Langerhans cell Histiocytosis in Adults

Langerhans cell histiocytosis (LCH) in adults is a rare disorder that occurs when the body produces too many Langerhans cells (histiocytes), which are a type of white blood cell that helps fight infection. While Langerhans cells are found in normal, healthy people, there is an over-production and build-up of these cells which can lead to organ damage in adults with LCH.

Although some forms of this disease were first described over a century ago, it has only been in recent years that LCH has received more attention, especially in adults.

The name for this disease has evolved over the years, as new information has been discovered. Previously known as Hashimoto-Pritzker syndrome, Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma and histiocytosis X, the name  “Langerhans cell histiocytosis” was later introduced. This name was agreed upon to recognize the central role of the Langerhans cell.

To date, no large-scale studies have been done on how often LCH occurs in adults. It is estimated that it occurs in 1-2 adults per million people. It is important to remember that there are still many undiagnosed/misdiagnosed patients. The length of time from presenting symptoms to diagnosis can be years, which emphasizes the importance of finding a physician who is knowledgeable about this disease.

Information has been collected in various studies, including the 2001 International Histiocyte Society Registry on 274 adults from 13 countries. In this study, it was reported that 31% of patients had disease in a single system, 68% had more than one system involved, and 30% had pituitary involvement with diabetes insipidus. According to another registry based in Germany, it is estimated that 46% of adult patients had bone lesions, 17% skin, 7% pituitary, 4% liver/spleen, 2% brain, and 2% GI tract.

It is estimated that 63% of adults with LCH have lung-only disease, pulmonary Langerhans cell histiocytosis (PLCH), although it can also occur with other involvement, such as bone, skin or diabetes insipidus. Although the cause is unknown, it is believed that 90-95% of adults with this disease are past or current smokers, suggesting that smoking is related. It has also been reported that children with LCH in organs other than the lungs who acquire the habit of cigarette smoking in adulthood may develop PLCH, sometimes years after the initial diagnosis.

There are no known environmental risk factors associated with LCH, with the exception of cigarette smoking in lung disease.

In recent years, there has been increasing evidence to support the idea that LCH is a “neoplasm,” which means that LCH tumors contains cells with mistakes in their genes, also called “gene mutations,” that cause the cells to make copies of themselves inappropriately. When cells are making too many copies of themselves, this causes LCH lesions to grow. There is a specific gene called BRAF that has a mutation in about one half of LCH tumors. Recent research has identified other genes with mutations in LCH lesions but this requires further research. As of 2020, according to most experts Langerhans cell Histiocytosis (LCH) is currently classified as a rare cancer, however this doesn't necessarily mean that all of the worrisome implications that come along with the term “cancer” are true of LCH for every patient; LCH and other histiocytic disorders have a wide spectrum of presentations.

LCH can be systemic, and most often an oncologist/hematologist takes the main role in treating patients. However, since LCH can affect so many areas of the body, sometimes a team approach may be appropriate, and the oncologist may enlist the help of various types of specialists such as surgeons, pulmonologists (lung), dermatologists (skin), dentists or endocrinologists (diabetes/hormones) to give their input.

Most patients will survive the disease. Some will remain symptom-free, while others may develop life-long problems. In some cases, especially those that are not treated and/or followed closely, the disease may become life-threatening.

The patient's chances for survival and maintaining good quality of life depend on the individual case, but research has suggested that the course is less favorable for elderly patients, those with multiple locations of disease and those who may have risk-organ (lungs, liver, spleen, bone marrow) involvement. Limited involvement can also become serious, depending on the particular sites involved, how quickly the disease continues to progress and the patient's response to treatment.

Overall, physicians will be able to discuss each patient's likelihood of responding and doing well, but it is often difficult for doctors to make definite predictions since LCH has clearly shown itself to be an unpredictable disease.

As of 2020:  According to most experts, Langerhans cell Histiocytosis (LCH) is currently classified as a rare cancer. However, this doesn't necessarily mean that all of the worrisome implications that come along with the term “cancer” are true of LCH for every patient; LCH and other histiocytic disorders have a wide spectrum of presentations.

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Symptoms

Langerhans cell histiocytosis (LCH) may be limited to only one part of the body, such as a bone, or it can involve many organs.  The disease may be more serious in young infants or if “risk” organs such as liver, spleen, or bone marrow are involved. When LCH affects certain bones in the skull, the patients can be at higher risk of developing diabetes insipidus and/or neurological complications.

