Which AiArthritis Diseases Can Be Considered Rare?

How Rare are Autoimmune and Autoinflammatory Arthritis Diseases?

Autoimmune and autoinflammatory arthritis diseases encompass a spectrum of conditions with varying prevalence. While individually some of these diseases are rare, collectively they affect millions worldwide, underscoring the importance of awareness, research, and support for those living with these chronic conditions.

The World Health Organization defines a rare disease as one that impacts fewer than 65 per 100,000 people. Here is a breakdown of how common AiArthritis Diseases are.

Considered  Rare  Globally

Cryopyrin-Associated Periodic Syndromes (CAPS):

Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare autoinflammatory disorders with an estimated prevalence of less than 1 in 1,000,000 caused by mutations in the NLRP3 gene. They all share common features such as recurrent episodes of fever, rash, joint pain, and systemic inflammation, but they vary in severity and specific symptoms.

• Familial Cold Autoinflammatory Syndrome (FCAS)-  FCAS is extremely rare, with an estimated prevalence of less than 1 in 1,000,000. It is primarily reported in families of North American and European descent and affects both males and females equally.
• Muckle-Wells Syndrome (MWS) - MWS is also a rare condition, with an estimated prevalence of around 1 in 360,000 people. This number may vary globally due to underdiagnosis or misdiagnosis.
• Neonatal-Onset Multisystem Inflammatory Disease (NOMID) - NOMID is the rarest and most severe form of CAPS, with an estimated prevalence of less than 1 in 1,000,000. It is characterized by chronic inflammation affecting multiple systems in the body from birth or early infancy.

Schnitzler Syndrome (SS):

Very rare, with an estimated prevalence of fewer than 1 in 1,000,000 people. Schnitzler Syndrome is a rare autoinflammatory disorder characterized by chronic urticaria (hives) and recurrent fever, along with bone pain, joint pain, and other systemic symptoms. Diagnosis is often challenging due to the rarity and variability of symptoms.

Chronic Nonbacterial Osteomyelitis (CNO) and Chronic Recurrent Multifocal Osteomyelitis (CRMO): 

The prevalence of CNO is not well-documented, but it is considered a rare condition, with fewer than 1 in 1,000,000 individuals affected. Chronic Nonbacterial Osteomyelitis (CNO) is a rare autoinflammatory bone disorder that primarily affects children and adolescents. 

Familial Mediterranean Fever (FMF): 

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder primarily affecting individuals of Turkish, Armenian, Middle Eastern, North African Jewish, and Arab descent. The prevalence of FMF varies significantly by region, with the highest rates observed in Turkey (1 in 150 to 1 in 10,000) and Armenia (1 in 500). FMF is less common in other regions but still notable among populations with Mediterranean ancestry.

VEXAS Syndrome

 VEXAS Syndrome is a rare condition, with an estimated prevalence of about 1 in every 13,591 adults. It is more common in middle-aged to older men.

Hyperimmunoglobulinemia D Syndrome (HIDS):

Rare, with several hundred cases reported globally. Hyperimmunoglobulinemia D Syndrome (HIDS) is a rare autosomal recessive genetic disorder. The syndrome typically presents in early childhood, with most patients experiencing their first attack within the first year of life. HIDS is more prevalent among individuals of Dutch and French ancestry, but cases have been reported worldwide. The exact prevalence is unknown, but it is estimated to affect several hundred people globally.

Relapsing Polychondritis (RP): 

Relapsing Polychondritis (RP) is a chronic autoimmune disorder characterized by recurrent inflammation of cartilage and other tissues throughout the body. The prevalence of RP is estimated to be around 1 in 285,000 people, making it quite rare

Undifferentiated Disease (UD):

Undifferentiated Disease (UD), is a term used to describe a condition where a person exhibits symptoms and lab test results indicative of a systemic autoimmune disorder or connective tissue disease, but these features are not specific or extensive enough to meet the criteria for a definitive diagnosis. UD is relatively common in rheumatology clinics, accounting for about 10% to 20% of referrals to rheumatology specialists

Common types of undifferentiated disease include:

• Undifferentiated Connective Tissue Disease (UCTD) is relatively common among patients seen by rheumatologists, with estimates suggesting that up to 25% of patients may have UCTD.
• Undifferentiated Spondyloarthritis (USpA) prevalence varies, but it is generally low, with estimates ranging from 0.0% to 0.7%.
• Unclassified Seronegative Spondyloarthritis is a condition that is part of the broader category of spondyloarthritis, which has a prevalence of about 0.5% to 1% globally.
• Undifferentiated Inflammatory Arthritis/Polyarthritis affects approximately 41 to 149 per 100,000 adults.

