Permanent Consequences of LCH


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 followup 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 sign up to become a member of the Histiocytosis Association by registering and creating a user name and password. You will have the opportunity to sign up to receive our newsletters, and you will also receive important announcements regarding the latest information and research developments on the histiocytic disorders. Once registered, you may choose to participate in the Online Discussion Groups and interact with a large community of families and patients. 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 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 will open for registration in 2012. 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.

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