Coexistence of acne inversa with psoriasis and Dowling-Degos disease harboring impaired PSENEN-Notch signaling

To the Editor:Acne inversa(AI),also known as hidradenitis suppurativa,is a chronic recurrent inflammatory skin disease characterized by deep painful nodules and abscesses with resultant scarring mainly distributed in intertriginous areas.Loss-of-function mutations in g-secretase(GS)genes are responsible for familial AI.[1]GS is a transmembrane protease composed of four essential protein subunits:one catalytic presenilin subunit(PSEN)and three cofactor subunits(nicastrin[NCSTN],presenilin enhancer 2[PSENEN],anterior pharynx defective 1).GS is involved in cleavage of various type I membrane proteins,including amyloid precursor protein and Notch proteins.PSENEN directly binds to PSEN and is required for its autocatalytic cleavage and protease activity.To date,six mutations have been reported in PSENEN,all of which result in frameshift truncations and altered protein products,predominantly leading to haploinsufficiency.[2]Psoriasis is a genetically-determined proliferative and inflammatory entity,resulting from complex interactions between aberrant keratinocyte proliferation and differentiation,and a T-lymphocytemediated immune process.Dowling-Degos disease(DDD),a rare autosomal dominant disorder,is characterized by progressive reticulate hyperpigmentation and small darkbrown hyperkeratotic papules,mainly affecting flexural areas.[3]Herein,we report a proband and three other members of a three-generation Chinese Han AI family with co-occurrence of psoriasis and DDD,respectively.