Reactive Arthritis

Overview

Definition

Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (ReA) is an autoimmune, post-infectious, seronegative spondyloarthritis.

Mnemonic

The seronegative arthropathies Seronegative Arthropathies Ankylosing Spondylitis can be remembered as “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

• ReA develops in:
  • 1%–3% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs)
  • 1%–4% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with an enteric infection
• 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: 0.6–27 cases per 100,000 worldwide
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 30–40 per 100,000 adults
• More common in men 
• Occurs more frequently in young adults (< 40 years of age)
• 70%–90% have the HLA-B27 allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics

Etiology

• Generally occurs 1–4 weeks after certain 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:
  • Genitourinary (GU):
    • Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia (most common)
    • Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria
    • Ureaplasma urealyticum
  • Gastrointestinal (GI):
    • Campylobacter jejuni Campylobacter jejuni A species of bacteria that resemble small tightly coiled spirals. Its organisms are known to cause abortion in sheep and fever and enteritis in man and may be associated with enteric diseases of calves, lambs, and other animals. Campylobacter (most common)
    • Shigella flexneri Shigella flexneri A bacterium which is one of the etiologic agents of bacillary dysentery and sometimes of infantile gastroenteritis. Shigella, S. dysenteriae S. dysenteriae A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is extremely pathogenic and causes severe dysentery. Infection with this organism often leads to ulceration of the intestinal epithelium. Shigella, and S. sonnei S. sonnei A lactose-fermenting bacterium causing dysentery. Shigella
    • Salmonella enterica Salmonella enterica A subgenus of Salmonella containing several medically important serotypes. The habitat for the majority of strains is warm-blooded animals. Salmonella
    • Yersinia enterocolitica Yersinia enterocolitica A species of the genus yersinia, isolated from both man and animal. It is a frequent cause of bacterial gastroenteritis in children. Yersinia spp./Yersiniosis and Yersinia pseudotuberculosis Yersinia pseudotuberculosis A human and animal pathogen causing mesenteric lymphadenitis, diarrhea, and bacteremia. Yersinia spp./Yersiniosis
    • Clostridioides difficile
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
  • Pulmonary (less common):
    • Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
• Genetic associations:
  • HLA-B27 (most common)
  • HLA-B51
  • HLA-DRB1
• The exact pathophysiology is unknown.

Clinical Presentation

Articular manifestations

Onset is acute, within 1–4 weeks of an inciting infection.

Peripheral arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis:

• Asymmetric oligoarthritis Oligoarthritis Ankylosing Spondylitis
• Predominantly of the large weight-bearing joints of the lower extremities:
  • Knees
  • Ankles
• Other common joints:
  • Shoulders
  • Wrists
  • Elbows
  • Small joints of hands and feet
• On exam, joints will be:
  • Tender
  • Warm
  • Swollen

Enthesopathy:

• 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, tendon, fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis, or joint capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides insertion to 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
• Causes focal tenderness and swelling Swelling Inflammation
• Common insertion sites:
  • Achilles tendon
  • Plantar fascia Plantar fascia Foot: Anatomy insertion site 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
  • Ischial tuberosities
  • Iliac crests
  • Tibial tuberosities
  • Ribs Ribs A set of twelve curved bones which connect to the vertebral column posteriorly, and terminate anteriorly as costal cartilage. Together, they form a protective cage around the internal thoracic organs. Chest Wall: Anatomy

Tendonitis and periostitis:

• 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 tendon or periosteum Periosteum Thin outer membrane that surrounds a bone. It contains connective tissue, capillaries, nerves, and a number of cell types. Bones: Structure and Types, respectively
• Common locations:
  • Achilles tendonitis
  • 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
  • Digital periostitis

Dactylitis Dactylitis Ankylosing Spondylitis:

• Swollen fingers and toes (“sausage digits”)

