Efficacy and safety of the Exfoliate-Dissolve-Repair skin care approach in the treatment of keratosis pilaris: a randomized controlled clinical trial study protocol

Abstract

Background

Keratosis pilaris (KP) is a chronic skin disease characterized by keratinized hair follicle papules, typically occurring on the arms, thighs, and buttocks. At present, the external treatment plan for KP is relatively singular. To optimize the existing clinical external drug treatment plan for KP, improve side effects, and enhance patients’ quality of life, we propose the Exfoliate-Dissolve-Repair (EDR) comprehensive skin care method. Based on the EDR concept, we have designed a treatment plan that combines body scrub and moisturizing lotion. This research plan aims to evaluate the safety and efficacy of a novel skincare combination therapy for KP through a randomized controlled trial.

Methods

This study is a single center, randomized, controlled clinical trial targeting cases of KP aged 18–35 years. Participants (n = 72) were randomly assigned to a treatment group and a control group. The treatment group received EDR comprehensive skin care intervention, while the control group received 0.1% retinoic acid cream intervention. The trial includes a 4-week treatment period, with indicator testing and data collection conducted at 7, 14, 21, and 28 days after the start of treatment. The main outcome measures include the improvement index of follicular papules and evaluation of skin keratinization degree. Secondary outcome measures include skin moisture content, transdermal moisture loss test, skin elasticity, etc. Use the skin lesion condition, blood pressure, heart rate, heart rhythm, and respiratory rate of the subjects as safety evaluation indicators. Exploratory evaluation of the effectiveness and safety of the EDR comprehensive skin care method for KP.

Discussion

This study will be the RCT to directly compare the effects of EDR comprehensive skincare approach and 0.1% retinoic acid cream in KP. Findings from the study will provide evidence to inform the clinical management of KP.

Trial registration

This protocol has been registered prospectively in ISRCTN under the ISRCTN14455606 on April 6, 2025.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-026-09423-x.

Introduction

Background and rationale {6a}

Keratosis pilaris (KP), commonly known as “chicken skin,” is a chronic skin keratinization disorder characterized by the presence of unique keratotic follicular papules. This condition typically occurs on the outer arms, thighs, and buttocks, and in some severe cases, it can also affect the face, shoulders, forearms, and calves, occasionally appearing in a generalized distribution [1]. Studies have shown that the prevalence of KP is about 80% among adolescents and approximately 40% among adults. Notably, this condition is more common in women, especially in those exhibiting signs of hyperandrogenism, with an incidence rate six times higher than that in men [2].

The formation of KP papules is essentially due to keratin plugs filling the follicular infundibulum and extending to the skin surface. Histological features show that KP is characterized by pronounced keratin plugs at the follicular openings, hyperkeratosis, epidermal hyperplasia, accompanied by lymphocytic infiltration in the per follicular dermis, and papillary layer hyperplasia [3]. The appearance of KP lesions varies widely, ranging from tiny follicular papules to more pronounced protrusions. Most papules are approximately 1 mm, presenting in a diffuse or clustered pattern, and are sometimes associated with erythema around the follicles. Additionally, KP can lead to changes in the stratum corneum surrounding the follicles, disrupting the barrier function of the epidermis, which in turn causes abnormal intercellular permeability. Although the exact pathogenesis of KP is not fully understood, most studies suggest that the condition has a genetic predisposition, typically becoming noticeable during puberty, with about a 50% chance of being inherited by offspring, independent of gender. Furthermore, it is closely related to factors such as impaired skin barrier function and abnormal stratum corneum metabolism. Current literature indicates that mutations in the filaggrin gene (FLG) play a crucial role in the mechanism of KP, affecting the proliferation of keratinocytes and the subsequent inflammatory response [4, 5]. The most widely accepted theory suggests that the typical keratin plugs in the follicular infundibulum stem from defects in the keratinization of follicular epithelium, leading to excessive accumulation of keratin and keratinocytes within the follicles. Hairs trapped in the papules can trigger KP when hair shaft distortion leads to rupture of the follicular epithelium, ultimately resulting in keratinization defects and inflammation of the follicles. Therefore, researcher Thomas and colleagues proposed that KP is not a primary disease of keratinocytes, but rather a type of hair shaft disorder [6].

