Am J Clin Dermatol DOI 10.1007/s40257-015-0136-6

SYSTEMATIC REVIEW

Treatment of Primary Craniofacial Hyperhidrosis: A Systematic Review Rebecca Nicholas1 • Ayyaz Quddus1 • Daryll M. Baker1

 Springer International Publishing Switzerland 2015

Abstract Background Primary craniofacial hyperhidrosis (CH) can have a profoundly negative impact on quality of life. No comprehensive review of its management exists. Objective The objective of this review is to present the best clinical evidence to guide CH management. Methods A systematic review was performed using PRISMA guidelines. MEDLINE and EMBASE were searched from 1966 to 2014 for articles using the MeSH terms ‘‘Hyperhidrosis’’, ‘‘Head’’, ‘‘Neck’’ and synonymous text words. Inclusion criteria were experimental and observational studies addressing CH treatment. Two reviewers independently assessed study quality and analysed data. Results Of 833 references yielded, 27 met inclusion criteria and were analysed. Twenty-two studies evaluated T2 sympathetic ablation (Level III evidence). Outcome measures were subjective and mean follow-up was 29 months. Reported efficacy was high (70–100 %), recurrence rates were generally low (0–8 %) and complications largely transient (e.g. pneumothorax 0–1 %). However, 8–95.4 % experienced troubling compensatory sweating. One randomised controlled trial and one observational study evaluated botulinum toxin A (Level Ib and III, respectively). Both employed objective outcome measures and demonstrated similar findings. Presented at the SARS (society of academic and research surgery annual meeting) conference held on 7 january 2015. & Ayyaz Quddus [email protected] Rebecca Nicholas [email protected] Daryll M. Baker [email protected] 1

Department of Surgery, Royal Free Hospital, Pond St, London NW3 2QG, UK

Efficacy was 100 %, lasted a median of 5–6 months and frontalis muscle inhibition was the main adverse effect (50–100 %). Three studies evaluated anticholinergic therapy: topical glycopyrrolate demonstrated high efficacy (96 %) with minimal adverse effects (Level Ib) and oral oxybutynin demonstrated relatively high efficacy (80–100 %) but with noticeable adverse effects (76.6–83.6 %) (Level III). Conclusion There are few quality studies evaluating CH treatment. Based on available evidence, we recommend topical glycopyrrolate, oral oxybutynin and intradermal botulinum toxin A as first-line therapies due to their efficacy and safety. T2 sympathectomy should be considered for patients refractory to first-line therapy. Key Points Craniofacial hyperhidrosis (CH) is a facial form of focal hyperhidrosis referring to excess sweating beyond normal physiological function, which can have a profoundly negative impact upon quality of life. Clinical evidence supporting the effective treatment of CH is weak due to a lack of published randomised controlled trials. Based on the findings from our systematic review, we recommend topical glycopyrrolate, oral oxybutynin and intradermal botulinum toxin A as first-line therapies due to their high efficacy and favourable safety profiles. T2 sympathectomy should be reserved for patients who are refractory to firstline therapy due to the high incidence of postoperative compensatory sweating and rare yet significant postoperative complications.

R. Nicholas et al.

1 Introduction Craniofacial hyperhidrosis (CH) is a facial form of focal hyperhidrosis referring to excess sweating beyond normal physiological function. The condition usually affects the forehead bilaterally but can also involve other regions of the face such as the scalp, nose, chin and cheeks less frequently [1]. It is predominantly a primary condition characterised by sudomotor dysregulation stimulated by triggers such as heat and stress [2]. Skin biopsies from patients with primary focal hyperhidrosis have shown that the eccrine glands are not morphologically abnormal but purely hyperactive [3]. Primary CH, if severe enough, can have debilitating effects on an individual’s quality of life [4] and, hence, it is of utmost importance to treat it successfully. 1.1 Incidence and Aetiology The incidence of primary hyperhidrosis is 2.9 %, with the greatest prevalence rate between the ages of 18 and 54 years [5]. Focal CH, however, only accounts for 22.8 % of this population, with the majority being axillary, palmar and plantar hyperhidrosis. Focal CH differs from other forms of focal hyperhidrosis in that it is more common in men and presents more frequently in an older subset of patients [6]. A genetic predisposition has been identified to developing focal palmar hyperhidrosis with evidence of variable penetrance, although no such genetic studies specific to CH have been conducted [7]. 1.2 Diagnosis

medication and invasive therapies such as intradermal injections of botulinum toxin A and endoscopic thoracic sympathectomy (ETS) in severe cases. However, to the best of our knowledge, no comprehensive review of its management exists. Our aim is to systematically review and evaluate the strength of available evidence from the last 48 years in order to propose evidence-based guidelines for the management of CH.

