Efficacy of oral zinc and nicotinamide as maintenance therapy for mild/moderate hidradenitis suppurativa: A controlled retrospective clinical study

To the Editor: Hidradenitis suppurativa (HS) is a chronic cutaneous disease that involves follicular occlusion in the apocrine gland-bearing regions. Treatment is a challenge because of the paucity of effective therapies and frequent exacerbations, with a negative impact on quality of life.1Offidani A. Molinelli E. Sechi A. et al.Hidradenitis suppurativa in a prepubertal case series: a call for specific guidelines.J Eur Acad Dermatol Venereol. 2019; 33: 28-31Crossref PubMed Scopus (19) Google Scholar Brocard et al2Brocard A. Knol A.C. Khammari A. Dréno B. Hidradenitis suppurativa and zinc: a new therapeutic approach. A pilot study.Dermatology. 2007; 214: 325-327Crossref PubMed Scopus (101) Google Scholar first described zinc gluconate (90 mg daily for 4 months) as an effective therapeutic alternative for the management of HS. In our study, the efficacy of oral zinc and nicotinamide as maintenance treatment in mild to moderate HS was investigated retrospectively. A total of 92 patients affected by Hurley stage I and II HS were evaluated (Table I). All included patients had previously been treated with oral tetracycline (minocycline 100 mg daily) for 12 weeks with clinical and ultrasonographic benefit. The patients were divided into 2 groups according to treatment received or not received at the end of systemic antibiotic course. Specifically, 47 patients started oral therapy with capsules containing 90 mg of zinc gluconate and 30 mg of nicotinamide once daily for 90 days. The treated group was compared with a control group of 45 patients who did not receive any treatment. Each participant was evaluated at baseline and at 90 and 180 days after treatment. At 12 and 24 weeks, we observed a significant reduction in the number and mean duration of acute flares in the treated versus control groups. Patients of the treated group correspondingly reported a marked reduction in mean Visual Analogue Scale, Dermatology Life Quality Index, and International HS Severity Score System scores compared with the control group both at 12 and 24 weeks (P < .005). Disease-free survival was significantly longer in the treated group, and it showed sustained improvement even after discontinuation of oral supplementation. Slightly decreased or stable International HS Severity Score System score and pain Visual Analogue Score during the maintenance treatment was collaterally observed in the treated group with no statistically significant difference at 24 weeks (Table II). Two patients reported nausea; neither stopped the treatment. The use of oral zinc as a helpful treatment in HS (as monotherapy or in association with topical therapy) has been rarely described in the literature.1Offidani A. Molinelli E. Sechi A. et al.Hidradenitis suppurativa in a prepubertal case series: a call for specific guidelines.J Eur Acad Dermatol Venereol. 2019; 33: 28-31Crossref PubMed Scopus (19) Google Scholar, 2Brocard A. Knol A.C. Khammari A. Dréno B. Hidradenitis suppurativa and zinc: a new therapeutic approach. A pilot study.Dermatology. 2007; 214: 325-327Crossref PubMed Scopus (101) Google Scholar, 3Hendricks A.J. Hirt P.A. Sekhon S. et al.Non-pharmacologic approaches for hidradenitis suppurativa - a systematic review.J Dermatolog Treat. 2019; 4: 1-8Google Scholar, 4Hessam S. Sand M. Meier N.M. Gambichler T. Scholl L. Bechara F.G. Combination of oral zinc gluconate and topical triclosan: an anti-inflammatory treatment modality for initial hidradenitis suppurativa.J Dermatol Sci. 2016; 84: 197-202Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar However, to our knowledge, no studies have investigated its usefulness as a maintenance treatment to potentiate the beneficial effects obtained with other agents, such as antibiotics, that are frequently used in HS. The efficacy of zinc could be related to its anti-inflammatory activity, inhibiting the chemotaxis of neutrophils, activating natural killer cells and the phagocytic function of granulocytes, and modulating the production of tumor necrosis factor α, interleukin 6, and metalloproteinases.2Brocard A. Knol A.C. Khammari A. Dréno B. Hidradenitis suppurativa and zinc: a new therapeutic approach. A pilot study.Dermatology. 2007; 214: 325-327Crossref PubMed Scopus (101) Google Scholar,4Hessam S. Sand M. Meier N.M. Gambichler T. Scholl L. Bechara F.G. Combination of oral zinc gluconate and topical triclosan: an anti-inflammatory treatment modality for initial hidradenitis suppurativa.J Dermatol Sci. 2016; 84: 197-202Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Additionally, it seems to have an antiandrogen activity, modulating 5α-reductase type I and II expression levels and activity.2Brocard A. Knol A.C. Khammari A. Dréno B. Hidradenitis suppurativa and zinc: a new therapeutic approach. A pilot study.Dermatology. 