The Initial Exploration of Polidocanol Sclerotherapy for the Treatment of Axillary Osmidrosis: A Retrospective Study

Abstract

BACKGROUND

Axillary osmidrosis (AO) is a strong, unpleasant odor that originates from the apocrine axillary glands. Treatments of AO include surgical treatment and nonsurgical treatment. The surgical procedure yields effective results with a low recurrence rate but requires a longer recovery time and has more postoperative complications. Nonsurgical treatments are minimally invasive and safe, but short-term recurrence may occur in some cases.

OBJECTIVE

Polidocanol sclerotherapy was first described for management of AO. This retrospective study explored the clinical efficacy in relieving symptom of AO assessed by AO severity using the axillary osmidrosis grading system and safety of polidocanol sclerotherapy in treating AO.

PATIENTS AND METHODS

This retrospective study included 25 patients with AO single-site study, with 12 patients receiving polidocanol (1%) sclerotherapy (the polidocanol group) and 13 receiving botulinum toxin A (BTX-A) injection (the BTX-A group). The short-term efficacy (7 days after injection), the long-term efficacy (6 months after injection), the recurrence rate, and complications were compared between the 2 groups. A p-value of <0.05 was considered statistically significant.

RESULTS

The short-term efficacies of polidocanol sclerotherapy and BTX-A injection were 100% and 69.2%, which was not clinically significant (p > .05), whereas their long-term efficacies were 100% and 46.2%, respectively (p < .05). The recurrence rates in the polidocanol and BTX-A groups were 25.0% and 84.6%, respectively (p < .05). The complications did not differ significantly between the 2 groups (p > .05). Although the short-term efficacy and complications were comparable between the 2 groups, the long-term efficacy of polidocanol sclerotherapy was superior to BTX-A injection. The polidocanol group has a lower recurrence rate than the BTX-A group.

CONCLUSION

Polidocanol sclerotherapy may provide an effective and safe treatment with longer efficacy compared to toxin, which is an effective and safe option for AO treatment.

Axillary osmidrosis (AO) is a strong, unpleasant odor that originates from the apocrine axillary glands. Its etiology is complex, with apocrine axillary sweat glands, axillary microorganisms, and sex hormones all playing a role.¹ Its treatments are classified as either surgical or nonsurgical.² The surgical treatments include laser treatment,^3,4 endoscopic thoracic sympathectomy,⁵ and conventional surgery,⁶ whereas nonsurgical treatments include topical agents, subdermal botulinum toxin A (BTX-A) injections,⁷ subcutaneous ethanol injections,^8,9 and microwave technology.¹⁰ The surgical procedure yields effective results with a low recurrence rate.¹¹ However, it requires a longer recovery time and has more postoperative complications, including skin necrosis, hematoma, embarrassing scarring, and hyperpigmentation.² In contrast, nonsurgical treatments are minimally invasive and safe, but short-term recurrence may occur in some cases.² For instance, BTX-A has a certain recurrence rate that necessitates additional treatments,¹² whereas ethanol sclerotherapy has a low recurrence rate but some complications.^8,9 Therefore, a less invasive treatment with long-term efficacy is required. Polidocanol, having chemical properties similar to ethanol, can be used for sclerotherapy.¹³ In this study, the authors first introduced polidocanol sclerotherapy as a treatment for AO and retrospectively compared its efficacy and safety to BTX-A injection, providing a novel option in treating AO with advantage of long-term efficacy and minimal invasiveness.

