Value of reflectance confocal microscopy for the monitoring of rosacea during treatment with topical ivermectin

Figures & data

Table 1. Demographic and baseline clinical characteristics.

	Rosacea patients (n = 20)
Age, years
Mean ± SD (min–max)	52.8 ± 14.5 (24–81)
Gender, n (%)
Female	11 (55)
Male	9 (45)
Skin photo type
I	2 (10%)
II	15 (75%)
III	3 (15%)
Investigator’s global assessment
3 = Moderate	16 (80%)
4 = Severe	4 (20%)
Inflammatory lesion count
Median (range)	36.5 (0–144)
Erythema scale
1 = Almost clear	2 (10%)
2 = Mild	3 (15%)
3 = Moderate	13 (65%)
4 = Severe	2 (10%)
Telangiectasia scale
1 = None	4 (20%)
2 = Mild	8 (40%)
3 = Moderate	8 (40%)

Figure 1. Clinical scores of all patients during 16 weeks of treatment with topical ivermectin and at week 28 (follow-up). (a–e) IGA scale, IGA success scale (IGA 0 or 1), papules and pustules scale, erythema scale, and telangiectasia scale. (f) Number of facial inflammatory lesions, expressed as median with range. IGA: investigator’s global assessment.

Figure 2. Rosacea in a 56-year old man, (a) at baseline, (b) at week 16 of treatment with topical ivermectin 1% once daily, and (c) 12 weeks post-treatment. Notice the disappearance of papules and pustules at the forehead and prominent erythema at the cheeks, while telangiectasias and residual erythema at both cheeks are persisting. The green dots serve as a tool to assess clinical erythema.

Figure 3. Demodex mites during 16 weeks of treatment with topical ivermectin and at week 28 (follow-up), measured with RCM. (a) Mite presence per 8x8 mm², expressed as present or absent. (b) Number of mites per 8 × 8 mm^2, expressed as median with range.

Figure 4. Confocal images of the cheek (0.5 × 0.5 mm²). (a) Follicle at the level of the stratum granulosum containing seven Demodex mites, clearly visible as bright, round contours. (b) Follicle at the level of the stratum granulosum with unclear content due to vague, white-roundish structures, included in mite category doubt. (c) Multiple bright, round to oval or fusiform cells with dendritic processes at the level of the dermo-epidermal junction, possibly melanocytes or Langerhans cells. (d) Multiple bright, round cells at the level of the dermo-epidermal junction, possibly inflammatory cells.

Table 2. Mite and follicle numbers per 8 × 8 mm².

	Baseline	Week 6	Week 12	Week 16	Week 28	Baseline versus week 16 p Value	Baseline versus week 28 p Value	Week 16 versus week 28 p Value
Mite presence
n patients present (%)	16 (80%)	10 (50%)	6 (30%)	6 (30%)	12 (63%)	–	–	–
Mites, n	13	0.5	0.0	0.0	1.0	<.001	.001	.13
Median (range)	(0.0–203)	(0.0–29)	(0.0–10)	(0.0–14)	(0.0–21)
Follicles, n	262	266	263	260	262	.21	>.99	.14
Median (range)	(162–331)	(213–355)	(129–402)	(183–386)	(162–384)
Infested follicles, n	6.0	0.5	0.0	0.0	1.0	<.001	<.001	.20
Median (range)	(0.0–73)	(0.0–9.0)	(0.0–6.0)	(0.0–6.0)	(0.0–7.0)
Mites/follicle, n	0.052	0.002	0.000	0.000	0.004	<.001	<.001	.15
Median (range)	(0.00–0.712)	(0.00–0.109)	(0.00–0.039)	(0.00–0.067)	(0.00–0.072)
Mites/infested follicle, n	2.0	0.5	0.0	0.0	1.0	<.001	.33	.036
Median (range)	(0.0–4.5)	(0.0–4.1)	(0.0–3.0)	(0.0–2.3)	(0.0–4.0)
Mites/follicle
Median % of follicles
0	91	96	97	97	96	–	–	–
1	1.2	0.0	0.0	0.0	0.0	–	–	–
≥2	1.6	0.0	0.0	0.0	0.0	–	–	–
Doubt^a	5.8	3.1	2.8	2.6	3.2	–	–	–

^a Unclear follicle content, not clearly distinguishable as mites.

Figure 5. (a) Vascular diameter and (b) vascular density scores during 16 weeks of treatment with topical ivermectin and at week 28 (follow-up), determined with RCM.

Table 3. Inflammatory parameters and epidermal thickness.

	Baseline	Week 6	Week 12	Week 16	Week 28	Baseline versus week 16 p Value	Baseline versus week 28 p Value	Week 16 versus week 28 p Value
Inflammatory cells, n	41	31	39	27	51	.089	.73	.21
Median (range)	(2.0–494)	(0.0–425)	(0.0–426)	(2.0–370)	(1.0–563)
Inflammatory nests, n	0.0 (0.0–2.0)	0.0 (0.0–4.0)	0.0 (0.0–2.0)	0.0 (0.0–1.0)	0.0 (0.0–1.0)	.17	.089	>.99
Median (range)
Spongiosis, n keratinocytes/mm^2	2519	2517	2378	2268	2377	.004	.031	.48
Median (range)	(1933–3435)	(1668–3186)	(1601–3131)	(1513–2602)	(1723–3108)
Thickness SC, µm	10.2	9.28	11.6	10.8	8.50	.58	.21	.48
Median (range)	(6.18–18.6)	(6.18–13.9)	(6.96–20.6)	(5.41–27.8)	(6.18–17.0)
Thickness viable epidermis, µm	55.3	54.9	54.9	55.7	54.9	.32	.30	.51
Median (range)	(44.8–70.9)	(47.9–70.4)	(43.3–68.8)	(44.1–66.5)	(42.5–67.3)

SC: stratum corneum.

Table 4. Mixed model logistic regression models determining RCM features associated with clinical success (IGA 0/1).

	IGA score 0 or 1	p Value
Mite presence, present/absent	2.10 (0.82–6.07)	.14
Demodex mites, n	1.11 (1.01–1.29)	.10
Infested follicles, n	1.28 (1.03–1.82)	.088
Mites/follicle, n	3.61^12 (55.5–2.49^31)^a	.095
Mites/infested follicle, n	1.49 (0.97–2.49)	.090
Inflammatory cells, n	0.9996 (0.9959–1.0039)	.85
Inflammatory nests, n	1.70 (0.65–9.76)	.41
Spongiosis, n keratinocytes/mm^2	1.0002 (0.9990–1.0017)	.64
SC thickness, µm	1.13 (0.94–1.44)	.22
Thickness viable epidermis, µm	1.03 (0.95–1.12)	.50
Vascular diameter, scale 1–5	0.84 (0.43–1.74)	.61
Vascular density, scale 1–5	0.77 (0.33–1.71)	.52

Values are given as odds ratios (95% confidence intervals). IGA: investigator’s global assessment.

^a Large OR + 95% CI due to low median value and highly skewed distribution of this variable (also see Table 2).