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Autoimmune Diseases

  • If it weren’t for the immune system—the human body’s natural defense against outside invaders—we would be sick all the time. This complex network of cells, organs and molecules fights off things like bacteria and viruses 24 hours a day, from our head to our toes. It’s a powerful protection when it’s working for us, but can also be a powerful threat when it turns against us, in what’s called an autoimmune disease (“auto” meaning “self”). 

    Autoimmune diseases in children are generally rare, and when they occur they can be challenging to diagnose and difficult to treat. Doctors are still learning about this large group of mostly chronic illnesses—more than 80 in all—and most have no cure yet. If your child has an autoimmune problem, much depends on figuring out what it is and treating it aggressively, both of which we specialize in at Boston Children’s Hospital. 

    • In an autoimmune disease, something causes the immune system to mistakenly begin attacking healthy cells and tissues.

    • Autoimmune diseases can affect almost any part of the body, though often target connective tissues (skin, muscle and joints).

    • Symptoms can range from fatigue and mild rashes to rare, serious warning signs, like seizures.

    • Diagnosis can be difficult because many symptoms tend to come and go, and are frequently nonspecific—they occur in different kinds of autoimmune diseases as well as other types of illnesses, like infection and cancer.

    • On the whole, autoimmune diseases occur most often in females (by a 3-to-1 margin over males).

    Autoimmune diseases that occur in children include:

    How Children’s Hospital Boston approaches autoimmune diseases

    While the health care team for children with autoimmune diseases may include many kinds of specialists, the doctors with the greatest expertise in these illnesses are called pediatric rheumatologists. And of the roughly 200 pediatric rheumatologists in the country, more than half a dozen work at Children’s Hospital Boston, making us a unique and powerful force in fighting autoimmune disease. 

    • Overall, the Rheumatology Department at Children’s is one of the biggest in the U.S., treating more than 4,000 outpatients and almost 1,000 inpatients every year.
       
    • Our Samara Jan Turkel Clinical Center for Pediatric Autoimmune Disease brings together pediatric rheumatologists and consulting specialists from across the hospital to offer comprehensive, coordinated care—from providing outpatient and inpatient treatment to helping children and families connect to a wide range of support services.
       
    • The Multiple Manifestations of Autoimmune Disease Clinic is a collaboration between Children's Division of Allergy and Immunology and Rheumatology Department. The clinic is aimed at helping children with multiple autoimmune symptoms that don’t fit a single diagnosis.
       
    • Similarly, Children's Dermatology-Rheumatology Center unites rheumatologists and dermatologists in caring for children with autoimmune diseases that involve the skin, such as psoriatic arthritis, scleroderma and juvenile dermatomyositis.

    Home to the world’s largest pediatric research enterprise, Children’s Hospital Boston is also looking toward the future. Through initiatives like the Manton Center for Orphan Disease Research and the Program in Cellular and Molecular Medicine, our clinicians and scientists are working together on new ways to identify, treat and potentially cure autoimmune diseases.

    Autoimmune diseases: Reviewed by Melissa Hazen, MD 
    © Children’s Hospital Boston, 2011

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  • Even though autoimmune diseases are estimated to affect some 23 million Americans, less than 13 percent of us can actually name an illness in this group. This underlines the fact that the study of the immune system (immunology) is still very much an evolving field, as doctors and researchers learn more about the body’s natural defense system—and what happens when it malfunctions. 

    To better understand your child’s autoimmune disease, it helps to know generally how the immune system works: 

    • Whether bacteria, a virus or grain of pollen, when a foreign invader (antigen) tries to enter the body, it first encounters the innate immune system.

    • The innate system is our inborn, nonspecific response to antigens. It’s a general set of defenses that includes barriers like skin and mucous membranes, and reactions like coughing and sneezing reflexes.

    • The innate system also includes roaming white blood cells called phagocytes (literally, “eating cells”), designed to devour any antigen that gets through the outer defenses.

    • The innate system will either destroy the invader or buy time for the more complex adaptive immune system to work.

    • The adaptive system is our continually evolving, specific response to antigens. It’s a targeted defense that identifies the invader andmakes unique proteins (antibodies) to mark it for attack.

    • Among the key players in the adaptive system are special white blood cells called B cells, which produce antibodies, and T cells, which coordinate and carry out the attack—and, importantly, also signal when it should stop. 

