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Xanthogranuloma

Juvenile xanthogranuloma (JXG) is a rare type of histiocytic disorder that mostly occurs in children (average age 2 years), but can rarely occur in adults as well, in which case it is called adult xanthogranuloma (AXG).

Juvenile xanthogranuloma (JXG) is a rare type of histiocytic disorder that mostly occurs in children (average age 2 years), but can rarely occur in adults as well, in which case it is called adult xanthogranuloma (AXG). The cause of JXG is unknown at this time, although it can sometimes be seen in association with conditions named as neurofibromatosis type 1 and juvenile myelomonocytic leukemia. Rarely, JXG can be driven by genetic changes (mutations) in the MAPK pathway, including the BRAF and ALK genes. These mutations occur in the tumor cells, and not in the DNA that is transmitted to children.

This disease may have been first reported by Rudolf Virchow in 1871 and again in 1905 by H.G. Adamson. In 1954, it was named juvenile xanthogranuloma to reflect the appearance of the cells under a microscope. JXG/AXG involves the over-production of a kind of histiocyte called a dendritic cell (not a macrophage). These cells then accumulate and lead to various symptoms, depending on location. The cause of this disease is not known, and the total number of patients is not known, but may be higher than reported on since this disease is sometimes misdiagnosed or may spontaneously improve.

It occurs most often in the skin of the head, neck, and trunk but can also occur in the arms, legs, feet, and buttocks. JXG/AXG can affect the eye, most commonly in young children with multiple skin lesions. Less commonly JXG/AXG may involve locations such as the lung, liver, adrenal gland, appendix, bones, bone marrow, pituitary gland, central nervous system, kidney, heart, small and large intestines, and spleen. Skin lesions cam be self-limited and rarely require treatment in most patients. Those with large abdominal masses, liver, bone marrow, or central nervous system involvement may do well with treatment such as chemotherapy similar to that used for Langerhans cell histiocytosis. In about 10% of patients, JXG occurs at birth, and is seen to affect more males than females.

Because JXG is so rare, no large studies have been performed, and there is no established, proven treatment for the more complicated cases. However, the Histiocytosis Association continues to work closely with an international group of physicians, known as the Histiocyte Society, who are dedicated to studying all of the histiocytic disorders. Through their combined efforts, awareness about JXG has increased, and progress has been made in the understanding of this disease.

Symptoms

Most commonly (90% of the time), it presents as a single skin lesion which varies in size, but children less than 6 months of age are more likely to have multiple lesions. It occurs at birth (congenital) in about 10% of patients, and more males are affected than females. Adult XG is less well understood at this time, and appears to sometimes share features with Erdheim-Chester disease, a related histiocytic disorder.

JXG can affect the skin only, the eye, and/or other locations in the body such as the lung, liver, adrenal gland, appendix, bones, bone marrow, pituitary gland, central nervous system, kidney, heart, small and large intestines, and spleen. The skin is the most common location of involvement and often does not require treatment. In one study of 129 patients (Kiel Pediatric Tumor Registry), 71% of the cases were diagnosed within the first year of life, and 81% were single skin lesions. There is an overall rate of 7% to 10% of patients (including adults) with multi-system JXG. Children younger than 6 months are more likely to have multiple lesions.

Skin lesions usually do not have symptoms such as pain or itching. They present as reddened, yellowish or brownish, slightly raised, and rubbery bumps on the skin. They may also appear in the fat layer beneath the skin.

Eye lesions may or may not occur in the presence of skin involvement. Eye involvement with JXG needs to be treated to prevent visual problems. JXG/AXG involving the eye, which is the second most common location, usually affects the iris, which is the colored, ring-shaped part of the eye. Lesions can, however, occur in other parts of the eye including the eyelid or inside of the eye, usually on one side only. Approximately one- half of patients with eye involvement also have skin lesions. Eye lesions are less likely to improve without treatment than skin involvement and can progress without treatment. Because many patients with JXG/AXG of the eye are without symptoms, the diagnosis may be delayed and/or difficult. Eye lesions may be discovered by accident, often noted by watchful parents or the primary care physician.

Systemic JXG, where lesions are present in more than one organ or body system, has been reported only in single- or small-case studies and usually requires treatment.

It is generally recommended that young children with multiple skin lesions be seen by an ophthalmologist every 3 months until 3 years of age.

Other symptoms related to JXG depend on the location of the disease. For example, if the bone marrow is involved, patients may have abnormalities in blood counts. Liver involvement can cause abnormalities in blood liver tests, as well as an elevated inflammation level (sedimentation rate) in the blood. Pituitary gland involvement can lead to diabetes insipidus.

