What Causes LCH?

LCH is caused by mutations in a cell signaling pathway known as the MAPKinase pathway. Key genes mutated in this pathway include BRAF (65-70%), MAP2K (20%), and other rarer genes, all of which lead to abnormal activation of a gene known as ERK. These mutations are “genetic accidents” which occur during DNA copying in dendritic cells and are not inherited. The maturation stage of the dendritic cell will determine what type of disease a patient will develop. If the mutation occurs when the dendritic cell is still in stem cell stage, this early precursor may go to any organ in the body-especially liver, spleen and bone marrow. Mutation in a more mature dendritic cell will lead to LCH in a variety of organs, but not the “high risk” ones mentioned before. An even more mature dendritic cell carrying this mutation may go to only skin and bone.

BRAF is the most common mutation in a cell. The mutation actually causes the cells to keep producing even though there is nothing telling it to turn on. There are receptors that usually tell the cells to multiply and when there's a mutation like the BRAF mutation it (the switch) is stuck on the "on" position. That's why the lesions develop.

They don't know why they develop in the places they do and they don't know why some form lesions and others eat away at things like bones or even white matter in the cerebellum. There is another theory that the faulty genes can cause the cells to multiply in an immune response, such as to infection. They rush in to try and protect the area but instead these immature defective cells cause more harm and damage that particular system. So with Dylan, for example, it is suspected that a chest infection and swollen lymph node he had early 2015 triggered his immune system to respond and sent these defective cells to his respiratory tract and lungs.

The same theory goes for adults that smoke. If they have one of the faulty genes then in theory the body sends these langerhans cells in to protect the lungs from the chemicals etc in cigarettes but of course they do more damage. Doctors do not think smoking itself actually causes LCH, it is the immune system's response that can cause it.

So in theory anything can trigger these rogue cells. There is no 'remission' for LCH only 'active' or 'non active' disease and it can reactivate at any point. Doctors are still trying to combat 'relapse' or reactivation rates by increasing the length patients receive Chemotherapy or by trialling new inhibitor drugs for those with particular gene mutations that haven't responded to Chemotherapy.

So when the question is asked.. is LCH cancer? The answer is vague. It is now classed as Cancer officially even if it it not fully recognised as one. It is an autoimmune disease at its baseline, that acts cancerous. So both, in the words of Gregory House (House M.D. episode 'Merry Little Christmas')..

"Also known as 'you got your Cancer in my Autoimmune' disease.."