What Is Rosai-Dorfman Disease

Our immune system works to protect our body’s own cells, tissues, and organs while battling harmful foreign substances that make us sick- bacteria, viruses, and even cancer. It is no surprise that having a weaker immune system makes us more susceptible to illnesses. The immune system comprises various types of soldiers, known as immune cells. But is it better to have more soldiers (immune cells) to win the battle? In the realm of immunity, the answer is quite the opposite! Having too many immune cells can cause problems in our body, as these excessive immune cells start to attack our body system, which is not pleasant to experience at all. 

Rosai-Dorfman Disease (RDD) is a rare and benign medical condition caused by the overgrowth of histiocytes, a type of immune cell. RDD is characterised by the accumulation of these histiocytes in a range of our body parts, ranging from a lymph node to different body systems. Clinical manifestations vary from person to person and are dependent on the location of histiocytic lesions. While the exact cause of RDD remains unclear, it may be linked to other severe conditions, such as autoimmune disorders and cancer. 

So far, RDD sounds like cancer in some ways and an autoimmune disorder in others. In fact, RDD is neither a cancer nor an autoimmune disorder but rather showcases both clinical phenomena. In this article, we’ll delve into this rare condition, exploring its history, symptoms, diagnosis and available treatments.

Overview 

The symptoms of Rosai-Dorfman Disease (RDD) were first reported in French literature by Pierre Paul Louis Lucien Destombes in 1956.¹ In 1969, RDD was first studied with additional patients with similar symptoms by Juan Rosai and Ronald Dorfman in English and therefore, RDD is also called Rosai-Dorfman-Destombes disease.²

RDD is a rare and benign condition characterised by an overgrowth of white blood cells known as histiocytes, which play a crucial role in the immune system. When the body produces too many histiocytes in the lymph nodes, they accumulate within and outside of the lymph nodes, affecting areas such as the skin, eyes, bones, and respiratory system. Although histiocytes tend to accumulate in the lymph nodes in the neck, other lymph nodes can also be affected and may also affect one or more groups of these organs. 

Classification and symptoms of rosai-dorfman disease (RDD)

Symptoms of RDD vary depending on the extent to which lymph nodes are affected by an excess of histiocytes. The disease can be mild or even asymptomatic if the histiocytes only affect lymph nodes in your neck. As histiocytes can accumulate in various body systems beyond the lymph nodes, RDD can be categorised into different groups based on their accumulation sites: 

• Classic (nodal) RDD,
• Extranodal RDD 
• Cutaneous RDD (CRDD). 

Patients may experience extranodal RDD in addition to classic RDD.^3,4,5

Classic (nodal) RDD

Classic RDD, also known as nodal RDD, is the most common form of RDD. It leads to swelling of the lymph nodes, mostly in the neck, but can also affect nodes in the groin, armpits, and the central portion of the chest (mediastinum). The affected lymph nodes can swell, and this enlargement is often painless but can sometimes be accompanied by fever. Patients with classic RDD may not experience symptoms other than swelling. Still, they could exhibit: 

• Fever
• Pale skin
• Fatigue
• Runny nose 

Extranodal RDD 

Approximately 43 % of RDD occur outside of lymph nodes, affecting various tissues and body systems.⁶ This form of RDD may lead to a range of symptoms based on the affected sites.^7,8 For instance, if surplus histiocytes accumulate in the lung, patients may exhibit persistent coughing. Extranodal sites can include: 

• Sinuses 
• Eyes
• Eyelids
• Bones 
• Kidneys
• Breasts
• Central Nervous System (CNS)⁹
• Respiratory system
• Gastrointestinal system

Cutaneous RDD (CRDD)

The skin is the most common extranodal site for RDD, and as a result, it is often classified separately as cutaneous RDD (CRDD). 

Cause of rosai-dorfman disease (RDD)

In most cases, the exact cause of RDD remains unknown.¹⁰ However, several factors have been suggested as potential causes such as various gene mutations.

Gene mutation

Researchers reported that mutation in the genes that are associated with cell growth leads to overgrowth of histiocytes.^3,11,12,13

Comorbidity with other conditions

RDD is often associated with other conditions, including: 

• Autoimmune conditions such as lupus, juvenile idiopathic arthritis, and autoimmune hemolytic anaemia¹⁴
• Cancer including Hodgkin lymphoma and non-Hodgkin lymphoma^11,15

It may also be related to altered immune responses and infections by agents such as:

• Viruses: varicella-zoster, herpes, Epstein-Barr, HIV, mononucleosis¹⁶
• Bacteria
  • Brucella: found in cattle, goats, dogs, and pigs that can be transmitted to humans through direct contact or consumption of contaminated food.
  • Klebsiella: found in the intestines of animals and humans, as well as in some plants.

