What is dysregulated immune response? Plus 16 common arthritic types with dysregulated immune response.

Understanding Dysregulated Immune Response in Inflammatory Arthritis

Inflammatory arthritis, a subset of autoimmune diseases, involves a dysregulated immune response where the body’s immune system mistakenly attacks healthy joint tissues, leading to chronic inflammation and joint damage[^1]. This dysregulation can result in several types of arthritis, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).

Types of Inflammatory Arthritis and Mechanisms of Inflammation

Inflammatory arthritis affects various parts of the body, primarily targeting joints but potentially impacting other organs[^2]. The most commonly affected joints include the hands, wrists, knees, ankles, and feet. Inflammation in these areas leads to joint swelling, stiffness, pain, and warmth.

The immune system’s dysregulation involves an overproduction of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukins, which contribute to the inflammatory cascade[^3]. This chronic inflammation damages cartilage, ligaments, and bones over time.

Impact on Quality of Life and Complications

Inflammatory arthritis significantly impacts an individual’s quality of life due to pain, decreased mobility, and fatigue[^4]. Complications may arise, including joint deformities, osteoporosis, cardiovascular disease, and increased susceptibility to infections[^5].

Joint swelling and tenderness are common manifestations of inflammation in arthritis, resulting from increased blood flow and immune cell infiltration into the affected joints[^6]. Cartilage damage occurs due to prolonged inflammation, leading to joint erosion and reduced range of motion.

List of 16 common types of Dysregulated Immune Response:

