AiArthritis logo showing stylized infinite loop symbol in red with black dots, above organization name for International Foundation for Autoimmune & Autoinflammatory Arthritis.

Diseases

Autoimmune Disease with Inflammatory Arthritis and Autoinflammatory Disease with Inflammatory Arthritis

There are over 100 "auto" diseases - autoimmune disease or autoinflammatory disease (originating from different parts of the immune system), but only a fraction of those include inflammation-driven arthritis as a clinical presentation in most patients.  Those are the diseases we represent.


Focusing on these diseases - including their similarities to each other and differences from other autoimmune/autoinflammatory diseases or types of arthritis - can help raise global awareness and expedite detection, referrals, diagnosis, and treatment, resulting in a better quality of life and higher rates of remission.


Whether a disease is autoimmune, autoinflammatory, or a combination of both is based on where it was triggered in the immune system. Learn more about the differences between autoimmune and autoinflammatory.

Diseases that most overlap in presentation and symptoms

 

*Over the past few years, research has shown that spondyloarthritis may be a little bit of both autoimmune to autoinflammatory, as most diseases fall somewhere along a continuum. AiArthritis is dedicated to keeping informed about this new information, including how it may impact other similar diseases. 

Undifferentiated Disease

When autoimmune and autoinflammatory diseases with inflammation-driven arthritis as a major component are not fully developed, or overlap so that a precise diagnosis cannot be determined, they are often given an "undifferentiated" diagnosis. 

Some common terms associated with Undifferentiated Disease include: Undifferentiated Connective Tissue Disease (UCTD), Undifferentiated Spondyloarthropathy (USpA), Unclassified Seronegative Spondyloarthritis, Undifferentiated Inflammatory Arthritis/Polyarthritis, and Seronegative Inflammatory Arthritis, Undifferentied Autoinflammatory Disease, Systemic Autoinflammatory Disease/Unclassified Systemic Autoinflammatory Disease,  Undifferentiated Autoinflammatory Disorder.* However, there is no agreed upon definitions or diagnostic criteria associated with many of these terms and, as a result, established treatment protocols vary. 

Furthermore, the percentage of patients who progress to a full AiArthritis disease is not clear, as reports range from 15% to over 50% and criteria for the research differs (i.e. In many a patient must have serologic positivity, or positive blood test results, to be included in the study. However, given many patients who have our diseases have negative blood work, our organization strongly believes sero-positive criteria should be removed from classification criteria and only used to help identify possible disease etiology.)  Based on our internal research and continued conversations with our community. We believe the percentage of patients who progress to full disease is over 50% (References 1, 2).  For these reasons, Undifferentiated Disease is a priority topic for us and will continue to be for years to come.


*We are currently working with medical advisers to construct a full list of undifferentiated terms, complete with definitions. We believe this is a vital step towards expediting detection and understanding the true prevalence and progression associated with early AiArthritis disease.

Additional diseases that may have more differentiating symptoms

These diseases are also under the AiArthritis umbrella. We separated them because there are disease features that could differentiate them easier from the conditions in the first group.

 

  • Crohn's Disease - arthritis associated is called enteropathic arthritis, possibly caused by bacteria in the bowel (Reference 3)
  • Sarcoidosis - Juvenile Systemic Granulomatosis/Pediatric Granulomatous Arthritis (PGA)/Early Onset Sarcoidosis
  • Relapsing Polychondritis (RP)
  • VEXAS Syndrome - Vacuoles, E1 mutation, X chromosome, Autoinflammation, Somatic, often associated with RP
  • Systemic Sclerosis/Scleroderma (SSc)
  • Behcet's Disease (BD)
  • Palindromic Rheumatism (PR)
  • Antisynthetase Syndrome (ASS) (typically associated with myositis, may include inflammatory polyarthritis as a major clinical component).
  • Mixed Connective Tissue Disease (MCTD) which typically consists of a blended diagnosis of three diseases: systemic sclerosis, lupus or rheumatoid arthritis, and polymyositis.

