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Rheumatoid Arthritis

Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder Autoimmune Disorder Septic Arthritis. Presentation occurs most commonly in middle-aged women with joint 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, and morning stiffness (often in the hands). Systemic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation can lead to extraarticular manifestations such as rheumatoid nodules, interstitial lung disease, Felty syndrome, and pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis. Prolonged and severe disease can lead to irreversible joint deformities. Diagnosis is based on strong clinical suspicion and confirmed by the presence of rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions, and characteristic imaging. Management involves long-term 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)), biologic agents Biologic Agents Immunosuppressants, and physical therapy Physical Therapy Becker Muscular Dystrophy. 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 and 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) are the treatment of choice for acute exacerbation.

Last updated: 11 Jul, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Epidemiology and Risk Factors

Epidemiology

  • Worldwide 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: 3 per 10,000 people per year
  • More prevalent in:
    • Native Americans
    • North America
    • Northern Europe
  • 2–3 times more common in women
  • Peak age of presentation is 30–50-years-old.

Risk factors

The cause of rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (RA) is unknown, but several risk factors play a role.

  • Genetic predisposition:
  • Environmental factors:
    • Lifestyle:
      • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 
      • 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 
    • Hormonal
    • Infectious Infectious Febrile Infant:
      • Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus ( EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus)
      • Parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19
      • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C 
      • Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
      • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia. Mycoplasma
      • Recurrent dental infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Pathophysiology

  • Not completely understood
  • An external trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation sets off the autoimmune response and ↑ expression of enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes that convert arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle to citrulline Citrulline Urea Cycle → creation of antigens
  • B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions produce antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions to citrullinated proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis bind BIND Hyperbilirubinemia of the Newborn to fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis 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 complement activation Complement Activation The sequential activation of serum complement proteins to create the complement membrane attack complex. Factors initiating complement activation include antigen-antibody complexes, microbial antigens, or cell surface polysaccharides. Systemic Lupus Erythematosus
  • Synovium is infiltrated by immune cells (e.g., macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation, B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions, CD4 T cells CD4+ T cells A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T cells: Types and Functions) → cytokine and chemokine production → synovial membrane Synovial Membrane The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. Hip Joint: Anatomy thickening and villus formation
  • Hyperplastic Hyperplastic Colon Polyps synovial tissue ( pannus Pannus A genus of cyanobacteria in the family synechococcaceae that is free-floating and occurs in various water environments attaching to algae and submersed plants. Septic Arthritis) releases: 
    • Collagenase
    • Stromelysin
    • Interleukins Interleukins Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins (IL)
    • Tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF))-alpha
  • Leads to:
    • Continued synovial inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • 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
    • Osteoclasts-mediated 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 destruction

Clinical Presentation

Articular manifestations

  • Symptoms:
  • Characteristics:
    • Gradual onset
    • Polyarticular
    • Symmetric
  • Commonly affected joints:
    • Wrists
    • 2nd and 3rd metacarpophalangeal (MCP) joints
    • Proximal interphalangeal (PIP) joints
    • Metatarsophalangeal (MTP) joints
    • Shoulders
    • Elbows
    • Hips
    • Knees
    • Ankles
  • Atlantoaxial subluxation Subluxation Radial Head Subluxation (Nursemaid’s Elbow) can occur in 20%–50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and shoulder stiffness and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Radiculopathy
  • Note: Distal interphalangeal (DIP) and carpometacarpal Carpometacarpal The articulations between the carpal bones and the metacarpal bones. Wrist Joint: Anatomy (CMC) joints are typically spared.

Physical exam

  • General:
    • Synovitis:
      • Joint tenderness
      • Swelling
      • Effusions may be noted in larger joints.
    • Interosseous muscle atrophy
    • Joint deformities
    • ↓ Range of motion
  • Common hand findings:
    • ↓ Grip strength
    • Ulnar deviation of MCP joints
    • Boutonniere deformity:
      • PIP flexion
      • DIP hyperextension
    • Swan neck deformity:
      • PIP hyperextension
      • DIP flexion
    • Hitchhiker thumb (“Z” deformity Deformity Examination of the Upper Limbs): 
    • Bowstring sign: prominence of the tendons in the extensor compartment of the 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
  • Common lower extremity findings:
    • Restricted hip movement
    • Baker’s cyst:
      • Caused by large knee effusions
      • Cyst caused by entrapment of the synovium between articular structures.
      • Swelling Swelling Inflammation or fullness will be noted behind the knee.
      • Also seen in 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, trauma, 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 meniscal tears
    • Hammertoe: MTP joint hyperextension

