Trichloroacetic Acid 15% Peel Alone versus in Combination with Microneedling in Patients with Acanthosis Nigricans

J Clin Aesthet Dermatol. 2024;17(4):28–32.

by Shrook A. Khashaba, MD; Salma Alaa, MSc; and Fatma Eldeeb, MD

Dr. Khashaba, Ms. Alaa, and Dr. Eldeeb are with the Dermatology, Venereology, and Andrology Department, and Faculty of Medicine at Zagazig University in Zagazig, Egypt. Additionally, Dr. Eldeeb is a member of the Interactive Dermatology Foundation.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors have no conflicts of interest relevant to the contents of this article. 

ABSTRACT: Background. Acanthosis nigricans is a common hyperpigmentation disorder with a profound aesthetic impact. The primary concern of most patients is the cosmetic improvement, that is way there is a continuous search for the most effective cosmetic therapeutic option.

Methods. 40 acanthosis nigricans patients were included, lesions are split into equal halves; right side treated with TCA 15% peel and left side was treated with microneedling followed by TCA 15% peel, both sides were treated monthly for three months. Response to treatment was assessed by acanthosis nigricans grade improvement along with the percentage of improvement in texture and pigmentation individually.

Results. There was statistically significant improvement in acanthosis nigricans grade after treatment in both sides. The combination side showed more improvement in terms of texture and pigmentation.

Conclusion. Both TCA 15% alone or combined with microneedling were effective in improving acanthosis nigricans with superior results in combination modality.

Keywords. Trichloroacetic acid, Acanthosis nigricans, Microneedling

Introduction

Acanthosis nigricans (AN) is a dermatosis with aesthetic implications, characterized by velvety, hyperpigmented thickening in intertriginous areas as the back of the neck, axilla, and groin.¹ AN usually reflects the presence of systemic disease. It can be associated with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine disorders, or drug reactions.² 

The definite pathogenesis for AN has not yet been ascertained, although multiple factors have been suggested to be involved.³ Histopathologically, AN reveals epidermal hyperkeratosis, papillomatosis, and dermal fibroblasts proliferation. Insulin and insulin-like growth factor (IGF) are suggested as the main promoters of this proliferation. Other mediators are involved as epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR).¹ The goal of therapy for AN is to correct the underlying disorder and to target AN lesions through cosmetic correction of the pigmentation and hyperkeratosis.⁴ 

Trichloroacetic acid (TCA) is a chemical exfoliating agent that is easy to prepare, inexpensive, and causes epidermal destruction to varying degree, with subsequent repair and rejuvenation.⁵ Both TCA 15% and 20% have been used for the treatment of AN with promising results.^6,7 

Microneedling is a minimally invasive procedure traditionally used as a collagen induction therapy for facial scars and skin rejuvenation, it is also widely used as a transdermal delivery system for therapeutic drugs.⁸ It has been used as a delivery system for topical 10% TCA preparation to treat hyperpigmentation disorders.⁹

The aim of this study is to compare the efficacy and adverse effects of 15% TCA peel alone versus its combination with microneedling in the treatment of AN. 

Methods 

Type of study. A randomized clinical trial conducted in outpatient clinic of Dermatology, Venereology and Andrology Department, Faculty of Medicine, Zagazig University Hospitals. The study is approved by the research ethics committee and the Institutional Review Board (IRB) of Zagazig University Hospitals IRB number: 9228. Informed written consents for photographic documentation and treatment procedures were obtained from all patients before the study. 

Patients. Forty patients, clinically diagnosed with AN, more thanle 10 years old, were included in the study. Patients with history of koebner phenomenon, active infections at the treated sites, history of keloid tendency, patients who received any local or systemic treatment for AN in the previous three months, pregnant and lactating female are excluded from the study. 

