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Genetics Home Reference: your guide to understanding genetic conditions
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Langerhans cell histiocytosis

Reviewed August 2011

What is Langerhans cell histiocytosis?

Langerhans cell histiocytosis is a disorder in which excess immune system cells called Langerhans cells build up in the body. Langerhans cells, which help regulate the immune system, are normally found throughout the body, especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow. In Langerhans cell histiocytosis, excess immature Langerhans cells usually form tumors called granulomas. However, Langerhans cell histiocytosis is not generally considered to be a form of cancer.

In approximately 80 percent of affected individuals, one or more granulomas develop in the bones, causing pain and swelling. The granulomas, which usually occur in the skull or the long bones of the arms or legs, may cause the bone to fracture.

Granulomas also frequently occur in the skin, appearing as blisters, reddish bumps, or rashes which can be mild to severe. The pituitary gland may also be affected; this gland is located at the base of the brain and produces hormones that control many important body functions. Without hormone supplementation, affected individuals may experience delayed or absent puberty or an inability to have children (infertility). In addition, pituitary gland damage may result in the production of excessive amounts of urine (diabetes insipidus) and dysfunction of another gland called the thyroid. Thyroid dysfunction can affect the rate of chemical reactions in the body (metabolism), body temperature, skin and hair texture, and behavior.

In 15 to 20 percent of cases, Langerhans cell histiocytosis affects the lungs, liver, or blood-forming (hematopoietic) system; damage to these organs and tissues may be life-threatening. Lung involvement, which appears as swelling of the small airways (bronchioles) and blood vessels of the lungs, results in stiffening of the lung tissue, breathing problems, and increased risk of infection. Hematopoietic involvement, which occurs when the Langerhans cells crowd out blood-forming cells in the bone marrow, leads to a general reduction in the number of blood cells (pancytopenia). Pancytopenia results in fatigue due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia).

Other signs and symptoms that may occur in Langerhans cell histiocytosis, depending on which organs and tissues have Langerhans cell deposits, include swollen lymph nodes, abdominal pain, yellowing of the skin and whites of the eyes (jaundice), delayed puberty, protruding eyes, dizziness, irritability, and seizures. About 1 in 50 affected individuals experience deterioration of neurological function (neurodegeneration).

Langerhans cell histiocytosis is often diagnosed in childhood, usually between ages 2 and 3, but can appear at any age. Most individuals with adult-onset Langerhans cell histiocytosis are current or past smokers; in about two-thirds of adult-onset cases the disorder affects only the lungs.

The severity of Langerhans cell histiocytosis, and its signs and symptoms, vary widely among affected individuals. Certain presentations or forms of the disorder were formerly considered to be separate diseases. Older names that were sometimes used for forms of Langerhans cell histiocytosis include eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.

In many people with Langerhans cell histiocytosis, the disorder eventually goes away with appropriate treatment. It may even disappear on its own, especially if the disease occurs only in the skin. However, some complications of the condition, such as diabetes insipidus or other effects of tissue and organ damage, may be permanent.

How common is Langerhans cell histiocytosis?

Langerhans cell histiocytosis is a rare disorder. Its prevalence is estimated at 1 to 2 in 100,000 people.

What genes are related to Langerhans cell histiocytosis?

Somatic mutations in the BRAF gene have been identified in the Langerhans cells of some individuals with Langerhans cell histiocytosis. Somatic gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are not inherited.

The BRAF gene provides instructions for making a protein that is normally switched on and off in response to signals that control cell growth and development. Somatic mutations cause the BRAF protein in affected cells to be continuously active and to transmit messages to the nucleus even in the absence of these chemical signals. The overactive protein may contribute to the development of Langerhans cell histiocytosis by allowing the Langerhans cells to grow and divide uncontrollably.

Some researchers believe that other factors, such as viral infections, environmental toxins, and changes in other genes, may also influence the development of this complex disorder.

Related Gene(s)

Changes in this gene are associated with Langerhans cell histiocytosis.

  • BRAF

How do people inherit Langerhans cell histiocytosis?

Langerhans cell histiocytosis is usually not inherited and typically occurs in people with no history of the disorder in their family.

A few families with multiple cases of Langerhans cell histiocytosis have been identified, but the inheritance pattern is unknown.

Where can I find information about diagnosis or management of Langerhans cell histiocytosis?

These resources address the diagnosis or management of Langerhans cell histiocytosis and may include treatment providers.

