What are the other Names for this Condition? (Also known as/Synonyms)

• Destombes-Rosai-Dorfman Syndrome
• RDD (Rosai-Dorfman Disease)
• Sinus Histiocytosis with Massive Lymphadenopathy (SHML)

What is Rosai-Dorfman Disease? (Definition/Background Information)

• Rosai-Dorfman Disease (RDD) is a rare, benign condition that causes proliferation of histiocytes, a type of white blood cells, within the lymph nodes and other organs of the body. It can cause lymph node enlargement; most commonly, the lymph nodes of the neck are affected
• The condition is usually seen in children and young adults. The cause of Rosai-Dorfman Disease is unknown, but it may be due to an abnormal immune response of the body to infections, according to some research scientists
• Apart from the lymph nodes, RDD can also involve other body tissues and organs, such as the skin, bone, breast, respiratory airways, and central nervous system. In such cases, it is known as extranodal Rosai-Dorfman Disease
• Rosai-Dorfman Disease may additionally cause signs and symptoms, such as fever, headache, anemia, and weakness. The involvement of the various organs of the body may lead to associated symptoms including bone fractures from weak bones, seizures from brain involvement, and skin lesions on the body
• The treatment of Rosai-Dorfman Disease is undertaken in case of significant signs and symptoms, and these may include steroid therapy and surgery to remove the swollen lymph nodes. In many cases, the healthcare provider may consider a ‘wait and watch’ approach and closely monitor the condition
• The prognosis of Rosai-Dorfman Disease is typically excellent, since it is a self-resolving condition in a majority of cases. Also, the condition is non-progressive in most cases. With appropriate treatment, as and when required, most individuals are able to make a complete recovery

Who gets Rosai-Dorfman Disease? (Age and Sex Distribution)

• Rosai-Dorfman Disease usually affects children, teenagers, and young adults. It is most common during the first decade of one’s life (up to age 10); however, the average age of manifestation is about 21 years
• Both male and female genders are affected, though a slight male preference is observed
• All racial and ethnic groups are at risk; although, more cases of RDD are seen in Africans and Afro-Americans than in Caucasians

What are the Risk Factors for Rosai-Dorfman Disease? (Predisposing Factors)

• The risk factors for Rosai-Dorfman Disease are not well-established
• However, some researchers believe that it may be influenced by certain viral and bacterial infections

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Rosai-Dorfman Disease? (Etiology)

The definitive cause of Rosai-Dorfman Disease is unknown. It may occur due to an abnormal immune system of the body, caused by a variety of triggers.

• Infectious etiology: Some researchers believe that RDD may be caused by viral infections, such as caused by varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes virus; and, by bacterial infections caused by Brucella sp and Klebsiella
• The abnormal immune response results in abnormal growth and multiplication of histiocytes within the lymph nodes. The histiocytes are a component of the white blood cells (WBCs or leukocytes) in the body
• An associated increase in leukocyte count in peripheral blood may also be seen

What are the Signs and Symptoms of Rosai-Dorfman Disease?

The signs and symptoms of Rosai-Dorfman Disease can vary from one individual to another. Some are known to have mild symptoms, while others may have severe symptoms. Also, in some individuals, the symptoms are known to ‘appear and disappear’ over time.

The signs and symptoms of RDD may include:

• Fever and night sweats
• Headache
• Joint pain
• Weight loss, fatigue
• Anemia, resulting in pale skin, tiredness, and shortness of breath
• Lymphadenopathy or swollen lymph nodes; the enlargement is usually painless
  • The most commonly involved lymph nodes are the cervical (neck) lymph nodes, when it is termed cervical lymphadenopathy. Usually a bilateral involvement is noted (involving both sides of the neck)
  • Other lymph nodes involved include those located in the inguinal (groin), axillary (armpits), mediastinal (chest), and para-aortic region
  • Lymph nodes at other regions of the body may also be affected

70% of the cases show nodal involvement, while 30% of the individuals may have additional extranodal involvement (termed extranodal Rosai-Dorfman Disease). The signs and symptoms, in case of extranodal involvement, depends on the body part or organ involved.

• The various parts/organs involved may include the skin, kidney, central nervous system (CNS), gastrointestinal tract (GI), bones, and orbit (eye)
• Signs and symptoms of the associated organ may be observed, such as:
  • Blood in sputum, if the lungs are involved
  • Skin lesions, if the skin is involved
  • Weak bones
  • Conjunctivitis-like symptoms, if the eye is involved
• The condition can also involve the upper respiratory tract, sinuses, and thyroid glands. This can lead to breathing difficulties, chronic sinusitis, and abnormal thyroid function respectively

How is Rosai-Dorfman Disease Diagnosed?

