Alternate Names: Histiocytosis X; Eosinophilic granuloma; Pulmonary histiocytosis X; Nonlipid reticuloendotheliosis; Pulmonary langerhans cell granulomatosis; Hand-Schuller-Christian disease; Letterer-Siwe disease; Langerhans cell histiocytoses

Causes and Risks:

One class of histiocytosis, which tends to occur more in adults, Pulmonary histiocytosis X, is characterized by inflammation of the small airways (bronchioles) and the small blood vessels in the lungs. This inflammation leads to stiffening (fibrosis) and destruction of the walls of the alveoli. The cause is unknown. People 30 to 40 years old are affected most often. Cigarette smoking is a risk factor for pulmonary histiocytosis (90% of patients). Spontaneous pneumothorax occurs frequently in this condition.

Most cases of histiocytosis, however, occur between the ages of 1 and 15 years old, the incidence peaking between 5 to 10 years of age. The total incidence of histiocytosis is thought to be roughly one in two hundred thousand people each year.

In children, histiocytosis is typified by bone involvement (80%) and may consist of single or multiple sites. The skull is a frequent site of involvement. The tumors produce a punched-out appearance in the bone X-ray. Tumors in the weight bearing bones such as the legs or spine may fracture spontaneously. However, there is often systemic involvement (whole body) causing rashes, pulmonary problems, gum infiltration, lymph gland involvement, endocrine problems, enlargement of the spleen and liver, anemia, and in some circumstances, death.

Children over 5 years old often have only bone involvement. However, those surviving for long periods often continue to have problems. Young children, especially infants, are more likely to have systemic involvement and a fatal outcome.

The non-malignant disease has been thought of a cancer like disease, but more recently researches feel it behaves similar to an autoimmune-like phenomenon. Some forms are genetic.

Prevention: No prevention is known. However, quitting smoking will lower the disease’s risk in pulmonary involvement.

Symptoms:

Note: There can be some overlap between the adult and children symptoms.

Adult:

• Cough
• Shortness of breath
• Chest pain
• Fever
• Weight loss
• General discomfort, uneasiness, or ill feeling (malaise)
• Increased amount of urine output
• Thirst/drinking a lot
• Bone pain

Children:

• Failure to thrive
• Weight loss
• Irritability
• Fever
• Seborrheic dermatitis of the scalp
• Abdominal pain
• Jaundice
• Vomiting
• Limping
• Thirst/frequent urine
• Short stature
• Delayed puberty
• Mental deterioration
• Head-ache
• Dizziness
• Seizures
• Increased eyeball protrusion
• Swollen lymph glands
• Generalized rash (petechiae or purpura)
• Chronically draining ears
• Bone pain may or may not be present

Signs and Tests:

Adult:

• Chest X-ray
• Bronchoscopy with biopsy showing typical X bodies in histiocytes
• Pulmonary function tests

Children:

• Bone X-ray showing punched-out appearance of bone lesions
• Skeletal survey X-ray (X-rays of the entire skeleton) to determine the degree of bone involvement
• Biopsy of bone to check for the presence of Langerhans cells
• Biopsy of skin to check for the presence of Langerhans cells
• Bone marrow biopsy
• CBC
• Other tests as clinical symptoms direct

Treatment:

This disorder is treated with corticosteroids.  Smoking may worsen the response to treatment and should be stopped.
 
Children may be given other medications depending on their estimated prognosis among other clinical conditions, including:

• Prednisone
• Methotrexate
• Vinblastine
• Cyclophosphamide
• Etoposide

Radiation therapy or limited surgery may also be used to treat bone lesions. 

Most importantly, patients are treated with supportive care to treat whatever adverse effects are occurring as a result of the disease such as antibiotics, ventilatory support (breathing assistance with a respirator), physical therapy, selenium-based shampoo, and hormone replacement.

Prognosis:

In pulmonary histiocytosis, the disease stabilizes or improves in about one-half of the affected people and the other half progress to a permanent loss of lung function.

In the pediatric versions, it depends on the actual disease category and severity of the disease. Some can be expected to have a normal life span with minimal disease involvement and some can expect a poor outcome.

Complications:

• Spontaneous pneumothorax
• Diffuse interstitial pulmonary fibrosis

Children may also develop:

• Pituitary dysfunction with growth failure
• Diabetes insipidus
• Bone marrow invasion with subsequent anemia
• Lung problems with eventually pulmonary failure

Call your health care provider or go to the emergency room (depending on the extent and severity of symptoms) if shortness of breath, chest pain, or other symptoms of this disorder develop.