The treatment of keratosis pilaris (KP) primarily aims to alleviate symptoms and improve the quality of life for patients. Frequently utilized pharmacological treatments encompass topical keratolytics or keratolytic agents, which include formulations containing lactic acid, salicylic acid, and urea. Studies have shown that lactic acid can effectively regulate skin keratinization and may be more effective than salicylic acid in treating KP. Salicylic acid, as a topical keratolytic agent, can reduce the adhesion between keratinocytes [7]. Additionally, urea, topical retinoids, tacrolimus, Aquaphor, coral calcium, spray-based nitrogen mist, and chlorine dioxide-based cleansing agents have also been demonstrated to have certain efficacy in the treatment of KP [8].

Topical retinoids are also commonly used in the treatment of KP, as these medications can promote skin cell turnover, thereby improving pore blockage and helping to alleviate KP symptoms. This includes pro-drugs of vitamin A, such as tazarotene, as well as retinoic acid creams [9]. If there are significant signs of inflammation in the skin, short-term treatment with glucocorticoid preparations, such as clobetasol propionate or hydrocortisone, or with tacrolimus ointment may be employed [10]. However, the treatment of KP still faces several urgent issues that need to be addressed, such as variable efficacy, high recurrence rates, and potential side effects from certain medications, including skin atrophy and pigmentation changes. For instance, while tazarotene may be used to treat KP, its efficacy is limited, and it may also cause side effects such as skin irritation, erythema, and desquamation. In addition to pharmacological treatments, phototherapy has shown certain potential in the management of KP [11–13]; however, most studies to date have been small-sample trials, and further exploration of its efficacy is needed. Given the limitations of current KP therapies, a multi-target approach is needed. The Exfoliate-Dissolve-Repair (EDR) strategy is designed to logically address the core pathological features of KP: physical exfoliation removes follicular plugs, chemical dissolution reduces hyperkeratosis, and barrier repair with lipids restores epidermal function. This integrated method aims to improve efficacy and potentially reduce relapse by synergistically targeting multiple aspects of the condition.

Objectives {7}

1. Primary objective

To evaluate the efficacy of the EDR comprehensive skincare regimen compared with 0.1% retinoic acid cream in improving keratotic papules in patients with KP, as measured by the Improvement Index of Keratotic Papules and the Investigator’s Global Assessment grading scale.

• 2.
  Secondary objectives

  • a
    To compare the effects of the EDR regimen versus 0.1% retinoic acid cream on skin hydration (Corneometer), erythema index (Mexameter), and trans‑epidermal water loss (TEWL, Aqua Flux).
  • b
    To assess changes in skin elasticity (Cutometer), surface roughness, smoothness, and scaling (VC98) following each intervention.
  • c
    To document participant‑reported improvement through follow‑up questionnaires.

Trial design {8}

This is a prospective, randomized, controlled clinical trial. We followed the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) in the conduction of this protocol [14]. The SPIRIT Checklist can be viewed in Supplementary file 1.

Methods

Study setting {9}

This trial planned to recruit patients with keratosis pilaris from the Beijing Technology and Business University Laboratory, scheduled from January 1 to December 31, 2025. The research protocol has been approved by the Ethics Committee of Beijing Technology and Business University (approval number: 2024-131). All participants will provide signed informed consent. The study will be conducted in strict accordance with the principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments to ensure the ethical conduct of research and the rights of participants.

Eligibility criteria {10}

Diagnostic criteria

The clinical diagnosis of keratosis pilaris is primarily based on the following features as referenced from the relevant standards of the UpToDate clinical decision support system: presence of keratotic papules, often spiny in appearance, affecting the extensor surfaces of the upper arms and thighs, accompanied by varying degrees of erythema. Skin biopsies are usually unnecessary; however, if performed, they may reveal dilated infundibula and keratinous plugs with regular keratinization.