Methods. All patients were subjected to full history taking, general examination to detect any associated medical conditions. Patients were diagnosed clinically. AN lesions were given a grade of 1 to 4 according to the novel qualitative scoring system for AN (SCANS). Grade 1 was characterized by hyperpigmentation affecting ≤50% of the area; Grade 2 was characterized by hyperpigmentation affecting >50% of the area, Grade 3 was indicated by Grade 2 characteristics plus velvety change; and Grade 4 was indicated by Grade 3 characteristics plus verrucous/ papillomatous change.¹⁰

Treatment procedure. Lesions were photographed at baseline, at every session, and during the follow-up period. Before the procedure, patients were instructed to apply lidocaine 2.5% + prilocaine 2.5% to the treatment area for 30 minutes. The lesion in every patient was divided into two sides. The right side of the lesion in each patient was treated with TCA only. Patients received peeling sessions of 2 to 4 coats of topical aqueous solution of TCA 15% using gauze, until a light uniform frost was observed, while in axillary folds, erythema was the endpoint.¹¹ The left side of the lesion in each patient received the combination therapy. Patients were treated with microneedling using a dermapen (Ultima A6, Dr. Pen®). The needle depth was adjusted between 1.5 and 2mm according to skin thickness. The lesion was stamped repeatedly using the dermapen until erythema was observed; then one coat of TCA was applied.¹²

 A topical antibiotic was prescribed to guard against secondary bacterial infection in the days following treatment; an emollient was also recommended. Treatment was repeated every two weeks for four sessions. Patients were followed up monthly for three months. 

Assessment of the response. The lesion was assessed before, after treatment and during follow up. Two blinded dermatologists compared the photos of each lesion before and after treatment. The responses were expressed according to improvement in color and texture; poor= 0–25%, mild= 26–50%, moderate= 51–75%, excellent= 76–100%.⁶ Grading was repeated on both sides after treatment and compared to the grade before. 

Patients were asked at the end of treatment to assess their degree of satisfaction as poor, mild, moderate and excellent.⁶ During the session, pain was assessed by the participants according to the visual analog scale (VAS) (0-10) where (0= no pain) and (10= the worst experienced pain).¹³ 

Statistical analysis. SPSS version 25 (IBM, 2017) was used for data processing. Data were expressed as numbers, percentages, and mean + standard deviation (SD). The comparison was done using Chi- square test (X²). The threshold of significance was fixed at 5% level (P-value). P-value of ≤ 0.05 indicates significant results, p– value of ≤ 0.001 indicates high significant results. 

Results 

Forty patients (39 female, 1 male) with AN were included in this study. Their mean age ± SD was 23.3±11.9 ranging from 10 to 45 years. Fitzpatrick Skin Type (FST) IV was the most common (65%) followed by FST III (20%), followed by skin type 5 (15%). Positive family history of AN was found in half of the studied group (50%). Fifty-five percent of patients had obesity, 60 percent were nondiabetic. Lesions were present in neck in (50%) of them, followed by axilla (35%) and antecubital (15%). Disease duration ranged from 1 to 2 years.

After treatment, both sides showed improvement with a significant decrease in AN grades (p-value=0.001*) (Table 1). On comparing AN grading between both groups after treatment, it was 55 percent, 35 percent and 10 percent in the combination side and was 47.5 percent, 35 percent and 17.5 percent in the TCA side for Grade 1, 2 and 3, respectively, with no statistically significant difference (p-value=0.6).

Separate assessment of the improvement in texture and pigmentation between both groups showed statistically significant difference between both sides in texture improvement (p-value=0.04*) and pigmentation improvement (p-value=0.03*) (Table 2).

Side effects reported for both sides were transient erythema, burning sensation, and post inflammatory hyperpigmentation (PIH). Erythema and burning were observed in all patients, with more severity on the combination side. PIH was reported in only two patients on both sides. There was no statistically significant difference in side effects between both sides. 

VAS was used for assessing degree of pain experienced during the microneedling procedure, on the combination side showed mean± SD was (3.5±0.88) ranging from 2 to 5. 

Patients were followed up for recurrence and there was no statistically significant difference in recurrence rate between both sides (20% versus 27.5%, p-value=0.7) 

Higher satisfaction level was recorded among the combination side than the TCA side (10% versus 2.5%, 62.5% versus 57.5%, 22.5% versus 30%, and 5% versus 10%) for excellent, moderate, mild and poor satisfaction level respectively with no statistically significant difference (p-value=0.4)

The improvement in pigmentation in the combination side showed statistically significant association with AN grade before treatment where lower grades showed better improvement (p-value 0.039*), while the improvement in texture showed statistically significant association with age where younger age showed better improvement. In TCA side, there was no statistically significant association with any of patient’s data. 

