Hyperhidrosis and other sweat gland disorders, including bromhidrosis and hidradenitis suppurativa (HS), have the potential to be deeply distressing conditions1.When severe, they impair an individual’s daily activities, reduce performance and productivity in the workplace, and lead to higher rates of depression and poor personal image. Despite the high physical and emotional impact of HS, some patients with hyperhidrosis and bromhidrosis do not seek treatment from their General Practitioners. Conversely, other patients present repeatedly until the diagnosis is made and treatment is initiated.
Hyperhidrosis is defined as the production of sweat in amounts greater than physiologically required. It is rarely a sign of significant underlying pathology. More often it is a chronic, primary, idiopathic problem. Idiopathic, primary focal hyperhidrosis is localised to certain areas of the body. The most commonly affected areas are the axillae, palms and soles.
Bromhidrosis refers to offensive body odour. It can cause significant embarrassment and social isolation and impair an individual’s quality of life2. Sudiferous (sweat) glands are divided into apocrine (underarm, breast, groin) and eccrine (entire body) glands3. Bromhidrosis is thought to occur through biotransformation of odourless secretions into volatile odorous molecules. In the axilla, Corynebacterium is the most common bacterium, which is implicated in the production of unpleasant smelling fatty acids4.
Hidradenitis suppurativa (HS) is also known descriptively as acne inversa. It is a chronic, relapsing inflammatory condition affecting the pilosebaceous unit5,6. HS most commonly affects the axillary, groin, perianal, perineal and genital skin. The inframammary skin may also be affected in some women. Patients repeatedly present to accident and emergency departments or their GP with a solitary painful ‘boil’. Delay in diagnosis and failure to initiate prophylactic treatment may result in the formation of sinus tracts, abscesses and scarring.
Clinical features and diagnosis
Sweating is important for thermoregulation, skin hydration, and fluid and electrolyte balance. Three types of sweat glands have been described, including eccrine, apocrine and apoeccrine glands. Eccrine gland overactivity is implicated in the palmer and plantar hyperhidrosis, while overactive apoeccrine glands cause axillary hyperhidrosis7. Eccrine sweat glands are innervated by the sympathetic nervous system, with different regions of the brain controlling thermal and emotional sweating. Acetylecholine is the primary neurotransmitter responsible for innervating eccrine sweat glands. Sweating on the face, chest and back is caused by thermal stimuli, whereas sweating of the palms and soles is triggered by emotional stimuli. Gustatory sweating, where both salivation and perspiration occur simultaneously in response to hunger or eating, is confined to the peri-oral region of the face. In primary hyperhidrosis, sweat glands appear histologically normal, and it is believed that the cause of emotional hyperhidrosis is an inappropriate or exaggerated central response to emotional stress. Emotional sweating is rarely experienced during sleep.
Excessive sweating is a common complaint, with a prevalence of between one and three per cent in the population. It is important for doctors to determine whether the hyperhidrosis is generalised or focal. The medical history should focus on8:
- Location of sweating: generalised versus focal, unilateral or symmetrical
- Age of onset
- Duration of symptoms
- Triggers such as heat, emotion, eating
- Concurrent medical and medication history
- Psychological, physical and social impact
- Modifications to personal and professional behaviour
Generalised hyperhidrosis affects the entire body, and a detailed history and examination can distinguish idiopathic from secondary causes, including systemic diseases and medications. The most common cause of generalised hyperhidrosis is excessive heat. Table 1 lists a number of causes to consider when assessing generalised hyperhidrosis8.
|Table 1: Causes of Generalised Hyperhidrosis to consider in General Practice|
· Selective serotonin reuptake inhibitors
· Tricyclic antidepressants
· Cholinesterase inhibitors
· Diabetes mellitus
· Carcinoid syndrome
Congestive heart failure
· Spinal cord injury with autonomic dysreflexia
· Parkinson disease
· Peripheral neuropathy
· Intracranial lesions
Focal hyperhidrosis most commonly affects the axilla, palms and soles1. Patients may also describe sweating of the scalp, face, inframammary and groin areas9. The most common causes of focal hyperhidrosis are listed in Table 28. Primary focal hyperhidrosis is commonly reported in healthy adults less than 25 years of age, with two-thirds of patients reporting a positive family history.
A diagnosis of primary focal hyperhidrosis can be made with a history of focal, visible, excessive sweating of at least six months duration without apparent cause, accompanied by two of10:
- Bilateral, symmetrical sweating
- Impairment of daily activity
- At least one episode per week
- Onset before age 25 years
- Family history of idiopathic hyperhidrosis
- Focal sweating that ceases during sleep
Rosacea, a common cause of facial flushing, is not generally associated with facial sweating.
|Table 2: Causes of focal hyperhidrosis|
|Primary focal hyperhidrosis (most common)
· Sweating around the mouth, nose and forehead associated with the consumption or sight of food that produces strong salivation
· Particularly associated with spicy or hot food
· Spinal cord injuries
· Peripheral neuropathy
While eccrine glands are responsible for thermoregulation, apocrine glands and apoeccrine glands are responsible for pheromonal odours. Apocrine and apoeccrine glands are present in the axillae, groin and inframammary regions. They secrete a small amount of non-odorous oil. Biotransformation of this oily fluid by resident microflora, notably Corynebacterium, creates volatile odorous molecules.
