Ankylosing Spondylitis

Overview

Definition

Ankylosing spondylitis (AS) 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 Axial Computed Tomography (CT) skeleton.

Mnemonic

To remember the seronegative arthropathies, use the mnemonic “PAIR.” 

• Psoriatic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 
• Ankylosing spondylitis
• Inflammatory bowel disease–associated arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis

Epidemiology

• 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: 0.4–14 per 100,000 people per year
• Highest prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in northern European countries
• Age at onset: 20–30 years
• 3 times more common in men
• 10–20 times more common in 1st-degree relatives of those with ankylosing spondylitis

Etiology

• Exact cause unknown
• Strong association with HLA-B27
• Possible triggers:
  • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella infection
  • Trauma

Pathophysiology

Proposed mechanism 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

• Innate immunity Innate immunity The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring anti-infective agents, constitutional factors such as body temperature and immediate acting immune cells such as natural killer cells. Innate Immunity: Phagocytes and Antigen Presentation is triggered:
  • Possibly from GI microbes invading the systemic circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment
  • Due to disruption of the gut mucosal barrier
• Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response and 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 ( ILs ILs 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) are released:
  • IL-17 and IL-23 
  • 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 alpha (TNF-alpha)
  • Transforming growth factor beta Transforming growth factor beta Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action. Pulmonary Fibrosis (TGF-beta)
• Development of enthesitis ( 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 at the site of ligament or tendon insertion into 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):
  • Micro-injury from mechanical stress may make entheses susceptible to 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.
  • Joints are infiltrated with 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 and with CD4 and CD8 T cells CD8+ T cells A critical subpopulation of regulatory T-lymphocytes involved in mhc class i-restricted interactions. They include both cytotoxic T-lymphocytes and CD8+ suppressor T-lymphocytes. T cells: Types and Functions.
  • Main joints involved:
    • Sacroiliac (SI) joints
    • Paravertebral joints

Axioskeletal changes

• Chronic inflammation Chronic Inflammation Inflammation of the ligaments and the annulus fibrosus Annulus Fibrosus Spinal Disk Herniation of the intervertebral disk → erosion Erosion Partial-thickness loss of the epidermis Generalized and Localized Rashes of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and destruction of articular tissues
• Erosion Erosion Partial-thickness loss of the epidermis Generalized and Localized Rashes → fibrocartilage Fibrocartilage A type of cartilage whose matrix contains large bundles of collagen type I. Fibrocartilage is typically found in the intervertebral disk; pubic symphysis; tibial menisci; and articular discs in synovial joints. Cartilage: Histology regeneration Regeneration The physiological renewal, repair, or replacement of tissue. Wound Healing → fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification → syndesmophyte formation
• Syndesmophytes bridge together → vertebral fusion

Clinical Presentation

Articular manifestations

• Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
  • Lower back and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
  • Progressive
  • Often nocturnal
  • Varies in intensity
  • Present for > 3 months
• Paraspinal muscle Paraspinal muscle Deep muscles in the back whose function is to extend and rotate the spine and maintain posture. It consists splenius, semispinalis, multifidus, rotatores, interspinales, intertransversarii and sacrospinalis. Parapharyngeal Abscess spasm
• Morning stiffness:
  • Improves with activity or exercise 
  • Worsened by inactivity
• Diminished 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 of the 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
• Oligoarthritis (50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
  • Asymmetrical involvement of ≤ 4 peripheral joints
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, warmth, swelling Swelling Inflammation, and stiffness

