CPD: Primary Hyperhidrosis

Treating Primary Hyperhidrosis

Dr Rakesh Anand and Dr Emma Craythorne present an overview of the diagnosis and management of primary hyperhidrosis

Hyperhidrosis is a common condition that can have a devastating impact on a sufferer. Not only is it underreported and underdiagnosed, but the significance and implications of the condition are often minimised.1,2 This article reviews the literature to help better guide healthcare professionals on the appropriate non-surgical approach to management, considering not only the location of involvement, but the individual as a whole.

Definition Hyperhidrosis, or excessive sweating, is a common condition that can have profound psychological and social implications for the sufferer.3 It is defined by the secretion of sweat in amounts greater than is physiologically needed for thermoregulation. Sweat is produced by the eccrine sweat glands, which are distributed all over the body but are most numerous on the palms and soles.4 Hyperhidrosis can be classified by the presence of an underlying cause (primary or secondary) or by location (focal or generalised). Most commonly, hyperhidrosis is a chronic primary (idiopathic) condition; however, secondary medical causes or side effects of medications need to be excluded (Table 1).4

Prevalence and epidemiology The estimated prevalence of hyperhidrosis ranges from 1-5% of the population.5,6,7 The true prevalence of hyperhidrosis is unknown as it is often underreported by patients and underdiagnosed by healthcare professionals.1,2 The condition tends to start in childhood or adolescence but can occur at any age,8 and males and females are affected equally.9 Hyperhidrosis is uncommon in the elderly, reassuringly suggesting primary hyperhidrosis symptoms often improve with age.10

Diagnosis Idiopathic hyperhidrosis that is localised to certain areas of the body is called primary focal hyperhidrosis. Primary focal hyperhidrosis (PFH) often affects the axillae, palms, and soles, but may also impact other sites, such as the face and scalp. It can also be multi-focal, affecting several sites of the body at the same, or alternating times. A consensus panel comprised of international practitioners suggested a diagnostic criteria for PFH.8,11 They proposed that the patient must display focal, visible, excessive sweating of at least six months duration without apparent cause, plus at least two of the following characteristics: • Bilateral and relatively symmetrical sweating • Interferes with daily activities • At least one episode per week • Onset before 25 years of age • Positive family history • Localised sweating stops during sleep Complications of hyperhidrosis Living with hyperhidrosis presents many challenges and impacts many aspects of daily life. The implications hyperhidrosis has on social and professional life, as well as mental and emotional health, cannot be underestimated. In addition, constant moisture from sweating can lead to chronic skin conditions.3,9,12 One study of 2,017 patients found the prevalence of anxiety and depression was 21.3% and 27.2% in patients with primary hyperhidrosis; higher than is reported in the general population.12

Some of the challenges and problems associated with hyperhidrosis include:11,13

• Effects on quality of life/impacts on activities of daily living – social embarrassment, relationship difficulties, impaired performance at work/school • Anxiety and depression • Bromhidrosis – unpleasant smell from by-products from bacteria living on the skin • Skin maceration with possible superadded bacterial or fungal infection • Pitted keratolysis – superficial infection on the soles of the feet characterised by pitting

Treatment Before selecting appropriate treatment, the practitioner must begin by considering the location of the sweating and combine this with factors such as the patient’s preference for treatment, as well as other factors such as availability, practicality, side effects, cost, safety, and efficacy. Table 2 outlines the suggested first and second-line therapies for hyperhidrosis dependent on location of involvement.13

Examples Psychological Anxiety

Physiological Pregnancy, menopause Cardiovascular Heart failure

Infections

Chronic infection e.g. TB, HIV, and malaria Malignancy Lymphoma, myeloproliferative disorders Endocrine or metabolic Hyperthyroidism, diabetes mellitus

Neurological Parkinson’s disease, hypothalamic lesions, stroke, peripheral nerve damage

Drugs Cholinesterase inhibitors, antidepressants, pilocarpine; propranolol, ciprofloxacin, aciclovir, esomeprazole, opioids

Other Drug/alcohol misuse or withdrawal

First-line therapies Axillary

• Topical antiperspirants • Topical glycopyrronium Palmar/plantar

• Topical antiperspirants • Iontophoresis Craniofacial

• Topical antiperspirants

Second-line therapies • Botulinum toxin • Microwave thermolysis • Systemic agents • Iontophoresis • Botulinum toxin • Systemic agents • Topical glycopyrronium • Botulinum toxin • Systemic agents

Table 2: Suggested first and second line therapies for primary focal hyperhidrosis13

Axillary hyperhidrosis Therapeutic options for axillary hyperhidrosis include topical agents, oral medications, botulinum toxin and microwave thermolysis.