Rheumatoid Arthritis (RA):
- Description: Autoimmune disease targeting synovial joints, causing chronic inflammation, joint damage, and systemic effects.
- Major Symptoms: Joint pain, swelling, stiffness, fatigue.
- Causes: Genetic predisposition, environmental triggers (e.g., infections, smoking).
- Minor Symptoms: Rheumatoid nodules, fever, weight loss.
- Major Causes: Autoimmune response against joint tissues (synovium).
- Triggers: Infections, stress, hormonal changes.
- Affected Joints/Motion: Primarily small joints (hands, feet); can lead to limited mobility and deformities.
- Remission Chances: Possible with early and aggressive treatment.
- Average Onset Age: 30-50 years; more common in women.
- Chronic Interrelated Diseases: Cardiovascular disease, osteoporosis, lung disease.
- Complications: Joint deformities, rheumatoid nodules, increased cardiovascular risk.
- Autoimmune Type: Yes.
Psoriatic Arthritis (PsA):
- Description: Autoimmune arthritis associated with psoriasis, affecting joints, skin, and nails.
- Major Symptoms: Joint pain, stiffness, skin lesions (psoriasis), nail changes.
- Causes: Genetic predisposition, immune dysfunction.
- Minor Symptoms: Fatigue, eye inflammation (uveitis).
- Major Causes: Immune-mediated inflammation affecting joints and skin.
- Triggers: Psoriasis flare-ups, infections, stress.
- Affected Joints/Motion: Fingers, toes, spine; may cause limited range of motion.
- Remission Chances: Varies; achievable with treatment.
- Average Onset Age: 30-50 years; equal incidence in men and women.
- Chronic Interrelated Diseases: Inflammatory bowel disease, cardiovascular disease.
- Complications: Joint damage, enthesitis, eye complications.
- Autoimmune Type: Yes.
Ankylosing Spondylitis (AS):
- Description: Inflammatory arthritis primarily affecting the spine and sacroiliac joints, leading to fusion and reduced mobility.
- Major Symptoms: Back pain, stiffness, reduced spinal flexibility.
- Causes: Genetic susceptibility (HLA-B27), immune system involvement.
- Minor Symptoms: Fatigue, peripheral joint pain.
- Major Causes: Chronic inflammation affecting spine and joints.
- Triggers: Infections, genetic factors.
- Affected Joints/Motion: Spine, sacroiliac joints; may cause posture changes.
- Remission Chances: Variable; early treatment can slow progression.
- Average Onset Age: Late teens to early 40s; more common in men.
- Chronic Interrelated Diseases: Inflammatory bowel disease, uveitis.
- Complications: Spinal fusion, breathing difficulties, cardiovascular issues.
- Autoimmune Type: Yes.
Systemic Lupus Erythematosus (SLE):
- Description: Systemic autoimmune disease affecting multiple organs, including joints, skin, kidneys, and heart.
- Major Symptoms: Joint pain, skin rash (butterfly rash), fatigue, kidney involvement.
- Causes: Genetic predisposition, environmental triggers (e.g., sunlight).
- Minor Symptoms: Fever, hair loss, mouth ulcers.
- Major Causes: Autoimmune attack on various tissues and organs.
- Triggers: Sun exposure, infections, hormonal changes.
- Affected Joints/Motion: Various joints; can cause pain and stiffness.
- Remission Chances: Periods of remission possible with treatment.
- Average Onset Age: 20s to 40s; more common in women.
- Chronic Interrelated Diseases: Kidney disease, cardiovascular complications.
- Complications: Kidney failure, cardiovascular disease, neuropsychiatric issues.
- Autoimmune Type: Yes.
Gout:
- Description: Inflammatory arthritis caused by uric acid crystal deposition in joints, leading to acute joint pain and swelling.
- Major Symptoms: Sudden joint pain (often in the big toe), swelling, redness.
- Causes: Elevated uric acid levels (hyperuricemia), dietary factors.
- Minor Symptoms: Tophi (uric acid deposits), kidney stones.
- Major Causes: Uric acid crystal formation in joints.
- Triggers: Diet high in purines, alcohol consumption.
- Affected Joints/Motion: Big toe, other joints; can limit mobility during flares.
- Remission Chances: Fluctuates; management of uric acid levels can prevent flares.
- Average Onset Age: Middle-aged to older adults; more common in men.
- Chronic Interrelated Diseases: Kidney disease, cardiovascular disease.
- Complications: Joint damage, kidney stones, tophi formation.
- Autoimmune Type: No.
Juvenile Idiopathic Arthritis (JIA):
- Description: Autoimmune arthritis in children under 16 years, involving various forms with joint inflammation.
- Major Symptoms: Joint swelling, stiffness, fever, rash.
- Causes: Genetic factors, abnormal immune response.
- Minor Symptoms: Eye inflammation (uveitis), growth problems.
