Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Topical Therapeutics
Introduction
Topical therapy is a mainstay of dermatological treatment and holds many advantages, including ease of use, relative lack of systemic side effects, and patient-directed application. In hidradenitis suppurativa (HS), topical therapeutics are often used for early-stage lesions or as a complement to systemic or surgical treatments. The four categories of disease-modifying topical therapy for HS are antibiotics, antiseptics, keratolytics, and bathing additives (each of which will be discussed in this chapter), while symptom-control therapies such as topical analgesia and antipruritics are reviewed in Chapter 19. Some complementary and alternative therapies are also thought to be helpful when applied topically, and these will be briefly reviewed as well.
Unfortunately, the level of evidence supporting the use of most topical therapies in HS is low ( Table 15.1 ). This chapter will provide an overview of dosing schedules, drug mechanisms of action ( Fig. 15.1 ), and contraindications of topical therapeutics for HS to better inform these decisions.
Table 15.1
Topical Therapeutics for Hidradenitis Suppurativa
BID , Two times per day; CBD , cannabidiol; NF-kB , nuclear factor kappa B; PMN , polymorphonuclear leukocyte; PRN , as needed; TID , three times per day.
| Topical Antibiotics | ||||||
|---|---|---|---|---|---|---|
| Therapy Name | Mechanism of Action | Dosing | Contraindications | Adverse Effects | Level of Evidence a | Notes on Use |
| Clindamycin | Inhibit bacterial ribosome, inhibit PMN chemotaxis, inhibit biofilm formation, potentiate phagocytosis of bacteria | BID Limit monotherapy to 3 months |
Hypersensitivity to clindamycin or lincomycin derivatives, history of regional enteritis or ulcerative colitis, history of antibiotic-associated colitis | Pruritis, xeroderma, erythema, burning, exfoliation, oily skin, bacterial resistance | B | Strongly consider in all mild HS patients and as adjunct therapy in moderate to severe cases. Safe for pregnant patients. |
| Fusidic Acid | Bind to elongation factor-G on bacterial ribosome inhibiting translation, suppress cytokine signaling | TID | Hypersensitivity to therapeutic vehicle or FA itself | Mild irritant or allergic contact dermatitis, bacterial resistance | B | Consider for Hurley stage 1 and early lesions. Avoid prolonged monotherapy as bacterial resistance is common. |
| Dapsone | Halt bacterial folate metabolism, reduce oxidative damage to tissue | BID | Hypersensitivity to therapeutic vehicle or dapsone itself | Methemoglobinemia, mild irritant or allergic contact dermatitis, bacterial resistance | D | Consider for Hurley I and early lesions or as adjunct therapy in later stages for patients who cannot use topical clindamycin. |
| Gentamicin | Inhibit bacterial ribosome | TID following surgery | Hypersensitivity to therapeutic vehicle or gentamicin itself | Mild irritant or allergic contact dermatitis, bacterial resistance | E | Use after de-roofing or local excision procedures. Consider for a secondarily infected HS lesion that grows gram negative species. |
| Topical Keratolytics | ||||||
| Resorcinol | Cytotoxic, modulate cytokine/chemokine release | BID with increasing concentration to therapeutic level (typically 15%–20%) | Concomitant use of intense pulsed light therapy, hypersensitivity to therapeutic vehicle or resorcinol itself | Desquamation, depigmentation, mild irritation, or allergic contact dermatitis | B | Use for acute lesions and to maintain quiescence. Check baseline pregnancy test. Not for use in women actively trying to get pregnant. |
| Azelaic Acid | Modulate keratinocyte proliferation | BID | Hypersensitivity to therapeutic vehicle or azelaic acid itself | Photosensitivity, desquamation, depigmentation, mild irritant or allergic contact dermatitis | E | Consider in children given low risk profile. |
| Bathing Additives and Complementary Therapies | ||||||
| Bleach baths | Creation of superoxide radicals, modulate NF-κB signaling | 2–3 times weekly | None | Caustic effects, bleaching of hair and fabrics | E | Consider in combination with other topical therapies for mild disease. |
| Magnesium Sulfate | Unknown | PRN | None known | Unknown | E | Not enough evidence to make a definitive conclusion. |
| CBD oil | Decrease pain perception, inhibit keratinocyte proliferation while regulating cellular differentiation and promoting apoptosis of both keratinocytes and sebocytes | PRN | None known | Unknown | E | Not enough evidence to make a definitive conclusion. |
| Turmeric | Disrupt bacterial membranes, inhibit bacterial replication, disrupt microbial biofilms | PRN | None known | Unknown | E | Not enough evidence to make a definitive conclusion. |
Grade A: Double-blind study . At least one prospective randomized, double-blind, controlled trial without major design flaws (in the author’s view).
Grade B: Clinical trial ≥ 20 subjects . Prospective clinical trials with 20 or more subjects; trials lacking adequate controls or another key facet of design that would normally be considered desirable (in the author’s opinion).