Topical antiperspirants Topical antiperspirants are often the first-line treatment for hyperhidrosis. They are inexpensive, well-tolerated, readily available and easy to use. Antiperspirants work by blocking sweat glands to reduce the amount of sweat, and deodorants control the odour associated with sweating.14 The concentration of metal salts (usually aluminium chloride) in commercially available antiperspirants is low and are only really effective in managing mild to moderate symptoms.14 Prescription antiperspirants such as 20% aluminium chloride hexahydrate may be effective at managing hyperhidrosis in those who fail to respond to commercially available preparations.14,15 When the topical metal salt is applied to the skin there is precipitation of metal ions with mucopolysaccharides. This leads to damage of epithelial cells within the sweat ducts, which in turn, leads to a formation of plugs which blocks these ducts.14 A common concern about aluminium in antiperspirants is that it’s linked to cancers, specifically breast cancer. However, no studies to date have produced evidence linking the use of aluminium-containing antiperspirants with an increased risk of breast cancer.16

Topical glycopyrronium Glycopyrronium is an anticholinergic drug that aims to prevent sweating through inhibiting the action of acetylcholine on the sweat glands. It is applied once daily with an impregnated disposable wipe.17 Glycopyrronium is an anticholinergic, and as it is not systemically absorbed, side effects are unlikely. However, patients have reported adverse anticholinergic effects.17 Trial data supports the use benefit of glycopyrronium when looking at both patient reported and objective measurement of sweat production. As with topical antiperspirants, local irritation can occur, and some people may also experience systemic anticholinergic effects such as dry mouth. However, as glycopyrronium is poorly absorbed by the gastrointestinal tract and systemic effects are unlikely with topical use. Topical glycopyrronium wipes can also be difficult to source and expensive.17

Botulinum toxin Botulinum toxin is licensed for the treatment of axillary hyperhidrosis and research suggests it is safe and effective.18 It is delivered by multiple intradermal injections into the dermis using a fine gauge needle; approximately 10-20 injections spaced 1-2cm apart are delivered in each axilla.18 Botulinum toxin works by inhibiting acetylcholine release from the sympathetic cholinergic nerve terminals that innervate sweat glands. By blocking the release of acetylcholine, botulinum toxin can temporarily reduce sweat production.18 Most of the literature either describes Botox or Dysport (Azzalure), although other formulations are likely to have the same benefit. The average doses per axilla is Botox: 50-100 units and Dysport/Azzalure: 100-300 units.18 In one randomised control trial involving 320 patients injected with 50 units of Botox into each axilla, 94% had an effective response at four weeks and 82% of patients at 16 weeks.19 The response to treatment is usually evident within the first few days and the effects usually persist for over three months. The duration of response is also likely to increase with subsequent injections.18 It should be noted that treatment can be painful, but topical anaesthetic can be applied to the axilla to reduce the pain from the procedure. It may also be expensive for some patients, which may be a limiting factor for its choice as a treatment.18

Microwave thermolysis The use of microwave energy has been supported by a randomised trial of 120 adults. Microwave energy is utilised to destroy eccrine glands and relieve hyperhidrosis in the axilla.20,21 Those who received active treatment reported a subjective reduction in axillary hyperhidrosis at 30 days, and this difference remained statistically significant at six months.22 An objective reduction in sweat was also seen, which was most significant for those that had a better response at 30 days.22 As the microwaves destroy the eccrine glands, the manufacturer reports that the benefits are permanent. Common side effects include altered skin sensation and localised discomfort. Transient ulnar and median nerve neuropathies have also been reported in some patients.23 The treatment is typically administered in two 20-30-minute treatment sessions separated by three months. The procedure is performed under local anaesthetic to minimise pain and discomfort however, the cost can limit the treatment choice.

Palmer hyperhidrosis Many of the therapies used for axillary hyperhidrosis are effective for palmar or plantar hyperhidrosis; however, the approach to treatment may be somewhat different, and iontophoresis often plays a greater role in treatment.