Bromhidrosis can be divided into apocrine and eccrine bromhidrosis4. Apocrine bromhidrosis is the most prevalent form, occurring exclusively after puberty and producing the distinctive axillary odour reported by many patients. Apocrine bromhidrosis is more commonly reported in males, possibly due to larger and more numerous apocrine glands. Eccrine bromhidrosis occurs when eccrine sweat degrades keratin, with subsequent bacterial degradation. Eccrine bromhidrosis is most common on the soles and the odour can linger in footwear and gym clothing. Ingestion of certain foods or medications may worsen eccrine bromhidrosis. Metabolic disorders including triethylaminuria, with its distinctive fishy odour, is another rare cause of bromhidrosis11. Genetic testing is available in Australia, with the condition managed with dietary modification.
The diagnosis of bromhidrosis is made clinically. A thorough history is important. Bromhidrosiphobia is the abnormal fear of producing body odour, and is associated with schizophrenia. Olfactory hallucinations can also be associated with intracranial lesions, and a neurological examination is prudent if no odour is clinically apparent. Although isolation of Corynebacterium, Staphylococcus, Micrococcus and Propionibacterium is common in patients with bromhidrosis, bacterial swabs are rarely beneficial for guiding treatment.
The prevalence of HS is estimated to be around one per cent of the population, and up to four per cent among young adults attending sexual health clinics6, 12. Hs can occur any time after the onset of puberty. It most commonly presents in the second and third decades of life. HS is more common in women. A positive family history in a first degree relative is common. Other risk factors include high body mass index, smoking, diet and hormonal factors. Mechanical stress on the skin, or skin friction is a factor in localizing HS to certain body sites.
Classically, apocrine glands have been implicated in the development of HS. However, recent research has demonstrated that follicular occlusion with secondary follicular rupture and localised inflammation are the primary events13. Hormonally-induced keratinocyte proliferation leads to follicular hyperkeratosis and follicular occlusion. Rupture of the sebofollicular junction and local inflammation results in destruction of the follicle. Sinus tracts form and are colonised with commensal bacteria. Infection is a late and secondary event.
HS begins in intertriginous regions, most commonly the axillae. Table 3 lists other intertriginous and non-intertriginous areas that may become affected progressively. The hallmark of early HS is an acute painful, tender nodules in the axilla or groin14. The nodules may rupture and drain malodourous material. The presence of chronic or relapsing inflammatory nodules, sinus tracts and scarring in intertriginous areas confirm the diagnosis of HS. The finding of comedones in the axilla or groin is pathognomonic for HS (Figure 1).
Any patient with a single “boil” in the axilla of groin should be suspected of having HS. Any patient who has had more than one episode should be referred to a dermatologist for diagnosis and treatment. The nodules of HS are not true “boils” or “furuncles.” HS lesions are more deep-seated, rounded and lack a central punctum. Table 4 outlines clinical features that distinguish HS from other differential diagnoses.
|Table 3: Body sites affected by hidradenitis suppurativa|
· Inguinal area
· Inner thighs
· Perianal and perineal area
· Mammary and inframammary
· Pubic area
· Scalp and retroauricular area (rare)
· Sites of skin compression or friction
· Waistbands, beltlines, brassiere straps
|Table 4: Characteristics of hidradenitis suppurativa and its differential diagnoses|
|Follicular pyodermas (folliculitis, furuncles, carbuncles)||· Superficial inflammatory papules (with or without pustules) that surround hair follicles
· Not as deep-seated as HS lesions
· Transient lesions that generally respond well to appropriate antibiotic therapy
· Do not progress to form sinuses or keloid scarring
|Acne vulgaris||· Like HS, hyperkeratinisaion leads to formation of comedos, inflammatory nodules and scarring
· Generally distributed on the face, upper chest and back
· Less likely to form sinus tracts and extensive scar formation
|Intergluteal pilonidal disease||· Infection of the skin and tissue of the natal cleft secondary to follicular occlusion
· Formation of a sinus, cavity or pit in the natal cleft
· May drain purulent, bloody and malodourous material
· May coexist with HS
|Crohn disease||· Perianal and vulvar skin manifestations include abscesses, fistulae, sinus tracts, scarring and “knife-cut” ulcers
· Most often associated with a history of gastrointestinal illness
· Cases of concomitant HS and Crohn disease rarely reported
|Granuloma inguinale||· Sexually transmitted infection caused by Klebsiella granulomatis
· Characterised by enlarging red ulcers with bleeding granulation tissue
· Ulcers confined to the vulva, penis, scrotum, glans, and inguinal and perianal skin
The Hurley clinical staging system is used to categorise patients into three disease severity groups15. Table 5 outlines the features of each. The severity of disease is directly related to impact on quality of life and mental health. Patients with severe HS are significantly more likely to suffer major depression16. Complaints of pain, odour and appearance negatively affect performance in social and professional settings.
|Table 5: Clinical features of the Hurley clinical staging system|
|Stage I||Abscess formation (single/multiple) without sinus tract development or scarring|
|Chronic/relapsing abscess formation with sinus tract formation and scarring
Single or multiple widespread lesions
|Diffuse involvement, with multiple connected sinus tracts and abscesses across the entire affected area|
HS is a clinical diagnosis. There are no useful diagnostic tests . Disease staging involves a directed history to ascertain the impact that the disease is having on social and professional functioning and examination of all potentially affected areas . A skin biopsy is rarely required, unless to exclude an overlying squamous cell carcinoma (firm, slow growing, ulcerated, non-fluctuant mass that is non-draining). HS is not an infectious diagnosis, making routine bacterial cultures unnecessary. However, bacterial cultures may be useful in cases of secondarily infected lesions or recurrent HS that is refractory to treatment.