- Major Causes: Immune-mediated inflammation affecting joints.
- Triggers: Unknown; may involve infections or environmental factors.
- Affected Joints/Motion: Various joints; can affect growth and development.
- Remission Chances: Varies; some forms can resolve with age.
- Average Onset Age: Childhood; onset before 16 years.
- Chronic Interrelated Diseases: Eye inflammation, growth disturbances.
- Complications: Joint damage, growth abnormalities, eye problems.
- Autoimmune Type: Yes.
Sjögren’s Syndrome:
- Description: Autoimmune disease affecting moisture-producing glands, causing dry eyes and mouth, and joint pain.
- Major Symptoms: Dry eyes, dry mouth, joint pain, fatigue.
- Causes: Autoimmune attack on glands, genetic predisposition.
- Minor Symptoms: Skin rashes, digestive issues.
- Major Causes: Immune system targeting salivary and lacrimal glands.
- Triggers: Unknown; may involve environmental factors.
- Affected Joints/Motion: Often affects small joints; can cause pain and stiffness.
- Remission Chances: Varies; symptoms can be managed with treatment.
- Average Onset Age: 40s to 60s; more common in women.
- Chronic Interrelated Diseases: Rheumatoid arthritis, lupus.
- Complications: Dryness-related issues (eye damage, dental problems), increased infection risk.
- Autoimmune Type: Yes.
Behçet’s Disease:
- Description: Chronic inflammatory condition affecting blood vessels, causing oral and genital ulcers, skin lesions, and arthritis.
- Major Symptoms: Oral ulcers, genital ulcers, skin lesions, joint pain.
- Causes: Autoimmune vasculitis, genetic predisposition.
- Minor Symptoms: Eye inflammation (uveitis), gastrointestinal symptoms.
- Major Causes: Inflammatory response affecting blood vessels.
- Triggers: Unknown; may involve infections or environmental factors.
- Affected Joints/Motion: Often affects large joints; can cause pain and swelling.
- Remission Chances: Varies; treatment focuses on symptom management.
- Average Onset Age: 20s to 30s; more common in certain ethnic groups.
- Chronic Interrelated Diseases: Eye inflammation, gastrointestinal issues.
- Complications: Vision loss (from eye inflammation), blood vessel damage, neurological problems.
- Autoimmune Type: Yes.
Systemic Sclerosis (Scleroderma):
- Description: Autoimmune disease causing thickening and fibrosis of skin and internal organs, including joint inflammation.
- Major Symptoms: Skin tightening, Raynaud’s phenomenon, joint pain.
- Causes: Autoimmune response leading to excess collagen production.
- Minor Symptoms: Gastrointestinal issues, lung involvement.
- Major Causes: Immune-mediated fibrosis affecting skin and organs.
- Triggers: Unknown; may involve environmental factors.
- Affected Joints/Motion: Can cause joint pain and stiffness.
- Remission Chances: Varies; treatment targets symptoms and organ involvement.
- Average Onset Age: 30s to 50s; more common in women.
- Chronic Interrelated Diseases: Pulmonary hypertension, kidney disease.
- Complications: Organ damage (lung, heart, kidneys), skin ulcers.
- Autoimmune Type: Yes.
Polymyalgia Rheumatica (PMR):
- Description: Inflammatory condition causing muscle pain and stiffness, typically in the shoulders and hips.
- Major Symptoms: Muscle pain, stiffness, fatigue.
- Causes: Immune system dysfunction, genetic factors.
- Minor Symptoms: Fever, weight loss.
- Major Causes: Immune-mediated inflammation affecting muscles.
- Triggers: Unknown; may involve infections or other factors.
- Affected Joints/Motion: Shoulders, hips; can cause limited mobility.
- Remission Chances: Good prognosis with treatment; resolves over time.
- Average Onset Age: Usually over 50 years; more common in older adults.
- Chronic Interrelated Diseases: Giant cell arteritis (often coexists).
- Complications: Rare; may be associated with giant cell arteritis.
- Autoimmune Type: Yes.
Mixed Connective Tissue Disease (MCTD):
- Description: Overlap syndrome involving features of lupus, scleroderma, and polymyositis.
- Major Symptoms: Joint pain, muscle weakness, Raynaud’s phenomenon.
- Causes: Autoimmune response affecting connective tissues.
- Minor Symptoms: Skin changes, lung involvement.
- Major Causes: Immune-mediated inflammation affecting multiple tissues.
- Triggers: Genetic factors, environmental influences.
- Affected Joints/Motion: Can cause joint pain and inflammation.
- Remission Chances: Varies; treatment focuses on symptom control.
- Average Onset Age: Usually between 20s and 50s.
- Chronic Interrelated Diseases: Lupus, scleroderma, polymyositis.