Discussion 

AN management depends primarily on controlling underlying causes and achieving metabolic control, then dermatologic therapeutic modalities for patients who desire cosmetic improvement.^14,15 Despite multiple available therapeutic options, AN remains a difficult dermatosis to treat.¹⁶

Microneedling is used to create micro channels for topical preparations to be transmitted into the skin in a painless and minimally invasive way.^17,18 It stimulates the release of growth factors to initiate new collagen and elastin formation in the papillary dermis.¹⁹ During microneedling, the epidermis remains intact with no dermabrasive reduction of thickness evident 24 hours after microneedling. Rapid closure of micro holes following treatment reduces the chance of postoperative infections.²⁰

TCA is a lipophilic peel that penetrates the skin quickly, causing coagulative necrosis of the epidermis followed by re-epithelialization with healthier skin.¹⁶ The peel depth can be variable depending on the number of layers applied during the session, number of treatment sessions performed, time interval between sessions, and skin thickness of the treated area.²¹

AN has higher incidence in adults between 20 and 40; however, it may occur in younger age groups, especially with the higher incidence of cases of metabolic syndrome and obesity among adolescents.¹⁵ 

The isolated pure (non-syndromic and non-IR-associated) familial AN is a rare autosomal dominant inherited condition with variable penetrance.²² It usually appears in infancy, stabilizes at puberty, and is not associated with obesity or diabetes. The term “familial AN” is confusing, as AN associated with insulin resistance also tends to be hereditary, and the term “familial AN” has been used in the literature in such cases.²³ Half of patients in this study reported family history of AN whether the affected relatives had diabetic or not, and none of the patients had AN since infancy, thus it does not necessarily indicate familial AN.

AN is common in individuals with darker skin tones.¹ In the current study, patients with FST IV were more affected (26 out of 40) this is consistent with the fact that most Egyptians are of FST III and IV. 

Regarding the site of AN lesions, neck, axillae, antecubital fossae, and knuckles are the most common.^15,24 This is consistent with our study, where the neck was the most affected site (n=20) followed by axillae (n=14) and then antecubital fossae (n=6). Other commonly affected sites, such as the knuckles, groin, inframammary area,  and face were not observed in this study. 

Patients in the current study were assessed before and after treatment based on the severity grading aspect of SCANS that was introduced by Karadag et al.¹⁰ In addition, the texture and pigmentation improvement were assessed based on Zayed et al.⁶ However, our study was the first to assess both texture and pigmentation separately. 

In our study, 3 to 4 coats of TCA 15% peel was used to treat AN every two weeks for four sessions. Similarly, Rajegowda et al¹⁶ and Zayed et al⁶ used TCA 15% peels every two weeks for four sessions, while Baldissera et al,¹¹ used it every week and Eldeeb et al,⁷ used TCA 20% every four weeks. Owing to the darker skin types of Egyptians with higher possibility of PIH and in order to allow complete regeneration between sessions, TCA 15% every two weeks was used in our study. Additionally, AN is an epidermal disorder and this concentration is safe and suitable as a superficial peel. 

In our study, the lesions treated with TCA alone showed a highly statistically significant decrease in AN grade after treatment. Out of 40 patients; 0 percent, 57.5 percent, 35 percent and 7.5 percent showed excellent, moderate, mild, and poor improvement in texture, respectively, while 2.5 percent, 55 percent, 35 percent and 7.5 percent showed excellent, moderate, mild, and poor improvement in color, respectively. These results are close to those reported by Eldeeb et al,⁷ where 0 percent 10 percent, 40 percent, and 35 percent showed excellent, marked, moderate and mild improvement respectively, while 15 percent of the patients had no improvement. Also, similar results were reported by Rajegowda et al¹⁶ where 0 percent, 5 percent, 85 percent, and 10 percent showed excellent, marked, moderate and mild improvement respectively. 

Our results, however, are slightly lower than the pilot study of Zayed et al,⁶ whose clinical results were 30 percent, 50 percent, and 20 percent of the treated lesions for excellent, moderate, and mild improvement, respectively. Their study was limited by the small sample size (N=6). 

