Types 2, 10, and 11 Collagen Diseases
• 4) DISEASES ASSOCIATED WITH DEFECTS IN FOLDING AND DEGRADATION OF MACROMOLECULES
– Mucopolysaccharidoses• 5) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC PATHWAYS (ENZYMES, ION
CHANNELS, AND TRANSPORTERS)– Osteopetrosis
• 6) DISEASES ASSOCIATED WITH DECREASED BONE MASS– Osteoporosis
• 7) DISEASES CAUSED BY OSTEOCLAST DYSFUNCTION– Paget Disease (Osteitis Deformans)
• 8) DISEASES ASSOCIATED WITH ABNORMAL MINERAL HOMEOSTASIS– Ricketts and Osteomalacia– Hyperparathyroidism– Renal Osteodystrophy
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1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS IN NUCLEAR PROTEINS AND
TRANSCRIPTION FACTORS
• Congenital absence of a, usually single, bone: phalanx, rib, clavicle
• Supernumerary digit (polydactyly)• Syndactyly• CRANIORACHISCHISIS
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2) DISEASES CAUSED BY DEFECTS IN HORMONES AND SIGNAL
TRANSDUCTION MECHANISMS
• Achondroplasia, dwarf (non-lethal)• Thanatophoria, dwarf (lethal)• a point mutation (usually Arg for Gly375) in the gene
that codes for FGF receptor 3 (FGFR3), which is located on the short arm of chromosome 4. In the normal growth plate, activation of FGFR3 inhibits cartilage proliferation;
• A MUTATION causes FGFR3 to be constantly activated.
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3) DISEASES ASSOCIATED WITH DEFECTS IN EXTRACELLULAR STRUCTURAL
PROTEINS
• OSTEOGENESS IMPERFECTA TYPES
• (“Brittle” bone disease, too LITTLE bone), BLUE sclerae
• Mutations in genes which code for the alpha-1 and alpha-2 chains of COLLAGEN 1
• Mutations of COLLAGEN 2,10, 11 manifest themselves as CARTILAGE diseases, ranging from joint cartilage destruction to fatal
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Osteogenesis Imperfecta
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4) DISEASES ASSOCIATED WITH DEFECTS IN FOLDING AND DEGRADATION OF
MACROMOLECULES
• MUCOPOLYSACCHARIDOSIS (one of MANY lysosome storage diseases)
• DECREASES in ENZYMES which degrade:– DERMATAN
– HEPARAN
– KERATAN
• Chiefly CARTILAGE disorders: short, chest wall, malformed bones
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MUCOPOLYSACCHARIDOSES
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5) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC
PATHWAYS (ENZYMES, ION CHANNELS, AND TRANSPORTERS)
• OSTEOPETROSIS, 4 types• One common one has a CARBONIC
ANHYDRASE deficiency• DECREASED osteoclast resorption• “MARBLE” bone, brittle, sclerosis
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OSTEOPETROSIS
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6) DISEASES ASSOCIATED WITH DECREASED BONE MASS
• OSTEOPOROSIS• “PEAK” bone mass is early adulthood• Normal decline, slow• Osteoporosis is accelerated bone loss• Factors:
– AGE– Physical activity– Estrogen– Nutrition (Ca++)– Genetics
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Categories of Generalized OsteoporosisPrimary
Postmenopausal Idiopathic
Senile
Secondary
Endocrine disorders Rheumatologic disease
Hyperparathyroidism Drugs
Hypo-hyperthyroidism Anticoagulants
Hypogonadism Chemotherapy
Pituitary tumors Corticosteroids
Diabetes, type 1 Anticonvulsants
Addison disease Alcohol
Neoplasia MiscellaneousMultiple myeloma Osteogenesis imperfecta
Carcinomatosis Immobilization
Gastrointestinal Pulmonary disease
Malnutrition, Malbs., Hepatic Insuf., Vit C,D Homocystinuria
Anemia
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OSTEOPOROSIS
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7) DISEASES CAUSED BY OSTEOCLAST DYSFUNCTION
Paget Disease (Osteitis Deformans)
• Matrix madness, Osteoblasts/-cytes gone wild• THREE PHASES:
– 1) Increased osteoclast resorption– 2) Increased “hectic” bone formation (osteoblasts)– 3) Osteosclerosis
• ELEVATED ALKALINE-PHOSPHATASE • ELEVATED urine HYDROXYPROLINE
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PAGET’s DISEASE (of BONE)
85% MONOSTOTIC, WHOLE BONE
15% POLY-OSTOTIC (skull, pelvis)
“JIGSAW”, NOT LAMINAR, BONE
CLINICAL: PAIN!!!
