Histiocytosis from Langerhans cells (histiocytosis X): causes, symptoms, diagnosis, treatment

Histiocytosis from Langerhans cells (granulomatosis from Langerhans cells, histiocytosis X) is the proliferation of dendritic mononuclear cells with diffuse or local organ infiltration. The disease is mainly found in children. The manifestation of the disease includes lung infiltration, bone damage, skin rash, hepatic, hemopoietic and endocrine dysfunction. Diagnosis is based on biopsy results. Treatment includes supportive therapy, chemotherapy or topical treatment with surgery, radiation therapy depending on the spread of the disease.

[1], [2], [3]

Epidemiology

The disease histiocytosis X occurs at a frequency of 1:50 000, with the majority of cases - children of young age, although there are cases of diseases of children in adolescence. However, adults, elderly people, mostly men, often fall ill.

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Risk factors

Factors predisposing to an unfavorable prognosis are the age of up to 2 years and the dissemination of the process, especially the involvement of the hematopoietic system, the liver and / or lungs.

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Pathogenesis

Histiocytosis from the cells of Langerhans (GCR) - a dysfunction of the dendritic cell. Clear clinical syndromes of such a disorder have been historically described as eosinophilic granuloma, Hend-Schuler-Crischen disease and Letterter-Sieve disease. Since these syndromes can be different manifestations of the underlying disease and due to the fact that most patients with histiocytosis from Langerhans cells have more than one syndrome, currently the definition of individual syndromes is mainly of historical significance.

Histiocytosis X is characterized by the development of pathological proliferation of dendrite cells in one or more organ. Bones, skin, teeth, gum tissue, ears, endocrine organs, lungs, liver, spleen, lymph nodes and bone marrow can be affected. The organs can be affected by proliferating cells that cause their dysfunction, or these organs experience the pressure of neighboring, enlarged organs. In half the cases, many organs are affected.

[11], [12], [13]

Symptoms of the histiocytosis X

Symptoms and signs are diverse and depend on which organs are infiltrated. Syndromes are described in accordance with historical guidelines, but only a small number of patients have classic manifestations of the disease.

Eosinophilic granuloma

The solitary or multifocal eosinophilic granuloma (60-80% of cases of histiocytosis X) occurs mainly in older children and young people, usually up to 30 years; The peak incidence falls on the age of 5 to 10 years. The most commonly affected bones, often with pain, inability to withstand gravity, with the formation of a sensitive soft tumor (often warm).

[14], [15]

Hend-Schuiller-Crischen disease

This syndrome (15-40% of cases of histiocytosis X) is more common in children aged 2 to 5 years, less often in older children and adults. This is a systemic disease in which the flat bones of the skull, ribs, pelvis and shoulder blade are classically affected. Long bones and lumbosacral spine are involved in the process less often; wrists, brushes, feet and cervical vertebrae are rarely affected. In classical cases, patients have exophthalmos due to the orbital tumor mass. Loss of vision or strabismus is rare and is caused by damage to the optic nerve or orbital muscles. In elderly patients loss of teeth, caused by apical and gingival infiltration, is common.

A typical manifestation of the disease is chronic middle and outer otitis caused by the involvement of the mastoid process and the stony part of the temporal bone with partial obstruction of the auditory canal. Non-diabetes mellitus is the last component of the classical triad, which includes the defeat of flat bones and exophthalmos diagnosed in 5-50% of patients, more often in children who have systemic involvement involving the orbit and skull. Up to 40% of children with systemic disease are characterized by low growth. Infiltration of the hypothalamus can lead to the development of hyperprolactinaemia and hypogonadism. In rare cases, other symptoms are possible.

Diseases of Letterter-Sive

This systemic disease (15-40% of cases of histiocytosis X) is the most severe form of histiocytosis X. It usually occurs in children under 2 years old in the form of an eczematoid rash accompanied by scaling and seborrhea detachment, sometimes purple in color, affecting the scalp, ear canals, abdomen, also characterized by the presence of zones of intertrigo in the neck and face. Deepithelization of the skin can promote microbial invasion, leading to the development of sepsis. Otitis, lymphadenopathy, hepatosplenomegaly often develop, and in severe cases, liver dysfunction with hypoproteinemia and a violation of the synthesis of coagulation factors. Often there is anorexia, irritability, developmental disorder, pulmonary symptoms (eg, cough, tachypnea, pneumothorax). Severe anemia and sometimes neutropenia occur; Thrombocytopenia is a poor prognostic sign. Parents often report premature dentition, when the gums are bare and the exposed dentin is exposed. Parents can show careless and rough treatment of a sick child.