Material and Methods

Patients

In this retrospective study, 25 AO cases treated in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from July 2022 to August 2022 were enrolled through diagnosis codes. The inclusion criteria was listed as follows: (1) patients ≥18 years and under 60 years of age with axillary odor; (2) patients who are willing to undergo an assessment of the level of axillary odor by physician, patient, and third party; and (3) patients who voluntarily signed the informed consent form and were willing to receive regular follow-up after the procedure. Patients meeting the below provided exclusion criteria were excluded from this study: (1) severe cardiac, hepatic, and renal insufficiency (myocardial ischemia or myocardial infarction; Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≥ upper limit ALT of normal value ×1.5 times; creatinine AST ≥ upper limit of normal value); (2) bleeding tendency, abnormal coagulation function (≥upper limit of normal value for more than 3 seconds), coagulation dysfunction cannot be corrected by treatment; (3) thromboembolic disease, or a high risk for thrombosis (e.g., patients with a known genetic predisposition to thrombosis or patients with multiple risk factors, such as those on hormonal contraceptives or hormone replacement therapy, obesity, smoking, and chronic inactivity); (4) diabetes mellitus, uncontrolled hypertension, tumors, psychiatric disorders, inflammatory skin disease in the treatment area, and patients with signs of microangiopathy or neuropathy; (5) active or chronic infections, tuberculosis, viral hepatitis, AIDS, or syphilis; (6) patients who underwent surgery, microwave therapy, botulinum toxin injection therapy, or other treatment of AO; (7) patients who are planning pregnancy, are pregnant, or lactating; (8) allergic to polidocanol injection or the components of BTX-A; and (9) with limited movement of upper limbs. The patients were withdrawn from the study if they or their legal guardians voluntarily requested to withdraw or if they violated any inclusion/exclusion criteria.

Among them, 12 patients received polidocanol (1%) sclerotherapy and were assigned to the polidocanol group, whereas 13 received BTX-A injections and were assigned to the BTX-A group. All patients were assessed for AO severity using the axillary osmidrosis grading system (TAOGS)¹³ by an experienced third party, who was experienced in TAOGS grading and blinded to the patient treatment procedure. The study was approved by the Ethics Committee of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The patients provided written informed consent for their participation in this study as well as the publication of any potentially identifiable images or data in this article.

Procedures of Injection

Compound lidocaine ointment (with 2.5% lidocaine) was applied to the skin of axilla for 30 minutes before injection. The treatment square was defined as 0.5 cm outside the hair growth area of the axilla and then divided into approximately 1 cm² (Figure 1). After injection, patients were monitored for more than 20 minutes to avoid acute adverse reactions and then followed up on for 7 days and 6 months by an experienced blind third party.

Figure 1.

The polidocanol sclerotherapy procedure for AO treatment (A) axillary condition before polidocanol sclerotherapy for AO treatment. (B) The axillary area was drawn at a scale of 1 cm² per square. (C) A uniform subcutaneous injection of polidocanol (1%) into each square of the designated area. (D) The postoperative efficacy of polidocanol sclerotherapy for AO treatment. AO, axillary osmidrosis.

In the polidocanol group, polidocanol (1%, 2 mg/kg/d; Hameln Pharmaceuticals GmbH, Germany) was used for AO sclerotherapy, with a maximum dose of 14 mg/d. For example, if the patient weighed 50 kg, the recommended dosage of polidocanol (1%) was 10 mg/d, with a maximum dose of 14 mg/d. Patients underwent a uniform subcutaneous injection in the designated area using a 26-gauge needle (a standard 1-mL injection syringe).

In the BTX-A group, 50 units of BTX-A (Allergan) were diluted into 2 mL of saline and superficially microinjected into multiple points using a 30-gauge needle insulin injection syringe. Each defined square (1 cm²) was injected with 2 units of BTX-A. The maximum dose of area injection was 50 units per side. During the treatment, intravascular injections should be avoided. After injection, all patients' conditions were closely monitored for 20 minutes before they were released with no adverse reactions.

Efficacy Assessment

In both groups, the short-term efficacy (7 days after the injection), the long-term efficacy (6 months after the injection), and recurrence rate were recorded. Axillary osmidrosis severity was graded based on TAOGS,¹⁴ ranging from 0 to 3, with a higher score indicating a more severe AO degree. The AO severity grade was determined via assessing TAOGS scores before injection, as well as 7 days and 6 months after injection. The change of TAOGS scores were used to assess efficacy, as described in the AO elimination grading system (TAOEGS; Table 1). Efficacy of injection was defined as grading of excellent, good, and fair. Recurrence of AO was defined as follows: after injection, according to the TAOGS score, relief of AO symptoms was found in the short term (7 days after injection), but a rebound in TAOGS score occurred during long-term follow-up (6 months after injection). Among them, a partial recurrence was defined as a rebound in the TAOGS score at 6 months after injection, but it was still lower than the initial TAOGS score before injection. A complete recurrence was defined as a rebound in the TAOGS score at 6 months after injection, which was equal to or exceeded the initial TAOGS score.

