SNP Shot: Genomic Insights

Langerhans cell histiocytosis (LCH) is a condition where an excessive amount of Langerhans cells, a type of immune cell, accumulates in the body. These cells, normally found throughout the body (especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow), play a role in immune system regulation. In LCH, these cells are immature and tend to form tumors called granulomas. While some consider LCH a form of cancer, this remains a topic of debate.

Approximately 80% of individuals with LCH develop granulomas in their bones, leading to pain and swelling. These granulomas commonly occur in the skull or long bones of the arms or legs and can weaken the bone, potentially causing fractures.

Skin involvement is also frequent, with granulomas appearing as blisters, reddish bumps, or rashes, ranging in severity from mild to severe. The pituitary gland, located at the brain's base and responsible for hormone production, can also be affected. This can lead to hormonal imbalances, potentially causing delayed or absent puberty or infertility. Pituitary gland damage can also cause excessive urine production (diabetes insipidus) and thyroid dysfunction. Thyroid problems can impact metabolism, body temperature, skin/hair texture, and behavior.

In 15-20% of cases, LCH affects the lungs, liver, or blood-forming system. Damage to these organs can be life-threatening. Lung involvement, characterized by swelling of the small airways (bronchioles) and blood vessels, can cause stiffening of the lung tissue, breathing difficulties, and increased susceptibility to infections. When LCH affects the blood-forming system, it can crowd out blood-forming cells in the bone marrow, leading to a reduction in all types of blood cells (pancytopenia). This results in fatigue (anemia), frequent infections (neutropenia), and clotting problems (thrombocytopenia).

Other symptoms of LCH vary depending on the affected organs and tissues. These may include swollen lymph nodes, abdominal pain, jaundice (yellowing of the skin and eyes), delayed puberty, protruding eyes, dizziness, irritability, and seizures. Neurological deterioration (neurodegeneration) occurs in approximately 1 in 50 affected individuals.

LCH is often diagnosed in childhood, typically between the ages of 2 and 3, but can occur at any age. Adult-onset LCH is frequently linked to smoking; in about two-thirds of adult cases, the disorder is limited to the lungs.

The severity and symptoms of LCH differ significantly from person to person. Previously, different presentations of LCH were considered distinct diseases, including eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.

In many cases, LCH resolves with appropriate treatment, or even spontaneously, particularly when confined to the skin. However, some complications, such as diabetes insipidus or permanent organ damage, may persist.

Inheritance:

LCH is generally not inherited and usually occurs in individuals with no family history of the condition. While some families with multiple cases have been identified, the inheritance pattern is currently unknown.