Sacroiliitis Sacroiliitis Inflammation of the sacroiliac joint. It is characterized by lower back pain, especially upon walking, fever, uveitis; psoriasis; and decreased range of motion. Many factors are associated with and cause sacroiliitis including infection; injury to spine, lower back, and pelvis; degenerative arthritis; and pregnancy. Ankylosing Spondylitis:

• 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 sacroiliac joints
• Signs and symptoms:
  • Low back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Decreased lumbar flexion Flexion Examination of the Upper Limbs

Extra-articular manifestations

Ocular:

• 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
• 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
• Episcleritis
• Keratitis Keratitis Inflammation of the cornea. Herpes Simplex Virus 1 and 2

Genitourinary:

• Urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs)
• Cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea
• 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
• Cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs)
• Salpingo-oophoritis

Mucocutaneous:

• Keratoderma blennorrhagicum
  • Vesicles Vesicles Female Genitourinary Examination of the palms, soles, and around nails
  • Become hyperkeratotic and form crusts
  • Appears similar to pustular 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
• Balanitis Balanitis Inflammation of the head of the penis, glans penis. Penile Anomalies and Conditions circinata
  • Shallow, painless ulcers of the glans penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy
• Painless oral ulcers Oral ulcers A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis; necrotizing gingivitis, toothbrushing, and various irritants. Chédiak-Higashi Syndrome
• Nail dystrophy
• 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 (uncommon)

GI:

• Intermittent 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
  • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis

Cardiac:

• Aortitis Aortitis Inflammation of the wall of the aorta. Ankylosing Spondylitis
• Aortic regurgitation Aortic regurgitation Aortic regurgitation (AR) 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

Clinical triad

This classic triad of symptoms is found in only about 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ReA: 

• Post-infectious arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
• 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
• Urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs) 

Diagnosis

Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis is a clinical diagnosis based on: 

• Acute oligoarthritis Oligoarthritis Ankylosing Spondylitis and typical articular manifestations
• Preceding GI or genitourinary (GU) infection
• Presence of ≥ 1 extra-articular manifestation
• Exclusion of other diagnoses 

Supporting work-up

Synovial fluid analysis Synovial Fluid Analysis Rheumatoid Arthritis:

• Performed in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with joint effusions
• ↑ leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology with neutrophil predominance may be seen
• Evaluations to rule out other etiologies:
  • Crystal analysis
  • Gram stain Gram stain Klebsiella and culture → rule out gonococcal arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis

Laboratory findings: 

• ↑ or normal erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess) and C-reactive protein (CRP)
• Mild leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus on complete blood cell count (CBC)
• Stool cultures → evaluate for causative organisms if the patient is having 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
• Urine or genital swab → evaluate for C. trachomatis
• Urine culture Urine culture Urinary tract infections (UTIs) → Ureaplasma or Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia
• HLA-B27 testing
• HIV HIV Anti-HIV Drugs and tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions testing in high-risk individuals (high association with ReA)
• Rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis ( RF RF Rheumatoid Arthritis) and anticyclic citrullinated peptide (anti-CCP) → rule out 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

Radiographs of affected joints:

• Can be used to evaluate for fractures
• Evaluate for evidence of 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 in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with sacroiliitis Sacroiliitis Inflammation of the sacroiliac joint. It is characterized by lower back pain, especially upon walking, fever, uveitis; psoriasis; and decreased range of motion. Many factors are associated with and cause sacroiliitis including infection; injury to spine, lower back, and pelvis; degenerative arthritis; and pregnancy. Ankylosing Spondylitis
• Findings are generally nonspecific.