- Complications: Organ involvement (lung, heart, kidneys), skin changes.
- Autoimmune Type: Yes.
Reactive Arthritis (ReA):
- Description: Inflammatory arthritis triggered by an infection, often affecting joints, eyes, and urogenital tract.
- Major Symptoms: Joint pain, swelling, eye inflammation (conjunctivitis).
- Causes: Immune response to bacterial infection (e.g., gastrointestinal or genitourinary infection).
- Minor Symptoms: Skin rashes, urinary symptoms.
- Major Causes: Immune response targeting joint tissues post-infection.
- Triggers: Bacterial infections (e.g., Chlamydia, Salmonella).
- Affected Joints/Motion: Typically involves large joints; may cause stiffness.
- Remission Chances: Generally good; resolves with treatment of underlying infection.
- Average Onset Age: Varies based on triggering infection.
- Chronic Interrelated Diseases: None specific; related to underlying infection.
- Complications: Chronic joint damage, eye inflammation, urinary issues.
- Autoimmune Type: Yes (triggered by immune response post-infection).
Undifferentiated Connective Tissue Disease (UCTD):
- Description: Autoimmune condition with symptoms overlapping multiple connective tissue diseases.
- Major Symptoms: Joint pain, fatigue, skin changes.
- Causes: Unknown; likely autoimmune in nature.
- Minor Symptoms: Raynaud’s phenomenon, mild organ involvement.
- Major Causes: Immune system dysfunction affecting connective tissues.
- Triggers: Genetic predisposition, environmental factors.
- Affected Joints/Motion: Joint symptoms similar to other connective tissue diseases.
- Remission Chances: Varies; may resolve or progress to specific disease.
- Average Onset Age: Typically between 30s and 50s.
- Chronic Interrelated Diseases: Lupus, scleroderma, rheumatoid arthritis.
- Complications: Progression to specific connective tissue disease, organ involvement.
- Autoimmune Type: Yes (mixed connective tissue pathology).
Adult Still’s Disease (ASD):
- Description: Rare systemic inflammatory disorder with features of fever, rash, and joint inflammation.
- Major Symptoms: Daily fevers, rash (salmon-colored), joint pain, swelling.
- Causes: Unknown; likely autoimmune or autoinflammatory.
- Minor Symptoms: Sore throat, enlarged spleen or lymph nodes.
- Major Causes: Dysregulated immune response leading to systemic inflammation.
- Triggers: Unknown; may involve viral infections.
- Affected Joints/Motion: Large and small joints; can cause stiffness and limited range of motion.
- Remission Chances: Varies; can have remissions and flares.
- Average Onset Age: Often between 16 and 35 years; affects all ages.
- Chronic Interrelated Diseases: None specific; can overlap with other autoimmune conditions.
- Complications: Chronic joint damage, systemic organ involvement (heart, lungs).
- Autoimmune Type: Likely (immune-mediated systemic inflammation).
Granulomatosis with Polyangiitis (GPA, formerly Wegener’s):
- Description: Rare autoimmune vasculitis affecting small- to medium-sized blood vessels, including joints and respiratory tract.
- Major Symptoms: Sinusitis, joint pain, lung involvement (cough, shortness of breath).
- Causes: Autoimmune vasculitis targeting blood vessels.
- Minor Symptoms: Eye inflammation, skin lesions.
- Major Causes: Immune-mediated inflammation of blood vessel walls.
- Triggers: Genetic factors, environmental exposures.
- Affected Joints/Motion: Large and small joints; may cause joint pain and swelling.
- Remission Chances: Varies; requires immunosuppressive therapy.
- Average Onset Age: Typically 40s to 60s; affects all ages.
- Chronic Interrelated Diseases: Kidney disease, lung damage.
- Complications: Kidney failure, respiratory failure, heart involvement.
- Autoimmune Type: Yes (autoimmune vasculitis).
Lyme Arthritis:
- Description: Inflammatory arthritis caused by Lyme disease infection (tick-borne illness), affecting joints.
- Major Symptoms: Joint pain, swelling, erythema migrans (bull’s-eye rash).
- Causes: Borrelia burgdorferi infection transmitted by tick bite.
- Minor Symptoms: Fatigue, fever, neurological symptoms.
- Major Causes: Immune response to Lyme bacteria in joints.
- Triggers: Tick bite carrying Lyme bacteria.
- Affected Joints/Motion: Large joints (knees), can cause pain and stiffness.
- Remission Chances: Good with prompt antibiotic treatment in early stages.
- Average Onset Age: All ages; associated with outdoor exposure.
- Chronic Interrelated Diseases: Neurological Lyme disease, cardiac manifestations.
- Complications: Chronic joint damage, neurological symptoms.
- Autoimmune Type: No (infection-triggered arthritis).