    In autoimmune disease, the adaptive immune system mistakenly begins attacking specific healthy cells and tissues—and fails to shut off that attack. This is different from other immune system malfunctions, such as acquired immunodeficiency disorders, like AIDS, in which the immune system is weakened or ineffective, and allergic disorders, in which the immune system overreacts to a foreign invader (pollen, for example). 

    Doctors have also begun to recognize autoinflammatory disorders—which happen when the innate immune system goes awry—as being distinct from autoimmune illnesses. Though both attack the body itself and cause inflammation, an autoimmune disease targets antigens in specific cells and tissues (like the lining of joints, in arthritis), while an autoinflammatory disease launches a less specific attack against the body.

    What are the types of autoimmune disease?

    With the ability to crop up in virtually any part of the body, autoimmune disease comes in many varieties. However, your child’s illness will likely fall into one of two basic groups: 

    The line between these two groups is a bit blurry, though, since organ-specific disorders can impact other parts of the body. Also, it’s not unusual for children to have more than one autoimmune disorder at the same time.

    Who is at risk for autoimmune disease?

    Because there are several dozen kinds of autoimmune diseases, risk factors depend somewhat on which illness you’re talking about. In general, though, researchers have found strong links to the following: 

    • Gender: Females are almost three times as likely as males to have an autoimmune disease, with adolescent girls and young women being at greatest risk. For some diseases, such as scleroderma and lupus (SLE), more than 85 percent of patients are female. (However, one of the more common autoimmune diseases in children, type 1 diabetes, occurs in boys and girls almost equally.)
       
    • Age: Most autoimmune diseases affect younger and middle-aged people. Some illnesses begin specifically in childhood (as their name suggests)—juvenile idiopathic arthritis and juvenile dermatomyositis, for example.
       
    • Genetics: A family history of autoimmune disease puts a child at higher risk. In fact, it’s been estimated that about one-third of the risk of developing an autoimmune disease is tied to something in a child’s genes.
       
    • Race: Some reports suggest that children of different races may be more prone to having certain autoimmune diseases. African-Americans, for instance, seem to be more likely than Caucasians to develop lupus (SLE) and scleroderma, but the opposite is true for type 1 diabetes and multiple sclerosis (MS).
       
    • Other illnesses: Children with one autoimmune disease tend to run a higher risk of developing another. For example, kids with type 1 diabetes appear to be more susceptible to developing celiac disease or Addison’s disease.

    Can autoimmune disease be prevented?

    So far, there’s no way to stop autoimmune disease before it starts. But prevention remains the long-term goal—especially since harmful autoimmune activity can be difficult to “turn off” once it’s begun. 

    In a recent report to Congress, the National Institutes of Health outlined the three challenges that researchers face: 

    • recognizing the specific genetic patterns of people susceptible to autoimmune disease
    • zeroing in on environmental factors (viruses, toxins, etc.) that may trigger disease
    • coming up with ways to intervene before the disease begins, along with creating public screening programs

    What are the potential complications of autoimmune disease?

    Complications depend on the specific disease, and can range from relatively mild to very serious. Among the more common complications in children with autoimmune disease are eye inflammation, rashes and stunted growth. Life-threatening complications, like inflammation of vital organs (kidneys, heart, etc.), tend to be rare.

    In addition, some of the more powerful medications used to treat autoimmune diseases can have significant side effects. If they are recommended for your child, your child’s doctor will discuss their potential complications in detail with you.

    What is the long-term outlook for my child?

    By and large, autoimmune diseases are considered lifelong conditions. There are certain illnesses, like juvenile dermatomyositis, can be “cured” in the sense that with successful treatment, the symptoms never recur. Other illnesses, like certain types of juvenile idiopathic arthritis, are things that many kids simply grow out of. But even when a child’s autoimmune disease “goes away” (this is called remission), she’ll need to keep a close eye on her health throughout her life, because her immune system has already shown it’s capable of attacking healthy tissue. 

    If your child has a more serious autoimmune disease, she may go through periods of getting better (remission) and getting worse (relapse). A sudden, severe return of symptoms, called a flare-up, isn’t uncommon. This seesawing back and forth can be difficult to deal with, especially over the long term, but both medical treatment and lifestyle changes can go a long way toward bringing these shifts under control. 

