This study guide was prepared by Fanconi.

AUTOIMMUNE DISEASES

§         Systemic lupus erythematosus

®      1 in 2500, 9 female: 1 male

®      Numerous autoantibodies, especially

o         Anti-nuclear antibody

o         Anti-dsDNA

o         Anti-Smith

o         Anti-phospholipid

o         Anti-cardiolipin (false positive VDRL)

o         Lupus anticoagulant is procoagulant in vivo

®      Heritable defects in the regulation of B-cell proliferation

®      Helper T cell hyperactivity

®      Organ systems affected:

o         Kidney:  five patterns of lupus nephritis

o         Skin:  Ig and C’ deposits at dermal/epidermal junction

o         Joints:  nonspecific, nonerosive synovitis, minimal joint deformity

o         CNS: endothelial injury, occlusion (anti-phospholipid antibody syndrome)

o         Serositis:  fibrinous pericarditis

o         Heart:  Libman-Sacks endocarditis, CAD with steroid use

o         Spleen:  fibrosis of blood vessels

o         Lungs

®      Death due to renal failure or infection

§         Discoid lupus erythematosus

®      Skin involvement

®      Only 35% have positive ANA

®      5-10% will develop systemic manifestations

§         Drug-induced lupus

®      Anti-histone antibody

®      Hydralazine, Procainamide, D-penicillamine, Isoniazid

®      HLA-DR4 = greater risk

§         Sjorgren’s syndrome

®      Keratoconjunctivitis sicca and xerostomia

®      Lymphocytic infiltrate and fibrosis of glands

®      SS-A (Ro) and SS-B (La) antibodies

®      “Pseudo-lymphoma” and 40X higher risk of developing lymphoma

§         Systemic Sclerosis (Scleroderma)

®      Excessive systemic fibrosis, especially of the skin

®      Female 3 : male 1

®      DNA topoisomerase I antibodies

®      Renal failure = death in 50%

§         CREST Syndrome

®      Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia

®      Anti-centromere antibodies

§         Inflammatory Myopathies

®      Dermatomyositis = heliotrope rash on eyes and Grotton lesions on knuckles, cancer assoc.

o         Antibodies to microvasculature in perimysial connective tissue

®      Polymyositis = skin involvement and cancer association is lacking

o         Damage to muscle fibers by CD8+ T cells

§         Mixed Connective Tissue Disease

®      Features of SLE, polymyositis, and systemic sclerosis

®      High ANA titers (but no anti-dsDNA or anti-Sm, in contrast to SLE)

®      Infrequent renal disease

®      Excellent response to steroids

DISEASES OF THE SKELETAL SYSTEM AND SOFT TISSUE TUMORS

§         Achondroplasia

®      Genetic derangement of epiphyseal cartilaginous growth = dwarfism

®      Most are acquired mutations

®      Heterozygotes = normal longevity with small bodies and big heads

®      Homozygotes die soon after birth

§         Osteogenesis Imperfecta

®      Abnormal synthesis of type 1 collagen

®      Osteopenia with thinning of cortices and rarefaction of trabeculae

§         Mucopolysaccharidoses

®      Lysosomal storage diseases

®      Chondrocytes play a role in metabolism of mucopolysaccharides

®      Abnormalities of hyaline cartilage (growth plates, costal cartilages, and articular surfaces)

®      Short stature and malformed bones

§         Osteoporosis

®      Reduction in bone mass

®      Primary

®      Secondary = endocrine disorders, neoplasia, GI problems, drugs

®      Slowing of osteoblastic function

®      Increased osteoclastic function (reduced estrogen, increased IL-1)

®      Bone pain due to microfractures

§         Osteopetrosis

®      Hereditary overgrowth, sclerosis of bone

®      Think cortex, narrow medullary cavity (impairs hematopoiesis)

®      Brittle bone breaks like chalk

®      Common hereditary defect is reduced osteoclastic function (reduced resorption)

§         Paget Disease (Osteitis Deformans)

®      Initial osteolytic stage

®      Mixed osteolytic-osteoblastic stage

o         Mosaic pattern

®      Burnt-out osteosclerotic stage

®      Slow viral infection of osteoblasts, osteoclasts (paramyxovirus)

®      Fractures, nerve compression, osteoarthritis, skeletal deformities

®      Coarsening of facial bones = lionlike facies

§         Rickets and Osteomalacia

®      Vitamin D deficiency or phosphate depletion

®      Failure of bone mineralization

§         Hyperparathyroidism

®      Demineralization first occurs

®      Osteitis fibrosa follows

®      “Moth-eaten” bones on x-ray

®      Brown tumors = reactive fibrous tissue (hemosiderin)

§         Renal Osteodystrophy

®      Bone changes in chronic renal disease

®      Osteitis fibrosa cystica, osteomalacia, and/or osteosclerosis

§         Fractures

®      Organization of hematoma, procallus

®      Procallus becomes fibrocartilagenous callus

®      Osseus callus

§         Osteonecrosis (Avascular necrosis)

®      Fracture, Caisson disease, vasculitis, radiation, steroid-induced

§         Pyogenic Osteomyelitis

®      Bacterial seeding of bone by

o         Hematogenous spread

o         Extension from contiguous infection

o         Open fracture or surgical procedure

®      Blood-borne infections = Staph aureus

®      Sickle cell patients = Salmonella

®      Suppurative reaction with ischemic necrosis, fibrosis, bony repair

®      Garre sclerosing osteomyelitis

®      Brodie abscess

§         Tuberculous Osteomyelitis

®      Pott disease in the spine

®      Granulomatous reaction

§         Syphilis

®      Congenital = periostitis with crew hair-cut like bone formation and Saber skin (tibia)

