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 National Comprehensive Cancer Network® (NCCN®) - an alliance of leading cancer centers - announced the publication of new NCCN Guidelines® for histiocytosis. These clinical practice guidelines provide the latest evidence and expert-consensus for diagnosing and treating the three most common forms of histiocytosis in adults: Langerhans cell histiocytosis (LCH), Erdheim-Chester Disease (ECD,) and Rosai Dorfman Disease (RDD). Although the guidelines are focused on adult patients, there may be insight for pediatric physicians as well. The Guidelines are listed as "histiocytic neoplasms" and can be found on NCCN's website.
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.
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.
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: