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Autoimmune Disorders—What Are They? What Causes Them? How Are They Treated?

Autoimmune disorders are caused by overactivity of the body’s immune system, which results in the body attacking its own tissues. Simply put, the immune system can’t tell the difference between healthy tissue and a foreign invader, so it starts attacking its own host. While the exact causes of autoimmune disorders are still not fully understood, there are risk factors that can increase your chances of developing an autoimmune disorder. These risk factors include certain medications, having a family history of autoimmune disease, smoking or being exposed to second-hand smoke as a child, already having an autoimmune disease (making you at greater risk of developing another one), exposure to environmental toxins, being obese, having an infection, and being female.1,2 Here we review five common autoimmune disorders and their treatments.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease distinguished by persistent polyarthritis (arthritis that affects at least 5 joints) on both sides of the body. RA most typically affects the hands and feet, but any joint lined with a synovial membrane can be affected. Tissue outside the joints can also be affected, including the skin, heart, lungs, and eyes. Researchers theorize that RA is triggered by environmental factors, such as cigarette smoking, infection, or trauma, in genetically susceptible individuals.3

Symptoms of RA include joint stiffness, tenderness, pain on motion, swelling, and deformity; limitation of motion; and rheumatoid nodules (firm lumps that appear under the skin, usually on the joints, but can appear elsewhere).3 Extra-articular (outside the joints) manifestations of the disease can occur and are considered very serious. These include cardio-pulmonary disease, eye disease, chronic skin ulcers, vasculitis, gastrointestinal disease, and neurologic disorders.3,4 Risk factors for RA are the same as the risk factors for autoimmune disorders in general.

Treatment. While there is no cure for RA, proper treatment options can reduce inflammation and pain, slow disease progression, and improve quality of life. Early treatment is important to mitigate joint damage and improve long-term outcomes.5 In addition to lifestyle modifications (e.g., smoking cessation, improved diet, weight loss), there are several pharmacologic treatment options for RA. These include nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, aspirin, naproxen, COX-2 inhibitors), steroidal anti-inflammatory drugs (e.g., prednisone, cortisone), disease-modifying antirheumatic drugs (DMARDs) (e.g., methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, and Janus-kinase [JAK] inhibitors [tofacitinib, baracitinib]), and biologics (e.g., etanercept, infliximab, adalimumab, anakinra, abatacept, rituximab, certolizumab, golimumab, tocilizumab).5 DMARDs suppress the entire immune system, whereas biologics block specific parts of the immune system.6 Oral methotrexate is considered the first-line treatment for RA; however, patients who don’t respond to DMARD therapy or who have high levels of persistent disease activity are eligible for biologic therapy.7 Biologic therapy is more potent than DMARD therapy and works more quickly; however, biologics carry a greater risk of side effects and are more expensive, compared to conventional DMARD therapy,6,7 which is why DMARDs, in particular methotrexate, are tried first.

Inflammatory Bowel Disease (IBD)

IBD is an umbrella term that describes chronic inflammation of the gastrointestinal tract. Symptoms include diarrhea, rectal bleeding, abdominal pain, loss of appetite, fatigue, and unintended weight loss and are usually indicative of one of two types of autoimmune diseases: Crohn’s disease or ulcerative colitis. Crohn’s disease more commonly involves inflammation of the small intestine, though the large intestine and upper gastrointestinal tract may also be affected. Ulcerative colitis involves inflammation and formation of ulcers in the lining of the colon and rectum.8

Crohn’s disease and ulcerative colitis have both been associated with increased risk of colon cancer, scarring of the bile ducts (which can cause liver damage), blood clots, and severe dehydration. Anal fissures, fistulas, and bowel obstruction can occur in Crohn’s disease, and toxic megacolon, in which the colon rapidly widens and swells, and perforated colon can occur in ulcerative colitis.8

Like other autoimmune disorders, causes of IBD are not fully understood but are thought to be linked to an immune system malfunction. Gene mutations have also been associated with IBD, making heredity an important part of the clinical picture; however, many people with IBD have no family history of IBD. Risk factors include younger age (most people are diagnosed with IBD under the age of 30 years, though men tend to be diagnosed later in life), white race, family history, cigarette smoking, and use of NSAIDs. In addition to these risk factors, female sex is a risk factor for Crohn’s disease and male sex is a risk factor for ulcerative colitis.8,9 Men with IBD are more likely to develop comorbid liver disease and colorectal cancer, compared to women.­9