TABLE 1.

The Axillary Osmidrosis Elimination Grading System

Grading	Axillary Osmidrosis Elimination	Score Changes
Excellent	No malodor could be smelled	From any score to 0
Good	A significant improvement was obtained, but a minimal malodor could be occasionally smelled only when sweating heavily	From 3 to 1
Fair	A slight improvement was obtained, but a light malodor could be occasionally smelled during daily activities	From 2 to 1; from 3 to 2
Poor	No improvement was obtained; the same degree of malodor could still be smelled after injection	No change

Safety Assessment

In both groups, complications such as skin pigmentation, redness, swelling, scarring, necrosis, and infection, as well as hair reduction and injection pain, were all recorded 7 days and 6 months after injection.

Statistical Analysis

The primary objective of the statistical analysis was to compare the short-term and long-term efficacy and the complication rate between polidocanol and BTX-A group. In this study, data were analyzed using the Statistical Package for Social Sciences (SPSS^©; Chicago, IL) for Windows, Version 22.0. Continuous data were expressed as means and standard deviations. Qualitative variables were compared using the chi-squared test, whereas level data were compared using the Mann–Whitney U test. A p-value of less than 0.05 was considered statistically significant. The alpha level is 2 sided.

Results

In this study, 25 patients were included, with 6 male and 6 female in the polidocanol group and 7 male and 6 female in the BTX-A group (p > .05). The mean age of patients was 25.0 ± 4.4 years (minimum–maximum, 19–33 years) in the polidocanol group and 25.1 ± 4.8 years (minimum–maximum, 17–33 years) in the BTX-A group (p > .05). According to TAOGS, the AO severity grades did not differ significantly between the polidocanol and BTX-A groups (p > .05). All patients had grades 2 and 3, with no patients with grades 0 or 1 included in the authors' study. In the polidocanol group, 6 patients had grade 2 and 6 had grade 3, whereas 7 patients had grade 2 and 6 had grade 3 in the BTX-A group (Table 2).

TABLE 2.

The Characteristics of Patients With Axillary Osmidrosis

Characteristics	Polidocanol Group (n = 12) n (%)	BTX-A Group (n = 13) n (%)	p *
Sex			1.0
Male	6 (50.0)	7 (53.8)
Female	6 (50.0)	6 (46.2)
Age (yr), mean ± SD	25.0 ± 4.4	25.1 ± 4.8	.9
TAOGS grades before injection			.9
0	0 (0.0)	0 (0.0)
1	0 (0.0)	0 (0.0)
2	6 (50.0)	7 (53.8)
3	6 (50.0)	6 (46.2)

BTX-A, botulinum toxin A; TAOGS, the axillary osmidrosis grading system.

^*A p-value of less than 0.05 was considered statistically significant.

Efficacy Assessment

According to data recorded, efficacy was 100% and 69.2% in the polidocanol and BTX-A groups 7 days after injection (p > .05). In the polidocanol group, the excellent, good, fair, and poor grades were 83.3%, 8.3%, 8.3%, and 0%, whereas they were 61.5%, 0%, 7.7%, and 30.8% in the BTX-A group, respectively (Table 3). Although the polidocanol group had a higher proportion of excellent and good grades, the short-term efficacy (7 days after the injection) implying relatively better short-term efficacy in polidocanol group, but result of data did not turn out to be clinically significant.

TABLE 3.

Assessment of Treatment Efficacy in the Study Patients

Outcomes	Polidocanol Group (n = 12) n (%)	BTX-A Group (n = 13) n (%)	p
Short-term efficacy (7 d after injection)
Excellent	10 (83.3)	8 (61.5)	.138
Good	1 (8.3)	0 (0.0)
Fair	1 (8.3)	1 (7.7)
Poor	0 (0.0)	4 (30.8)
Long-term efficacy (6 mo after injection)
Excellent	9 (75.0)	2 (15.4)	.001*
Good	1 (8.3)	2 (15.4)
Fair	2 (16.7)	2 (15.4)
Poor	0 (0.0)	7 (53.8)
Recurrence
Yes	3 (25.0)	11 (84.6)	.002*
No	9 (75.0)	2 (15.4)

^*A p-value of less than 0.05 was considered statistically significant.

BTX-A, botulinum toxin A.

