Frequently asked questions about Langerhans Cell Histiocytosis (LCH)

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General information about histiocytoses

1 - What does histiocytosis mean?

Histiocytoses are defined as histiocytic disorders due to an abnormal accumulation of histiocytes. They include a wide variety of conditions that affect both children and adults.

2 - What is a histiocyte?

A histiocyte is one kind of white blood cell which belongs to the immune system. There are histiocytes in many parts of the body, especially in the bone-marrow, blood, skin, liver, lungs, lymphatic glands and spleen. Their functions are associated to the immune response like the destruction of foreign bodies and infection defence.

3 - What is the basis for the classification of histiocytic disorders?

"Histiocytic disorders" are generally defined by their constitutive cell, on the basis of pathological criteria (tissue examination) but require also the correct clinical context.

There have been many difficulties to classify this group of diseases. Since 1987, the Histiocyte Society has proposed the classification according to the relationship to normal histiocyte subsets. The revision done in 1997 took into account the biologic behaviour. The disorders are now divided in two broad groups, those of varying biological behaviour and those that are truly malignant. Within each category the disorders are subclassified according to their affiliation of different cell types.

General information about Langerhans Cell Histiocytosis

1 - Why is the disease called Langerhans Cell Histiocytosis?

Langerhans Cell Histiocytosis is characterised by the accumulation of cells which have the characteristics of Langerhans cells (LCs). These cells enable the body to recognize foreign substances. For some reason which is not yet known, these histiocytes migrate to tissues where they usually do not appear and damage these tissues. Nowadays this disorder is called Langerhans's Cells Histiocytosis (LCH), but some years ago, it was called Histiocytosis X. There are still many unknown aspects, and different names are used for some forms of LCH, like eosinophilic granuloma for bone lesions.

2 - What is a Langerhans cell?

The Langerhans cell is one of the several types of histiocytes. Its function is the protection of both the skin and the upper respiratory tract. These cells are a part of the immune system.

3 - What is the cause of Langerhans Cell Histiocytosis?

So far, the cause is unknown.

4 - What are the main types of LCH?

There are two main types of LCH:
1. Single system, when only one organ or organ system is involved, e.g. only the bones.
2. Multisystem, when two or more organs or organ systems are involved.

5 - How common is LCH?

So far it is assumed that Langerhans Cell Histiocytosis (LCH) is more frequent in children than in adults. Nevertheless, the LCH rate in adults has never been systematically evaluated. The LCH rate in children is approximately 1 case per 200 000 children per year. There is no known racial predilection.

6 - Is the course of Langerhans Cell Histiocytosis the same in all patients?

No. The behaviour of the disease varies a lot. The disease is mild in many cases and spontaneous recovery is possible. In other patients however, the lesions in different organs progress and therapy is needed for stopping the progression.

7 - Is there any association between LCH and cancers?

Association of LCH with cancer is very rare. Cancer can occur before, concurrently or in most of the cases after LCH. Most of these cases are probably due to previously used treatments like radiotherapy or some chemotherapy which is no longer recommended for LCH.

Diagnosis of LCH

1 - How is LCH diagnosed?

LCH is diagnosed by examination of the affected tissue (biopsy). When the diagnosis of LCH is made, some additional tests are necessary to determine the extent of the disease.

2 - What additional tests may be needed to know the disease extent?

Additional tests may be blood studies and imaging (x-rays of bones and lungs, abdominal ultrasound, bone scan, computed tomography, magnetic resonance). As many organs may be involved, some tests are needed in all patients for a general evaluation and other tests depend on symptoms and physical signs. It is important to make a systematic study of the organs most often affected: skeleton, skin, lung, liver, spleen, lymphatic system, central nervous system (brain) and blood.

3 - How can I be sure that the diagnosis LCH is correct?

Definitive diagnosis of LCH must always be made by biopsy which means that a sample of the affected tissue is taken and examined with microscope. According to the criteria of the Histiocyte Society, “definitive diagnosis” requires classical histopathology confirmed by demonstration of certain characteristics of these cells. (Demonstration of CD1a or Langerin (CD207) or ultrastructural presence of Birbeck granules.) This means the identification of the typical lesional cells by immunostaining techniques and the typical morphology.) Anything less is regarded as “presumptive diagnosis”. However, in some patients biopsy may be too risky a procedure. In these cases management should be referred to an expert.