After reviewing the literature, we noticed that there was lack of studies discussing the combination of microneedling with TCA for the treatment of AN, while TCA peel alone has been used in several studies. Hence, this study was conducted to compare the results of TCA peel alone and TCA combined with microneedling as a topical treatment for AN. 

The combination side showed better results than TCA alone with statistically significant decrease in AN grade after treatment, along with better improvement in texture and pigmentation. 

Combined TCA peel and microneedling has been used in other hyperpigmentation disorders as melasma and infraorbital hyperpigmentation. Hofny et al¹² conducted a study on 40 women with facial melasma where 20 patients were treated bimonthly with TCA 25% peeling with microneedling every other session and the other 20 patients were treated by bimonthly TCA 25% peel alone. They reported significant improvement in each group. At 1 and 3 months, the mean percentages of change of all scores were significantly higher in combination group.¹²

Similarly, Kontochristopoulos et al⁹ used TCA as an adjuvant to microneedling in treatment of infraorbital hyperpigmentation. TCA can reach the dermis using a low-concentration solution applied to an epidermis that has been more permeable by microneedling. TCA stimulates neo-collagenesis, and melanin dispersion. According to the results of the study, both methods complement each other to give excellent cosmetic results even though infraorbital skin is very thin.⁹ 

The most prominent side effects of TCA peel are burning sensation and transient erythema, which were experienced by all patients in our study and all the previously cited studies.^6,16 Burning sensation and pain were experienced by all patients in combination group, similar to the study of Hofny et al¹² reported similar side effects. The difference in side effects was insignificant. 

Regarding PIH, only two of the studied patients (FST IV) showed PIH after treatment in both sides. This can be explained by the inevitable friction at this site and the lack of adherence to post-operative care. Rajegowda et al¹⁶ as well reported PIH in 4 percent of their patients, while Eldeeb et al⁷ reported it in 20 percent of the patients. This mostly occurs when TCA is applied to darker skin phototypes (IV–VI) or intertriginous areas, which are commonly the predilection sites of AN. 

Less recurrence was reported in the combination side, with no significant difference between the two sides. Recurrence was noted in patients with obesity who were not following a weight reduction regimen and in patients with an ongoing, uncontrolled associated hormonal disorder, such as diabetes.  

On assessing patient satisfaction of the combination group, good satisfaction was associated with a younger age group and shorter disease duration, showing high statistical significance. 

Our study has some limitations regarding the small sample size, lack of control lesions, and short follow-up period.

Conclusion

In our study, combining TCA 15% with microneedling yielded greater improvements in the texture and pigmentation of AN lesions when compared to TCA alone. Larger, controlled studies are necessary to further confirm our results. 