It is important to remember that the diagnosis of JXG cannot be made on symptoms alone as it may present very similarly to LCH. It is therefore necessary to consult a knowledgeable physician to receive a thorough work-up and accurate diagnosis.

Diagnosis and Treatment

Diagnosis and Workup

The diagnosis of JXG relies on reviewing the biopsy of a tissue lesion under the microscope. Occasionally, the dermatologist may make a presumptive diagnosis based on the appearance of the skin lesions. When a biopsy is performed, 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 characteristics, the diagnosis of JXG can be made. JXG cells are negative for the presence of proteins called CD1a and CD207, while LCH cells are positive for those markers. Instead JXG cells are positive for proteins called CD68 and factor XIIIa. The pathologist may sometimes do additional tests on the tissues including mutational testing to help with arriving at a diagnosis. It is difficult to distinguish between JXG and Erdheim-Chester disease under the microscope. In patients with skin-limited lesions and no systemic symptoms or signs, evaluations should include a complete blood count, liver function tests, and ophthalmologic (eye) examinations.

An ultrasound may be performed to see if the JXG is in the abdominal organs such as liver or spleen. In addition, depending on the symptoms other tests such as CT scans, MRI scans, or bone X-rays may be done. Rarely, the physician might order a PET scan to look for various sites of involvement.

Treatment

Treatment varies according to the extent and severity of disease involvement. Most children with skin-limited lesions do not require treatment and can be observed with serial examinations. Surgical removal may be undertaken for several reasons: to obtain a biopsy for diagnosis, when there is an organ-function problem because of disease, for cosmetic reasons or to remove scar tissue. For the small percentage of individuals who have symptomatic or rapidly growing disease, treatment with chemotherapy or low-dose radiation has been reported, although there is no standard treatment that is agreed upon. With eye involvement, steroids may be applied to the surface of a lesion, injected within the lesion, or taken in pill form. Rarely low dose radiation treatment may be given to the eye to prevent visual loss. XG in adults (AXG) tends to be more complicated and is not known to improve spontaneously without treatment. This may involve surgical removal alone or additional therapy depending on the clinical situation. Most common treatment regimens for JXG or AXG are derived from LCH, such as cladribine, cytarabine, or vinblastine + prednisone. If there is a presence of a mutation (BRAF, ALK, etc.), specific pills targeting those genes can be utilized.

FAQ

JXG/AXG involves the over-production of a kind of histiocyte called a dendritic cell. What triggers these cells to accumulate is not known.

We usually don’t use the term “cure” with this disease, although most patients with only skin or soft tissue JXG/AXG have spontaneous remission over time without treatment. Children with liver, bone marrow, CNS involvement and masses in the abdominal cavity usually survive with chemotherapy treatment. There is no established period of inactive disease before JXG is considered cured.

Patients with a single lesion or just a few lesions, as well as children with skin-only JXG often require no therapy. Surgical removal may be required if the mass is causing organ dysfunction. A small percentage of patients with rapidly growing disease may require treatment with chemotherapy or low-dose radiation, however there is no standard of therapy that has been agreed upon. Steroids have been used to treat eye lesions and in some cases low dose radiation has been effective in preventing visual loss.

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.

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 Finder 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.

  1. Use words and ideas that are appropriate for your child’s age.
  2. Share information at a level that is in keeping with his/her ability to understand.
  3. Use your child’s questions as a guide to what he/she wants to know.
  4. Encourage your child to talk about his/her fears and concerns.
  5. 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.

  1. Give information that is appropriate for your child’s age.
  2. Explain that no one did anything to cause the illness, and reassure them that it is not contagious.
  3. Give them a chance to talk about how the illness is affecting them or you. Be willing to answer questions.
  4. 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:

  1. Results of various tests.
  2. A listing of allergies.
  3. A listing of medications and dosages.
  4. Names and phone numbers of your medical care team.
  5. Health information, such as your hospital number, social security number, and insurance information.
  6. Records of what was discussed during a medical visit/phone conversation and by whom.
  7. 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 diagnosis. The following is a list of essential tips for becoming a successful advocate:

  1. Learn about the diagnosed type of histiocytosis and become acquainted with the basic medical terms. Knowledge is empowerment.
  2. Know the warning signs that mean you may need emergency help.
  3. Know who to call in case of an emergency, and keep phone numbers handy.
  4. Keep a list of healthcare members involved in your medical care, along with contact information.
  5. 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.
  6. 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.
  7. Keep a healthcare notebook with a listing of allergies, medications, symptoms, and communications with healthcare providers.
  8. 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.
  9. 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

Articles

Links

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.

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.