Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a 
recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and 
desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report 
on a 2-year-old girl presenting with pustular lakes within areas of erythema and 
large accumulations of intraepidermal neutrophils, which initially led to our 
misdiagnosis of generalized pustular psoriasis. No mutation was found in either 
the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations 
of erythroderma with severe itching, hypotrichosis, enamel defects, 
onychodystrophy, palmoplantar keratoderma and the crucial result of de novo 
missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by 
next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The 
eruptions significantly improved after a 4-week treatment with oral acitretin 
and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 
4 months, relieving her skin pruritus and suggesting that early treatment with 
pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may 
even inhibit multiple allergies induced by skin barrier injury. In this work we 
also review the clinical features, differential diagnoses and pathological 
manifestations of SAM-DSP syndrome.