Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach.

BACKGROUND: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients. OBJECTIVE: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases. METHODS: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease. RESULTS: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL. CONCLUSION: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged.

An oral supplementation based on myo-inositol, folic acid and liposomal magnesium may act synergistically with antibiotic therapy and can improve metabolic profile in patients affected by Hidradenitis suppurativa: our experience.

BACKGROUND: Over recent years, the link between obesity, metabolic syndrome and Hidradenitis suppurativa (HS) has been explored. It has been demonstrated that HS patients have a high prevalence of the metabolic syndrome and an increased frequency of insulin resistance. The objective of our study is to estimate the effectiveness of an oral supplementation based on myo-inositol (MI), folic acid and liposomal magnesium (Levigon®, Sanitpharma; Milan, Italy) on the clinical and metabolic profile of patients affected by HS. METHODS: Twenty subjects with HS and an impaired glucose metabolism were enrolled. Group A: 10 subjects received for 6 months MI 2000 mg, liposomal magnesium and folic acid associated to topical antibiotic therapy (clindamycin gel 1%), systemic antibiotic therapy (clindamycin 300 mg b.i.d. and rifampicin 600 mg daily for 6 weeks) and a normocaloric diet group B: 10 subjects received topical and systemic antibiotic therapy associated to a normocaloric diet for 6 months. RESULTS: After 6 months group A patients showed an average reduction of Sartorius Score from 38.3±7.75 to 27.3±13.53 (P value <0.04) while in the control group there was a reduction of the Sartorius from 38.4±7.88 to 31.1±8.02 (P value =0.55). Moreover in group A Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly reduced from 2.43±0.35 to 2.1±0.31 (P<0.01) whereas in group B HOMA-IR did not significantly decrease (2.51±0.65 at T0 at 2.40±0.67 at T1). CONCLUSIONS: Our study underlines the importance of the evaluation of metabolic profile in patients with HS. Moreover, it suggests that the supplementation of MI, folic acid and liposomal magnesium in HS can improve the efficacy of concomitant therapies and the metabolic profile.