Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of the immune system primarily affecting young infants and children, although it can develop for the first time at any age.
According to a large, population-based study published in Sweden, it was estimated to occur in 1.2 cases per million children, which corresponds to 1 in 50,000 births. However, this number must be considered minimal, as there are probably many patients today who are not diagnosed. For the autosomal-recessive forms of HLH (FHL), there is believed to be an equal number of males and females diagnosed with this disease. In addition, there are two known X-linked forms of FHL, affecting only males.
HLH involves over-production and activation of normal infection-fighting cells called histiocytes and T cells. In contrast, often NK (natural killer) cell function is decreased. Decreased NK function is related to the consequence of genetic mutations which cause HLH. HLH is often referred to as either the “primary” form which is hereditary, or the “secondary” form associated with infections, viruses, autoimmune diseases, and malignancies (or cancers).
In the primary form, also known as familial hemophagocytic lymphohistiocytosis (FHL or FHLH), defective genes are inherited from either both parents (autosomal recessive) or from the mother alone. Since 1999, five genes have been identified which correspond with five subtypes of autosomal recessive HLH. The genes are PRF1 (perforin), MUNC13-4, STX11 (Syntaxin), STXBP2, and RAB27A. PRF1 encodes the protein (or toxin) normally involved in “killing” or eliminating abnormal immune cells. The proteins encoded by the other four genes facilitate the delivery of perforin to the cells which are to be killed.
While great progress has been made through research in recent years to define these genes, there remains a considerable proportion of FHL patients with as yet unknown underlying gene defects.
The onset of disease occurs under the age of 1 year in an estimated 70% of cases. FHL is suspected if siblings are diagnosed with HLH or if symptoms recur when therapy has been stopped. Each full sibling of a child with FHL has a 25% chance of developing the disease, a 50% chance of carrying the defective gene (which is very rarely associated with any risk of disease), and a 25% chance of not being affected and not carrying the gene defect.
So-called “secondary HLH” is often diagnosed in older patients, and there is no family history of this disease. It may be associated with vaccinations, viral infections such as Epstein-Barr, cytomegalovirus (CMV), or herpes virus, and other underlying diseases, principally autoimmune disorders and cancers, as mentioned previously.
It is difficult to know whether a patient has primary or secondary HLH on the basis of symptoms, which may be very similar. Therefore, genetic testing is usually recommended in order to make the proper diagnosis, regardless of age.
The first description of HLH was published in 1952, but it has only been in recent years that it has received more widespread attention. In 1985, physicians from around the world who were interested in studying the histiocytic disorders gathered in Philadelphia and formed the Histiocyte Society. Funds raised by the Histiocytosis Association, as well as national subgroups, have financed research that has led to significant breakthroughs in the diagnosis and treatment of HLH during the past 15 years. As awareness and understanding of this disease have increased worldwide, the diagnosis and survival rates have improved significantly. However, HLH remains a rapidly progressive disease requiring effective immunosuppressive and anti-inflammatory therapy.
Latest HLH Educational Webinar
The symptoms of the primary and secondary forms of hemophagocytic lymphohistiocytosis (HLH) include:
- Persistent fever, often high. Sometimes a microbial (often viral) cause is found, but this is common as a trigger of HLH/FHL.
- Abnormal blood tests such as a) low red blood cells, b) low platelets, and c) low neutrophils.
- Other blood abnormalities (liver dysfunction, elevated triglycerides, low sodium level, and low albumin level).
- Enlarged spleen.
- Skin rash, variable (30% of patients).
- Enlarged lymph nodes.
Combined with evidence of immunologic dysfunction:
- Decreased NK-cell function.
- Increased T-cell activation as evidenced by increased sIL2ra (soluble IL-2 receptor alpha) in the blood.
- Increased histiocyte activation as evidenced by increased ferritin.
CNS (central nervous system) involvement occurs in 50% of patients and may be present at the time of disease onset, or it can develop later.
A wide variety of symptoms of CNS disease include:
- Low or abnormally increased muscle tone.