(MICROFRACTURES)
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PAGET’s DISEASE
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8) DISEASES ASSOCIATED WITH ABNORMAL MINERAL HOMEOSTASIS
– Ricketts and Osteomalacia• VITAMIN D deficiency/dysfunction
– Hyperparathyroidism, PRIMARY (PTH ADENOMA)• ENTIRE SKELETON• OSTEITIS FIBROSIS CYSTICA (von Recklinghausen’s disease
(of bone)• “BROWN” TUMOR
– Hyperparathyroidism, SECONDARY (RENAL) (NOT AS SEVERE AS 1º)
– Renal Osteodystrophy = ANY bone disorder due to chronic renal disease
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PRIMARY HYPERPARATHYROIDISM
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OSTEITIS FIBROSA CYSTICA
“BROWN” “TUMOR”
RENAL OSTEODYSTROPHY
• PHOSPHATE RETENTION• HYPOPHOSPHATEMIA• HYPOCALCEMIA• INCREASED PTH• INCREASED OSTEOCLASTS• METABOLIC ACIDOSIS release of
HYDROXYAPATITES from matrix
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FRACTURES
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FRACTURES, adjectives
• Complete, incomplete• Closed, open (communicating)• Communited (splintered)• Displaced (NON-aligned)• PATHOGENIC, (non-traumatic, 2º to other
disease, often metastases)• “STRESS” fracture
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FRACTURES
• THREE PHASES– HEMATOMA, minutes days PGDF, TGF-β, FGF– SOFT CALLUS (“PRO”-CALLUS), ~1 week– HARD CALLUS (BONY CALLUS), several weeks
• COMPLICATIONS– PSEUDARTHROSIS– INFECTION (especially OPEN [communicating]
fractures)
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FRACTURES
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OSTEONECROSIS• Also called AVASCULAR necrosis• Also called ASEPTIC necrosis
• CAUSE: ISCHEMIA– Trauma– Steroids– Thrombus/Embolism– Vessel injury, e.g., radiation– INCREASED intra-osseous pressurevascular
compression– Venous hypertension too
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OSTEONECROSIS
Disorders Associated with Osteonecrosis
Idiopathic Pregnancy
Trauma Gaucher disease
Corticosteroid administration Sickle cell and other anemias
Infection Alcohol abuse
Dysbarism Chronic pancreatitis
Radiation therapy Tumors
Connective tissue disorders Epiphyseal disorders
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OSTEONECROSIS
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OSTEONECROSIS
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OSTEOMYELITIS• Pyogenic: Staph, E. coli, Pseudom, Kleb
– Hematogenous – Contiguous– Direct implantation
• TB• Syphilis
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OSTEOMYELITIS• DX: X-ray, Bone scan
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OSTEOMYELITIS• DX: Histology
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OSTEOMYELITIS
• COMPLICATIONS– Subperiosteal abscess– Draining sinus– Joint involvement
• SEQUESTRUM vs. INVOLUCRUM
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OSTEOMYELITIS• Tuberculous
– Usually blood borne– TB of spine is known as POTTS disease
• Syphilis– CONGENITAL– TERTIARY, “SABRE” shins
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POTT’s DISEASE
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SABER SHINS
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Classification of Primary Tumors Involving BonesHistologic Type Benign MalignantHematopoietic (40%) Myeloma
Malignant lymphomaChondrogenic (22%) Osteochondroma Chondrosarcoma
Chondroma Dedifferentiated chondrosarcoma
Chondroblastoma Mesenchymal chondrosarcoma
Chondromyxoid fibroma
Osteogenic (19%) Osteoid osteoma Osteosarcoma
OsteoblastomaUnknown origin (10%) Giant cell tumor tumor
Giant cell tumorAdamantinoma
Histiocytic origin Fibrous histiocytoma Malignant fibrous histiocytoma
Fibrogenic Metaphyseal fibrous defect (fibroma) Desmoplastic fibroma
FibrosarcomaNotochordal ChordomaVascular Hemangioma Hemangioendothelioma
HemangiopericytomaLipogenic Lipoma LiposarcomaNeurogenic Neurilemmoma www.freelivedoctor.com
BONE TUMORS
• BONE• CARTILAGE• FIBROUS• MISC.