References

1. Salati AS. Acanthosis nigricans: An extensive review. J Pak Assoc Dermatol. 2021, 31(2), 273–288. 
2. Patel NU, Roach C, Alinia H, et al. Current treatment options for acanthosis nigricans. Clin Cosmet Investig Dermatol. 2018, 11, 407– 413. 
3. Popa ML, Popa AC, Tanase C, et al. Acanthosis nigricans: To be or not to be afraid. Oncol Lett. 2019, 17(5), 4133–4138
4. Ehsani A, Noormohammadpour P, Goodarzi A, et al. Comparison of long-pulsed alexandrite laser and topical tretinoin ammonium lactate in axillary acanthosis nigricans: A case series of patients in a before-after trial. Caspian J Intern Med. 2016, 7(4), 290–293. 
5. Zakopoulou N and Kontochristopoulos G. Superficial chemical peels. J Cosmet Dermatol. 2006, 5(3), 246–253. 
6. Zayed A, Sobhi RM, and Abdel HDM. Using trichloroacetic acid in the treatment of acanthosis nigricans: a pilot study. J Dermatolog Treat, 2014, 25(3), 223–225. 
7. Eldeeb F, Wahid RM and Alakad R. Fractional carbon dioxide laser versus trichloroacetic acid peel in the treatment of pseudo-acanthosis nigricans. J Cosmet Dermatol. 2022, 21(1), 247–253. 
8. Singh A and Yadav S. Microneedling: Advances and widening horizons. Indian Dermatol Online J. 2016, 7(4), 244–254. 
9. Kontochristopoulos G, Kouris A, Platsidaki E, et al. Combination of microneedling and 10% trichloroacetic acid peels in the management of infraorbital dark circles. J Cosmet Laser Ther. 2016, 18(5), 289–292. 
10. Karadağ, AS, You Y, Danarti R, et al. Acanthosis nigricans and the metabolic syndrome. Clin Dermatol. 2018, 36(1), 48–53. 
11. Baldissera RL, Yang EJ, Schmitt JV, et al. Trichloroacetic acid peels for the treatment of acanthosis nigricans. JAAD. 2022, 86(1), 203–204. 
12. Hofny ER, Abdel-Motaleb AA, and Hamed SA. Trichloroacetic Acid with microneedling versus trichloroacetic acid alone for treating melasma. Dermatol Surg. 2023, 49(1), 66–71. 
13. Seong GH, Jin EM, and Ryu TU, et al. Fractional radiofrequency microneedling combined with fractional carbon dioxide laser treatment for striae distensae. Lasers Surg Med. 2021, 53(2), 219–226. 
14. Elmasry MF, Khalil MMF, Badawi A, et al. Efficacy of Fractional Carbon Dioxide (CO2) Laser versus Q-Switched Neodymium Doped Yttrium Aluminum Garnet (Nd: YAG) and Potassium-Titanyl Phosphate (KTP) Lasers in the Treatment of Acanthosis Nigricans. Clin Cosmet Investig Dermatol. 2023, 23(16),705–715. 
15. Radu AM, Carsote M Dumitrascu MC, et al. Acanthosis Nigricans: Pointer of Endocrine Entities. Diagnostics. 2022, 12(10), 2519. 
16. Rajegowda HM, Kalegowda D, Madegowda SB, et al. To compare the efficacy and safety of trichloroacetic acid peel with topical tretinoin in the treatment of acanthosis nigricans: A randomized controlled study. J Pak Assoc Dermatol. 2019, 29(2), 170–171 
17. Rai VK, Saha I, Alam M, et al. Microneedle arrays for cutaneous and transcutaneous drug delivery, disease diagnosis, and cosmetic aid. J Drug Deliv Sci Technol. 2022, 79, 104058. 
18. Ghandehari R, Robati RM, Niknezhad N, et al. Efficacy and safety of fractional CO2 laser and tranexamic acid versus microneedling and tranexamic acid in the treatment of infraorbital hyperpigmentation. J Dermatolog Treat. 2022, 33(3), 1391–1396. 
19. Ashraf Mohammed Abd Allah M, Mohammad Abd El-Kareem I, and Abd El-Aal AEM. Skin microneedling plus spot trichloroacetic acid peel in the treatment of atrophic post acne scars: comparative split face study. AMJ. 2020, 49(3), 1279–1289. 
20. Sharad J. Combination of microneedling and glycolic acid peels for the treatment of acne scars in dark skin. J Cosmet Dermatol. 2011, 10, 317–323.
21. El-Taweel AI, Mustafa AI, and Qiresh IQ. Combination of Microneedling and 10% Trichloro-Acetic Acid Peeling Versus Platelet Rich Plasma in the Treatment of Infraorbital Dark Circles. BJAS. 2020, 5(3), 7–12. 
22. Cheon M, Cho BK, Park H, et al. Atypical presentation of familial acanthosis nigricans: Papular skin lesions in siblings. JAAD. 2012, 66(4), 43. 
23. Berk DR, Spector EB, and Bayliss SJ. Familial acanthosis nigricans due to K650T FGFR3 mutation. Arch dermatol. 2007, 143(9), 1153–1156. 
24. Das A, Datta D, Kassir M, et al. Acanthosis nigricans: A review. J Cosmet Dermatol. 2020, 19(8), 1857-1865. 
25. Ozlu E, Uzuncakmak T, Takir M, et al. Comparison of cutaneous manifestations in diabetic and nondiabetic obese patients: A prospective, controlled study. North Clin Istanb. 2018, 5(2):114–119.