Development or exacerbation of hidradenitis suppurativa in two transgender men after initiation of testosterone therapy

Abstract

single-nucleotide polymorphism (c.2268G>A) according to sequenced mRNA, whereas Sanger sequencing of the patient's blood detected the single-nucleotide polymorphism in a heterozygous form. The allele carrying the missense mutation is successfully transcribed into mRNA, but no protein is detected in the epidermis or keratinocytes. We assume protein degradation due to potential conformational change of the protein, resulting in protein instability and/or failure of protein-protein interaction. For now, this remains unresolved.AP1B1 encodes the large b-subunit of the adaptor protein (AP)1 complexes, which play an important role in polarized vesicular transport in eukaryotic cells. AP1 is involved in the formation of clathrin-associated vesicles and the selection of cargo proteins in the trans-Golgi network and/or endosomes for basolateral transport. 5,6 The pathophysiological causes of KIDAR have not yet been clarified, but previous studies have indicated that cell-polarity defects may cause at least deafness and hyperproliferation, 2,7 whereas epidermal consequences remain to be investigated.In summary, we demonstrate that compound heterozygous mutations in AP1B1 can induce complete loss of protein in human epidermis and may cause the symptoms described in our index patient. In addition to expanding the extremely short list of diagnosed AP1B1-deficient patients and specification of the main clinical features of this new syndrome, we describe the molecular consequences of AP1B1 mutations at the mRNA and protein levels.

The Role of Hormones in Hidradenitis Suppurativa: A Systematic Review

“…Mortimer et al discovered early on that female HS patients have an elevated testosterone and free androgen index [ 17 ]. There are three cases reported where cross-sex hormone therapy (CSHT) with testosterone resulted in an exacerbation or manifestation of HS [ 18 , 19 ]. In contrast to the above results, Harrison reports that there is no difference in testosterone between HS and healthy controls [ 20 ].…”

“…However, this connection has not yet been proven. A subdivision between hormone-dependent and hormone-dependent HS could be interesting in the future to provide further information, as well as that cross-sex hormone therapy worsens HS, showing that androgens should be considered in HS pathogenesis [ 18 , 19 ].…”

Unraveling the Role of Sex Hormones on Keratinocyte Functions in Human Inflammatory Skin Diseases

“…Further confirming the importance of hormones in the pathogenesis of HS, Buonomo et al observed the development or exacerbations of clinical manifestations in two transgender men following the administration of testosterone therapy [ 58 ].…”

Sex-biased immunological processes drive hidradenitis suppurativa

“…Numerous studies have also associated HS with acne, hirsutism, and polycystic ovarian syndrome, supporting a role for androgens on disease ( 21 ). Furthermore, recent case reports have described new-onset and exacerbation of HS symptoms in gender dysphoric patients undergoing supplemental testosterone therapy ( 22 ). Higher proportions of androgen receptor–positive keratinocytes are found in HS lesional skin relative to healthy skin, and microarray studies indicate enrichment of androgen receptor–regulated genes in HS lesional skin ( 23 ).…”