Rosai-Dorfman disease (RD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare histiocytic disorder which involves the over-production of a type of white blood cell called non Langerhans sinus histiocyte.
These cells then accumulate, most often in the lymph nodes, but may occur in other areas of the body and can lead to organ damage. The reason that these cells over-produce is not known, although many possibilities have been considered, including viral, bacterial, infection, environmental, and genetic causes.
In 1969, two pathologists, Juan Rosai and Ronald Dorfman, reported a distinct histiocytic disorder in several patients with massive enlargement of the lymph nodes, as well as other symptoms. They named this condition sinus histiocytosis with massive lymphadenopathy, and the name has since come to be known as Rosai-Dorfman disease.
The true number of RD cases is not known, although it does occur worldwide and seems to affect equal numbers of males and females. It is most commonly seen in the first 10 years of life, but it also occurs in adult patients.
Because this disease is so rare, no large studies have been performed, and there is no established, widely-accepted treatment. However, RD is usually not life-threatening, and many patients do not require treatment.
The Histiocytosis Association continues to work closely with an international group of physicians, known as the Histiocyte Society, who are dedicated to studying the histiocytic disorders. Through their combined efforts, awareness about the disease has increased, more research has been undertaken, and progress has been made in the understanding of this disease.
Rosai-Dorfman may affect lymph nodes only, it can affect lymph nodes plus other body systems, or it can occur in body systems without lymph node involvement. However, more than 87% of patients present with enlargement of the lymph nodes in the neck. This is usually on both sides and is painless but often get very big. Within the lymph node system, it can also occur in the nodes in the groin, armpits, and in the central part of the chest.
Location of this disease outside of the lymph nodes occurs in approximately 40% of cases. In order of frequency, this disease affects skin and soft tissue (16%), nasal cavity (16%), eyes/eyelids (11%), bones (11%), central nervous system (7%), salivary glands (7%), kidney (3%), airway (respiratory tract) 3%, and liver 1%. The breast, digestive tract, and heart are affected in less than 1% of cases.
Symptoms of RD depend on the site of involvement and can include:
- Lymph node enlargement (with or without pain).
- Weight loss.
- Shortness of breath.
- Blockage/discharge of the nose.
- Deformity of the nose (saddle-nose).
- Inflammation of the tonsils/sinuses.
- Difficulty swallowing or speaking.
- High-pitched breathing.
- Eye bulging/decreased vision.
- Night sweats.
- Decreased sensation.
- Blood abnormalities (low red blood cells, white cell abnormalities, increased sedimentation/inflammatory cell rate, abnormal protein levels, etc).
- Joint pain.
- Slowly growing, painless mass.
Many adults with RD experience severe and sometimes overwhelming pain associated with this disease. While pain can be caused by bone lesions or bone defects that do not heal completely with therapy, some patients have pain even when there is no active disease seen on x-ray. The cause of this pain is not understood; however, it is being currently explored in research. Pain is considered a complication of RD that should be fully evaluated by a physician and treated with appropriate medications.
It is important to remember that symptoms alone do not make the diagnosis of RD disease. Thus, it is important to consult a physician to receive a thorough workup and accurate diagnosis.
Diagnosis and Treatment
The diagnosis of Rosai-Dorfman (RD) is made following a biopsy of the affected tissue. A small piece of the tissue is obtained so that it can be viewed under a microscope by a pathologist. If the cells in the tissue have certain specific characteristics, the diagnosis of RD can be made. This procedure can be performed of the lymph nodes, skin, bone, liver, lung, or bone marrow. RD cells stain with S100 and CD68.
Once the diagnosis is made, the extent of disease should be established. Further diagnostic testing will depend on the individual case and may include testing similar to that used for Langerhans cell histiocytosis: Physical exam, blood and urine tests, and x-ray procedures such as CT, MRI, ultrasound, and/or bone scanning. The severity of the disease is determined according to the number of lymph node groups affected and the sites outside of the lymph nodes.
