What is Langerhans cell histiocytosis?
Langerhans cell histiocytosis (LCH) is a disease that originates in certain blood and blood-forming cells. They multiply at an unusually high rate, clump together and accumulate as nodules (granulomas) in various organs and tissues. They belong to the dendritic cells (as well as monocytes, macrophages or B lymphocytes), which in turn are part of the immune system.
Langerhans cell histiocytosis used to be called histiocytosis X. There are various subgroups, such as eosinophilic granuloma, Hand-Schüller-Christian’s disease and Abt-Letterer-Siwe syndrome. In principle, LCH can affect all organs and parts of the body. However, the damage is often found in the bones, skin and pituitary gland in the brain (hypophysis).
The symptoms depend on the type and number of organs and tissues affected. In some patients, only individual foci form in the skull bones and they experience no symptoms. Some develop only individual papules on the skin, while in others it is diseased over a large area and in many places. A very severe form is when several organs are affected at the same time – then it can also become life-threatening.
The causes of Langerhans cell histiocytosis are still unknown, but the immune system plays an important role. LCH is not inherited and does not run in the genes or the family. It has the characteristics of a benign disease, but can also take a malignant course and develop into cancer.
The treatment depends on where the LCH occurs and how many organs it affects. We therefore treat them with various strategies, for example with medication, surgery and chemotherapy. Sometimes the disease heals on its own.
Langerhans cell histiocytosis – frequency and age
Langerhans cell histiocytosis is one of the rare diseases (orphan diseases). LCH usually manifests itself in childhood. Experts estimate that only around three to five children in a million contract the disease. Around 70 to 80 percent of children are under ten years old when doctors diagnose the disease. In principle, however, LCH can occur at any age, even in adults.
Experts believe that the incidence could be higher in adulthood. This is because Langerhans cell histiocytosis often causes no symptoms. In addition, LCH is so diverse that it is not easy for us to diagnose. And sometimes the disease stops on its own or we stop it by chance with a different treatment. Even then it is not discovered. Men are more frequently affected by LCH than women.
Langerhans cell histiocytosis: Causes
The causes of Langerhans cell histiocytosis are still unknown. Doctors assume that the immune system is disturbed and does not react as it should. LCH is not inherited and is not contagious. It has its origin in certain blood and hematopoietic cells that play an important role in the regulation of the immune system. These cells multiply and accumulate as small nodules (granulomas) in various organs and areas of the body, where they disrupt their function.
Langerhans cell histiocytosis: forms
There are various manifestations of Langerhans cell histiocytosis. In addition, the disease can be acute or chronic:
- Localized LCH: The disease only affects one body structure, for example the bones or skin.
- Disseminated LCH: It affects two or more organs or systems and can cause a very severe clinical picture.
The acute disseminated form often occurs before the age of two. Between the second and fifth year of life, the chronic disseminated form predominates. Localized LCH particularly often affects people after the age of five. Experts find a single LCH focus in around 70 percent of adult cases, usually in the lungs. Doctors have identified an important risk factor in this case: smoking.
Langerhans cell histiocytosis: these organs are often affected
Langerhans cell histiocytosis is often seen in the following organs and structures:
- Bone: approx. 80 percent of cases
- Skin: approx. 33 percent
- Pituitary gland (hypophysis): 25 percent
- Liver: approx. 15 percent
- Spleen: approx. 15 percent
- Blood-forming system: approx. 15 percent
- Lungs: approx. 15 percent
- Lymph nodes: approx. 5 to 10 percent
- Central nervous system (CNS, without pituitary gland): approx. 2 to 4 percent
Symptoms: Langerhans cell histiocytosis
The symptoms of Langerhans cell histiocytosis depend on the type and number of organs and structures affected. Some patients experience no symptoms at all. Some show isolated skin changes, others very extensive ones. And some people can develop a very severe clinical picture if the LCH affects several organs and they no longer function adequately. This can be life-threatening, especially in infants and small children.
Some complaints are of a general nature and can also occur with many other illnesses. These include, for example:
- Tiredness, exhaustion
- Pain in the affected area of the body
- Fever
- Loss of appetite, weight loss
- Growth and failure to thrive
The following symptoms can occur with LCH – depending on the organ:
- Bones: swelling, pain, sudden fractures
- Skin: brown-red skin changes, yellow-brown papules covered with scales and crusts, sometimes they are also infected with pathogens and inflamed, skin rash (similar to diaper rash) – the skin changes can vary in severity from person to person
- Eyes: visual disturbances, squinting, bulging of the eyes
- Hematopoietic system: pallor, increased susceptibility to infections
- Lungs: cough, breathing problems
- Lymph nodes: swollen lymph nodes
- Digestive tract: Diarrhea
- Ears: chronic middle ear infections, discharge from the ear, hearing loss
- Mouth and teeth: loose teeth, tooth loss, swollen gums
- Central nervous system: great thirst and increased urine output – an indication of the hormone deficiency disease diabetes insipidus, which can develop due to damage to the pituitary gland; growth and failure to thrive, balance and memory problems
Always visit us yourself or with your child if you notice such symptoms.