Rosai-Dorfman Disease is diagnosed using the following methods:

• A thorough physical examination and assessment of one’s complete medical history
• Radiological studies (X-ray, CT scan, MRI scan, etc.) of the affected area
• Complete blood count
• Tests to diagnose any underlying bacterial or viral infections
• Liver and kidney function tests
• Pulmonary function test, if there are breathing difficulties
• Thyroid function test, if symptoms of thyroid gland dysfunction are noted

A biopsy on the affected lymph node may be performed:

• Lymph node biopsy: A lymph node biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. The pathologist may use special techniques, such as immunohistochemistry stains, to help reveal the presence of the pathogen (if any)
• The lymph node biopsy may be performed through any of the following procedures:
  • Fine needle aspiration biopsy (FNAB): A device called a cannula is used to extract tissue or fluid from the lymph nodes
  • Lymph node core biopsy of the enlarged lymph node
  • Lymph node open biopsy of the enlarged lymph node
• Flow cytometry to rule-out lymphoma: The test helps identify cells as they flow through an instrument, called a flow cytometer. Flow cytometry measures the number and percentage of cells in a blood sample, and cell characteristics, such as size, shape, and the presence of biomarkers on the cell surface

A differential diagnosis may be undertaken to eliminate the following conditions, prior to arriving at a definite diagnosis of RDD:

• Erdheim-Chester disease
• Gaucher disease
• Hodgkin and non-Hodgkin lymphoma
• IgG4-related disease
• Juvenile xanthogranuloma
• Langerhans cell histiocytosis and Langerhans cell sarcoma
• Leukemia
• Melanoma
• Sarcoidosis
• Tuberculosis
• Wegener granulomatosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Rosai-Dorfman Disease?

The complications of Rosai-Dorfman Disease depend on the body organs affected. It may include the following:

• Emotional stress: Prolonged enlargement of the lymph nodes raising a concern for malignant conditions such as lymphomas
• Brain involvement can lead to seizures
• Easy bone fractures due to weakening of the involved bones
• Chronic sinusitis
• Impairment of vision in case of involvement of the eye and surrounding tissues
• Severe hypothyroidism due to extensive involvement of the thyroid gland

How is Rosai-Dorfman Disease Treated?

No treatment may be required for individuals affected by Rosai-Dorfman Disease, if no significant symptoms are observed. The healthcare provider may choose to undertake close observation of the individual, in such cases.

However, if the symptoms are significant, then the following treatment measures may be considered:

• Steroid therapy
• Surgical removal of enlarged lymph nodes
• Rarely, chemotherapy and radiation therapy may be recommended on a case-by-case basis
• Specific treatments may be considered based on the body part/organ involved

How can Rosai-Dorfman Disease be Prevented?

There are currently no preventive methods available for Rosai-Dorfman Disease.

What is the Prognosis of Rosai-Dorfman Disease? (Outcomes/Resolutions)

The prognosis of Rosai-Dorfman Disease is based on the severity of the signs and symptoms. Nevertheless, it has an excellent prognosis, since it is self-limited (i.e., goes away without treatment on its own), in a majority of patients.

• Up to 80% of the affected individuals are known to get better on their own without any treatment
• In 90% of the individuals, the condition is not progressive i.e., RDD does not become worse with time. In the remaining 10% though, it can be a progressive condition
• In some individuals, severe complications may develop when vital organs, such as the brain, kidneys, or digestive system, are involved. In such individuals, the prognosis may be guarded

Additional and Relevant Useful Information for Rosai-Dorfman Disease:

General information on lymph nodes:

The lymph nodes are part of one’s immune system. The lymph nodes are present throughout the body, usually in groups. In normal healthy adults, one cannot feel (see or touch) the lymph nodes readily. However, if they are enlarged, they can be felt either by the individual himself/herself or by the healthcare provider.

Enlarged lymph nodes can occur in both benign and malignant conditions. Hence, the cause of enlarged lymph nodes should be evaluated. If no obvious cause for enlargement of lymph nodes is found, then the possibility of a lymph node malignancy should be ruled out.

In a majority of individuals, a lymph node swelling is caused by a benign process such as an inflammation or infection. In many cases, swollen lymph nodes are part of other signs and symptoms. This can help a healthcare provider arrive at a list of follow-up tests and ensure an accurate diagnosis. Superficial enlarged lymph nodes can be felt by the healthcare provider through palpation. Enlarged lymph nodes deep in the body are often detected by radiological studies such as X-rays, ultrasound scan, CT and MRI scans.

Some enlarged lymph nodes can be painful, while others may be painless. Depending upon the underlying cause, enlarged lymph nodes can be localized to a particular area of the body, or they can be generalized, meaning that they are present throughout the body.