The following symptoms may indicate disease involvement but are not necessarily diagnostic of LCH.  This disease varies greatly from patient to patient, and some but not all of these symptoms may be present.

Langerhans cell histiocytosis (LCH) can involve nearly any part of the body, though some sites are more common than others. A patient may have very limited involvement in one body system or widespread involvement in several different sites and systems. It is also possible to have LCH in a particular location without symptoms.

The following symptoms may indicate disease involvement but are not diagnostic of LCH. This disease varies greatly from patient to patient, and some but not all of these symptoms may be present:

  • Skin (scalp, face, groin, trunk, armpits, arms, legs, ear canals, vulva, anal area, fingernails)
    Rash, ulceration, redness, pain, oozing, hair loss. Lesions may appear as small, solid, reddish elevations on the skin surface; knots under the skin; purplish-red spots; bleeding under the skin; rashes that are scaly and greasy; ulcerations; and small abscesses. Skin lesions may signal that other areas in the body are affected.
  • Bones (skull, bones around eyes, back bones, ribs, pelvis, feet, toes, hands, fingers)
    Pain, swelling, lumps, headaches, spontaneous fracture, ulceration at the site, limp, collapse of disc in the back, inability to walk.
  • Bone Marrow
    Low blood counts (red blood cells, white blood cells, platelets/clotting cells).
  • Lungs
    Chest pain, shortness of breath, collapsed lung, dry cough, weight loss, fatigue, loss of appetite, night sweats, coughing up blood.
  • Teeth/Gums
    Loosening or loss of teeth, swollen or bleeding gums, ulcerations, pain, swelling of face.
  • Ears
    Chronic ear infections, drainage/discharge, balance problems, bleeding, decreased hearing. Ear involvement can be a result of skull lesions expanding to the ear and may cause balance problems. Ear canals may be affected as part of the skin system, causing bleeding/drainage.
  • Endocrine System (pituitary gland/diabetes insipidus, hypothalamus, and thyroid gland)
    Excessive thirst, excessive urination, fatigue, sweats, temperature swings, weight gain, weight loss, nipple tenderness/discharge, menstrual problems in women, erectile dysfunction in men.
  • Female Genital/Reproductive Tract (vulva, vagina, cervix, ovaries)
    Inflammation, rash, and/or ulceration of the vulva, vagina, and/or cervix, but it may also affect the ovaries, causing dysfunction or failure of these organs.
  • Liver/Spleen/Lymph Nodes
    Swelling/tenderness of abdomen; enlargement of lymph nodes, spleen and/or liver; fatigue.
  • Gastrointestinal System (stomach or intestines)
    Diarrhea, nausea, vomiting, and/or weight loss.
  • Central Nervous System (spinal cord, brain lesions, pituitary gland)
    Staggering when walking, seizures, weakness of the arms, legs, or weakness of one side of the body. Since the pituitary gland could be affected, lesions of this system may also cause some of the same endocrine problems mentioned above.
  • Additional Non-specific Symptoms
    Fever, weakness, fatigue, chronic pain, weight loss, night sweats.

Pulmonary LCH (PLCH) can occur as part of multi-system disease, or it can occur alone. Nearly 20% of adults with PLCH have no presenting symptoms. An estimated 10%-15% of patients present with lung collapse as the first symptom, while others may show abnormalities in lung function tests. Dry cough and shortness of breath are the most common complaints, and weight loss, fever, sweats, and loss of appetite occur in approximately 33% of patients.

Many adults 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, it has also been observed that 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 LCH that should be fully evaluated by a physician and treated with appropriate medications.

Diagnosis and Treatment

NCCN Guidelines Published in 2021

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 LCH 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.  A diagnosis of Langerhans cell histiocytosis (LCH) is made following a biopsy and microscopic examination of the affected tissue. If the biopsy is positive for LCH, some other tests may be carried out to determine the extent of disease so that a treatment plan can be made. This procedure can be performed on any location but usually is done on the skin, bone, lymph nodes, liver, lung or bone marrow.