Onset, Lifespan, and Autoimmunity

Inflammatory arthritis often presents in adulthood, with an average onset between 30 and 50 years old[^7]. The disease’s progression varies widely, but early diagnosis and proactive management can improve outcomes.

While the exact causes of inflammatory arthritis are not fully understood, a combination of genetic predisposition and environmental triggers, such as infections or hormonal changes, are believed to play a role[^8].

Inflammatory arthritis is considered an autoimmune disease because the immune system mistakenly attacks the body’s own tissues, including joints and other organs[^9]. This autoimmune response leads to chronic inflammation and tissue damage.

Risk Factors and Complications

Risk factors for developing inflammatory arthritis include genetic susceptibility, family history, smoking, and certain infections[^10]. Complications can range from joint deformities and disability to cardiovascular complications, including an increased risk of heart attack and stroke[^11].

Proactive Management and Quality of Life

Proactive management involves a multidisciplinary approach, including physical therapy, exercise, dietary modifications, and stress reduction techniques[^12]. Maintaining a healthy lifestyle, managing stress, and adhering to treatment plans can improve quality of life and reduce disease progression.

Podagra and Interconnected Conditions

Podagra, a specific type of inflammatory arthritis affecting the big toe joint due to uric acid crystal deposits, is associated with gout[^13]. Interconnected conditions may include psoriasis, inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE), which share similar immune-mediated mechanisms[^14].

Conclusion

Inflammatory arthritis, characterized by a dysregulated immune response, has far-reaching implications for joint health, overall well-being, and systemic health. Understanding its impact, symptoms, and proactive management strategies is crucial for improving outcomes and enhancing quality of life for individuals affected by these conditions.

References

McInnes, Iain B., and Georg Schett. “Pathogenetic insights from the treatment of rheumatoid arthritis.” The Lancet. 2017. Link
Scott, David L., and Paul Emery. “Rheumatoid arthritis.” The Lancet. 2010. Link
Smolen, Josef S., et al. “Rheumatoid arthritis.” Nature Reviews Disease Primers. 2018. Link
Singh, Jasvinder A. “Impact of arthritis on quality of life.” BMC Musculoskeletal Disorders. 2009. Link
Avina-Zubieta, J. Antonio, et al. “Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies.” Arthritis & Rheumatology. 2008. Link
Firestein, Gary S. “Evolving concepts of rheumatoid arthritis.” Nature. 2003. Link
Crowson, Cynthia S., et al. “Lifetime risk of symptomatic knee osteoarthritis.” Arthritis & Rheumatology. 2011. Link
MacGregor, Alexander J., et al. “The genetic contribution to radiographic hip osteoarthritis in women: results of a classic twin study.” Arthritis & Rheumatology. 2000. Link
Klareskog, Lars, et al. “Immunity to citrullinated proteins in rheumatoid arthritis.” Annual Review of Immunology. 2016. Link
Silman, Alan J., and Deborah PM Symmons. “Epidemiology of rheumatoid arthritis.” Rheumatology. 2002. Link
Goodson, Nicola J., et al. “Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s.” Annals of the Rheumatic Diseases. 2005. Link
Metsios, George S., et al. “Individualised exercise improves endothelial function in patients with rheumatoid arthritis.” Annals of the Rheumatic Diseases. 2008. Link
Neogi, Tuhina. “Gout.” New England Journal of Medicine. 2011. Link
Reich, K., et al. “Psoriasis and psoriatic arthritis.” Dermatology. 2015. Link