Conservative management of generalised and focal hyperhidrosis involves identifying and treating any associated underlying cause, frequent use of commercially available antiperspirants and deodorants, and lifestyle modifications, such as more frequent showering, wearing lightweight clothing made from natural fibres, regular changing of socks and other affected clothing and avoiding relevant triggers such as spicy food and hot environments8.
Most antiperspirants contain a low-dose metal salt (generally aluminium), which physically obstructs the opening of the sweat gland on the skin. This obstruction damages the epithelial cells within the sweat duct leading to the formation of occlusive plugs17. Antiperspirants containing aluminium chloride hexyhydrate are more effective than agents containing aluminium chloride or aluminium chlorohydrate8, 18. A concentration of 10-20% aluminium chloride hexahydrate is appropriate for axillary hyperhidrosis, 25% for palmar and plantar hyperhidrosis and 35% for refractory cases2, 19.
Treatment with stronger antiperspirants is often limited by skin irritation and burning sensations, particularly in the axilla. To minimise this reaction, antiperspirant should be applied to dry skin at night, when hyperhidrosis is reduced, and washed off in the morning20. Skin irritation can be controlled with 1% hydrocortisone1.
Botulinum Toxin A
Periodic injection of botulinum toxin A is a safe and effective treatment for focal hyperhidrosis. By blocking the presynaptic release of neuronal acetylcholine from the presynaptic junction of the neuromuscular and autonomic nerves, a single injection of botulinum toxin reduces sweat production for up to 12 months. Several clinical trials support the efficacy of botulinum toxin A in the treatment of axillary hyperhidrosis21, 24.
Medicare subsidises the use of botulinum toxin A or Dysport for severe primary focal axillary hyperhidrosis when administered by a dermatologist8. Patients must be aged 12 years or more and failed or are intolerant to topical aluminium chloride hexahydrate for one to two months. Botox and Dysport treatment of the palms and soles are also highly effective but are not subsidised by Medicare. The typical dose of Botox is 50IU for each axilla. Sweating is reduced within two to four days, and usually persists for six to nine months. Limiting factors for botulinum toxin A include pain during injections and non-subsidised cost.
Iontophoresis utilises a direct electrical current to deliver polar molecules through intact skin to the sweat glands. Patients place affected hands and/or feet on moistened pads in the iontophoresis unit (Figure 5) for 15 to 20 minutes per session. Tap water is generally utilised in iontophoresis devices available for home use26. Glycopyrronium bromide solution is the most effective liquid medium, however it is only available in specialist centres. Iontophoresis is a safe, efficacious treatment for palmar and plantar hyperhidrosis, alleviating symptoms in 40-85% of cases depending on the solution used25. Iontophoresis is not available in every Australian state. Reported side effects include dry, cracked hands and feet, erythema and skin irritation, and transient vesiculation25. Iontophoresis cannot be used for patients with a pacemaker or implantable device. Patients often trial iontophoresis in specialist skin clinics prior to purchasing a home device.
Microwave thermolysis utilises microwave energy to destroy eccrine glands and is an emerging therapy for axillary hyperhidrosis27-29. Treatment is generally administered through two thirty-minute sessions separated by three months. A device is available in some Australian specialised skin clinics, however cost and limited availability preclude many patients from this therapy.
The efficacy of anticholinergic medications in focal hyperhidrosis is well established30, 31. The most commonly prescribed anticholinergic medication in Australia are propantheline bromide and oxybutynin. These are cheap medications that can be used regularly to control hyperhidrosis. Glycopyrrolate is an effective alternative if not tolerated, although this medication is significantly more expensive. Anticholinergic side-effects are invariably reported, most commonly dry mouth, blurred vision, headache and urinary retention. Commencing oral oxybutynin at a low dose (2.5 mg/day) and increasing the dose slowly up to a maximum of 10 mg/day reduces the likelihood of experiencing significant anticholinergic side effects. Drowsiness may occur. These agents may aggravate glaucoma. They are contraindicated in myasthenia gravis. There are numerous drug interaction and these agents all need to be used with caution. Specialist referral may be indicated.
Surgery is reserved for patients who have failed topical and systemic therapy and are experiencing serious social, emotional and professional consequences due to hyperhidrosis. Significant cost is a barrier for many patients. Liposuction or local excision of axillary eccrine and apocrine glands may improve symptoms of axillary hyperhidrosis. Surgical excision is often associated with poor cosmetic outcomes, scarring, restriction of arm movements, and compensatory hyperhidrosis where sweating is paradoxically increased elsewhere on the body32. Other complications include bruising, infection, haematoma and dysesthesia33,34. A randomised trial found that Botulinum toxin A injection is superior to suction curettage in reducing resting and exercise-induced hyperhidrosis33.
Endoscopic thoracic sympathectomy (ETS) involves cauterising, clipping or cutting the sympathetic chain supplying the upper extremities or cervicofascial region. This surgery is reserved as a last resort for patients with morbidly debilitating disease. While effective for upper limb (including axillary) hyperhidrosis, there is a substantial risk of Horner syndrome, pneumothorax, paraesthesia and bradycardia35. Up to 67% of patients will experience compensatory hyperhidrosis following ETS36.