In addition, the following tests may be performed depending on particular symptoms:

  • Physical examination and history: Recording of height, weight, temperature, pulse, family history, history of symptoms, past illnesses, etc.
  • Neurological examination: Testing of ability to walk, muscle testing, coordination, and cognition.
  • Complete blood count (CBC): Checking levels of red blood cells, white blood cells, and clotting cells.
  • Blood chemistry tests: Studies for kidney, coagulation, thyroid and immune function; abnormal level can be a sign of disease. Complete blood count, sedimentation rate, liver function tests, electrolytes may be studied.
  • Liver function tests: Checking blood levels of substances released by the liver; an abnormal level can be a sign of disease in the liver.
  • Urinalysis: Testing the amount of red cells, white cells, protein and sugar in the urine.
  • Water deprivation test: Checks how much urine is made and whether it becomes concentrated when water is withheld; used when diabetes insipidus is suspected.
  • Bone marrow biopsy: The removal of bone marrow, blood and a small piece of bone by inserting a hollow needle into the hipbone; the sample is studied under a microscope to look for signs of LCH.
  • X-ray/Skeletal X-ray: Performed of the lungs or the bones to determine if there are abnormalities.
  • Bone scan: A scan for bone lesion in which a small amount of radioactive material is injected into a vein, collects in any abnormal parts of the bones and is shown on a scanner.
  • CT scan: For this x-ray dye may be injected into a vein or swallowed to help find any abnormalities; the scan takes a number of detailed pictures at different angles inside the body.
  • MRI: Using a substance called gadolinium injected into a vein to highlight areas of disease involvement, this scan then takes a number of detailed pictures inside the body.
  • PET scan: A small amount of radioactive sugar is injected into a vein, and diseased cells show up brighter on the scanner.
  • Ultrasound: High-energy sound waves are bounced off organs and tissue and make echoes, which form a picture of the internal body.
  • Endoscopy: When involvement of the digestive tract is suspected, a tube is passed into a body opening such as mouth or rectum to look at internal tissue; often, biopsies are also taken at the same time.

If there are symptoms of diabetes insipidus, a water-deprivation test should be done. When the bones near the ears or eyes are involved, a head CT scan is indicated. An MRI of the brain may be necessary if the lesions are near the eyes or ears or there is suspicion of central nervous system (CNS) involvement. Chest CT and lung function studies are performed when indicated. Other testing may be done, depending on symptoms. Other biopsies may be performed if test results or abnormal findings during the physical exam cause the physician to suspect involvement of another area.

When lung involvement is suspected, a chest x-ray is usually done and is abnormal in most patients. These abnormalities are subtle, can be easily missed, or can be mistaken for other diseases such as emphysema. The most common abnormality (in 70% to 90% of cases) is a reduced DLCO, which is a lung function test that measures the rate which carbon dioxide moves from the lung to the blood. The most sensitive diagnostic test is a high-resolution CT scan (HRCT), another type of x-ray, which can reveal lung cysts that are characteristic of LCH. It is possible to make a diagnosis with a bronchoalveolar lavage (BAL). The BAL is a medical procedure in which a tube is passed through the mouth or nose into the lungs, and fluid is squirted into part of the lung and then collected for examination. If the BAL and HRCT do not provide a diagnosis, then surgical lung biopsy may be necessary. In patients with diagnosed LCH in other areas of the body such as skin or bone, the diagnosis of lung involvement can be made if the HRCT shows findings consistent with pulmonary Langerhans cell histiocytosis (PLCH).

There is no established, widely agreed-upon treatment of LCH in general. It depends upon the individual patient and the extent and areas of involvement. Some patients have had success with vinblastine (chemotherapy) and steroids, while others have benefited from limited surgery, other chemotherapy agents such as 2-chlorodeoxyadenosine (2CdA) or methotrexate, and even low-dose external beam irradiation. Some patients may have limited involvement, which does not progress to other areas and may not need systemic treatment.

There are medications called “targeted therapies” which block the activity of genes with mutations in them. For example, there are medications that block mutations in BRAF specifically. In small clinical trials, these medicines have been very effective in treating LCH. These treatments should be considered for certain instances of LCH, such as severe cases or those for which other treatments have not been successful. Targeted treatments for genes other than BRAF are under investigation.