- Difficulty with coordination.
- Weakness of face/eye nerves.
- Sudden blindness.
- Paralysis and coma (very rare).
On bone marrow examination, an abnormality in which histiocytes are “eating” other blood cells (also known as hemophagocytosis) can be detected. When prominent, this is a very useful diagnostic marker. Although the disease was named after this phenomenon, this symptom may be absent at onset or even throughout the course of the disease.
The Histiocyte Society has created diagnostic guidelines and recommendations concerning the treatment of HLH. The HLH-2004 research study, concluded at the end of 2011, is used only at institutions with IRB (Institutional Review Board) approval and appropriate informal patient/family consent. The Histiocyte Society recommends the use of the HLH-94 treatment in conjunction with HLH-2004 diagnostic criteria as the standard of care until further analysis/publications recommend otherwise.
Diagnosis and Treatment
It is sometimes difficult to establish the diagnosis of hemophagocytic lymphohistiocytosis (HLH), and the combination of the physical symptoms and certain laboratory tests is required. A set of diagnostic criteria was recommended by the Histiocyte Society for use in the HLH-2004 research protocol, and this was revised in 2007. This includes diagnosis of a specific gene defect and/or the presence of at least five of the following eight criteria: (Note: The understanding of pathology underlying HLH/FHL disease is evolving, and recommended “diagnostic” criteria will be revised in upcoming years.)
- Low or absent NK (natural killer) cell function.
- Prolonged fever.
- Blood cell abnormalities (low white cells, low red cells, low platelets).
- Enlarged spleen.
- Increased triglycerides (fat) or decreased fibrinogen (protein necessary for clotting) in the blood.
- Increased ferritin (protein that stores iron) in the blood.
- Abnormal bone marrow test evidence of hemophagocytosis but not malignancy or other cause.
- Abnormally high CD25 (also known as sIL2ra) in the blood indicating abnormally increased T-cell activation.
The test for low or absent natural killer cell (NK) function has been found useful in assisting to make a clinical diagnosis of HLH. This abnormality is found in many patients with FHL, as well as in many cases of secondary disease but rarely in the X-linked forms.
However, it is just one piece of information and should not be used to determine the diagnosis of HLH as primary or secondary. NK function cannot be determined before birth, and it may not be reliably studied until a child is at least 6 weeks of age. FHL is suspected if siblings have been diagnosed with HLH, if symptoms intensify during treatment for HLH, or if symptoms return after therapy has been stopped.
Since it is difficult to tell the difference between secondary HLH and FHL, any case of HLH should be considered for genetic testing to confirm the diagnosis. Since 1999, at least seven defective genes have been identified. Autosomal recessive: PRF1 (perforin), MUNC13-4, STX11 (Syntaxin), STXBP2, and RAB27A. X-linked: SH2D1A, BIRC4.
There are some FHL patients (approximately 30%) with no identified gene defect, so normal genetic test results do not necessarily rule out the diagnosis of FHL. Genetic testing is usually done on blood, although other kinds of tissue samples can be used. Once the genetic cause is known, the parents can quickly be tested to confirm that they are carriers for that specific genetic type of FHL. Other siblings can also be easily tested, even before birth, once the genetic cause of the disorder in the family is known. Even in the event of death, salvaged tissue can be tested to determine if siblings are at risk.
It is recommended that genetic testing be coordinated through and requested by a referring physician or genetic counselor. Test results are generally available in about one month to six weeks. The cost of genetic testing is covered by most insurance companies. There are several hospitals that provide information and perform genetic testing on a clinical basis, including:
Karolinska University Hospital, Stockholm, Sweden
Jan-Inge Henter, MD
University Medical Center, Hamburg, Germany
Gritta Janka, MD
Gene Tests Clinic Directory
New Treatment Approved in 2018
US Federal Drug Administration (FDA) Approves Gamifant® (emapalumab-lzsg), the First and Only Treatment Indicated for Primary Hemophagocytic Lymphohistiocytosis (HLH). Read the full press release to get more information here.