®      Acquired = periostitis and gummas in bone

§         Osteoarthritis (DJD)

®      Deterioration of articular cartilage

®      DIP = Heberden nodes

®      Primary or secondary (to trauma)

®      “Joint mice” in the joint space

®      IL-1, TNF-a, TGF-b

®      Morning stiffness, decreased ROM

§         Rheumatoid Arthritis

®      Severe, chronic synovitis

®      Women 3:1, peak prevalence in 20s-30s

®      HLA-DR4, HLA-DR1

®      First affects small proximal joints

®      Pannus = exuberant synovium

®      Villous hypertrophy of synovium

®      Autoantibody against Fc portion of IgG = rheumatoid factor (usually IgM)

®      Does not contribute to pathogenesis, but may be related to vasculitis

®      Variants = JRA, Felty’s syndrome, RA with ulcerative colitis, and RA with Sjogren’s syndrome

§         Seronegative Spondylarthropathies

®      Ankylosing spondylitis

o         Inflammation of vertebra and sacroiliac joint

o         Autoantibodies directed against joint elements

®      Reiter syndrome = arthritis, nongonococcal urethritis, and conjunctivitis.

o         Men in 20s-30s, HLA-B27

®      Psoriatic arthritis

o         5% of patients with skin disease

o         Less severe joint destruction than in RA

®      Enteropathic arthritis

o         10-20% of patients with inflammatory bowel disease

o         Remits spontaneously within a year

§         Infectious Arthritis

®      Suppurative arthritis

o         Gonococcus, staph, strep, H. influenzae, GNR

o         Usually single joint affected

o         Gonococcal arthritis = oligoarticular and skin rash, associated with a genetic deficiency of C5, C6, or C7

®      Tuberculous arthritis

o         More destructive than suppurative

®      Lyme arthritis

o         Several days or weeks after initial skin infection

o         Remitting, migratory, large joints

o         Looks like RA

o         Clears spontaneously or with therapy

§         Gout and Gouty Arthritis

®      Hyperuricemia

®      Attacks of acute arthritis triggered by crystallization of urates in joints

®      Asymptomatic intervals

®      Chronic tophaceous gout = pathognonomic lesion

®      Men >20 years old

®      Pathogenesis

o         Primary = X-linked partial deficiency of HGPRT (90%)

o         Secondary = increased nucleic acid turnover (blood cancers), drugs, or chronic renal disease.

·         Saturnine gout = lead intoxication

·         Von Gierke disease = glycogen storage disease

·         Lesch-Nyhan syndrome = total lack of HGPRT (only men)

®      Needle-shaped negatively birefringent crystals

o         Activate Hageman factor, C3a and C5a are produced (chemoattractants)

§         Calcium Pyrophosphate Deposition Disease

®      Chrondrocalcinosis = pseudogout

®      Hereditary, sporadic, or associated with trauma or surgery

®      Weakly positive birefringent rhomboid crystals

§         Ganglion and Synovial Cyst

®      Herniations of synovium

§         Villonodular Synovitis

®      Giant cell tumor of tendons, pigmented with hemosiderin

§         Lipoma

®      Most frequent soft tissue tumor

§         Liposarcoma

®      Much less common

®      Bulky, from primitive mesenchymal cells, lipid vacuoles

®      Appear anywhere without regard to adipose tissue

®      Myxoid variant has 12:16 balanced translocation

§         Nodular Fasciitis

®      Commonly mistaken for a neoplasm

®      Small masses on extremities

®      Fibroblasts in myxoid background, mitoses

®      Recurrence after excision is very rare

§         Myositis Ossificans

®      Quads or brachialis muscle

®      Periphery of mineralized bone

®      Should not be confused with osteogenic sarcoma

§         Palmar, Plantar, and Penile Fibromatosis

®      Dupuytren contracture on palm

®      Plantar fibromatosis on feet

®      Peyronie disease on penis

®      May recur after excision or spontaneously resolve

§         Desmoid = Aggressive Fibromatosis

®      Intra-abdominal = Gardner syndrome

®      Banal, tame fibroblasts

®      Recur when incompletely removed

§         Fibroma

®      Most common in ovary

§         Fibrosarcoma

®      Fish-flesh masses, spindled growth in a herring-bone patterns

®      Infiltrative, 60-80% 5 year survival

§         Benign Fibrous Histiocytoma

®      Benign giant cells and fat-laden foamy cells

®      Skin = dermatofibromas

®      Vascular variant = sclerosing hemangioma

§         Rhabdomyosarcoma

®      Cardiac rhabdomyomas ® seen in tuberous sclerosis

®      Rhabdomyosarcoma is more common, esp. in kids

®      Head, neck, urogenital regions

o         Embryonal

o         Botyroid (grape-like mass in the vagina)

o         Alveolar (2:13 translocation)

o         Pleomorphic (seen in older patients, rare, poor prognosis)

®      Special staining techniques = ribosomal-myosin complexes or desmin/myoglobin immunoperoxidase

§         Leiomyoma

®      Benign smooth muscle tumors, esp. in female genital tract

§         Leiomyosarcoma

®      Uncommon, more frequent in women

®      AIDS

§         Synovial Sarcoma

®      Around joints, but not in joint spaces

®      Also occur in parapharyngeal region and abdominal wall

o         Biphasic pattern of cell growth

o         Epithelial (gland components) and spindle cell components

®      Reciprocal translocation between X and 18