– Ewing’s “sarcoma”– Giant Cell Tumor– METASTASES
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BONE- BONE TUMORS
• OSTEOMA
• OSTEOID OSTEOMA
• OSTEOBLASTOMA
• OSTEOSARCOMA (OSTEOGENIC SARCOMA)
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OSTEOMA• SOLITARY• MIDDLE AGE• FROM SUBPERIOSTEAL or ENDOSTEAL surfaces• SKULL, FACE, most common• Totally BENIGN• To be distinguished from REACTIVE BONE
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FRONTAL SINUS
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OSTEOID OSTEOMA
• At least 2 cm in diameter• Teens, twenties, APPENDICULAR skeleton• M>>F• PAINFUL• Has a NIDUS• Responds to aspirin• Induces a MARKED bony reaction
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NIDUSwww.freelivedoctor.com
OSTEOBLASTOMA
• AXIAL SKELETON, i.e., SPINE
• NO Nidus
• NO bony reaction
• NOT relieved by aspirin
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OSTEOSARCOMA(OSTEOGENIC SARCOMA)
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LATE TEENSKNEESMETAPHYSESPAINFUL!!!
TYPES of OSTEOSARCOMAS
• • The anatomic portion of the bone from which they arise (intramedullary, intracortical, or surface)
• • Degree of differentiation • • Multicentricity (synchronous, metachronous) • • Primary (underlying bone is unremarkable) or secondary
(e.g., osteosarcoma associated with pre-existing disorders such as benign tumors, Paget disease, bone infarcts, previous irradiation)
• • Histologic variants (osteoblastic, chondroblastic, fibroblastic, telangiectatic, small cell, and giant cell)
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The most common subtype is osteosarcoma that arises in the metaphysis of long bones; is primary, solitary, intramedullary, and poorly differentiated; and produces a predominantly bony matrix
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BONE- CARTILAGE TUMORS
• OSTEOCHONDROMA (EXOSTOSIS)
• CHONDROMA
• CHONDROBLASTOMA
• CHONDROMYXOID FIBROMA
• CHONDROSARCOMA
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OSTEOCHONDROMA (EXOSTOSIS)
• Common, Cartilage AND Bone present• Often MULTIPLE as a hereditary syndrome• M>>>F• PELVIS, SCAPULAE, RIBS
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CHONDROMA• Chondroma vs. EN-chondroma• PURE Hyaline Cartilage• MULTIPLE enchondromas = Ollier’s dis.• Maffucci synd. if hemangiomas present
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CHONDROBLASTOMA
• RARE, in teenagers• M>>F• KNEES, usually• Epiphyses• MUCH LESS matrix than a chondroma
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CHONDROMYXOID FIBROMA
• RAREST of all• TEENS, MALES• “MYXOID” concept• “ATYPIA”
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CHONDROSARCOMA
• ANATOMY– INTRAMEDULLARY– JUXTACORTICAL
• HISTOLOGY– CONVENTIONAL