In cases of pulmonary LCH, an essential part of treatment is discontinuing cigarette smoking or smoking of illegal drugs. In some cases, this can lead to stabilization of symptoms and even improvement. There are no established guidelines for the treatment of PLCH; however, some patients are treated with steroids, while others may receive treatment with systemic chemotherapy agents such as vinblastine, 2-CdA, cyclophosphamide, methotrexate, and even thalidomide. A small number of patients develop severe and disabling lung disease and may require a lung transplant.

Even if it is determined that no treatment is necessary at the time of diagnosis, the physician will likely monitor the disease regularly to be sure that there is not further progression of the existing areas and that new areas of involvement can be detected and treated early. The ultimate goal of an overall treatment plan, of course, is to use as little treatment as possible to keep the disease under control to preserve quality of life and prevent the histiocytosis from damaging vital organs.

Permanent Consequences

More recent advances in research and treatment of histiocytic disorders have provided a high survival rate for patients with this disease. At the same time, as more patients have been followed long-term, the risk for permanent consequences has become more obvious. It is now known that survivors can have significant consequences related to the disease and/or its treatment, sometimes following long-term remission. Most of these issues tend to be directly related to sites of original disease involvement and may affect quality of life. It is believed that more than half of patients will develop permanent consequences.

Also known as “late effects,” some consequences such as neurologic symptoms may not show up until 10 or more years after diagnosis, while other consequences such as diabetes insipidus can occur when histiocytosis is diagnosed, or even before. For this reason, “permanent consequences” has been suggested as a better term than “late effects.” Although some consequences such as tooth loss, bone defects, and scarring of the skin may be the result of surgical treatment, it is believed that the disease process itself is responsible for most of the effects.

Permanent consequences occur more often with multisystem patients but are also seen in patients with single-system disease at diagnosis. In one study, over 70% of multisystem LCH patients had one or more permanent consequences, compared to 24% of single-system patients. Children are more at risk to develop consequences because the disease can interfere with growth and development, and the consequences have a longer time to develop.

Some examples of permanent consequences include:

  1. Diabetes insipidus (DI)
  2. Stunted growth/failure to achieve sexual maturity
  3. Defects of bone/skull defects/facial asymmetry
  4. Loss of spinal height
  5. Loss of teeth/part of jawbone
  6. Bulging of the eyes
  7. Hearing loss
  8. Scarring of the skin
  9. Scarring of the liver
  10. Scarring of the lung
  11. Secondary cancers
  12. Neurologic/cerebellar problems, which can include:
    • Poor coordination/difficulty walking
    • Bad handwriting
    • Tremor/abnormal eye movements
    • Difficulty with balance/unsteadiness/clumsiness
    • Problems with speech and/or swallowing
    • Loss of short-term and/or long-term memory
    • Learning difficulty/poor school performance
    • Difficulties with concentration/attention/processing
    • Lower IQ score
    • Organizational difficulties
    • Behavior changes including aggression, eating disorders, depression, and difficulties with interpersonal relationships

The exact incidence of diabetes insipidus (DI) is not known, but it is believed to be in the range of 5% to 50% of LCH patients, depending on the location and extent of disease. The risk of developing DI in patients with multisystem LCH is 4 to 6 times greater than those with single-system disease. Patients with skull, facial, and/or eye bone lesions are at much higher risk of developing DI, and this risk is increased further if the disease remains active for a longer period or if it recurs. Although once established, diabetes insipidus cannot be cured, it can be successfully treated with a hormone called DDAVP.

Stunted growth is the most common endocrine abnormality and occurs in approximately 10% of children with histiocytosis. It was shown in one study to occur in 43% of patients who had diagnoses of both LCH and diabetes insipidus. Stunted growth can be successfully treated with daily injections of growth hormone, usually for as long as the child is growing. This treatment appears to be safe and effective and is not associated with an increased risk of disease reactivation.

Orthopedic problems from lesions of the spine, leg bones, and arm bones are one of the more common consequences and may be seen in 20% of patients. These problems include collapse of the vertebrae, instability of the spine that may lead to abnormal spinal curvature, decreased spinal height, fractured bones, and inequality of leg length. In addition, since the skull and facial bones are frequent sites of lesions, abnormalities and asymmetry of the face may occur. Some bone/facial abnormalities can be corrected by orthopedic or cosmetic surgery.