Sarcoidosis (Sarc):

Sarcoidosis and Juvenile Systemic Granulomatosis (also called Blau Syndrome or Early Onset Sarcoidosis) are rare inflammatory diseases. They are very uncommon, occurring in less than 1 person per 1.5 million people each year.

• Sarcoidosis is an inflammatory disease that causes small clusters of immune cells called granulomas to form in various organs, most commonly the lungs and lymph nodes. The exact cause is unknown, but it is believed to be a combination of genetic and environmental factors. Symptoms can vary widely depending on the organs affected and may include fatigue, fever, swollen lymph nodes, and lung issues like a persistent cough and shortness of breath. In many cases, sarcoidosis resolves on its own, but some people may require treatment to manage symptoms and prevent complications.
• Juvenile Systemic Granulomatosis (Blau Syndrome) and Early Onset Sarcoidosis are rare inflammatory diseases that start in early childhood. Both involve the formation of clusters of immune cells in various organs. Blau Syndrome is caused by mutations in the NOD2 gene and leads to joint, eye, and skin inflammation. Early Onset Sarcoidosis affects children and shares similar symptoms due to the same gene mutations.

Behcet's Disease (BD):

The prevalence of Behcet's Disease varies by region, being more common in the Middle East, Asia, and the Mediterranean basin, and less common in the United States and Europe. The disease typically begins in the 20s to 40s age range and affects both men and women equally

Still's Disease

Both Adult Onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (sJIA) share similar systemic symptoms and are part of the Still's disease spectrum, but they differ in the age of onset and specific clinical manifestations.

• Adult Onset Still's Disease (AOSD) is a rare type of arthritis that shows up unexpectedly in early adulthood. It causes symptoms like high fevers, joint pain, and a unique salmon-colored rash. AOSD is very rare, affecting about 0.22 to 0.34 people per 100,000 each year, and around 0.73 to 1.47 people per 100,000 overall. The disease mostly occurs in two age groups: 15-25 years old and 36-46 years old.
• Systemic Juvenile Idiopathic Arthritis (sJIA) is  a rare subtype of juvenile idiopathic arthritis that causes body-wide inflammation. It is the only subtype of JIA considered an autoinflammatory disease rather than autoimmune.sJIA accounts for approximately 10% to 20% of all cases of juvenile idiopathic arthritis. It affects both boys and girls equally and can occur at any age during childhood, most commonly starting around two years of age.

Palindromic Rheumatism (PR): 

Palindromic Rheumatism (PR) is a rare type of inflammatory arthritis PR typically affects people between the ages of 20 and 50. It's estimated to affect about 1 in 20,000 people.

Antisynthetase Syndrome (ASS): 

Antisynthetase Syndrome is a rare autoimmune disorder that causes inflammation in various parts of the body, including muscles, joints, lungs, and skin. Antisynthetase Syndrome is quite rare. It affects approximately 1 to 3 people per 100,000 worldwide. It's more common in women, with about 1 in 25,000 to 33,000 people being affected.

Mixed Connective Tissue Disease (MCTD): 

Mixed Connective Tissue Disease (MCTD) is a rare autoimmune disorder that exhibits features of three different connective tissue diseases: systemic lupus erythematosus (SLE), scleroderma, and polymyositis. The prevalence and incidence rates vary, but it's estimated to affect about 2 to 3.8 persons per 100,000 in the general population. MCTD is more commonly diagnosed in females, with a female-to-male ratio ranging from 3:1 to 16:1.

Systemic Sclerosis (Scleroderma):

Systemic Sclerosis (Scleroderma) is a rare autoimmune disorder characterized by the hardening and tightening of the skin and connective tissues, potentially affecting internal organs like the lungs, heart, kidneys, and digestive system. There are two main types:

• Limited Cutaneous Systemic Sclerosis (formerly known as CREST syndrome), which primarily affects the skin of the hands, arms, and face, progresses more slowly, and generally has a better prognosis
• Diffuse Cutaneous Systemic Sclerosis, which affects larger areas of the skin including the torso, upper arms, and legs, is more likely to involve internal organs, and can lead to significant organ damage. 

Considered Less  Rare Globally

Sjögren's Disease (SD): 

• Sjögren's Disease (SD) is a chronic autoimmune disorder that primarily affects the body's moisture-producing glands, leading to symptoms like dry eyes and dry mouth. It's more common in women, particularly those over the age of 40. The prevalence of SD varies widely, but it is estimated to affect between 0.3 to 180 per 10,000 people globally. In the United States, it is estimated that there are between 499,950 to 1,433,190 cases.
• Juvenile Sjögren's Disease (juvenile SD) is much rarer and often presents differently than in adults. Children with juvenile SD may not exhibit the classic symptoms of dry eyes and dry mouth as prominently. Instead, they might experience recurrent parotitis (inflammation of the salivary glands), joint pain, and other systemic symptoms. There have been 145 recorded cases of primary juvenile SD in international pediatric literature.

