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54-615: Some conditions which biologics are used to treat are rheumatic disorders such as psoriatic arthritis , ankylosing spondylitis and non-radiographic axial spondyloarthritis , and inflammatory bowel disease . Biologics provide immunotherapy and can function as disease-modifying antirheumatic drugs . Biologics can generally be grouped by their "class", that is, their specific mechanism of action and affected targets. Some classes are TNF inhibitors , anti- IL-17A antibodies, and IL-23 antibodies. For people with moderate to severe psoriatic arthritis , biologics can provide some relief of

108-676: A genetic predisposition , other cases have been associated with infectious triggers or exposure to environmental factors, implying a complex interplay between genes and environment in their etiology. Some of the most common diseases that are generally categorized as autoimmune include coeliac disease , type 1 diabetes , Graves' disease , inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis ), multiple sclerosis , alopecia areata , Addison's disease , pernicious anemia , psoriasis , rheumatoid arthritis , and systemic lupus erythematosus . Diagnosing autoimmune diseases can be challenging due to their diverse presentations and

162-658: A biologic first. Most biologics are injections so are not appropriate for use by someone with intense fear of needles . A person with any infection should not use biologics. Other contraindications for biologics include cancer, certain neurologic disorders, being pregnant or breastfeeding, history of heart failure, or history of tuberculosis. Common adverse effects of biologic administration are injection site reactions including redness , pain, and itching . Other adverse effects include headache, skin reactions, respiratory tract infection , and urinary tract infection . Adverse effects may be class-dependent, and so switching to

216-463: A biologic of another class may ameliorate those effects. Potential serious adverse effects include allergic reactions , liver damage, cancer, and serious infections including tuberculosis , pneumonia , staph infection , and fungal infection . Patients with systemic lupus erythematosus (SLE) who are treated with the standard of care, including biologic response modifiers, experience a higher risk of mortality and opportunistic infection compared to

270-457: A crucial step in triggering autoimmune diseases. The exact mechanisms by which they contribute to disease onset remain to be fully understood. For instance, certain autoimmune conditions like Guillain-Barre syndrome and rheumatic fever are thought to be triggered by infections. Furthermore, analysis of large-scale data has revealed a significant link between SARS-CoV-2 infection (the causative agent of COVID-19 ) and an increased risk of developing

324-403: A function that is compromised in autoimmune diseases. In healthy individuals, immune tolerance prevents the immune system from attacking the body's own cells. When this process fails, the immune system may produce antibodies against its own tissues, leading to an autoimmune response. The elimination of self-reactive T cells occurs primarily through a mechanism known as "negative selection" within

378-473: A genetic component. Some conditions, like lupus and multiple sclerosis, often occur in several members of the same family, indicating a potential hereditary link. Additionally, certain genes have been identified that increase the risk of developing specific autoimmune diseases. Evidence suggests a strong genetic component in the development of autoimmune diseases. For instance, conditions such as lupus and multiple sclerosis frequently appear in multiple members of

432-519: A higher concordance rate among identical twins compared with fraternal twins. For instance, the rate in multiple sclerosis is 35% in identical twins compared to 6% in fraternal twins. There is increasing evidence that certain genes selected during evolution offer a balance between susceptibility to infection and the capacity to avoid autoimmune diseases. For example, variants in the ERAP2 gene provide some resistance to infection even though they increase

486-484: A pivotal role in the diagnosis of autoimmune diseases. These tests can identify the presence of certain autoantibodies or other immune markers that indicate a self-directed immune response. In some cases, imaging studies may be used to assess the extent of organ involvement and damage. For example, chest x-rays or CT scans can identify lung involvement in diseases like rheumatoid arthritis or systemic lupus erythematosus, while an MRI can reveal inflammation or damage in

540-442: A potential causative factor in the development of autoimmune diseases, such as dermatomyositis. Furthermore, exposure to pesticides has been linked with an increased risk of developing rheumatoid arthritis. Vitamin D, on the other hand, appears to play a protective role, particularly in older populations, by preventing immune dysfunctions. Infectious agents are also being increasingly recognized for their role as T cell activators —

594-440: A thorough evaluation of the patient's medical history and a comprehensive physical examination. Clinicians often pay close attention to the patient's symptoms, family history of autoimmune diseases, and any exposure to environmental factors that might trigger an autoimmune response. The physical examination can reveal signs of inflammation or organ damage, which are common features of autoimmune disorders. Laboratory testing plays

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648-427: A wide range of new-onset autoimmune diseases. Women typically make up some 80% of autoimmune disease patients. Whilst many proposals have been made for the cause of this high weighting, no clear explanation is available. A possible role for hormonal factors has been suggested. For example, some autoimmune diseases tend to flare during pregnancy (possibly as an evolutionary mechanism to increase health protection for

702-594: Is a close overlap between the term soft tissue disorder and rheumatism. Sometimes the term "soft tissue rheumatic disorders" is used to describe these conditions. The term "Rheumatic Diseases" is used in MeSH to refer to connective tissue disorders . The branch of medicine devoted to the diagnosis and therapy of rheumatism is called rheumatology . Many rheumatic disorders of chronic, intermittent pain (including joint pain , neck pain or back pain ) have historically been caused by infectious diseases. Their etiology

756-421: Is a systemic autoimmune disease that affects multiple organs, including the skin, joints, kidneys, and the nervous system. It is characterized by a widespread loss of immune tolerance. The disease is characterized by periods of flares and remissions, and symptoms range from mild to severe. Women, especially those of childbearing age, are disproportionately affected. Type 1 diabetes is a condition resulting from

810-427: Is associated with an increased risk of central nervous system cancer, primarily in the brain. Rheumatoid arthritis (RA) primarily targets the joints, causing persistent inflammation that results in joint damage and pain. It is often symmetrical, meaning that if one hand or knee has it, the other one does too. RA can also affect the heart, lungs, and eyes. Additionally, the chronic inflammation and over-activation of

864-492: Is correlated with lymphoproliferative disorders . Graves' disease is a condition characterized by development of autoantibodies to thyroid-stimulating hormone receptors. The binding of the autoantibodies to the receptors results in unregulated production and release of thyroid hormone , which can lead to stimulatory effects such as rapid heart rate, weight loss, nervousness, and irritability. Other symptoms more specific to Graves' disease include bulging eyes and swelling of

918-529: Is equipped with several mechanisms to maintain a delicate balance between defending against foreign invaders and protecting its own cells. To achieve this, it generates both T cells and B cells , which are capable of reacting with self-proteins. However, in a healthy immune response, self-reactive cells are generally either eliminated before they become active, rendered inert via a process called anergy, or their activities are suppressed by regulatory cells. A familial tendency to develop autoimmune diseases suggests

972-442: Is estimated that over 80 recognized types of autoimmune diseases exist, this section provides an overview of some of the most common and well-studied forms. Coeliac disease is an immune reaction to eating gluten , a protein found in wheat , barley , and rye . For those with the disease, eating gluten triggers an immune response in the small intestine , leading to damage on the villi , small fingerlike projections that line

1026-491: The ESR and CRP is possible. After a purine-restricted diet, another urine test will help determine whether the body is producing too much uric acid or the body isn't excreting enough uric acid. Rheumatoid factor may be present, especially in the group that is likely to develop rheumatoid arthritis . A fine needle is used to draw fluid from a joint to determine if there is any build-up of fluid. The presence of uric acid crystals in

1080-520: The Late Latin rheumatismus , ultimately from Greek ῥευματίζομαι "to suffer from a flux", with rheum meaning bodily fluids, i.e., any discharge of blood or bodily fluid. Before the 17th century , the joint pain which was thought to be caused by viscous humours seeping into the joints was always referred to as gout , a word adopted in Middle English from Old French gote "a drop;

1134-638: The United States treatment with biologic drugs typically costs US$ 2,000 –6,000 per month, compared to US$ 12 –600 per month for conventional (small-molecule) DMARDs . Rheumatic disorder Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue . Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including arthritis and "non-articular rheumatism", also known as "regional pain syndrome" or "soft tissue rheumatism". There

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1188-470: The bacterium that causes strep throat , Streptococcus pyogenes , might trigger rheumatic fever , an autoimmune response affecting the heart. Similarly, some studies propose a link between the Epstein–Barr virus , responsible for mononucleosis, and the subsequent development of multiple sclerosis or lupus. Another area of interest is the immune system's ability to distinguish between self and non-self,