Extra-articular 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
  • Weakness
  • Low-grade fever Low-Grade Fever Erythema Infectiosum
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
• Periarticular:
  • Enthesitis
    • Plantar fasciitis Plantar fasciitis Inflammation of the plantar fascia (aponeurosis) on the bottom of the foot causing heel pain. The etiology of plantar fasciitis remains controversial but is likely to involve a biomechanical imbalance. Though often presenting along with heel spur, they do not appear to be causally related. Ankle and Foot Pain
    • Costochondral junctions
  • Tendinitis
    • Achilles
    • Patellar
  • Dactylitis (sausage fingers)
• Ocular:
  • Anterior 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
  • 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
• Cardiac:
  • Aortitis
  • Aortic valve insufficiency Aortic valve insufficiency Aortic regurgitation is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation
  • Conduction abnormalities
    • Due to fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of the conduction system
    • Varying degrees of atrioventricular block Atrioventricular block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block) may result.
  • 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
• Pulmonary
  • Restrictive lung disease
  • Nontuberculous apical fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
    • Can result in cavitation Cavitation Imaging of the Lungs and Pleura
    • Secondary bacterial or fungal ( Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins) 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
• Cutaneous:
  • 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
  • Painless oral ulcerations
• GI:
  • Asymptomatic ileal and colonic 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
  • Inflammatory bowel disease
• Renal:
  • Immunoglobulin A ( IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions) nephropathy
  • Renal amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis
• Genitourinary: prostatitis Prostatitis Prostatitis is inflammation or an irritative condition of the prostate that presents as different syndromes: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain, and asymptomatic. Bacterial prostatitis is easier to identify clinically and the management (antibiotics) is better established. Prostatitis
• Neurologic:
  • Radiculitis
  • Cauda equina Cauda Equina The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. Spinal Cord Injuries syndrome

Physical examination

• 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:
  • Cervical and upper thoracic vertebrae Thoracic vertebrae A group of twelve vertebrae connected to the ribs that support the upper trunk region. Vertebral Column: Anatomy:
    • Accentuated thoracic kyphosis Kyphosis Deformities of the spine characterized by an exaggerated convexity of the vertebral column. The forward bending of the thoracic region usually is more than 40 degrees. This deformity sometimes is called round back or hunchback. Osteoporosis
    • Stooped, forward-flexed position (when fused)
    • Distance between chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma and sternum Sternum A long, narrow, and flat bone commonly known as breastbone occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck. Chest Wall: Anatomy with flexed head > 2 cm
  • Lumbar vertebrae Lumbar vertebrae Vertebrae in the region of the lower back below the thoracic vertebrae and above the sacral vertebrae. Vertebral Column: Anatomy:
    • Reduced 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 (Schober test)
    • Loss of lumbar lordosis 
• Sacroiliac joint Sacroiliac Joint The immovable joint formed by the lateral surfaces of the sacrum and ilium. Pelvis: Anatomy:
  • Localized tenderness
  • Mennell sign
  • FABER (Flexion, Abduction, and External Rotation) test
• Tenderness at the following points:
  • Achilles tendon insertion
  • Insertion of the plantar fascia Plantar fascia Foot: Anatomy on the calcaneus Calcaneus The largest of the tarsal bones which is situated at the lower and back part of the foot, forming the heel. Foot: Anatomy or the metatarsal heads
  • Base of the 5th metatarsal head
  • Tibial tuberosity Tibial tuberosity Leg: Anatomy
  • Superior and inferior poles of the patella Patella The flat, triangular bone situated at the anterior part of the knee. Knee Joint: Anatomy
  • Iliac crest
• Reduced chest expansion (< 4 cm) on deep inspiration Inspiration Ventilation: Mechanics of Breathing

Diagnosis

Physical examination tests

• Schober’s test:
  • Tests limitation of lumbar movement 
  • Procedure:
    • Place a mark 5 cm below and 10 cm above the L5 spinous process. 
    • Have the patient touch the toes.
    • If distance does not increase by > 5 cm, the patient has reduced lumbar flexion Flexion Examination of the Upper Limbs.
• FABER test:
  • Also known as Patrick test Patrick Test Back Pain
  • Nonspecific test that detects joint dysfunction in the sacroiliac joint Sacroiliac Joint The immovable joint formed by the lateral surfaces of the sacrum and ilium. Pelvis: Anatomy 
  • Procedure:
    • The patient’s leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy is flexed at the hip, abducted, and placed in a figure-4 position.
    • Force is applied to the ipsilateral knee.
    • Test is deemed positive if it reproduces pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the ipsilateral sacroiliac joint Sacroiliac Joint The immovable joint formed by the lateral surfaces of the sacrum and ilium. Pelvis: Anatomy.
• Mennell sign:
  • Helps determine whether pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is coming from the hip, lumbar 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, or sacroiliac joint Sacroiliac Joint The immovable joint formed by the lateral surfaces of the sacrum and ilium. Pelvis: Anatomy
  • Procedure:
    • Performed with the patient facedown
    • Passive hyperextension of the upper leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy 
    • This procedure provokes pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the sacroiliac joint Sacroiliac Joint The immovable joint formed by the lateral surfaces of the sacrum and ilium. Pelvis: Anatomy, hip, or lumbar 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 depending on where the physician fixates (places 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) on the 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 or hip.
• Chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma–brow vertical angle (CBVA)
  • An assessment for kyphotic deformity Deformity Examination of the Upper Limbs 
  • Procedure:
    • Measures the angle between a vertical line and a line connecting the brow to the chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma while the patient is standing
    • Any degree greater than zero is abnormal.
      

