Tumor Necrosis Factor (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 interacts with 2 receptors, which initiate signal transduction pathways leading to different cellular responses ( 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, cell survival, or apoptosis). Inappropriate or unrestrained activation of TNF signaling produces chronic 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, as seen in autoimmune conditions (e.g., rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis, 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). The mechanism of TNF inhibition has been used in treating these inflammatory diseases.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Tumor necrosis factor (TNF)

  • Other names: TNF-ɑ, cachectin
    • Originally, the protein derived from macrophages was named tumor necrosis factor and a second, related, one derived from lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes was named lymphotoxin. 
    • Being bound to the same receptor and sharing similarities in amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids sequences, these proteins were previously called:
      • TNF-α (for TNF)
      • TNF-β (for lymphotoxin)
    • Further studies on the protein sequences now identify multiple members (ligands and receptors) of the TNF superfamily.
  • Major cytokine, released primarily by macrophages in response to stimuli (such as lipopolysaccharides or other toll-like receptor-activating stimuli)
  • Other cells (e.g., T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells, mast cells, fibroblasts) also produce TNF.

General functions of tumor necrosis factor

  • Proinflammatory:
    • Endothelial activation:
      • ↑ Endothelial adhesion molecules (e.g., P-selectin, E-selectin)
      • ↑ Mediators (other cytokines, chemokines, eicosanoids Eicosanoids Eicosanoids are cell-signaling molecules produced from arachidonic acid. With the action of phospholipase A2, arachidonic acid is released from the plasma membrane. The different families of eicosanoids, which are prostaglandins (PGs), thromboxanes (TXA2s), prostacyclin (PGI2), lipoxins (LXs), and leukotrienes (LTs), emerge from a series of reactions catalyzed by different enzymes. Eicosanoids)
      • ↑ Procoagulant activity
    • Activation of immune cells (such as leukocytes)
    • Acute-phase response: lipid and protein mobilization and ↓ appetite (leading to weight loss and cachexia)
  • Cell proliferation and differentiation
  • Apoptosis 
  • Antitumor activity

Tumor Necrosis Factor Superfamily

Members of the superfamily

  • 19 ligands interacting with 29 receptors; each ligand able to interact with > 1 receptor 
  • Proinflammatory properties are predominantly present in the ligands.
  • Most members have protective roles but also have harmful effects (with links to a variety of diseases).

Notable members

  • TNF: 
    • 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 (pyrogenic)
    • Antitumor
    • Mediator of 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 and sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock
  • Lymphotoxin:
    • Mediator of 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
    • Antiviral response
    • Antitumor
    • Control of secondary lymphoid organ development
  • CD40 ligand (CD40L): 
    • Expressed in T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells and interacts with the CD40 on B cells B cells B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells
    • ​​CD40L–CD40 induces B-cell proliferation, class-switch recombination, and somatic hypermutation.
  • Fas ligand (FasL):
    • Expressed in cytotoxic T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells
    • Interaction of FasL and Fas (a death receptor) → Fas-associated protein with death domain (FADD) → caspase 8 activation → apoptosis

Effects of Tumor Necrosis Factor

Induction

  • TNF produced by various cells (predominantly macrophages); stimuli include:
    • Microbial products (e.g., lipopolysaccharide)
    • Dead cells
    • Immune complexes
    • Foreign antigens/bodies
    • Physical injury
    • IL-1
  • Starts initially as membrane-bound (pro-TNF):
    • Then expressed as a transmembrane protein
    • Requires proteolytic cleavage by TNF-α–converting enzyme (TACE) → releasing the soluble form of TNF

Tumor necrosis factor receptors

  • The functions of TNF are mediated by 2 receptor types:
    • TNFR1: 
      • Extensively studied
      • More prevalent
      • Expressed universally on almost all cell types
      • Contains death domain (DD) and is a member of the death receptor family, with capacity to induce apoptotic death
    • TNFR2: 
      • Mainly restricted to immune cells and some tumor cells 
      • Does not have DD, but has TNF-receptor–associated factor (TRAF) binding site
      • Believed to have a role in cell survival and regeneration
  • Receptors trigger distinct, but also interconnected, signaling pathways.