*This is not an endorsement of any specific treatment or drug. All treatment should be reviewed by your medical team to ensure the best treatment plan is developed for you.
In 1994, as a result of an international cooperative effort, the Histiocyte Society created the first treatment protocol for patients with HLH/FHL. This included a combination of chemotherapy, immunotherapy and steroids, as well as antibiotics and antiviral drugs, followed by a stem-cell transplant in patients with persistent or recurring HLH or those with FHL. The HLH-2004 protocol was based on the HLH-94 protocol with minor changes such as cyclosporin, an immunosuppressant drug, being started at the onset of therapy rather than week #8. This protocol has been widely accepted internationally and is used in numerous countries on all continents but should only be used as a research study. HLH-2004 closed at the end of 2011. A new pilot clinical trial for the treatment of HLH, called "HIT HLH," has opened in the U.S. at a network of participating sites (see www.clinicaltrials.gov) and a companion study is expected to open in Europe soon. This protocol combines two effective strategies for HLH treatment. In order to participate in this trial, patients must be treated at a participating center. There is also an update article available about the study and the role played by interferon gamma (INFγ) in the development and maintenance of HLH available here.
There are cases of secondary HLH that can resolve spontaneously or after treatment of the underlying disease, without the use of chemotherapy. The treatment should be guided in part by the severity of the condition, as well as the cause of the disease.
FHL, however, when not treated, is usually rapidly fatal with an average historical survival of about 2 months. The treatment included in the HLH-2004 research protocol is intended to achieve stability of the disease symptoms so that a patient can then receive a stem-cell transplant, which is necessary for a cure.
In recent years, some transplant centers have adopted the use of reduced intensity conditioning (or “RIC”) to prepare for the stem cell transplant. This approach offers the possibility of better survival with stem cell transplant than the intensive chemotherapy protocols previously used.
As research continues, the outcome for patients with HLH/FHL has improved greatly in recent years. Approximately two-thirds of children with HLH who undergo transplantation can expect to be cured of their disease. However, there are a number of complications that can occur during the process of transplant, including severe inflammatory reactions, anemia, and graft-versus-host disease.
Long-term follow-up of survivors of transplants for HLH/FHL indicates that most children return to a normal or near-normal quality of life. The results of transplantation are generally better when the procedure is performed at a major pediatric transplant center where the doctors are familiar with this disease. Early and accurate diagnosis is essential. However, there is still a high rate of death, indicating the education of the medical community regarding prompt diagnosis and management of the diseases, as well as improvement in managing therapy to provide optimal outcome still requires support for clinical research of this group of disorders.
HLH can either be acquired (secondary HLH) or inherited (FHL). Both forms of the disease can be triggered by infections, although it is not known why this happens. Secondary HLH may be triggered by vaccinations, viral infections such as Epstein-Barr, CMV (cytomegalovirus), herpes virus, or other underlying diseases such as cancer. In FHL, defective genes are inherited from one or both parents. Some other rare inherited immunodeficiencies may also be associated with HLH. The underlying immune defect and/or triggering events result in an abnormal immune response with activation of certain types of white blood cells (lymphocytes and macrophages) and the release of inflammatory proteins which then cause disease. The true cause of HLH/FHL is not known.
HLH patients with an underlying genetic defect can only be cured when the defective immune system is replaced by a healthy one which is what happens with a hematopoietic stem cell transplant. Secondary HLH cases can usually be cured by treating the underlying disease and sometimes additional immunosuppressive/immunomodulating therapy.
Some cases of secondary HLH can resolve spontaneously or after treatment of the underlying disease. Other cases are treated with a combination of chemotherapy (VP-16, methotrexate), immunotherapy (ATG, cyclosporin), and steroids. Any triggering infection has to be treated with appropriate antimicrobial drugs. Patients with persistent or recurring HLH or those with FHL additionally require a hematopoietic stem-cell transplant for recovery. In November 2018, the US FDA approved the use of Gamifant for children and adults with primary HLH. You can read more about this major announcement here. Be sure to always seek your doctor's advice when seeking a treatment method.
