Perianal Hyperhidrosis Successfully Treated with Botulinum Toxin A

Abstract

Perianal hyperhidrosis (HH) is a rare form of primary focal HH and may become a major problem for the patient with a significant psychosocial burden and negative impact on the quality of life. Botulinum toxin injections are widely used as a second-line treatment option for axillary, palmar, and plantar HH with a good safety profile. Herein, we pre­sent a case of primary perianal HH successfully treated with Botulinum toxin A at a dose higher than that previously reported in literature, with a longer response, a higher degree of satisfaction, and no adverse effects. Moreover, we review the main aspects of the perianal anatomy that are essential to carry out the technique correctly and make dermatologists achieve expertise with the procedure.

Established Facts

• Already known fact 1: A wide array of therapies is available for the treatment of primary hyperhidrosis (HH), ranging from topical to systemic medications. Nevertheless, they are very often associated with significant adverse events.

• Already known fact 2: Treatment of focal HH with Botulinum toxin A is known to be effective in the axillary, palmar, and plantar region. However, there is little research to date evaluating its usefulness and safety in the perianal region.

Novel Insights

• New information 1: Intradermal injections of Botulinum toxin A (BTX-A) seem to be an effective and safe therapeutic approach for the treatment of perianal hyperhidrosis achieving a high degree of satisfaction and reducing the impact of this disease on the quality of life of affected patients.

• New information 2: Administering 2I U of BTX-A per injection point spaced 1–1.5 cm apart on the affected area may be a suitable regimen achieving long-term responses without severe adverse events.

Introduction

Hyperhidrosis (HH) is defined as overactivity of eccrine sweat glands beyond what is expected for environmental conditions and thermoregulatory needs. It severely affects the patient's daily activities due to the social and professional disadvantages. HH can be primary, which accounts for 93% of HH patients and presents before 25 years of age, or secondary to an underlying medical condition or use of medications [1]. Whereas primary HH is usually focal, symmetric and mostly affects axillae, palms, soles, and craniofacial region, secondary HH tends to be asymmetric or generalized and requires a complete study to exclude infection, diabetes mellitus, Parkinson's disease, hyperthyroidism, anxiety, phaeochromocytoma, and menopause [2, 3]. Various non-surgical and surgical therapies are available for the treatment of primary HH including topical aluminium chloride, topical glycopyrrolate, iontophoresis, oral oxybutynin, and local surgery. However, efficiency is variable, and none of them is exempt from side effects. In this context, Botulinum toxin A (BTX-A) injection has emerged as a new therapeutic approach for the management of focal HH with higher satisfaction rates than with other treatment methods [1, 4, 5]. We focus on the treatment of perianal HH with injectable BTX for which little scientific information is available in medical literature.

Case Report

A 22-year-old man presented with a 4-year history of increased sweating in the perianal region that stained clothing and embarrassed him. Sweating worsened with psychological stress and discouraged him from developing social activities. He denied associated systemic symptoms and had not received any treatment. His past medical history included dust mite and pollen allergy. On physical examination, multiple sweat drops accompanied by mild diffuse erythema were observed on the anal fold. To precisely detect the hyperhidrotic area, a Minor's (starch-iodine) test was performed (shown in Fig. 1). Laboratory tests were normal including complete blood cell count, biochemistry, thyroid-stimulating hormone, thyroxine, antithyroid antibodies, cortisol, liver function tests, and urine metanephrines. Topical treatment with a solution containing zinc, aluminium, and copper was prescribed with no improvement. Oral medication was suggested to the patient, which he declined. Therefore, after obtaining written informed consent, intradermal injections of BTX-A were administered. In order to diminish pain at the injection site, a topical mixture of lidocaine and prilocaine was applied 30 min prior to the technique. The commercial preparation used was a 100 U vial of on a BTX-A (Botox, Allergan, Inc., Irvine, Calif®) diluted with 5 mL of 0.9% saline solution. The total dose injected was 50 U by leaving 1 U at a 1 cm interval using a 30-gauge needle, oriented at 45° to the skin surface with the needle's bevel faced up. Patients' satisfaction was high during the first weeks, nevertheless, 3 months after the procedure enhanced sweating relapsed. Consequently, he underwent a second session leaving 2 U of BTX-A at a 1–1.5 cm interval on the affected area, receiving a total dose of 100 U (shown in Fig. 2). With this dosage, sustained response was achieved for almost 6 months with only mild symptoms reappearing in the last weeks. Following 2 sessions with 100 U of BTX-A, the reported degree of satisfaction was very high, and Minor's test showed a reduction in the sweating area, only requiring a total dose of 80 U the last session. Apart from the pain derived of the punctures, no other side effects were observed.

