Vitamin D

There is evidence to suggest a relationship between vitamin D and the pathogenesis of HS. While the exact role vitamin D plays in HS is unknown, it appears to modulate immune function systemically within the folliculo-pilosebaceous subunit. Vitamin D supplementation increases the synthesis of antimicrobial peptides, which subsequently may reduce secondary infections and skin inflammation.

Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-10, IL-17, and IL-18 are elevated in lesional and non-lesional skin of HS patients. Vitamin D and its metabolites can promote anti-inflammatory activity through inhibition of IL-1, IL-17, TNF-α, or other proinflammatory pathways, such as the nuclear factor-κB (NF-κB) pathway. In-vitro studies have shown that vitamin D can reduce cytokine production and downregulate antigen presentation. Additionally, vitamin D has demonstrated some potential benefit in wound healing for patients with diabetic foot ulcers.

HS patients have abnormal hair growth cycles as well as keratinocyte proliferation and differentiation. Vitamin D receptors play a significant role in epidermal homeostasis; activation of vitamin D receptors regulates keratinocyte proliferation and differentiation. In HS, supplementation with vitamin D may help control and normalize keratinocyte proliferation and differentiation to reduce follicular obstruction.

Two previous studies have established a potential relationship between vitamin D deficiency and patients with HS. Serum levels of 25-hydroxyvitamin D were tested in patients with HS; the majority had insufficient (< 50 nmol/L) levels, while over a third of HS patients in one study were severely deficient (< 10 nmol/L). Serum vitamin D deficiency correlated with disease severity based on Hurley stage. Patients with insufficient vitamin D levels who received supplementation according to their level of deficit had a significant decrease in the number of HS nodules at six months. These findings suggest that vitamin D may have a role in immune modulation and inhibiting keratinocyte proliferation.

The North American HS clinical management guidelines report that there is insufficient evidence to support routine use of vitamin D, so the inclusion of vitamin D supplementation is a grade C recommendation, which indicates recommendation based on opinion, consensus, case series, or disease-oriented evidence. Supplementation should be done with caution as excess vitamin D can lead to hypercalcemia and hypercalciuria.

Vitamin B ₁₂ (Cobalamin)

Vitamin B ₁₂ , also known as cobalamin, is generally safe, inexpensive, accessible, and has been shown to contribute to improvement in other dermatologic conditions. Some patients are thought to have reduced S-adenosyl-L-methionine due to impairment of the vitamin B ₁₂ -dependent enzyme, methionine synthetase. S-adenosyl-L-methionine has been shown to reduce serum TNF-α levels in mouse models. Therefore, patients with reduced S-adenosyl-L-methionine may have higher TNF-α levels contributing to HS pathogenesis. Cobalamin deficiency has also been associated with increased TNF-α expression. Supplementation with vitamin B ₁₂ therefore may help to overcome impaired methionine synthetase activity and to reduce TNF-α levels.

Three patients with HS and concomitant inflammatory bowel disease who were given high dose vitamin B ₁₂ (1000 micrograms for six weeks and then monthly thereafter) experienced reduction in the eruption of new lesions. Vitamin B ₁₂ has a low potential for toxicity but has been implicated in the development of acne in certain individuals. Future investigations are warranted to better understand the role of vitamin B ₁₂ as a potential adjuvant therapy for HS.

Zinc

Zinc is essential for cellular processes such as cell proliferation, differentiation, and apoptosis. As a result, zinc plays a role in the modulation of both the innate and adaptive immune functions. There is evidence to suggest that zinc deficiency can decrease natural killer (NK) cell activity, including cell signaling and recognition. Zinc also inhibits granulocyte chemotaxis, keratinocyte activation, and production of damaging free radicals and proinflammatory cytokines. Both IL-17 producing cells and neutrophils are implicated in the pathogenesis of HS; zinc suppresses the development of IL-17 producing cells, which consequentially reduces the neutrophil count .

Toll-like receptors (TLRs) lead to inflammatory cytokines production. Enhanced TLR2 expression by infiltrating macrophages and dendritic cells in HS lesions is thought to contribute to the disease pathogenesis. Zinc exhibits anti-inflammatory effects by downregulating TLR response and inhibiting keratinocyte expression of TLRs.