However, 6 months after injection, efficacies in the polidocanol and BTX-A groups were 100% and 46.2%, respectively (p < .05). In the polidocanol group, the excellent, good, fair, and poor grades were 75.0%, 8.3%, 16.7%, and 0%, respectively, whereas they were 15.4%, 15.4%, 15.4%, and 53.8% in the BTX-A group, respectively (Table 3). Therefore, the long-term efficacy (6 months after the injection) was better in the polidocanol group than in the BTX-A group, with a significant difference between the 2 groups.

Recurrence rates were 25.0% and 84.6% in the polidocanol and BTX-A group, respectively (p < .05). In the recurrent cases in polidocanol group, treatment was effective in 2 patients 7 days after injection, but recurrence occurred 6 months later, and 1 patient reported incomplete efficacy immediately after treatment. In the BTX-A group, there were 6 patients reported recurrence 6 months after injection, and 5 patients reported incomplete efficacy or no efficacy 7 days after injection (Table 3). Accordingly, the recurrence rate was lower in the polidocanol group than in the BTX-A group, with a significant difference between the 2 groups.

Safety Assessment

No patients in the polidocanol or BTX-A groups had skin pigmentation, scarring, necrosis, infection, or hair reduction. However, 4 patients in the polidocanol group and 2 in the BTX-A group had skin redness and swelling 7 days after injection, with no significant difference between the 2 groups (p > .05). In addition, 3 patients in the polidocanol group felt pain during the first 7 days after the injection, whereas none in the BTX-A group did (p > .05). The details of the complications in each group are listed in Table 4. Furthermore, these complications were transient and tolerable. The axillary skin changes in 1 patient are shown in Figure 2. The polidocanol and BTX-A groups were comparable in terms of treatment safety, with no significant difference between them.

TABLE 4.

The Treatment Complications in the Polidocanol and BTX-A Groups

Complications	Polidocanol Group (n = 12) n (%)	BTX-A Group (n = 13) n (%)	p *
Short term (7 d)
Injection pain	3 (25.0)	0 (0.0)	.096
Skin redness and swelling	2 (16.7)	2 (15.4)	1.000
Skin infection	0 (0.0)	0 (0.0)
Skin necrosis	0 (0.0)	0 (0.0)
Long term (6 mo)
Skin pigmentation	0 (0.0)	0 (0.0)
Skin scarring	0 (0.0)	0 (0.0)
Hair reduction	0 (0.0)	0 (0.0)

BTX-A, botulinum toxin A.

^*A p-value of less than 0.05 was considered statistically significant.

Figure 2.

Axillary skin changes in 1 patient after injection polidocanol sclerotherapy. (A) One day of after injection, (B) 7 days of after injection, and (C) 6 months after injection.

Discussion

Axillary osmidrosis treatment can be divided into surgical and nonsurgical.² Although surgery for AO is generally known to be more thorough, it may result in physical damage, scarring, and other complications.¹⁵ However, nonsurgical treatments are less invasive options, including laser therapy,^3,4 microwave therapy,¹⁰ BTX-A injection,⁷ and ethanol injection therapy,^8,9 all of which have been clinically studied in different countries.

An ideal perfect treatment for AO would need to possess the following conditions simultaneously: complete alleviation of symptoms, minimal trauma, long-lasting efficacy, and should be safe and simple. Results in this study indicated that this treatment method had optimistic short-term and long-term therapeutic effects, while also demonstrating treatment safety. It was easy to handle the injection procedures for operator, and patients can resume their normal lives early after injection, which provided a potential novel option in treating AO with advantage of long-term efficacy and minimal invasiveness.

First introduced as a temporary treatment for axillary hyperhidrosis, the effects of the BTX-A injection could persist for 6 to 8 months.^16,17 In 2018, McConaghy and Fosselman recommended BTX-A injection as a first- or second-line treatment for not only AO but also palmar, plantar, or craniofacial hyperhidrosis.¹⁸ The mechanism of BTX-A was chemodenervation of cholinergic nerve terminals to the eccrine and apocrine glands,¹⁹ presumably inhibiting bacterial overgrowth and reducing axillary sweating.⁷ Current studies found BTX-A injection for treating AO to have good efficacy but had a predictable possibility of half-year recurrence and required further treatment, which was consistent with the authors' findings.^15,20–22 In order to achieve long-term control of symptoms, treatment of AO with BTX-A injections requires repeated injections every 6 months or so. This repeated injection increases the treatment cost and psychological burden, which also reduces the quality of life. Accordingly, it is necessary to explore other treatment methods with higher efficacy and a lower recurrence rate that do not require repetitive injections.