[16], [17], [18], [19], [20], [21], [22]

Diagnostics of the histiocytosis X

Hystiocytosis X is suspected in patients (especially young ones) with unexplained pulmonary infiltration, bone or eye lesions or abnormalities in the facial skull bones, and in children under 2 years old with a typical rash or severe unexplained multi-organ pathology.

When identifying the characteristic symptoms, an x-ray examination is performed. Bone lesions usually have sharp edges, round or oval, with a bevelled edge, giving the impression of depth. Some lesions are sometimes indistinguishable from Ewing sarcoma, osteosarcoma, other benign and malignant pathologies or osteomyelitis.

The diagnosis is based on a biopsy. Langerhans cells are usually clearly defined, except for old lesions. These cells are identified by a morphologist with experience in diagnosing histiocytosis X, according to their immunohistochemical characteristics, which include the determination of surface CD1a and S-100. Once the diagnosis is established, it is necessary to determine the prevalence of the disease using appropriate laboratory and visual diagnostic methods.

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Treatment of the histiocytosis X

Patients should regularly go to specialized medical institutions to correct the treatment of histiocytosis X. General supportive therapy is of great importance and includes careful observance of personal hygiene in order to limit the damage to the ears, skin, and oral cavity. Surgical treatment and even resections with severe lesions of gum tissue limit the amount of damage to the oral cavity. The use of selenium-containing shampoos 2 times a week is an effective remedy for seborrheic dermatitis of the scalp. In the absence of a positive effect of the use of shampoo, glucocorticoids are applied topically in small amounts in the non-extensive areas of the lesion.

Many patients need hormone replacement therapy for diabetes insipidus or other manifestations of gipo-popitourism. Patients with systemic manifestations of the disease need to be monitored to detect chronic functional disorders, in particular cosmetic or functional orthopedic and skin disorders, neurotoxicity, and psychological problems, and may require psychosocial support.

Chemotherapy is indicated for patients with multiple organ failure. The protocols recommended by the Society of Histiocytosis, divided according to the risk category, are used. Practically all patients with a good response to therapy can be stopped. Protocols with poor response to therapy are under development.

Local surgical intervention or radiation therapy is used in case of disease with the defeat of one bone or less often with multiple lesions of bones. With access to affected lesions in non-critical areas, surgical scraping is performed. Surgical intervention should be avoided in cases of probability of impaired function or significant cosmetic or orthopedic complications. Radiation therapy can be shown to patients with a risk of skeletal deformation, loss of vision, as a consequence of exophthalmos, pathological fractures, spinal fracture and spinal cord injury or in patients with severe pain syndrome. Used doses of radiation therapy are relatively less than the doses used in the treatment of oncological diseases. Surgical and radiotherapy should be used by specialists with experience in the treatment of histiocytosis X.

In patients with multi-organ damage and progression of the process, standard therapy is ineffective and more aggressive chemotherapy is needed. Patients who do not respond to salvage therapy may receive bone marrow transplantation, experimental chemotherapy or immunosuppressive and immunomodulatory therapy.

Forecast

The disease, limited to lesions of the skin, lymph nodes and bones in patients younger than 2 years, has a good prognosis. A significant level of morbidity and mortality occurs in young patients with multi-organ damage. Patients with multiorgan lesions are at high risk. About 25% of patients are at low risk. Criteria for low risk are age over 2 years, no damage to the hematopoietic system, liver, lungs, spleen. The risk criteria are the age of up to 2 years or the involvement of these bodies. Overall survival in patients with multiorgan lesions during treatment is about 80%. Lethal outcomes are virtually absent in the group of low-risk patients, but are possible in a group of high-risk patients who did not respond to initial therapy. Often there are relapses of the disease. There may be periods of exacerbation of the chronic course of the disease, especially in adult patients.

[26], [27]