Langerhans cell histiocytosis: Diagnosis with us
The diagnosis of Langerhans cell histiocytosis is not easy for us and requires some experience. In addition, the diagnostics are very extensive. It is important to rule out other diseases as the cause of the symptoms.
The diagnosis of LCH usually begins with a discussion of the patient’s medical history (anamnesis). Among other things, we ask about the type, location, intensity and time of the first onset of symptoms. Existing illnesses or diseases in the family also provide further clues as to the cause of the symptoms. For adults, we also ask whether you are a smoker.
During a physical examination, we examine the entire body and look for or ask about abnormalities, for example:
- Skin and mucous membrane changes
- Swelling, pain, fever
- Restricted mobility of body parts
- Weight and growth
- neurological abnormalities
The diagnosis of Langerhans cell histiocytosis can be confirmed by means of a tissue sample (biopsy). We take cells from the suspicious areas and a pathologist then analyzes the tissue under a microscope. Immunohistochemical examination of the cell material is also helpful, using specific staining methods. We look for certain characteristics on the cell surface, such as the CD1a antigen and Langerin (CD207). A biopsy is not always possible due to the risks involved (e.g. in the case of LCH of the pituitary gland) or it is not always possible to obtain sufficient material from the affected part of the body.
We then determine the stage and spread of the LCH in the body. “Staging” is the technical term for this. What is important for the treatment is which and how many organs are affected. This is achieved with the help of blood tests and imaging procedures.
Blood test
We can tell a lot from the blood. The following values are determined, for example:
- Complete blood count with hemoglobin, leukocytes and differential blood count, platelets (thrombocytes)
- Total protein, albumin
- Bilirubin – a breakdown product of the red blood pigment hemoglobin
- Liver values GPT and GOT
- alkaline phosphatase (AP)
- Gamma-glutamyltransferase (gamma-GT)
- Hormones
- Creatinine
- Electrolytes
- Blood coagulation: INR value/prothrombin time (PT), activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT), fibrinogen
Imaging techniques
- Ultrasound examination of the abdomen (abdominal sonography): This allows us to see the size and structure of the liver and spleen, as well as assess the lymph nodes in the abdomen.
- X-ray examination of the chest (chest X-ray) and the entire skeleton: we can assess the condition of the lungs and bones.
- Computed tomography (CT): This is a method that works with X-rays and provides cross-sectional images of the body.
- Magnetic resonance imaging (MRI = magnetic resonance imaging): It works with strong magnetic fields and we obtain high-resolution sectional images of the inside of the body.
- Scintigraphy: This is a nuclear medicine procedure that shows changes in the bones.
In addition, many other examinations relating to a specific organ may be necessary. Examples include lung function tests, eye and ear examinations (e.g. vision and hearing tests) or neurological examinations to check the function of the nervous system.
If diabetes insipidus is suspected, we carry out a so-called thirst test. Those affected may only drink very little for 24 hours. We then take a urine sample and analyze it. The concentration of antidiuretic hormone (ADH), which regulates and limits the body’s fluid excretion, is too low.
Langerhans cell histiocytosis: prevention, early detection, prognosis
The causes of Langerhans cell histiocytosis are still unknown. Therefore, you cannot prevent LCH. In adults, smoking appears to promote the onset of the disease. So give up smoking – not only your lungs will benefit, but your entire body.
No special medical measures for the early detection of Langerhans cell histiocytosis are known. The general advice is therefore: always consult a doctor promptly if you or your child have any unusual symptoms. They can determine what is actually behind the complaints.
Course and prognosis of Langerhans cell histiocytosis
Langerhans cell histiocytosis is basically a benign disease, but it can become malignant. Sometimes the LCH also regresses spontaneously. Some patients experience relapses (recurrences) and the disease returns at certain intervals. Late effects are also possible, especially in the case of a course with repeated relapses. These include, for example:
- Hormone deficiencies: Growth hormone deficiency with delayed puberty, deficiency of the thyroid hormone TSH and hypothyroidism as a result
- Hearing damage
- Orthopaedic problems, e.g. bone fractures, vertebral fractures or asymmetries if the facial bones are affected
- Neurocognitive disorders: Disorders of movement coordination, speech and language, learning difficulties
- Damage to the liver and lungs
Individual LCH foci are usually unproblematic and can be treated effectively. The situation is different if the disease has affected several structures and organ systems. This is particularly the case with infants and small children. The disease can take a rapid, severe and life-threatening course – and in some cases can be fatal. But overall, the prognosis for Langerhans cell histiocytosis is good.