Langerhans Cell Histiocytosis

  • What is Langerhans cell histiocytosis?

    Langerhans cell histiocytosis is a group of rare disorders that overproduce and accumulate certain types of white blood cells (histiocytes) in organs and tissues in the body.

    Histiocyte cells are part of the body’s immune system. In normal numbers, they help fight infection. When the body produces too many histiocyte cells, they actually attack the body’s healthy systems causing bone lesions to all-over body disease.

    Langerhans cell histiocytosis is rare. Only 1,200 cases are reported annually. It usually affects children under 12 years old and is more common among whites than blacks.

    Specific types of Langerhans cell histiocytosis have different manifestations, presenting with different symptoms and widely different outcomes.

    The three syndromes that make up Langerhans cell histiocytosis are:

    • Eosinophilic granuloma (most common)
    • Letterer-Siwe disease
    • Hand-Schüller-Christian disease

    Single tumors (localized eosinophilic granuloma) occur most frequently in children aged 5-15 years. Boys are twice as likely as girls to have eosinophilic granuloma. The condition usually manifests in the thoracic section of the spine, which is middle or chest area of the body.

    Letterer-Siwe disease is a rare, usually fatal condition that generally affects children age 3 or younger. It is characterized by skin lesions; enlarged liver, spleen and lymph nodes; anemia and bleeding tendencies.

    Hand-Schüller-Christian disease, a chronic form of Langerhans cell histiocytosis, is typically diagnosed before age 5. Hand-Schüller-Christian disease is often accompanied by diabetes insipidus, a condition in which the kidneys are unable to maintain water and causes frequent urination.

  • Causes

    The cause of Langerhans cell histiocytosis is unknown. It is not inherited or communicable. It can’t be passed from person-to-person like the flu or HIV. Langerhans cell histiocytosis may simply be an abnormality in a person's immune system.

    Doctors at The Children’s Hospital of Philadelphia (CHOP) have participated in several research projects on this condition, looking into its causes and treatment outcomes.

  • Signs and symptoms

    Langerhans cell histiocytosis often causes no symptoms in children. Depending on the type of histiocytosis, symptoms may include:

    • Localized pain for short periods of time, often at night
    • Anemia
    • Diabetes insipidus
    • Ear pain or recurring ear infections
    • Enlarged liver or spleen
    • Fractures, particularly when the tumor is located in weight-bearing bones
    • Lethargy
    • Low-grade fever
    • Osseous lesion (an infected bone) on the skull or femur (thigh bone)
    • Skin rash
    • Spine issues such as painful scoliosis or kyphosis
    • Weight loss
    • Cradle cap (scalp rash often in infants)
  • Testing and diagnosis

    Diagnosing Langerhans cell histiocytosis requires a careful and complete medical workup and examination of your child. Symptoms of Langerhans cell histiocytosis can be similar to other conditions, such as aneurysmal bone cysts, fibrous dysplasia, osteosarcoma, Ewing's sarcoma and others.

    Because of this, clinicians at CHOP use a variety of diagnostic tests to correctly identify Langerhans cell histiocytosis.

    Diagnostic testing may include:

    • Biopsy, which is a short surgical procedure to take a large sample of the growth, may be necessary to confirm any findings.
    • Blood tests, which can help determine drug usage and effectiveness, biochemical diseases and organ function.
    • X-rays, which produce images of bones and internal organs on film.
    • Radioisotope bone scan, which can help locate an area of abnormal bone growth.
    • Magnetic resonance imaging (MRI), which uses a combination of large magnets, radiofrequencies and a computer to produce detailed images of organs and structures within the body.
    • Computed tomography (CT) scan, which uses a combination of X-rays and computer technology to produce cross-sectional images ("slices") of the body.
    • Urinalysis, which can help detect metabolic disorders by testing a child’s urine.
    • Positron emission tomography (PET) scan, which uses radioactive sugar injected into a vein and a scanner to make detailed, computerized pictures of areas of the body.
    • EOS imaging, an imaging technology that creates 3-dimensional models from two planar images. Unlike a CT scan, EOS images are taken while the child is in an upright or standing position, enabling improved diagnosis due to weight-bearing positioning.
  • Treatments

    Treatment for Langerhans cell histiocytosis depends on how many organ systems are affected in your child.

    If there are no neurological problems as a result of the tumor, your child’s physician may recommend “watchful waiting” — regular monitoring. Some cases of Langerhans cell histiocytosis resolve on their own.

    In more severe cases of Langerhans cell histiocytosis, active treatment may be recommended.

    Surgery 

    Surgically removing the tumor is generally the recommended treatment for solitary bone lesions (eosinophilic granuloma).

    Though surgery is highly effective, we understand that any surgery can be a stressful experience for your child and family. At CHOP, we offer a wealth of resources about how to prepare your child for surgery and what to expect during surgery.

    Additionally, we employ numerous best practices before, during and after surgery to decrease the risk of infection and increase positive outcomes. Safety in surgery is a top priority.

    Radiation (used less frequently)

    Radiation therapy may be used alone to treat Langerhans cell histiocytosis, or in conjunction with surgery to shrink or destroy the tumor.

    Chemotherapy 

    Low-dose chemotherapy is often required when Langerhans cell histiocytosis is more widespread throughout a child’s body and is affecting multiple organs.

    Other therapies 

    If Langerhans cell histiocytosis has affected your child’s spine, additional treatment may be recommended including:

    • A back brace to treat or avoid kyphosis, a forward curve of the spine that can lead to a “hunchback” look. Kyphosis can also prevent normal lung development and function and, in rare cases, lead to thoracic insufficiency syndrome.
  • Follow-up care

    At The Children's Hospital of Philadelphia, we offer ongoing support and services for patients and families at our Main Campus and throughout our CHOP Care Network. Our team is committed to partnering with parents and referring physicians to provide the most current, comprehensive and specialized care possible for your child.

    One third to one half of all patients with a form of Langerhans cell histiocytosis will experience some complications ranging from physical disabilities to neuropsychological defects.

    Langerhans cell histiocytosis can affect different areas of the body depending on the condition, so your child may need to follow up with a variety of clinical specialists in addition to an orthopedic surgeon. Annual monitoring by experienced medical staff is strongly encouraged.

    In rare cases, patients with Langerhans cell histiocytosis can later get secondary malignancies, such as leukemia or solid tumors.

  • Outlook

    Most children do well after a diagnosis of Langerhans cell histiocytosis. While some lesions resolve on their own, many will require some form of treatment.

    Patients with unifocal disease generally have an excellent prognosis. Those with multifocal Langerhans cell histiocytosis fare almost as well; while patients with disseminated disease — such as those with Letterer-Siwe disease — face the most challenges.

Reviewed by John P. Dormans, MD, FACS, Jason L. Katz, PA-C, MHS, ATC-R on May 19, 2014