    Even after diagnosing your child’s particular autoimmune disease, doctors can’t predict exactly what will happen. But they’ll be able to give you a general sense of what the future holds, and work with you and your child to develop a treatment plan that ensures the best possible outcome.

    Causes

    The exact reason that some children’s immune systems begin attacking their own bodies is still a mystery. But we do know that autoimmune diseases are not contagious, and they don’t appear to be caused by any one thing in particular. Instead, scientists believe there’s a multi-step process at work: 

    • Heredity: A child inherits certain genes from her parents that make her susceptible to a particular disease.

    • Environmental factors: The disease doesn’t actually reveal itself until it’s “triggered” by something—an infection, say, or exposure to certain toxins or drugs.

    • Hormonal factors: Given that many autoimmune diseases tend to affect adolescent girls and young women, the presence or amount of certain naturally occurring hormones in the body may also play a role in when these illnesses come to the fore.  

    Researchers are now working to discover which genes are involved and how they interact—and are likewise investigating a number of potential environmental and hormonal triggers—in order to bring us closer to one day curing these diseases.

    Signs and symptoms

    There’s no single set of symptoms that covers the spectrum of autoimmune disease, and the most common symptoms tend to be nonspecific—meaning they could be caused by some non-autoimmune diseases, too. This can make it harder for doctors to diagnose your child, and why your child may also need a number of tests to narrow down the possibilities. 

    Signs that your child may be having a problem with her immune system include: 

    • low-grade fever
    • fatigue or chronic tiredness
    • dizziness
    • weight loss
    • rashes and skin lesions
    • stiffness in the joints
    • brittle hair or hair loss
    • dry eyes and/or mouth
    • general "unwell" feeling 

    Recurring fever, fatigue, rashes, weight loss and so on are not concrete proof that your child has an autoimmune disease, but they do mean something is making her ill and needs medical attention. You should take her to see her pediatrician, who will refer you to a specialist—likely a pediatric rheumatologist—if an autoimmune disease is suspected.

    FAQ

    Q: Why did my child get an autoimmune disease?
    A: We don’t know exactly why some children’s immune systems begin attacking their own bodies—it’s related to something in their genes and likely a number of other, unknown factors. It’s important to remember that your child’s disease wasn’t caused by anything you did, and there’s nothing you could have done to prevent it. 

    Q: Why are girls more likely to have an autoimmune disease?
    A: Researchers are still puzzling out why this group of illnesses so often tends to affect adolescent girls and young women, but many think that high levels of certain female hormones—which increase after puberty and through the childbearing years—may be playing a role. 

    Q: Why are there so many kinds of autoimmune diseases?
    A: The immune system is designed to protect the entire body. When it malfunctions, it can attack virtually anywhere, from the skin to the joints to the blood vessels—which all respond in different ways and often require different treatment strategies. 

    Q: Can autoimmune disease be fatal?
    A: In some cases, severe autoimmune diseases—especially those affecting the kidneys, lungs, blood vessels and other vital organs—can be fatal. Fortunately, though, these illnesses are very rare, and treatment is aimed at keeping these vital organs healthy. Infection is another potentially life-threatening problem for certain children; however, with the recognition of its signs and symptoms, appropriate treatment can be life-saving. 

    Q: Is there a test that can show which illness my child has?
    A: There’s no single test that can identify autoimmune disease. In addition, some lab tests—like rheumatoid factor, often used to help classify juvenile idiopathic arthritis—may give false positives or false negatives. This is why your child’s doctor may use an array of tests, along with careful consideration of your child’s symptoms and physical exam findings, in making a diagnosis.

    Q: How are autoimmune diseases treated?
    A: Broadly speaking, doctors prescribe medications that 1) fight the harmful inflammation caused by autoimmune attack and 2) suppress the overall immune system or block specific things that it’s doing. Surgical therapies for autoimmune diseases are very rare.  

    Q: What kinds of doctors treat autoimmune disease?
    A: Rheumatologists, who specialize in diseases of the joints and connective tissue, often diagnose autoimmune illnesses and tend to be at the center of the health care team. Depending on which tissues or organs are affected, other specialists—such as dermatologists (skin) and nephrologists (kidneys)—may be involved in caring for your child.

