The application of microwaves in axillary hyperhidrosis: Curative effect observation of a pathological examination over 1 year

In Asia, axillary hyperhidrosis is a frequent problem for many people, and the consequent excessive sweating can seriously affect many aspects of daily life and even lead to mental disorders. Microwave therapy is a new, non‐invasive treatment method for axillary hyperhidrosis, whose energy and long‐term effectiveness still needs to be clinically validated.


| INTRODUC TI ON
Although a benign condition, axillary hyperhidrosis has a considerable impact on the quality of life of affected individuals and compromises daily activities, work, and social interactions.Sweating symptoms can also cause local skin moisture and maceration, which increases the chance of microbial infection.It severely exacerbates chromhidrosis and axillary odor disorders and may also lead to such limiting issues as embarrassment, insecurity, low self-esteem, barriers to building social and intimate relationships, reduced leisure activities, and even depression and anxiety. 1,2The quality of life impairment experienced with axillary hyperhidrosis is equivalent to that of severe psoriasis, rheumatoid arthritis, multiple sclerosis, and end-stage renal disease. 3Topical antiperspirants, systemic agents, iontophoresis, surgical procedures, and treatment with botulinum toxin A are commonly used to treat hyperhidrosis nowadays, but such treatments are either invasive or non-permanent, and most are associated with attendant side effects. 4,5 2012, Glaser et al. 6 reported on the treatment of axillary hyperhidrosis using microwaves with a randomized controlled trial.
Microwave treatment of both axillary hyperhidrosis and osmidrosis was subsequently carried out in Canada, Australia, the United States, Taiwan, and other places.Both the efficacy and satisfaction of this treatment have been recognized, but one study also reported that a complication from a brachial plexus injury had not been fully resolved by the 6-month follow-up.
The purpose of this study was to evaluate the safety and efficacy of microwave therapy for axillary hyperhidrosis and axillary odor by increasing the treatment energy level and improving the anesthetic injection method, as well as assessing the histological changes and changes in the grading index during the 12-month follow-up period after one round of treatment.

| Object of study
Twenty patients with a diagnosis of primary axillary hyperhidrosis were enrolled in the study.Inclusion criteria were patients between 18 and 50 years old, who met the primary standard diagnostic criteria for hyperhidrosis, 1 with armpit sweating and osmidrosis symptoms that had not been treated by physical, chemical, or other means within the past 6 months, had a positive bilateral axillary iodine starch test, and had a HDSS grade of more than 3. Patients with a history of allergy to swelling anesthetic fluids or with severe systemic disease were excluded.Although underarm odor was not included in the standard, all subjects suffered from underarm odor.
All patients signed an informed consent form that was approved by the Ethics Committee prior to treatment.

| Sweat and odor assessment
The histological changes of axillary sweat glands were detected by hematoxylin-eosin (HE) staining and CAM5.2 (Maixin Biotechnology Company, Fuzhou, MAB-0687) immunohistochemical staining.The distribution range of axillary sweat was marked as the experimental area using the starch-iodine test, and the area was calculated by taking the average of the left and right axillary readings.We evaluated efficacy using the HDSS scale, which is divided into four levels as proposed by Kowalski et al., 7 and the effect of hyperhidrosis symptoms on quality of life before and after treatment using the Dermatologic Life Quality Index (DLQI) scale.Axillary odor was assessed using the axillary odor severity grading VAS, where one represents no odor at all and 10 represents very severe odor; axillary odor was also assessed using the Odor-5 subscale: (1) not noticeable at all; (2) slightly noticeable; (3) somewhat noticeable; (4) very noticeable; (5) extremely noticeable, as well as Park grading, 8 with grade I and 0 being significant and grade II or higher being ineffective.SCL-90 scores were used to assess psychological changes before and after treatment.

| Treatments
The MiraDry microwave apparatus (Miramar Labs) was used as the test instrument.Photographs were taken with a Nikon digital SLR camera (NIKON-D60) parallel to the armpit area.
One month after the axillary skin biopsy, the subject's bilateral axillary hair was removed, an iodine starch test was performed, and the area of color development was recorded.The skin of the treated for sweat glands was initially 104 (59.75-132.5)but was 41.5 (29.75-62) after the procedure.None of the patients experienced any serious adverse reactions.