1242-527: The biopharmaceutical products which could be extracted from organisms without biotechnology from the Information Age , such as blood for transfusion, early insulin extracted from animals, and vaccines from eggs. When biologic drugs became available they led to significant changes in the management of various autoimmune diseases . The term "biologic therapy" is nonspecific, and can refer to any biopharmaceutical medication. However, many sources use

1296-477: The body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved. Autoimmune diseases are a separate class from autoinflammatory diseases . Both are characterized by an immune system malfunction which may cause similar symptoms, such as rash, swelling, or fatigue, but

1350-492: The body's immune system mistakenly attacking its own cells and tissues, causing inflammation and damage. However, due to the broad range of autoimmune diseases, the specific presentation of symptoms can significantly vary based on the type of disease, the organ systems affected, and individual factors such as age, sex, hormonal status, and environmental influences. An individual may simultaneously have more than one autoimmune disease (known as polyautoimmunity), further complicating

1404-497: The body's self-molecules. This phenomenon, known as molecular mimicry , can lead to cross-reactivity, where the immune response to such infections inadvertently results in the production of antibodies that also react with self-antigens. An example of this is Guillain–Barré syndrome , in which antibodies generated in response to a C. jejuni infection also react with the gangliosides in the myelin sheath of peripheral nerve axons. Diagnosing autoimmune disorders can be complex due to

1458-923: The cardinal cause or mechanism of the diseases are different. A key difference is a malfunction of the innate immune system in autoinflammatory diseases, whereas in autoimmune diseases there is a malfunction of the adaptive immune system . Symptoms of autoimmune diseases can significantly vary, primarily based on the specific type of the disease and the body part that it affects. Symptoms are often diverse and can be fleeting, fluctuating from mild to severe, and typically comprise low-grade fever , fatigue , and general malaise . However, some autoimmune diseases may present with more specific symptoms such as joint pain , skin rashes (e.g., urticaria ), or neurological symptoms. The exact causes of autoimmune diseases remain unclear and are likely multifactorial, involving both genetic and environmental influences. While some diseases like lupus exhibit familial aggregation, suggesting

1512-422: The child), when hormone levels are high, and improve after menopause, when hormone levels decrease. Women may also naturally have autoimmune disease trigger events in puberty and pregnancy. Under-reporting by men may also be a factor, as men may interact less with the health system than women. Certain viral and bacterial infections have been linked to autoimmune diseases. For instance, research suggests that

1566-442: The complexity and multifaceted nature of these conditions. Various environmental triggers are identified, some of which include: Chemicals, which are either a part of the immediate environment or found in drugs, are key players in this context. Examples of such chemicals include hydrazines , hair dyes , trichloroethylene , tartrazines , hazardous wastes, and industrial emissions. Ultraviolet radiation has been implicated as

1620-447: The development and progression of various autoimmune diseases, either directly or as catalysts. Current research suggests that up to seventy percent of autoimmune diseases could be attributed to environmental influences, which encompass an array of elements such as chemicals, infectious agents, dietary habits, and gut dysbiosis. However, a unifying theory that definitively explains the onset of autoimmune diseases remains elusive, emphasizing

1674-424: The diagnosis of an autoimmune condition, often in conjunction with tests for specific biological markers, but also help monitor disease progression and response to treatment. Ultimately, due to the diverse nature of autoimmune diseases, a multidimensional approach is often needed for the management of these conditions, taking into consideration the variety of symptoms and their impacts on individuals' lives. While it

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1728-430: The diagnostic criteria established for any one connective tissue disease. Some 30–40% transition to a specific connective tissue disease over time. The exact causes of autoimmune diseases remain largely unknown; however, research has suggested that a combination of genetic, environmental, and hormonal factors, as well as certain infections, may contribute to the development of these disorders. The human immune system

1782-402: The early 1900s, and since then, advancements in understanding and management of these conditions have been substantial, though much more is needed to fully unravel their complex etiology and pathophysiology . Autoimmune diseases represent a vast and diverse category of disorders that, despite their differences, share some common symptomatic threads. These shared symptoms occur as a result of