Crohn's Disease

Arthritis is a common extraintestinal manifestation of Crohn's disease, affecting up to 30% of individuals with the condition. The number of people diagnosed with Crohn's disease is increasing, and it is considered one of the highest prevalence rates of IBD in the world. Ulcerative Colitis, another type of IBD does not include arthritis as a symptom. 

Juvenile Idiopathic Arthritis (JIA):

The most common type of arthritis in children, with several subgroups including oligoarticular JIA, polyarticular JIA, and enthesitis-related arthritis (ERA).

• Oligoarticular JIA: This is the most common form, affecting about 50% of children with juvenile idiopathic arthritis (JIA). It involves fewer than five joints, often the knees and ankles.
• Polyarticular JIA: This type affects 5 or more joints and is less common than oligoarticular JIA. It can be more severe and persistent.
• Enthesitis-related arthritis (ERA): This form is less common but still significant, involving inflammation where tendons and ligaments attach to bones.

Psoriatic Arthritis (PsA) and Juvenile Psoriatic Arthritis (JPsA):

• Psoriatic Arthritis (PsA) is a chronic inflammatory arthritis that often occurs in association with psoriasis. The global prevalence of PsA is estimated to be around 112 per 100,000 adults. It's more common in Europe and North America compared to Asia and South America.
• Juvenile Psoriatic Arthritis (JPsA) is a subtype of juvenile idiopathic arthritis (JIA) and constitutes about 5% of JIA cases making it relatively rare. Girls are slightly more likely to develop JPsA than boys.

Systemic Lupus Erythematosus (SLE) and Juvenile Systemic Lupus Erythematosus (JSLE):

• Systemic Lupus Erythematosus (SLE), commonly known as lupus, is more common in women, particularly those of childbearing age, and its prevalence varies globally, being more prevalent among certain racial and ethnic groups.
• Juvenile Systemic Lupus Erythematosus (JSLE), or childhood-onset SLE, occurs in children and adolescents. While it shares many similarities with adult SLE, JSLE tends to be more severe and can lead to earlier organ damage. It affects approximately 1.1 to 9.7 per 100,000 children and adolescents worldwide.

Lupus is generally considered a rare disease in many countries, though classifications vary based on prevalence thresholds:

• In Europe, lupus is considered rare, with an estimated prevalence of fewer than 5 in 10,000 people.
• In the United States, it's classified as rare if it affects fewer than 200,000 people.
• In India, lupus is deemed rare when it affects fewer than 1 in 2,500 people.

Despite these classifications, lupus affects over 5 million people worldwide. It's a complex autoimmune disease that can impact multiple organs and presents with a wide range of symptoms

Rheumatoid Arthritis (RA):

Thought to be the most common autoimmune arthritis, though axial spondyloarthritis may be taking the lead now. RA affects millions of people worldwide. Rheumatoid arthritis (RA) is not extremely rare, but it's not incredibly common either. Approximately 1% of the worldwide population is affected by RA. In the United States, over 1.3 million Americans are living with RA. The prevalence tends to be higher in industrialized countries, and women are about two to three times more likely to develop RA than men.

Axial Spondyloarthritis (AxSpA):

Ankylosing Spondylitis (AS) and Non-Radiographic Axial Spondyloarthritis (nr-axSpA) are subtypes of Axial Spondyloarthritis (AxSpA), a chronic inflammatory condition affecting the spine and sacroiliac joints. AxSpA is significant, affecting about 0.9% to 1.4% of the U.S. population.

• Ankylosing Spondylitis (AS) is diagnosed when there is radiographic evidence of sacroiliitis (inflammation of the sacroiliac joints) seen on X-rays. It's relatively rare globally, with a prevalence ranging from 0.1% to 1.4%. Higher rates are observed in Northern Arctic communities, while lower rates are seen in Sub-Saharan Africa. AS typically presents with chronic back pain and stiffness and can lead to the fusion of vertebrae, resulting in reduced flexibility and mobility.
• Non-Radiographic Axial Spondyloarthritis (nr-axSpA) presents similar symptoms to AS, such as persistent pain and stiffness in the lower back and buttocks, but lacks definitive radiographic evidence of sacroiliitis. Its prevalence is less well-documented but is believed to be more common than AS. Studies show that 5% to 30% of individuals with nr-axSpA may progress to AS over a period of 2 to 30 years.
• Juvenile Axial Spondyloarthritis refers to AxSpA occurring in children and adolescents. It is rare and can present similarly to adult AxSpA but may involve other joints and cause symptoms like enthesitis (inflammation of tendons and ligaments) and uveitis (eye inflammation).