Grade C: Clinical trial < 20 subjects . Small trials with fewer than 20 subjects with significant design limitations, very large numbers of case reports (at least 20 cases in the literature), or retrospective analyses of data.
Grade D: Series ≥ 5 subjects . Series of patients reported to respond (at least five cases in the literature).
Grade E: Anecdotal case reports . Individual case reports amounting to published experience of fewer than five cases.
Antibiotics
The occlusion of the folliculopilosebaceous unit that heralds the onset of HS is followed by bacterial growth, inducing inflammation that leads to abscesses, sinus tracts, and destruction of adnexal structures. Given that bacteria are thought to contribute to the development and perpetuation of these lesions, it is no surprise that antibiotic therapy can be a useful approach to treatment. Topical antibiotics are postulated to work by two complementary methods in the treatment of HS: the reduction of bacterial burden and the prevention of inflammation. Their antibacterial effects decrease bacterial colonization, which then tempers the local inflammation associated with the body’s response to the resident bacteria. A number of topical antibiotics also have antiinflammatory effects independent of their antibacterial properties, and many are also delivered in vehicles that themselves may soothe inflamed skin via emollient, cooling, hydrating, or barrier-forming properties. In this section, various topical antibiotics that have been used in the treatment of HS will be discussed.
Clindamycin
Clindamycin is a broad-spectrum antibiotic of the lincosamide class that interferes with the synthesis of bacterial proteins by binding to the 50S ribosomal subunit, providing a bacteriostatic effect with concentration-dependent bactericidal activity against staphylococci, streptococci, and some anaerobes. It also boasts independent immunomodulatory effects. Though the mechanism of these additional properties is poorly understood, studies have postulated that clindamycin may inhibit complement-derived chemotaxis of polymorphonuclear leukocytes, potentiate the uptake of microorganisms by phagocytic cells of the innate immune system, and inhibit biofilm formation, thus assisting in the clearance of bacteria without drawing in additional inflammatory milieu. Given its localized effect, topical clindamycin is most effective for limited disease in the absence of deep abscesses and sinus tracts. Treatment has been shown to reduce pustules but has limited effect on abscesses and nodules. However, it can be used as an adjunct in more severe stages of HS along with the addition of systemic medications and surgical intervention.
Clindamycin is the only topical antibiotic treatment for HS to have been validated in randomized controlled trials. In these trials, topical clindamycin treatment was responsible for a significant reduction in the number of abscesses, inflammatory nodules, and pustules compared to the placebo, with effects equivalent to systemic tetracycline. Interestingly, the efficacy of clindamycin in one trial was independent of the presence of bacteria at the onset of treatment, as measured by culture of aseptic aspirate from inflamed HS lesions, indicating that the antiinflammatory properties of the drug may have played a major role.
Though HS treatment guidelines recommend various formulations of topical clindamycin such as solution, gel, or lotion, the original studies demonstrating efficacy were performed using clindamycin 1% solution. Availability, price, and patient preference are all considerations when choosing the most appropriate vehicle. Most consensus clinical guidelines recommend twice-daily application of topical clindamycin to areas affected by HS. However, use as monotherapy should not exceed 3 months, as studies have shown the emergence of resistant Staphylococcus aureus in the lesions of patients treated for prolonged periods. The addition of benzoyl peroxide (BPO) can mitigate the development of bacterial resistance and allow prolonged use.
Contraindications to the use of topical clindamycin either alone or in combination with other therapies are rare and limited to those with a history of hypersensitivity to preparations containing clindamycin or lincomycin derivatives, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis. Cutaneous adverse effects experienced by some patients include pruritis, xeroderma, erythema, burning, exfoliation, or oily skin.
Fusidic Acid
Fusidic acid (FA) inhibits the activity of the bacterial ribosome. FA binds to elongation factor G on the ribosome, preventing translocation of the bacterial ribosome. FA is most active against gram-positive bacteria, particularly Staphylococcus species (which are one of the most commonly found bacteria in HS wound cultures), and likely responsible for a significant amount of subsequent inflammation. Although biochemically comparable to many steroids, FA does not possess any steroid activity. There is excellent penetration of FA into deeper layers of the skin due to its lipophilic steroid-like structure and independent antiinflammatory activity due to suppression of cytokine signaling.
Evidence for FA utility in HS patients is limited to case reports and a single prospective cohort study. In this study involving 627 patients with Hurley stage 1 axillary HS, FA 2% ointment was applied thrice daily after washing with antibacterial soap. All patients had complete healing within 4 weeks of treatment. These data have, to our knowledge, not yet been replicated elsewhere.