Extraarticular manifestations

  • General:
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • 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
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
  • Cutaneous:
    • Rheumatoid nodules:
      • Not painful
      • Seen on extensor surface of the elbow, heel, ischial tuberosities, and fingers
      • Can also occur in the viscera 
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions ulcers
    • Neutrophilic dermatosis:
  • Ocular: 
    • Sjögren syndrome ( keratoconjunctivitis Keratoconjunctivitis Simultaneous inflammation of the cornea and conjunctiva. Stevens-Johnson Syndrome sicca)
    • Episcleritis
    • Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
  • Neurologic:
    • Myelopathy and radiculopathy
    • Mononeuritis multiplex Mononeuritis Multiplex Chronic Diabetic Complications or polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy
    • Carpal tunnel Carpal Tunnel The carpal tunnel is formed by the transverse carpal ligament (flexor retinaculum) superiorly and the carpal bones inferiorly. Carpal Tunnel Syndrome syndrome
    • Depression
  • Respiratory:
    • Interstitial lung disease
    • Upper airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction due to:
      • Cricoarytenoid Cricoarytenoid Larynx: Anatomy arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
      • Rheumatoid nodules of the vocal cords Vocal cords A pair of cone-shaped elastic mucous membrane projecting from the laryngeal wall and forming a narrow slit between them. Each contains a thickened free edge (vocal ligament) extending from the thyroid cartilage to the arytenoid cartilage, and a vocal muscle that shortens or relaxes the vocal cord to control sound production. Larynx: Anatomy
    • Pleuritis Pleuritis Pleuritis, also known as pleurisy, is an inflammation of the visceral and parietal layers of the pleural membranes of the lungs. The condition can be primary or secondary and results in sudden, sharp, and intense chest pain on inhalation and exhalation. Pleuritis
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
    • Pulmonary nodules Pulmonary nodules A number of small lung lesions characterized by small round masses of 2- to 3-mm in diameter. They are usually detected by chest ct scans. Such nodules can be associated with metastases of malignancies inside or outside the lung, benign granulomas, or other lesions. Granulomatosis with Polyangiitis
  • Cardiac:
    • Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
    • Pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
    • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
    • Pericardial effusion Pericardial effusion Fluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
    • Valvular insufficiency (from rheumatoid nodules)
    • Conduction abnormalities (from rheumatoid nodules) 
  • Vascular:
    • Vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus
    • Peripheral vascular disease
    • Deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus 
  • Hematologic:
    • Felty syndrome:
      • RA
      • Neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia
      • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types of chronic disease
Isolated rheumatoid nodules

Rheumatoid nodules in RA:
Firm, non-tender, subcutaneous swelling Swelling Inflammation on the extensor surface of the elbow in a RA patient

Image: “Right elbow” by Department of Medicine, Woodhull Medical Center, Brooklyn, NY 11206, USA. License: CC BY 3.0

Diagnosis

Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (RA) diagnosis is based on high clinical suspicion and confirmed by serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus and imaging.

Laboratory testing

  • General:
    • Complete blood count (CBC):
      • ↓ Hemoglobin → anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types of chronic disease
      • Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
      • Neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia → Felty syndrome
      • Mild leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus may be present.
    • Inflammatory markers:
      • Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess
      • ↑ C-reactive protein (CRP)
      • Ferritin Ferritin Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store iron in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (apoferritins) made of 24 subunits of various sequences depending on the species and tissue types. Hereditary Hemochromatosis
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus:
    • Rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis (RF):
      • Present in 70%–80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
      • RF is present in 15% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without RA.
    • Anti-cyclic citrullinated peptide (anti-CCP) antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions: highly specific
    • Antinuclear antibody (ANA): 
      • Nonspecific
      • Positive in 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Synovial fluid analysis:
    • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus (5,000–50,000 cells/microliter) with neutrophil predominance
    • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
    • Gram stain Gram stain Klebsiella and gram culture both negative
    • Negative for crystals

Imaging

Management and Prognosis

Management

The goal is to prevent deformity Deformity Examination of the Upper Limbs and permanent damage. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be referred to a rheumatologist.