Inclusion criteria

1. Chinese participants aged 18 to 35 years who meet the diagnostic criteria for keratosis pilaris.

2. Participants should voluntarily accept treatment, complete the course, attend follow-up appointments punctually for photographs, and sign the informed consent form.

Exclusion criteria

1. Individuals with serious organic diseases of major organs such as cardiovascular disease, diabetes, liver or kidney diseases, bleeding disorders, severe primary hematological diseases, or mental health disorders.

2. Patients with documented hypersensitivity to the investigational pharmaceuticals.

3. Patients with active viral infections at treatment sites such as herpes simplex or warts, or those who have undergone cryotherapy, radiation, phototherapy, or surgery within the past 6 months.

4. Individuals who have taken oral corticosteroids within the last 3 months.

5. Patients with immunodeficiency disorders or a history of keloid formation.

6. Individuals currently participating in or having participated in other clinical studies or treatments within the last 3 months.

7. Women who are planning to become pregnant, currently pregnant, or breastfeeding.

8. Patients whose history, physical examination, and laboratory tests allow for the exclusion of keratosis pilaris secondary to other diseases.

Rejection criteria

1. Participants were re-evaluated and found not to meet the inclusion criteria.

2. Participants who interrupt treatment before completing the prescribed observation period or who independently seek other treatment methods.

3. Individuals who cannot tolerate the treatment plan or who are allergic to the medication.

4. Participants who discontinue treatment due to adverse reactions will be included in the intention‑to‑treat (ITT) analysis for efficacy evaluation; their last observation will be carried forward for the primary outcome. Safety data from these participants will be recorded and analyzed separately.

5. Participants for whom efficacy cannot be determined, or who have incomplete data affecting efficacy or safety judgment.

Informed consent {26a}

Qualified candidates will be asked to review the informed consent form and other educational materials, including a video explaining the purpose of the trial and the implications of participation. If patients wish to participate, they will be required to schedule their first visit with the principal investigator or a designated trained research coordinator. The informed consent discussion will be conducted during this initial visit by the principal investigator or the research coordinator, who will explain the study procedures, potential risks, benefits, and the right to withdraw at any time.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

Participants will be informed that clinical photographs of the treatment area (upper arm) will be taken using a dermatoscope for the purpose of evaluating treatment efficacy and analyzing skin characteristics. These images will be anonymized and cropped to exclude facial or identifying features. By signing the informed consent form, participants agree that these images may be used for study analysis, scientific presentations, and publication in peer‑reviewed journals.

Intervention methods

Explanation for the choice of comparators {6b}

Retinoic acid cream belongs to the first generation of all trans vitamin A acid drugs and is a widely used topical dermatological medication in clinical practice. 0.1% retinoic acid cream is commonly used for the treatment of keratosis around hair, which can achieve the goal of softening and dissolving keratin to improve appearance.

Intervention description {11a}

The treatment group will receive the EDR skincare intervention once daily in the evening. This involves gently massaging the upper arm with a scrub containing 0.2% Mandelic Acid for 20–30 s per side, followed by thorough rinsing and drying. Subsequently, a body lotion containing 0.5% Ceramide NP will be applied to the same upper arm side. The amount used per side is standardized to approximately 1.5 mL (≈ a pea‑sized amount, diameter ~1.5 cm). The lotion is to be massaged gently until fully absorbed.

The control group will receive treatment with 0.1% retinoic acid cream. First, the local skin will be cleaned with a mild soap and dried gently, and the area will be allowed to dry completely for 20–30 min. After washing their hands, participants will wear gloves or finger cots to avoid direct contact with the drug. Taking an appropriate amount of cream (based on the size of the affected area) with their fingertip or a cotton swab, they will apply the cream in circular motions starting from the center of the lesion, either clockwise or counterclockwise. A gentle massage will be applied to enhance absorption until the cream disappears completely.

Note: A washout period of at least 1 week will be established before testing begins (i.e., maintaining regular bathing habits and product use without any scrubs or body lotions). Participants are to continue their bathing habits and product use throughout the study duration until the final follow-up visit.

Criteria for discontinuing interventions {11b}

The criteria for halting interventions for a trial participant encompass participants who request a temporary suspension for personal reasons or whose deteriorating condition prompts them to withdraw from active participation.