A potential relationship between HS and zinc deficiency has been demonstrated by patients who developed new-onset HS or had worsening HS following bariatric surgery and weight loss. After bariatric surgery, these patients were found to exhibit several nutritional deficiencies, including zinc deficiency. Patients who developed HS or had worsening HS following bariatric surgery had significantly lower serum zinc levels than typical HS patients.

The efficacy of zinc supplementation in HS patients has been evaluated in open label studies. The most commonly studied zinc formulation is zinc gluconate; zinc picolinate has better absorption but is more expensive. HS patients with Hurley stage I and II who were treated with 90mg of zinc gluconate daily in conjunction with topical triclosan experienced improvement in their HS disease and quality of life, as measured by the modified HS score and Dermatology Life Quality Index (DLQI), respectively. Patients who initially achieved remission experienced exacerbation when their zinc dosage was reduced to 30 to 60 mg/day, indicating the potential suppressive rather than curative nature of zinc treatment. Oral zinc gluconate in combination with nicotinamide for maintenance therapy has also demonstrated a significant reduction in the number and duration of acute flares as well as extended disease-free survival. Based on insufficient evidence to support routine use, the North American clinical management guidelines for HS lists zinc with a grade C recommendation, indicating support of use based on opinion, consensus, case series, or disease-oriented evidence.

Common side effects of zinc supplementation include nausea, vomiting, and loss of appetite; these can be mitigated by adhering to the recommended dose. Zinc can also affect the intestinal absorption of copper at the mucosal level by stimulating the production of metallothionein, a metal-binding protein which sequesters copper. Therefore, it is recommended that patients who chronically receive high dose zinc supplementation also take copper to avoid copper deficiency. The typical ratio for co-administration of zinc:copper is 10:1. Even with copper co-supplementation, patients should be monitored for signs and symptoms of copper deficiency, which include hair loss, diarrhea, eye and skin sores, loss of appetite, hypochromic microcytic anemia, and neutropenia.

Cannabinoids

Cannabinoids have drawn increasing public attention with expanding legalization and accessibility. Cannabinoids are a group of compounds that are biologically and structurally similar to the chemical compounds of Cannabis sativa . There are three classes of cannabinoids: plant-derived cannabinoids (phytocannabinoids), endogenous cannabinoids (endocannabinoids), and synthetic cannabinoids. Phytocannabinoids are plant-derived cannabinoids that are historically derived from cannabis sativa. The most notable phytocannabinoids are Δ -tetrahydrocannabinol (THC), which can have psychotropic effects, and cannabidiols (CBD), which are mostly non-psychotropic. Endocannabinoids are endogenous lipids that function as ligands for cannabinoid receptors. Synthetic cannabinoids are developed in laboratories and mimic phytocannabinoids and endocannabinoids.

The effects of cannabinoids are mediated by cannabinoid receptors CB1 and CB2. CB1 is responsible for the psychoactive effects through the release of various neurotransmitters, while CB2 is presumed to mediate immunomodulation and the anti-inflammatory effects of cannabinoids. Generally, oral cannabinoids have been shown to target systemic symptoms such as anorexia, nausea, and pain, whereas topically applied cannabinoids often target localized pain and inflammation.

The pathogenesis of HS includes a complex relationship between pilosebaceous unit occlusion due to keratinocyte proliferation, sebaceous gland disruption, and an overlapping, autoinflammatory response. Cannabinoids have been shown to inhibit keratinocyte proliferation in vitro CBD, and other phytocannabinoids have also been shown to inhibit a number of inflammatory pathways, including the NF-κB pathway.

Anandamide is a CB1 agonist that interacts with vanilloid receptors to transduce and regulate nociceptive signals (including pain and itch) to the peripheral nervous system. Phytocannabinoids and cannabinoid agonists have demonstrated clinical improvements for patients with pain associated with chronic medical conditions. CB1 and CB2 agonists have been shown to reduce itch for patients with lichen simplex chronicus, uremic pruritus, atopic dermatitis (AD), and prurigo nodularis. In a study of acne patients, application of topical cannabis seed extract cream resulted in significant decreases in skin sebum and erythema. Cannabinoids may have an analgesic effect in HS due to inhibition of the release of calcitonin gene-related peptide, which is stored in sensory neurons and involved in the transmission of pain.