Dental problems with loss of teeth have been a significant problem for some patients, either directly related to disease affecting the jaw or related to aggressive surgery for jaw disease. The potential for restoration/cosmetic repair can be discussed with a knowledgeable physician. Residual eye bulging can affect one or both eyes. Hearing loss was found in one study to affect 16% of children treated for LCH. Of those with CT or MRI abnormalities of the mastoid, 59% had hearing loss. Inner ear involvement has been known to cause loss of balance. Hearing aids or surgically inserted electronic hearing devices (cochlear implants) may be necessary.

Liver disease may lead to scarring and destruction of the liver and, in rare cases, liver failure which may require transplantation. Lung disease is believed to occur in less than 10% of patients, causes scarring and damage of lung tissue, and can result in long-term poor lung function with a higher risk for infections, shortness of breath, and lung collapse. In cases of severe damage, a lung transplant may be necessary for survival. Permanent damage, however, is less common in children, whose lung tissue can more easily regenerate. Patients with a history of lung involvement may have a lifelong susceptibility to lung disease associated with cigarette smoking.

Patients with histiocytosis have a slightly higher chance of developing secondary cancers when compared to the unaffected population; secondary cancers could include leukemia, brain tumors, and cancer of the lung, liver, bone, lymph nodes, and eyes. It has not been determined whether this is caused by treatment or a genetic predisposition. Cancer can occur at the same time as histiocytosis or can occur years afterwards.

Neurologic problems with cognitive deficits, behavioral disturbances, and neuromotor dysfunction, also known as central nervous system (CNS) involvement, are reported to affect at least 10% of all LCH patients (19% of all multisystem patients). (For other histiocytic disorders, studies of greater numbers of patients are necessary to better define how often this occurs.) It is believed that this phenomenon is more frequently recognized now that more patients with histiocytosis are being followed long-term. It is characterized by symptoms in the brain that may not manifest until 10 or more years after initial diagnosis. Although this is usually seen on MRI scans, it may occur when there are no abnormal findings on MRI. The CNS complications can remain stable for years or can be progressive and become debilitating. No effective treatment has yet been developed; however, various forms of rehabilitation and teaching assistance can be helpful for these patients. These include assistance with learning and life skills; education about permanent consequences; teaching of repetition, reinforcement, and organizational skills; and placement of school/job accommodations. While the neurologic issues cannot be reversed, caregivers can provide tools that will help the patient increase his/her level of success.

In addition to compromised physical/cognitive function, histiocytosis survivors may experience quality-of-life issues such as anxiety/fear about possible relapse, sadness, anger, and depression. These feelings may be especially strong before follow-up visits, on illness-related anniversaries, or with onset of symptoms not related to the disease. For many people, these feelings will go away over time, while others may need psychological or psychiatric support. Finding a supportive network of other histiocytosis survivors can also be helpful.

  • On-line: You can subscribe to receive our emails so that you receive our newsletters, and you will also receive important announcements regarding the latest information and research developments on the histiocytic disorders. The Association also maintains a Facebook page and private Facebook group 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 survivors of histiocytic disorders, rare diseases in general, or even cancer. Establishing face-to-face relationships with others going through similar experiences can be helpful.

Because of the possible impact of permanent consequences on school/job performance, ability to lead an independent life, and overall quality of life, it is important that the patient be evaluated and followed long term, especially those with multisystem disease. Early recognition of any deficit will be important, so that appropriate rehabilitation and assistance can be planned and put into place.

After years of research and discussion among researchers, there are still considerable gaps in the understanding of histiocytosis and its neurological complications. Some authorities believe it is a process separate from disease activity, and others believe that early, effective therapy may prevent or reduce the complications.

In order to make further progress in this field, the Histiocyte Society has developed a clinical trial/study called LCH-IV which opened for registration in 2012 and is on-going. This includes new guidelines for diagnosis and treatment of CNS LCH, including repeated MRIs, standardized neurologic evaluation, and neuropsychological tests for all patients with CNS disease. The study will test whether longer therapy for active disease will reduce the rate of reactivation and development of complications. You may consult your health care provider to find out about possible treatment options.

If you are a histiocytosis survivor with permanent consequences, it will be important to educate yourself about available resources and stay updated about the latest research findings. This information will help you make informed decisions and play an active role in acquiring the best support and services available. In doing so, you will create the best chance for a successful outcome.

