Epidemiology and Risk Factors

Epidemiology

• WorldwideincidenceIncidenceThe 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 rheumatoidarthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis (RA) is unknown, but several risk factors play a role.

• Genetic predisposition:
  • 2–3 times more likely in those with a 1st-degree relative with RA
  • Associated with:
    • HLA-DR1
    • HLA-DR4HLA-DR4Goodpasture Syndrome
• Environmental factors:
  • Lifestyle:
    • CigarettesmokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases 
    • ObesityObesityObesity 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:
    • Epstein-Barr virusEpstein-Barr VirusEpstein-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 (EBVEBVEpstein-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 B19Parvovirus B19Primate 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 BHepatitis BHepatitis 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 
    • RubellaRubellaAn 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
    • MycoplasmaMycoplasmaMycoplasma 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 dentalinfectionsInfectionsInvasion 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 externaltriggerTriggerThe type of signal that initiates the inspiratory phase by the ventilatorInvasive Mechanical Ventilation sets off the autoimmune response and ↑ expression ofenzymesEnzymesEnzymes 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 convertarginineArginineAn essential amino acid that is physiologically active in the l-form.Urea Cycle tocitrullineCitrullineUrea Cycle → creation of antigens
• B cellsB cellsLymphoid 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 produceantibodiesAntibodiesImmunoglobulins (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 citrullinatedproteinsProteinsLinear 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 →bindBINDHyperbilirubinemia of the Newborn tofibrinogenFibrinogenPlasma 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 andcollagenCollagenA 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 activationComplement ActivationThe 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.,macrophagesMacrophagesThe 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 cellsMast cellsGranulated 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 cellsB cellsLymphoid 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 cellsCD4+ T cellsA 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 membraneSynovial MembraneThe 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
• HyperplasticHyperplasticColon Polyps synovial tissue (pannusPannusA 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
  • InterleukinsInterleukinsInterleukins 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)
  • TumorTumorInflammationnecrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage factor (TNFTNFTumor 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 synovialinflammationInflammationInflammation 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
  • CartilageCartilageCartilage 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-mediatedboneBoneBone 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:
  • JointpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
  • JointswellingSwellingInflammation
  • Early morning stiffness ( > 1 hour)
• 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
• AtlantoaxialsubluxationSubluxationRadial Head Subluxation (Nursemaid’s Elbow) can occur in 20%–50% ofpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship:
  • NeckNeckThe part of a human or animal body connecting the head to the rest of the body.Peritonsillar Abscess and shoulder stiffness andpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
  • Radiculopathy
• Note: Distal interphalangeal (DIP) andcarpometacarpalCarpometacarpalThe articulations between the carpal bones and the metacarpal bones.Wrist Joint: Anatomy (CMC) joints are typically spared.

