Efficacy of Trichloroacetic Acid in Patients with Alopecia Areata: A Clinico-Histopathological Study

Article information Background: Alopecia areata is an autoimmune disorder caused by a breakdown in the follicular immune privilege system, resulting in non-scarring hair loss. Many therapeutic options have been tested with variable results. Aim of the work: To assess the efficacy of trichloroacetic acid [TCA] 35% in patients of alopecia areata. Patients and Methods: This prospective cross-sectional study included 40 patients recruited from department of dermatology and venereology, Al-Hussein hospital. Every patient was treated by 3 sessions of TCA 35% with one-month intervals. The assessment was done by clinical, trichoscopy, and histopathological examination. Results: The study included 40 patients, 22 males [55%] and18 females [45%]. The mean age of studied patients was 25.6 ± 8.6 years with a minimum age of 16 years and a maximum age of 50 years. The duration of the disease ranged between 2 months and 10 years with a mean duration of 2.7 ± 2.5 years. Thirty patients [75%] showed improvement at the end of TCA sessions. Conclusion: Based on our findings, topical application of TCA 35% is a safe and effective treatment option for patients with alopecia areata. Moreover, it can be used in wide areas of the scalp and cases of alopecia totalis.


INTRODUCTION
Alopecia areata [AA] is an autoimmune disorder characterized by hair loss in small, irregular areas.Hair loss is most commonly seen on the scalp, although it can also appear in other hairy parts of the body and can manifest in many different patterns.Although it is a benign condition and most patients are asymptomatic, it can cause emotional and psychosocial distress [1]   .Alopecia areata can progress to complete loss of scalp hair [alopecia totalis] or loss of all body hair [alopecia universalis] [2] .It can affect children, adults, and hair of all colors, also both sexes equally [3] .
The cause of AA remains incompletely understood, but many factors include autoimmune process, genetic susceptibility, environmental factors, psychological stress, and oxidative stress are all suggested to contribute to the disease [4][5][6][7][8] .
Alopecia areata is primarily a hair follicle cycle disease [9] .An unexplained trigger is thought to initiate an autoimmune lymphocyte invasion upon a hair bulb in AA.This inflammatory process is particular for anagen hairs and generates anagen arrest, resulting in aberrant anagen hair loss, which is clinically known as dystrophic anagen hair with tapering proximal ends and a paucity of root sheaths.Once AA becomes chronic, hair follicles often stay in a protracted telogen phase with no discernible attempt to revert to an anagen growing phase [10,11] .Alopecia areata frequently occurs in association with other autoimmune disorders such as vitiligo, thyroid disease, type 1 diabetes mellitus, pernicious anemia, Addison's disease, lupus erythematosus, atopic dermatitis, and psoriasis [12][13][14][15] .A hallmark of active alopecia areata is the presence of peribulbar lymphocytes around the bulb region of anagen hair follicles upon histopathological examination [10] .
The stimulated synthesis of cytokines and growth factors [particularly platelet-derived growth factors, keratinocyte derived growth factor, vascular endothelial growth factor [VEGF], and IL-10] may be the postulated action mechanism of Trichloroacetic Acid [TCA] in AA.IL-10 has an anti-inflammatory effect, and its concentration was raised after treating with diphenylcyclopropenone.Moreover, VEGF induces new blood vessels formation, so enhancing the follicular nutrition.Immunomodulatory effect via sensitization and elimination of reactive T lymphocytes is another possible method of action [16] .
In this study, we aimed to assess the therapeutic effect of trichloroacetic acid [TCA] 35% in patients with alopecia areata.

Study design and population
This study is a prospective cross-sectional study that included 40 patients recruited from the department of Dermatology and Venereology, Al-Hussein hospital.Exclusion criteria: Age more than 60 years old, patient receiving any other line of treatment within the last 2 months, pregnant and lactating females.

Treatment protocol
All patients were subjected to full history taking followed by clinical examination of the scalp to evaluate the clinical forms and the severity of alopecia.The region to be treated was cleaned with 70% alcohol, then a semi saturated cotton tip was applied in 2-3 layers till frosting.Patients received a total of 3 regular sessions of TCA 35% one month apart.Patients were advised to use topical antibiotic cream twice daily for one week and desquamation occurred within 5 days of treatment.

Clinical evaluation
All patients were subjected to evaluation by MacDonald hull and Norris grading system 17 for density, pigmentation, and texture of growing hair before treatment, after every session, and at the end of treatment protocol.
Serial photographs using Nikon D5300 camera with lens [18-55] were taken, and to reduce potential bias, scoring was performed by two independent blinded dermatologists.Dermoscopic evaluation: All patients were examined using DermLite DL4 handheld dermoscope, attached to iphone 13 pro camera and was evaluated by non-treating blinded dermatologist pre-every-and 3 months post procedural to assess exclamation marks, dystrophic hairs, yellow dots and black dots.

Histological evaluation
From the scalp lesion to be treated, a 2-mm punch biopsy [down to the level of subcutaneous tissue to fully evaluate the follicular area] was obtained at the first visit and 4 weeks after the last session.Each biopsy was fixed in 10% formalin solution at 4 °C overnight, dehydrated with alcohol, and embedded in paraffin, sectioned, and then examined histologically using hematoxylin and eosin [HE] stain [staining epidermis and dermis].Specimens were graded descriptively and examined by two dermatopathologists.AA of the face was excluded as most patients would refuse the biopsy from face due to cosmetic reasons.
All parameters [epidermal changes, sebaceous glands, hair follicle structure, number of hair follicles, collagen deposition around hair follicle and cellular infiltrate] were assessed in each of the stained sections.
Follow-up: During sessions, weekly follow-up was performed to examine any side effects like pain, erythema, dyspigmentation, and/or scarring.After the end of sessions, a monthly follow-up evaluation was done for 3 months to assess the results and exclude the relapse of treated patches of AA.

RESULTS
The study included 22

DISCUSSION
Before making a decision on the most propriate treatment for alopecia areata, the patient's age in addition to the extension of the condition should be taken into account.Chikhalkar et al. [18] carried out a prospective trial in 2011 using topical phenol 88% for patchy areas of AA and reported a 78% improvement in hair regrowth.The most common adverse reaction was hypopigmentation.Additionally, lactic-acid 15% was applied topically every other day and shown to be effective.The most prevalent side effect was transitory erythema [18] .
The first trial to use TCA topically in treating alopecia was done by Mahgoub et al. [19] and they reported a significant improvement.
The mean age of our studied patients was 25.6 ± 8.6 years.El-Husseiny et al. [21] showed that the mean age was 30 and the age range was between 18 and 47 years.While in Majid et al. [22]   , the age ranged between 11 and 48 years, and Wang et al. [25] showed higher mean of age among patients with alopecia [34 years].Even higher mean of age was seen among patients in the study conducted by Al-Dhalimi et al. [20] for the study of fractional laser in treatment of alopecia which was 45 years.
The duration of alopecia among our patients ranged between 2 months and 10 years, with a mean duration of 2.7 ± 2.5 years.El Husseiny et al. [21] and Zaher et al. [24] showed the mean duration [13.2 months & 1.8 years] respectively.In Wang et al. [25] 's study, the mean duration of the disease was much higher [7 years].
There was a statistically significant difference regarding the duration of alopecia.Patients with shorter duration of alopecia responded to our treatment better than those with longer duration of the disease.
Among our patients, 8 [20%] had a family history of alopecia.It was slightly higher in El-Husseiny et al. [21] study, where about 25% of the patient reported family history of alopecia.In Zaher et al. [24] there was no family history among the patient [15 patients], and this could be explained by the smaller number of the patients in their study.
The higher percentage of response in the present study was observed in patients with active alopecia [14 patients, 100%] when compared to patients without active alopecia [16  patients, 61.5%] with statistically significant difference.This could be explained that an early treatment when the hair follicles are not destroyed, will give the ability of successful hair regrowth.
Trichoscopic evaluation in our study showed marked reduction of dermoscopic finding of AA as follow exclamation mark [EM], yellow dot [YD], brown dot [BD] and dystrophic hair [DH] and coincided with Mahgoub et al. [19] who showed that trichoscopic features were substantially reduced, denoting disease activity.
Histopathological evaluation of our study showed marked reduction of lymphocytic infiltrates around the bulb region of anagen hair follicles [swarm of bees] in active case of alopecia areata and there was an increase in the diameter and number of hair follicles.
Although our study has limitations such as: single center study, lack of immunohistochemistry, small number of subjects, and short duration of follow-up.

Conclusion:
Our study shows that topical TCA 35% is a simple, in-office, safe, and efficient line of therapy in cases with AA.It's considered a good option in wide area of the scalp and alopecia totalis.Moreover, TCA 35% is a great option for children with AA as it's nearly painless technique and doesn't include needles.
The study was approved by the local ethical committee of Al-Azhar University [0000030].Informed consent was signed by each patient after explaining the nature of the study.Inclusion criteria: All clinical forms of alopecia areata affecting the scalp [monolocularis, multilocuolaris, ophiasis and alopecia totalis].

Statistical analysis :
Data were fed to the computer and analyzed using SPSS version 20.0.[Armonk, NY: IBM Corp].Proper tests were performed according to each variable.

Table 3 ] . Table [ 1
males [55%] and18 females [45%].The mean age of our studied patients was 25.6 ± 8.6 years with a minimum of 16 years and a maximum of 50 years of age.]: Response to treatment according to the type of AA

Table [ 2
]: Overall response to treatment according to MacDonald hull and Norris grading system

Table [ 3
]: Histopathological findings before and after treatment