Antiperspirants As with axillary hyperhidrosis, prescription-strength antiperspirants can help with the symptoms of hyperhidrosis. However, research suggests there is a lower likelihood of success.14

Iontophoresis Sites of hyperhidrosis are immersed in water (or a wet contact applied) through which a weak electric current is passed. The exact mechanism of action is unclear, but treatment may temporarily inhibit the sweat glands.24 Iontophoresis is safe and simple to perform; it

In one case series of 34 patients, where patients were prescribed glycopyrrolate alone or in combination with topical therapies, 67% reported an improvement in symptoms

should initially be performed by a healthcare professional, but once an improvement has been seen the machine can be purchased/ rented for home use.14 In one study with 18 patients it appeared to alleviate symptoms in approximately 85% of users with palmar or plantar hyperhidrosis. Reductions in sweating were noted within approximately two to four weeks with a 20-30-minute, three times weekly regimen. Side effects included dry cracked skin, erythema, discomfort and vesiculation.25 Time is generally reported as the biggest limitation for this therapy. Occasionally, the frequency and duration of treatments can be reduced, whilst maintaining adequate control of sweating. Special electrodes are available for use in other sites such as the axilla. The problem is that they do not always provide uniform contact with the skin and therefore can be less effective.26

Botulinum toxin Multiple studies support the use of botulinum toxin for palmar hyperhidrosis,27,28 but there are fewer studies in the use of plantar hyperhidrosis.29,30 The pain during the procedure is reportedly significant, but can be limited by a number of techniques including topical anaesthesia, cryo-analgesia and nerve block.31 The benefits of the procedure are noted within seven to 10 days and the effects persist for up to six months (ranging from 2-22 months).32,33 As with axillary hyperhidrosis, duration of benefit may increase with repeated procedures. Common complications include bruising and temporary muscle weakness.27 Average dose per palm or sole are: Botox: 50-100 units or Dysport/Azzalure: 100-240 units.32

Craniofacial hyperhidrosis The location on the face and scalp is a limiting factor for some hyperhidrosis therapies. The major treatment options include topical agents, oral medications or botulinum toxin.

• Antiperspirants: Topical antiperspirants on the face are easy to apply and safe to use. Irritation can be significant and a limiting factor to their use.14 • Topical glycopyrronium: A small number of studies have shown some benefit of topical glycopyrronium for facial hyperhidrosis.34

The effects appear to last between one to two days; however, more studies are needed to explore the benefit as well as safety of treatment.35

• Botulinum toxin: A number of uncontrolled studies and case studies have documented the benefit of botulinum toxin for hyperhidrosis.36,37 Treatments needs to be carefully administered by those who have a good understanding of facial anatomy to avoid both cosmetic and functional compromise. Precautions and doses of botulinum toxin are dependent areas of the face requiring treatment.

Systemic treatments for primary focal and generalised hyperhidrosis Systemic therapies can be effective for generalised, focal, or multifocal hyperhidrosis. It is often considered when hyperhidrosis is not satisfactorily managed with other methods, as the potential adverse effects inhibit their regular and routine use.38 The most used agents are anticholinergics, which include propantheline, glycopyrronium bromide, oxybutynin, and benztropine.38 Oral anticholinergics, such as oxybutynin39 and glycopyrrolate40 (glycopyrronium bromide) decrease sweat secretion by competitive inhibition of acetylcholine at the muscarinic receptors near eccrine sweat glands. The use of oral glycopyrrolate is supported by retrospective case series. In one case series of 34 patients, where patients were prescribed glycopyrrolate alone or in combination with topical therapies, 67% reported an improvement in symptoms.41 Additionally, another study of 31 patients found that 71% achieved an improvement in symptoms during treatment with glycopyrrolate (with or without concomitant topical aluminium chloride).42 The use of oral oxybutynin is supported by randomised controlled trials.43,44 In one study of 60 patients over six weeks, 48% noted a great improvement and 26% a moderate improvement.45 Responses to oral anticholinergics usually take around one week for the maximal effect. Doses need to be carefully titrated to achieve acceptable reduction in sweating, whilst minimising any adverse effects. Potential adverse effects of anticholinergics include dry mouth, blurred vision, constipation, or urinary retention.40,42 Up to one third of patients cannot tolerate these symptoms and have to stop treatment.40 Anticholinergics are not recommended for those with glaucoma or urinary retention and caution should be practiced in older patients as there is an increased risk of adverse effects.46 Typical doses range for glycopyrronium bromide are from 1-2mg per day, but doses up to 8mg per day may be required.39 Typical adult doses of oxybutynin are a total dose of 5-10mg per day.45 This can be given as two divided doses for immediate release oxybutynin or once daily for modified-release oxybutynin.39 Higher doses of up to 20mg daily have been used, but this is very much dependent on the adverse effects the patient experiences.45