Effects

  • TNF, via TNFR1:
    • Inflammatory effect: 
      • Certain proteins (TNF-receptor type 1–associated death domain (TRADD), TNF-receptor–associated factor 2 (TRAF2), and receptor interacting protein (RIP)) are sequentially recruited.
      • Proinflammatory pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways are activated.
      • NF-κB activation → transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of inflammatory proteins, cell survival and proliferation, induction of antiapoptotic genes
    • Apoptotic effect: 
      • TRADD and FADD are recruited.
      • Activation of caspase 8 is triggered → proteolytic cascade → apoptosis
  • TNF, via TNFR2:
    • TRAF2 is recruited → activation of different pathways, such as NF-κB and MAPK
    • Effects: 
      • Tissue/cell regeneration, proliferation, and survival
      • Host defense against pathogens ( 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)
Tnf-receptor-tnfr-pathway-of-signaling-two-complex-model-is-shown-upon-ligation-with tumor necrosis factor

Tumor necrosis factor (TNF) receptor (TNFR) pathway of signaling:
On the left (labeled as complex I), with ligation of TNF-α, TNFR recruits various adapter molecules, resulting in the activation of nuclear factor kappa-B (NF-κB), which induces several antiapoptotic genes and the survival signal. FLICE inhibitory protein (FLIP) and inhibitor of apoptosis proteins (IAPs) modulate and inhibit the apoptosis pathway.
On the right (labeled as complex II), TNFR without certain adapter proteins (TNF-receptor–associated factor 2 (TRAF2), receptor-interacting protein (RIP)) leads to recruitment of Fas–associated death domain (FADD).
Caspase 8 is activated and released into the cytoplasm, where it activates effector caspases to induce apoptosis.
IKK: IκB kinase

Image: “TNF receptor (TNFR) pathway of signaling” by Gupta S et al. License: CC BY 2.0

Tumor Necrosis Factor and Diseases

Diseases

  • Binding to 2 different receptors, TNF initiates signal transduction pathways that produce varying cellular responses, including cell survival, differentiation, proliferation, and cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death.
  • Inappropriate or unrestrained activation of TNF signaling produces chronic 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 → pathologic complications such as autoimmune diseases 
  • Abnormal secretion of TNF has been associated with:
    • Rheumatoid arthritis
    • Inflammatory bowel disease (Crohn’s disease and ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis)
    • Psoriatic arthritis
    • Psoriasis
    • Noninfectious 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

Anti–tumor necrosis factor therapy

Tumor necrosis factor has multiple biologic effects, and in certain conditions (e.g., rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis), elevated levels of TNF have been noted. The mechanism of TNF inhibition has been used in treating inflammatory diseases.

Table: Indications for anti–tumor necrosis factor therapy
Anti-TNF therapy Mechanism of action Indications
Infliximab Recombinant chimeric antibody (having a murine variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region and a human IgG1 constant region) that binds to TNF, preventing receptor interaction
  • Crohn’s disease
  • Rheumatoid arthritis
  • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis
  • Plaque 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
  • Ulcerative colitis
Etanercept Fusion protein that binds and neutralizes TNF and lymphotoxin
  • Plaque 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
  • Polyarticular juvenile idiopathic arthritis Juvenile Idiopathic Arthritis Juvenile idiopathic arthritis (JIA), formerly known as juvenile rheumatoid arthritis, is a heterogeneous group of inflammatory diseases characterized by inflammation of 1 or more joints and is the most common pediatric rheumatic disease. Juvenile Idiopathic Arthritis
  • Psoriatic arthritis
  • Rheumatoid arthritis
Adalimumab Fully humanized IgG1 monoclonal antibody that blocks TNF binding to receptors
  • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis
  • Crohn’s disease
  • Hidradenitis suppurativa Hidradenitis suppurativa Hidradenitis suppurativa (HS) is a chronic skin condition due to the inflammation of apocrine sweat glands and hair follicles. Most commonly, it occurs due to occlusion of the follicular component of pilosebaceous units (PSUs). Hidradenitis Suppurativa
  • Juvenile idiopathic arthritis
  • Psoriatic arthritis
  • Rheumatoid arthritis
  • Ulcerative colitis
  • Uveitis
Golimumab Fully humanized IgG1 monoclonal antibody with high affinity and specificity for TNF
  • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis
  • Psoriatic arthritis
  • Rheumatoid arthritis
  • Ulcerative colitis
Certolizumab Pegylated humanized monoclonal antibody specific to TNF
  • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis
  • Crohn’s disease
  • Psoriatic arthritis
  • Plaque 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
  • Rheumatoid arthritis

