Rheumatologic Disorders PDF

Unit 3-2: Rheumatologic Disorders DiPiro Chs. 110-113 Learning Objectives: Know differences in hereditary and congenital disorders of bone Compare metabolic bone disorders Augustin Jacob Landré- Know differences in different Beauvais (1772–1840):...

Unit 3-2: Rheumatologic Disorders DiPiro Chs. 110-113 Learning Objectives: Know differences in hereditary and congenital disorders of bone Compare metabolic bone disorders Augustin Jacob Landré- Know differences in different Beauvais (1772–1840): French surgeon best known for his metabolic bone disorders description of rheumatoid arthritis. His Know etiology of metabolic bone description of rheumatoid arthritis, now regarded as the first modern-day disorders. account of the disease, incorrectly Terminology identified it as a form of gout. 1  Unit 3-2: Terminology Osteogenesis imperfecta Osteocytes Hip dysplasia Osteoblasts Subluxated Osteogenic cells Luxated Osteoclasts Scoliosis Ossification RA Metabolic bone disorders Osteopenia Osteoporosis Osteomalacia Rickets Hyperparathyroidism Hyperthyroidism Bisphosphonates Calcitonin Paget’s Disease 2  Hereditary and Congenital Deformities Multifactorial causes: – Unknown, genetic influences, exposure to external agents – Abnormalities of bone matrix, deficient collagen synthesis, decreased bone mass Osteogenesis imperfecta: – Occurrence: 20,000-50,000 US cases – Defective synthesis of collagen I alpha chains (COL1A) on chromosomes 17 and 7 – Clinical manifestations: Thin poorly developed bones Short limbs Prone to multiple fractures Hearing loss due to otosclerosis Stillborn – Prevention and treatment of fractures 3 Hereditary and Congenital Deformities 4  Hereditary and Congenital Deformities Developmental hip dysplasia: – Unstable, subluxated, or complete dislocated – Occurrence: 1 in 100 infants have instability; 1 in 1000 complete dislocation – More frequently in girls – Etiology: Positive family history; Increased maternal hormones (estrogen and other pelvic relaxation hormones) – 60%-80% identified cases resolve – Treatment: Therapy Harnesses Hip casts Surgery 5  Scoliosis Lateral deviation of spine Idiopathic Girls most affected Classified based on age of onset – Infantile: 0-3 years; Rare – Juvenile: 4-9 years; Uncommon – Adolescent: >10 years; 80% of all cases Diagnosis (5 cardinal signs) – Uneven shoulders or iliac crest – Prominent scapula – Malalignment of spinous process – Asymmetrical rib cage – Rib hump or paraspinal muscle prominence Treatment – Early diagnosis – Milwaukee to Wilmington braces – Surgery 6  Arthritis Descriptive term applied to >100 diseases Commonality: Inflammation of joint resulting from immune response 7  Rheumatoid Arthritis Systemic inflammatory disease that affects women 3x greater than men Etiology: Cause is unknown – Genetic predisposition: HLA-DRB1 (Human Leukocyte Antigen – DRB1 isotype) is an MHC (major histocompatibility complex) cell surface receptor – Ligand for the T-cell receptor (TCR) involved in several autoimmune conditions and is upregulated in infection – T-helper cell mediated response to release TNF and ILs – Autoimmune response: Rheumatoid factor (RF) – Autoantibody precipitates when the blood cools; Binds with IgG to form complex to contribute to disease Pannus – Destructive vascular granulation tissue caused by inflammation Matrix Metalloprotease-1 (MMP-1) – Destroys collagen I – Nongenetic or environmental factors: Cigarette use, coffee consumption, and obesity – Occupational hazards: Exposure to silica, may also play a role in susceptibility to disease Clinical Manifestations: – Progressive joint destruction leading to subluxation and joint deformities – Systemic disease – Fatigue, anorexia, anemia, low-grade fever 8  Rheumatoid Arthritis Diagnosis: 4 categories 1. Joint involvement – Swelling, tenderness, warmth in joint(s) 2. Serology – RF+ and anti-citrulinated protein autoantibody (ACPA)+ 3. Acute phase reactants – Nonspecific inflammation markers (increased erythrocyte sedimentation rate and C-reactive peptide) 4. Duration