Side effects include:
- Mouth sores/swollen, tender gums
- Nausea/vomiting/diarrhea/decreased appetite
- Low blood counts
More unusual side effects may include:
- Blurred vision or loss of vision
- Weakness/difficulty moving one or both sides of the body
- Loss of consciousness
- Lung damage
- Allergic reactions
If an infant is suspected to have HLH because of an affected sibling, and if the affected sibling has a known genetic defect, then genetic screening can be performed at birth.
Although HLH may occur more frequently than some of the diseases routinely tested for, genetic testing for this disease is very complicated and very expensive.
The clinical symptoms and laboratory findings do not differ in genetic or acquired HLH. Specific immunologic testing can raise the suspicion of genetic disease. In families with more than one affected child or in cases with disease reactivations there is a high probability of genetic disease. However, the identification of a genetic defect is necessary to prove it. Genetic testing is therefore recommended, regardless of age. Depending on the ethnic background up to 30% of patients with FHL have no identified gene defect, so negative test results do not necessarily rule out FHL.
Each sibling of a child with FHL has a 25% chance of being affected. In related genetic disorders, including X-linked lymphoproliferative disease, each male child has a 50% chance of being affected. If a genetic defect is known in your family, genetic testing (before or after onset of symptoms) is available to identify siblings who may also be affected. There are several hospitals that provide information and perform genetic testing on a clinical basis, including:
Cincinnati Children’s Hospital, Cincinnati, Ohio
Karolinska University Hospital, Stockholm, Sweden
Jan-Inge Henter, MD
University Medical Center, Hamburg, Germany
Gritta Janka, MD
Gene Tests Clinic Directory
If a genetic defect has been identified in your family, prenatal diagnosis is possible by performing either amniocentesis or chorionic villus sampling (CVS) to test if the fetus is affected.
Macrophage activating syndrome is a severe, life-threatening illness caused by the excessive production of types of white blood cells called T cells and macrophages. MAS has strong similarities with familial hemophagocytic lymphohistiocytosis (FHL) and virus-associated hemophagocytic lymphohistiocytosis (HLH). The exact relationship between MAS and HLH is yet to be determined, although some researchers believe that MAS is a secondary HLH disorder. The term is typically used for the HLH-like syndrome that can occur in patients with systemic onset juvenile arthritis.
Reduced-intensity conditioning is a less toxic pre-transplant therapy with the goal of suppressing the patient’s immune system enough so that it will accept donor stem cells while reducing the side effects of high dose chemotherapy The RIC may be used in some HLH patients, as well as some LCH patients with severe, resistant disease.
What Do I Do Now?
A new diagnosis of a histiocytic disorder can bring feelings of being overwhelmed, bewildered, scared, angry, sad, disappointed, helpless, and sometimes even feelings of guilt. It is a time filled with unknowns, change, and new people and situations. Most parents feel ill-equipped to understand what is happening to their child and how to navigate through the illness to recovery. There are, however, strategies and resources that can help you, your child, and other family members get through the uncertain times that lie ahead. One step at a time, you can gather information, create a support system, learn how to cope with stress, and become a strong advocate for your Histio Warrior as part of the medical team. The following tips and suggestions are provided to help guide you through this journey toward your Histio Warrior's good health.
Histiocytosis can be considered a systemic illness; especially in cases where the disease is found in more than one system within the body. Some patients and caregivers may prefer to consult several specialists, depending on the different locations of symptoms. In this case, it is helpful to have one physician coordinate your care. An oncologist is usually the most appropriate choice.
Make sure that your doctor is someone you can trust and with whom you can communicate. Important qualities to look for in a doctor are:
- feeling as though you are heard,
- being given the opportunity to ask questions, and
- feeling respected.