Sclerotherapy is another option for AO treatment. Only 2 studies investigated ethanol injection in AO, demonstrating this method as a simple, minimally invasive, low-cost, highly effective treatment. Complications of ethanol injection were also reported in the 2 studies including severe pain, skin necrosis, pigmentation, suggesting unsatisfied safety of treatment.^8,23

Polidocanol, an agent similar to ethanol in chemical properties, can be used for sclerotherapy. It was first used as a local anesthetic in 1936 and was later developed as a blood vessel sclerosing agent.²⁴ As a nonionic detergent sclerosant, polidocanol adsorbs to and disrupts the architecture of phospholipid membranes.^24,25 Polidocanol sclerotherapy has been allied in treating varicose veins disease, cystic hepatic/thyroid nodules, hemorrhoids, venous and lymphatic head and neck malformations, demonstrated that polidocanol is an effective and safe agent in sclerotherapy.^26–28 Up to now, there has been no literature reporting on the sclerotherapy method of treating AO by subcuticular injection of polidocanol. Therefore, the authors are honored to be the first team to report on this treatment method and conduct this study.

The AO grading system varied across studies.² In 2006, Lee and colleagues introduced a malodor grading system for patients to assess themselves.²⁹ Asilian and colleagues followed the grading system, but the grades were assessed by the patients and their family members, which was subjective and could introduce data bias.⁹ In this study, AO severity was objectively assessed using TAOGS (Table 1) before injection as well as 7 days and 6 months after the injection by an experienced third party who was experienced in TAOGS grading and blinded to the patient treatment procedure. The score changes from before to after injection were determined using The Axillary Osmidrosis Elimination Grading System to assess treatment efficacy (Table 2). With these 2 grading systems, the bias in subjective assessment can be minimized.

The short-term efficacy did not differ significantly between the polidocanol and BTX-A groups (p = .138), with 83.3% of patients experiencing complete AO disappearance with polidocanol sclerotherapy in 7 days, indicating a good short-term curative effect of polidocanol sclerotherapy in AO treatment. Furthermore, the long-term efficacy of polidocanol sclerotherapy was superior to BTX-A injection (p = .001), with 75.0% of patients experiencing complete AO disappearance with polidocanol sclerotherapy in 6 months, indicating a good long-term curative effect of polidocanol sclerotherapy in AO treatment. However, only 15.4% of patients had complete AO disappearance with BTX-A injection. These findings indicate that polidocanol sclerotherapy is an effective treatment for AO with long-term efficacy.

In terms of safety, patients were followed for 6 months to record complications. Overall, polidocanol sclerotherapy for AO treatment had no serious complications, such as skin pigmentation, scarring, necrosis, infection, or hair reduction. However, temporary skin redness and swelling, as well as short-term injection pain lasting 7 days, were the main side effects. The recovery process of polidocanol sclerotherapy for AO treatment was recorded 1 day, 7 days, and 6 months after injection (Figure 2). Skin redness and swelling faded after 7 days. These complications were transient and tolerable, indicating that polidocanol sclerotherapy is a safe method for AO treatment.

Limitations

This study has some limitations. First, the number of patients in this study was small, and the follow-up period was only 6 months. Therefore, more patients and a longer follow-up period are required to confirm the efficacy and safety of polidocanol sclerotherapy. Second, histopathologic evidence to confirm the mechanism of polidocanol sclerotherapy for AO treatment was lacking in all participants. Finally, there are some limitations due to the retrospective nature of the study. And also, there was selection bias in patient selection, for some patients received botox and others polidocanol without randomized selection and grouping. Therefore, more randomized and parallel studies with a large sample size are warranted in the future to evaluate the efficacy and safety of polidocanol sclerotherapy for AO treatment and strengthen the authors' findings.

Conclusion

Compared with BTX-A injection, polidocanol sclerotherapy may be is another effective alternative for AO treatment, which has lower recurrence rates and fewer complications.