Clinical Relevance

  • Crohn’s disease (CD): chronic, recurrent condition that causes patchy transmural 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 that can involve any part of the GI tract. The terminal ileum and proximal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix are usually affected. Crohn’s disease presents with intermittent, nonbloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and crampy abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Extraintestinal manifestations may include calcium oxalate renal stones, gallstones, erythema nodosum Erythema nodosum Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum, and arthritis. Diagnosis is established via endoscopy with biopsy. Management is with corticosteroids, azathioprine, antibiotics, and anti-TNF agents (infliximab and adalimumab). 
  • Ulcerative colitis ( UC UC Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis): idiopathic inflammatory condition that involves the mucosal surface of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix. The rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal is always involved in UC UC Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis, and 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 may extend proximally through the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix. Ulcerative colitis causes diffuse friability, erosions with bleeding, and loss of haustra, which are visible on endoscopy. Individuals present with bloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, colicky abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, tenesmus, and fecal urgency. Diagnosis is established via endoscopy with biopsy. Management includes topical mesalamine, 6-mercaptopurine, and anti-TNF agents or colectomy for severe cases.
  • Psoriasis: common T-cell–mediated inflammatory 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. Structure and Function of the Skin condition. The etiology is unknown, but 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 is thought to be due to genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics and environmental triggers. Plaques are well circumscribed, are salmon-colored, and have silvery scales. The plaques commonly appear on the scalp and extensor surfaces of the extremities. The diagnosis is clinical. Treatment options include topical corticosteroids, retinoids, calcineurin inhibitors, 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), biologics such as anti-TNF agents, and phototherapy. 
  • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis: also known as Bechterew’s disease or Marie-Strümpell disease. Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew's disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis is a seronegative spondyloarthropathy characterized by chronic and indolent 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 of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. The condition is most often seen in young men and is associated with HLA-B27. Individuals will have progressive back pain Back pain Back pain is a common complaint among the general population and is mostly self-limiting. Back pain can be classified as acute, subacute, or chronic depending on the duration of symptoms. The wide variety of potential etiologies include degenerative, mechanical, malignant, infectious, rheumatologic, and extraspinal causes. Back Pain (which improves with activity), morning stiffness, and decreased range of motion of the spine. Extraarticular manifestations are also noted. Diagnosis is based on the clinical history, exam, and imaging (sacroiliitis and bridging syndesmophytes). Management involves physical therapy and NSAIDs. More severe cases may require TNF inhibitors or surgery.
  • Rheumatoid arthritis: symmetric, inflammatory polyarthritis. Rheumatoid arthritis is a chronic, progressive autoimmune disorder. Presentation includes joint swelling, pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and morning stiffness (often in the hands). Prolonged and severe disease can lead to irreversible joint deformities. 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, including 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. Diagnosis is clinical and is confirmed by the presence of rheumatoid factor, anti–cyclic citrullinated peptide 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, and characteristic imaging findings. Management involves physical therapy, long-term DMARDs, and biologics such as anti-TNF agents. 
  • Hidradenitis suppurativa Hidradenitis suppurativa Hidradenitis suppurativa (HS) is a chronic skin condition due to the inflammation of apocrine sweat glands and hair follicles. Most commonly, it occurs due to occlusion of the follicular component of pilosebaceous units (PSUs). Hidradenitis Suppurativa (HS): chronic 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. Structure and Function of the Skin condition due to the 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 of apocrine sweat glands and hair follicles. Hidradenitis suppurativa Hidradenitis suppurativa Hidradenitis suppurativa (HS) is a chronic skin condition due to the inflammation of apocrine sweat glands and hair follicles. Most commonly, it occurs due to occlusion of the follicular component of pilosebaceous units (PSUs). Hidradenitis Suppurativa commonly occurs because of occlusion of the follicular component of pilosebaceous units (PSUs). Hidradenitis suppurativa Hidradenitis suppurativa Hidradenitis suppurativa (HS) is a chronic skin condition due to the inflammation of apocrine sweat glands and hair follicles. Most commonly, it occurs due to occlusion of the follicular component of pilosebaceous units (PSUs). Hidradenitis Suppurativa is characterized by the formation of abscesses, fistulas, draining 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. Structure and Function of the Skin lesions, keloids, and pilonidal sinuses. The diagnosis of HS is primarily clinical. Management includes lifestyle changes (weight loss and smoking cessation) and medical treatment with antibiotics, retinoids, and anti-TNF agents. Resistant disease requires surgery.

References

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