Nonpharmacological therapies:

Acute exacerbation management:

  • 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)
  • 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:
    • Can be used as a bridge to disease-modifying antirheumatic drug ( DMARD DMARD 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)) therapy or for acute flares
    • Options: systemic or intraarticular injection

Long-term pharmacological therapy:

  • 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):
    • Should be initiated in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship upon diagnosis
    • Methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy is usually the 1st choice.
    • Additional options: sulfasalazine Sulfasalazine A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid released in the colon. Sulfonamides and Trimethoprim, hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants, azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants, leflunomide Leflunomide An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of rheumatoid arthritis. Disease-Modifying Antirheumatic Drugs (DMARDs)
  • TNF-alpha inhibitors:
  • Other biologic therapy options:
    • IL-6 inhibitors ( tocilizumab Tocilizumab Immunosuppressants)
    • CD20 monoclonal antibody ( rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants)
    • Selective T cell costimulation Costimulation Adaptive Cell-mediated Immunity blocker ( abatacept Abatacept A fusion protein immunoconjugate of the extracellular domain of ctla4 and the fc domain of human igg1. It functions as a t-cell co-stimulation blocker that inhibits tnf-alpha and prevents the activation of T-lymphocytes. It is used in the treatment of rheumatoid arthritis. Immunosuppressants)

Surgery:

  • Indicated for severe damage and limited function
  • Can be considered if pharmacologic therapy is unsuccessful
  • Options:
    • Joint replacement
    • Joint fusion
    • Synovectomy

Additional considerations:

  • While on glucocorticoid treatment, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be monitored for:
    • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
    • 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
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Appropriate vaccinations should be given to prevent infectious Infectious Febrile Infant complications of immunosuppressive medications.
  • All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be screened for tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis and hepatitis.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship require ongoing laboratory monitoring for drug toxicity Toxicity Dosage Calculation:
    • CBC
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function
    • Creatinine
  • Cervical 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 imaging prior to surgical procedures:

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • RA is a chronic, progressive disease:
  • Associated with an increased risk of:
    • Cardiovascular disease
    • Infection
    • Respiratory disease
    • Gastrointestinal bleeding Gastrointestinal bleeding Gastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding
    • Lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum (especially with Felty syndrome)
  • 2–3 times higher risk of death than the general population
  • Risk factors for a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:

Differential Diagnosis

  • 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): a “wear and tear” form of arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis due to 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 and changes of the subchondral 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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop gradual joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, stiffness lasting < 30 minutes, and decreased 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. The PIP, DIP, and CMC joints are frequently affected. Diagnosis is clinical and supported with radiographic joint findings. Inflammatory markers, RF, and anti-CCP are negative. Management includes analgesics, intraarticular steroid injections, and surgery for advanced 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: 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, which leads to arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis from the 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 1st MTP joint. Diagnosis is confirmed by the 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: intraarticular 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 with unclear etiology. 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 confirmed by the 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.
  • Psoriatic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: a spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis occurring 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. Psoriatic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis is inflammatory, frequently asymmetric, and involves both small and large joints, including 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. Symptoms may also include enthesopathy Enthesopathy Reactive Arthritis and dactylitis Dactylitis Ankylosing Spondylitis. 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.
  • Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis: a spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis 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 asymmetric arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, typically of the lower extremities. Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis 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 and 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.

References

  1. Firestein, G.S., and Guma, M. (2020). Pathogenesis of rheumatoid arthritis. In Romain, P.L. (Ed.), Uptodate. Retrieved February 5, 2021, from https://www.uptodate.com/contents/pathogenesis-of-rheumatoid-arthritis
  2. Venables, P.W.J., and Bchir, M.B. (2019). Clinical manifestations of rheumatoid arthritis. In Romain, P.L. (Ed.), Uptodate. Retrieved February 5, 2021, from https://www.uptodate.com/contents/clinical-manifestations-of-rheumatoid-arthritis
  3. Matteson, E.L., and Davis, J.M. (2021). Overview of the systemic and nonarticular manifestations of rheumatoid arthritis. In Romain, P.L. (Ed.), Uptodate. Retrieved February 5, 2021, from https://www.uptodate.com/contents/overview-of-the-systemic-and-nonarticular-manifestations-of-rheumatoid-arthritis
  4. Cohen, S., and Mikulus, T.R. (2020). Initial treatment of rheumatoid arthritis in adults. In Romain, P.L. (Ed.), Uptodate. Retrieved February 5, 2021, from https://www.uptodate.com/contents/initial-treatment-of-rheumatoid-arthritis-in-adults
  5. Kontzias, A. (2020). Rheumatoid arthritis (RA). [online] MSD Manual Professional Version. Retrieved February 5, 2021, from https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/joint-disorders/rheumatoid-arthritis-ra
  6. Smith, H.R., and Brown, A. (2020). Rheumatoid arthritis (RA). In Diamond. H.S. (Ed.), Medscape. Retrieved February 5, 2021, from https://emedicine.medscape.com/article/331715-overview
  7. Chauhan, K., Jandu, J.S., Goyal, A., Bansal, P., and Al-Dhahir, M.A. Rheumatoid arthritis. [online] StatPearls. Retrieved February 5, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK441999/

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