Value of high‐frequency ultrasound in the treatment of moderate and severe acne vulgaris

Abstract

Background

Acne treatment may fail or cause undesirable side effects due to inaccurate evaluation. High‐frequency ultrasound (HFUS) can monitor systemic treatment in patients with moderate‐to‐severe acne vulgaris.

Materials and methods

In this prospective study, consecutive patients with moderate‐to‐severe acne vulgaris were recruited. Patients were graded by a comprehensive clinical assessment before and after therapy. Simultaneous HFUS grading was independently evaluated according to the sonographic scoring system for acne (SSSA). Clinical and HFUS grades were compared through kappa analysis.

Results

A total of 70 patients were enrolled. At baseline, 36 (51.4%) and 34 (48.6%) patients were graded as moderate and severe, respectively, through clinical assessment. However, 27 patients (38.6%) scored SSSA‐Grade II and 43 (61.4%) scored SSSA‐Grade III in the HFUS grading. Sixty‐one patients (87.1%) were in the consistent category as per clinical assessment and HFUS grades, with Kappa₁ = 0.745, whereas higher HFUS grades were observed in nine patients. By the end of the observation, 65 of all patients (92.9%) showed significant improvement and 5 (7.1%) showed no apparent improvement after the treatment. According to the clinical assessment, 14, 52, and 4 patients were graded as mild, moderate, and severe, respectively. On the other hand, 11, 51, and 8 patients had SSSA‐Grade I, II, and III, respectively. Of all patients, 63 (90.0%) had consistent evaluation results, with Kappa₂ = 0.762, whereas the remaining seven patients had an HFUS grade higher than the clinical.

Conclusion

HFUS is a useful tool for dermatologists to monitor the treatment of moderate and severe acne vulgaris.

1. INTRODUCTION

Acne vulgaris is a chronic inflammatory skin disease affecting the pilosebaceous follicles of the skin. Acne vulgaris tends to occur in teenagers as one of the most common facial skin diseases. Proper treatment reduces scarring and psychological effects, especially in patients with moderate and severe disease. ¹ , ² Clinical recommendations and guidelines recommend systemic treatment, such as systemic antibiotics or retinoids, for moderate‐to‐severe acne. ³ , ⁴ , ⁵ However, the side effects of long‐term systemic therapy are concerning, for example, isotretinoin may cause inflammatory bowel disease, arthritis, hyperlipidemia, depression, and suicide. ⁶ Thus, the accurate evaluation of therapeutic response is crucial for a systemic treatment strategy. However, the evaluation of acne severity often relies on the experience of dermatologists. ³ , ⁷ Such subjective inspection also fails to identify deeper or nonpalpable involvement of the hair follicles.

High‐frequency ultrasound (HFUS) is a noninvasive, objective imaging method for identifying deep lesions in the skin. It has recently been widely accepted in the field of dermatology. ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ Previous studies have shown that HFUS is of great value in observing the severity and grading of acne, detecting deep changes in acne, and assessing the size and features of lesions accurately. ¹⁶ , ¹⁷ A recent study has reported the value of HFUS in monitoring the treatment of acne. In 14 patients with acne vulgaris who underwent 4 chemical peelings at 2‐week intervals, a decrease in the thickness of entrance echo and an increase in the density of dermis were observed on HFUS after treatment. ¹⁸ However, the response evaluation of systemic treatment in moderate‐to‐severe acne vulgaris using HFUS has not been previously reported. If HFUS can objectively evaluate lesion improvement, it can benefit patients getting systemic treatment for downstaging or conversion to topical treatment.

Therefore, the purpose of this study was to determine the value of HFUS in monitoring systemic therapy for moderate‐to‐severe acne vulgaris.

2. METHODS

2.1. Study design and cohorts

This prospective study was conducted on patients diagnosed with moderate‐to‐severe acne vulgaris in the Peking Union Medical College Hospital from October 2020 to June 2021. This study was approved by the Medical Ethics Committee of the Peking Union Medical College Hospital, and written informed consent was obtained from all patients. The inclusion criteria were as follows: (1) moderate‐to‐severe acne vulgaris diagnosed by two senior dermatologists, (2) no administration of local treatment 1 month prior to the study, and (3) no administration of systemic therapy 6 months prior to the study. The exclusion criteria were as follows: (1) no regular and continuous treatment and (2) incomplete clinical information or ultrasound images.