Strategies to improve adherence to interventions {11c}

Explain the pathological mechanism, treatment goals, and usage of experimental products of KP to patients through graphic manuals, videos, or one-on-one guidance. Adopting remote follow-up methods to reduce the physical costs of participating in the trial.

Relevant concomitant care permitted or prohibited during the trial {11d}

During this trial, participants will not be able to undergo other treatments such as the use of any other scrubs or body lotions.

Ancillary and post trial care {30}

As a form of care after the experiment, all participants will receive a report that includes a comparison of the effects before and after the intervention, as well as daily care methods for KP.

Research procedures and follow-up

Subject screening and enrollment: a test area will be defined on the subject’s upper arm, and photographs will be taken to count the number of keratotic papules. Eligible individuals will be enrolled.

Test area marking: a 3 × 3 cm² test area will be marked at the site of “chicken skin” on the subject’s upper arm.

Data collection before sample use:

1. Photographs will be taken with a dermatoscope to count the number of keratotic papules.

2. Relevant instruments will be utilized to collect data on secondary endpoints.

Sample use: participants will utilize the specified samples in the test area according to provided usage instructions and frequency.

Data collection after sample use: follow-up assessments will be conducted 7, 14, 21, and 28 days after sample use to test primary and secondary endpoints and to gather participant feedback on improvement.

End of study assessment: the improvement index for keratotic papules will be calculated based on established formulas.

Outcomes {12}

Demographic data

Demographic data will include age, gender, ethnicity, height, weight, medical history, medication history, menstrual history, smoking history, and alcohol consumption history.

Efficacy indicators

1. Primary Indicators

   • a
     Improvement Index of Keratotic Papules
     Photographs will be taken using a dermatoscope (DHS2100) to record the number of keratotic papules, and the improvement index will be calculated as follows:
     $$\text{Improvement index}=\left(\text{Number of follicular papules before sample use},-,\text{number of follicular papules after sample use}\right)/\text{Number of follicular papules before sample use}\times 100\%$$
   • b
     Grading assessment: the severity will be determined based on the following criteria:

     • Grade I (mild): average of 0–5 papules/cm² of skin
     • Grade II (moderate-mild): average of 6–10 papules/cm² of skin
     • Grade III (moderate-heavy): average of 11–15 papules/cm² of skin
     • Grade IV (severe): Average of > 16 papules/cm² of skin
2. Secondary indicators

   • a
     Skin moisture content (Corneometer)
   • b
     Erythema Index (EI) (Mexameter)
   • c
     Trans-epidermal water loss (TEWL) (Aqua Flux)
   • d
     Skin elasticity: measured using a skin elasticity tester (R2, R5, R7, F4)
   • e
     Dermatoscopic assessment (DHS2100): photographing and counting the number of papules
   • f
     VC98: evaluation of skin roughness (SEr), smoothness (SEsm), and scale index (SEsc)
   • g
     Image analysis: analyze L* and a* values of images captured under white light with a dermatoscope (indicators of skin redness)
   • h
     Questionnaire survey: participants will complete a questionnaire regarding improvement during each follow-up visit

Participant timeline {13}

The participant’s timeline can be observed through the flowchart in Fig. 1, and the schedule of enrollment, interventions, and assessments is shown in Table 1.

Fig. 1.

Overview of trial design

Table 1.

Schedule of enrolment, interventions, and assessments

Randomization

The study will implement a random selection method for group assignments. After all patients are numbered, random draws will assign them to different groups for the treatment study.

Patient and public involvement

During the conception phase of the study, patients were actively engaged to gain a deeper understanding of the challenges within the KP patient journey, with the aim of enhancing the overall participant experience.

Safety evaluation

Observations and recordings of patients’ skin lesions and general conditions, including blood pressure, heart rate, rhythm, and respiratory rate, will be conducted before and after treatment. Records of any serious adverse events occurring before and after treatment will also be maintained.

