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

• Giant Cell Histocytomatosis
• Lipoid Dermatoarthritis
• Nicolau-Balus Syndrome

What is Multicentric Reticulohistiocytosis? (Definition/Background Information)

• Multicentric Reticulohistiocytosis (MRH) is a systemic and severe disorder that primarily involves the skin, mucus membranes, and joints. However, the condition can affect any of the internal organs, such as the lungs, liver, thyroid gland, heart, and gastrointestinal tract, among others
• Multicentric Reticulohistiocytosis is characterized by skin lesions (papules and nodules) and severely disabling arthritis (termed arthritis mutilans). The cause of the condition is not well-understood. In about 1 in 4 cases, it is observed in the background of an underlying malignancy such as lung cancer or breast cancer
• There is no cure for the condition, and it is frequently managed symptomatically. However, Multicentric Reticulohistiocytosis is typically progressive, and the condition can present severe complications such as cachexia (wasting away), deformed joints, and facial scarring and disfigurement

Who gets Multicentric Reticulohistiocytosis? (Age and Sex Distribution)

• Multicentric Reticulohistiocytosis is a very rare disorder, with just about 200 cases being reported in the medical literature
• The age of onset is typically in adulthood (mean age 47 years), although individuals of a wide age range (between 8 and 74 years), including children, may be affected
• Both men and women may be affected by this disorder. A higher number of cases are reported in women (women-men ratio is 3:1)
• Individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Multicentric Reticulohistiocytosis? (Predisposing Factors)

A pre-existing cancer/malignancy may be a risk factor for Multicentric Reticulohistiocytosis. It is reportedly noted in nearly 25% of the cases. The common cancers include:

• Breast cancer
• Cervical cancer
• Colorectal cancer
• Lung cancer
• Ovarian cancer
• Stomach cancer

In some individuals, it is also associated with the following conditions:

• Hyperlipidemia
• Primary biliary cirrhosis
• Sjögren syndrome
• Vasculitis - a condition causing inflammation of the blood vessels

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 Multicentric Reticulohistiocytosis? (Etiology)

The exact cause of development of Multicentric Reticulohistiocytosis is presently not well-established. The condition is believed to be a reactive process to an (as yet) unidentified stimulus.

• Since it is associated with an underlying malignancy in some cases, some research experts believe that it may be a paraneoplastic condition
• However, no single cancer type has been consistently associated with Multicentric Reticulohistiocytosis
• Moreover, information on regression of the condition following treatment/excision of the underlying cancer is non-confirmatory

Some experts believe that owing to molecular abnormalities involving certain pathways (such as MAP2K1 and TT2 gene pathways), the cause of development of Multicentric Reticulohistiocytosis may be genetic.

What are the Signs and Symptoms of Multicentric Reticulohistiocytosis?

The signs and symptoms of Multicentric Reticulohistiocytosis may vary form one individual to another and may include skin and arthritic signs and symptoms. In nearly 50% of the individuals, the onset of arthritis is noted first. However, in 25% of the cases, skin lesions are noted first. In the remaining 25%, both skin and joint signs and symptoms may develop together.

The signs and symptoms may include:

• Arthritis involving any of the joints, including the knees, hips, shoulders, hands, and fingers
• The arthritis signs and symptoms may wax and wane, and may include:
  • Joint pain and tenderness
  • Swelling of tissue around the joint
  • Stiffness, decreased range of motion of the joint
  • Joint deformity and joint destruction (observed in nearly 1 in 2 cases)
• The arthritis affects the joints symmetrically and is progressive; the condition can become severe and disabling
• Skin and mucosal lesions may be observed on any part of the body, but commonly involves the upper half of the body (above the waistline). Over half of the cases present mucosal lesions
  • Presence of red-brown-yellow lesions that range in size from a few mm to several cm
  • There may be solitary or multiple lesions in the form of papules and nodules
  • When present on the nose or ears, the lesions have a potential to destroy the cartilage
  • The affected skin regions include the chest, back, hands, and face and neck
  • The mucosal surfaces affected include the mouth (gums, tongue, and lips), throat, and nostrils
  • When around the nails, the lesions are called coral-beading
• Generally, no pain or irritation may be felt; however, in some (nearly 35%) of the cases, itchiness may be present
• Involvement of the tendons, muscles, and bones, apart from the joints

Additionally, the following systemic signs and symptoms may be noted in individuals with Multicentric Reticulohistiocytosis:

• Fever 
• Muscle pain and muscle weakness
• Tiredness
• Swallowing difficulties
• Swollen lymph nodes

How is Multicentric Reticulohistiocytosis Diagnosed?

Multicentric Reticulohistiocytosis is diagnosed on the basis of the following information:

• A thorough physical examination and a complete medical history
• Dermoscopy: Dermoscopy is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Blood tests such as complete blood count (CBC), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)
• Radiological studies of the affected joints
• Investigative studies to detect any underlying malignancy, if necessary
• Skin biopsy: A skin biopsy is performed and sent to a laboratory for a pathological examination, who 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. A skin biopsy is performed to rule out other similar conditions
• Histopathological and immunohistochemical of biopsy specimens (characteristic reticulohistiocytic granulomas mainly composed of CD68 positive cells may be indicative of Multicentric Reticulohistiocytosis)

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 Multicentric Reticulohistiocytosis?

The complications of Multicentric Reticulohistiocytosis may include:

• Chronic pain and stiffness within the affected joint that may prevent individuals from performing their routine daily activities
• Anemia that presents pale skin, fatigue, and shortness of breath
• Disfigurement of the face, in case of severe involvement by the facial lesions
• Cachexia - extreme weight loss and muscle loss
• Extreme difficulty with movement
• Involvement of internal organs - a simultaneous involvement of several organs, such as the heart, liver, lung, GI tract, kidney, thyroid, larynx, salivary glands, eye, and bone marrow, may take place
• Complications associated with an underlying malignancy if any

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Multicentric Reticulohistiocytosis Treated?

There is no well-defined treatment measures available for Multicentric Reticulohistiocytosis. The healthcare provider may recommend the following:

• Non-steroidal anti-inflammatory drugs (NSAIDs) for pain
• Systemic corticosteroids (usually short course)
• Administration of immunosuppressants and chemotherapeutic agents
• Antimalarial drugs such as hydroxychloroquine
• Bisphosphonate medication to treat osteoporosis
• The treatment for arthritis may include conservative measures, such as rest, cold compress, NSAIDs for pain, physical therapy, steroid injections, and surgery, if the condition is severe

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

How can Multicentric Reticulohistiocytosis be Prevented?

The cause of Multicentric Reticulohistiocytosis is not clearly known, and therefore, no methods or guidelines are presently available for its prevention.

What is the Prognosis of Multicentric Reticulohistiocytosis? (Outcomes/Resolutions)

The prognosis of Multicentric Reticulohistiocytosis (MRH) is dependent upon the severity of the signs and symptoms and associated complications.

• If there is an internal malignancy, the outcome may be dictated by the severity of the malignancy and its treatment response
• Individuals with MRH may experience reduced quality of life due to debilitating arthritis, which is known to occur in about 45% of cases
• Many cases are known to go into remission (period of decrease in signs and symptoms severity) after an average of about 8 years. However, the presence of severe arthritis and longstanding skin lesions may seriously disrupt one’s daily life

Additional and Relevant Useful Information for Multicentric Reticulohistiocytosis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/