Risk factors

RDD is diagnosed more frequently in younger individuals, with an average onset at 20.6 years of age. However, cases have also been reported in older patients, including those in their 60s.^11,17 African descent males are at a higher likelihood of being diagnosed with RDD.¹¹ In the case of CRDD, it is found more commonly in individuals of Asian and Caucasian descent, with an average onset at 43.5 years of age.

Diagnosis

Your GP will conduct a physical examination and ask about your symptoms. They may also consider your medical history especially, if there are any conditions associated with RDD.⁵ To diagnose RDD, a biopsy and blood test can be performed as well as imaging techniques such as X-rays, ultrasounds, MRIs, CT scans, PET scans, PET/CT scans or bone scans depending on the suspected area of histiocytic lesions.^18,19  

Management and treatments for rosai-dorfman disease (RDD)

While there is no specific treatment for RDD, approximately 80% of the symptoms disappear without any treatment after a few months or years (spontaneous remission).²⁰ However, the condition may not improve on its own and/or the cells can regrow after remission. 

Observation 

If the symptoms do not significantly affect your quality of life or are not associated with other severe conditions, your GP may recommend monitoring RDD without treatment.

Chemotherapy

Certain medications including corticosteroids can be prescribed to reduce lymph node swelling and provide relief from symptoms.^3,10

Surgery

Histiocytic lesions can be surgically removed particularly, when the symptoms are severe or located in critical areas of the body, such as those blocking your airway or affecting the spinal cord.²¹ 

Radiation therapy 

Radiation therapy can be applied directly to the RDD-affected area to destroy histiocytes. This approach is considered when histiocytic lesions cannot be surgically removed. 

Immunotherapy 

Immunotherapy may be a consideration, especially when the RDD is associated with autoimmune disorders.^3,9

Summary

Rosai-Dorfman Disease is a rare medical condition characterised by the overgrowth and accumulation of histiocytes, a type of white blood cells crucial to the immune system. These surplus histiocytes can accumulate in lymph nodes, known as classic or nodal RDD, or other areas of the body (extranodal RDD), including the skin (cutaneous RDD), which is the most common site within the extranodal region. Histiocytes can accumulate in one or more areas of the body and sometimes in both nodal and extranodal regions. 

Symptoms can vary significantly among individuals, mainly depending on the location of histiocytic lesions and the number of body parts involved, from no symptoms to severe manifestations. Patients with classic RDD typically experience lymph node swelling, sometimes accompanied by fever, while patients with extranodal RDD can exhibit a wide range of clinical symptoms based on the location of histiocytic lesions. 

While many patients experience spontaneous remission without treatment, not all do, and clinical interventions such as medications for symptom relief, surgical histiocytic lesions removal, radiotherapy or even immunotherapy can be considered, as there is no specific treatment for RDD. 

The exact cause of RDD remains unknown, but studies reported that it can result from mutations in genes associated with cell growth and altered immune response by bacterial and viral infections. RDD can also serve as a sign of other conditions, such as autoimmune disorders and cancer. Risk factors include a younger age of onset in classic RDD and a higher prevalence in individuals of Asian and Caucasian for CRDD. However, it is important to note that the condition is not limited to a specific gender or age. Diagnosis of RDD involves biopsy, blood tests and a range of imaging techniques based on the suspected area. 

FAQs

How common is rosai-dorfman disease (RDD)?

RDD is a rare condition, with an estimated incidence of approximately 1 in 200,000 individuals.³ 

Is rosai-dorfman disease serious?

No. Rosai-Dorfman Disease is rarely life-threatening. However, the severity of the condition can vary depending on the affected area and the number of body parts involved.

Is rosai-dorfman disease (RDD) cancer?

No. RDD is a benign condition, which means it does not spread to other parts of your body, unlike malignancies (cancer). 

Is rosai-dorfman's disease an autoimmune disorder?

While RDD has been associated with autoimmune phenomena, it remains unclear whether there is any underlying connection between RDD and autoimmune disorders. Therefore recent study suggests that RDD should remain within differential diagnosis.²²

Do I need to see a doctor?

Yes. While most symptoms can resolve on their own without any treatment, timing can be unpredictable and there’s a possibility of them being linked to other conditions. Therefore, it is advisable to consult with your GP.