Types of Rheumatic Disease

Original Editor - Khloud Shreif

Top Contributors - Khloud Shreif, Lucinda hampton and Vidya Acharya  

Introduction

Historically, "rheumatism" was a term used to describe a range of painful conditions affecting muscles, tendons, joints, and bones. Nowadays, we prefer the more precise term "rheumatic disease." which are a group of inflammatory, often autoimmune, conditions that affect joints, muscles, bones, and organs. Osteoarthritis and rheumatoid arthritis are the most common of the rheumatic diseases but the group of diseases is much more, encompassing over 200 different conditions.

Rheumatic diseases can be divided into subsets:

• Autoimmune disease.
• Autoinflammatory disease.
• Degenerative.
• Metabolic disorders.

Pathogenesis of Rheumatic Disease

The pathogenesis of rheumatic disease is still under debate and not totally understood, it is suggested that complex interactions between genetic and environmental. One environmental factor considered is infection, long considered as an important risk and causative factor for rheumatic disease. eg this Epstein-Barr virus (EBV) and the development of systemic lupus erythematosus (SLE). It is postulated that our immune response gets confused and our immune system and inflammation responses get mixed up.

A Little Background (see more details here immune system)

There are different immune types of cells in our body, like T and B cells, monocytes/macrophages, to name a few.

• T cells especially (CD4+ T cells have subsets like Th1, Th2, Th17, and T regulatory cells which are a type of immune cell that plays a crucial role in coordinating the body's immune response. These subsets have distinct functions and are characterized by the specific proteins and molecules they produce and the roles they play in maintaining immune balance .
• B cells assume a crucial role in the pathogenesis of several rheumatic and immune disorders their primary function involves the production of antibodies (immunoglobulins) in response to pathogens, and their function in these conditions extends beyond antibody generation. These cells have special receptors on their surfaces, these receptors act like switches. When they come into contact with certain things, like antigens or other cells, they turn on and become active..

Hyperactive Immune System

In autoimmune and inflammatory rheumatic conditions, the immune system's cells become hyperactive, releasing a multitude of signaling molecules. These molecules not only summon more immune cells but also trigger inflammation and potential tissue damage. T cells, distributed throughout the body, can become autoreactive, meaning they mistakenly attack the body's own tissues. This can also disrupt the function of regulatory T cells, which normally help keep the immune system in check.

In addition to T cells, B cells play a significant role in these conditions. They produce autoantibodies, which erroneously target the body's tissues, leading to inflammation and tissue damage. Furthermore, B cells can produce cytokines, act as antigen-presenting cells to activate other immune cells, and create immune complexes. All of these actions contribute to the immune response and the associated inflammatory processes in these disorders. Picture it as a chain reaction: one switch activates another, setting off a series of events that ultimately impact our genes and drive the development and progression of these conditions..

Targeting B cells directly is a promising approach to treat immune and rheumatic diseases. B-cell depletion therapies have shown success in reducing disease activity by modulating the immune response. Understanding the complex role of B cells in immune regulation and dysregulation is essential for managing these conditions, leading to targeted therapies and ongoing research in the field.

General Classification Criteria of Rheumatic Diseases

There are still no accurate solo diagnostic procedures to diagnose or confirm Rheumatic Diseases, the Classification criteria will help to distinguish between similar diseases and confirm or exclude a specific disease based on specific factors. These criteria are guidelines, not the only way to diagnose. Diagnosis of rheumatic disease can be challenging, it relies on clinical assessment, gathering complete patient history, and carefully evaluating the musculoskeletal system is very important, hence match the findings during clinical examination with lab, X-ray, and sometimes tissue samples to confirm the diagnosis.

Rheumatoid arthritis classification criteria

In 1987, the American College of Rheumatology (ACR) introduced the initial classification criteria for RA, which required meeting 4 out of 7 criteria for over 6 weeks. Subsequently, a new classification criteria set was developed jointly by ACR/ EULAR in 2010. These updated criteria take into consideration the prognostic markers while maintaining high specificity and sensitivity. This allows for early patient identification and timely treatment with disease-modifying antirheumatic drugs DMARDs or inclusion in clinical trials for new therapies, enhancing care for those with early arthritis and enabling personalized treatment strategies.

Systemic Lupus Erythematosus Classification Criteria

In 2012, International Collaborating Clinics (SLICC) improved the 1997 criteria for categorizing lupus patients. These criteria help in research but aren't perfect for diagnosing patients. The new criteria are more sensitive (better at finding lupus cases) but less specific (may include some false positives). To be classified with lupus, a person must meet at least 4 out of 17 criteria, including one clinical and one immunologic sign. If a biopsy confirms lupus in the kidneys and there are positive autoantibodies, that's enough for classification.

Spondyloarthritis

Spondyloarthritis (SpA) includes diseases like ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, enteropathic-related spondylitis. There are different criteria for diagnosing SpA, mainly used in research, but the latest from the Assessment of SpondyloArthritis International Society suggests MRI is better for detecting early disease in the spine and sacroiliac area. They also defined inflammatory back pain and criteria for diagnosing axial and peripheral spondyloarthritis in early phases. ASAS introduced non-radiographic axial spondyloarthritis, which is similar to the radiographic form but lacks findings on plain X-rays and shows less ossification and inflammation on MRIs.

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  Axial spondyloarthritis

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  Peripheral spondyloarthritis

Psoriatic arthritis classification criteria

Psoriatic arthritis (PsA) is an inflammatory joint condition with diverse clinical subcategories. Various classification criteria have been proposed but lack widespread validation, complicating the diagnosis, particularly for patterns like seronegative polyarthritis and psoriasis.