• HYALINE• MYXOID
– CLEAR– DE-DIFFERENTIATED– MESENCHYMAL
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CHONDROSARCOMA
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BONE- FIBROUS TUMORS
• FIBROUS CORTICAL DEFECT/NON-OSSIFYING FIBROMA
• FIBROUS DYSPLASIA
• FIBROSARCOMA/MALIGNANT FIBROUS HISTIOCYTOMA
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FIBROUS CORTICAL DEFECT
• COMMON, usually LESS THAN 1 CM
• CHILDREN >2• IF MORE THAN 5-6 CM,
they are then called NON-OSSIFYING FIBROMA
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FIBROUS DYSPLASIA
• BENIGN TUMOR
• THREE TYPES– SINGLE BONE (70%)– POLY-OSTOTIC (27%)– POLY-OSTOTIC (3%) with café-au-lait and
endocrine disorders, especially precocious puberty
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1) CURVED spicules
2) LACK of osteoblastic rimmingwww.freelivedoctor.com
FIBROSARCOMA/MFH
• METAPHYSES of LONG BONES
• PELVIC FLAT BONES
• LYTIC
• FRACTURES
• OF COURSE, SARCOMATOUS METASTASIS
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FIBROSARCOMA/MFHwww.freelivedoctor.com
MISC. TUMORS of BONE
• EWING sarcoma/PNET (Primitive NeuroEctodermal Tumor)
• GIANT CELL TUMOR
• METASTASES
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EWING/PNET• SAME TUMOR• SMALL ROUND• NEUROENDOCRINE• IDENTICAL CHROMOSOME TRANSLOCATION• SECOND most COMMON bone malignancy in
CHILDREN• ARISE IN MEDULLARY CAVITY of BONE• LOOK LIKE LYMPHOMA
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GCT (Giant Cell Tumor), BONE
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METASTASES
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MALE: PROSTATEFEMALE: BREASTRENAL, THYROID also seek bone early also
LYTIC?BLASTIC?
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SYNOVIAL JOINTS
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JOINT DISEASES
• “ARTHRITIS”– DEGENERATIVE (OSTEOARTHRITIS)– RHEUMATOID– “JUVENILE” RHEUMATOID– NON-INFECTIOUS: Ankylosing Spond., Reactive,
Psoriasis, IBD– INFECTIOUS: Supp., TB, Lyme, Viral– GOUT (URATE)– PSEUDOGOUT (PYROPHOSPHATE)
• Tumors– Ganglion (Synovial Cyst)– Giant Cell Tumor (Pigmented VilloNodular Synovitis[PVNS])– Synovial Sarcoma
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DEGENERATIVE ARTHRITIS
• Etiology/Risk Factors: Age, Trauma, Genes
• Pathogenesis: Progressive EROSION of articular cartilage
• Morphology: X-Ray, “eburnation”, “joint mice”, osteophytes
• Clinical Expression: PAIN, Limitation of motion
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HEBERDEN’S NODES
DIP, NOT MP or PIP www.freelivedoctor.com
RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may affect many tissues and organs—skin, blood vessels, heart, lungs, and muscles—but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints.