FAQ

What causes LCH?

To date, the cause has not been determined. Multiple potential causes have been explored, including viruses, molds, infections, genetics, geographic location, racial clustering, seasonal changes, and environmental exposure. Results of these studies are still insufficient to provide a definitive answer. Further studies are needed. Scientific discussions on the definition of LCH continue to be debated in terms of its classification as either an immune dysfunction or a rare cancer (neoplastic and malignant or not malignant). However, the National Comprehensive Cancer Network recently released Guidelines indicating it as a "rare cancer".

Is there a cure for LCH?

While some patients go into remission and may live normal lives with or without treatment, we usually don’t use the term “cure” with this disease. No specific amount of time without active disease has yet been established for adults to determine when a patient is considered to be cured.

What is considered to be remission?

Complete remission means that there is no evidence of disease, whereas partial remission means that most of the signs and symptoms of LCH are gone, but some still remain. Doctors use the term response and “non-active” to describe patients who are free of symptoms and signs of LCH. Usually a cure is linked to being in remission for a certain period of time. There is no established period of “non-active” disease before LCH is considered cured, but the chance for recurrence is low after five years from end of treatment.

Where did LCH get its name?

In 1868, the German pathologist Paul Langerhans discovered a type of white blood cell which eventually came to bear his name. The various manifestations of LCH were previously known by a number of different names (histiocytosis-X, eosinophilic granuloma, Letterer-Siwe disease, Hand-Schüller-Christian syndrome, etc.). In 1983, it was suggested that this disorder be named “Langerhans cell histiocytosis,” to recognize the key role of the Langerhans cell in all of the different manifestations. This name was later approved by the scientists comprising the Histiocyte Society.

Is LCH a rare cancer?

There has been much discussion concerning whether or not Langerhans cell histiocytosis (LCH) is considered a cancer. The discovery of gene mutations, such as BRAF, in LCH has raised the possibility that LCH is a disease that bears some similarities to cancer, even if it is not a cancer in every way. However, the National Comprehensive Cancer Network recently released Guidelines indicating it as a "rare cancer".

Is LCH fatal?

It can be. A small percentage of patients, most often those with multisystem risk-organ involvement that is unresponsive to treatment, may not survive.

What are the different therapies/treatments commonly used to treat LCH?

Treatment is based upon the organ(s) involved, extension of disease, and in some cases, age of the patient. In some cases, no treatment is necessary. Others may respond to surgical removal, steroids, or anti-inflammatory drugs (NSAIDs). Low-dose radiation is helpful in some situations, but should be carefully used in children. There are patients who require chemotherapy such as vinblastine, vincristine, etoposide (VP-16), methotrexate, cytosine-arabinoside (Ara-C), and/or 6-MP. In patients with severe disease that does not respond to initial treatment, stronger chemotherapy combinations may be used. Ultraviolet light (PUVA) may be helpful for limited skin disease. In very rare instances, a transplant of the liver, lung, or bone marrow may be necessary.

Is LCH hereditary?

Although there are rare families (less than 2% of all cases) documented with more than one member diagnosed with LCH, at this point, there is no clear evidence that this disease is inherited.

Does LCH spread?

The exact mechanism that causes lesions to appear in other locations in the body is not yet known. However, some researchers believe that abnormal LCH cells travel through the blood like tumor cells and “seed” in different locations, creating new lesions. Others believe that there are different manifestations of the same disease.

Is there a blood test to diagnose LCH?

LCH is diagnosed with a biopsy of the affected tissue. Blood tests may be done to help determine the extent and/or severity of involvement, but blood tests are not diagnostic of the disease.

Is it true that LCH is mostly a childhood disease?

Not necessarily. Although we do know the incidence of childhood LCH, there is not enough data to determine how many adults are affected by this disease.

With a history of LCH, can I become pregnant?

Drugs used as part of the usual LCH treatment are not associated with infertility. These include vinblastine, vincristine, 2-CdA, methotrexate, Ara-C, and etoposide (VP-16). LCH can, however, affect the endocrine system, and complications can result in infertility. This is especially true if hormone loss is not diagnosed in time and if no hormone replacement is given. However, in some cases, hormone replacement therapy may restore fertility.

What are permanent consequences of LCH?

