Resorcinol peels as a possible self-treatment of painful nodules in hidradenitis suppurativa

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1 Clinical dermatology Original article Clinical and Experimental Dermatology Resorcinol peels as a possible self-treatment of painful nodules in hidradenitis suppurativa J. Boer and G. B. E. Jemec* Department of Dermatology, Deventer Hospital, Deventer, The Netherlands; and *Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Denmark doi: /j x Summary Background. Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by abscess formation localized to apocrine sweat gland-bearing skin. The most important factor in patients overall assessment of disease severity is pain. The duration of abscesses takes days to weeks and are always painful. Aim. To assess the efficacy of self-treatment with topical 15% resorcinol in an open study. Methods. The case notes of 12 women with stage 1 or 2 HS treated with topical resorcinol and followed up for at least 1 year were reviewed. The patients rated the efficacy of treatment on global maximum pain of nodules and abscesses on a visual analogue scale (VAS) and by self-report of the mean duration (days) of a painful lesion. Results. All patients experienced a significant decrease in pain as assessed by VAS and reported a reduction in mean duration of the painful abscesses. Conclusions. Topical treatment with 15% resorcinol reduced pain from painful nodules in all patients with HS. Further trials are warranted to confirm these results. Introduction Hidradenitis suppurativa (HS) is a clinically defined disease that causes a high degree of morbidity, with pain and painful boils as the main signs. 1 3 Treatments for acute lesions usually include systemic antibiotic treatment, intralesional corticosteroids, excision or carefully considered lancing in selected cases. 4 6 The evidence base of these interventions is limited. Most patients have very frustrating experiences of lancing, with subsequent predictable rapid recurrences. It has been noted that the spontaneous duration of each flare (on average 6.9 days) is not greatly reduced by a conventional course of oral penicillin, 2,4 but the role of antibiotics is still unclear. In a randomized controlled trial of antibiotics, a progressive improvement of the disease was found, although pain did not change during the study. 6 Correspondence: Dr J. Boer, Department of Dermatology, Deventer Hospital, Postbox 5001, 7400GC Deventer, The Netherlands. boerj@dz.nl Conflict of interest: none declared. Accepted for publication 26 September 2008 There is therefore a continued need for a fast-acting, noninvasive therapy for lesions, particularly to lessen the pain. Because of the chronic recurrent nature of the disease, it would be preferable if patients could apply such a therapy themselves. Recently, encouraging case reports about the use of topical resorcinol in the management of painful boils in HS have been published and summarized. 7 9 These pilot studies suggest that topical resorcinol may be helpful in the management of acute lesions, even though the treatment has no influence on scarring, fibrosis or deep-seated lesions, which also occur in HS. Resorcinol peels allow nontraumatic drainage and shrinkage of lesions. We report on the clinical results of topical resorcinol therapy used in cases with long-standing HS, particularly focusing on the changes in pain, i.e. the extent of pain and the duration of painful boils. The patients were followed up for at least 1 year. Methods We reviewed the case notes of 12 women (mean age 37.8 years) with active, long-standing HS referred to Journal compilation Ó 2009 British Association of Dermatologists Clinical and Experimental Dermatology 1