Physical exam

• General:
  • Synovitis:
    • Joint tenderness
    • SwellingSwellingInflammation
    • Effusions may be noted in larger joints.
  • Interosseous muscleatrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation
  • Joint deformities
  • ↓Range of motionRange of motionThe 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
• CommonhandHandThe 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 findings:
  • ↓ Grip strength
  • Ulnar deviation of MCP joints
  • BoutonnieredeformityDeformityExamination of the Upper Limbs:
    • PIPflexionFlexionExamination of the Upper Limbs
    • DIP hyperextension
  • SwanneckNeckThe part of a human or animal body connecting the head to the rest of the body.Peritonsillar AbscessdeformityDeformityExamination of the Upper Limbs:
    • PIP hyperextension
    • DIPflexionFlexionExamination of the Upper Limbs
  • Hitchhiker thumb (“Z”deformityDeformityExamination of the Upper Limbs):
    • MCPflexionFlexionExamination of the Upper Limbs
    • Interphalangeal joint (IP) hyperextension
  • Bowstring sign: prominence of the tendons in the extensor compartment of thehandHandThe 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 cyst:
    • Caused by large knee effusions
    • Cyst caused by entrapment of the synovium between articular structures.
    • SwellingSwellingInflammation or fullness will be noted behind the knee.
    • Also seen inosteoarthritisOsteoarthritisOsteoarthritis (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,goutGoutGout 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:
  • FatigueFatigueThe 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
  • FeverFeverFever 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 lossWeight lossDecrease in existing body weight.Bariatric Surgery
  • MyalgiasMyalgiasPainful 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 
  • SkinSkinThe 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:
    • SterileSterileBasic Procedures neutrophil infiltration 
    • Symmetric, erythematous papules
• Ocular:
  • Sjögren syndrome (keratoconjunctivitisKeratoconjunctivitisSimultaneous inflammation of the cornea and conjunctiva.Stevens-Johnson Syndrome sicca)
  • Episcleritis
  • UveitisUveitisUveitis 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 multiplexMononeuritis MultiplexChronic Diabetic Complications orpolyneuropathyPolyneuropathyPolyneuropathy 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 tunnelCarpal TunnelThe 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 obstructionUpper Airway ObstructionAirway Obstruction due to:
    • CricoarytenoidCricoarytenoidLarynx: AnatomyarthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis
    • Rheumatoid nodules of thevocal cordsVocal cordsA 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
  • PleuritisPleuritisPleuritis, 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 effusionPleural EffusionPleural 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 nodulesPulmonary nodulesA 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 infarctionMyocardial infarctionMI 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
  • PericarditisPericarditisPericarditis 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
  • MyocarditisMyocarditisMyocarditis 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 effusionPericardial effusionFluid 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:
  • VasculitisVasculitisInflammation 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 veinthrombosisThrombosisFormation and development of a thrombus or blood clot in the blood vessel.Epidemic Typhus 
• Hematologic:
  • Felty syndrome:
    • RA
    • NeutropeniaNeutropeniaNeutrophils 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
    • SplenomegalySplenomegalySplenomegaly 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
  • AnemiaAnemiaAnemia 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

Diagnosis

RheumatoidarthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis (RA) diagnosis is based on high clinical suspicion and confirmed byserologySerologyThe study of serum, especially of antigen-antibody reactions in vitro.Yellow Fever Virus and imaging.

Laboratory testing

• General:
  • Complete blood count (CBC):
    • ↓ Hemoglobin →anemiaAnemiaAnemia 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
    • ↑PlateletsPlateletsPlatelets 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
    • NeutropeniaNeutropeniaNeutrophils 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
    • MildleukocytosisLeukocytosisA transient increase in the number of leukocytes in a body fluid.West Nile Virus may be present.
  • Inflammatory markers:
    • ↑Erythrocyte sedimentation rateErythrocyte Sedimentation RateSoft Tissue Abscess (ESRESRSoft Tissue Abscess) 
    • ↑ C-reactive protein (CRP)
    • ↑FerritinFerritinIron-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
• SerologySerologyThe study of serum, especially of antigen-antibody reactions in vitro.Yellow Fever Virus:
  • Rheumatoid factorRheumatoid factorAntibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins.Autoimmune Hepatitis (RF):
    • Present in 70%–80% ofpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
    • RF is present in 15% ofpatientsPatientsIndividuals 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)antibodiesAntibodiesImmunoglobulins (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% ofpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
• Synovial fluid analysis:
  • LeukocytosisLeukocytosisA transient increase in the number of leukocytes in a body fluid.West Nile Virus (5,000–50,000 cells/microliter) with neutrophil predominance
  • ↓GlucoseGlucoseA 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 stainGram stainKlebsiella and gram culture both negative
  • Negative for crystals

Imaging

• Radiographs:
  • May be normal in early disease
  • Soft tissueSoft TissueSoft Tissue AbscessswellingSwellingInflammation
  • PeriarticularosteopeniaOsteopeniaOsteoporosis
  • BonyerosionErosionPartial-thickness loss of the epidermisGeneralized and Localized Rashes
  • Joint-space narrowing
  • JointsubluxationSubluxationRadial Head Subluxation (Nursemaid’s Elbow)
• Ultrasonography:
  • ErosionErosionPartial-thickness loss of the epidermisGeneralized and Localized Rashes
  • Joint-space narrowing
  • Synovitis
• Magnetic resonance imaging (MRI):
  • More sensitive than radiographs
  • DetectserosionErosionPartial-thickness loss of the epidermisGeneralized and Localized Rashes earlier
  • Evaluates hypertrophic and inflamed synovial tissue

