Osteoarthritis (Clinical)

Epidemiology and Etiology

Epidemiology^[1,6,7]

• Most common arthropathy Arthropathy Osteoarthritis (> 70% of all arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis)
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: approximately 492 cases per 100,000 people worldwide
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency increases with age.
  • 80%–90% of individuals > 65 years have radiographic osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis ( OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis).
  • Symptoms are generally not noticed until after the age of 50.
• Women are more commonly affected.

Classification and etiology^[5,7,12]

• Primary OA Primary OA Osteoarthritis: 
  • Idiopathic Idiopathic Dermatomyositis
  • Nodal OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
• Secondary OA Secondary OA Osteoarthritis: 
  • Trauma or surgery
  • Congenital disorders
    • Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
    • Epiphyseal dysplasia
    • Legg-Calve-Perthes disease
    • Joint hypermobility Joint Hypermobility Ehlers-Danlos Syndrome
    • Slipped femoral capital epiphysis Epiphysis The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united. Bones: Structure and Types
    • Congenital hip dislocation
  • Metabolic disorders
    • Hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis
    • Wilson’s disease
    • Crystal deposition disease ( gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout)
    • Hemoglobinopathies Hemoglobinopathies A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. Anemia: Overview and Types ( thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia)
  • Infection
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types disorders
    • Paget disease
    • Osteonecrosis
  • Neuropathic (Charcot joint)
    • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
    • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis

Risk factors^{[1,2,6,12,17]}

• Age
• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
• Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria
• Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics and family history Family History Adult Health Maintenance
• Physical activity and repetitive use
• Muscle weakness or dysfunction

Pathophysiology

• Hypertrophic repair of articular cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology: mechanical stress → cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology damage → ↑ proteoglycan and collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology synthesis Synthesis Polymerase Chain Reaction (PCR) → swelling Swelling Inflammation of joint cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology^[2,5‒7,12]
• Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology destruction:^[2,5‒7]
  • Continued damage → ↑ chondrocyte proliferation and activity → matrix metalloproteinase Matrix metalloproteinase A family of zinc-dependent metalloendopeptidases that is involved in the degradation of extracellular matrix components. Pulmonary Fibrosis production → matrix degradation
    • Inflammatory mediators and matrix protein Matrix protein Proteins associated with the inner surface of the lipid bilayer of the viral envelope. These proteins have been implicated in control of viral transcription and may possibly serve as the ‘glue’ that binds the nucleocapsid to the appropriate membrane site during viral budding from the host cell. Parainfluenza Virus fragments continue chondrocyte stimulation.
    • Ultimately leads to chondrocyte death
  • ↓ Collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology and proteoglycans Proteoglycans Glycoproteins which have a very high polysaccharide content. Basics of Carbohydrates → ↓ cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction → ↓ joint integrity
  • Loss of cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology → ↓ joint space → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types becomes denuded
• Subchondral bone Subchondral Bone Osteochondritis Dissecans response:^[2,5‒7]
  • Articulation of exposed bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types with an opposing surface → ↑ stress on the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
  • Vascular invasion and ↑ cellularity → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types becomes thickened and dense ( subchondral sclerosis Subchondral Sclerosis Osteochondritis Dissecans)
  • Chronic impaction and osseous necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage → cystic degeneration Cystic Degeneration Fat Necrosis of the Breast ( subchondral cysts Subchondral Cysts Osteoarthritis)
  • Osseous metaplasia Osseous Metaplasia Osteoarthritis and ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology → outgrowth of new bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types (osteophytes)

Clinical Presentation

Commonly affected joints^[4‒7]

• Hands:
  • Proximal interphalangeal (PIP) joints
  • Distal interphalangeal (DIP) joints
  • 1st carpometacarpal Carpometacarpal The articulations between the carpal bones and the metacarpal bones. Wrist Joint: Anatomy (CMC) joints
• Hips 
• Knees
• Spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy:
  • Intervertebral disks
  • Zygapophyseal (facet) joints
• Feet: 1st metatarsophalangeal (MTP) joints

Symptoms^[4‒7]

• Joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Gradual onset
  • Asymmetric
  • More severe with:
    • Activity
    • Weight bearing
  • Relieved with rest
  • Later in the disease:
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is more constant.
    • Affects sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep and level of activity
• Morning stiffness
  • Duration < 30 minutes
  • Improves with movement
• Inguinal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways due to hip involvement
• Restricted joint movement
• Sensation of joint instability and locking
• Radicular pain Radicular Pain Spinal Disk Herniation results from:
  • Spondylolisthesis Spondylolisthesis Displacement of a vertebra forward in relation to the vertebra below Back Pain
  • Nerve impingement

Physical exam^[4‒7]

• Joint line tenderness
• Limited range of motion Range of motion The distance and direction to which a bone joint can be extended. Range of motion is a function of the condition of the joints, muscles, and connective tissues involved. Joint flexibility can be improved through appropriate muscle strength exercises. Examination of the Upper Limbs (ROM)
• Crepitus Crepitus Osteoarthritis with passive ROM
• Evidence of osteophytes
  • DIP joints: Heberden nodes
  • PIP joints: Bouchard nodes
  • First CMC joint: thumb squaring
• Synovitis Synovitis Inflammation of the synovial membrane. Rheumatoid Arthritis
  • Seen in erosive OA Erosive OA Osteoarthritis
    • An inflammatory subset of primary OA Primary OA Osteoarthritis
    • Etiology is unknown.
  • Signs:
    • Soft-tissue swelling Swelling Inflammation
    • Warm
• Popliteal or Baker cyst
• Knee varus or valgus deformities

Diagnosis

Clinical criteria^[8,9,12]

• Age > 50 years (≥ 45 years in the UK)
• Activity-related joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• No morning joint stiffness or morning joint stiffness lasting < 30 minutes

Imaging

Osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis is a clinical diagnosis that is confirmed with imaging.  Imaging is not routinely required but may be needed to diagnose atypical presentations of osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis, such as morning joint-related stiffness > 30 minutes, rapid progression of symptoms, recent trauma, hot swollen joint, or history suggestive of infection or malignancy Malignancy Hemothorax.^[8,9]

• Radiography:
  • Classic findings:^[10,11]
    • Joint space narrowing
    • Subchondral sclerosis Subchondral Sclerosis Osteochondritis Dissecans
    • Subchondral cysts Subchondral Cysts Osteoarthritis
    • Osteophytes
    • “Seagull wing” appearance in erosive OA Erosive OA Osteoarthritis (due to central subchondral erosions Subchondral Erosions Ankylosing Spondylitis)
  • Insensitive for early disease
  • Findings do not correlate well with symptoms.
  • Kellgren-Lawrence classification of osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis (widely accepted scale Scale Dermatologic Examination of osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis severity):^[11,12]
    • Grade 0: no radiologic findings of osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
    • Grade 1: possible osteophytic lipping, doubtful joint space narrowing
    • Grade 2: definite osteophytes, possible joint space narrowing
    • Grade 3: moderate multiple osteophytes, definite narrowing of joint space and some sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor, and possible deformity Deformity Examination of the Upper Limbs of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types ends
    • Grade 4: large osteophytes, marked narrowing of joint space, severe sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor, and definite deformity Deformity Examination of the Upper Limbs of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types ends.
• Magnetic resonance imaging (MRI)^[10–12]
  • Order if radiographs are normal or reveal a joint effusion Joint Effusion Septic Arthritis with persistent pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.
  • More sensitive for early disease
  • Additional findings:
    • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology defects
    • Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis lesions
    • Joint effusions

Supporting workup

The following tests are not used for the diagnosis of OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis, but are used to exclude other causes of arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis.

• Arthrocentesis Arthrocentesis Puncture and aspiration of fluid (e.g., synovial fluid) from a joint cavity. It is used sometimes to irrigate or administer drugs into a joint cavity. Septic Arthritis with synovial fluid analysis Synovial Fluid Analysis Rheumatoid Arthritis (can use US or fluoroscopy Fluoroscopy Production of an image when x-rays strike a fluorescent screen. X-rays)^[10,12]
  • Non-inflammatory with a WBC count < 2,000 cells/μL
  • Crystal analysis to rule out gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout and pseudogout
• Laboratory testing^[12]
  • Negative rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis ( RF RF Rheumatoid Arthritis) and anti-cyclic citrullinated peptide (anti-CCP)
  • Normal erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess) or C-reactive protein (CRP)
  • Negative antinuclear antibody (ANA)

Management

The goals of management include alleviating pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and minimizing the loss of physical function. Therapy is individualized and different methods are used. The following recommendations are based on US, UK, and international guidelines.