Despite the growing interest in the therapeutic applications of cannabinoids, there remains a lack of high quality randomized controlled trials that evaluate their effects in dermatology. In a recent HS CAM survey, marijuana and topical CBD oil were both among the more commonly used CAM methods by respondents. Most users reported them as helpful, with 57% reporting marijuana as helpful and 45% reporting topical CBD oil as helpful. Systemic toxicity can occur as a result of overstimulation of the endocannabinoid system from exogenous cannabinoid use through ingestion or inhalation. Notable side effects of cannabinoid systemic toxicity include tachycardia (acute), bradycardia (chronic), decreased systemic vascular resistance, nystagmus, conjunctival injection, decreased intraocular pressure, lethargy, decreased concentration, and generalized psychomotor impairment.

Curcumin/Turmeric

Curcumin (diferuloylmethane) is a naturally occurring, active polyphenol derived from the plant Curcuma longa (turmeric) of the ginger family. There has been a growing interest in the potential therapeutic applications of curcumin because of its low cost and good safety profile. To date, there have been no studies examining the efficacy of curcumin in the treatment of patients with HS. However, there have been some promising findings with topical and oral curcumin in other inflammatory skin conditions (such as psoriasis and AD). Curcumin is known for its anti-inflammatory properties and is thought to inhibit the production of cytokines that have been implicated in HS, such as IL-6, IL-8, macrophage inflammatory protein-1α, IL-1β, and TNF-α. Inhibition of proinflammatory cytokine production may help restore skin homeostasis by hindering the cyclical immune activation. Curcumin also appears to play a role in microbiome modulation, such as inhibiting the growth of Cutibacterium acnes .

Concomitant use of both oral curcumin and curcumin topical cream had more improvement compared to placebo, oral curcumin alone, and oral curcumin combined with a curcumin topical gel in a phase II clinical trial of patients with acne vulgaris. In dermatology clinical trials, oral curcumin has been administered with benefit at doses ranging from 2000 to 6000 mg/day. Oral curcumin has poor bioavailability due to rapid elimination, fast metabolism, and poor absorption. As a result, it is recommended to consume piperine (black pepper) with curcumin, at a curcumin to piperine ratio of 100 to 1 to increase its bioavailability.

Diarrhea, headache, yellow stool, rash, and nausea have been reported with curcumin use, often at higher doses. In some cases, the symptoms resolved with continued use or improved with reduction in the curcumin dose. Gastrointestinal side effects may be reduced by taking curcumin with food and yogurt concurrently. For bothersome symptoms despite dose reduction, cessation of use may be recommended. Curcumin use may inhibit platelet aggregation and should be avoided in patients taking anticoagulants or antiplatelet medications. Future investigations are warranted to further understand the relationship of curcumin in HS, especially since 60% of respondents in a recent survey stated that they use curcumin for their HS, although the route of administration was unknown.

Magnesium

Magnesium is a noncompetitive inhibitor of N -methyl-D-aspartate and inhibits the entry of calcium ions into cells, leading to an anti-nociceptive effect. Magnesium therapy has been shown effective in reducing pain for a number of conditions, including primary dysmenorrhea, headaches, and perioperative pain. Elevations in C-reactive protein have been seen in magnesium depletion and may be a predisposing factor to chronic inflammatory stress. Magnesium intake has also been inversely associated with other markers of systemic inflammation including high-sensitivity C-reactive protein, IL-6, and TNF-α receptor 2. Supplementation with magnesium may be beneficial in alleviating pain associated with HS lesions as well as minimizing inflammatory stress. Hypermagnesemia is relatively uncommon but can occur in patients with renal disease or increased magnesium intake. Patients who receive magnesium supplementation should be monitored for symptoms of hypermagnesemia which range from weakness, nausea, dizziness, and confusion in mild cases, to serious systemic symptoms including cardiovascular complications, flaccid paralysis, lethargy, and coma.