of symptoms Treatment: Aimed at reducing symptoms and target remission – Personal – Rest, weight loss, exercise, physical therapy, hot-cold modalities – Pharmacological – Non-steroidal anti-inflammatory drugs (NSAIDs) Disease-modifying anti-rheumatic drugs (DMARDs) - Conventional and biologics Corticosteroids 9  Rheumatoid Arthritis Slows immune cell-mediated damage Interferes with purine metabolism to reduce inflammation (MTX) Scavenges circulating/local TNF 10  Metabolic Bone Disorders Dysfunction of bone remodeling Breakdown of bone > Formation of bone Osteopenia: – Term used to describe lack of bone mass – Reduction in bone mass greater than expected based on age, race, or sex – Not a diagnosis – Includes all metabolic bone diseases Osteoporosis Osteomalacia Malignancies Endocrine disorders: Hyperparathyroidism and hyperthyroidism 11 Metabolic Bone Disorders 12  Metabolic Bone Disorders Osteoporosis: Loss of mineralized bone mass causing porosity – Associated with aging, gender, genetics, activity level, and nutrition – Susceptible to fractures – Postmenopausal Caucasian and Asian women have higher rates Decreased estrogen is associated with increased TNF, IL-1, IL-6 cytokines that stimulate osteoclast precursors – Osteoblastic activity occurs but is less than osteoclastic activity 13  Secondary osteoporosis: Associated with multiple Metabolic Bone Disorders conditions – Endocrine disorders: Hyperparathyroidism and hyperthyroidism, Cushing syndrome (hypercortisolism), diabetes mellitus – Alcohol: Direct inhibitor of osteoblasts and calcium inhibition – Long-term corticosteroid use: Drug-related osteoporosis as a result of treatment of rheumatoid arthritis and COPD – Prolonged use of medications: Meds that increase calcium excretion (anticonvulsants and aluminum-containing antacids) 14 Metabolic Bone Disorders 15 Metabolic Bone Disorders 16  Metabolic Bone Disorders Treatment: – Prevention and early detection – Increased exercise – Women: Estrogen replacement therapy SERMs (Selective Estrogen Receptor Modulators) – Men: Testosterone: Stimulates osteoblast and inhibits osteoclast Contraindicated in men with prostate cancer – Bisphosphonates: Analogs of endogenous inorganic pyrophosphates Bind to hydroxyapatite to prevent bone reabsorption by inhibiting osteoclast activity Reduce risk of hip, vertebral, and non-vertebral fractures – Calcitonin: Endogenous peptide that partially inhibits osteoclastic activity 17  Osteomalacia and Rickets Softening of bones not involving bone matrix loss Osteomalacia: Inadequate mineralization of bone (adults) Rickets: Failure/delay in calcification of growth plate (children) Etiology – Nutritional deficits – Malabsorptive syndromes (celiac diseases and cystic fibrosis) – Medications: Anticonvulsants, antacids – Insufficient calcium absorption due to lack of dietary calcium – Deficiency or resistance to vitamin D – Phosphate deficiency caused by renal losses or decreased intestinal absorption Treatments targeted to underlying causes 18 Osteomalacia and Rickets 19 Recommended Levels of Calcium and Vitamin D 20  Paget Disease (Osteitis Deformans) Local areas of excessive bone turnover lesions with increased osteoblastic deposition of bone Chaotic in fashion; causes bone deformities 2nd most common bone disease Manifests in Northern European heritage usually ~40 years old Causes: – Genetics: First degree family member with disease – Paramyxovirus particles in osteoclasts Treatment: – Bisphosphonates and calcitonin – Pain treatment 21 Unit 3-2: Rheumatologic Disorders DiPiro Chs. 110-113 Learning Objectives: Know differences in hereditary Part 1 and congenital disorders of bone Compare metabolic bone disorders Augustin Jacob Landré- Know differences in different Beauvais (1772–1840): French surgeon best known for his metabolic bone disorders description of rheumatoid arthritis. His Know etiology of metabolic bone description of rheumatoid arthritis, now regarded as the first modern-day disorders. account of the disease, incorrectly Terminology identified it as a form of gout. 22