Sample size {14}

Based on previous research data, the assessment scores for the treatment and control groups are 2.0 and 3.0, respectively. Using PASS 11.0 software with a significance level of α = 0.05 and a power of 1-β = 0.90, and with the trial groups in a 1:1 allocation, it was calculated that each group should have 30 cases. Considering a dropout rate of approximately 20%, the final sample size for both the treatment and control groups will be adjusted to 36 cases each.

Recruitment {15}

Patients will be recruited from the Beijing area through announcements, brochures, posters, emails, social media, and school invitations.

Assignment of interventions: allocation

Sequence generation {16a}

The randomization sequence will be generated using the website https://www.random.org/lists. The researchers will not have access to the randomization list to avoid bias.

Concealment mechanism {16b}

Randomization concealment: after the study protocol has been fully designed, the randomization scheme will be placed in consecutively ordered, sealed, opaque envelopes, which will be managed by the principal investigator. The envelope will be opened to determine case grouping only after eligible cases are identified.

Implementation {16c}

The sequence generation will be generated by the statistical department. Participants will be registered by other doctors who will prescribe the designated topical product after randomization, but will not have access to the sequence. All patients in the study will receive counseling under the supervision of the researchers.

Assignment of interventions: blinding

Who will be blinded {17a}

The study will be an open RCT. All researchers and participants will know which intervention the patient is randomized to receive. However, outcome assessors and data analysts will remain blinded to group allocation throughout the trial.

Procedure for unblinding if needed {17b}

Unblinding will not be necessary, as the study is an open-label trial.

Data collection and management

Plans for assessment and collection of outcomes {18a}

Data collection methods

Data recording and documentation management: the recorder will fill in the case report form with the basic information and observations of the patients’ local and systemic symptoms. Local photographs will be taken both before and after treatment. All study documents will be standardized. The accuracy and completeness of all recorded research data, reports, and case report forms will be checked and confirmed to ensure they are consistent with the original data.

Plans to promote participant retention and complete follow-up {18b}

To promote participant retention and follow-up, any patient missing a consultation will be contacted by telephone, and a new appointment scheduled. Patients who are lost to follow-up will also be contacted by phone and invited for a new consultation or asked about missing information by phone.

Data management {19}

Verification of case report forms: case report forms will be checked for completeness and logical errors. A dual verification method will be employed to input the research data into the database. For database verification, randomly selected recorded data will be thoroughly cross-checked with the original data in the case report forms, followed by descriptive statistical analysis and exploratory analysis to assess the integrity and logical consistency of the entered data. Any discrepancies will be logged, corrected, and re-verified. The database will be stored and backed up.

Confidentiality {27}

All patients will be identified only by their trial and hospital numbers, with no names associated with the data. All data will be collected from the patients’ medical charts and transcribed into the trial database, which only the research team will have access to.

Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

N/A. Biological specimens are not relevant to our trial.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

All statistical analyses will be performed using SPSS 26.0. Chi-square tests will be used for non-rank count data; t-tests will be used for continuous data; Ridit analysis will be used for rank count data. Comparisons of mean age, disease duration, index scores (semi-quantitative data), values, and efficacy (rank count data) will be analyzed using non-parametric rank sum tests; comparisons of gender (non-rank count data) will utilize chi-square tests. A significance level of α = 0.05 will be used, with p < 0.05 considered statistically significant.

Interim analyses {21b}

No detrimental problems to the study participants are anticipated. No interim analyses are planned.

Methods for additional analyses (e.g., subgroup analyses) {20b}

Further subgroup analysis will be conducted in line with the primary analysis.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

Missing data in Clinical Trials, sensitivity analyses will be conducted with diverse strategies for handling missing data, incorporating adjustments for clustering. This will encompass considering missing data scenarios such as completely at random, missing at random, and missing not at random.

Plans to give access to the full protocol, participant-level data, and statistical code {31c}

The datasets analyzed during the current study and statistical code are available from the corresponding author on reasonable request, as is the full protocol.

Oversight and monitoring

Composition of the coordinating center and trial steering committee {5d}

The coordination center is located at Beijing Technology and Business University. The main researchers and data collection team are responsible for ensuring that the protocol is implemented as planned, regularly reviewing research progress, and consistently adhering to good clinical practice. The main researcher, collaborating researcher, and research assistant will be responsible for all aspects of the logistics and organization of the experiment.