FA for treatment of HS is typically formulated as a 2% sodium fusidate ointment or cream. Other formulations of FA are available and used for dermatologic conditions, such as combination formulations of FA with 1% hydrocortisone or 0.1% betamethasone, which can be used to treat eczema complicated by staphylococcal infection. While each of these formulations is available to those suffering from HS, further study of the relative efficacy of combined versus FA-only topicals is needed before a particular formulation can be recommended. There are significant concerns about the development of resistant bacteria with FA monotherapy, given that a single point mutation is enough to confer significant resistance and contribute to outbreaks of multi-drug-resistant bacteria. Prolonged monotherapy with FA is therefore generally avoided. Adverse events during treatment are uncommon and generally limited to reactions to components of the vehicle, which can lead to mild allergies or irritant contact dermatitis. Contraindications are limited to hypersensitivity to components of the topical therapeutic vehicle or FA itself.
Dapsone
Dapsone is an antibiotic with significant independent antiinflammatory activity commonly used for the treatment of a variety of dermatological conditions. The antibiotic activity of dapsone is mediated through the inhibition of dihydropteroate synthesis, halting folate metabolism and resulting in the stasis of bacterial growth. Its antiinflammatory activity is accomplished through inhibition of myeloperoxidase, an enzyme vital for oxidative destruction of microbes by neutrophils that often causes simultaneous damage to local tissues. Dapsone has also been postulated to inhibit neutrophil chemotaxis, a function that may serve to lessen inflammation in HS abscesses and sinus tracts. Limited evidence based on expert opinion suggests topical dapsone may be useful in early disease.
Commercially available topical dapsone for use in dermatological conditions is currently limited to gel form, with 5% and 7.5% formulations available. Initial dosing begins at twice-daily application, which is the recommended frequency for treatment of acne vulgaris. While concerns of antibiotic resistance would theoretically also apply to the use of topical dapsone, the literature currently suggests that monotherapy over periods up to 12 weeks does not lead to bacterial resistance. However, further study must be undertaken over longer periods to establish the safety of long-term dapsone monotherapy for conditions such as HS, which often requires more than 12 weeks of therapy.
While dapsone is structurally similar to sulfonamide drugs, allergy to sulfonamides is not a contraindication to its use. Although various dermatological side-effects of oral dapsone have been described, including severe reactions (such as toxic epidermal necrolysis), these effects have not been seen with topical dapsone. Unlike with the use of systemic dapsone, a glucose-6-phosphate dehydrogenase (G6PD) level does not need to be checked before commencing treatment with topical dapsone as there is no evidence of clinically relevant hemolysis or anemia after topical administration. Dapsone may also induce methemoglobinemia in the presence of other pharmaceuticals with similar propensities (such as local anesthetics), and this is true of both oral and topical dapsone.
Gentamicin
Gentamicin is an aminoglycoside antibiotic that inhibits the production of bacterial proteins by binding to ribosomal subunits, preventing the translation of messenger ribonucleic acid. Its broad spectrum of action makes it an attractive candidate for use in treating infected wounds. Thus far, study of topical gentamicin in HS has been limited to postoperative application as a strategy to reduce the rate of post-operative infection. While short-term complications, including dehiscence and infection, were mitigated by topical gentamicin use, the rate of recurrence of HS lesions was unaffected in the long term.
Gentamicin is available commercially as gentamicin sulfate 0.1% cream and ointment. Given the paucity of data and the lack of published success in treating HS lesions, guidelines tend to recommend that topical gentamicin be used only if other topical antibiotics are not available or cannot be used. Generally, topical gentamicin can be applied 3 to 4 times daily for treatment of superficial skin and soft tissue infections.
Contraindications are limited to hypersensitivity to product components, and adverse effects include skin irritation and the potential emergence of superinfection with atypical, resistant organisms. Given the varied bacterial milieu within HS wounds and the importance of bacterial control for mitigation of HS symptoms, such emergence should not be taken lightly.
Antiseptics
As opposed to the more narrowly targeted effects of antibiotic compounds, antiseptic washes are not absorbed into the body and have a broad spectrum of antimicrobial activity that relies on a variety of mechanisms to slow or stop microbial growth, resulting in reduced selective pressure and rare development of resistance. Antiseptic washes provide an additional method of minimizing bacterial colonization and reducing concomitant inflammation for HS patients, and are even more frequently utilized in some practices than topical antibiotics (though they are often used in tandem.) Given that lesions of HS are often polymicrobial on culture, antiseptic washes are theorized to be of similar utility to antibiotics without the risk of bacterial resistance or insufficient breadth of coverage that can accompany antibiotic use. However, such intervention comes with risk of both allergic and irritant contact dermatitis. There are few studies evaluating their effectiveness in preventing and treating HS flares. Patient adherence to using antiseptic washes has been reported to be low, with only 70% of patients using the recommended wash at all, and only 30% of those patients using it daily. Reported barriers to use included difficulty finding and affording the recommended wash with little perceived benefit. In this section, antiseptic washes commonly prescribed as treatment for early-stage HS will be discussed.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here