Treatment of rosacea and demodicosis with benzyl benzoate: effects of different doses on Demodex density and clinical symptoms

Abstract

Background Patients with rosacea or demodicosis have high facial skin Demodex densities (Dds). Topical ivermectin, benzyl benzoate (BB) and crotamiton have been shown to decrease Dds in vivo, but there are few data on the clinical and acaricidal effects of BB among patients with rosacea. Objective To evaluate the impact of topical BB (+crotamiton) treatment on Dds and clinical symptoms of rosacea and demodicosis, and compare three BB treatment regimens. Methods In this retrospective observational study, 394 patients (117 with rosacea, 277 with demodicosis) were included. Three BB (+crotamiton) treatment regimens were compared: 12% once daily, 12% twice daily and 20% once daily. Dds were measured using two consecutive standardized skin surface biopsies [superficial (SSSB1) and deep (SSSB2)] before treatment and at the first follow‐up. Symptoms were evaluated using investigator global assessment. Treatment was considered effective if the Dd had normalized (SSSB1 ≤ 5 D/cm2 AND SSSB2 ≤ 10 D/cm²) or symptoms had cleared and curative if the Dd had normalized and symptoms had cleared. Results At an average of 2.7 months after treatment start, the total Dd (SSSB1 + 2) had decreased by 72.4 ± 2.6% from the initial value across the whole cohort. Dds had normalized in 139 patients (35%), and symptoms had cleared in 122 (31%). Treatment was effective in 183 (46%) patients and curative in 78 (20%). Compliance was good: 77% of patients correctly followed treatment instructions. Results were similar in patients with rosacea and those with demodicosis. The 12% once‐daily regimen was less effective than the other doses and had poorer compliance than the 12% twice‐daily regimen. Conclusion Topical treatment with BB (+crotamiton) may be an effective treatment for rosacea and demodicosis, indirectly supporting a key role of the mite in the pathophysiology of rosacea. The two higher dose regimens were more effective than the lower dose.

The Pathogenic Role of Demodex Mites in Rosacea: A Potential Therapeutic Target Already in Erythematotelangiectatic Rosacea?

“…Deeper and larger [102,105,113] Pruritus Usually considered more frequent in demodicosis [70,72,74,79,241,242,99] Evolution over time The 2 forms may occur successively in the same patient [10] Often after pityriasis folliculorum More often after ETR than the reverse [8,57,136] Treatment Acaricide Anti-inflammatory, acaricide of benzyl benzoate (with crotamiton) on Demodex density and on clinical symptoms in a real-life study [159,160]. In our practice, we successfully used benzyl benzoate (with crotamiton) cream for more than 20 years; however, the development of ivermectin has provided an effective alternative [172,223,224] with better tolerance and this is now our treatment of choice.…”

“…If Demodex mites induce the immune response that leads to the papules and pustules of PPR [ 8 , 10 , 29 , 31 , 34 , 35 , 56 – 58 , 99 , 108 , 110 , 111 , 128 , 132 – 134 , 159 – 170 ], then rosacea-like demodicosis and PPR are probably two phenotypes of the same disease [ 10 ]. Indeed, the descriptions of demodicosis and rosacea seem to indicate two different approaches to the same condition (Table 1 ): their definitions cannot be compared because they are based on different criteria (etiological for demodicosis [ 101 , 102 ] and clinical for rosacea [ 5 , 6 ]); their symptoms are similar [ 10 , 31 ] with no single criterion being specific for either and most patients presenting a mixture of characteristics that can be attributed to both of the entities [ 10 ]; they may occur successively in the same patient [ 10 ]; their histological characteristics are similar [ 31 ]; their Demodex densities are similar [ 10 ]; and both respond very well to acaricidal treatment, in terms of reduced Demodex densities and improved clinical symptoms [ 159 , 160 , 171 , 172 ]. It is therefore increasingly difficult to defend the view that, in these two similar diseases, the exaggerated proliferation of parasites has a different role, causal in one and epiphenomenal in the other.…”

“…Our randomized clinical study comparing six topical treatments reported that benzyl benzoate had marked acaricidal action and crotamiton moderate action [ 218 ]. We recently demonstrated the short- and long-term actions of benzyl benzoate (with crotamiton) on Demodex density and on clinical symptoms in a real-life study [ 159 , 160 ]. In our practice, we successfully used benzyl benzoate (with crotamiton) cream for more than 20 years; however, the development of ivermectin has provided an effective alternative [ 172 , 223 , 224 ] with better tolerance and this is now our treatment of choice.…”

“…However, its efficacy may, at least in part, be explained by its other important property: acaricidal effects against the Demodex mite [ 172 , 173 , 225 , 228 , 230 , 232 – 236 ]. Indeed, two other acaricidal treatments which have no known anti-inflammatory properties also improve clinical symptoms of rosacea: permethrin (5% applied twice daily) improved the vascular component of rosacea (erythema [ 221 ], telangiectasia [ 220 ]), and benzyl benzoate was shown to be an effective treatment for PPR [ 159 , 160 ]. These observations provide indirect support for the role of the mite in PPR, as already suggested by numerous other studies [ 8 , 10 , 29 , 31 , 34 , 35 , 56 – 58 , 99 , 108 , 110 , 111 , 128 , 132 – 134 , 161 – 170 ].…”

“…Topical acaricidal treatment is certainly the most appropriate treatment for patients with pityriasis folliculorum with vascular symptoms/ETR with follicular scales: this therapy kills the mites and decreases subsequent inflammation and associated persistent erythema. In our experience, topical acaricidal treatment leads to disappearance of follicular scales [ 159 , 160 ] as well as subjective complaints, such as burning sensation and hypersensitive skin. If only mild erythema is present, it may completely, or almost completely, resolve after eradication of the mites, so that supplementary treatment (e.g., light therapy) may not be needed.…”