Composition of the data monitoring committee, its role and reporting structure {21a}

An independent committee composed of senior researchers without competitive interests will be appointed as the Data Security Monitoring Committee. The Data Security Monitoring Committee will review and evaluate the cumulative research data of participants’ security and research progress on a monthly basis. As individuals, they will provide their professional knowledge and advice throughout the entire research process. The committee will provide recommendations to the research team regarding the continuation, modification, or termination of the experiment.

Adverse event reporting and harms {22}

Given the intervention’s nature and the patient population’s potential for complications inherent to their biological or medical state, individual reporting of serious adverse events will not occur.

Frequency and plans for auditing trial conduct {23}

The independent data safety monitoring board and investigators will communicate throughout the trial period to notify the Ethics Review Committee of Beijing Technology and Business University, if there are any issues. Any protocol amendments will be properly notified to the Ethics Review Committee, and approval will be obtained prior to the implementation.

Plans for communicating important protocol amendments to relevant parties (e.g., trial participants, ethical committees) {25}

Any amendment to the protocol will be submitted by the principal investigator to be approved by the Research Ethics Committee of Beijing Technology and Business University.

Dissemination plans {31a}

The findings of the trial will be published in peer-reviewed scientific journals.

Discussion

KP presents persistent therapeutic challenges due to its chronic course, complex pathogenesis, and limited effective interventions. This trial evaluates an innovative Exfoliate-Dissolve-Repair (EDR) strategy integrating mechanical exfoliation, chemical dissolution, and barrier restoration—a three-pronged approach addressing KP’s key pathological features: hyperkeratosis, follicular occlusion, and compromised epidermal barrier.

Current vitamin A-based therapies primarily target keratinocyte hyperproliferation but inadequately address barrier dysfunction, contributing to suboptimal outcomes and frequent relapse. The EDR protocol represents a paradigm shift by synergizing physical exfoliation with free fatty acids and ceramide-mediated barrier repair. This combination therapy potentially disrupts the pathogenic cycle of follicular plugging and inflammation more comprehensively than single-mechanism approaches.

Notably, the regimen’s emphasis on barrier restoration through lipid-rich emollients may yield dual benefits: improving both objective clinical signs (papule resolution) and subjective symptoms (pruritus, xerosis). Such holistic improvement could significantly enhance quality of life for patients burdened by KP-related psychosocial distress and treatment dissatisfaction.

Furthermore, the EDR framework offers practical advantages by utilizing non-prescription components, potentially reducing dependence on long-term corticosteroid use while improving treatment accessibility. If validated, this strategy could establish a new standard for KP management through multimodal targeting of its multifactorial etiology.

Trial status {3}

This trial has been recruiting since June 1, after SRCTN approval ISRCTN14455606 was granted on April 6, 2025. The protocol version is V1.0, dated April 1, 2025. Recruitment is expected to be completed by December 31, 2025.

Abbreviations

KP

Keratosis pilaris

EDR

Exfoliate-Dissolve-Repair

EI

Erythema Index

TEWL

Trans-epidermal water loss

SEr

Evaluation of skin roughness

Authors’ contributions {31b}

Authors HM and YZ made significant contributions to the conceptualization and design of the work. The following authors contributed to the following designs: research designs (HM, YD, and LC); writing (FQ and YD); language polishing (YZ and YD). All authors agree to be responsible for all aspects of the work to ensure that any issues related to the accuracy or completeness of any part of the work are appropriately investigated and resolved.

Funding {4}

No funding.

Data availability {29}

The principal investigator YD will have access to the final trial dataset. Any data required to support the protocol can be supplied on request.

Declarations

Ethics approval and consent to participate {24}

This study has received approval from the Research Ethics Committee of Beijing Technology and Business University (Approval No. 2024-131). The findings are intended for submission to peer-reviewed scientific journals for publication.

Consent for publication {32}

The model consent form will be available upon request.

Competing interests {28}

The authors declare that they have no competing interests.