2.2. Treatment and clinical evaluation

Evaluation of each patient for clinical grading was conducted according to the Chinese Guidelines for the Management of Acne Vulgaris, and depending on it they received appropriate systemic and topical treatments ⁵ (Table 1). Patients were regularly assessed for the most severe lesion at that time every 2 until 8 weeks based on the clinical grade. The most severe lesions may not be the same after the effective treatment, particularly in patients with multiple lesions. To standardize the evaluation process, the most severe lesion was decided by the dermatologist's clinical assessment at the baseline and follow‐up. The index lesion was marked to ensure that the US measurement was performed at the same point. The downgrade of clinical grade was considered to be a clinically significant improvement of disease. All the previous observations were made independently by two senior dermatologists. In addition, for all disagreements between the two doctors, the consensus was reached through discussion.

TABLE 1.

Clinical and ultrasonic grading of acne

Clinical grade		Definition	Ultrasonic grade	Definition
Mild	Grade I	Comedones	Grade I	Widened hypoechoic band, with or without surrounding heterogeneous dermal echogenicity
Moderate	Grade II	Involving inflammatory papules	Grade II	Focal area of dermal hypoechogenicity (<5 mm)
	Grade III	Involving pustules
Severe	Grade IV	Involving nodules and/or cysts	Grade III	Pseudocyst (≥5 mm), with or without apparent epidermal bulging

2.3. Ultrasound imaging

The HFUS images were also stored on the most severe lesion by the same operator following clinical examination. The device used for HFUS was an MD‐300S type II diagnostic system (MEDA Co., Ltd. Tianjin, China) operating with 20 and 50 MHz probes. Both 50 and 20 MHz probes were used to scan each lesion. Under HFUS, the involved hair follicle showed as a widened hypoechoic band. The the involved inflammatory papule or pustule showed as a focal hypoechogenic lesion (<5 mm) in the dermis with surrounding heterogeneous dermal echogenicity representing folliculitis or perifolliculitis. Moreover, the pseudocyst (≥5 mm) showed as a round or oval‐shaped hypoechoic structures without well‐defined wall within the dermis and/or the hypodermis, with or without apparent epidermal bulging. ¹⁶ Ultrasound grades of lesions were independently evaluated by two experienced doctors according to the sonographic scoring system for acne (SSSA) ¹⁷ (Table 1). Numerical codes were randomly assigned to each patient to ensure blinding. In the case of disagreements between the two doctors, a consensus reading was achieved.

2.4. Statistical analyses

The consistency of evaluation between clinical and ultrasound grading was measured using the Kappa value, which was interpreted as follows: Kappa < 0, poor agreement; 0 < Kappa < 0.20, slight agreement; 0.20 < Kappa < 0.40, fair agreement; 0.40 < Kappa < 0.60, moderate agreement; 0.60 < Kappa < 0.80, substantial agreement; and 0.80 < Kappa < 1, perfect agreement. The analyses were performed using SPSS software (version 25.0; IBM Corp, Armonk, NY, USA).

3. RESULTS

3.1. Demographic characteristics

In this study, of the total 70 patients with acne vulgaris, mean age of 24.4 ± 4.6 years, 28 (40.0%) were men, and 42 (60.0%) were women. All patients were treated based on disease severity according to the guidelines, ⁵ including oral minocycline, oral isotretinoin, topical retinoids, benzoyl peroxide, or antibiotics.

3.2. Clinical evaluation of the treatment response

At baseline, 0 (0.0%), 8 (11.4%), 28 (40.0%), and 34 (48.6%) scored Grade I (mild), II (moderate), III (moderate), and IV (severe), respectively, according to the clinical classification. After treatment, as per clinical examination, 14 (20.0%), 52 (74.3%), 0 (0.0%), and 4 (5.7%) patients scored Grade I (mild), II (moderate), III (moderate), and IV (severe), respectively (Figure 1). Notably, 35 (35/36, 97.2%) moderate and 30 (30/34, 88.2%) severe cases at baseline showed significant improvement after the treatment (Figure 1).

FIGURE 1.

The results of clinical response evaluation before and after treatment. The results of clinical response evaluation before and after treatment. The X‐axis represents the number of patients, whereas the Y‐axis represents the clinical classification.