4 - Why did it take so long to diagnose LCH?

Diagnosis of LCH is sometimes a difficult issue for physicians due to several aspects:
1. There are a variety of symptoms in different organs.
2. LCH is a very rare disease. It may present with symptoms similar to those in a more common disease and make final diagnosis difficult.

Therapy of LCH

1 - What is the prognosis of LCH?

The prognosis is variable and depends mainly on the affected organs and the degree of dysfunction. It is worse when liver, spleen or hematopoietic system (blood) are affected. For these reasons liver, spleen and blood are named "high risk organs or systems" in LCH. A good initial response to therapy seems to correlate with a better prognosis. Previously, very young age and lung involvement were considered to be bad prognostic factors, but this has proven to be incorrect.

2 - What is the optimal treatment of LCH?

The different clinical features and rarity of the disease make it difficult to carry out clinical trials to determine the best treatment. Most of the recommendations for therapy are based on studies (in children) by groups like the Histiocyte Society, national collaborative groups or on expert opinion.

3 - What is the best treatment for isolated LCH bone lesions?

Bone is affected in around 80% of LCH patients. The lesions can be in one bone, multiple in different bones or associated with disease in other organs. The bone lesions can resolve spontaneously or after biopsy or curettage. Some publications show a role for intralesional glucocorticoids or systemic biphosphonates or indomethacin in some patients. If there is no risk of deformity, fractures or damage to adjacent structures they can be just observed, since sometimes spontaneous resolution may occur.

Some patients with isolated bone LCH disease need to be treated with systemic therapy. Bone lesions localised in facial bone, vertebrae associated with soft tissue mass or adjacent to vital structures might benefit from systemic therapy. This may include steroids and chemotherapy, to control the disease and avoid deformities and sequelae.

4 - What is the best treatment for isolated LCH skin lesions?

Skin lesions improve spontaneously in some patients. Topical treatment with steroids, photochemotherapy (PUVA) or nitrogen mustard have been used. Sometimes, oral or intravenous therapy may be needed.

5 - What is the best treatment for isolated LCH lung lesions?

This form is more frequent in adulthood and it can improve just when smoking is given up. When there is lung involvement, the initial treatment consists of smoking cessation, avoiding exposure to cigarette smoke in daily life, and possibly administration of steroids. In resistant cases, it is possible to use other drugs. In cases of extensive damage, lung transplant may be necessary.

Reactivations of LCH

1 - How often do reactivations of the disease occur?

The majority of patients do not have a reactivation. However, some have one or more, most of them localised to low risk organs like skin or bone. The percentage of patients with reactivations is variable in the different pediatric clinical trials but it is around 20% in patients with single system disease and about 40-50% in patients with multisystem disease. Reactivations occur mainly in the first two years after diagnosis. A longer length of therapy seems to be associated with a lower rate of reactivations in the last clinical trials of the Histiocyte Society. However, the best length or the best combination of drugs for lowering the high rate of reactivations is still unknown.

Risks and Permanent Consequences

1 - Is diabetes insipidus reversible?

It is usually not reversible. Occasionally the need for medication may decrease.

2 - What behaviour may cause development of or worsening of lung involvement?

LCH patients should not be exposed to cigarette smoke in their daily life and should never smoke or start smoking, even if their disease has been non-active for many years.

Research

1 - How can research help?

It is common for all rare diseases that patients are dispersed, what makes difficult to carry out clinical trials with a significant number of samples. They are needed in order to establish the diagnostic criteria. For the correct diagnosis, previous knowledge of the professionals is needed, since the clinical signs are often very different. For the same reasons, it is necessary to have a multidisciplinary point of view in LCH research. Working in multidisciplinary teams, it is possible to optimise the patients´ care.

If you have any further questions please do not hesitate to contact the Histio Net team.