Efficacy of magnesium chloride in the treatment of H ailey– H ailey disease: from serendipity to evidence of its effect on intracellular C a 2+ homeostasis

Background Hailey–Hailey disease ( HHD ), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited intraepidermal blistering genodermatosis. Mutations in the ATP 2 C 1 gene encoding for the G olgi secretory pathway C a 2+ / M n 2+ ‐ ATP asi protein 1 ( SPCA 1) affect the processing of desmosomal components and the epidermal suprabasal cell–cell adhesion by deregulating the keratinocyte cytosolic C a 2+ concentration. We report the unexpected, dramatic, and persistent clinical improvement of the skin lesions of a patient affected with longstanding HHD with daily intake of a solution containing magnesium chloride hexahydrate ( M g C l 2 ). Materials and methods We investigated the effect of M g C l 2 on the intracellular C a 2+ homeostasis and on the activity of particular C a 2+ ‐effectors in H e L a cells transfected with chimeric aequorins (cyt AEQ , mt AEQ , er AEQ and G o AEQ ) targeted to different subcellular compartments (cytosol, mitochondria, endoplasmic reticulum, and G olgi, respectively). Results Experimental investigations on H e L a cells showed the effect of M g C l 2 on the function of C a 2+ ‐extrusor systems, resulting in increased cytosolic and mitochondrial C a 2+ levels, without altering the mechanisms of intraluminal C a 2+ ‐filling and C a 2+ ‐release of stores. Conclusions Based on our clinical observation and experimental results, it can be hypothesized that M g C l 2 could act as an inhibitor of the C a 2+ ‐extruding activity in keratinocytes favoring intracellular C a 2+ ‐disponibility and C a 2+ ‐dependent mechanisms in desmosome assembly. This may represent the molecular basis of the good response of the HHD clinical features with M g C l 2 solution in the patient described.