Treatment. The main goal of IBD treatment is reduction of inflammation, and anti-inflammatory drugs are usually the first-line treatment for mild-to-moderate disease. Pharmacologic treatment options for IBD include nonsteroidal and steroidal anti-inflammatory drugs (e.g., aminosalicylates, prednisone), immunomodulators (e.g., methotrexate, cyclosporine A, tacrolimus, JAK inhibitors [tofacitinib, upadacitinib]), and biologics (e.g., vedolizumab, natalizumab, ustekinumab, infliximab, adalimumab, certolizumab pegol, golimumab), which are targeted immunotherapies. Additionally, antibiotics may be used adjunctively if infection is a concern (e.g., perianal Crohn’s disease). Fiber and vitamin supplements may be prescribed, as well as pain relievers. Nutritional support (e.g., enteral or parenteral nutrition or low-residue diet) may also be necessary. Finally, surgery may be required in severe cases. In ulcerative colitis, removal of the entire colon and rectum may be necessary for some patients; in Crohn’s disease, surgical removal of damaged portions of the digestive tract is performed in nearly two-thirds of patients with the disease, though this is usually a temporary fix, with disease recurrence frequently observed near where the intestinal tract was reconnected.8,10

Multiple Sclerosis (MS)

MS is an autoimmune disorder that affects the brain, spinal cord, and optic nerves. In MS, an abnormal immune system response attacks the central nervous system (CNS), causing inflammation and damage to the layer of cells (myelin) that protect and insulate CNS nerve fibers. This damage causes a disruption in communication between the brain and the rest of the body, resulting in a number of systemic symptoms, including numbness or tingling of the face, body, or extremities; difficulty walking; involuntary muscle spasms; mood changes; memory problems; pain; weakness and fatigue; vertigo/dizziness; sexual problems; bladder and/or bowel problems; blindness; and/or paralysis.11

As with many other autoimmune diseases, researchers believe that MS is triggered by environmental factors in genetically susceptible individuals. Risk factors associated with MS include being female (female individuals are 4 times more likely to develop MS than male individuals), living in northern regions (MS occurs more frequently in regions further from the equator), low vitamin D levels (which may explain why MS is more prevalent in northern regions, compared to southern regions [i.e., sunlight is a source of vitamin D, and northern regions have less sun exposure]), smoking, being obese, and being exposed to certain viral or bacterial infections. While MS is not considered hereditary, in that it isn’t passed down generation to generation, researchers do believe genetics play a role in the disease’s development, though this area of research needs further exploration.12

Treatment. Disease-modifying therapies (DMTs) are the first-line treatment for MS, and there are a number of available drugs and methods of delivery (e.g., infusion, injection, by mouth) from which to choose, with several factors that impact drug selection. MS treatment is usually approached using one of two strategies: escalation or induction. Using the escalation strategy, a moderately effective DMT with a solid safety profile is initiated. If the individual fails to respond adequately to that DMT or cannot tolerate its side effects, a more potent DMT is then selected, and so on until symptoms remit. Common DMTs used in the escalation strategy include fumarates, glatiramer acetate, interferon therapies, and teriflunomide. In the induction strategy, a high-potency DMT is initiated right from the start. These may include ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod, alemtuzumab, cladribine, mitoxantrone, and natalizumab. While these high-potency DMTs tend to work more quickly and more effectively, they have greater potential for side effects and are more expensive.13 Corticosteroids (e.g., prednisone, methylprednisolone) may also be used to reduce nerve inflammation.14 Plasma exchange, in which the individual’s plasma is removed and separated from blood cells and blood cells are then mixed with a protein solution and put back into their body, may be used in people with new but severe symptoms that haven’t responded to steroids.14 Other complementary treatments include physical therapy, muscle relaxants, medications to reduce fatigue (e.g., methylphenidate, modafinil), selective serotonin reuptake inhibitors for depression, medications to increase walking speed (dalfampridine), and/or medications to treat other symptoms of MS, such as pain, insomnia, sexual problems, and incontinence.14

Type 1 Diabetes (T1D)

T1D, an organ-specific autoimmune disease, is caused by the selective destruction of pancreatic beta-cells by an abnormal immune system. This autoimmune process results in the pancreas being unable to make any or very little insulin, a hormone that plays a critical role in allowing blood sugar to enter the body’s cells and be converted into energy. As a result, sugar builds up in the blood stream causing system-wide damage to the body, including cardiovascular disease, nerve damage, kidney damage, eye damage (e.g., diabetic retinopathy, glaucoma, cataracts), diabetic neuropathy of the foot, gum disease, skin infections, and pregnancy complications.15

Like MS, T1D isn’t considered a hereditary disease, but genetics are believed to play a role in its development. Some researchers theorize that infection may trigger T1D in some individuals, but more research is needed to confirm this theory.16,17 Established risk factors for T1D include family history (i.e., having a parent or sibling with T1D slightly increases the risk of developing the condition), genetics, living in northern regions (i.e., the number of people with T1D increases the further you travel from the equator), and young age (i.e., T1D primarily appears between 4 and 7 years of age or 10 and 14 years of age).15 T1D has a higher prevalence in male individuals.15 Symptoms of T1D include feeling more thirsty than usual, increased urination, sudden bed-wetting in children who did not previously wet the bed, increased hunger, unintended weight loss, irritability and/or mood changes, fatigue, and blurry vision.18