Management and Prognosis

Management

The goal is to preventdeformityDeformityExamination of the Upper Limbs and permanent damage.PatientsPatientsIndividuals 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:

• Physical andoccupational therapyOccupational TherapySkilled treatment that helps individuals achieve independence in all facets of their lives. It assists in the development of skills needed for independent living.Fetal Alcohol Spectrum Disorder
• SmokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases cessation

Acute exacerbation management:

• Nonsteroidal antiinflammatory drugsNonsteroidal Antiinflammatory DrugsNonsteroidal 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) (NSAIDsNSAIDSPrimary vs Secondary Headaches)
• GlucocorticoidsGlucocorticoidsGlucocorticoids 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 (DMARDDMARDDisease-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:

• DMARDsDMARDsDisease-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 allpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship upon diagnosis
  • MethotrexateMethotrexateAn 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:sulfasalazineSulfasalazineA 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,hydroxychloroquineHydroxychloroquineA 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,azathioprineAzathioprineAn 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,leflunomideLeflunomideAn 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:
  • May be added ifDMARDDMARDDisease-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 is not effective
  • Options:etanerceptEtanerceptA recombinant version of soluble human tnf receptor fused to an IgG Fc fragment that binds specifically to tumor necrosis factor and inhibits its binding with endogenous tnf receptors. It prevents the inflammatory effect of tnf and is used to treat rheumatoid arthritis; psoriatic arthritis and ankylosing spondylitis.Immunosuppressants,adalimumabAdalimumabA humanized monoclonal antibody that binds specifically to tnf-alpha and blocks its interaction with endogenous tnf receptors to modulate inflammation. It is used in the treatment of rheumatoid arthritis; psoriatic arthritis; Crohn’s disease and ulcerative colitis.Disease-Modifying Antirheumatic Drugs (DMARDs),infliximabInfliximabA chimeric monoclonal antibody to tnf-alpha that is used in the treatment of rheumatoid arthritis; ankylosing spondylitis; psoriatic arthritis and Crohn’s disease.Disease-Modifying Antirheumatic Drugs (DMARDs),golimumabGolimumabDisease-Modifying Antirheumatic Drugs (DMARDs),certolizumabCertolizumabDisease-Modifying Antirheumatic Drugs (DMARDs)
• Other biologic therapy options:
  • IL-6 inhibitors (tocilizumabTocilizumabImmunosuppressants)
  • CD20 monoclonal antibody (rituximabRituximabA 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 cellcostimulationCostimulationAdaptive Cell-mediated Immunity blocker (abataceptAbataceptA 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,patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship should be monitored for:
  • OsteoporosisOsteoporosisOsteoporosis 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
  • DiabetesDiabetesDiabetes 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
  • HypertensionHypertensionHypertension, 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 complications of immunosuppressive medications.
• AllpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship should be screened fortuberculosisTuberculosisTuberculosis (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.
• PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship require ongoing laboratory monitoring for drugtoxicityToxicityDosage Calculation:
  • CBC
  • LiverLiverThe 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
• CervicalspineSpineThe 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:
  • Evaluate for cervicalsubluxationSubluxationRadial Head Subluxation (Nursemaid’s Elbow) (most often at the atlantoaxial joint).
  • IntubationIntubationPeritonsillar Abscess can be fatal in those with cervical instability.

PrognosisPrognosisA 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:
  • The majority ofpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient RelationshiprelapseRelapseRelapsing Fever.
  • 10% will be severely disabled despite adequate management.
• Associated with an increased risk of:
  • Cardiovascular disease
  • Infection
  • Respiratory disease
  • Gastrointestinal bleedingGastrointestinal bleedingGastrointestinal 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
  • LymphomaLymphomaA general term for various neoplastic diseases of the lymphoid tissue.Imaging of the Mediastinum (especially with Felty syndrome)
• 1.5–3 times higher risk of death than the general population
• Risk factors for a poorprognosisPrognosisA 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:
  • Extraarticular manifestations
  • Advanced age
  • Women
  • Caucasians
  • EarlyerosionErosionPartial-thickness loss of the epidermisGeneralized and Localized Rashes on imaging
  • CigarettesmokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases
  • High inflammatory markers and/or antibody titers
  • ≥ 20 affected joints