Inflammatory articular disease (joint, spine, or entheseal) with ≥ 3 of the following:
1. Evidence of psoriasis: (one of a,b,c)	a. Current psoriasis	Psoriatic skin or scalp disease present today as judged by a rheumatologist or dermatologist
	b. Personal history of psoriasis	A history of psoriasis that may be obtained from the patient, family doctor, dermatologist, rheumatologist, or other qualified healthcare provider
	c. Family history	A history of psoriasis in a first or second-degree relative according to the patient’s reporting.
2. Psoriatic nail dystrophy	Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis observed on current physical examination
3. A negative rheumatoid factor	By any method except latex but preferably by ELISA or nephelometry, according to the local laboratory reference range
4. Dactylitis (a or b)	a. Current swelling of entire digit b. A history of dactylitis recorded by a rhematologist
5. Radiological evidence of juxta-articular new bone formation	III-defined ossification near joint margins (but excluding osteophyte formation) on plain X-rays of hands or feet

Systemic Sclerosis classification criteria

For sclerosis, ACR created criteria for diagnosing systemic sclerosis (SSc) based on skin symptoms. These criteria lacked accuracy for early disease diagnosis. In 2013, the ACR and EULAR collaborated to develop improved criteria to enhance early SSc and limited cutaneous SSc diagnosis, mainly for use in SSc trials, although they may be less suitable for scleroderma-like syndromes.

Antiphospholipid syndrome classification criteria

Antiphospholipid syndrome (APS) is an autoimmune disease known for causing blood clots in arteries and veins, as well as adverse pregnancy outcomes, associated with the presence of antiphospholipid antibodies (aPL), these antibodies can also be found in healthy individuals. The first classification criteria for APS were proposed in 1998 in Japan, involving positive antibody testing and at least one clinical manifestation of the disease. Due to its limitation in 2006, the criteria were modified in Sydney to address these limitations and improve accuracy in diagnosing APS, however, we need more understanding of the pathogenesis, and there i a need to detect laboratory studies to detect who are at risk.

Differences between autoimmune, autoinflammatory, metabolic, and anti-inflammatory disorders

• Autoimmune Disorders: characterized by the immune system mistakenly identifying the body's own tissues and cells as foreign invaders, resulting in an abnormal and overactive immune response against self-antigens. This immune dysregulation leads to chronic inflammation and damage to various organs and tissues. Examples of autoimmune disorders include rheumatoid arthritis, systemic lupus erythematosus (SLE) and dermatomyositis.
• Autoinflammatory disorders: characterized by recurrent episodes of inflammation, typically without a clear autoimmune or infection-triggered cause, many of autoinflammatory disorders have a genetic basis and tend to run in families, they result from a dysregulation of the immune response itself. Examples of autoinflammatory disorders include Familial Mediterranean fever (FMF).
• Metabolic disorders: involve disruptions in the body's normal metabolic processes. They affect functions such as energy production, nutrient storage, and hormone regulation, but they are not primarily related to immune responses. However metabolic disorders can indirectly impact the immune system due to imbalances in biochemical pathways, they are distinct from autoimmune disorders. Diabetes, both type 1 and type 2, is an example of metabolic disorder.
• Anti-inflammatory disorders: characterized by chronic inflammation even when there's no infection or injury. Normally, inflammation helps us fight infections and heal wounds, but in these disorders, the immune system gets confused and keeps causing inflammation that can harm the body. For example asthma, crohn's disease, and psoriasis.

Autoimmune	Autoinflammatory	Degenerative and metabolic disorders
Systemic lupus erythematosus Rheumatoid arthritis Psoriatic Arthritis Ankylosing Spondylitis Systemic sclerosis (Scleroderma) Idiopathic inflammatory myopathies Antiphospholipid syndrome Sjogren’s syndrome Primary vasculitis Dermatomyositis	Familial Mediterranean fever Mevalonate kinase deficiencies Muckle-Wells syndrome Familial cold urticaria NOMID syndrome NLRP12-associated syndrome/NLRP12-associated periodic fever syndrome PAPA syndrome Chronic recurrent multifocal osteomyelitis Adult-onset Still disease	OsteoarthritisOsteoporosis Parathyroid disorders Paget’s disease Calcium and phosphorus disorders (Hypercalcemia/ Hypocalcemia/ Hyperphosphatemia/ Hypophosphatemia) Vitamin D deficiency/osteomalacia Renal osteodystrophy Gout Hemochromatosis Ochronosis

Rheumatoid Arthritis and Osteoarthritis

Rheumatoid Arthritis	Osteoarthritis
Autoimmune inflammatory arthritis, more aggressive course. A family history of RA or specific genetic markers like HLA-DRB1 can increase the risk. Smoking, age usually develops between (40-60), and females are predisposing factors. Symmetrical joint involved, narrowing in joint space, soft tissue swelling, erosion, and joint deformities are common findings Pain, swelling, and Morning stiffness lasting > 1 hour that improves with use. Systemic symptoms (fever, fatigue, weight loss), and extraarticular manifestations are common.	Degenerative joint disorder/Mechanical—wear and tear that destroys articular cartilage. Age, obesity, and joint trauma are risk factors Narrowing in joint space (asymmetric), osteophytes, noninflammatory synovial fluid, and no joint deformities are common findings Pain will aggravate during weight-bearing on the joint after activities e.g.: at the end of the day) and improve with rest. No systemic symptoms were involved.
		N.B: Arthritis is a common feature in many rheumatic conditions, but it is not synonymous with rheumatic disease. Rheumatic diseases are a group of conditions that can involve arthritis as a symptom, while arthritis is a more specific term describing joint inflammation that can occur in various rheumatic diseases.