Very Rare Diseases

There are also some very rare autoinflammatory diseases that often include inflammatory arthritis as a major clinical component. These include:

 

  • Familial Mediterranean Fever (FMF)
  • HIDS (hyper-IgD syndrome, a mevalonate kinase deficiency)
  • Cryopyrin-Associated Periodic Syndromes (CAPS) - Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome
  • Schnitzler Syndrome
  • Chronic Nonbacterial Osteomyelitis (CNO)/Chronic Recurrent Multifocal Osteomyelitis (CRMO)



Note: There are other types of arthritis, other than autoimmune/autoinflammatory or degenerative, such as gout. Reactive Arthritis is not included on this list because it is often a 'reaction' to an infection from another part of the body (not necessarily immune-inspired).  Fibromyalgia is not listed because it is a nerve condition, not an AiArthritis disease. There are also over 80 other types of autoimmune and autoinflammatory diseases that may involve arthritis, but it is not usually considered a major disease feature in most patients and is not a diagnostic feature early in onset*.


*The underlying rationale behind our formation was to unite the small group of similar diseases that were either autoimmune or autoinflammatory, which also had the same type of arthritis present early in the disease. We believe doing this will help expedite detection, referrals, and diagnosis, resulting in earlier intervention, higher rates of remission, and better disease outcomes.  If there is an autoimmune or autoinflammatory disease where arthritis is a core disease feature, is present in most patients, and it is not on this list please email info@aiarthritis.org and type "Disease Addition" in the Subject Line. We annually review our disease list with a team of medical specialists and will update as necessary.


Associated Conditions

These are some of the conditions that often occur with these diseases. In some cases, these conditions are natural parts of the diseases above. For example, lupus nephritis is the evolution of kidney disease in patients with Systemic Lupus Erythematosus. In several of our diseases, eye inflammation is a primary part of the condition - but in others, it is a comorbidity (complication caused by uncontrolled inflammation).


 

  • Fibromyalgia (nerve condition, often misunderstood to be an autoimmune disease)
  • Heart disease
  • Lung issues
  • Dysautonomia
  • Neuropathy/Peripheral
  • Raynaud's Phenomenon
  • Eye Inflammation (uveitis/iritis/scleritis/occular)
  • Potential dental issues (such as inflammation in the gums, decay)
  • Vasculitis
  • Myositis/Polymyositis/Dermatomyositis
  • Celiac's Disease
  • Thyroidism
  • Lupus Nephritis
  • IgG4
  • Ulcerative Colitis

 

Common Symptoms of Core Diseases (Auto + Inflammatory Arthritis = AiArthritis)

The following list of early disease features is based on our research into patient-reported symptoms of our core diseases , which is based on our Early Symptoms of AiArthritis study, publications by scientific societies and rheumatology clinics, and feedback from patient organization partners.  These symptoms were reported by at least 30% of all patients in early disease, regardless of core disease diagnosis .  We define early disease as 

0 < 12 months from onset.


Autoimmune/Autoinflammatory OR "AUTO" disease features, regardless of diagnosis:

 

  • Fatigue that is severe and unusual, not immediately corrected with rest or caffeine. ( > 95%)
  • Flu-like symptoms, without having the flu- nausea, muscle weakness, and general malaise. ( > 50%)
  • "Brain fog", or finding it difficult to put thoughts together. This symptom historically has been mostly associated with lupus, but it is common in the other core diseases.  ( > 30%)
  • Fever, typically low grade in autoimmune (with exception of juvenile idiopathic arthritis) and higher grade in autoinflammatory (% strongly varies per core disease)

 

Inflammatory Arthritis features:

  • Joint pain in at least one joint lasting for longer than six weeks and not due to injury, other condition, or medication. (Required for differentiating this type of arthritis from mechanical pain and osteoarthritis)
  • Severe stiffness, which is worse after rest or inactivity. Many patients report they suddenly feel like their bed is uncomfortable because of the severe stiffness after rest. ( > 50%)
  • Redness and/or swelling around the joints ( > 30%)

 


Typically the joint pain will coincide with the autoimmune and autoinflammatory disease features and start and stop suddenly - for no apparent reason (which is called a "flare").  Some people will experience all of the above symptoms, others only a few.   If you have any of the arthritis features, and at least one of the autoimmune/autoinflammatory features, please consult your physician about a referral to a specialist.


The Mystery Patient

Patient-Led Diagnosis Tools

Did you go through a complex diagnosis journey?  Tell us about it. Your story can help us identify patterns and, in turn, create patient-inspired guidance to improve diagnosis.

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References:

 

  1. Our  Early Symptoms of AiArthritis Study
  2.  Undifferentiated Connective-Tissue Disease, Hildebrand, B., et al; Medscape, 2018.
  3. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Spondyloarthritis 

 



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