It is important to assess the patient’s goals of treatment and expectations. Conservative management, including routine washing, removal of axillary hair and removal of sweaty clothing, is sufficient for mild cases. However improvement may be temporary and incomplete. Patients have generally utilised commercially available deodorants and fragrances by the time they present to their General Practitioner. These measures remain first-line therapy, and their routine use should be encouraged. Deodorants containing antimicrobial metal ions, including calcium phosphate and zeolite antimicrobial ceramics, inhibit axillary bacterial production2. Antiseptic soaps and topical antibiotics can be used to reduce the amount of contributory bacteria. In very severe cases topical or oral metronidazole can be helpful.
For cases where bromhidrosis is associated with excessive sweating, referral to a specialist for treatment of focal hyperhidrosis may be required. Topical aluminium-containing antiperspirants, botulinum toxin A injection and iontophoresis are possible treatment options for bromhidrosis associated with hyperhidrosis.
The goals of treatment of HS are pain relief, specific treatment of individual nodules, prevention of scarring and sinus tract formation and interventions to reduce the risk of developing further new lesions. Evidence-based European guidelines are currently being developed37.
Lifestyle modifications and general measures to reduce the risk of developing new lesions include5, 37:
- Education and support: given an increased risk of major depression, all patients should be asked about psychological impact and offered resources for support16
- Hygiene: daily washing of affected areas will improve odour and minimise the risk of secondary infection. Using non-abrasive soap and no abrasive material is essential. Bleach baths may be helpful
- Non-irritating antiperspirants are recommended. For patients unable to tolerate antiperspirants, Botox injections are helpful
- Weight management: excess weight has been associated with HS. Although a causative association has not been established, excess weight is associated with skin occlusion, skin trauma, and hormonal variations38
- Smoking cessation: an association between smoking and HS has been identified in numerous patient populations5, 38, 39. Continuing smoking appears to be a significant factors in patients who fail to achieve remission
- Diet: dairy and high-glycaemic diets have been implicated in exacerbations of HS40, 41. Although the effect of dietary modifications has not been evaluated in clinical trial, some dermatologists recommend a low glycaemic diet for patients with HS
- Avoidance of skin trauma: skin maceration and trauma may perpetuate inflammation, follicular occlusion and rupture. Patients likely benefit wearing loose, light clothing and avoiding excessive heat5. Patients must not squeeze or disturb lesions5. Shaving and depilatory creams may aggravate HS. Hair removal laser is a generally well tolerated alternative.
Medical and surgical therapy
Treatment is dependent on disease severity, and includes topical therapy, systemic therapy, and surgery. Antibiotics used to treat HS are thought to act both as anti-inflammatory agents as well as antibacterial agents.
Treatment of mild disease (Hurley stage I) includes topical clindamycin, topical resorcinol, and minor surgery. Patients should be encouraged to bathe using a topical antiseptic or antibacterial soap that is not abrasive to damaged skin. Clindamycin 1% lotion, applied twice daily to affected areas, is first-line therapy for mild HS. Clindamycin appears to decrease the number of inflammatory nodules and prevent secondary infection42. Although not confirmed in clinical trials, the short-term use of oral antibioitcs, typically doxycycline or minocycline, can alleviate acute flares of mild HS. Topical resorcinol is a chemical exfoliant with keratolytic, anti-inflammatory and antiseptic actions43. Application of resorcinol cream to new nodules (not the entire region) appears to reduce pain and promote healing of new lesions43. Localised desquamation is an expected side effect. However, the availability of resorcinol is limited in Australia.
Given that sinus tract formation is likely due to rupture of the follicular unit, removal of the entire nodule and unit through punch debridement reduces the risk of recurrence and disease progression44. Other specialist treatment for mild HS includes intralesional corticosteroid therapy, which may help settle acute flares.
Treatment for moderate disease (Hurley stage II) includes systemic antibiotics, hormonal therapy and surgery. The suggested antibiotic regimen for moderate HS is doxycycline or minocycline 50 to 100mg twice daily for three to six months. Patients with moderate disease should be referred early for further treatment if not responding to systemic antibiotics. Clindamycin and rifampin are suggested for patients who fail to respond to tetracyclines45, 46. These antibiotics are rarely used as initial therapy given the risk of Clostridium difficile infection.
Given that androgens contribute to the development of HS, antiandrogen medications can be effective for lesion resolution and prevention of new lesions in a sub-population of affected women47, 48. Combined oral contraceptive pill containing cyproterone acetate, drospirenone, desogestrel or gestodene are generally used. Spironolactone 25 to 50mg daily, increasing up to 100mg daily is an alternative for women unable to tolerate oral contraceptive medications. All of these agents are contraindicated in pregnancy, which should be excluded prior to initiating therapy. Male patients may respond to either dutasteride or finasteride.
Surgery for moderate HS includes punch debridement of new lesions and debridement of extensive sinuses. Surgery does not arrest the underlying disease process, and should accompany medical maintenance treatment.