  • Autoimmune diseases present a special challenge for physicians. Many of the earliest symptoms—like fever and fatigue—are nonspecific, meaning they’re found in a variety of illnesses. Symptoms often come and go. A single autoimmune disease can show up in different ways in different people, or include features of other autoimmune diseases (called overlap). 

    For reasons like these, getting to a diagnosis can be a long and stressful journey for many families. But it’s important to remember that the difficulties are an unfortunate part of the process, not a sign that there’s something uniquely wrong with your child. And even when doctors aren’t 100 percent sure which specific autoimmune illness your child has, they often can learn enough from the diagnostic process to begin treatments to improve her health and quality of life. 

    Your child’s rheumatologist will first look at her full health history—including any family history of autoimmune disease—and conduct a thorough physical exam. If autoimmune disease is suspected, the doctor will gather more information through lab tests, including: 

    • antinuclear antibody (ANA), which can detect certain abnormal proteins—called antinuclear antibodies—that the immune system makes when attacking the body’s own tissues.
       
    • complete blood count (CBC), which is a collection of tests measuring the size, number and maturity of different blood cells in a specific amount of blood. Two important tests are:
    • white blood cell count (WBC)—the number of white blood cells present. Low levels may point to a problem with the immune system; high levels, on the other hand, may indicate an infection.
    • hematocrit—the number of red blood cells present. Anemia, or low levels of red blood cells, is often a symptom of certain autoimmune diseases, including lupus and systemic juvenile idiopathic arthritis.|
       
    • complement, which measures the blood’s level of complement, a group of proteins that are part of the immune system. Low levels of complement may indicate an autoimmune problem.
       
    • C-reactive protein (CRP), which measures the amount of a special protein made in the liver. CRP levels tend to shoot upward when there’s severe inflammation—like the kind seen in autoimmune diseases—somewhere in the body.
       
    • erythrocyte sedimentation rate (ESR or sed rate), which measures how quickly red blood cells fall to the bottom of a test tube. If the cells to clump together and fall more rapidly than normal, it can signal there is inflammation in the body.
       
    • rheumatoid factor (RF), which, like ANA, can detect an abnormal protein that the immune system makes when attacking the body. It can be useful in classifying a certain kind of juvenile idiopathic arthritis (JIA). However, children with some non-autoimmune ailments may test positive for RF, and most kids who actually have arthritis may test negative.
       
    • anti-cyclic citrullinated peptide (anti-CCP) antibody, a relatively new blood test that may be ordered along with an RF test to help characterize a certain kind of JIA.

    Your child’s doctor may also want to take a closer look at her actual organs and tissues, to rule out things like infections, tumors and fractures. To do this, the doctor might use such imaging tests as: 

    • magnetic resonance imaging (MRI), which uses a combination of large magnets, radiofrequencies and a computer to produce detailed pictures of the body’s organs, bones and tissues. Because children have to lie very still for an MRI, which can last half an hour or more, some may need general anesthesia or a sedative.
    • ultrasound, also known as sonography or ultrasonography, which uses high-frequency sound waves to create pictures of internal structures. Though ultrasound shows less detail than an MRI, it’s very fast and doesn’t require a child to be sedated.
    • x-rays, which are good for seeing breaks or other damage to bones, but are less useful in showing soft tissues, like organs.

    In some cases, your child’s doctor will actually take a sample of your child’s tissues—called a biopsy—to help identify the disease or to get an idea of how it’s progressing. 

    Overall, today’s diagnostic tools can help physicians home in on autoimmune disease, but can’t do much to differentiate one illness from another. To solve that problem, many researchers are now working on identifying biomarkers—things that the body is doing or making that point to a specific illness—for autoimmune diseases. Such biomarkers could allow doctors to make faster, more accurate diagnoses, and get started on treatment that much sooner.

    Useful medical terms

    Antibody: A protein molecule made by the immune system in response to a foreign invader (antigen), like bacteria or a virus. The antibody binds itself to the antigen and either kills it or marks it for attack by other cells.

    Antigen: A substance or organism, like a virus, that the immune system recognizes and tries to eliminate. 

    Anti-inflammatory: Capable of reducing inflammation, an immune system reaction to infection and foreign substances. 