On occasion, the immunoglobulin (antibody levels) in the blood is very high and they may need to be removed from the blood by a treatment called plasmapheresis. These levels should be checked as part of the diagnostic investigation.
Treatment depends upon the individual patient and is planned after thorough testing to determine the extent of disease. Ideal treatment, however, has not been established, and there is no ongoing clinical trial. It is believed that 70% to 80% of patients have spontaneous improvement of symptoms without treatment, although they may have alternating episodes of worsening and relieving of symptoms for a long period of time. Some patients with severe or persistent disease or cases where organ function is threatened (such as breathing obstruction or kidney failure) may require treatment with surgery, steroids, and/or chemotherapy. Rarely radiation therapy may be used. Chemotherapy may include vinblastine, 6-MP, methotrexate, thalidomide, or Gleevec. The ultimate goal of an overall treatment plan, of course, is to use as little treatment as possible to keep the disease under control and preserve quality of life.
Rosai-Dorfman does not usually threaten life or organ function. It is believed that 5% to 10% of patients have progressive disease that may damage tissue. However, for most patients, the disease is self-limited, and the outcome is good.
Rosai-Dorfman involves over-production of a type of white blood cell called a non-Langerhans sinus histiocyte. The cause of this over-production is not yet known.
While many patients go into remission and live normal lives with or without treatment, we usually don’t use the term “cure.” There is no established period of inactive disease before RDD is considered cured.
Many Rosai-Dorfman patients do not require treatment. Some patients with severe or persistent disease may need treatment with surgery, steroids, and/or chemotherapy. Rarely, radiation therapy is used.
A biopsy of the affected tissue, rather than a blood test, is required for diagnosis and would therefore not be appropriate as a routine test unless this disease is suspected.
Some pain and cramping can be a side effect of treatment, such as vinblastine and steroids. Pain may also be directly related to active disease. In cases of more chronic pain, some researchers suspect that cytokines, which are a type of messenger, stimulate white blood cells to release inflammatory molecules that produce pain.
Side effects include:
- Low blood counts (with higher risk of infection)
- Mild nausea/vomiting/constipation
- Easily sunburned
- Skin irritation at site of injection
- Thin or brittle hair
- Bone pain
- Shortness of breath
- Nerve damage (especially in adults) with tingling, numbness and/or pain of the hands and feet
Side effects include:
- Increase in blood sugar
- Increase in appetite
- Bloating/fluid retention/weight gain
- Difficulty sleeping
- Mood/behavior/personality changes
- Higher risk of infection
- Slow wound healing
- Muscle weakness
- Loss of bone calcium
- Increased hair growth
More unusual side effects may include:
- Problems with vision/eye pain
- Muscle twitching
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
More common signs/symptoms include:
- Low blood counts (red cells, white cells, and clotting cells)
- Nausea/vomiting/decreased appetite
- Rash/darkening of the skin
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
- Overview of Histiocytosis
- The Importance of Clinical Trials in the Fight Against Histiocytosis
- LCH Information from the National Cancer Institute
- Histiocitosis de células de Langerhans - del Instituto Nacional del Cáncer (en Español)
- Improved Outcome of Treatment-Resistant High-Risk Langerhans Cell Histiocytosis After Allogenic Stem Cell Transplantation with Reduced-Intensity Conditioning
- Improved Outcome in Multisystem LCH
- Health-Related Quality of Life, Cognitive Functioning, and Behaviour Problems in Children with Langerhans Cell Histiocytosis
- Neuropathology of CNS Disease in Langerhans Cell Histiocytosis
- Central Nervous System Disease in Langerhans Cell Histiocytosis
- Dermatology Online Journal: LCH
- BRAF, A Piece of the LCH Puzzle
- Notch is Active in Langerhans Cell Histiocytosis and Confers Pathognomic Features on Dendritic Cells
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.