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RHEUMATOID ARTHRITIS
• Etiology/Risk Factors: Autoimmune• Pathogenesis: Progressive SYNOVITIS• Morphology: Synovial lymphocytes,
macrophages, plasma cells, neutrophils, osteoclasts, “pannus”, hyperemia, rheumatoid “nodules”, vasculitis
• Clinical Expression: PAIN, Limitation of motion, malaise, fatigue, rheumatoid factor IgM-IgGFc,
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The rheumatoid “nodule” shows “palisading” fibroblasts
HANDSWRISTELBOWS
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DIAGNOSIS• CLINICAL FEATURES (1% of population F>>M)
– MORNING STIFFNESS– ARTHRITIS in MORE THAN 3 JOINT AREAS– “TYPICAL” hand findings– SYMMETRIC ARTHRITIS– SERUM RHEUMATOID FACTOR– “TYPICAL” X-RAY findings
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“JUVENILE” Rheumatoid Arthritis
• Begins BEFORE age 16, by definition
• Generally LARGER joints than RA
• Often POSITIVE ANA
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“SERONEGATIVE” ARTHRITIDES
• ANKYLOSING SPONDYLITIS (aka, “rheumatoid” spondylitis, or Marie-Strumpell Disease [HLA-B27] (M>>F)
• “REACTIVE” ARTHRITIS (FOLLOWS GU or GI INFECTIONS)– REITER SYDROME (urethral & conjunctival
inflammation too) [HLA-B27]– Arthritis associated with IBD
• PSORIATIC ARTHRITIS
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Ankylosing Spondylitis
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INFECTIOUS ARTHRITIS
• From OSTEOMYELITIS• USUALLY SUPPURATIVE
• GC, staph, strep, H. flu, E. coli, (Salmonella in sicklers)
• 4 cardinal signs, fever,
leukocytosis, ESR
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INFECTIOUS ARTHRITIS
• TB• LYME Disease, i.e., Borrelia
burgdorferi• VIRAL
– Parvovirus B19– Rubella– Hepatitis C
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GOUT• Endpoint of HYPERURICEMIA from
ANY cause resulting in JOINT deposition of Monosodium crystals (TOPHI)– ACUTE– CHRONIC
• 10% of population has hyperuricemia (>7 mg/dl), but only 1/20 of these has gout
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Classification of GoutClinical Category Metabolic Defect
Primary Gout (90% of cases)
Enzyme defects unknown (85%–90% of primary gout)
■ Overproduction of uric acid
Normal excretion (majority)
Increased excretion (minority)
Underexcretion of uric acid with normal production
Known enzyme defects—e.g., partial HGPRT deficiency (rare)
■ Overproduction of uric acid
Secondary Gout (10% of cases)
Associated with increased nucleic acid turnover—e.g., leukemias
■ Overproduction of uric acid with increased urinary excretion
Chronic renal disease ■ Reduced excretion of uric acid with normal production
Inborn errors of metabolism—e.g., complete HGPRT deficiency (Lesch-Nyhan syndrome)
■ Overproduction of uric acid with increased urinary excretion
HGPRT, hypoxanthine guanine phosphoribosyl transferase.
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HYPERURICEMIA GOUT
• Age of the individual and duration of the hyperuricemia are factors. Gout rarely appears before 20 to 30 years of hyperuricemia.
• Genetic predisposition is another factor. In addition to the well-defined X-linked abnormalities of HGPRT, primary gout follows multifactorial inheritance and runs in families.
• Heavy alcohol consumption predisposes to attacks of gouty arthritis.
