From Big Medical Encyclopedia

LETTERERA-SIVE DISEASE (E. Letterer, is mute. pathologist, sort. in 1895; S. A. Siwe, Swedish pediatrician, sort. in 1897; synonym: the acute system progressing histiocytosis, children's form of a malignant histiocytosis) — the disease which is characterized by formation of the centers of growth of atipichesky histiocytes in skin, bones, internals. L. — Page. is one of forms of a histiocytosis of X.

For the first time the clinic of a disease was described by Letterer in 1924, and in 1933 to Siwa introduced the idea of belonging of this disease to reticuloendothelioses with disbolism. More often children of early age are ill.

Etiology diseases it is not clear. A number of scientists is supporters of its tumoral nature, others attach great value in a course of a disease of a viral infection. The cases which are coming to the end with monocytic leukemia so-called ksantoleykozy are described (according to the WHO classification of 1976 — a malignant histiocytosis reticulosis).

A pathogeny

at the heart of a pathogeny of L. — Page. proliferation lies histiocytes (see), to-rye received the name «atypical» thanks to a number of features of morphology and cellular exchange, in particular accumulation in them of large numbers of difficult lipids like cholesterol. Ultrastructural markers — paracrystal little bodies of X are found in atypical histiocytes. These little bodies called by also necklace-shaped structures, described Bass and Nezelof (F. Basset, S. of Nezelof) in 1965, on the ultrathin structure remind a myelin of nervous tissue.

Pathological anatomy

growths of atypical histiocytes are Characteristic of a disease, to-rye are localized in skin, limf, nodes, a spleen, marrow, a thymus, liver, lungs.

Fig. 1. Microdrug of a lymph node at Letterer's disease — Siwa: growth of histiocytes (1) and huge multinucleate cells (2), small accumulations of lymphoid cells (3).

Moderate increase in all groups limf, nodes is noted. The sizes and weight of a spleen and liver are in most cases increased by 2 — 3 times, dystrophic changes of parenchymatous bodies are noted. Knotty tumoral growths in flat bones (bones of a skull, a basin, in edges, etc.), a thymus, serous and mucous membranes are sometimes observed. In zones of growth of histiocytes sites of hemorrhages and a necrosis quite often meet owing to what fabric on a section can have a motley appearance. Atypical histiocytes — cells of the average sizes, have oval or irregular shape a kernel with the basphilic indistinctly outlined kernel, slabobazofilny cytoplasm, edges often contains fagotsitirovanny inclusions. In places of accumulation of atypical histiocytes (fig. 1) can be found multinuclear colossal cells (see), lymphocytes (see), plasmocytes (see), eosinophils. Sometimes accumulations of the ksantomny cells appearing as a result of adjournment in cytoplasm of atypical histiocytes of neutral fats and cholesterol come to light. In a circle of the centers of a necrosis accumulations of segmentoyaderny leukocytes meet. Development of tyazhy fibrous fabric is possible.

At microscopic examination in skin find extensive histiocytic proliferata in a superficial part of a derma, sometimes with penetration of cells into epidermis, a partial atrophy and amotio of epidermis. Various volume gnezdny accumulations of atypical histiocytes, as a rule, come to light in fabric and gleams of sine limf, nodes, in a spleen, a thymus. In a liver infiltrates are located on the course of portal paths, development of fibrosis, stagnation of bile is quite often noted. Accumulations of atypical histiocytes can be observed also on the course went. - kish. a path, in kidneys, serous covers, a pleura, interalveolar partitions and around bronchial tubes. Damage of marrow can be expressed in various degree. In most cases against the background of the centers of a hemopoiesis large fields of atypical histiocytes come to light that is combined with the expressed rassasyvaniye of a bone tissue; sometimes atypical histiocytes contain in a small amount in the form of small accumulations or odinochno scattered cells; in these cases establishment of the diagnosis by an intravital research of marrow can be complicated.

The clinical picture

the Disease develops sharply. The earliest manifestations — seborrhea on the head, skin moknuty pleated, the papular and squamous rash which is localized more often on skin of an upper half of a trunk. At the height of a disease petechias can appear. Fever, increase in the sizes of a liver, spleen, peripheral limf, the nodes which are quite often forming conglomerates is noted.