Treatment for severe and refractory disease (Hurley stage III) requires specialist multidisciplinary care involving dermatologists, plastic surgeons and often psychologists. Medical management includes the addition of TNF-alpha inhibitors, oral retinoids, immunosuppressants and surgery. These agents can be used in addition to the topical and systemic treatments outlined above. Intravenous TNF-alpha inhibitors, notably infliximab, are effective biological agents for severe HS49-51. Early trials have found infliximab superior to adalimumab and etanercept. Availability, cost and significant adverse effects are limitations to biological agents for some patients.
Oral retinoids, including isotretinoin and acitretin benefit only a minority of patients. Retinoids can also aggravate HS in some patients52-54. This aggravation may be due to the mechanism of action of isotretinoin, which increases intrafollicular pressure and ruptures the follicular wall. This may trigger an unwanted inflammatory progress and worsen the disease.
Immunosuppressants, including prednisolone and cyclosporine, are used to settle acute inflammation. A three- to four- day course of prednisolone 40 mg to 60 mg daily is usually sufficient to settle acute flares. Cyclosporine can also be used in early disease to prevent new lesions forming. Cyclosporine is less useful in established disease with scarring and sinus tract formation.
Surgery is used in severe HS to remove acute nodules and sinus tracts, and to remove scarred tissue. Surgical procedures considered in severe HS include incision and drainage of lesions, punch debridement of whole follicular units, un-roofing of nodules and sinus tracts, and excision of entire affected regions. Surgery is usually combined with general measures and maintenance medical therapy.
Hyperhidrosis and bromhidrosis
Untreated, focal hyperhidrosis generally develops after puberty and rarely improves. With early diagnosis and initiation of therapy, patients should generally experience significant symptomatic relief. It is important to assess each patient’s goals of treatment. Patients experiencing significant social and professional consequences should be referred to a specialist early to initiate first- and second-line treatments. While carefully considering the adverse effects of each treatment, and the severity and location of the disease, many patients are likely to experience clinical improvement. Bromhidrosis is generally well managed with an approach including lifestyle modifications, managing excess sweating and the application of fragrances.
The impact of severe HS on a patient’s quality of life can be profound. The average duration of untreated HS is 20 years The prognosis is improved by early diagnosis accompanied by, lifestyle modifications and intermittent medical treatment. Moderate disease requires specialist intervention and maintenance treatment. Severe HS is very difficult to treat and requires intensive medical and surgical treatment.
There have been reports that clonidine, an alpha-2 adrenergic agonist that diminishes the sympathetic outflow, is effective in reducing hyperhidrosis55, 56. Some studies have suggested that patients experiencing emotional hyperhidrosis may benefit from beta-blocker or benzodiazepine therapy57, 58. However, these should not be considered as part of routine management of hyperhidrosis.
Other treatments with limited data include topical botulinum, laser therapy and ultrasound therapy59-61.
A number of studies have suggested that non-invasive treatment of bromhidrosis with laser therapy is effective in reducing axillary bromhidrosis62-64. The data available for these therapies is limited and requires further investigation.
Based on current case reports, numerous emerging therapies may benefit patients with severe HS. A number of patients have experienced improvement following subcutaneous injections of interleukin inhibitors, Ustekinumab or Anakinra65-67. Other emerging adjuvants therapies for severe or refractory HS include metformin, zinc supplementation, hair removal laser therapy, botulinum toxin, vitamin D3 and external beam radiation. The evidence for these therapies is limited, and should not be included in routine management regimens.
A 26-year-old man presents to his General Practitioner complaining of excessive sweating during the day. He reports that he has a supply of shirts at work for when he invariably saturates the underarms of his clothing. He is unable to wear light coloured shirts and describes feeling increasingly self-conscious. His work colleagues make light-hearted comments, which compound his poor personal image. He also reports problems dating, given that he is constantly preoccupied by the thought that he will saturate his shirt. He describes a symmetrical pattern of hyperhidrosis affecting both axillae. The excessive sweating began during his teenage years and occurs multiple times per week. Surprisingly to the patient, he never needs to change his bedclothes due to excessive sweating.
The patient has already trialled “Driclor”, an antiperspirant containing 20% aluminium chloride. He reports difficulty using the antiperspirant due to stinging, and was dissatisfied with the effect. It is discovered that the patient is using the aluminium antiperspirant in the mornings as a normal deodorant. The patient is happy to trial “Driclor” again, applying the antiperspirant to dry skin at night and washing the area in the morning. These measures, along with a 1% hydrocortisone ointment, minimise skin irritation. However, after two months of treatment, the patient is unhappy with the degree of improvement.
The patient is referred to a dermatologist, where further treatment options are discussed. He is concerned about the possible side effects of anticholinergic medications. Given the substantial time and effort required to undergo iontophoresis, the patient elects to trial botulinum toxin A injections. Following a 50 IU dose into each axilla, the patient experiences a significant reduction in the rate of sweat production. He returns to the dermatologist six months later for repeat injections. Apart from mild pain at the injection sites during the procedures, the patient tolerates treatment well and reports a significant improvement in his quality of life.
A 34-year-old woman presents to her General Practitioner with recurrent boils in her left axilla and inner thighs. The nodules are exquisitely painful, malodourous and ooze into her clothing. She is highly embarrassed of the condition, becoming socially isolated. She has been unable to become intimate with a recent partner, who became frustrated and ended the relationship. She has presented repeatedly to another General Practitioner, who has treated her for folliculitis and boils.
