We describe a rare case of a patient with severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome with a novel mutation in DSG1 with histology showing a psoriasiform pattern. The article underscores the importance of genetic testing for conclusive diagnosis. Treatment challenges, including unresponsiveness to acitretin and subsequent use of ciclosporin, highlight the need for a multidisciplinary approach in managing SAM syndrome.