2 Table 1 Summary of patient outcomes. Patient Age (years) Disease duration (years) Treated area Prior treatment Pain on VAS (cm) Before treatment After treatment Average duration of painful boils (days) Without resorcinol With resorcinol Effect of topical resorcinol* on boils Groins Antibiotic Shrinkage Groins Antibiotics, surgery Shrinkage and or breakthrough Groins Antibiotics, surgery Permanent 14 Shrinkage Groins Antibiotics, surgery Breakthrough Groins Antibiotics, surgery Shrinkage Groins Antibiotics Breakthrough Groins Antibiotics, surgery, Shrinkage and or breakthrough etanercept Groins Surgery Shrinkage Groins Isotretinoin, surgery Breakthrough Groins Surgery Shrinkage Axillae Antibiotics, surgery Shrinkage Groins Surgery Shrinkage and or breakthrough VAS, visual analogue scale; 10-cm scale, with 0 being least pain and 10 being worst pain ever. *Cremor lanette, consisting of the following components: alcohol cetylicus et stearylicus emulsificans b (cetostearyl alcohol type b), acidum sorbicum (sorbates), Cetiol v (decyloleaat), sorbitolum liquidum cristallisabile (sorbitol), aqua purificata (water). our clinic between 2005 and 2006, who were treated in an open trial with resorcinol 15% (Table 1). All patients had a history of long-term cigarette smoking. All were in the early stages of HS (Hurley stage 1 or 2), with single abscesses without sinus tracts or with recurrent but widely separated abscesses with sinus tracts and scarring. 10 The mean duration of disease was 14.8 years (range 3 27 years). All patients experienced flares, which could be either revival of an old lesion or formation of a new one. Eleven patients had 3 6 flares a year in their groins and one patient (patient 11) in her axillae. Pain was present in all cases and varied from mild to unbearable. Some patients might have a few flares a year with (almost) unbearable pain, followed by a period of remission, whereas others might have continuous pain (generally mild to moderate) with a few flares a year. All the patients had previously been treated with topical clindamycin and or systemic treatments including antibiotics, isotretinoin and etanercept, and many had been treated surgically. Treatment results were generally disappointing and most of the patients were no longer motivated to try conventional treatments (Table 1). All patients were treated for a minimum of 12 months. They were given resorcinol 15% [incorporated in an oil water cream with emulsifying waxes; ingredients listed as cremor lanette, consisting of the following components: alcohol cetylicus et stearylicus emulsificans b (cetostearyl alcohol type b), acidum sorbicum (sorbates), Cetiol v (decyloleaat), sorbitolum liquidum cristallisabile (sorbitol), aqua purificata (water)] as topical monotreatment for the flares, i.e. the abscesses and painful boils. Patients were instructed to apply the cream once daily to any persistent painful lesions that failed to settle down, and in cases of flares, to start immediate (within hours) treatment of the painful boil twice daily with resorcinol cream. Patients were allowed to continue the topical treatment as a maintenance treatment once daily after the flare, but most used the topical medication only when flares occurred. Treatment efficacy was assessed by self-reported patient pain [evaluated on a 10-cm visual analogue scale (VAS) at the time of examination, with patients asked to assess the worst pain experienced during a flare] and duration (days) of painful lesions with and without treatment. These two parameters were scored routinely before and after treatment of at least two flares. In addition, clinical photographs were taken for documentation. Results During resorcinol treatment, a marked decrease in pain as assessed by VAS and in mean duration of the painful lesions were seen (Table 1). Patients reported a rapid response after starting topical treatment, with half of the patients experiencing disappearance of the pain within 2 days. Topical resorcinol treatment reduced the average duration of painful abscesses to 3.7 days (range Journal compilation Ó 2009 British Association of Dermatologists Clinical and Experimental Dermatology

3 days), whereas without treatment patients reported duration of pain ranging from 5 days to permanently. The VAS score without treatment varied greatly between the cases, from mild (patient 10: VAS score of 2.4) to unbearable (patients 4 and 12: VAS score of 10). Without topical resorcinol, three of four patients with unbearable painful abscesses were forced to visit the emergency department for lancing (patients 3, 4 and 12), while in one case (patient 6), her husband lanced the boils. In four cases (patients 1, 2, 9 and 10), after limited surgery on earlier sinus tracts, the pain of the remaining lesions still caused a moderate but permanent pain (VAS scores of 5.2, 4.3, 5.1 and 2.4, respectively). Topical resorcinol reduced pain to an acceptable level (VAS scores of 0.5, 0.8, 0.6 and 0.3, respectively) in these four patients. All four had immediate