The active agent ciclosporin, which is approved for treatment of severely pronounced neurodermitis, may also be used for severe, atopic hand eczema. Other substances that suppress the immune system have also shown effectiveness in some cases. However, these substances are not approved for hand eczema. In the last couple of years an internal medicine has been approved for the first time for the treatment of chronic hand eczema. This involves a derivative of vitamin A, called alitretinoin, which is also naturally present in the human body. Alitretinoin can be used to treat all forms of severe chronic hand eczema which have not reacted to external cortisone preparations. The effectiveness of this form of treatment has been tested extensively in clinical study programs and proven prior to its approval. The trial results showed that two thirds of patients did not have a recurrence 6 months after application of the medication, and that re-treatment is effective if hand eczema reoccurs. The duration of alitretinoin treatment is 3 to 6 months. During treatment and one month prior to beginning and one month after completion, women of childbearing-age must use contraceptives and also test for pregnancy each month since, as with all derivatives of vitamin A, the substance involved is teratogenic. Side effects mainly include temporary headaches during the initial days of treatment, as well as a possible increase in blood fat and cholesterol values. Regular laboratory tests of blood values are recommended to monitor this.
Mutations were mainly found in exons 12-22 of the intracellular TKD, including 10 missense mutations that have a single nucleotide deletion and a single codon deletion that consists of a triplet of nucleotides that have been removed causing a whole amino acid to not be coded. Additionally, three splice site mutations were identified that caused an in-frame deletion of an exon, an expressed nucleotide sequence, leading to the removal of more than 40 amino acids in the TKD.This determination has based upon genetic studies of 14 HDLS families confirming mutations in this gene. The CSF1 receptor protein primarily functions in regulation, survival, proliferation, and differentiation of microglial cells. The mechanism of microglial dysfunction due to mutations in CSF1R to the myelin loss and axonal spheroid formation remains unknown. Further research is needed to better understand disease pathogenesis. Pathology
In HDLS, there is enlargement of the lateral ventricles and marked thinning or weakening of cerebral white matter. The loss of white matter is caused by myelin loss. These changes are associated with diffuse gliosis, moderate loss of axons and many axonal spheroids.Activated or ameboid microglia and macrophages that contain myelin debris, lipid droplets and brown autofluorescent pigment granules are found in the areas with demyelination and axonal spheroids. In severely degenerated areas there are many large, reactive astrocytes filled with glial fibrils.In autopsy cases, it has been shown that white matter abnormalities are relatively confined to the cerebrum while avoiding the cerebellum and many of the major fiber tracts of the nervous system.