Fig. 1.

Minor's test: the affected skin area turns dark blue when iodine and starch interact in the presence of sweat.

Fig. 2.

Immediate post-BTX-A injection. Appreciate the small bumps at each injection site corresponding to the deposit of the solution at the dermal-subcutaneous junction.

Discussion

Perianal HH is a rare form of primary focal HH that mainly occurs in men between 20 and 40 years and predisposes to eczema and fungal superinfection. There are no guidelines for first- or second-line treatment in the region, and experience is based on isolated case reports. As a natural fold subjected to constant friction and moisture, topical formulations of astringent agents become particularly irritating. Furthermore, topical anticholinergics such as glycopyrrolate solution are expensive, difficult to obtain and can produce a dry syndrome similar to that secondary to their oral administration. On the other hand, the anatomical peculiarities of the region are not suitable for existing iontophoresis devices. To date, surgical approaches and psychotropic drugs (topiramate and antidepressants) have not been described for this special form of focal HH. Although numerous studies have shown the efficacy of BTX-A injections as a therapy for focal axillary, palmar, and plantar HH, there is only one research report concerning the perianal region. Bechara et al. [3] conducted a study in which 11 male patients with primary focal perianal HH received 38 U on average (range, 30–54 U) of intradermal BTX-A, using 1 U per injection point, with 1 injection in a square of 1 × 1 cm of skin. A reduction of the hyperhidrotic area of 78.5% was achieved 4 weeks after injection [3]. The time of reassessment was concurrent with the greatest cholinergic innervation blockade of the sweat glands by the toxin; nevertheless, no long-term results were evaluated. Duration of clinical efficacy depends on the new synaptic junctions formed which take approximately 6–8 months to fully restore sweat glands secretory function [1]. In our case, the patient was symptom-free scarcely 3 months after receiving BTX-A using the same dosage as Bechara et al. [3]. Hence, we propose treatment of perianal HH with 2 U per injection point to achieve maximum efficiency and a long-lasting effect. With regard to potential undesirable adverse events, toxin diffusion and consequent faecal incontinence are the most concerning. To minimize the diffusion phenomena, the clinician should use the most effective dose at the smallest volume which helps to localize the toxin and contain the biologic effect of muscle paralysis [6]. Besides, thoroughly understanding the perianal region anatomy allows precise delivery of the toxin in the dermis-subcutaneous cellular tissue transition. Dermal-subcutaneous junction of the anal fold lies approximately 2 mm deep [7], distant from the internal anal sphincter, which is the major contributor to the resting pressure in the anus (shown in Fig. 3). Faecal incontinence is an infrequent adverse effect even when BTX-A is injected intrasphincteric. This was observed in a meta-analysis conducted by Bobkiewic et al. [8] in which a total of 1,577 patients received BTX-A injections in the internal anal sphincter (5–150 U per session) for the treatment of chronic anal fissure. The overall incontinence rate was established of 5.01%, being mostly transitory with an average duration of 8 weeks. Moreover, no difference in postprocedural complication rate was observed in regard to BTX dose [8].

Fig. 3.

Anatomy of the perianal region and anal canal.

In conclusion, although larger studies are required to support the efficacy and safety of this procedure, clinicians should consider intradermal injections of BTX-A as a therapeutic approach for the treatment of perianal HH in case of failure or intolerance to other treatments. Uniformly distributing 2I U of BTX-A spaced 1–1.5 cm apart on the affected area may be a suitable regimen achieving long-term responses, only requiring 2 or 3 sessions per year. Further research will help to standardize the technique. Mild pain at the injection site is the most frequent adverse event and can be prevented by applying topical anaesthesia prior to the procedure. The absence of local irritation or anticholinergic effects like those usually seen with conventional therapies improves adherence to therapy and helps enhancing patient's quality of life.

Statement of Ethics

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors received no specific funding for this work.

Author Contributions

Leandra Reguero del Cura: literature review, acquisition of data, and writing. Marta Drake Monfort: conception and design and revising the article. Adrian De Quintana Sancho: literature review and revising the article. Marcos Antonio González López: design and revising the article.