If you are unsure about your physician, it is reasonable to schedule another appointment to discuss your concerns. While it is ideal to find a physician experienced and knowledgeable about histiocytic disorders, it is not always possible to find one who is nearby. If this is the case, ask the physician if he/she is open to a consultation with a knowledgeable physician and is willing to learn more about the disease. The Histiocytosis Association maintains a listing of doctors in a Physician Directory who have are knowledgeable about histiocytosis. You may also call us at +1 856-589-6606 for help finding other physicians in your area or for more information.
Call your insurance company to find out whether your plan will cover visits to the physician you are considering. Oftentimes a Team Social Worker and/or the hospital financial counselor can help smooth out insurance problems. Ask for help from a trusted friend if you feel overwhelmed in dealing with insurance issues.
Talking with your child: If your child is old enough to understand, sharing information can help him/her build trust in both you and his/her/your medical caregivers. It can also help your child cooperate with treatment and become a part of his/her/your medical team.
- Use words and ideas that are appropriate for your child’s age.
- Share information at a level that is in keeping with his/her ability to understand.
- Use your child’s questions as a guide to what he/she wants to know.
- Encourage your child to talk about his/her fears and concerns.
- Remind your child how much you love him/her.
If you are uncertain about how to talk to your child, your healthcare team can be of assistance.
Talking with family and friends: In the days and weeks following diagnosis, extended family and friends will need to be notified and periodically updated. However, explaining your situation multiple times can be exhausting and time-consuming. The Association offers a private Facebook group to help connect you with others. Some patients and families find that journaling is therapeutic and can provide an easy way to track their history and progress.
Talking with your child’s siblings: When your child is diagnosed with a histiocytic disorder, everyone in the family is affected, including brothers and sisters. They may feel anxious, lonely, resentful about the attention their sibling is getting, guilty about being healthy, or even responsible for the illness.
- Give information that is appropriate for your child’s age.
- Explain that no one did anything to cause the illness, and reassure them that it is not contagious.
- Give them a chance to talk about how the illness is affecting them or you. Be willing to answer questions.
- Remember that it will be easy for them to feel overlooked and unimportant, so it will be important to show that you love them and are proud of them.
Talking with your child’s school: Contact your school principal/counselor regarding your child’s diagnosis or if your diagnosis may affect your child. You may want to take brochures and other basic information about your histiocytic disorder. If your child is the patient, provide a written description of the health needs, such as what medications may need to be given at school, dosages, and times, signed by your physician. (Some schools will provide the form to be filled out and signed by your child’s physician.) Ask for a plan to take care of your child’s needs at school. You may need to provide written permission for the school to communicate with your physician, in case of an emergency.
Appointments: A calendar is a useful tool for remembering appointments and planning for changes to your established schedule. Calendars that show a week at a time also provide room on each day to record additional brief notes and reminders.
Medical Information: While some basic medical notes can be kept in a calendar, some patients and parents may choose to enter medical information in a laptop or keep a separate notebook. Be sure to date all entries. This information will be especially helpful when a new or different caregiver is involved. Examples that you may want to keep track of include:
- Results of various tests.
- A listing of allergies.
- A listing of medications and dosages.
- Names and phone numbers of your medical care team.
- Health information, such as your hospital number, social security number, and insurance information.
- Records of what was discussed during a medical visit/phone conversation and by whom.
- Notation of changing symptoms.
Adults may find it helpful to collect and organize medical records, starting as soon as possible after diagnosis. Although the original reports must remain in the physician or hospital file, you are legally entitled to copies of your records. You must submit a signed request for each physician’s office and the hospital. By keeping all records in one place, you can easily share these with other health care providers that you may see in the future. Follow this link to read more about obtaining your medical records.
If you have health insurance, it’s important that you know what your plan covers. Read your policy carefully to understand the health and medical services covered. Find out the portion of medical expenses you'll be responsible for paying. When you have questions or there are things you don’t understand, reach out to other experts available to you, such as the human resources personnel at your place of employment or financial counselors at your medical treatment center. If filing and tracking claims feels overwhelming, you may want to ask a trusted friend or relative to assist in managing your insurance issues.