2007; 214: 325-327Crossref PubMed Scopus (101) Google Scholar Nicotinamide, as zinc, has anti-inflammatory and antioxidant activity by inducing the expression of the enzyme zinc/copper superoxide dismutase and reducing the accumulation of free radicals.2Brocard A. Knol A.C. Khammari A. Dréno B. Hidradenitis suppurativa and zinc: a new therapeutic approach. A pilot study.Dermatology. 2007; 214: 325-327Crossref PubMed Scopus (101) Google Scholar,5Dhaliwal S. Nguyen M. Vaughn A.R. Notay M. Chambers C.J. Sivamani R.K. Effects of zinc supplementation on inflammatory skin diseases: a systematic review of the clinical evidence.Am J Clin Dermatol. 2020; 21: 21-39Crossref PubMed Scopus (14) Google Scholar The main limitations of the study are the retrospective nature, with absence of a randomized, blinded control group. This study seems to suggest that zinc and nicotinamide supplementation in patients who have previously been treated with tetracyclines (minocycline) may be a valuable and a well-tolerated maintenance approach for mild to moderate HS, extending the disease-free survival and reducing the rate and duration of flares.Table ICharacteristic of patients (treated group and control group)FactorsTreated GroupControl GroupSex, n (%) Female36 (76.6)33 (73.3) Male11 (23.4)12 (26.7)Average age, y, mean ± SD31.6 ± 4.734.82 ± 5.9Average BMI, kg/m2, mean ± SD28.6 ± 5.927.7 ± 7.3Smokers, n (%)18 (38.3)20 (44.4)Age of onset, y, mean ± SD21.5 ± 8.219.2 ± 10.7Disease duration, y, mean ± SD5.1 ± 5.96.7 ± 6.1Family history, n (%)10 (21.3)15 (33.3)Comorbidities, n (%) Acne10 (21.3)14 (31.1) Psoriasis1 (2.1.3)0 Pilonidal cyst5 (10.6)7 (15.5) Hashimoto disease1 (2.1)1 (2.2) PCOS5 (10.6)3 (6.6) Neurologic/psychiatric disorders (epilepsy, schizophrenia)1 (2.1)1 (2.2) Arterial hypertension1 (2.1)1 (2.2) Diabetes02 (4.4) Systemic lupus erythematosus01 (2.2) Rheumatoid arthritis10No comorbidities, n (%)20 (42.5)22 (48.9)Hurley stage, n (%) I25 (53.2)23 (51.1) II22 (46.8)22 (48.9)IHS4, n (%) Mild21 (44.7)23 (51.1) Moderate26 (55.3)22 (48.9)SOS-HS, n (%) I10 (21.3)10 (22.2) II37 (78.7)35 (77.8)BMI, Body mass index; IHS4, International Hidradenitis Suppurativa Severity Score System; PCOS, polycystic ovary syndrome; SD, standard deviation; SOS-HS, Sonographic Scoring of Hidradenitis Suppurativa. Open table in a new tab Table IIPatient disease characteristics at baseline and at weeks 12 and 24 (treated and control groups)HS score and acute flareTreated group, mean ± SDControl group, mean ± SDP valueP valueT0T12T24T0T12T24Treated versus control group T12Treated versus control group T24IHS45.1 ± 2.84.0 ± 1.74.7 ± 2.14.8 ± 2.76.2 ± 3.27.8 ± 2.2.004∗The t test for continuous variables was used to assess statistical significance, with a P value < .005..003∗The t test for continuous variables was used to assess statistical significance, with a P value < .005.Pain VAS2.3 ± 2.32.0 ± 2.12.4 ± 1.92.4 ± 3.36.5 ± 3.110.5 ± 5.1.003∗The t test for continuous variables was used to assess statistical significance, with a P value < .005..002∗The t test for continuous variables was used to assess statistical significance, with a P value < .005.DLQI6.2 ± 7.62.9 ± 5.43.5 ± 5.05.2 ± 6.97.5 ± 7.110.6 ± 8.7.002∗The t test for continuous variables was used to assess statistical significance, with a P value < .005..001∗The t test for continuous variables was used to assess statistical significance, with a P value < .005.Number of acute flares—2.2 ± 2.13.9 ± 3.5—6.5 ± 3.28.9 ± 3.4.003∗The t test for continuous variables was used to assess statistical significance, with a P value < .005..002∗The t test for continuous variables was used to assess statistical significance, with a P value < .005.Duration of acute flare, days—3.8 ± 2.94.9 ± 4.5—5.6 ± 3.78.9 ± 3.6.003∗The t test for continuous variables was used to assess statistical significance, with a P value < .005..001∗The t test for continuous variables was used to assess statistical significance, with a P value < .005.Disease-free survival, weeks—20.4 ± 3.2—5.4 ± 2.1.001∗The t test for continuous variables was used to assess statistical significance, with a P value < .005.DLQI, Dermatology Life Quality Index; IHS4, International Hidradenitis Suppurativa Severity Score System; SD, standard deviation; T0, baseline; T12, week 12; T24, week 24; VAS, Visual Analogue Scale.∗ The t test for continuous variables was used to assess statistical significance, with a P value < .005. Open table in a new tab BMI, Body mass index; IHS4, International Hidradenitis Suppurativa Severity Score System; PCOS, polycystic ovary syndrome; SD, standard deviation; SOS-HS, Sonographic Scoring of Hidradenitis Suppurativa. DLQI, Dermatology Life Quality Index; IHS4, International Hidradenitis Suppurativa Severity Score System; SD, standard deviation; T0, baseline; T12, week 12; T24, week 24; VAS, Visual Analogue Scale.