Management

Management of arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis

Symptoms of ReA typically resolve in 3‒4 months, but prolonged or recurrent symptoms can occur in up to 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Acute ReA (duration < 6 months):

• Physical therapy Physical Therapy Becker Muscular Dystrophy
• Nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches) are the mainstay of therapy.
  • Naproxen Naproxen An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Diclofenac Diclofenac A non-steroidal anti-inflammatory agent (nsaid) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
• Intraarticular or systemic glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Reserved for those with an inadequate response to NSAIDs NSAIDS Primary vs Secondary Headaches
• 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))
  • Indicated if a patient fails the above treatments

Chronic ReA (duration > 6 months):

• 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
  • 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
• Tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)) inhibitors
  • Considered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who do not respond to 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)
  • Limited data 

Management of extra-articular manifestations

Ocular:

• Referral for ophthalmologic evaluation
• 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: corticosteroid and mydriatic eye drops
• 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: symptomatic treatment

Mucocutaneous: 

• Symptomatic treatment for mild lesions
• Topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
• Topical salicylates
• Severe keratoderma blennorrhagica: 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) or 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
• Balanitis Balanitis Inflammation of the head of the penis, glans penis. Penile Anomalies and Conditions circinata: genital hygiene and topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors

Management of underlying 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

• GI infection GI infection Microsporidia/Microsporidiosis
  • Antibiotics are generally not indicated.
  • Exceptions:
    • Severe disease
    • Elderly
    • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• GU infection
  • C. trachomatis treatment
    • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
    • Doxycycline
    • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones (alternative therapy)
  • N. gonorrhoeae: ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins

Differential Diagnosis

• Gonococcal arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: an infection due to N. gonorrhoeae. Disseminated disease can present similar to ReA with an acute, inflammatory, asymmetric arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis with urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs). Diagnosis is based on the clinical history, synovial fluid analysis Synovial Fluid Analysis Rheumatoid Arthritis, and culture results. Management includes antibiotics. 
• Behcet’s disease: an inflammatory vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus of small and large vessels. Symptoms can include arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis and painful oral and genital ulcers, unlike the painless lesions in ReA. Ocular, neurologic, GI, and vascular manifestations are also seen. Diagnosis is based on clinical criteria. Management depends on the clinical manifestations and includes corticosteroids Corticosteroids Chorioretinitis, 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 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.
• 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: an 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. Diagnosis is made with positive RF RF Rheumatoid Arthritis and 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.
• Psoriatic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: a spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis that occurs in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis. This inflammatory arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis is frequently asymmetric. The small and large joints are involved, 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 and dactylitis Dactylitis Ankylosing Spondylitis 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.
• 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: a spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis involving 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, resulting in back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, 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, and loss of lumbar lordosis. Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may also have peripheral joint involvement, 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, aortic insufficiency, aortitis Aortitis Inflammation of the wall of the aorta. Ankylosing Spondylitis, cardiac conduction abnormalities, and cavitary lung lesions. Diagnosis is based on lumbosacral radiographic findings ( sacroiliitis Sacroiliitis Inflammation of the sacroiliac joint. It is characterized by lower back pain, especially upon walking, fever, uveitis; psoriasis; and decreased range of motion. Many factors are associated with and cause sacroiliitis including infection; injury to spine, lower back, and pelvis; degenerative arthritis; and pregnancy. Ankylosing Spondylitis and “ bamboo spine Bamboo Spine Ankylosing Spondylitis”) and the presence of HLA-B27. Management includes NSAIDs NSAIDS Primary vs Secondary Headaches, 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, or interleukin-17 Interleukin-17 A proinflammatory cytokine produced primarily by T-lymphocytes or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene. Interleukins antagonists.
• Inflammatory bowel disease (IBD): includes Crohn’s disease and ulcerative colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis, and is characterized by 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 of the GI tract due to a cell-mediated immune response to the GI mucosa. Symptoms include 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, abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery. Extraintestinal manifestations can include a migratory peripheral arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis of large joints. Inflammatory bowel disease is also associated with other disorders, such as 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, sacroillitis, and 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. Diagnosis includes imaging, endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD), and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment involves steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, aminosalicylates, immunomodulators, and biologic agents Biologic Agents Immunosuppressants