The flares started with a single, painful lesion in her inner thigh that affected her ability to walk long distances. She was given a course of oral cephalexin, which did not settle the lesion. She noticed a number of other lesions developing in the inner thigh and in her right axilla. The lesions tended to regress spontaneously within approximately two weeks. The patient describes her worst flair consisting of eight painful lesions. An abscess on her inner thigh was incised and drained by her General Practitioner, with a significant improvement in her pain. The patient also suffers from polycystic ovarian syndrome, has smoked one pack of cigarettes each day since adolescence and has a body mass index of 31.
On examination during her worst flare, the General Practitioner counts 13 painful, deep-seated lesions in the left axilla and inner thighs. The lesions are widely separated. The lesions are accompanied by intercommunicating sinuses releasing malodourous bloody discharge. There is extensive scarring in the inner thigh. A diagnosis of hidradenitis suppuratives Hurley Stage II is made.
The patient is encouraged to bathe regularly using a non-soap cleanser, cease smoking, modify her diet and avoid skin trauma. It is imperative that she does not squeeze or manipulate the lesions in any way. Topical 1% clindamycin cream is applied twice daily for three months. A course of oral doxycycline 100 mg daily is prescribed and, given the patient has no contraindications and is not currently planning to become pregnant, a combined oral contraceptive pill containing cyproterone acetate is commenced.
Given there have been worsening acute attacks, the patient is referred to a specialist dermatologist. Punch debridement is performed to remove recurring lesions and the offending follicular units. With aggressive medical management and minor surgical management, the patient experiences significant clinical improvement within three months. The patient follows up routinely with the General Practitioner and dermatologist to monitor recurrence and encourage ongoing lifestyle modifications.
Hyperhidrosis, bromhidrosis and hidradenitis suppurativa are conditions that cause major distress and have significant deleterious effects on quality of life. Accurate diagnosis and early referral of patients with debilitating disease may minimise the effects these conditions have on personal and professional functioning.
- Accurate clinical evaluation of hyperhidrosis will help differentiate primary focal hyperhidrosis from generalised hyperhidrosis, which is likely secondary to medications or a systemic illness. The history should include questions about the consequences of hyperhidrosis on a patient’s life
- Patients with significant hyperhidrosis unresponsive to aluminium-based antiperspirants should be referred early to a specialist for further treatment, including topical, systemic and surgical therapies. The selection of each treatment follows careful consideration of their specific adverse effects
- Bromhidrosis can have substantial negative consequences in social and professional settings. A clinical diagnosis is generally sufficient. Treatment consists of reducing the volume of sweating, optimisation of hygiene and application of fragrances to mask body odour
- Hidradenitis suppuratives is a chronic follicular occlusive disorder that is characterised by recurrent nodules, sinus tracts and keloid scarring. It is not a primary disorder of apocrine glands as previously thought. It classically affects the intertriginous axillary, groin, perianal, perineal and mammary skin. The severe pain, odour, discharge and permanent scarring greatly impacts quality of life and psychological wellbeing
- All patients with HS should be encouraged to undertake general measures and lifestyle modifications to prevent developing new lesions, particularly smoking cessation and dietary modification. Treatment thereafter depends on the clinical stage, with topical, systemic and surgical therapies available. Early referral to a dermatologist will help prevent disease progression
- Patients with moderate to severe HS are at high risk of developing major depression. Resources for psychological support are beneficial for patients whose quality of life is negatively affected
- Treatments for HS to consider prior to dermatology referral include topical antibiotics, oral antibiotics and hormonal therapy. Severe disease may require immunological therapy or extensive surgical treatment.
1. International Hyperhidrosis Society: www.sweathelp.org
2. British Association of Dermatology hyperhidrosis leaflet: http://www.bad.org.uk/shared/get-file.ashx?id=93&itemtype=document
3. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa: http://onlinelibrary.wiley.com/store/10.1111/jdv.12966/asset/jdv12966.pdf;jsessionid=7AC81F99D02EA99FB765FE241AEB2541.f01t04?v=1&t=in5u8290&s=1ed0e28bb86d0fe0f419940e6a4fcd515a18577b
4. British Association of Dermatology Hidradenitis Suppurativa leaflet: http://www.bad.org.uk/shared/get-file.ashx?id=88&itemtype=document
1. Strutton DR, Kowalski JW, Glaser DA. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey. Journal of the American Academy of Dermatology. 2004;51(2):241–8.
2. Kanlayavattanakul M, Lourith N. Body malodours and their topical treatment agents. International Journal of Cosmetic Science. 2011 Mar 15;33(4):298–311.
3. He J, Wang T, Dong J. A close positive correlation between malodor and sweating as a marker for the treatment of axillary bromhidrosis with Botulinum toxin A. J Dermatolog Treat. 2012 Dec;23(6):461–4.
4. James AG, Austin CJ, Cox DS, Taylor D, Calvert R. Microbiological and biochemical origins of human axillary odour. FEMS Microbiology Ecology. 2012;83(3):527–40.
5. Jemec GBE. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012 Jan 11;366(2):158–64.
6. Dufour DN, Emtestam L, Jemec GB. Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease. Postgraduate Medical Journal. 2014 Mar 18;90(1062):216–21.
7. Lonsdale-Eccles A, Leonard N, Lawrence C. Axillary hyperhidrosis: eccrine or apocrine? Clinical and Experimental Dermatology. 2003;28(1):2–7.
8. Perera E, Sinclair R. Hyperhidrosis and bromhidrosis — a guide to assessment and management. Australian Family Physician. 2013 May;42(5):266–9.