1836-462: The fluid would indicate gout. In many cases there may be no specific test, and it is often a case of eliminating other conditions before getting a correct diagnosis. Initial therapy of the major rheumatological diseases is with analgesics , such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). Steroids, especially glucocorticoids , and stronger analgesics are often required for more severe cases. The term rheumatism stems from

1890-450: The gastrointestinal tract and some lymphoproliferative cancers. Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system attacks myelin , a protective covering of nerve fibers in the central nervous system, causing communication problems between the brain and the rest of the body. Symptoms can include fatigue, difficulty walking, numbness or tingling, muscle weakness, and problems with coordination and balance. MS

1944-454: The general population. Biologics for immunosuppression include adalimumab , certolizumab , etanercept , golimumab , infliximab , ixekizumab , belimumab , and ustekinumab . Extracts from some medicinal mushrooms are natural biological response modifiers. Genetically engineered cell cultures in pharmaceutical labs produce the biologics. Biologics are the second generation of biopharmaceutical products. The first generation were

1998-464: The gout, rheumatism". The English term rheumatism in the current sense has been in use since the late 17th century, as it was believed that chronic joint pain was caused by excessive flow of rheum which means bodily fluids into a joint. Autoimmune disease An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system , wherein it mistakenly targets and attacks healthy, functioning parts of

2052-452: The immune system attacking insulin-producing beta cells in the pancreas , leading to high blood sugar levels. Symptoms include increased thirst , frequent urination , and unexplained weight loss . It is most commonly diagnosed in children and young adults. Undifferentiated connective tissue disease occurs when people have features of connective tissue disease, such as blood test results and external characteristics, but do not fulfill

2106-406: The immune system creates an environment that favors further malignant transformation of other cells, perhaps explaining the associations with cancer of the lungs and skin as well as the increased risk of other hematologic cancers, none of which are directly affected by the inflammation of joints. Psoriasis is a skin condition characterized by the rapid buildup of skin cells, leading to scaling on

2160-624: The location and type of autoimmune response. For instance, in rheumatoid arthritis, an autoimmune disease primarily affecting the joints, symptoms typically include joint pain, swelling, and stiffness. On the other hand, type 1 diabetes, which results from an autoimmune attack on the insulin-producing cells of the pancreas, primarily presents with symptoms related to high blood sugar, such as increased thirst, frequent urination, and unexplained weight loss. Commonly affected areas in autoimmune diseases include blood vessels, connective tissues, joints, muscles, red blood cells, skin, and endocrine glands such as

2214-420: The lower legs . Inflammatory bowel disease encompasses conditions characterized by chronic inflammation of the digestive tract, including Crohn's disease and ulcerative colitis . In both cases, individuals lose immune tolerance for normal bacteria present in the gut microbiome . Symptoms include severe diarrhea, abdominal pain, fatigue, and weight loss. Inflammatory bowel disease is associated with cancers of

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2268-579: The overactive immune response. In certain cases, intravenous immunoglobulin may be administered to regulate the immune system. Despite these treatments often leading to symptom improvement, they usually do not offer a cure and long-term management is often required. In terms of prevalence, a UK study found that 10% of the population were affected by an autoimmune disease. Women are more commonly affected than men. Autoimmune diseases predominantly begin in adulthood, although they can start at any age. The initial recognition of autoimmune diseases dates back to

2322-675: The risk of autoimmunity (positive selection). In contrast, variants in the TYK2 gene protect against autoimmune diseases but increase the risk of infection (negative selection). This suggests the benefits of infection resistance may outweigh the risks of autoimmune diseases, particularly given the historically high risk of infection. Several experimental methods such as the genome-wide association studies have been used to identify genetic risk variants that may be responsible for diseases such as type 1 diabetes and rheumatoid arthritis. A significant number of environmental factors have been implicated in

2376-538: The same family, signifying a potential hereditary link. Furthermore, certain genes have been identified that augment the risk of developing specific autoimmune diseases. Experimental methods like genome-wide association studies have proven instrumental in pinpointing genetic risk variants potentially responsible for autoimmune diseases. For example, these studies have been used to identify risk variants for diseases such as type 1 diabetes and rheumatoid arthritis. In twin studies, autoimmune diseases consistently demonstrate

