Color Doppler ultrasonographic evaluation of management of papulopustular rosacea

To the Editor: Rosacea is a chronic inflammatory disorder that commonly affects the face and presents several phenotypes; however, to date, there are still gaps in the understanding of rosacea pathophysiology.1Gallo R.L. Granstein R.D. Kang S. et al.Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee.J Am Acad Dermatol. 2018; 78: 148-155Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Particularly, in papulopustular rosacea lesions (PPR), topical ivermectin and metronidazole are first-line treatments.1Gallo R.L. Granstein R.D. Kang S. et al.Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee.J Am Acad Dermatol. 2018; 78: 148-155Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar,2Tan J. Berg M. Rosacea: current state of epidemiology.J Am Acad Dermatol. 2013; 69: S27-S35Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar Color Doppler ultrasonography (CDU) is a noninvasive imaging technique that can support a broad spectrum of dermatologic conditions.3Wortsman X. Common applications of dermatologic sonography.J Ultrasound Med. 2012; 31: 97-111Crossref PubMed Scopus (146) Google Scholar A double-blind randomized controlled clinical trial was conducted in patients with rosacea from March to September 2018. The aim of this study was to evaluate the ultrasonographic findings in patients with PPR rosacea treated with topical ivermectin and metronidazole. The study was approved by the institutional review board (no. 472920), and the clinical trial number is NCT24435875. The CDU examination recorded the thickness and vascularity of the dermis and subcutis of the right cheek and nasal tip as well as at the alar cartilage in patients (baseline and at the 12-week follow-up) and 10 healthy control individuals. Statistical significance was assessed at a P value of less than .05. More details on the methodology, inclusion and exclusion criteria, and statistics are described in the supplemental materials (available via Mendeley at https://doi.org/10.17632/bn89h9kkn3.1). Twenty-seven patients entered the study, and 23 completed the follow-up. The clinical and ultrasonographic characteristics of the patients and healthy control individuals are described in Table I and Supplemental Tables I to III (available via Mendeley at https://doi.org/10.17632/bn89h9kkn3.1).Table IBaseline color Doppler ultrasonography features of healthy control individuals and patients with PPRCharacteristicsControl individuals (n = 10)Baseline (n = 27)P valueRight cheek Dermal thickness, mm, mean ± SD1.6 ± 0.21.6 ± 0.4.95 Dermal echogenicity, n (%)Hyperechoic3 (30.0)6 (22.2).30Hypoechoic0 (0)21 (77.8)<.01Mix (hyperechoic and hypoechoic)7 (70.0)0 (0)<.01 Dermis-subcutis hypervascularity, n (%)Absent6 (60.0)1 (3.7)<.01Present4 (40.0)26 (96.3)<.01 Thickness of vessels, mm, mean ± SD0.7 ± 0.31.0 ± 0.2.15 Peak systolic velocity of arterial vessels, cm/s, mean ± SD4.2 ± 1.56.3 ± 2.3.11Nasal region Dermal thickness, mm, mean ± SD1.5 ± 0.31.8 ± 0.4.07 Dermal echogenicity, n (%)Hyperechoic1 (10.0)0 (0).04Hypoechoic8 (80.0)27 (100).08Mix (hyperechoic and hypoechoic)1 (10.0)0 (0).04 Dermis-subcutis hypervascularity, n (%)Absent10 (100)1 (3.7)<.01Present0 (0)26 (96.3)<.01 Thickness of vessels, mm, mean ± SD—0.7 ± 0.4— Peak systolic velocity of arterial vessels, cm/s, mean ± SD—6.4 ± 4.0—Alar nasal cartilages Thickness, mm, mean ± SD1.7 ± 0.32.0 ± 0.6.11 Hypervascularity, n (%)Absent7 (70)13 (48.1).11Present3 (30)14 (51.9).11 Thickness of vessels, mm, mean ± SD0.9 ± 0.20.8 ± 0.4.41 Peak systolic velocity of arterial vessels, cm/s, mean ± SD46.8 ± 3.2.81Significant Values are indicated by bold text.PPR, Papulopustular rosacea; SD, standard deviation. Open table in a new tab Significant Values are indicated by bold text. PPR, Papulopustular rosacea; SD, standard deviation. At baseline, patients with PPR presented a significantly higher dermal and subcutis vascularity in the right cheek and nasal region and higher hypoechogenicity of the dermis of the cheek (P < .01). At the nasal region, the dermis was hypoechoic or heterogeneous in both groups; however, a slight raising or undulation of the epidermis was noted only in PPR cases. Overall, 96.3% of patients with PPR presented with dermal and subcutis facial hypervascularity, and 51.9% showed hypervascularization of the alar nasal cartilages. Regardless of the type of treatment, none of the ultrasonographic parameters showed significant changes at the follow-up. Additionally, no association was found between the clinical variables and the presence of vascularity within the nasal cartilages (Fig 1). The clinical number of inflammatory lesions significantly decreased in both groups; however, the investigator's global assessment score significantly decreased only for metronidazole. Despite the high prevalence of rosacea worldwide, we found only 1 reference on ultrasonography of rosacea based on personal experience.4Wortsman X. Color Doppler ultrasound.in: Kaminsky A. Piquero-Martin J. Herane M.I. Diez de Medina J. Florez White M. Iberian-Latin American Acne and Rosacea Study Group GILEAR Rosacea: A Comprehensive View. 1st ed. 2020: 259-266Google Scholar In our PPR sample, even though there was a clinical improvement, there were anatomic alterations of deeper layers and a lack of significant ultrasonographic changes after the administration of both topical treatments. This means that rosacea is not only a superficial cutaneous condition and that clinical evaluation alone can underestimate the degree of the inflammatory process. In addition, topical agents may be insufficient to treat the involvement of deeper layers. Limitations of our study are the small sample and the impossibility of detecting ultrasonographically alterations of less than 0.1 mm.3Wortsman X. Common applications of dermatologic sonography.J Ultrasound Med. 2012; 31: 97-111Crossref PubMed Scopus (146) Google Scholar Subclinical ultrasonographic alterations and activity have been found in other inflammatory diseases such as hidradenitis suppurativa.5Wortsman X. Moreno C. Soto R. Arellano J. Pezo C. Wortsman J. Ultrasound in-depth characterization and staging of hidradenitis suppurativa.Dermatol Surg. 2013; 39: 1835-1842Crossref PubMed Scopus (100) Google Scholar In rosacea, this may explain the frequent relapses and rhinophyma. In conclusion, regardless of the type of treatment, ultrasonography shows evidence of deeper inflammation in PPR, and this should require further research.