Medical management

Initial assessment:^[14,15]

• Locate the sites of OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
• Identify comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
• Clinical status:
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, severity, and functional limitations Limitations Conflict of Interest
  • Misalignment, effusion, and instability
• Emotional status:
  • Social network
  • Mood
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement
  • Health beliefs and expectations

Core approaches (all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):^[13‒15]

• Lifestyle modifications:
  • Minimize weight-bearing (utilizing proper assistive device).
  • Avoid a slumping posture while sitting.
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep on a firm bed.
  • Wear supportive shoes.
• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery:^[8,12,13]
  • Improves overall quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life and physical function
  • Generally, ≥ 5% weight loss Weight loss Decrease in existing body weight. Bariatric Surgery has clinical benefits.
• Consider early referral to physical therapy Physical Therapy Becker Muscular Dystrophy.
• Physiotherapy Physiotherapy Spinal Stenosis (structured land-based exercises, with aquatic exercises as alternative) to increase:
  • Strength
  • Flexibility
  • Range of motion Range of motion The distance and direction to which a bone joint can be extended. Range of motion is a function of the condition of the joints, muscles, and connective tissues involved. Joint flexibility can be improved through appropriate muscle strength exercises. Examination of the Upper Limbs
  • Endurance
• Assistive devices (remove or redistribute the load on the joint):
  • Cane
  • Tibiofemoral knee brace
  • 1st carpometacarpal Carpometacarpal The articulations between the carpal bones and the metacarpal bones. Wrist Joint: Anatomy joint orthoses 
  • Splints 
  • Taping
• Hot and cold therapy

Pharmacotherapy

Initial medical management: 

• Topical capsaicin/ nonsteroidal antiinflammatory drugs Nonsteroidal Antiinflammatory Drugs Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs) ( NSAIDs NSAIDS Primary vs Secondary Headaches) (knee, hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy)^[8,13,14]
• Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen (knee, hip, hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy)^[13‒16]
• Oral (nonselective) ( NSAIDs NSAIDS Primary vs Secondary Headaches (knee, hip, hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy)^[13‒16]
  • Diclofenac Diclofenac A non-steroidal anti-inflammatory agent (nsaid) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Nonsteroidal Antiinflammatory Drugs (NSAIDs) (1st choice)^[12,17]
  • Naproxen Naproxen An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. Nonsteroidal Antiinflammatory Drugs (NSAIDs) (2nd choice)
• COX-2 inhibitors (GI protective)

2nd-line medical therapy:^[13‒16]

• Combine 2 of the initial treatments.
• Duloxetine Duloxetine A thiophene derivative and selective neurotransmitter uptake inhibitor for serotonin and noradrenaline (SNRI). It is an antidepressant agent and anxiolytic, and is also used for the treatment of pain in patients with diabetes mellitus and fibromyalgia. Serotonin Reuptake Inhibitors and Similar Antidepressants:^[12]
  • Antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants with analgesic effect
  • Can be used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to NSAIDs NSAIDS Primary vs Secondary Headaches
  • Alternative for those who do not respond to the above interventions
• Corticosteroids Corticosteroids Chorioretinitis:
  • Should not be used chronically
  • Can be used orally or as an intra-articular injection
  • Consider intra-articular corticosteroid injections in the following:
    • Knee OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
    • Hip OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis should be performed under ultrasound guidance.
    • Should not be performed in the 3 months leading up to joint replacement surgery
• Hyaluronic acid Hyaluronic acid A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidase bonds. It is found in the umbilical cord, in vitreous body and in synovial fluid. A high urinary level is found in progeria. Connective Tissue: Histology:^{[8,9,13‒16]}
  • Intra-articular injection
  • Controversial, and evidence is limited
• Supplements:^[8,12‒16]
  • Glucosamine, chondroitin, turmeric, ginger extract, and vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies may reduce pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in knee OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis.
  • Evidence is limited.
• Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics:^[12‒17]
  • Generally best to avoid in most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis but can be considered for short-term use.
  • Tramadol Tramadol A narcotic analgesic proposed for severe pain. It may be habituating. Opioid Analgesics may be beneficial for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship for whom other treatments have failed or who are not candidates for other treatments (e.g., other agents are contraindicated).
  • Non-tramadol opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics may be used when other agents have been exhausted, but these carry the risk of toxicity Toxicity Dosage Calculation and dependence.
  • Consider referral to a chronic pain Chronic pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. Pain Management management clinic.