Permanent consequences are also known as late effects of LCH, although they can occur early on. They are believed to be mostly related to the disease rather than treatment and include:

  • Diabetes Insipidus
  • Stunted growth
  • Bone abnormalities
  • Hearing loss
  • Neurological problems, including poor coordination, unsteadiness, difficulty with handwriting, abnormal eye movements, problems with speech, learning disabilities/decreased school performance, memory loss, and behavior difficulties.
  • Loss of teethLoss of spinal height
  • Delayed puberty
  • Bulging eyesScarring of lungs
  • Scarring of liver/cirrhosis
  • Secondary cancers
With the diagnosis and treatment of LCH, am I more likely to develop cancer?

Although this occurs rarely, LCH is associated with cancer more often than would be expected by chance. This can occur before, during, or after the diagnosis of LCH. Some cancers following the LCH diagnosis might be related to the treatments given. When cancer occurs before LCH, the histiocytosis might represent a “reaction” to the cancer itself.

What is Neurodegeneration?

Neurodegeneration is progressive loss of brain function. It occurs as a permanent consequence in some cases of LCH.

Can neurodegeneration be prevented/reversed/treated?

It is not currently known whether neurodegeneration can be prevented. It is believed that neurodegeneration cannot be reversed, and there is controversy whether patients with neurodegeneration can be successfully treated. There have been some promising results with Ara-C but more extensive scientific studies are required.

What should I look for in a doctor?

Many adults with LCH have been seen by a number of specialists, depending on their symptoms. It will be important to find a physician knowledgeable about adult LCH who is willing to serve as the primary “hub” and coordinate input from the specialists. Ideally, this physician would be an oncologist who specializes in cancer-like illnesses and is qualified to provide systemic treatment. Accessibility and good communication skills with you, as well as other physicians, are important. Find a Physician in your area today.

What should I look for in a doctor?

LCH is most often followed and treated by an oncologist, who specializes in cancer-type illnesses. The level of experience with LCH can vary widely among physicians. If he/she is not knowledgeable about this disease, a willingness to learn more and consult with the experts can go a long way. Other qualities to look for are accessibility and good communication skills with you, as well as other physicians.

What causes chronic pain in adults with LCH?

Some pain and cramping can be a side effect of treatment, such as vinblastine and steroids. Pain may also be directly related to active disease. In cases of more chronic pain, some researchers suspect that cytokines, which are a type of messenger, stimulate white blood cells to release inflammatory molecules that produce pain.

What healthcare workers should I see to help with pain management?

The primary oncologist/physician can treat and manage chronic pain in many cases. However, if the pain does not respond to the usual therapy and/or if the pain compromises quality of life, referral to a pain clinic may be necessary. Clinics differ in their approach and what they offer, but most include a team of health care providers with a variety of ways to manage pain and restore quality of life.

What is “PLCH?”

PLCH (pulmonary Langerhans cell histiocytosis) is LCH of the lung. It affects mostly adults who smoke and often occurs without other LCH involvement.

Why is cigarette smoking dangerous for me?

It is believed that there is a strong link between cigarette smoking and pulmonary LCH. An estimated 90-95% of pulmonary-only LCH patients currently smoke or have smoked. Although the exact mechanism is not understood, it is believed that smoking can cause an accumulation of Langerhans cells in the lungs.

Can adults with a history of LCH donate blood or bone marrow?

Although there is no data to prove a risk, adults with a history of LCH are advised against donating blood or platelets. They should also not be organ donors.

What are risk organs?

Risk organs include bone marrow, spleen, and liver and are more difficult to treat than other sites of involvement with LCH.

What is reduced-intensity conditioning (RIC)?

Reduced-intensity conditioning is a less toxic pre-transplant therapy with the goal of suppressing the patient’s immune system enough so that it will accept donor stem cells while reducing the side effects of high dose chemotherapy The RIC may be used in some HLH patients, as well as some LCH patients with severe, resistant disease.

What is chemo brain?

Chemo brain is a term used for mild brain impairment that may occur during treatment. It can include symptoms such as difficulty concentrating, feeling disorganized, trouble with multi-tasking, memory lapses, slower thinking, word-finding difficulty, etc. For most patients, it lasts a short time.

What are the side effects of vinblastine?