Treatment. There currently is no known way to cure or prevent T1D. Treatment focuses on managing the amount of sugar in the blood using insulin and diet. However, because people with T1D are at higher risk of heart disease, kidney disease, nerve damage, and other complications, compared to the general population, adhering to a healthy lifestyle, including making good food choices, getting plenty of exercise, and avoiding bad habits, such as cigarette smoking, are particularly important. According to the American Diabetes Association (ADA), there is no “one-size-fits-all” diabetes diet, and they recommend that people with T1D work with a registered dietitian to determine the best eating plan based on their individual needs. Overall, the ADA recommends including plenty of fiber and lots of non-starchy vegetables in the diet, minimizing added sugars and refined grains, and choosing whole, minimally processed foods. The following foods are considered low glycemic index foods and are recommended for people with T1D: beans, dark leafy greens, citrus fruit, sweet potatoes, berries, tomatoes, fish high in omega-3 fatty acids, whole grains, nuts, and fat-free yogurt and milk.19,20

Psoriasis

Psoriasis is an autoimmune disorder of the skin in which the inflammation caused by an overactive immune system causes skin cell growth to speed up. Normal skin cells grow and are shed over the course of a month; however, in individuals with psoriasis, skin cells grow in 3 or 4 days but aren’t shed. Instead, these skin cells start to pile up on each other, resulting in plaques or inflamed, raised, red, scaly patches of skin that may itch, burn, or sting. These plaques can appear anywhere on the body, but the most common locations are elbows, knees, and scalp. This is known as plaque psoriasis, which is the most common form of psoriasis (80–90% of people with psoriasis have this type). Plaque psoriasis tends to be cyclical, flaring for a few weeks then remitting for a period of time. The inflammation caused by psoriasis can affect other parts of the body, including joints and other organs. Psoriatic arthritis occurs in one-third of the individuals with psoriasis.21–23

Other types of psoriasis include guttate psoriasis, inverse psoriasis, pustular psoriasis, pustular psoriasis generalized, and erythrodermic psoriasis. Guttate psoriasis usually presents as tiny red bumps all over the torso, legs, and arms. This form of psoriasis usually develops in children or young adults who’ve had an infection, such as strep throat. When the infection clears, guttate psoriasis usually clears as well and never returns. But some people have guttate psoriasis for life. Inverse psoriasis usually appears as smooth, red patches of skin in areas where skin touches skin, such as the armpits or genital areas. Pustular psoriasis presents as red, swollen skin that is dotted with pus-filled bumps, usually on the hands and feet. Pustular psoriasis generalized is a rare, but life-threatening form of psoriasis in which red, swollen skin with pus-filled bumps cover most of the body. This form of psoriasis is usually accompanied by fever, headache, muscle weakness, and fatigue. Erythrodermic psoriasis is a serious, life-threatening condition that presents with very red, inflamed, burned looking skin on most of the body, accompanied by chills, fever, muscle weakness, rapid pulse, and severe itch.23

Like other autoimmune disorders, the exact cause of psoriasis is not well-understood but researchers do know that an abnormal immune system and genetics play a role in its development. A triggering event can change the way the immune system functions, resulting in the development of psoriasis. Triggering events may include stress, infection (particularly strep infections) or other illness, skin trauma, medications, or environmental factors, such as exposure to cold weather or allergens or consuming certain foods or alcohol.22

Most people with psoriasis start exhibiting symptoms between the ages of 15 and 25, but psoriasis can appear at any age. Psoriasis affects male and female individuals at about the same rate. Though anyone from any race/ethnicity can develop psoriasis, its prevalence is greatest among White people, followed by Black and Hispanic people. Asian people have lower rates of psoriasis compared to individuals of European descent.24

Treatment. Treatment for psoriasis includes topical medications, phototherapy, systemic treatments, and complementary and integrative medicine. Topicals are the first line of treatment for psoriasis and include topical steroids and nonsteroids and over-the-counter creams, lotions, bath solutions, cleansing solutions, shampoos, and other skin care products. Phototherapy involves exposing affected skin to ultraviolet light B or ultraviolet light A with psoralen (a light-sensitizing agent). Phototherapy slows the growth of affected cells. Systemic therapy includes conventional medications, such as acitretin, cyclosporine, and methotrexate, which suppress the entire immune system, and biologics, such as etanercept, adalimumab, and infliximab, which block specific parts of the immune system. Complementary and integrative therapies include healthy diet, exercise, mind-body techniques to reduce stress, acupuncture, and physical therapy.

