Oral Retinoids for Hidradenitis Suppurativa 17
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Chapter 17 Oral Retinoids for Hidradenitis Suppurativa 17 Jurr Boer Key points 17.1 Introduction Q Therapy with isotretinoin for patients Isotretinoin is well recognized as the most suc- with HS has only limited therapeutic cessful therapy for acne vulgaris. It is tradition- benefit ally thought that hidradenitis suppurativa (HS) and acne are closely related, and because of this Q There are claims that etretinate and isotretinoin has also been tested in HS, as have acitretin are superior to isotretinoin. the related compounds etretinate and acitretin. These data, however, wait confirmation in larger patient series 17.2 Isotretinoin 17.2.1 Mechanism of Action [1, 2] #ONTENTS The mechanism of action of isotretinoin in HS is unknown. In HS, the initial event is believed 17.1 Introduction ..........................128 to be poral occlusion. Retinoids can normalize 17.2 Isotretinoin ..........................128 follicular cornification, although etretinate and 17.2.1 MechanismofAction[1,2] .............128 acitretin have a clearly greater effect than 17.2.2 Clinical Experience ....................129 17.2.2.1 Isotretinoin Monotherapy for HS .......129 isotretinoin in disorders of keratinization [3]. It 17.2.3 IsotretinoinTherapyinPatients has also been shown that isotretinoin can re- with Acne and Coexistent HS ..........129 duce ductal hypercornification [4]. Isotretinoin 17.2.4 IsotretinoininthePre- possesses anti-inflammatory effects, reduces and Postoperative Phase ...............131 the chemotaxis of polymorphonuclear leuco- 17.2.5 Isotretinoin in Combination Treatment cytes and has been reported to enhance immune of HS ................................131 function [5, 6]. These properties may be of ben- 17.2.6 Side-Effects ...........................131 efit in the treatment of HS. The main effect of 17.3 Etretinate and Acitretin ................132 isotretinoin is to decrease of the size and secre- 17.3.1 MechanismofAction ..................132 tions of the sebaceous glands. 17.3.2 Clinical Experience: Etretinate and Acitretin for HS ...................132 However, in contrast to what happens in 17 17.3.3 Side-Effects ...........................134 acne, the size of sebaceous glands is not in- creased in HS. Isotretinoin also reduces the References ............................134 ductal population of Propionibacterium acnes, and although this has a very important effect on acne pathogenesis, it does not appear to be use- ful for the treatment of HS, because Propioni- bacterium acnes has not been cultured in HS lesions. Isotretinoin does not affect the size of apocrine glands. Oral Retinoids for Hidradenitis Suppurativa Chapter 17 129 17.2.2 Clinical Experience culoid lesions exist and undermining sinus tracts have not yet developed, isotretinoin alone 17.2.2.1 Isotretinoin Monotherapy for HS can produce complete suppression and pro- longed remission. Boer and van Gemert [12] Isotretinoin monotherapy for patients with HS also found some indication that the response of has limited therapeutic benefit. This is both the HS to isotretinoin is more successful in the general overall impression of many experts as milder (furunculoid, papulo-pustular lesions) well as the outcome of a study in which a large cases. It may be that treatment with isotretinoin case series of 68 patients were followed over a at the earliest stages of HS corrects the follicular period of almost 9 years [7–12]. The results of abnormality that is the root of this chronic dis- case reports and studies with case series are ease [15]. summarized in Table 17.1. All studies lack control groups with antibiot- ics or other agents as a comparison, so no state- 17.2.3 Isotretinoin Therapy in Patients ment as to relative efficacy can be made. How- with Acne and Coexistent HS ever, in all the referred case studies many patients did not respond to oral antibiotics or It is well known that acne and HS can occur in surgery, or relapsed after such treatment. the same person. In addition to the coexistence It is well known that acne patients with epi- of acne and HS, there are the so-called acne tri- thelial sinus tracts with recurrent inflammation ad (acne conglobata, HS and perifolliculitis ca- respond poorly to isotretinoin and are in fact pitis abscedens et suffodiens) and acne tetrad most of the isotretinoin “failures,” at a high cu- (original acne triad and pilonidal sinus) condi- mulative dose of isotretinoin as well [6, 13, 14]. tions [16]. This clinical overlap of acne and HS These lesions are identical to those found in the has led to the inclusion of inhomogeneous pa- axillae and groin in patients with HS [13, 14]. tients in the treatment groups. It