Abstract: A topical composition including erlotinib and a pharmaceutically acceptable excipient for use in the treatment of a keratoderma in a child, preferably a palmoplantar keratoderma (PPK), wherein the composition is topically administered. The composition may further include a penetration enhancer. The treated subject may be younger than three years old. Also, woven or non-woven fabric support including erlotinib and to dressings, patches, gloves and socks having the support useful in the treatment of a PPK.

Abstract: The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

Abstract: An increasing body of evidence suggests that Nav1.7 encoded by SCN9A gene may play a key role in various pain states, including acute, inflammatory and/or neuropathic pain. The inventors now report an efficient treatment for severe cases of primary erythromelagia linked to a specific SCN9A mutation. In particular the inventors demonstrated that the inhibition of JAK2 produces a rightward shift in the voltage dependent activation of mutant Nav1.7 channels, thereby normalizing the function of mutant Nav1.7 channels. On this basis, the inventors treated a patient suffering from PE with very severe refractory pain with a JAK2 inhibitor (ruxolitinib) and showed the therapy leads to considerable reduction of pain. Accordingly, the present invention relates to the use of JAK inhibitors for the treatment of painful conditions involving Nav1.7 channels.

Abstract: Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques. The inventors obtained remarkable results with a treatment with a EGFR inhibitor (e.g. erlotinib) in 3 patients with Olmsted Syndrome and erythemalgia linked to different TRPV3 mutations. In less than 3 months, the drug induced a complete disappearance of the hyperkeratosis and the pain. Anorexia and insomnia disappeared with an improvement of the growth. Accordingly, the present invention relates to the use of EGFR inhibitors for the keratodermas.

Abstract: The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

Abstract: The present invention relates to methods and pharmaceutical composition for the treatment of inflammatory skin diseases associated with desmoglein-1 deficiency. The inventors show, for the first time, that the structural protein DSG1 directly acts as a novel and unexpected inhibitor of epithelial inflammation via the inhibition of NF-?B signaling pathway. In particular, the present invention relates to a method of treating an inflammatory skin disease associated with desmoglein-1 deficiency in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an agent capable of restoring the expression of desmogelin-1. Particularly, the inventors carried out the whole exome sequencing, histopathological, electron microscopy, immunofluorescence and immunological analyses in two unrelated patients presenting with SAMEC syndrome.