3.3. Comparison between clinical and ultrasonic response evaluation

A comparison of staging between clinical and ultrasound examinations for each patient was performed before and after treatment (Tables 2 and 3). At baseline, the grades of the clinical and ultrasound findings were consistent in 61 cases (87.1%) and inconsistent in 9 cases (12.9%), Kappa₁ = 0.745, whereas after treatment, they were consistent in 63 cases (90.0%) and inconsistent in 7 cases (10.0%), Kappa₂ = 0.762.

TABLE 2.

Comparison between clinical and ultrasonic evaluation at baseline

	Baseline
	Ultrasound grade
Clinical grade	I	II	III	Total
Mild	0	0	0	0
Moderate	0	27	9	36
Severe	0	0	34	34
Total	0	27	43	70

TABLE 3.

Comparison between clinical and ultrasonic evaluation after treatment

	Posttreatment
	Ultrasound grade
Clinical grade	I	II	III	Total
Mild	11	3	0	14
Moderate	0	48	4	52
Severe	0	0	4	4
Total	11	51	8	70

Of the 65 patients with significant improvement (clinically downgraded) after the treatment, HFUS categorized 11 (16.9%), 50 (76.9%), and 4 (6.2%) patients as SSSA‐Grade I, II, and III, respectively. Concordance results were achieved between the clinical and HFUS evaluations in 58 (89.2%) patients (Figure 2). However, there was a discordance between clinical findings and HFUS in seven (10.8%) patients (Figure 3). Of the five patients who did not respond to treatment, HFUS assessed one patient as SSSA‐Grade II and four as SSSA‐Grade III.

FIGURE 2.

The 27‐year‐old female patient with acne vulgaris: (A) At baseline, some comedones, follicular papules, and nodules were visible on her face; (B) the patient took minocycline 100 mg/day orally and applied benzoyl peroxide gel and adapalene gel topically for 8 weeks, significant improvement was observed and only a few papules and pustules were left; (C) the most severe lesion was a cyst (white circle), and the pretreatment clinical grading was severe (Grade IV); (D) the most severe lesion after treatment was inflammatory papule (white circle) with a clinical grading of moderate (SSSA‐Grade III); (E) pretreatment ultrasound (20 MHz) identified a pseudocyst of ∼9 mm (>5 mm) within the dermis and subcutaneous tissue, deep to the adipose layer with indistinct borders and posterior echogenic enhancement (SSSA‐Grade III); (F) posttreatment ultrasound (20 MHz) showed significant improvement in the lesion, with only a focal hypoechoic lesion of ∼3 mm within the dermis (SSSA‐Grade II); and (G) and (H) schematic diagrams of the most severe lesion before and after treatment

FIGURE 3.

The 21‐year‐old male patient with acne vulgaris: (A) At baseline, multiple nodules and cysts were seen on his face; (B) after taking 20 mg/day of oral isotretinoin and 1 g/day of erythromycin, the lesions improved significantly, and cysts and nodules disappeared; (C) the most severe lesion (white circle) before treatment was cyst, and the pretreatment clinical grading was severe (Grade IV); (D) the most severe lesion (white circle) after treatment was inflammatory papule with a clinical grading of Grade II; (E) pretreatment ultrasound (50 MHz) showed a pseudocyst of ∼11 mm (>5 mm) in the dermis with poorly defined borders and uneven internal echogenicity (SSSA‐Grade III); (F) although the lesion significantly reduced after treatment, ultrasound (50 MHz) still showed a pseudocyst of about 6 mm (Grade III); and (G) and (H) schematic diagrams of the most severe lesion before and after treatment

4. DISCUSSION

As a noninvasive imaging modality, HFUS allows for the precise assessment of therapeutic interventions owing to its ability to provide a spatial resolution of the superficial structures of the skin and appendages. It is widely used for treatment monitoring in hidradenitis suppurativa, plaque psoriasis, atopic dermatitis, and skin tumors. ¹⁰ , ¹³ , ¹⁴ , ¹⁹ A recent study ¹⁸ evaluated the effect of chemical peel treatment in 14 patients with mild acne vulgaris by 33 MHz HFUS. The results demonstrated that HFUS is objective and enables the quantitative presentation of skin parameters and effects of the therapy. Thus, HFUS can be a useful tool for monitoring responses during the treatment of acne vulgaris. Moreover, we recruited 70 patients with moderate or severe acne and compared the ultrasound and clinical manifestations at the point of significant improvement after treatment.