Differential Diagnosis

• OsteoarthritisOsteoarthritisOsteoarthritis (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 (OAOAOsteoarthritis (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 ofarthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis due tocartilageCartilageCartilage 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 thesubchondral boneSubchondral BoneOsteochondritis Dissecans.PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship develop gradual jointpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways, stiffness lasting < 30 minutes, and decreasedrange of motionRange of motionThe 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.
• GoutGoutGout 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 byhyperuricemiaHyperuricemiaExcessive 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 toarthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis from the precipitation ofmonosodium urate crystalsMonosodium Urate CrystalsGout in the joints.GoutGoutGout 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 involvespainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways, tenderness,swellingSwellingInflammation,erythemaErythemaRedness 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 theidentificationIdentificationDefense Mechanisms of negatively birefringent, needle-shaped crystals in the synovial fluid. Management includesNSAIDsNSAIDSPrimary vs Secondary Headaches,colchicineColchicineA 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,corticosteroidsCorticosteroidsChorioretinitis, anduric acidUric acidAn 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 withallopurinolAllopurinolA xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms.Gout Drugs.
• Pseudogout: intraarticularcalciumCalciumA 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.PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship present with acute flares of jointswellingSwellingInflammation, warmth, andpainPainAn 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 theidentificationIdentificationDefense Mechanisms of positively birefringent, rhomboid crystals in the synovial fluid. Management includesNSAIDsNSAIDSPrimary vs Secondary Headaches,corticosteroidsCorticosteroidsChorioretinitis, andcolchicineColchicineA 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 arthritisPsoriatic ArthritisA 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: aspondyloarthropathySpondyloarthropathyAnkylosing Spondylitis occurring inpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship withpsoriasisPsoriasisPsoriasis 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 arthritisPsoriatic ArthritisA 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 is inflammatory, frequently asymmetric, and involves both small and large joints, including DIP joints and the sacroiliacspineSpineThe 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 includeenthesopathyEnthesopathyReactive Arthritis anddactylitisDactylitisAnkylosing Spondylitis. Diagnosis is clinical and should be suspected inpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship withpsoriasisPsoriasisPsoriasis 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 includesDMARDsDMARDsDisease-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) andbiologic agentsBiologic AgentsImmunosuppressants.
• ReactivearthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis:aspondyloarthropathySpondyloarthropathyAnkylosing Spondylitis often precipitated by a gastrointestinal or genitourinary infection.PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship may present with asymmetricarthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis, typically of the lower extremities. ReactivearthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis can be associated withfeverFeverFever 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,tendinitisTendinitisAnkylosing Spondylitis,enthesitisEnthesitisAnkylosing Spondylitis, mucocutaneous ulcers, andconjunctivitisConjunctivitisConjunctivitis 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 includesNSAIDsNSAIDSPrimary vs Secondary Headaches,DMARDsDMARDsDisease-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

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2. England, B. R. (2025). Articular manifestations of rheumatoid arthritis. UpToDate. Retrieved August 14, 2025, fromhttps://www.uptodate.com/contents/articular-manifestations-of-rheumatoid-arthritis
3. Matteson, E.L., and Davis, J.M. (2025). Overview of the systemic and nonarticular manifestations of rheumatoid arthritis. In Romain, P.L. (Ed.), Uptodate. Retrieved August 14, 2025, fromhttps://www.uptodate.com/contents/overview-of-the-systemic-and-nonarticular-manifestations-of-rheumatoid-arthritis
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6. Smith, H.R., and Brown, A. (2023). Rheumatoid arthritis (RA). In Diamond. H.S. (Ed.), Medscape. Retrieved August 14, 2025, fromhttps://emedicine.medscape.com/article/331715-overview
7. Chauhan, K., Jandu, J.S., Goyal, A., Bansal, P., and Al-Dhahir, M.A. (2023). Rheumatoid arthritis. [online] StatPearls. Retrieved August 14, 2025, fromhttps://www.ncbi.nlm.nih.gov/books/NBK441999/