2 Methods A systematic literature review was performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. MEDLINE and EMBASE databases were searched for articles indexed with the MeSH (Medical section Heading) terms ‘‘Hyperhidrosis’’, ‘‘Head’’ and ‘‘Neck’’, alongside text words ‘‘craniofacial’’, ‘‘sweating’’, ‘‘scalp’’, ‘‘face’’, ‘‘forehead’’, ‘‘fore-head’’, ‘‘facial’’ and ‘‘neck’’ from 1966 to 2014. The following inclusion criteria were established to choose the studies: 1.

2. 3. 4.

Experimental, observational and comparative studies published in scientific journals with five or more patients specific to primary focal CH; Written in English; Addressing the efficacy of treatment modalities for primary CH; and Clear statistical evidence of differentiating outcomes of treatment modalities of primary CH from gustatory sweating, Frey’s syndrome and facial blushing, where relevant.

Before a diagnosis of primary CH can be made, it is essential to rule out secondary conditions such as the onset of menopause, diabetes mellitus, endocrine disorders and certain medications such as nortriptyline hydrochloride and pilocarpine [1]. Subjective assessment of sweating plays an important role in the diagnosis of focal CH; however, objective evaluation of the intensity of sweating is essential in determining qualification for surgery and for the assessment of the results of the intervention [8]. Gravimetry has been shown to be an effective and reproducible means of objectively assessing sweating in facial hyperhidrosis [9]. The Minor iodine starch test is a useful clinical tool to evaluate distribution of CH but does not provide accurate objective measurement of the degree of sweating [10].

2.1 Data Extraction

1.3 Objective

The literature search identified 1552 articles. After eliminating duplicates and publications in foreign languages, 833 papers remained for detailed analysis. All titles and abstract were examined independently by two reviewers

Current treatment modalities for CH include topical application of aluminium chloride, oral anticholinergic

Numerical and qualitative data were extracted from the original publications and collated in a table of substantive characteristics (number of patients, treatment, outcome measure, immediate success rate, recurrence, rate of adverse effects, mean follow-up) and methodology (type of study). We graded each type of study according to the Centre of Evidence-Based Medicine, Oxford (CEBM) scale (Ia–V) and subsequently assigned the treatment modality a grade of recommendation (A–D) according to guidance from CEBM [11].

3 Results

Treatment of Primary Craniofacial Hyperhidrosis

against the inclusion criteria, leading to 754 articles being excluded and 79 potential relevant studies left. The full text of all 79 publications was fully accessed and assessed, and 52 papers were excluded due to non-compliance with the aforementioned criteria. This led to final inclusion of 27 original articles in the present review. The reasons for article exclusion were animal studies, expert opinions, case reports, review articles, studies involving less than five patients specific to focal CH, an unclear differentiation of the population of patients with CH from other forms of focal hyperhidrosis, and lack of quantitative data on the efficacy of the treatment modality in question (Fig. 1). The 27 articles that met all of the inclusion criteria involved a total of 10,237 patients, of which 1140 (11.1 %; mean n = 42.2, range 5–190) patients were specified to have primary focal CH (Tables 1, 2, 3). Three main modalities of treatment for focal CH were identified, including ETS, anticholinergics and intradermal botulinum toxin A injections. Of these studies, 22 (81.5 %) evaluated the surgical ablation of the upper thoracic sympathetic ganglions, specifically at T2 level, either by clipping or cauterisation (Table 3). Three (11.1 %) studies [12–14] looked at anticholinergic therapy, of which one was topical glycopyrrolate 2 % [12] and the other two were oral oxybutynin [13, 14]. The remaining two (7.4 %) studies looked at the use of botulinum toxin A injections [15, 16]. Of the 27 studies, only nine (33.3 %) were specific to focal CH (two botulinum toxin A, two anticholinergic and five ETS studies) and the remaining articles incorporated different forms of focal hyperhidrosis including axillary, palmar and plantar forms as well as facial hyperhidrosis. Each study was graded using the CEBM scale (Tables 1, 2, 3). Only two (7.4 %) [12, 15] studies employed randomised, case-controlled study designs (Level 1b evidence) and the remaining 25 (92.6 %) studies were nonrandomised, retrospective/prospective observational studies (Level III evidence). Outcome measures were variable, with 20 (74.1 %) studies reporting treatment outcome subjectively on either written or telephone questionnaire alone. One study [17] (3.7 %) used a visual analogue scale and three studies (11.1 %) [14, 18, 19] used clinical followup in addition to using questionnaires. Only four studies incorporated objective quantification of the degree of sweating pre- and post-intervention. These included gravimetry with patient questionnaire [12], starch iodine photography in isolation [15], sympathetic skin response with clinical follow-up and interview in a study [20], and gravimetry with starch–iodine photography [16]. The mean immediate success rate reported for ETS and its variants over 22 studies was 93.3 % (range 70–100 %), for topical or oral anticholinergic medication was 92 %