Imaging

• Radiography:
  • Diagnostic and assesses severity of the disease
  • Should be performed in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in whom AS is suspected
  • Bilateral sacroiliitis:
    • Subchondral erosions Erosions Corneal Abrasions, Erosion, and Ulcers (“pseudo-widening” of the SI joint)
    • Subchondral sclerosis Subchondral Sclerosis Osteochondritis Dissecans
    • SI joint narrowing
    • Fusion of the SI joint (end-stage)
  • 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 findings:
    • Small erosions Erosions Corneal Abrasions, Erosion, and Ulcers with reactive sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
    • Squaring of vertebrae
    • Ligament calcifications
    • Evolving syndesmophytes
    • Bridging syndesmophytes (“bamboo 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”)
• MRI:
  • Aids in early detection
  • May reveal inflammatory changes not seen on radiographs

Laboratory Tests

• Nonspecific
• ↑ CRP 
• ↑ Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess)
• Mildly ↑ alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma
• Negative rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis ( RF RF Rheumatoid Arthritis)
• Negative ANA test
• Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies for HLA-B27:
  • May be considered if clinical evaluation and radiography are inconclusive
  • Positive in approximately 90% of Caucasian patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with AS
  • Not required for diagnosis

Management and Complications

Management requires a multidisciplinary approach to reduce pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, increase 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, decrease 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 improve quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life.

Conservative measures

• Lifestyle changes:
  • Urge smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation.
  • Encourage regular Regular Insulin physical activity.
• Physical therapy Physical Therapy Becker Muscular Dystrophy:
  • Crucial for maintaining mobility
  • Exercises for:
    • Mobilization of the vertebral joints and muscle stability 
    • Maintenance of adequate posture and 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
• Depression and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder screening Screening Preoperative Care
• Psychosocial support

Medical management

• Initial therapy:
  • Nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches)
  • 70% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship achieve clinical improvement.
• 2nd line:
  • 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) inhibitors
    • Etanercept Etanercept A 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, adalimumab Adalimumab A 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), golimumab Golimumab Disease-Modifying Antirheumatic Drugs (DMARDs), infliximab Infliximab A 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)
    • Used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in whom NSAID NSAID 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) therapy fails
  • IL-17 inhibitors
    • Secukinumab Secukinumab Immunosuppressants or ixekizumab Ixekizumab Immunosuppressants
    • Alternative to 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) 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) ( 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))
    • 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 or 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
    • Used for persistent peripheral arthritis Peripheral Arthritis Reactive Arthritis
• 3rd line: JAK inhibitors JAK inhibitors Targeted and Other Nontraditional Antineoplastic Therapy for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with inadequate response or intolerance to biologic therapy.

