Histiocytosis

Group of disorders that have in common, as a primary event, the accumulation and infiltration of histiocytes, monocytes, macrophages, and dendritic cells in the affected tissues. Involves mainly the skin, bones, brain, lungs, spleen, and liver. Presents as nonmalignant growths that represent accumulation of histiocytes. Poor prognosis (70% mortality).

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Langerhans Cell Histiocytosis; LCH.

Estimated annual incidence ranges from 0.5-5.4: 1,000,000 persons per year, but this probably is underestimated. Male-to-female ratio is 2:1.

Consanguinity has been reported.

LCH could arise secondary to a somatic mutation of a gene with clonal proliferation of the specific cells as a consequence. LCH cells synthesize various cytokines, including interleukin (IL)-1, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF), which can explain certain systemic signs of the disease.

Clinically evocated and confirmed by laboratory investigations. Different levels of probability have been described for the diagnosis:

• Presumed: Light morphologic characteristics
• Probable: Light morphologic features plus two or more supplemental positive stains for the following: adenosinetriphosphatase, S-100, α-d-mannosidase protein, and peanut lectin
• Definitive: Light morphologic characteristics plus Birbeck granules in the lesional cell (electron microscopy) and/or staining positive for CD1a antigen (T6) on the lesional cell.

Because of the dissemination of the disease, clinical signs are multiple and can involve a large part of the body.

Bones (78%): Typical punched-out cavity. Lesions can be asymptomatic or revealed by pathologic fracture or regional complications (loss of teeth, pain, periosteal inflammation). Most frequently involved bones are skull (49%), innominate bone 23%, femur 17%, orbit 11%, and ribs 8%.

Skin (50%): Lesions occur during the first months of life. Rash is frequent. Bronzing of the skin can occur. Infiltrates (maculoerythematous, petechial xanthomatous, nodular papula) have a predilection for the midline of the trunk and the peripheral and flexural areas of skin. Scalp lesion can lead to alopecia. There is no pruritus.

Chest (20-40%): Interstitial syndrome (nodular images) caused by a restrictive syndrome with clinical manifestations such as cough tachypnea and dyspnea. Diagnosis is based on bronchoalveolar washing. Pulmonary fibrosis and pneumothorax can occur.

Digestive System: Relatively rare, ranging from focal intestinal infiltration without any signs to severe serous diarrhea or bleeding. Liver can be variously involved, from simple, moderate biologic signs to hepatomegaly or even sclerosing cholangitis complicated by biliary cirrhosis and, finally, hepatic failure.

Nervous System: Rare; cerebral tumor or parenchymatous infiltration (usually the cerebellum) that could lead to intracranial hypertension, localization signs, ataxia, or seizures. Pituitary gland can be involved, causing diabetes insipidus and deficit of growth hormone and/or thyroid-stimulating hormone.

Other: Features can include lymph node enlargement, hematopoiesis dysfunction (anemia, thrombopenia, rarely neutropenia), abnormalities of spleen, eye, or heart (pericarditis).

Because of the great variety of lesions, preanesthetic evaluation must start by obtaining full history of the disease and meticulous clinical examination. Because of the high frequency of organ involvement, some evaluation should be systematic: evaluate pulmonary function (clinical, pulmonary function test, arterial blood gas analysis, chest radiographs, CT), liver function (clinical, echography, CT, MRI, laboratory investigations including albumin, transamidinases, bilirubin, prothrombin), and nervous function (clinical, CT, MRI, EEG). Other evaluations based on clinical signs (cardiac echography, hormonal investigations, hydration, platelet count, blood cell count).

The high risk rate is dependent on the clinical features. Lung ventilation with low pressure must be used because of the risk of pneumothorax. Careful intraoperative positioning is needed because of bone fragility. Regional anesthesia is not contraindicated but should be evaluated in each case, considering cutaneous lesions, nervous involvement, platelet count, and hepatic function.

Consider interaction between anesthetic drugs and antiepileptic treatment and hepatic function. Succinylcholine should be avoided if there is a large bone defect because of the risk of fracture during fasciculation. Nitrous oxide should be avoided because of the increased frequency of pneumothorax. In case of steroid treatment, intraoperative steroid supplementation must be used. Avoid situations and drugs that can affect intracranial pressure in case of central neurologic lesions.

Histiocytosis X disseminated form, which includes the following:

Eosinophilic Granuloma: Mildest form with only bone involvement.

Hand-Schüller-Christian Disease: Affects children older than 2 to 3 years of age who have diabetes insipidus, cranial bone cavities, and exophthalmia.

FamilialLipochrome Histiocytosis: Autosomal recessive medical condition with immunologic involvement and susceptibility to infection.

Letterer-Siwe Disease (LSD): Childhood disorder characterized by a pathologic proliferation of histiocytes caused by the Langerhans cells. Involves mainly the skin, bones, brain, lungs, spleen, and liver. Presents as nonmalignant growths that represent accumulation of histiocytes. Poor prognosis (70% mortality).

Erdheim-Chester Disease (ECD): Systemic non-Langerhans cell histiocytic disorder characterized by development of lipoid granulomas in many organs and tissues of the body. Clinical manifestations range from asymptomatic to fatal multisystem involvement.