9. Walling HW. Primary hyperhidrosis increases the risk of cutaneous infection: a case-control study of 387 patients. Journal of the American Academy of Dermatology. 2009.
10. Hornberger J, Grimes K, Naumann M, Anna Glaser D, Lowe NJ, Naver H, et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. Journal of the American Academy of Dermatology. 2004 Aug;51(2):274–86.
11. Chalmers RA, Bain MD, Michelakakis H, Zschocke J, Iles RA. Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children. J Inherit Metab Dis. 2006 Feb;29(1):162–72.
12. Matusiak Ł, Bieniek A, Szepietowski J. Psychophysical Aspects of Hidradenitis Suppurativa. Acta Dermato Venereologica. 2010;90(3):264–8.
13. Danby FW, Margesson LJ. Hidradenitis Suppurativa. Dermatologic Clinics. 2010;28(4):779–93.
14. Jemec G, Gottlieb A, Forman S. Efficacy and Safety of Adalimumab in patients with moderate to severe hidradenitis suppurativa: Results from PIONEER II, a Phase 3, randomized, …. Journal of the American Academy of Dermatology. JOURNAL OF …; 2015. 1 p.
15. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach. Dermatologic surgery. New York: Marcel Dekker; 1989.
16. Onderdijk AJ, van der Zee HH, Esmann S, Lophaven S, Dufour DN, Jemec GBE, et al. Depression in patients with hidradenitis suppurativa. Journal of the European Academy of Dermatology and Venereology. 2012;27(4):473–8.
17. Holzle E, Braun-Falco O. Structural changes in axillary eccrine glands following long-term treatment with aluminium chloride hexahydrate solution. British Journal of Dermatology. 1984 Apr;110(4):399–403.
18. Scholes KT, Crow KD, Ellis JP, Harman RR, Saihan EM. Axillary hyperhidrosis treated with alcoholic solution of aluminium chloride hexahydrate. Br Med J. 1978.
19. Walling HW, Swick BL. Treatment options for hyperhidrosis. Am J Clin Dermatol. 2011 Oct 1;12(5):285–95.
20. Pariser DM, Ballard A. Topical Therapies in Hyperhidrosis Care. Dermatologic Clinics. 2014 Oct;32(4):485–90.
21. Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum Toxin A for Axillary Hyperhidrosis (Excessive Sweating). N Engl J Med. 2001 Feb 15;344(7):488–93.
22. Naumann M, Lowe NJ, Kumar CR. Botulinum toxin type A is a safe and effective treatment for axillary hyperhidrosis over 16 months: a prospective study. Archives of Dermatology. 2003;139(6).
23. Schnider P, Moraru E, Kittler H, Binder M. Treatment of focal hyperhidrosis with botulinum toxin type A: long‐term follow‐up in 61 patients. British Journal of …. 2001.
24. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. BMJ. 2001;323(7313):596–6.
25. Pariser DM, Ballard A. Iontophoresis for Palmar and Plantar Hyperhidrosis. Dermatologic Clinics. 2014;32(4):491–4.
26. Dolianitis C, Scarff CE, Kelly J, Sinclair R. Iontophoresis with glycopyrrolate for the treatment of palmoplantar hyperhidrosis. Australasian Journal of Dermatology. 2004;45(4):208–12.
27. Hong HCH, Lupin M. Clinical evaluation of a microwave device for treating axillary hyperhidrosis. Dermatologic …. 2012.
28. Johnson JE, O’Shaughnessy KF, Kim S. Microwave thermolysis of sweat glands. Lasers in Surgery and Medicine. 2011;44(1):20–5.
29. Glaser DA, Coleman WP, Fan LK. A randomized, blinded clinical evaluation of a novel microwave device for treating axillary hyperhidrosis: the dermatologic reduction in underarm perspiration study. Dermatologic …. 2012.
30. Wolosker N, de Campos J, Kauffman P. A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis. Journal of Vascular Surgery. 2012;55(6):1696–700.
31. Schollhammer M, Brenaut E, Menard-Andivot N, Pillette-Delarue M, Zagnoli A, Chassain-Le Lay M, et al. Oxybutynin as a treatment for generalized hyperhidrosis: a randomized, placebo-controlled trial. Br J Dermatol. 2015 Nov;173(5):1163–8.
32. Keaveny TV, Fitzgerald PAM, Donnelly C, Shanik GD. Surgical management of hyperhidrosis. British Journal of Surgery. 1977;64(8):570–1.
33. Ibrahim O, Kakar R, Bolotin D, Nodzenski M, Disphanurat W, Pace N, et al. The comparative effectiveness of suction-curettage and onabotulinumtoxin-A injections for the treatment of primary focal axillary hyperhidrosis: a randomized control trial. Journal of the American Academy of Dermatology. 2013 Jul;69(1):88–95.
34. Darabaneanu S, Darabaneanu H-A, Niederberger U, Russo PAJ, Lischner S, Hauschild A. Long-term efficacy of subcutaneous sweat gland suction curettage for axillary hyperhidrosis: a prospective gravimetrically controlled study. Dermatol Surg. 2008 Sep;34(9):1170–7–discussion1177.