2430-484: The skin's surface. Inflammation and redness around the scales is common. Some individuals with psoriasis also develop psoriatic arthritis , which causes joint pain, stiffness, and swelling. Sjögren syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands (lacrimal and salivary), and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system. Systemic lupus erythematosus , referred to simply as lupus,

2484-457: The small intestine and promote nutrient absorption. This explains the increased risk of gastrointestinal cancers , as the gastrointestinal tract includes the esophagus, stomach, small intestine, large intestine, rectum, and anus, all areas that the ingested gluten would traverse in digestion. The incidence of gastrointestinal cancer can be partially reduced or eliminated if a patient removes gluten from their diet. Additionally, coeliac disease

2538-631: The symptomatology. Symptoms that are commonly associated with autoimmune diseases include: Specific autoimmune diseases have a wide range of other symptoms, with examples including dry mouth, dry eyes, tingling and numbness in parts of the body, unexpected weight loss or gain, and diarrhoea. These symptoms often reflect the body's systemic inflammatory response. However, their occurrence and intensity can fluctuate over time, leading to periods of heightened disease activity, referred to as flare-ups, and periods of relative inactivity, known as remissions. The specific presentation of symptoms largely depends on

2592-850: The symptoms, and even slow down or halt the progression of the disease. Classes of biologics typically used for psoriatic arthritis include TNF inhibitors, anti-IL17-A antibodies, IL-23 antibodies, and those that act on both IL-12 and IL-23. Biologics can treat inflammatory bowel disease . Classes of biologics typically used for inflammatory bowel disease include TNF inhibitors, and anti- CD28 antibodies. Biologics are generally used after considering other less invasive treatments. Before using biologics to treat psoriasis , treatment with topical moisturizers or steroids , or light therapy may provide relief. Other drugs which may provide relief include acitretin , ciclosporin , and methotrexate , but since these drugs have their own major side effects, doctors and patients should discuss whether to try one of these or

2646-645: The term to refer to immunotherapy treatments. The explanation for this is that while "biologic" or "biopharmaceutical" refers to the chemical composition of medications which might be used to treat a range of medical conditions, when the term "biologic" became popular, many biologic medications available provided immunosuppression. Biosimilar is a term used to describe a biopharmaceutical product which seems so close in composition and effect to another that they are functionally identical, analogous to generic drugs . In this context, some publications describe "biologics" as "biosimilars". Biologic drugs are expensive. In

2700-414: The thymus, an organ responsible for the maturation of T cells. This process serves as a key line of defense against autoimmunity. If these protective mechanisms fail, a pool of self-reactive cells can become functional within the immune system, contributing to the development of autoimmune diseases. Some infectious agents, like Campylobacter jejuni , bear antigens that resemble, but are not identical to,

2754-400: The thyroid gland (in diseases like Hashimoto's thyroiditis and Graves' disease) and the pancreas (in type 1 diabetes). The impacts of these diseases can range from localized damage to certain tissues, alteration in organ growth and function, to more systemic effects when multiple tissues throughout the body are affected. The appearance of these signs and symptoms can not only provide clues for

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2808-405: The transient nature of many symptoms. Treatment modalities for autoimmune diseases vary based on the type of disease and its severity. Therapeutic approaches primarily aim to manage symptoms, reduce immune system activity, and maintain the body's ability to fight diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are commonly used to reduce inflammation and control

2862-414: The wide range of diseases within this category and their often overlapping symptoms. Accurate diagnosis is crucial for determining appropriate treatment strategies. Generally, the diagnostic process involves a combination of medical history evaluation, physical examination , laboratory tests , and, in some cases, imaging or biopsies . The first step in diagnosing autoimmune disorders typically involves

2916-540: Was unknown until the 20th century and not treatable. Postinfectious arthritis, also known as reactive arthritis , and rheumatic fever are other examples. In the United States, major rheumatic disorders are divided into 10 major categories based on the nomenclature and classification proposed by the American College of Rheumatology (ACR) in 1983. Blood and urine tests will measure levels of creatinine and uric acid to determine kidney function, an elevation of

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