Refractory acne and 21-hydroxylase deficiency in a selected group of female patients

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.

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.

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.

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).

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.