    Autoantibody: An antibody that reacts against a person’s own cells and tissues. 

    Autoimmune disease: An illness that results when the immune system mistakenly attacks healthy tissues. 

    Biologics: A relatively new class of medications based on compounds made by living cells. These compounds “block” specific actions of the immune system that fuel inflammation and tissue destruction. 

    Biomarkers: Biologic molecules that can indicate if a particular illness is present, and/or how it’s progressing. 

    Chronic: Long-lasting; without a cure or a definite endpoint. 

    DMARDs (disease-modifying anti-rheumatic drugs): A class of medications that can slow or potentially stop the activity of autoimmune disease, often by suppressing the overactive immune system. 

    Flare: When symptoms of a disease suddenly reappear or worsen. 

    Immune system:The body’s network of cells, tissues and organs that provides immunity, or protection, against foreign organisms. 

    Immunosuppressant: Describes a kind of medication that reduces the activity of the immune system. 

    Inflammation: An immune system reaction to infection and foreign substances, marked by swelling, heat, redness and pain. 

    NSAIDs (nonsteroidal anti-inflammatory drugs): A class of medications that work to reduce pain, fever and inflammation by blocking certain enzymes and proteins in the body. 

    Remission: When symptoms of a disease decrease or disappear. 

    Systemic: Involving the whole body.

  • While there's no cure for the vast majority of autoimmune diseases, doctors aim to do far better than just manage your child's symptoms. Yes, they will work to immediately relieve things like soreness and stiffness, and restore important substances to your child's body that the disease may be taking away (like insulin, in type 1 diabetes). But the big goals are to quench the inflammation of the autoimmune reaction—to keep it from doing further damage—and to “reset” the immune system so that it will work normally on its own. 

    Autoimmune illnesses don't tend to be “wait and see” conditions, where doctors might start with a mild medication and ramp up to stronger therapies only if that doesn't work. Instead, doctors often favor aggressive upfront treatment with an array of drugs (some of which have significant side effects, which your doctor will discuss with you in detail). Therapies commonly prescribed for autoimmune disease include:

    •  nonsteroidal anti-inflammatory drugs (NSAIDs), which help ease symptoms like pain, swelling and stiffness. Among the most common NSAIDs are ibuprofen and naproxen, given in therapeutic doses (that is, higher than the over-the-counter versions).
       
    • disease-modifying anti-rheumatic drugs (DMARDs),which slow down—or even halt—the progress of a disease (that's why they're called “disease-modifying”). The workhorse of this group ismethotrexate; other DMARDs include sulfasalazine (brand name Azulfidine) and leflunomide (Arava).
       
    • biologics, which are a relatively new class of DMARDs made of synthetic proteins. The major category within biologics is tumor necrosis factor (TNF) blockers, which counteract high levels of inflammatory proteins. Etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) are the most widely used. Another promising group is interleukin-1 (IL-1) blockers like anakinra (Kineret).
       
    • corticosteroids, which are extremely powerful drugs that suppress the immune system and fight inflammation. Doctors sometimes prescribe corticosteroids in tablet form or by IV for short-term use, but tend to avoid high doses over the long term because of serious side effects. Prednisone—which has a number of brand names—is the most common of the corticosteroids.
       
    • IVIg (intravenous immunoglobulin), which is a blood product made up of antibodies that is delivered by IV, and can help get the immune system back on track without suppressing its normal function. 

    Depending on your child's autoimmune disease, she may need other kinds of medical treatment, such as: 

    • plasmapheresis, a process that removes plasma—the part of the blood that carries antibodies—from a patient's blood. Because it removes good antibodies along with the bad, however, it leaves the immune system less able to fight off sickness and infection. That's why doctors typically recommend plasmapheresis only for the most serious autoimmune diseases.

    • surgery, to deal with certain complications of autoimmune disease: joint damage in juvenile idiopathic arthritis, for example, or bowel obstruction in Crohn's disease 

    Though essential, medication is just one part of your child's treatment program. Most kids with autoimmune diseases also require physical and occupational therapy, to increase their mobility and muscle strength and to learn ways to make day-to-day activities easier on their bodies. And because chronic illnesses like these can be mentally and emotionally tough to deal with, psychotherapy or counseling can be valuable in helping kids keep the positive outlook they need to “beat” their disease.