Conclusion:
The treatment demonstrated high effectiveness, safety, and short-lived adverse reactions.Prior to treatment, a small amount of lubricant was applied to the treatment area to ensure that the bioTip treatment head attracted negative pressure to the skin and avoided thermal damage to the skin above the superficial dermis.The treatment parameters elected were energy level 5/5 (3 s for each zone of tissue heating), and the microwave treatment was carried out in the zones marked on the bilateral axillae in strict accordance with the transfer paper markings.
During the treatment process, patients were asked about their subjective feelings, whether they felt any burning sensation or pain in the treatment area or any tingling or burning sensation in the upper arm, forearm, or fingertips on the treatment side.If any such symptoms occurred during the treatment process, the microwave heating in the area was stopped and switched to cooling mode.After the procedure, an ice pack was applied intermittently for 20-30 min to alleviate the burning sensation and reduce the occurrence of side effects.One ibuprofen tablet was administered orally in the evening.
The armpits were cleaned twice daily and excessive friction or upper extremity movement was avoided for 1 week.Subjects were followed up at 30 days, 3, 6, 9, and 12 months after completion of the entire course of treatment.

| Study efficacy measures
The primary treatment endpoint was a reduction in HDSS classification to grade 1 or 2. The primary endpoint of underarm odor treatment was a 50% reduction in VAS.Therefore, at each follow-up visit, statistics were performed with HDSS, VAS, odor-5, and Young-Jin Park scores.The DLQI average score was calculated for all subjects at the baseline compared to the end of the follow-up period.For the SCL-90 score, all subjects at the baseline were compared with the average score at the end of the 12-month period after the procedure sessions were complete.Furthermore, changes in SCL-90 scores were calculated for average scores above 160 (symptomatic) after treatment.Changes in the intensity and number of axillary sweat gland distribution were evaluated using an iodine starch experiment and CAM5.2 staining immunohistochemistry.We calculated satisfaction as the percentage of patients who rated themselves as having at least a 50% reduction in symptoms (satisfied and very satisfied).Safety evaluations were recorded during the treatment and at all follow-up visits, which included arm numbness, tingling in the fingers, armpit lumps, armpit nodules, arm weakness, compensatory hyperhidrosis, and skin scald incidence, as well as the duration of any such symptoms.

| Statistical analysis
SPSS 21.0 was used for statistical analysis of the normal distribution data of measurement data, data normalized measurement data, paired samples t-test, or two independent samples t-test, depending on the type of design.The statistical description is presented as the mean ± standard deviation.Depending on the type of design, non-normally distributed data were tested using the Wilcoxon signed-rank test for paired samples (Wilcoxon signed-rank test), the Friedman rank sum test for K correlated samples (Friedman test), or a non-parametric test for two independent samples (Mann-Whitney U analysis).The median (25% and 75% quartiles) was used for corresponding statistical descriptions.The McNemar's test was used for dichotomous information in paired designs, and parametric t-test (one sample t-test) or non-parametric test (one sample Wilcoxon signed-rank test) was used for testing one-sample rates according to normality.A difference of p < 0.05 was considered statistically significant, and p < 0.001 indicated a significant difference.

| RE SULTS
The recruited subjects ranged from 20 years old to under 50 years old (average 29.95 ± 9.64), with a total of 20 cases, six males and 14 females.All 20 subjects have combined osmidrosis; 17 had a family history, 18 have wet ear cerumen, and 13 have colored hyperhidrosis.
After transcribing the mark, the skin of both sides of the axillary region was treated with a microwave of 5/5 energy level, and the transfer mark partition was pressed with microwave heating without scalding or ulcerating the skin.
The study did not include a control group, but the data presented a time-series correlation.The positive numbers of immunohistochemical staining of sweat glands before and after surgery showed normal distribution.The others demonstrated non-normal distribution.In the assessment of the difference in the efficacy of preoperative and postoperative axillary hyperhidrosis, the HDSS score was significantly lower than that of the preoperative baseline (Figure 1A), with a statistically significant difference (p < 0.001).The HDSS scores for 18/20 subjects (90%) dropped from levels 3 and 4 to below level 1 or 2. In the evaluation of underarm odor, 75% of patients' VAS dropped to 50% or less (Figure 1B).Following treatment, | 137 Young-Jin Pack classification (Figure 1C) and odor-5 score (Figure 1D) were significantly lower than before treatment at the 30-day, 3-, 6-, 9-, and 12-month visits.The difference was statistically significant (p < 0.001).In terms of the effect of axillary hyperhidrosis on quality of life, in DLQI, 14/20 patients (70%) experienced at least moderate effects (11-20 score).After treatment, the proportion decreased to 25%, with statistical significance (p < 0.001; Figure 1E).The effect of underarm odor on psychological status (scl-90 score) before and after treatment decreased from 113.5 to 94, demonstrating a significant difference (p < 0.001; Figure 1F).A score greater than 160 required a positive screening.The proportion of preoperative and postoperative were 20% and 0.05%, respectively.The results of the Friedman rank sum test showed a statistically significant difference (Figure 1G).Sweat gland distribution ImageIron Plus 6.0 software was used to analyze the color area of iodized starch (Figure 2) and the number of positive immunohistochemical staining of sweat glands (Table 1).
We calculated the intensities for histopathology CAM5.2 immunohistochemistry using average optical density (OD) values.Intensity was significantly reduced (p < 0.05), while pathological HE staining and immunohistochemistry showed a significant reduction in the number of sweat glands (Figure 3).Among the 20 subjects enrolled, those with combined axillary folliculitis, artificial urticaria, dermatophytosis, and superficial scar formation after long-pulse Nd:YAG 1064 nm laser treatment for axillary hyperhidrosis did not show significant changes in rashes after microwave treatment and had no special adverse reactions; the efficacy was not significantly affected.
In the subjective efficacy evaluation of patient satisfaction, 90% of patients with axillary hyperhidrosis improved by more than 50%, that is, reached satisfactory and very satisfactory results, while 60% of patients with axillary odor improved by more than 50%, that is, reached satisfactory and very satisfactory results (p < 0.001; Table 2).

| DISCUSS ION
The experimental study showed differences in the improvement of symptoms before and after the treatment of axillary hyperhidrosis and axillary odor using MiraDry microwave, thus confirming the effectiveness of microwave therapy in destroying sweat glands in the target tissue and reducing clinical symptoms.Comparing the before treatment and 1 month after treatment, we observed a significant statistical difference; furthermore, after treatment, no significant difference was found in each node of follow-up.The 12-month follow-up showed no significant fluctuations in efficacy, with 90% of patients achieving the primary treatment endpoint of a reduction in axillary hyperhidrosis symptoms to below grade 2 on the HDSS scale; 75% of patients with axillary VAS had at least a 50% reduction Due to its clinical symptoms, patients with axillary hyperhidrosis suffer from disrupted social interactions and are susceptible to psychological disorders.The impact on the life of patients is no less than that caused by vitiligo, acne, and psoriasis. 9The investigation of this trial showed a median pretreatment DLQI of 8.00 and a median The involvement of armpit glands in axillary hyperhidrosis is still debated, but evidence of exocrine sweat glands has been more fully observed.Exocrine sweat glands are active under light microscopy and can be eight times larger in patients with axillary hyperhidrosis. 10,11The principle of microwave therapy is to damage the target tissue with heat, but the heat range is relatively selective.In the axillary tissue, water molecules are high dipole moment, fat is low dipole moment, and glandular tissue contains a high-water content, which is the target of the heat damage via microwaves.
The 5.8 GHz deep microwave instrument treatment energy settings are divided into five levels according to the heating time and the range depth of different levels of damage to the tissue.At a depth of 2-5 mm, the three sweat glands present in the armpit can basically be covered and heated until destroyed.Histology shows that they are replaced by fibrosis. 12In 2014, Suh et al. 13 reported injury to the median and ulnar nerves using microwave level 1 energy levels, with incomplete recovery at the 6-month follow-up.To avoid the occurrence of serious adverse effects of nerve damage, a level 1 energy level is generally used in the lateral axillary wall, which is heated to a depth of 2-3 mm and does not completely cover the sweat gland distribution area.However, the area of the lateral axillary wall occupies 1/3 of the axillary treatment area, which will undoubtedly affect the efficacy of the treatment in patients with moderate or severe hyperhidrosis or axillary odor.This finding is similar to the decrease in the proportion of patients opting for a second treatment after experiencing swelling anesthesia and using the five levels of energy levels reported by Sánchez-Carpintero et al. 14 With five levels of energy in this device, the depth of thermally damaged tissue can reach 5 mm, which can cover the depth of distribution of sweat glands, reaching the reticular layer of the dermis and the superficial layer of subcutaneous fat, covering the range of parietal sweat glands, exocrine sweat glands, and parietal small sweat gland tissue. 15According to previous studies, treatment efficacy does not appear to correlate with the number of treatments, 16 and reducing the number of treatments also reduces the formation of fibrous tissue.This study aimed to compare the safety and effectiveness of the treatment before and after implementation by increasing the treatment energy level and adjusting the swelling anesthetic injection.With regard to the efficacy and safety of deep microwave therapy, all subjects had higher HDSS scores than those reported by Sang-Jun Lee et al. 12 (83.3%had at least a 2-point reduction in HDSS, showing good results), with improved efficacy and reduced adverse effects.Early clinical trials found that the dose of swelling anesthesia had an effect on the treatment efficacy, so this study reduced the total amount of swelling anesthesia, appropriately increasing the dose of anesthesia in the lateral axillary wall, and the swelling anesthesia solution injection was lowered to the fat layer.This injection method elevated the skin so that it could be better absorbed by negative pressure in the treatment handpiece via microwave heating, but the downward pressure on the blood vessels and nerves in the lateral axillary wall remained outside the heating range to improve the safety of the trial.In this study, one patient with axillary hyperhidrosis combined with axillary odor had no significant improvement in either hyperhidrosis or axillary odor symptoms.The reason for this was determined to be due to the extensive formation of collagen fibers following a subcutaneous local injection of sclerosing agents in the axilla 30 years prior to this study, which prevented the sweat gland tissue from entering the microwave negative pressure heating area. 17 present, the main adverse effects observed in the 20 patients during the follow-up period were related to tissue damage caused by the thermal effects of microwave treatment, which were mild.One patient developed axillary nodules (90 days), and the remaining adverse effects resolved within 5 weeks.No serious adverse events of burning skin or inability to lift arms occurred.In all 20 cases, axillary hairs were reduced.This phenomenon is due to damage to the hair follicles after microwave heating, which provides a new entry point for hair removal treatment of low-pigmented hair.Although energy levels were increased in this trial, the combination of improved anesthetic injections resulted in a concomitant increase in axillary hyperhidrosis and axillary odor efficacy in all 20 subjects with no serious adverse effects.Nevertheless, the trial was only followed for 12 months, and no evidence of its long-term effectiveness has yet been demonstrated.However, based on the fact that the sweat glands originate from embryonic tissue and are not renewable, the treatment's long-term efficacy can be speculated.In the future, we will continue to follow the efficacy of follow-up participants to confirm the long-term effectiveness of the therapy.
Axillary hyperhidrosis is a chronic autonomic disorder resulting in social embarrassment and impaired quality of life.There are many therapeutic modalities for axillary hyperhidrosis.Note: The patient satisfaction evaluation at the 12-month follow-up percentage improvement in symptoms; <25% considered very unsatisfactory; 25%-50% considered slightly satisfactory; 50%-75% considered satisfactory; 75%-100% considered very satisfactory.$ One sample Wilcoxon signed-rank test was used.