• Obesity increases the risk of asymptomatic gout. • Certain drugs (e.g., thiazides) predispose to the development
of gout. • Lead toxicity increases the tendency to develop saturnine gout
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FEATURES• TOPHACEOUS
ARTHRITIS
• GOUTY NEPHROPATHY
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GOUTY NEPHROPATHY
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GOUT• Associated with ATHEROSCLEROSIS
• Associated with HYPERTENSION
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Pseudo-GOUT• Gout: Monosodium Urate• Pseudo-GOUT: Calcium Pyrophosphate
• PSEUDOGOUT is also called CHONDROCALCINOSIS, or CPPD (Calcium Phosphate Deposition Disease)
• IDIOPATHIC, HEREDITARY, SECONDARY
– Secondary joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, and diabetes
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GOUT vs. PSEUDOGOUT
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JOINT TUMORS• BENIGN
– GANGLION (SYNOVIAL CYST)– GIANT CELL TUMOR of TENDON SHEATH,
aka PVNS, Pigmented VilloNodular Synovitis
• MALIGNANT– SYNOVIAL SARCOMA
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GANGLION
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PVNS/GCT
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“SOFT TISSUE” TUMORS
• FAT• FIBROUS TISSUE• FIBROHISTIOCYTIC• SKELETAL MUSCLE• SMOOTH MUSCLE• VASCULAR• PERIPHERAL NERVE• UNCERTAIN: SYNOVIAL SARCOMA, ALVEOLAR SOFT PART
SARCOMA, EPITHELIOD SARCOMA
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CAUSES• MOSTLY UNKNOWN• RADIATION association• CHEMICAL BURN association• THERMAL BURN association• TRAUMA association• VIRUS association (HHV8 for Kaposi)• GENETICS• Parts of many SYNDROMES• MANY TRANSLOCATIONS
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Chromosomal and Genetic Abnormalities in Soft Tissue Sarcomas
Tumor Cytogenetic Abnormality Genetic Abnormality
Extraosseous Ewing sarcoma and primitive neuroectodermal tumor
t(11:22)(q24;q12) FLI-1-EWS fusion gene
t(21:22)(q22;q12) ERG-EWS fusion gene
t(7;22)(q22;q12) ETV1-EWS fusion gene
Liposarcoma—myxoid and round cell type
t(12:16)(q13;p11) CHOP/TLS fusion gene
Synovial sarcoma t(x;18)(p11;q11) SYT-SSX fusion gene
Rhabdomyosarcoma—alveolar type t(2;13)(q35;q14) PAX3-FKHR fusion gene
t(1;13)(p36;q14) PAX7-FKHR fusion gene
Extraskeletal myxoid chondrosarcoma t(9;22)(q22;q12) CHN-EWS fusion gene
Desmoplastic small round cell tumor t(11;22)(p13;q12) EWS-WT1 fusion gene
Clear cell sarcoma t(12;22)(q13;q12) EWS-ATF1 fusion gene
Dermatofibrosarcoma protuberans t(17:22)(q22;q15) COLA1-PDGFB fusion gene
Alveolar soft part sarcoma t(X;17)(p11.2;q25) TFE3-ASPL fusion gene
Congenital fibrosarcoma t(12;15)(p13;q23) ETV6-NTRK3 fusion gene
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SOFT TISSUE TUMORS
• ALL “SPINDLY”
• Deep (desmoid) vs. Superficial
• Importance of MITOSES
• Importance of STAGING
• Importance of IMMUNOPEROXIDASE
• Importance of CONSULTATION
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FAT• LIPOMA• LIPOSARCOMA
www.freelivedoctor.comNORMAL FAT
LIPOMA, encapsulated
LIPOSARCOMA, often retroperitoneal
FIBROUS TISSUE• NODULAR FASCIITIS
(pseudosarcomatous)• FIBROMATOSES
(plantar, palmar, penile)• FIBROSARCOMA
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MYOSITIS OSSIFICANS
• BENIGN FIBROUS TISSUE PROLIFERATION PLUS OSSEOUS METAPLASIA
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FIBROHISTIOCYTIC
• FIBROUS HISTIOCYTOMA
• DERMATOFIBROSARCOMA PROTUBERANS
• MALIGNANT FIBROUS HISTIOCYTOMA
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SKELETAL MUSCLE• RHABDOMYOMA
• RHABDOMYOSARCOMA
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SMOOTH MUSCLE
• LEIOMYOMA
• LEIOMYOSARCOMA
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VASCULAR
• HEMANGIOMA
• LYMPHANGIOMA
• HEMANGIOENDOTHELIOMA
• HEMANGIOPERICYTOMA
• ANGIOSARCOMA
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PERIPHERAL NERVE
• NEUROFIBROMA
• SCHWANNOMA
• GRANULAR CELL TUMOR
• MALIGNANT (SCHWANNOMA)
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UNCERTAIN
• SYNOVIAL SARCOMA• ALVEOLAR “SOFT PART”
SARCOMA• EPITHELIOD SARCOMA
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