Niacinamide (Nicotinamide)

Niacinamide has demonstrated some clinical benefit in acne and may be beneficial for patients with HS, though more research is needed. In patients with acne vulgaris, C. acnes interacts with TLR2, leading to activation of IL-8. Through the NF-κB and mitogen-activated protein kinase pathway, nicotinamide decreases the production of IL-8 and subsequently reduces inflammation. Combined supplementation of nicotinamide 750 mg, zinc 25mg, copper 1.5mg, and folic acid 500 μg has been shown to improve acne. Another study found that topical 4% niacinamide exhibited comparable clinical efficacy for acne as topical clindamycin, particularly in patients with oily skin types. Oral niacinamide in combination with zinc gluconate as maintenance therapy has been shown to extend disease-free survival and significantly reduce the rate and duration of flares . Burning, pruritus, and erythema have been reported with topical niacinamide.

Bathing Regimens

For HS patients with multiple widely separated areas of involvement, bathing treatments can be useful, as they treat a wide body surface area. Sodium hypochlorite (bleach) baths are discussed in Chapter 15 . In addition to bleach baths, HS patients may consider using magnesium sulfate (Epsom salt) baths. A magnesium sulfate bath was among the most common CAM methods (60%) used by survey respondents, and 48% of users found magnesium sulfate baths helpful for their HS. A discussion about magnesium sulfate baths can be found in Chapter 15 .

Balneotherapy is a method of bathing or immersing in mineral water. Often, studies examining balneotherapy are conducted using mineral water with elevated levels of magnesium along with other Dead Sea minerals such as sodium, potassium, calcium, chloride, sulfate, and carbonate. In patients with AD, balneotherapy has been shown to control flare symptoms in refractory cases, clear lesions, reduce itch, and reduce the amount of Staphylococcus aureus on the skin surface. Balneotherapy has also demonstrated benefits for patients with psoriasis and acne. Dead sea water and selenium-rich thermal spring water have been shown to decrease levels of psoriasis-associated inflammatory markers such as human β-defensin-2, skin-derived antileukoproteinase, TNF-α, IL-6, and IL-1α. Side effects of balneotherapy are rare and include itch and skin irritation.

In addition to the anti-inflammatory and anti-itch benefits of different bathing techniques, the act of bathing has been shown to reduce stress, pain, and fatigue. The heat from thermal baths stimulates the release of β-endorphin and enkephalin, endogenous opioid peptides which can influence pain reception. It should be noted that not every patient has access to a bathtub for the purpose of implementing bathing techniques.

Acupuncture and Acupressure

Acupuncture is a practice of traditional Chinese medicine in which the body’s meridian lines are stimulated via insertion of thin needles through the skin. The meridian lines are thought to host channels in which energy known as Qi flows, and may influence the autonomic system. Acupuncture helps to reduce inflammation, pain, and itch. The anti-inflammatory effects of acupuncture are thought to be mediated by downregulation of pro-inflammatory cytokines, pro-inflammatory neuropeptides, and neurotrophins while altering the Th1/Th2 cytokine balance. The precise mechanism of acupuncture pain reduction is not completely understood but may be due to stimulation of inhibitory nerve fibers to reduce pain signals to the brain, endorphin release, and/or neurotransmitter modulation. .

Battlefield acupuncture involves five sequentially placed acupoints on the ear: intertragic notch, antitragus, helix, helix crus, and antihelix crura. The use of battlefield and ear acupuncture among veterans has consistently resulted in immediate pain reduction. The immediate pain reduction associated with acupuncture may be beneficial for patients with HS, especially during acute flares where pain is often a predominant symptom. Battlefield acupuncture has also demonstrated some success and benefit in opioid weaning for patients with chronic pain. An alternative to acupuncture for patients that have a fear of needles is acupressure, which consists of applying external pressure without puncturing the skin to similarly designated acupoints. Both acupuncture and acupressure have resulted in improvements to psoriasis and AD symptoms, such as pruritus as well as improvement in disease severity measures including the Eczema and Psoriasis Area and Severity Indexes. Research is needed to investigate whether the notable improvements in pain and pruritus seen in other chronic cutaneous diseases may be achieved in HS. Adverse effects reported with acupuncture-related techniques include fever, pain, and dizziness. Potential side effects of acupressure include bruising, soreness, and itch at the pressure sites.