Side effects include:

  • Low blood counts (with higher risk of infection).Mild nausea/vomiting/constipation
  • Easily sunburned
  • Skin irritation at site of injection
  • Thin or brittle hair
  • Fatigue
  • Bone pain
  • Hoarseness
  • Seizures
  • Shortness of breath
  • Nerve damage (especially in adults) with tingling, numbness and/or pain of the hands and feet
What are the side effects of prednisone?

Side effects include:

  • Increase in blood sugar
  • Increase in appetite
  • Heartburn
  • Bloating/fluid retention/weight gain
  • Difficulty sleeping
  • Mood/behavior/personality changes
  • Higher risk of infection
  • Slow wound healing
  • Muscle weakness
  • Loss of bone calcium
  • Increased hair growth

More unusual side effects may include:

  • Problems with vision/eye pain
  • Seizures
  • Confusion
What are the side effects of methotrexate?

Side effects include:

  • Mouth sores/swollen, tender gums
  • Nausea/vomiting/diarrhea/decreased appetite
  • Low blood counts
  • Dizziness/drowsiness
  • Headache

More unusual side effects may include:

  • Blurred vision or loss of vision
  • Seizures
  • Confusion
  • Weakness/difficulty moving one or both sides of the body
  • Loss of consciousness
  • Lung damage
  • Allergic reactions
What are the possible side effects of 6-MP (mercaptopurine)?

More common signs/symptoms include:

  • Low blood counts (red cells, white cells, and clotting cells)
  • Nausea/vomiting/decreased appetite
  • Headache
  • Weakness/fatigue/achiness
  • Rash/darkening of the skin
What are the possible side effects of 2-CdA (cladribine/leustatin)?

More common signs/symptoms include:

  • Flu-like symptoms (Fever, chills, headache, fatigue, nausea/vomiting)
  • Decreased appetite
  • Constipation
  • Low blood counts (red cells, white cells, and clotting cells)
  • Skin rash/redness/itching

What Do I Do Now?

A new diagnosis of Langerhans cell histiocytosis (LCH) 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 patients feel ill-equipped to understand what is happening to them and how to navigate through the illness to recovery.  There are, however, strategies and resources that can help you and your family 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 self-advocate and part of the medical team.  The following tips and suggestions are provided to help guide you through this journey toward recovery.

Choosing a Doctor

Langerhans cell histiocytosis in children is considered a systemic illness; especially in cases where the disease is found in more than one system within the body.  Some 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 child’s 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 LCH, 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 Directory who have agreed to perform consultations and/or second opinions or you may call +1 856-589-6606 for contact information of other physicians in your area.

Call your insurance company to find out whether your plan will cover visits to the physician you are considering. Oftentimes your child’s 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.

Sharing Information

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 medical caregivers.  It can also help your child cooperate with treatment and become a part of his/her 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. Some patients and families find that the 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 LCH, 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.  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. You may want to take brochures and other basic information about LCH.  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.

Getting Organized

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 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 with LCH 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.

Insurance

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.

Creating a Support Network

Online:  You can subscribe to receive our emails so that you receive our newsletters, and you will also receive important announcements regarding the latest information and research developments on the histiocytic disorders. The Association also maintains a Facebook page and private Facebook group for families and patients with this disease.

Local support:  The hospital where your child is being treated may have a support group for parents of children with histiocytic disorders, rare diseases in general, or even cancer.  Establishing face-to-face relationships with parents going through similar experiences can be helpful.

The Association sponsors parent and patient Regional meetings and webinars, 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.

Educate Yourself

Self-education about LCH is an important part of advocating for your child.  It will help you to make informed decisions about your child’s care and play a more active role in his/her 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 LCH 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.

Advocating for Your Child

It is essential to take an active role in your child’s health care.  However, many caregivers have little experience being advocates when they first find out that their child has a rare disease.  The following is a list of essential tips for becoming a successful advocate:

  1. Learn about LCH 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 phones 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.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. 
  6. Keep a healthcare notebook with a listing of allergies, medications, symptoms, and communications with healthcare providers.
  7. 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. 
  8. Be persistent in getting the care you feel that 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 your child better than anyone else.

Self Care

Caring for a sick child 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 your child’s needs, but it’s important to remember that caring for yourself is essential.  When your needs are taken care of, your child 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. More extensive information can be found in the Disease Information section of our website.

Choose from the following Fact Sheets: