Treatment of periorbital syringomas: review of scientific literature in the last 5 years
Tratamento de siringomas periorbitários: revisão da literatura científica nos últimos 5 anos

INTRODUCTION

The term “syringoma” comes from the Greek word syrinx, which means tube. According to their histopathological characteristics, they are benign adnexal tumors arising from the eccrine ducts. The proliferation of cells in the lumen of the duct results in the development of spiral structures in which sweat can no longer move freely or come out to the surface of the skin¹. Clinically, they comprise small, firm, yellowish or flesh-colored papules, 1 to 3 mm, commonly found in the lower periorbital region, causing cosmetic problems.

Although the variety on the eyelids in middle-aged women is the most frequent, many other clinical variants that differ in age at onset, location, and clinical appearance have been reported in the literature^2,3. Friedman & Butler⁴ proposed a classification for syringomas with four variants: localized, familial, generalized, and associated with trisomy 21. In 2013, Lau & Haber⁵ published a new classification proposal based on hereditary patterns and clinical presentation.

Cho et al.⁶ and Kang et al.⁷ reported that the depth of periorbital syringomas varies, on average, from 1.06±0.34 mm and 0.70±0.20 mm, respectively, confirming that they are located in the dermis, but quite deep, and therefore are a challenge that involves the skin.

Treatment should be selective and should avoid injury to adjacent tissues. The goal is to improve the cosmetic appearance through complete tumor destruction using methods that may include topical tretinoin and atropine, chemical peels, surgical excision, electrodissection, electrosurgery, cryosurgery, laser therapy, use of botulinum toxin and combined therapies.

AtIn the literature, there are multiple treatment options with varying degrees of success, but little is known about the effectiveness of the different proposals. In 2016, Williams & Shinkail² carried out a systematic review of the literature in which they described the clinical features, systemic associations and effective treatment strategies for syringomas. Of 826 cases, 215 were found that reported treatment, including conventional destructive methods, destructive methods such as lasers, peels, electrodissection, and surgical methods. A series of 18 cases were treated with low voltage electrocoagulation⁸. Intralesional electrodissection⁹ was described in 12 cases, with complete resolution and no recurrence report.

Seo et al.¹⁰ reported a retrospective series of 92 cases of patients with periorbital syringomas, in which they treated one group with CO₂ laser and the other with botulinum toxin injection. Barzegar et al.¹¹ published a case treated with electrodissection. Other treatments with Laser Erbium Yttrium Aluminum Garnet (YAG)¹² and Neodymium-Doped Yttrium Aluminum Garnet (ND-YAG)¹³ have been described.

In 2019, two studies were published based on the treatment of syringomas: Ahn et al.¹⁴ reported a retrospective series of patients treated with intralesional electrocoagulation with microneedle alone; and Bae et al.¹⁵ reported a case of syringomas in the neck, treating one side with CO₂ laser and the other with radiofrequency with a microisolated needle.

As mentioned above, periorbital syringomas remain a therapeutic challenge because, although they are benign tumors that cause only cosmetic complaints, we face a clinical scenario in which complete removal is usually not successful. Side effects have been described, such as prolonged erythema, scarring and changes in the treated skin’s pigment, and frequent recurrence.

As specialists, our responsibility is to know and better understand the various therapeutic options, considering the results and complications reported in the literature to avoid the greatest number of sequelae.

OBJECTIVE

The objective of this work was to review the national and international scientific production that addresses the treatment of periorbital syringomas, and secondarily to compare the various treatment techniques proposed during the last five years.

METHODS

This is a narrative review of the literature on journal publications. A bibliographic search was carried out through the search sources constituted by electronic resources in the following databases: Latin American and Caribbean Literature in Health Sciences (LILACS), Health Information from the National Library of Medicine (Medline), and in the Scientific Electronic Library Online (SciELO), published from 2014 to 2019.

The descriptors used were: Siringoma/Siringoma/Syringoma, Pálpebras/párpados/eyelids, Glândulas ecrinas/Glándulas ecrinas/Eccrine glands and Neoplasias cutâneas/Neoplasias cutáneas/Skin neoplasias. It should be noted that the descriptors mentioned above are found in the Descriptors in Health Sciences (DeCS).

Data collection was performed by the author, identifying articles in Portuguese, English, and Spanish that were published in the last five years and additional articles identified during the manual review of the references that had initially been captured in the primary review. The articles were analyzed and included in the present study.

RESULTS

The primary literature search yielded a total return of 45 articles, of which the abstract review excluded 32 articles. The references of the 13 articles identified in the primary search were reviewed, totaling 33 articles that included multiple treatments for periorbital syringomas published in the literature over time.

After a complete review of these 33 articles, those published in the last five years were selected, which had a record of the number of patients, description of the treatment performed, scales of evaluation of results and follow-up, totaling six articles.

A total number of six articles were found: a systematic review, and five retrospective studies, one being a comparative one. A number was assigned to each article analyzed, and the number of patients included in the study, treatment performed, assessment scales and results, complications and conclusions were collected.

The results are described in Tables 1, 2 and 3.

Table 1 - Selected articles

Table 2 - Data collected in each article

Table 3 - Article conclusions

DISCUSSION

The syringomas are benign adnexal tumors with histopathological features that demonstrate that they arise from the intradermal portion of the eccrine ducts¹ and are often located in the orbital region but can be found on the vulva, penis, scalp and axillae^2,3 in the form of small yellowish papules or skin color, with a size between 1 and 3 mm, which cause cosmetic problems and, in some cases, itching. The classification most used to date is the one proposed by Friedman & Butler⁴, with four variants: localized, familial, generalized, and associated with trisomy 21. There is a predominance in females, and the lesions begin to appear in adolescence or early adult age.

The objective of the treatment of periorbital syringomas is to improve the cosmetic appearance since these lesions are considered benign, non-progressive and typically asymptomatic.

Wheeland et al.¹⁶ described CO₂ laser vaporization in a patient with no evidence of scarring or recurrence for 2 years. Castro et al.¹⁷ described the use of low-power super-pulsed CO₂ laser, highlighting the reduction of thermal energy deposition with this modality, and had good results.

Gomez et al.¹⁸ performed the treatment with topical tretinoin in a case of eruptive syringomas, and the patient had moderate improvement due to the flattening of the lesions but had a recurrence in untreated areas. The use of topical atropine¹⁹ showed moderate efficacy, but there are few reported cases.

Karam & Benedetto²⁰ presented a case report using intralesional electrodissection, with the total disappearance of syringomas and hyperpigmentation that resolved at 3 months post-treatment, and in 1997 they reported moderate efficacy in another series of 20 cases treated with the same technique and had two cases of post-inflammatory hyperpigmentation in Fitzpatrick IV phototype patients, which improved at 3 months⁹. In both publications, no recurrence was reported.

Kang et al.⁷ evaluated the histopathology and efficacy of placing 50% trichloroacetic acid (ATA) in the lesions after making three to four holes with a CO₂ laser with low parameters in 20 patients and demonstrated the removal of deep syringomas, reducing the adverse effects. The presence of necrotic dermal collagen could explain the results for tissue regeneration and the stimulation of ATA to produce type I collagen. Intralesional ATA caused extra necrosis in the lesions, but a fixed CO₂ laser protocol was used that did not project the size difference, and this could lead to an inconsistent result when applied to more patients. The benefits of the laser would be precisely to be able to adapt the controlled ablation of tissues of different depths. From our point of view, the fixed protocol ends up compromising the result.

The CO₂ laser has been used in different modalities: Wang &Roenigk²¹reported the use of high-energy CO₂ laser in 10 patients with Fitzpatrick phototype III and IV without sequelae; Sajben & Ross²² showed an efficiency of high energy pulsed CO₂ laser using a 1 mm handpiece in the treatment of 4 patients; Frazier et al.²³ combined ATA 35% (medium peel) and low-energy CO₂ laser in an African-American patient, and achieved cosmetic improvement, even though the syringomas were not completely removed.

Park et al.²⁴, after vaporizing periorbital syringomas with CO₂ laser in 6 patients, introduced black ink into the dermis and later used Q-Switched Laser to remove the lesions, with no evidence of recurrence at 8 weeks of follow-up. Park et al.²⁵ treated 11 patients using CO₂ laser with multiple perforation method and observed good results without complications when the treatment was performed repeatedly. The fractional mode could be an option considered.

Bagatin et al.²⁶ reported the experience in the surgical treatment of 38 patients using excision with Castroviejo scissors and healing by second intention. Thirty-six cases were described with excellent and good results, but 12 cases had hypochromia, 1 had a depressed scar, and 1 had a hypertrophic scar. Even if this method has shown good results, it would be important to evaluate the Fitzpatrick skin phototype due to the risk of hyperpigmentation in the healing process by the second intention, which can appear in larger phototypes. Some preventive dermatological protocols could be associated to avoid these complications.

Al Aradi⁸ carried out a pilot study of the efficacy of low-voltage electrocoagulation in 20 patients with phototype IV and V, placing the electrode superficially in each syringoma, with moderate clinical improvement after the third session. However, 40% of cases developed post-inflammatory hyperpigmentation and 10% hypopigmentation.

Akita et al.²⁷ performed a fractional laser protocol using a 1550 nm Erbium laser in two Japanese patients. Cho et al.⁶ treated 35 patients, and Meesters et al.²⁸ treated one patient with a 10,600 nm CO₂ laser, with good cosmetic results, which would be a less invasive method and with a good neocollagenesis response; however, several treatments would be necessary to obtain full or near full resolution.

Hong et al.²⁹ presented 2 cases treated with fine needle intralesional electrocoagulation, with excellent results and without complications or recurrence, due to the fact that introducing the needle into the lesion allows selectivity in the destruction of dermal lesions without damaging the epidermis. It is necessary to carry out this treatment with more patients and follow-up.

Lee et al.³⁰ reported 29 cases treated with CO₂ laser in the pinhole method. After the second session, they observed almost complete clinical improvement in 58.6% of patients, prolonged erythema in 5 patients and one case of post-inflammatory hyperpigmentation. Through this method, the CO₂ laser can be directed on the lesion and provide high energy for its destruction, concomitantly stimulating neocollagenesis and dermal matrix remodeling, resulting in clinical improvement of the skin texture. This method proved to be effective, but it is operator-dependent, requires a longer procedure time depending on the number of lesions, and the treatment of invisible lesions cannot be performed. More prospective studies are needed.

Seo et al.¹⁰ performed a retrospective analysis of 92 cases comparing CO₂ laser therapy with multiple perforations combined with botulinum toxin A. In a previous study carried out by the authors, they described the effectiveness of deep tumor removal using CO₂ laser with multiple perforations, and in this new proposal, the authors decided to combine botulinum toxin A. The rate of improvement was significantly higher in the combination therapy, but the recurrence was similar in both groups. Post-inflammatory hyperpigmentation was described in 3 cases of combination therapy and 5 cases of CO₂ laser therapy; other adverse effects were not reported.

The eccrine hidrocystomas have been treated with botulinum toxin A^31-33, with good results. The results of this study could be explained by the similar origin of syringomas and the action of botulinum toxin, which blocks the cholinergic terminals of the autonomic nerve that regulate the secretion of eccrine sweat glands³⁴; however, studies with transdermal or intralesional monotherapy are necessary.

A systematic review of the literature performed by Williams & Shinkail² analyzed 215 cases treated in different medical and surgical modalities, such as treatment with topical isotretinoin and atropine, peels, dermabrasion, cryotherapy, electrodissection, intralesional electrocoagulation, laser therapy and laser treatment combinations. The authors noted that CO₂ laser therapies and intralesional electrocoagulation might present the best treatment options.

CO₂ laser has shown moderate efficacy and cosmetic improvement in most reported cases and, even though it does not offer complete resolution of the lesions, most adverse effects improve with time and are well tolerated by patients. Intralesional electrocoagulation decreased the size and number of lesions while sparing epidermal damage such as scarring and hyperpigmentation, and cases with post-inflammatory hyperpigmentation showed spontaneous improvement within 2 to 3 months.

Kitano¹² described the treatment of periorbital syringomas with Erbium YAG laser using the multiple ablation method with an ovoid shape of 2 to 4 mm in 49 patients with disseminated and/or accumulated periorbital syringomas, with a mean of 3.77 and 4.23 sessions, respectively. Sessions were performed every 2 months, and lesions disappeared by more than 75% in 43 patients. A hydrocolloid dressing was used for 2 weeks.

The Erbium YAG, 2490 nm laser, has an absorption coefficient for water approximately 13 times higher than the CO₂ laser, causing less thermal damage to underlying tissues and a very thin coagulation layer. It has been used for removing lesions, nevi, xanthomas and tattoos. In the case of syringomas, they do not infiltrate adjacent tissues and could be removed precisely, preserving deep tissue, as the thermal damage is confined to an extremely thin layer. The results were good; however, it was a retrospective study with variable goals according to the type of lesions of each patient, which limits the evaluation of their effectiveness.

Kim et al.¹³ treated 19 patients with Fitzpatrick IV skin phototypes with a 1,444 nm fiber optic ND-YAG laser with low parameters. All patients showed an improvement of more than 50% of satisfaction in the first session and 89.5% after the second session. Erythema was observed in 63.2% of patients, and post-inflammatory hyperpigmentation in 1 case. They reported worsening in 2 patients after the first session and 1 after the second.

The ND YAG wavelength 1,444 nm is well absorbed in water, making it a therapeutic option for treating cystic lesions such as eccrine hidrocystomas when fiber optic is used subdermally through a cannula 11 or 12. Due to its effectiveness for lipolysis and the low diffusion of heat from adjacent tissues, it is used to treat skin diseases related to adipose tissue. In the case of syringomas, it is believed that the absorption peaks for water and lipids target the lumen and the lipid membrane, which surround the syringomas, and in this way can be effective without causing damage to adjacent tissues. The 1,444 nm ND YAG laser is considered a good treatment option when used with low parameters. However, it is necessary to carry out prospective studies with a larger number of patients and in other skin phototypes.

Ahn et al.¹⁴ performed a retrospective analysis of a case series with 55 patients who underwent 3 sessions of intralesional electrocoagulation, using monopolar radiofrequency with an isolated needle. The evaluators, dermatologists, did not know the number of treatments performed. A scale created by the authors, called Periorbital Syringoma Severity Index, was used, which evaluated number, size, involvement and density. Half of the patients had a marked improvement greater than 50% after the first session, and the severity of the injury decreased with the remaining sessions. The erythema improved until the fourth day, and there was one case of post-inflammatory hyperpigmentation improved with time.

With this method, a thermal coagulative zone is induced within the ductal structure through the microneedle, and the difference in electrical impedance between the epidermis (high) and dermis (low) allows radiofrequency energy to flow into the target dermal tissue. The treatment described is a safe and effective treatment for periorbital syringomas, and the evaluation scale represents an objective way of describing the involvement. However, it is necessary to carry out prospective, comparative studies with different skin phototypes.

Bae et al.¹⁵ reported a case of syringomas in the neck, treating one side with a CO₂ laser and the other with radiofrequency with a microisolated needle, finding better results on the radiofrequency side. The lesions disappeared after 3 sessions, and there was no record of recurrence on this side. It was necessary to use corticosteroids on the side of the CO₂ laser due to the presence of hypertrophic scars. This study is a case report from another location, but it is worth naming as it is the only one that compares these forms of treatment in the same patient.

CONCLUSIONS

Periorbital syringomas remain a therapeutic challenge, and so far, no treatment has been shown to be consistently effective. The CO₂ laser is considered the first choice of treatment for syringomas due to its penetration power and the demonstrated success: when performing a deep ablation, it can completely remove lesions and those that are hidden, but post-procedure care must be taken into account, mainly in phototypes IV, V and VI, due to the high risk of side effects such as post-inflammatory hyperpigmentation and inadequate healing; when it is performed in the fractionated modality or the multiple-hole technique and/or pinhole method, with low parameters, the pulse energy is delivered more safely; however, the resolution is partial, and several treatments are necessary.

Intralesional electrocoagulation represents a second alternative with moderate results and lower risk of complications; however, it has a small number of cases reported in the literature, and it is necessary to carry out studies with a greater number of cases, establish treatment parameters and that they are performed in different skin phototypes.

New treatments such as Erbium YAG and ND YAG laser and monotherapy with botulinum toxin A could be good treatment alternatives with a lower risk of sequelae. However, further studies are needed to demonstrate their effectiveness.

Prospective, comparative studies with various skin phototypes are needed to assess the effectiveness and determine the best option.