recurrences after stopping resorcinol treatment and consequently used topical resorcinol once daily on a continual basis. The remaining four patients (5, 7, 8 and 11) developed new lesions on various locations in the groins and axillae. When flares occurred, the patients had barely bearable pain (mean VAS score 7.7; range ), but with resorcinol the pain significantly decreased (mean VAS score 3.4 range ). After topical resorcinol, the pain seemed to be reduced after approximately 2 days and in most patients it reduced rapidly. Resorcinol caused desquamation in all patients. In cases of irritation the concomitant use of a simple moisturizer was prescribed to soften the skin and soothe irritation. 11 In 4 of 12 patients, a reversible brown discoloration developed during treatment. Discussion HS is characterized by recurrence of lesions and chronicity, and treatment is often frustrating. Management of the disease may benefit from greater self-care by the patients, allowing them to participate actively in the prevention and treatment of minor flares. Pain management is of particular relevance to patients, as this appears to be the key factor in patient assessment of the disease. It is known that the variation in individual pain thresholds may be important in coping with HS. 3,4 This study suggests that self-administered chemical peels using resorcinol can reduce the pain associated with acute lesions of HS. It is speculated that this may offer an opportunity for selected patients to self-manage this highly troublesome disease. Patients with HS should be clearly informed of the multifocal character of their disease, i.e. that in addition to the high risk of recurrence, there is also the possibility of developing new lesions in the same or other anatomical regions. Patients also need to understand that treatment with topical resorcinol in general does not cure the HS lesions, but is mainly aimed at providing more control over disease activity. In our study, adherence to topical treatment appeared to be very high in this selected group of patients with recurrent inflamed nodules. We speculate that this may be due to two reasons: firstly, patients were able to apply resorcinol within hours of a new flare starting and secondly, the degree of pain relief made it worthwhile to continue using the cream once the effect set in. Adherence was clearly lower between flares, as most of the patients stopped using the cream as a maintenance treatment. Nevertheless, the continued patient demand for this treatment may offer indirect support for the usefulness of this treatment. Resorcinol [(BP,USP) C 6 H 4 (OH) 2, 1,3-dihydroxybenzene] is a phenol derivate, used in dermatology for > 100 years mainly because of its keratolytic properties, although it also has effects on controlling inflammation by stimulating prostaglandin E2 formation Its concentration-dependent peeling effects depend on the disruption of the weak hydrogen bonds of keratin. 16 It has been observed that in inflamed nodules, selfadministered resorcinol peels will cause an earlier breakthrough or an earlier resorption (shrinkage) of the lesions (Fig. 1). Resorcinol is mainly used as a peeling agent at concentrations of 5 15%, 14,15 and has traditionally been used for acne treatment. The peeling effect starts only at concentrations of 10%; concentrations of 5 10% resorcinol appear ineffective Our clinical experience suggests that the peeling effect starts only at a concentration of 15% in most patients. 7,8 In the treatment of acne, a resorcinol concentration of 20 30% has traditionally been used in peeling pastes. 14,18 21 Systemic toxicity is very rare but has been reported in the older literature and in one recent case report in which high concentrations (40 50%) were used in large amounts or on large injured surfaces. 18,22,23 The toxic effects range from cold sweats, dizziness, and discoloration of the urine, to collapse and signs of hyperthyroidism. 15,18,23,24 There have been reports of acute poisoning in babies, in two cases with fatal outcome. 24 Resorcinol in concentrations up to 20% can be considered safe. 14,15,19 Whether this is also valid for HS is unclear, because the HS lesions are most often naturally occluded. Therefore we used the lower concentration of 15% as standard. There are insufficient data on the use of resorcinol in pregnancy to assess the risk accurately. Journal compilation Ó 2009 British Association of Dermatologists Clinical and Experimental Dermatology 3