Surgery Although beyond the remit of this review, it is important to consider surgical options for hyperhidrosis. These should be considered as last-line therapies when a patient has not responded well to topical or systemic treatments. Local surgical treatments, such as surgical excision, liposuction, and curettage have been tried.47 Endoscopic thoracic sympathectomy (ETS) can successfully reduce sweating in the problem area, but is often reserved for the most severe cases

Aesthetics Clinical Advisory Board Member and independent nurse prescriber Jackie Partridge says... Hyperhidrosis is a fact of life for many of our patients. It has a profound impact on their daily lives, as is well documented in this article. Gaining a full medical history is of paramount importance in order to give best advice for our patients and ensure that we aren’t treating something that could be masking a possible serious underlying health concern. Hyperhidrosis treatment should only be undertaken by a CQC regulated clinic in England and a HIS registered clinic in Scotland as it’s a medical condition. In my experience, patients suffering with this condition tend to become patients of your clinic for a long period of time, and it’s important as a practitioner to build up a trusting relationship with your patients. In some cases, you might be sharing their treatment sessions with the NHS, and it would be wise to discuss sharing your clinical notes with the patient’s GP to ensure a continuation of medical care is adapted. Obviously, this should only be done with explicit permission of the patient. By sharing the treatment regime, you are making the NHS team aware of the ongoing condition and its impact on the patient. This could potentially encourage more frequent NHS appointments, which will save the patient money and demonstrate your ethical stance as a medical practitioner.

owing to its potentially severe and irreversible side effects, such as compensatory sweating, extreme hypotension, arrhythmia, and heat intolerance.48 In ETS, surgeons interrupt the sympathetic chain by clipping the sympathetic nerves, in turn preventing activation of the sweat glands. It has been used for palmar, axillary, craniofacial, and sometimes plantar hyperhidrosis.47,48

Emerging therapies Alternative therapies that deliver energy to destroy or disrupt the eccrine glands are under investigation and have a limited number of studies supporting their use. These include ultrasound,44,49 laser,50,51,52 and radiofrequency microneedling.53 Radiofrequency microneedling is an emerging therapy in which energy is delivered into the deep dermis via insulated microneedles. In the short term, these therapies are likely to be expensive and scarce. Methods of combating the side effects of anticholinergic medications to make them more tolerable have also had positive results.54

Conclusion Hyperhidrosis can be primary or secondary, focal, multifocal or generalised. Secondary causes need to be excluded before treatment can be considered. Treatment should consider the location of involvement and the impact it is having on the patient. The psychological and social implications of the condition are not to be underestimated and this is why when selecting a treatment for hyperhidrosis a holistic approach is best employed. Treatment ladders are helpful as they recommend the use of the safest and most convenient options first and then progressing to those with broader side effect profiles if there are treatment failures or unacceptable control of symptoms.

Dr Rakesh Anand is a London-based consultant dermatologist and fellow in Mohs micrographic surgery at the St John’s Institute of Dermatology. He has an interest in the procedural aspects of dermatology. Dr Anand believes in a holistic approach in achieving and maintaining healthy skin. This is informed by his training in psychology and behavioural neuroscience. QUAL: BSc (Hons), MSc, MB BS, MRCP (Derm)

Dr Emma Craythorne is a consultant dermatologist, dermatological and laser surgeon and Mohs micrographic surgeon at the St John’s Institute of Dermatology at Guy’s and St Thomas’s Hospital NHS Trust. Dr Craythorne has expertise in all areas of skin scarring, skin cancer, general dermatology, and cosmetic dermatology. QUAL: MBChB, FRCP Test your knowledge! Complete the multiple-choice questions below and go online to receive your CPD certificate!

Questions Possible answers

1. Which of the following is not a cause of hyperhidrosis?

a. Anticholinergic medication b. Hyperthyroidism c. Pregnancy d. Infection 2. Hyperhidrosis is associated with… a. Warts b. Impetigo c. Scabies d. Pitted keratolysis

3. Iontophoresis cannot be considered for primary focal hyperhidrosis affecting the… a. Face b. Hands c. Axilla d. Feet

4. What is not a potential adverse effect of an anticholinergic? a. Constipation b. Urinary retention c. Excessive salivation d. Blurred vision

5. What concentration of aluminium chloride containing antiperspirants should be considered if commercially available preparations fail? a. 5 b. 20 c. 60 d. 10

Answers: 1. A, 2. D, 3. A. 4. C, 5. B

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