Substantial agreement between the clinical grading and HFUS before and after treatment was observed (Kappa₁ = 0.745, Kappa₂ = 0.762) in this study. This highlights that HFUS could be useful for evaluating the improvement of acne lesions. A downgrade on HFUS depicts a significant improvement in lesion size and degree of inflammation and objectively reflects the therapeutic effect. Furthermore, once the lesions improve significantly, it is important to modify the systemic therapeutic strategy to reduce the associated side effects of drugs. We further analyzed the grading of treated cases in this study. In 65 cases of moderate or severe acne with an apparent downgrade, a good agreement on the scores of clinical and ultrasound was found in the majority (89.2%) of cases, including 47 cases of SSSA‐Grade II and 11 cases of SSSA‐Grade I. HFUS manifested the treatment efficacy from a new observation dimension and met the criteria for adjusting the treatment regimen.

However, discordance between ultrasound and clinical evaluation was observed in nine patients before treatment. Interestingly, all patients were evaluated as moderate on the clinical grading, whereas HFUS revealed more severe lesions (SSSA‐Grade III), namely, pseudocysts appearing as round or oval‐shaped hypoechoic structures within the dermis or even within the subcutaneous tissue. These results were consistent with the findings of a previous study by Martorell et al., ¹⁰ where the underestimation of the severity of hidradenitis suppurativa was identified using HFUS. It emphasized that HFUS could be used to observe subclinical changes in lesions and help in making appropriate clinical decisions. For this reason, HFUS might be helpful in optimizing the treatment regimen and facilitating more effective local interventions in the most severe lesions.

In addition, there were seven more patients who had inconsistent grades between clinical and ultrasonic assessment. A downgrade in clinical classification indicates the effectiveness of treatment; however, most of the patients (6/7) showed no obvious change in the ultrasound classification. On reviewing the posttreatment information of these patients, it was found that there were no cysts that can be observed by the naked eye in four patients with moderate grade; however, local lesions (>5 mm) could still be observed on ultrasound, namely, SSSA‐Grade III (Figure 3). For the remaining three patients with mild acne after treatment, focal hypoechogenic lesions were observed on ultrasound (SSSA‐Grade II). The fact that more serious lesions were observed on ultrasound after treatment suggests that the treatment still needs to be maintained or topical medication should be intensified.

Both clinical and ultrasonic grading are direct assessment methods that are based on the most severe lesions. Clinical grading is mainly based on direct observation by the naked eye, which is simpler and faster, but may sometimes misjudge the severity of skin lesions. HFUS can effectively overcome this deficiency. Therefore, HFUS combined with clinical evaluation can more accurately assess the most severe lesions and achieve precise classification before and after treatment, thus providing objective and valuable imaging information for clinical decision‐making and subsequent treatment modification, such as strengthening systemic treatment or changing to topical treatment.

Our study has some limitations. First, SSSA has difficulties in the evaluation of SSSA‐Grade III with diameters larger than the field of view of HFUS. It is difficult for such lesions to decrease in size (<5 mm, SSSA‐Grade I or II) after 8 weeks of treatment. Therefore, in HFUS, SSSA grade would remain as SSSA‐Grade III; however, it will be downgraded in clinical assessment as the lesions shrink after effective treatment. Further refined HFUS criteria are warranted for such severe cases. Second, this study did not explore the changes observed in HFUS for mild acne during treatment; however, present results have suggested that ultrasound has good efficacy in assessing therapeutic effects.

5. CONCLUSION

HFUS provides a new perspective for evaluating treatment efficacy in moderate or severe acne vulgaris. The combination of HFUS and naked‐eye observation can effectively assist dermatologists in assessing the severity of acne and treatment effects to develop an optimal and precise treatment strategy.

CONFLICT OF INTEREST

None declared.

Luo Y, Wang J, Gao Y, et al. Value of high‐frequency ultrasound in the treatment of moderate and severe acne vulgaris. Skin Res Technol. 2022;28:833–839. 10.1111/srt.13208

DATA AVAILABILITY STATEMENT

Research data are not shared.