(range 80–100 %) and for intradermal botulinum toxin A injection was 100 %. Only 14 (51.9 %) of the total studies documented recurrence rates. For ETS and its modifications this was reported to be between 0 and 8 %; however, one study described a recurrence rate of 27.3 % [21]. Although this was documented as late recurrence, no objective demarcation specifying the time difference between late and immediate recurrence rates was defined. One study of topical anticholinergic medication [12] using 2 % glycopyrrolate cited 28 % recurrence of symptoms in 1 day, and one study using intradermal botulinum toxin A injections [15] reported a 0 % recurrence rate. The follow-up periods for the two intradermal botulinum toxin A injection studies [15, 16] were 5 and 6 months, respectively. The follow-up time was lower in two of the anticholinergic studies, ranging between 1 and 12 weeks for oral oxybutynin. However, one study [14] looking at the long-term efficacy of oral oxybutynin had a mean follow-up period of 17 months (range 6–61 months). Only 19 (86.4 %) ETS studies reported an objective follow-up period. Two studies [22, 23] did not cite any follow-up period, whereas one study [24] documented ‘‘no long term follow up’’. The remaining studies displayed a wide variation in follow-up (range 1 month to 14.6 years, mean 29 months).

4 Discussion 4.1 Anticholinergic Therapy Eccrine glands that are responsible for focal hyperhidrosis are innervated by cholinergic fibres, part of the autonomic nervous system. Anticholinergic medication aims to block receptor sites at parasympathetic nerve endings and therefore disrupts normal sympathetic neurotransmission [25]. Evidence regarding the efficacy of oral anticholinergic medication in the treatment of focal CH is limited to two studies. One study was a prospective, randomised uncontrolled study (Level III evidence) involving five patients [13] and the second study [14] was a prospective, nonrandomised uncontrolled study (Level III evidence) involving 61 patients. In the study conducted by Wolosker et al. [13] with five CH patients, four (80 %) reported some benefit, subjectively measured using questionnaires. No objective analysis was employed. Systemic anticholinergic medication, such as oxybutynin, causes non-specific blockade of the muscarinic acetylcholine receptors leading to adverse effects such as urinary retention, headache and dry mouth. Wolosker et al. [13] reported a 66.6 % rate of dry mouth on oxybutynin 5 mg, which increased to 76.6 % on

R. Nicholas et al. Fig. 1 Flowchart of the study selection process for the management of primary craniofacial hyperhidrosis (CH)

Articles initially identified through EMBASE and MEDLINE

(n = 1552)

Duplicates and foreign publications excluded

Titles and abstracts of studies selected for further evaluation (n = 833)

Studies selected for full text evaluation (n = 79)

Excluded articles (n = 754) • • • • •

Animal studies Expert opinions Case reports Review articles Studies with

Treatment of Primary Craniofacial Hyperhidrosis: A Systematic Review.

Primary craniofacial hyperhidrosis (CH) can have a profoundly negative impact on quality of life. No comprehensive review of its management exists...
573KB Sizes 1 Downloads 8 Views