When you call the insurance company, ask to work with one case manager. This may help simplify the process by having one person that knows your needs and can manage your claims. If possible, communicate with the same person on an ongoing basis. Remember to keep a journal of all encounters.
If you don’t have health insurance, if coverage is not adequate, or if you are not able to get insurance because of your pre-existing condition, you may qualify for your state’s high-risk insurance pool. You can obtain more information about whether your state participates at the National Association of State Comprehensive Health Insurance Plans website. If your state does not participate, you may qualify for the federal high-risk insurance pool. For more information, contact the U.S. Department of Health and Human Services.
Online: You can subscribe for our emails and you will receive important announcements regarding the latest information on the histiocytic disorders. The Association also maintains a Facebook page for families and patients with this disease.
Local support: The hospital where you or your child is being treated may have a support group for patients or parents of children with histiocytic disorders, rare diseases in general, or even cancer. Establishing face-to-face relationships with others going through similar experiences can be helpful.
The Association sponsors patient and family Regional meetings, which are held in various locations around the U.S. and hosted by Association staff and volunteers. They are a good opportunity to meet other families and patients, learn from expert physicians, receive and give emotional support, and share practical coping skills while also providing a time to relax, knowing you are with people who understand.
Fundraising events for histiocytic disorders are another way to make connections with families in your region. A listing of dates and fundraising events is provided on the Upcoming Events page.
Virtual opportunities to connect are also available.
Self-education about histiocytic disorders is an important part of advocating for your and your child. It will help you to make informed decisions about care and play a more active role in recovery.
The Association website provides education on a number of topics, including disease information, family resources, and past and ongoing research projects. The Histio Resource Directory provides an extensive listing of global, national, and state-by-state resources for patients and families. Some of the resources listed are informational, while others are service-based. A listing of past and current research projects funded by the Association can be found on the Grant Awards page, providing a glimpse into the past trends and current progress of research into the histiocytic disorders. The Disease Information section of the website features detailed, reliable information on all of the histiocytic disorders. This can be printed out and shared with medical caregivers, family, and friends if needed.
The Internet is a good source of information about histiocytosis and the treatment options, but the amount of information can be overwhelming, and the information is not always reliable. Some of it, in fact, is inaccurate. Reliable information is more likely to be found in more current documents that are free of grammatical and spelling errors, appear to be objective, are free of advertisements, and clearly state their sources.
It is essential to take an active role in your or your child’s health care. However, many patients and caregivers have little experience being advocates when they first receive a rare disease diganosis. The following is a list of essential tips for becoming a successful advocate:
- Learn about the diagnosed type of histiocytosis and become acquainted with the basic medical terms. Knowledge is empowerment.
- Know the warning signs that mean you may need emergency help.
- Know who to call in case of an emergency, and keep phone numbers handy.
- Keep a list of healthcare members involved in your medical care, along with contact information.
- If possible, take a companion (family member or friend) along on important medical appointments. The companion can help with remembering details of what was said and may assist by taking notes.
- Write down your questions before entering appointments or meetings and write down further questions as you think of them during the meeting. Don’t be afraid to ask these questions. This will be an important step in beginning to understand more about the disease. Medical information is often confusing and the language used by medical professionals is not easily understood, especially during stress. Whenever someone uses a word that you don’t understand, stop the conversation for a minute and ask the person to explain.
- Keep a healthcare notebook with a listing of allergies, medications, symptoms, and communications with healthcare providers.
- Find out about resources that the hospital provides, such as a social worker or patient representative. They can often assist with transportation costs, temporary housing if needed, parking fees, insurance issues, counseling, and other services.
- Be persistent in getting the care you feel that you or your child needs. Don’t hesitate to ask for what you need, and if you do not feel responded to, ask again or ask someone who will respond.
Trust your intuition. It can be a powerful decision-making tool. You know yourself or your child better than anyone else.