  • Cincinnati Children's Hospital Medical Center (http://www.cincinnatichildrens.org/health/h/lch/)
  • Cleveland Clinic (http://my.clevelandclinic.org/childrens-hospital/health-info/diseases-conditions/langerhans-cell-histiocytosis)
  • Genetic Testing Registry: Langerhans cell histiocytosis, multifocal (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0019621)
  • National Cancer Institute: Langerhans Cell Histiocytosis Treatment (http://www.cancer.gov/cancertopics/pdq/treatment/lchistio/Patient)
  • Seattle Children's Hospital (http://www.seattlechildrens.org/medical-conditions/heart-blood-conditions/langerhans-cell-histiocytosis/)
  • St. Jude Children's Research Hospital (http://www.stjude.org/stjude/v/index.jsp?vgnextoid=d1d067f714773210VgnVCM1000001e0215acRCRD&vgnextchannel=bc4fbfe82e118010VgnVCM1000000e2015acRCRD)
  • Sydney Children's Hospital (http://www.kids-cancer.org/cancer-blood-disorders/what-is-cancer/langerhans-cell-histiocytosis.aspx)

You might also find information on the diagnosis or management of Langerhans cell histiocytosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Langerhans cell histiocytosis?

You may find the following resources about Langerhans cell histiocytosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Langerhans cell histiocytosis?

  • Hashimoto-Pritzger disease
  • histiocytosis X
  • Langerhans cell granulomatosis
  • LCH

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Langerhans cell histiocytosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Langerhans cell histiocytosis?

anemia ; bone marrow ; cancer ; cell ; clotting ; diabetes ; gene ; granuloma ; hematopoietic ; hormone ; immune system ; infection ; infertility ; inheritance ; inheritance pattern ; inherited ; jaundice ; lymph ; metabolism ; neurological ; neutropenia ; nucleus ; pituitary gland ; platelets ; prevalence ; protein ; puberty ; thrombocytopenia ; thyroid ; tissue ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: Current concepts and treatments. Cancer Treat Rev. 2010 Jun;36(4):354-9. doi: 10.1016/j.ctrv.2010.02.012. Epub 2010 Feb 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20188480?dopt=Abstract)
  • Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010 Sep 16;116(11):1919-23. doi: 10.1182/blood-2010-04-279083. Epub 2010 Jun 2. (http://www.ncbi.nlm.nih.gov/pubmed/20519626?dopt=Abstract)
  • Egeler RM, van Halteren AG, Hogendoorn PC, Laman JD, Leenen PJ. Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell-macrophage lineage. Immunol Rev. 2010 Mar;234(1):213-32. doi: 10.1111/j.0105-2896.2009.00883.x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20193021?dopt=Abstract)
  • Gasent Blesa JM, Alberola Candel V, Solano Vercet C, Laforga Canales J, Semler C, Pérez Antolí MR, Rodríguez-Galindo C. Langerhans cell histiocytosis. Clin Transl Oncol. 2008 Nov;10(11):688-96. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19015065?dopt=Abstract)
  • Margo CE, Goldman DR. Langerhans cell histiocytosis. Surv Ophthalmol. 2008 Jul-Aug;53(4):332-58. doi: 10.1016/j.survophthal.2008.04.007. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18572052?dopt=Abstract)
  • Ng-Cheng-Hin B, O'Hanlon-Brown C, Alifrangis C, Waxman J. Langerhans cell histiocytosis: old disease new treatment. QJM. 2011 Feb;104(2):89-96. doi: 10.1093/qjmed/hcq206. Epub 2010 Nov 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21084318?dopt=Abstract)
  • Satoh T, Smith A, Sarde A, Lu HC, Mian S, Trouillet C, Mufti G, Emile JF, Fraternali F, Donadieu J, Geissmann F. B-RAF mutant alleles associated with Langerhans cell histiocytosis, a granulomatous pediatric disease. PLoS One. 2012;7(4):e33891. doi: 10.1371/journal.pone.0033891. Epub 2012 Apr 10. Erratum in: PLoS One. 2012;7(6). doi:10.1371/annotation/74a67f4e-a536-4b3f-a350-9a4c1e6bebbd. Mian, Sophie [corrected to Mian, Syed]. (http://www.ncbi.nlm.nih.gov/pubmed/22506009?dopt=Abstract)
  • Weitzman S, Egeler RM. Langerhans cell histiocytosis: update for the pediatrician. Curr Opin Pediatr. 2008 Feb;20(1):23-9. doi: 10.1097/MOP.0b013e3282f45ba4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18197035?dopt=Abstract)
  • Windebank K, Nanduri V. Langerhans cell histiocytosis. Arch Dis Child. 2009 Nov;94(11):904-8. doi: 10.1136/adc.2007.125872. Epub 2009 May 19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19457881?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2011
Published: December 16, 2014