Damage of mucous membranes in the form of persistent aphthous is characteristic stomatitises (see) and vulvovaginitis (see), emergence of recurrent purulent otitises (see) and mastoidites (see), not giving in to antibacterial treatment. Specific defeat of pulmonary fabric in the form of intersticial is observed pneumonia (see). In more remote terms of a disease widespread damages of bones of a skull, a basin, extremities are possible. There can be an exophthalmos, a syndrome of not sugar mocheiznureniye. There are no continuous specific variations in blood, however in some cases the accelerated ROE, a neutrocytosis, an eosinophilia, a monocytosis, a thrombocytosis, in hard cases — a pancytopenia is observed.

Fig. 2. The roentgenogram of pelvic bones at Letterer's disease — Siwa at the child of 3 years; the extensive center of destruction in the right ileal bone with wavy contours is visible (it is specified by an arrow).

At L. — Page. most often flat bones (a skull, a basin, shovels) are surprised. On survey roentgenograms sites of the expressed depression with a clear boundary come to light, the separate centers reach the sizes 1 — 2 cm. Several small centers can merge among themselves; in this case on the roentgenogram the serious defects of a bone tissue having wavy, sometimes clear scalloped contours (fig. 2) are found. The destructive centers, destroying first of all spongy substance of a bone, can break an integrity and cortical substance; characteristic of L. — Page. lack of reaction of a periosteum even is when at a rapid current of process there is destroyed also a cortical substance.

Diagnosis the wedge, symptoms, rentgenol, changes and tsitol, pictures of puncture and biopsy material from infiltrirovanny bodies and fabrics is put on the basis of typical. In puncture and biopsy material cells of system of the englobing mononuklear prevail: atypical histiocytes, multinucleate cells (result of an endomitosis of atypical histiocytes) and ksantomny cells, to-rye are a form of aging of atypical histiocytes.

Differential diagnosis carry out mainly with an acute leukosis (see. Leukoses ), neuroblastoma (see), inborn syphilis (see), a disease to Gosha (see. to Gosha disease ), Nimann's disease — Peak (see. Nimanna — Peak a disease ), mukopolisakharidozam (see), sepsis (see). In cases when in a wedge, a picture one symptom dominates, the disease should be differentiated according to dermatitis, otitis, pneumonia, etc.


Treatment is carried out by cytostatic and hormonal drugs. Appoint them in the acute period of a disease often in the form of polychemotherapy Cyclophosphanum, Oncovinum (vinblastine) of N of Prednisolonum (TsOP). Treatment is carried out by 6 — 8 courses with breaks to 2 — 4 weeks. The supporting treatment — 6 Mercaptopurinum, a methotrexate and leukeranum. According to indications appoint radiation therapy.

Before use of cytostatic drugs the disease quickly led the forecast to a lethal outcome. At treatment these drugs possible to achieve permanent remission from most of patients (up to 5 years and more).

See also Histiocytoses .

Bibliography: Moskacheva K. A., Nebolsina L. I. and Znamenskaya I. V. Retikulo-gistiotsitoz at children, M., 1967; Reynberg S.A. Radiodiagnosis of diseases of bones and joints, t. 1 — 2, M., 1964; Soboleva N. I. and Yeremeyeva A. S. To a question of a disease of Letterer — Siwe, Arkh. patol., t. 22, No. 3, page 64, 1960; Sh e r and P.'s N and d river. Letterer's disease — Ziva (A tumoral form with a lipidosis), in the same place, t. 27, No. 5, page 19, 1965; A b t A. F. a. DenenholzE. J. Letterer— Siwe’s disease, Amer. J. Dis. Child., v. 51, p. 499, 1936; L a h e at E. Histiocytosis Х — an analysis of prognostic factors, J. Pediat., v. 87, p. 184, 1975; Letterer E. Aleukamische Re-tikulose, Frankfurt. Z. Path., Bd 30, S. 377, 1924, Bibliogr.; Lichtenstein L. Histiocytosis X (Eosinophilic granuloma of bone Letterer — Siwe disease and Schuller — Christian disease), J. Bone Jt Surg., v. 46-A, p. 76, 1964; Siwe S. A. Die Re-tikuloendotheliose — ein neues Krank-heitsbild unter den Hepatosplenomega-lien, Z. Kinderheilk., Bd 55, S. 212, 1933, Bibliogr.

P. V. Lenskaya; S. A. Sviridov (rents.), M. P. Khokhlova (stalemate. An.).