concerns two Shalita and co-workers [13] suggested that in possible different types of HS; firstly the disease early cases in which only inflammatory furun- that only affects the inguinal folds and the axil- Table 17.1. Reported results of isotretinoin therapy for hidradenitis suppurativa (HS) No.ofpatientswithan - (almost) clear score Author (s) No.ofpa tients Dose (mg/kg per day) Duration of treatment (months) Follow-up (months) Duration of HS (years) Severity of HS At the end At the end of treatment of follow-up Jones et al. [7] 3 1.0 4 – 20–30 Severe 0 (0%) – Dicken et al. 8 0.71–1.2 4 2–6 5–35 Severe 4 (50%) 1 (12.5%) [8] Norris and 6 1.0 4 2 many years Severe 0 (0%) – Cunliffe [9] Brown et al. 1 1.0 4 4 3 Severe 1 (100%) 1 (100%) [10] Mengesha 1 1.0 8 12 1 Severe 0 (0%) – et al. [11] Boer and 68 0.5–0.81 4–6 6–107 1–30 Mild to 16 (23.5%) 11 (16.2%) van Gemert severe [12] 130 Jurr Boer Table 17.2. Reported results of isotretinoin treatment of patients with acne and coexisting HS Author (s) No. of Dose (mg/kg Duration Improvement of HS Recurrence patients per day) of treatment (months) Jones et al. [18] 1 0.1–1.0 4 No change – Plewig et al. [19] Un- 1.0–2.0 3 To a certain extent – specified Peck et al. [20] 2 High, No data Improvement – no precise data Shalita et al. [13] Uns- 0.5–1.0 4–5 Only suppressed – pecified furunculoid lesions. No change in sinus tracts Harms [21] 2 0.5–1.0 6 Improvement – Harms [2] 5 No data No data Considerable improve- No ment in 4 out of 5 patients Libow and Friar [22] 1 0.2–1.0 9 Quiescent No lae (“Verneuil’s disease”), and secondly inguinal apy did not always totally suppress this type of and axillary involvement in patients with acne lesion. The conclusion of the authors was that affecting the face and back [2, 13, 17]. The last sinus tracts require surgical removal [13, 14]. disease has also been called acne ectopica and In several initial trials of isotretinoin in acne, acne tetrad. the investigators often included some patients It has been suggested that patients of these with HS in addition to their severe acne. Jones, two categories would respond to isotretinoin in Blanc, and Cunliffe reported one case who failed different ways [2, 13, 14, 17]. The data are sum- to respond after a 4-month course on an un- marized in Table 17.2. specified dose of between 0.1 and 1.0 mg/kg per Harms [2] treated eight patients suffering day [18]. Plewig and colleagues treated an un- from HS, of whom five had concurrent acne of specified number of patients with acne tetrad the face and three did not. Four out of five who responded to a certain extent [19]. Peck et patients with the combination of acne and HS al. included two patients with HS in the groin improved considerably under treatment with and axilla in addition to their cystic acne, who isotretinoin and did not suffer any recurrence. showed improvement of the HS after the cystic The three patients who had only inguinal in- acne had begun to improve and when the dos- volvement did not improve (data about the dos- age had been further increased above the level es, duration of isotretinoin course and follow- required to improve their acne (the actual doses up were not mentioned). It was concluded that used were high but not specified) [20]. Harms patients with lesions only in inverse areas (axil- described in a case series of 56 patients with 17 lae, groin) should not be treated with isotreti- nodulocystic acne including two patients with noin and that there may be patients with HS ano-inguinal lesions which only improved on who respond very well to isotretinoin, namely isotretinoin at a dosage of 0.5–1.0 mg/kg per day those with a combination of acne and additional for 6 months [21]. Libow and Friar reported ef- HS [2, 17]. fective treatment of a patient with arthropathy Other authors [13, 14] found that patients with associated acne triad condition with with sinus tracts in the areas of acne with coex- isotretinoin [22]. A patient has been described isting HS of the axillae and groin were often with arthropathy associated with cystic acne, isotretinoin “failures,” in that isotretinoin ther- HS (in this case papulo-pustules and cysts in- Oral Retinoids for Hidradenitis Suppurativa Chapter 17 131 volving the genital and inguinal areas, no sinus only poorly to oral antibiotics and isotretinoin tracts), and perifolliculitis capitis abscedens et (dose were not mentioned) [27]. The authors did suffodiens who showed a dramatic response to not observe preoperative “conditioning” of the isotretinoin (1.0 mg/kg per day) for 6 months, HS regions and in their case series they did not followed by isotretinoin (0.5 mg/kg per day ev- recognize any minimalization of the areas in- ery other day) for another 3 months before be- volved by the HS lesions.