Surgical interventions

• Indications:
  • Severe deformities resulting in functional impairment
  • Severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways causing diminished quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life
  • Acute fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures
  • Neurologic deficits Neurologic Deficits High-Risk Headaches
• Options:
  • Spinal fusion
  • Osteotomy
  • Total hip arthroplasty Arthroplasty Surgical reconstruction of a joint to relieve pain or restore motion. Osteoarthritis

Complications

• In addition to the manifestations of this disease, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may develop:
  • 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
    • Most frequent complication
    • Predisposes patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship to fractures
  • Vertebral fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures
    • Most serious complication
    • 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 fractures can lead to paralysis or death.
  • Respiratory compromise
• Adverse effects on the patient’s quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life:
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbances
  • Disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment
  • Diminished psychologic health (depression)

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

• Ankylosing spondylitis is a chronic disease.
• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship retain complete functionality.
• Indicators of 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:
  • Younger age at onset
  • Peripheral arthritis Peripheral Arthritis Reactive Arthritis
  • ↑ Inflammatory markers
  • Poor response to NSAIDs NSAIDS Primary vs Secondary Headaches
• Severe and long-standing AS is associated with ↑ risk of mortality Mortality All deaths reported in a given population. Measures of Health Status.

Differential Diagnosis

• Lumbar spinal stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS): narrowing of the lumbar spinal canal Spinal Canal The cavity within the spinal column through which the spinal cord passes. Spinal Cord Injuries resulting in compression Compression Blunt Chest Trauma of nerve rootlets. This condition is more common in older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may experience chronic back, buttock, and thigh Thigh The thigh is the region of the lower limb found between the hip and the knee joint. There is a single bone in the thigh called the femur, which is surrounded by large muscles grouped into 3 fascial compartments. Thigh: Anatomy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that is relieved by flexing the back. Neurologic signs and symptoms, including paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome, weakness, and diminished reflexes, are also prominent. The diagnosis is based on clinical evaluation and MRI. Management includes physical therapy Physical Therapy Becker Muscular Dystrophy, analgesics, and surgery for severe cases.
• Psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis: a seronegative spondyloarthropathy that occurs in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis. This asymmetric, inflammatory arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis involves small and large joints, including the distal interphalangeal joints Interphalangeal joints Hand: Anatomy and the sacroiliac spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy. Enthesopathy Enthesopathy Reactive Arthritis and dactylitis are also seen. The diagnosis is clinical, and the condition 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 Arthritis Acute or chronic inflammation of joints. Osteoarthritis: a seronegative spondyloarthropathy that is often precipitated by a GI 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. This arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis can be associated with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tendinitis, enthesitis, 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. The diagnosis is clinical. Treatment 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 underlying infection.
• Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (RA): a seropositive autoimmune disease resulting in joint 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 destruction. This arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis is typically symmetric, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will frequently have tender 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 in the joints of the hands and feet (although any peripheral joints can be involved). The axial Axial Computed Tomography (CT) skeleton is less commonly included. The diagnosis is made with the presence of positive RF RF Rheumatoid Arthritis and anti–cyclic citrullinated peptide (anti-CCP) laboratory studies. 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), corticosteroids Corticosteroids Chorioretinitis, immunosuppressive medications, biologics, and 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) inhibitors. 
• Fibromyalgia Fibromyalgia Fibromyalgia is a chronic pain syndrome characterized by widespread body pain, chronic fatigue, mood disturbance, and cognitive disturbance. It also presents with other comorbid symptoms such as migraine headaches, depression, sleep disturbance, and irritable bowel syndrome. Fibromyalgia: a nonarticular disorder of unknown etiology that causes generalized pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, including the muscles, points of tendon insertion (which can mimic enthesitis), and soft tissues. Associated symptoms include 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, muscle stiffness Muscle Stiffness Ion Channel Myopathy, cognitive disturbances, depression, and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder. The diagnosis is based on clinical criteria. Imaging and laboratory testing will be unrevealing. Management includes exercise, nonopioid analgesics, and efforts to improve sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep and stress.
• Diffuse idiopathic Idiopathic Dermatomyositis skeletal hyperostosis: a noninflammatory disease causing ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification of spinal ligaments and entheses. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic or may have progressive back and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways with reduced 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 (particularly of the thoracic 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). The diagnosis is made with imaging, which may show the changes of AS. However, the SI joints are usually spared, and there may be extra-axial joint involvement. Management involves analgesics and physical therapy Physical Therapy Becker Muscular Dystrophy for pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways relief.