Refractory Acne and 21-Hydroxylase Deficiency in a Selected Group of Female Patients

Abstract

Background: Excessive androgen production, suspected in women when acne is accompanied by hirsutism and menstrual irregularities, may be due to congenital adrenal hyperplasia. This inherited disorder of cortisol biosynthesis is caused in more than 90–95% of all cases by 21-hydroxylase deficiency (21-OHD). The steroid 21-hydroxylase gene (CYP21) has a high degree of variability. Objective: This study was conducted to evaluate CYP21 gene mutations in a selected group of women with papulopustular and comedonal acne refractory to treatment, irregular menses and hirsutism. Methods: 30 out of 61 women enrolled underwent pelvic ultrasound examination and hormonal screening. In 9 patients with a polycystic ovary and hormonal pattern of adrenal hyperandrogenism a significant elevation of adrenocorticotropic hormone (ACTH) stimulated 17-hydroxyprogesterone was detected. These women positive in the ACTH stimulation test were submitted to CYP21 gene analysis. Results: Genetic testing revealed several different point mutations and demonstrated that a cohort of patients resistant to acne therapy can be carriers or affected by non-classical 21-OHD (late onset). Conclusion: Persistent acne can be the unique presenting sign of non-classical 21-OHD. Evaluation of CYP21 gene mutations may identify female carriers or patients for genetic counselling.

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

“…A further 242 SNPs with a P discovery o1.3 Â 10 À 3 were selected as either proxies for the lead SNPs or located in close proximity to genes highly expressed in skin (SDC1 and TYRP1), published candidate genes (CYP21A2 (ref. 44) or other putative roles in tissue remodelling (FGF2 and FGF22) or the immune response (IL1R1/2, IL1RL1/2, IL18R1, ICAM4 and CFB). We preferentially selected genotyped over imputed SNPs and SNPs with a minor allele frequency of 40.02, including manual inspection of cluster plots of genotyped SNPs.…”

Acne‐associated syndromes: models for better understanding of acne pathogenesis

“…NCAH was found in 2.2% of Spanish women with hirsutism, irregular menses, acne or androgenic alopecia 22 . A recent study of 30 adult female patients with refractory acne, hirsutism and menstrual irregularities, showed in nine patients the presence of PCO and NCAH confirmed by CYP21 genotyping 18 . CAH was found in 0.6% and NCAH in 1.6% of 408 patients presenting with clinical signs of androgen excess, including acne 23 .…”

“…NCAH is also associated with hyperandrogenic symptoms such as acne, hirsutism, androgenetic alopecia or seborrhoea 15,16 . Severe cystic acne refractory to oral antibiotics and isotretinoin has been associated with NCAH 17–19 . Some women with NCAH present with PCOS 20 .…”

Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome

“…It has been estimated that around a quarter of NCAH women have PCO on ultrasound [19], and it should be noted that the clinical presentation of PCOS and NCAH can be identical [18,19]; thus, in order to diagnose PCOS, it is a prerequisite that the latter has been excluded [20]. An overrepresentation of both undiagnosed patients with NCAH and female carriers (i.e., patients with only one CYP21A2 allele mutated) has been seen in clinics treating severe acne [21][22][23]. Some individuals are not diagnosed with NCAH until a very old age due to mild symptoms [24].…”