Erythematotelangiectatic Rosacea and Subclinical Demodicosis: A Case-Control Study

1. Erythematotelangiectatic rosacea may be associated with a subclinical stage of demodicosis. A case control study. F. FORTONand V. DE MAERTELAER Free University of Brussels (ULB) British Journal of Dermatology. DOI: 10.111/bjd.17817

2. Fabienne FORTON MD, Dermatologist rue Frans Binjé, 8 B - 1030 Brussels Belgium e-mail: fabienne.forton@skynet.be

3. Introduction What’s already known? Pityriasis folliculorum • Facial skin density of Demodex mites (Dd) in patients with papulopustular rosacea (PPR) and demodicosis (a skin condition caused by Demodex) is greater than that in healthy control patients. • In patients with erythematotelangiectatic rosacea (ETR), facial Dd has been observed to be similar to or greater than that of healthy controls.  Erythema and telangiectasia, characteristics of ETR, are often observed among patients with pityriasis folliculorum, a discreet demodicosis.

4. Objective • To compare facial Demodex densities of patients with clinical ETR and patients with • healthy skin • demodicosis • rosacea with papulopustules, and • other dermatoses

5. Methods (1) • Retrospective study of • 23 patients with ETR • 20 healthy control patients • 590 patients with demodicosis • 254 with rosacea with papulopustules • 180 with other facial dermatoses. • Demodex densities measured using two consecutive standardised skin biopsies :superficial (SSSB1) & deeper (SSSB2)

6. Methods (2): Study population • Patients who attended authors’ dermatology practice in Brussels between 2002 to 2010. • All patients who attended a first consultation with centro-facial papules and/or pustules consistent with rosacea or signs of demodicosis • 2 SSSBs performed (routine in authors’ practice). • Other patients in whom measurement of Dd was not routine were included if consultation time was sufficient for two SSSBs to be performed.

7. ETR Methods (3): Clinical Diagnosis • ETR: flushing, telangiectasia or/and persistent erythema. • Careful examination to ensure patients did NOT have pityriasis folliculorum (by tangential illumination and close examination after cleaning the skin with ether). Pityriasis folliculorum • Healthy control patients also carefully examined to ensure they did NOT have pityriasis folliculorum or ETR. J Am AcadDermatol2005; 52: 74-87

8. Results(1): Mean Demodex densities • In patients with rosacea with papulopustules & with demodicosis > in patients • with ETR. • In patients with ETR > in patients with healthy skin or other facial dermatoses.

9. Results (2): Comparison of the mean Demodex densities (D/cm²) in the different clinical groups.

10. Results (3): According to the recent diagnostic criterion: SSSB1 >5 D/cm² or SSSB2 >10 D/cm² Acta Derm Venereol (Stockh) 2017; 97: 242-8. 19 patients with high Dds but no visible signs of demodicosis or rosacea with papulopustules on clinical examination

11. Discussion (1): “Subclinical demodicosis” • 19 patients, including 10/23 with ETR, who were expected to have normal Dds, had a high Dd • may represent the start of demodicosis. Clinical ETR ?Subclinical demodicosis Pityriasis folliculorum

12. Discussion (2): This suggests that ETR may favour D proliferation And, because the inflammatory reaction to Demodex includes vasodilation, our observations support the hypothesis of the existence of a vicious cycle between Demodex proliferation and vascular dilation: J EurAcadDermatolVenereol2018; 32:1011- 6.

13. Discussion (3): Important clinical implications • Dermatologists should consider a diagnosis of subclinical demodicosis when faced with a patient with ETR and measure Dd • When high, use topical acaricidal treatment (e.g., ivermectin OR 20% benzyl benzoate [with 10% crotamiton] cream) until the Dd normalises. • Future clinical studies in patients with ETR, but perhaps also with other facial dermatoses (such as acne vulgaris or seborrheic dermatitis, which are relatively frequently associated with demodicosis), should include measurement of Dd to identify or exclude possible associated subclinical demodicosis, so that patients are correctly characterised.

14. Conclusions: What does this study add? • Patients with ETR had higher mean Demodex densities than healthy control subjects and patients with other dermatoses, but lower densities than patients with rosacea with papulopustules or demodicosis. • In the early phases of demodicosis, proliferation of Demodex mites may not be clinically visible, potentially giving rise to subclinical demodicosis, particularly among patients with ETR. • These findings suggest that ETR may be associated with Demodex proliferation, raising the possibility of a pathophysiological link between erythematotelangiectatic and papulopustular rosacea.

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