    Coping and support

    We understand that you may have a lot of questions when your child is diagnosed with an autoimmune disease. How will it affect my child's life? What do we do next? We've tried to provide some answers to those questions here, but there are also a number of other resources to help you and your family in dealing with your child's unique illness, such as: 

    • Parent-to-parent connections: Want to talk with someone whose child has faced the same disease? A number of Children's parents volunteer for special training to help the families of newly diagnosed kids. Alternatively, your child's doctor may be able to put you in touch with a mom or dad of another patient who can share their experiences with you.
       
    • Social work: Our Rheumatology Department includes social workers—in both inpatient and outpatient settings—who have assisted many other families whose children have an autoimmune disease. Your social worker can offer counseling and problem-solving advice on issues such as coping with your child's diagnosis; dealing with financial difficulties; and finding temporary housing near the hospital if your family is traveling to Boston from another area.
       
    • Behavioral Medicine Clinic: This program has an experienced team of pediatric psychologists, psychiatrists and other mental health professionals to help children and families deal with the extra stress that autoimmune disease can bring. Offering evaluations, short-term therapy and family counseling, the clinic staff can teach you ways to prevent or better deal with the emotional and behavioral problems associated with chronic illness. 

    In addition, there are many groups that help connect and educate people across the country who are coping with autoimmune diseases. Your doctor may be able to recommend which ones are best for your child's specific illness, but in general, three of the most high-profile groups are: 

    • The American Autoimmune Related Diseases Association, which is a leading advocate for autoimmune research and awareness. Among other things, it spotlights research news on its website as well as in its quarterly newsletter, InFocus.
    • The Arthritis Foundation, which offers resources for all kinds of childhood arthritis, as well as for a number of closely related autoimmune diseases, like lupus, scleroderma and fibromyalgia.

    • The Lupus Foundation of America, which is dedicated to improving the health and well-being of anyone affected by this major autoimmune disease. Among the highlights of its website are links to programs that help pay for medications, message boards for patients and families and a list of local support groups.

  • The pace at which our understanding of the immune system—and, along with it, autoimmune diseases—has increased dramatically in the past few decades. So, too, has the pace of diagnostics and treatment.

    Here at Children’s Hospital Boston, the Samara Jan Turkel Clinical Center for Pediatric Autoimmune Diseases is helping to pioneer some of the most promising new therapies for these illnesses, including the use of biologics: protein-based drugs made from living cells cultured in a lab. 

    Our physicians have participated in a number of multicenter studies that focus on biologics, including: 

    • Rituximab in Myositis (RIM), which examined rituximab—a man-made antibody initially used to treat certain types of cancer—as a therapy for juvenile dermatomyositis, an autoimmune disease marked by muscle weakness and skin rash that affects an estimated 3,000 to 5,000 children in the U.S.
       
    • Trial of Early Aggressive Therapy (TREAT) in JIA, which involved etanercept (a.k.a. Enbrel), one of a key group of biologics calledtumor necrosis factor (TNF) blockers that counteract high levels of inflammatory proteins in the body. In this study, doctors looked at both etanercept and the more well-established drug methotrexate as early treatments for juvenile idiopathic arthritis, an autoimmune disease that affects about 50,000 children in the U.S.

    Learn more about research at Children's.

    Clinical trials

    There are many ways in which your child might benefit from Children’s Hospital Boston’s medical research program. Children’s doctors and scientists have made many breakthrough discoveries about diseases like polio and leukemia; our ongoing research continues to push the boundaries of the way pediatric medicine is practiced. 

    It’s possible that your child will be eligible to participate in one of Children’s current clinical trials. These studies are useful for a multitude of reasons: Some trials are designed to evaluate the effectiveness of a particular drug, treatment or therapy on a specific disease; others help doctors to better understand how and why certain conditions occur. At any given time, Children’s has hundreds of clinical trials under way. 

    Alternately, your child’s doctor might ask you to participate in a registry, a list of patients with JIA that is matched to an archive of biospecimens (such as serum and DNA) to serve as a resource for research into this disease.

    And participation in any clinical trial or registry is completely voluntary: We’ll take care to fully explain all elements of the treatment plan prior to the start of the trial, and you may remove your child from the medical study at any time. 

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