K
E Y W O R D S axillary hyperhidrosis, efficacy, microwave, osmidrosis, safety area was cleaned with water after alcohol deiodination.A transfer paper marker card was used to mark the upper and lower boundaries of the axillary hair distribution area on the outer 1 cm lateral axis, and the transfer range was determined according to the marker card size.The iodine starch experimental color development area was covered.The corresponding sized transfer paper was fixed by transfer using 75% ethanol according to the markings, and the bilateral axillae were disinfected with iodophor.Bilateral axillary was anesthetized with 1% lidocaine with 1:100 000 epinephrine and sodium bicarbonate in a fan-in injection outside the bilateral axillary transfer border.The transfer area was covered with the injection level located in the superficial fat layer.The amount of swelling anesthetic injected into the lateral axillary wall was approximately 1/2 of the total amount injected into the unilateral axilla and infiltrated for 10 min.Depending on the size of the axillary treatment area, the amount of swelling anesthetic injected within the range of 100*60 to 140*80 markers was approximately 60-100 mL/side.

F I G U R E 1
Axillary hyperhidrosis and underarm odor statistical changes across various indicators before and after treatment.Hyperhidrosis disease severity scale HDSS (A), VAS (B), and Yang-Jin Pack rating (C) for patients with hyperhidrosis, and Odor −5 (D).The Wilcoxon signed rank sum test showed a significant difference before and after treatment.The quality-of-life scale (DLQI) and mental state self-rating scale (SCL-90; F, G) showed statistically significant differences.in endpoint odor, and the iodine starch test showed a 99% reduction in the area of color development from the baseline to the end of the 12-month follow-up (p < 0.001).The proportion of subjects achieving a moderate impact on quality of life in DLQI scores was 70%, compared to 25% after treatment (p < 0.001).The SCL-90 decreased from 113.5 (96.5-159.25) to 94 (90.25-101.25;p < 0.001) after treatment.At the 12-month post-treatment visit, the statistics of those with SCL-90 scores >160 requiring positive screening were 19.95% lower than pre-treatment (p < 0.05).Pathological immunohistochemistry showed the same results supporting the destruction and reduction of sweat gland tissue after microwave treatment (p < 0.05).Satisfaction with the improvement of armpit sweating and odor was 90% and 60%, respectively (p < 0.001).

F I G U R E 2 F I G U R E 3 TAN
Abbreviations: M, median; Q L , lower quartile; Q U , upper quartile.*The p value was calculated using the Wilcoxon signed-rank test.
For example, topical therapies are the first-line treatment of axillary hyperhidrosis because of their ease of use, clinical, and cost-effectiveness.Topical anticholinergics are an emerging therapeutic class in the treatment of focal hyperhidrosis, and one study indicated that 2% glycopyrronium bromide cream is effective for 12 weeks of TA B L E 2 Subjective efficacy assessment of patient satisfaction with improvement of axillary hyperhidrosis and axillary odor symptoms.