Histiocytosis is a general name for a group of syndromes. These syndromes all include an abnormal increase in the number of certain immune cells, called histiocyte cells. Histiocyte cells include monocytes, macrophages, and dendritic cells.

There are 3 major classes of histiocytoses, but this article focuses on Langerhans cell histiocytosis, which is also called histiocytosis X.

The other 2 classes are non-Langerhans cell histiocytosis (also known as hemophagocytic syndrome) and malignant histiocytosis syndrome (now known as T-cell lymphoma).

Most cases of histiocytosis X affect children between ages 1 and 15 years old. The incidence peaks amongst children between 5 and 10. Histiocytosis X is thought to affect roughly 1 in 200,000 people each year.

The extra immune cells may form tumors, which can affect various parts of the body. In children, histiocytosis X usually involves the bones (80%), and may affect one or more sites. The skull is frequently affected.

The tumors produce a punched-out appearance on bone x-ray. Tumors in weight-bearing bones, such as the legs or spine, may cause the bones to fracture without apparent reason. There is often systemic (whole body) involvement as well, causing rashes, lung problems, gum problems, lymph gland swelling, hormonal problems, enlargement of the spleen and liver, and anemia. Not surprisingly, with a disease that affects so many systems and organs, histiocytosis can be deadly.

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

Histiocytosis X has typically been thought of as a cancer-like condition, but more recently researchers have begun to suspect that it is actually an autoimmune phenomenon, in which rogue immune cells attack the body, rather than fight infections. Some forms of the disorder are genetic.

Another type of this disorder, pulmonary histiocytosis X, is characterized by inflammation of the small airways (bronchioles) and the small blood vessels in the lungs. It is most common in adults. The inflammation leads to stiffening (fibrosis) and destruction of the walls of the alveoli (parts of the lung). The cause is unknown. People 30 - 40 years old are affected most often. Cigarette smokers make up 90% of patients. Spontaneous pneumothorax occurs frequently in this condition.

The symptoms that affect children and adults are listed below, although there can be some overlap.

Adult:

• Cough
• Shortness of breath
• Chest pain
• Fever
• Weight loss
• General discomfort, uneasiness, or ill feeling (malaise)
• Increased amount of urine output
• Thirst and increased drinking of fluids
• Bone pain
• Rash

Children:

• Failure to thrive
• Weight loss
• Irritability
• Fever
• Seborrheic dermatitis of the scalp
• Abdominal pain
• Jaundice
• Vomiting
• Limping
• Thirst and frequent urination
• Short stature
• Delayed puberty
• Mental deterioration
• Headache
• Dizziness
• Seizures
• Increased eyeball protrusion
• Swollen lymph glands
• Generalized rash (petechiae or purpura)
• Chronically draining ears
• Possible bone pain

Adult:

• Chest x-ray
• Bronchoscopy with biopsy showing typical abnormalities 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 how much of the skeleton is affected
• Biopsy of skin to check for the presence of Langerhans cells
• Bone marrow biopsy to check for the presence of Langerhans cells
• Complete blood count (CBC)
• Other tests as needed

This disorder is treated with corticosteroids, which suppress immune function (including the dangerous cells). Smoking may worsen the response to treatment and should be stopped.

Children may be given other medications depending on their estimated prognosis, including:

• Methotrexate
• Vinblastine
• Cyclophosphamide
• Etoposide

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

Patients are also treated with supportive care to reduce symptoms and treat infections that may occur when the immune system is compromised. Treatment may include antibiotics, breathing assistance with a respirator, physical therapy, selenium-based shampoo for scalp problems, and hormone replacement to deal with hormonal dysfunction.

For additional information, patients may wish to contact the Histiocytosis Association of America at 800-548-2758.

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, the outlook 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.

• Spontaneous pneumothorax
• Diffuse interstitial pulmonary fibrosis

Children may also develop:

• Pituitary dysfunction with growth failure
• Diabetes insipidus
• Bone marrow invasion by the tumors, with subsequent anemia
• Lung problems with eventual lung 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.

Avoid smoking. Quitting smoking can improve the outcome in people whose lungs are affected with histiocytosis. No prevention is known for the childhood forms of the disease.