Editor’s note

Please consult with your physician if you experience concerning symptoms indicative of an autoimmune disorder.

Sources

1. Cleveland Clinic website. Autoimmune diseases. 21 July 2021. https://my.clevelandclinic.org/health/diseases/21624-autoimmune-diseases. Accessed 14 Mar 2023.

2. Angum F, Khan T, Kaler J, et al. The prevalence of autoimmune disorders in women: a narrative review. Cureus. 2020 May; 12(5): e8094.

3. Smith HR. Rheumatoid arthritis (RA). 31 Jan 2022. Medscape website. https://emedicine.medscape.com/article/331715-overview. Accessed 14 Mar 2023.

4. Cojocaru M, Cojocaru IM, Silosi I, et al. Extra-articular manifestations in rheumatoid arthritis. Maedica (Bucur). 2010 Dec; 5(4): 286–291.

5. Cleveland Clinic website. Rheumatoid arthritis. 18 Feb 2022. https://my.clevelandclinic.org/health/diseases/4924-rheumatoid-arthritis. Accessed 14 Mar 2023.

6. Rath L. Biologics. 3 Sep 2022. Arthritis Foundation website. https://www.arthritis.org/drug-guide/biologics/biologics. Accessed 14 Mar 2023.

7. National Rheumatoid Arthritis Society website. Biologics. https://nras.org.uk/resource/biologics/#:~:text=The%20NICE%20RA%20Guideline%20states,be%20eligible%20for%20biologic%20therapy. Accessed 14 Mar 2023.

8. Mayo Clinic website. Irritable bowel disease (IBD). https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/symptoms-causes/syc-20353315. Accessed 14 Mar 2023.

9. Erhlich AC. How men and women experience IBD differently. 9 Feb 2021. Temple Health website. https://www.templehealth.org/about/blog/how-women-men-experience-ibd-differently#:~:text=Women%20are%20more%20likely%20to,women%20of%20the%20same%20age. Accessed 14 Mar 2023.

10. UChicago Medicine website. Understanding biologics and inflammatory bowel disease (IBD). https://www.uchicagomedicine.org/conditions-services/inflammatory-bowel-disease/treatment/understanding-biologics-and-inflammatory-bowel-disease-crohns-colitis#:~:text=Different%20Types%20of%20Biologics%20for%20IBD&text=They%20work%20by%20blocking%20a,can%20help%20heal%20the%20intestine. Accessed 14 Mar 2023.

11. National Multiple Sclerosis Foundation website. What is MS? https://www.nationalmssociety.org/What-is-MS. Accessed 14 Mar 2023.

12. National Multiple Sclerosis Foundation website. What causes MS? https://www.nationalmssociety.org/What-is-MS/What-Causes-MS. Accessed 14 Mar 2023.

13. Wexler M. Disease-modifying therapies for multiple sclerosis. 12 Jan 2023. Multiple Sclerosis News Today website. https://multiplesclerosisnewstoday.com/treatments-that-modify-the-disease-course/#:~:text=DMTs%20administered%20by%20infusion&text=Mitoxantrone%3A%20the%20only%20therapy%20approved,via%20infusion%20every%20three%20months. Accessed 14 Mar 2023.

14. Tobin O. Multiple sclerosis. Mayo Clinic website. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/diagnosis-treatment/drc-20350274#:~:text=Interferon%20beta%20medications.,frequency%20and%20severity%20of%20relapses. Accessed 14 Mar 2023.

15. Mayo Clinic website. Type 1 diabetes. https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011. Accessed 14 Mar 2023.

16. Kawasaki E. Type 1 diabetes and autoimmunity. Clin Pediatr Endocrinol. 2014 Oct; 23(4): 99–105.

17. United States Centers for Disease Control and Prevention website. What is Type 1 diabetes? https://www.cdc.gov/diabetes/basics/what-is-type-1-diabetes.html. Accessed 14 Mar 2023.

18. United States Centers for Disease Control and Prevention website. Morbitity and mortality weekly report. Prevalence of diagnosed diabetes in adults by diabetes type—United States 2016.

19. DiLonardo MJ. What to eat when you have Type 1 diabetes. 11 May 2021. WebMD website. https://www.webmd.com/diabetes/diet-type-1-diabetes. Accessed 15 Mar 2023.

20. American Diabetes Association website. Healthy living. https://diabetes.org/healthy-living. Accessed 15 Mar 2023.

21. Mayo Clinic website. Psoriasis. https://www.mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840. Accessed 15 Mar 2023.

22. National Psoriasis Foundation website. About psoriasis. https://www.psoriasis.org/about-psoriasis/. Accessed 15 Mar 2023.  

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