Being sick or caring for a sick child/loved one can be stressful and may take a toll on your physical and emotional health. Recognizing your own needs for support, help, health, and comfort can be difficult when you’re focused on the needs of others, but it’s important to remember that caring for yourself is essential. When your needs are taken care of, your loved ones will also benefit. Give yourself time for regular physical activity and rest. Pay attention to signs of stress, and consult your physician if you need further help.
Articles and Links
- US FDA Approves Gamifant® (emapalumab-lzsg), the First and Only Treatment Indicated for Primary Hemophagocytic Lymphohistiocytosis (HLH)
- Overview of Histiocytosis (Including Hemophagocytic Syndromes)
- The Importance of Clinical Trials in the Fight Against Histiocytosis
- How We Treat Hemophagocytic Lymphohistiocytosis
- Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis)
- Hemophagocytic Lymphohistiocytosis, Familial
- Treatment of HLH with HLH-94
- Approach to Hemophagocytic Syndromes
- Familial Haemophagocytic Lymphohistiocytosis: Advances in the Genetic Basis, Diagnosis and Management from Clinical and Experimental Immunology
- US National Library of Medicine list of articles on L
- Familial Hemophagocytic Lymphohistiocytosis (FHL)-Information on Genetic Testing
- Histiocytic Disorders of Children and Adults: Basic Science, Clinical Features and Therapy
- Search National Institutes of Health Medical Dictionary and Drug Information
- HLH Study Information
Printable Fact Sheets
Learn more about the different types of histiocytic disorders from these helpful fact sheets. Printing these for family and friends is a quick and easy way to teach them about the disease. More extensive information can be found in the Disease Information section of our website.
Choose from the following Fact Sheets:
Histiocytic Disorders Overall FAQ
Histiocytic disorders are a diverse group of diseases caused by over-production of white blood cells known as histiocytes, which can lead to organ damage and tumor formation. They include a wide variety of conditions that can affect both children and adults.
The disorders are classified into three groups based on the types of histiocyte cells involved.
- The first group is called a dendritic cell disorder, and the most common disease in this group is Langerhans cell histiocytosis. Also included in this group are more rare diseases, juvenile xanthogranuloma (JXG) and Erdheim Chester.
- The second group is called a macrophage cell disorder, and includes primarily hemophagocytic lymphohistiocytosis (HLH) and Rosai-Dorfman.
- The third group is called malignant histiocytosis and includes certain kinds of leukemia and tumors.
All of the diseases are caused by the over-production of white blood cells called histiocytes. Their different classifications depend on the type of histiocyte involved.
The Histiocytosis Association’s online community provides a number of informational documents and articles, as well as links to medical articles about the histiocytic disorders. While the Internet does provide a significant volume of information about histiocytic disorders, some of this information is not accurate. It is important to look for documents that are current, are free of grammatical and spelling errors, appear to be objective, are free of advertisements, and clearly state their sources.
Histiocytosis is a rare disease that is caused by the over-production of a type of white cell that can lead to organ damage and the formation of tumors. The Histiocytosis Association’s Disease Fact Sheets are also a great way to help explain these complicated diseases to family and friends.
According to the Rare Disease Act of 2002, an orphan disease, also known as a rare disease, affects less than 200,000 persons in the U.S., or less than 1 in 1500 people. The criteria may vary in other countries. For example in Europe, an orphan disease is defined to occur in less than 1 in 2000.
According to the National Institutes of Health there are approximately 6800 such diseases. Combined, they affect nearly 30 million Americans.
- The National Organization for Rare Disorders (NORD) - Provides a patient information center, networking program, patient assistance programs, news about clinical trials, and a rare disease database.
- The National Institutes of Health (NIH) Office of Rare Diseases Research (ORDR) - Provides information on various topics related to rare diseases and links to numerous resources.
- EURORDIS – The Voice of Rare Disease Patients in Europe - An alliance of patient organizations representing 45 countries.
- Orphanet – Database/information about rare diseases with translation available in numerous languages.