Important pharmacotherapy considerations

• Prescribe the lowest effective dose of acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen, NSAIDs NSAIDS Primary vs Secondary Headaches, COX-2 inhibitors, or opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics for the shortest possible time.
• Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen: Use the lowest effective dose, preferably  ≤ 3 g/day (because of hepatotoxicity Hepatotoxicity Acetaminophen).^[12–15]
• NSAIDs NSAIDS Primary vs Secondary Headaches/COX-2 inhibitors:^[8,14,15]
  • Use with caution in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cardiovascular disease, chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease, or gastrointestinal (GI) comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus.
  • Consider adding a proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitor in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have GI comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus.
  • Avoid in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with estimated GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests < 30 mL/min/1.73 m²

Surgical management^[12,17]

• Reserved for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with advanced disease who have failed other treatments
• Total joint arthroplasty Total Joint Arthroplasty Osteoarthritis (replacement) is the most common procedure.

Differential Diagnosis

• Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: an autoimmune disease of the joints, causing an inflammatory and destructive arthritis Destructive Arthritis Juvenile Idiopathic Arthritis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically have swelling Swelling Inflammation and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways of the peripheral joints (e.g., hands, wrists, knees, ankles). The DIP joints are generally spared, and morning stiffness typically lasts > 60 minutes. Diagnosis is based on the clinical picture, inflammatory markers, RF RF Rheumatoid Arthritis, and anti-CCP. Management starts with glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-Modifying Antirheumatic Drugs (DMARDs) ( DMARDs DMARDs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-Modifying Antirheumatic Drugs (DMARDs)), and NSAIDs NSAIDS Primary vs Secondary Headaches.
• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: a spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis that is often precipitated by a gastrointestinal or genitourinary infection. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with an asymmetric arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, typically of the lower extremities. Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis can be associated with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tendinitis Tendinitis Ankylosing Spondylitis, enthesitis Enthesitis Ankylosing Spondylitis, mucocutaneous ulcers, and conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis. Diagnosis is clinical. Management includes NSAIDs NSAIDS Primary vs Secondary Headaches, DMARDs DMARDs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-Modifying Antirheumatic Drugs (DMARDs), and treatment of the infection. 
• Psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis: a spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis that occurs in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis. This inflammatory arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis is frequently asymmetric. Small and large joints are involved, including the DIP joints and the sacroiliac spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy. Enthesopathy Enthesopathy Reactive Arthritis and dactylitis Dactylitis Ankylosing Spondylitis are also seen. The diagnosis is clinical, and should be suspected in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis. Management includes DMARDs DMARDs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-Modifying Antirheumatic Drugs (DMARDs) and biologic agents Biologic Agents Immunosuppressants.
• Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout: a disease caused by hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout that leads to arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis from precipitation of monosodium urate crystals Monosodium Urate Crystals Gout in the joints. Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout is often monoarticular, and usually involves pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, tenderness, swelling Swelling Inflammation, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, and warmth of the first MTP joint. The diagnosis is made with identification Identification Defense Mechanisms of negatively birefringent, needle-shaped crystals in the synovial fluid. Management includes NSAIDs NSAIDS Primary vs Secondary Headaches, colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs, corticosteroids Corticosteroids Chorioretinitis, and uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis reduction with allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs.
• Pseudogout: intra-articular calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes pyrophosphate deposition. The etiology is not clear. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with acute flares of joint swelling Swelling Inflammation, warmth, and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Pseudogout usually affects larger joints, such as the knee. Diagnosis is with identification Identification Defense Mechanisms of positively birefringent, rhomboid crystals in the synovial fluid. Management includes NSAIDs NSAIDS Primary vs Secondary Headaches, corticosteroids Corticosteroids Chorioretinitis, and colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs.
• Septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: a joint infection due to bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology (rarely, viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology) in the synovial or periarticular tissues. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with an acute onset of monoarticular swelling Swelling Inflammation, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, and warmth. Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever may also be present. Diagnosis is made with synovial fluid analysis Synovial Fluid Analysis Rheumatoid Arthritis, including Gram stain Gram stain Klebsiella, culture, and WBC count > 20,000 cells/μL. Management includes intravenous antibiotics and drainage of pus from the joint.