4 (a) (b) (c) Figure 1 Patient 5 (a) before, (b) during and (c) after treatment; photographs taken at weeks 0, 1 and 3, respectively. The US Food and Drugs Administration rates resorcinol as a category C drug, which includes drugs for which a risk cannot be excluded, due to inadequate data. It is therefore suggested that a negative pregnancy test and use of adequate contraception is required before, during and up to 1 month after the end of treatment. The most striking subjective effect of topical resorcinol treatment noticed in this group of patients with HS was the disappearance of the pain and shortening of the duration of flares. The empowerment of patients to selftreat may be an important factor in helping them to cope with the disease. 25 These positive results indicate the need for a randomised, controlled trial of this topical treatment for HS. References 1 Werth JM, Williams HC. The natural history of hidradenitis suppurativa. J Eur Acad Dermatol Venereol 2000; 14: Jemec GBE, Heidenheim M, Nielsen NH. Hidradenitis suppurativa: characteristics and consequences. Clin Exp Dermatol 1996; 21: Werth JM, Jemec GBE. Morbidity in patients with hidradenitis suppurativa. Br J Dermatol 2001; 144: Jemec GBE. Medical treatment of hidradenitis suppurativa. Expert Opin Pharmacother 2004; 5: Clemmensen OJ. Topical treatment of hidradenitis suppurativa with topical clindamycin. Int J Dermatol 1983; 22: Jemec GBE, Wendelboe P. Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa. J Am Acad Dermatol 1998; 39: Boer J, Dijkstra AT, Baar TJM, van der Meer JB. Hidradenitis suppurativa (acne inversa): lokale behandeling met resorcine. Ned Tijdschr Derm Venereol 2001; 11: Boer J, Bos WH, van der Meer JB. Hidradenitis suppurativa (acne inversa); behandeling met deroofing en resorcine [English abstract]. Ned Tijdschr Derm Venereol 2004; 14: Sartorius K, Boer J, Jemec GBE. Topical treatment. In: Hidradenitis Suppurativa (Jemec GBE, Revuz J, Leyden JJ, eds). Heidelberg: Springer Verlag, 2006: Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach. In: Dermatologic Surgery: Principles and Practice (Roenigk RK, Roenigk HHJ, eds). New York: Marcel Dekker, 1989: Overgaard Olsen L, Jemec GB. The influence of water, glycerin, paraffin oil and ethanol on skin mechanics. Acta Derm Venereol 1993; 73: Alanko J, Riutta A, Mucha I et al. Modulation of arachidonic acid metabolism by phenols: relation to positions of hydroxyl groups and peroxyl radical scavenging properties. Free Radic Biol Med 1993; 14: Levy BD, Clish CB, Schmidt B et al. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2001; 2: Polano MK. Topical Therapeutics. Edinburgh: Churchill Livingstone, 1984: De Groot AC. Dermatological drugs, topical agents and cosmetics. In: Meyler s Side Effects of Drugs (Dukes MNG, Aronson JK, eds). Amsterdam: Elsevier, 2000: Wilkinson DS. Topical therapy. In: Textbook of Dermatology (Rook A, Wilkinson DS, Ebling FJG, eds). Oxford: Blackwell Scientific Publications, 1972: Mills OH, Kligman AM. Drugs that are ineffective in the treatment of acne vulgaris. Br J Dermatol 1983; 108: Wüthrich B, Zabrodsky S, Storck H. Perkutane vergiftungen durch resorcin, salicylsäure und weisse präcipitatsalbe. Pharm Acta Helv 1970; 45: Häckh G, Schwartzmüller E. Codex Dermatologischer Wirkstoffe. In: Dermatika (Niedner R, Ziegenmeyer J, 4 Journal compilation Ó 2009 British Association of Dermatologists Clinical and Experimental Dermatology

5 eds). Stuttgart: Wisenschaftliche Verlagsgesellschaf, 1992: Ghersetich I, Teofoll P, Gantcheva M et al. Chemical peeling: how, when, why? J Eur Acad Dermatol Venereol 1997; 8: Ghersetich I, Brazzini B, de Lotti T et al. Resorcinol. In: Color Atlas of Chemical Peels (Tosti A, Grimes PE, Padova MP, eds). Heidelberg: Springer Verlag, 2006: Cassano N, Alessandrini G, Mastrolonardo M, Vena GA. Peeling agents: toxicological and allergological aspects. J Eur Acad Dermatol Venereol 1999; 13: Bontemps H, Mallaret M, Besson G et al. Confusion after topical use of resorcinol. Arch Dermatol 1995; 131: Cunningham AA. Resorcine poisoning. Arch Dis Child 1956; 31: Jemec GBE, Revuz J, Leyden JJ. Hidradenitis Suppurativa. Heidelberg: Springer Verlag, Journal compilation Ó 2009 British Association of Dermatologists Clinical and Experimental Dermatology 5