35. Moraites E, Vaughn OA, Hill S. Endoscopic Thoracic Sympathectomy. Dermatologic Clinics. 2014;32(4):541–8.
36. Herbst F, Plas EG, Függer R, Fritsch A. Endoscopic thoracic sympathectomy for primary hyperhidrosis of the upper limbs. A critical analysis and long-term results of 480 operations. Annals of Surgery. Lippincott, Williams, and Wilkins; 1994 Jul;220(1):86–90.
37. Zouboulis CC, Desai N, Emtestam L, Hunger RE, Ioannides D, Juhász I, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015 Apr;29(4):619–44.
38. Sartorius K, Emtestam L, Jemec G. Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity. British Journal of Dermatology. 2009;161(4):831–9.
39. Revuz JE, Canoui-Poitrine F, Wolkenstein P. Prevalence and factors associated with hidradenitis suppurativa: results from two case-control studies. Journal of the American Academy of Dermatology. 2008;59(4):596–601.
40. Melnik BC. Evidence for acne-promoting effects of milk and other insulinotropic dairy products. 2011.
41. Cordain L, Lindeberg S, Hurtado M. Acne vulgaris: a disease of Western civilization. Archives of …. 2002.
42. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol. 1983;22(5):325–8.
43. Boer J, Jemec G. Resorcinol peels as a possible self‐treatment of painful nodules in hidradenitis suppurativa. Clinical and Experimental Dermatology. 2010;35(1):36–40.
44. Danby FW, Jemec G, Marsch WC. Preliminary findings suggest hidradenitis suppurativa may be due to defective follicular support. British Journal of Dermatology. 2013;168(5):926–7.
45. Gener G, Canoui-Poitrine F, Revuz JE, Faye O, Poli F. Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa: a series of 116 consecutive patients. Dermatology. 2009;219(2):148–54.
46. van der Zee HH, Boer J, Prens EP, Jemec G. The effect of combined treatment with oral clindamycin and oral rifampicin in patients with hidradenitis suppurativa. Dermatology. 2009;219(2):143–7.
47. Nazary M, van der Zee HH, Prens EP, Folkerts G. Pathogenesis and pharmacotherapy of Hidradenitis suppurativa. European Journal of Pharmacology. 2011;672(1-3):1–8.
48. Kraft JN, Searles GE. Hidradenitis suppurativa in 64 female patients: retrospective study comparing oral antibiotics and antiandrogen therapy. Journal of cutaneous medicine and surgery. 2007.
49. Blok JL, Van Hattem S, Jonkman MF. Systemic therapy with immunosuppressive agents and retinoids in hidradenitis suppurativa: a systematic review. British Journal of Dermatology. 2013;168(2):243–52.
50. van Rappard DC, Leenarts M. Comparing treatment outcome of infliximab and adalimumab in patients with severe hidradenitis suppurativa. Journal of …. 2012;23(4):284–9.
51. Grant A, Gonzalez T, Montgomery MO. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. Journal of the American Academy of Dermatology. 2010;62(2):205–17.
52. Boer J, Nazary M. Long-term results of acitretin therapy for hidradenitis suppurativa. Is acne inversa also a misnomer? British Journal of Dermatology. 2010;164(1):170–5.
53. Soria A, Canoui-Poitrine F, Wolkenstein P, Poli F, Gabison G, Pouget F, et al. Absence of efficacy of oral isotretinoin in hidradenitis suppurativa: a retrospective study based on patients’ outcome assessment. Dermatology (Basel). 2009;218(2):134–5.
54. Boer J, van Gemert M. Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa. Journal of the American Academy of Dermatology. 1999;41(4):658.
55. Walling HW. Systemic therapy for primary hyperhidrosis: a retrospective study of 59 patients treated with glycopyrrolate or clonidine. Journal of the American Academy of Dermatology. 2012.
56. Kuritzky A, Hering R, Goldhammer G, Bechar M. Clonidine Treatment in Paroxysmal Localized Hyperhidrosis. Archives of Neurology. 1984 Nov 1;41(11):1210–1.
57. Mack GW, Shannon LM. Influence of beta-adrenergic blockade on the control of sweating in humans. Journal of applied …. 1986.
58. Quraishy MS, Giddings AE. Treating hyperhidrosis. BMJ. 1993 May 8;306(6887):1221–2.
59. Glogau RG. Topically Applied Botulinum Toxin Type A for the Treatment of Primary Axillary Hyperhidrosis: Results of a Randomized, Blinded, Vehicle-Controlled Study. Dermatologic Surgery. 2007 Jan;33:S76–S80.
60. Nestor MS, Park H. Safety and efficacy of micro-focused ultrasound plus visualization for the treatment of axillary hyperhidrosis. J Clin Aesthet Dermatol. 2014.
61. Bechara FG, Georgas D, Sand M. Effects of a Long‐Pulsed 800‐nm Diode Laser on Axillary Hyperhidrosis: A Randomized Controlled Half‐Side Comparison Study. Dermatologic …. 2012.
62. Kunachak S, Wongwaisayawan S, Leelaudomlipi P. Noninvasive Treatment of Bromidrosis by Frequency-Doubled Q-Switched Nd:YAG Laser. Aesthetic Plastic Surgery. 2000 Jul 1;24(3):198–201.
63. Lee KG, Kim SA, Yi SM, Kim JH, Kim I-H. Subdermal Coagulation Treatment of Axillary Bromhidrosis by 1,444 nm Nd:YAG Laser: A Comparison with Surgical Treatment. Ann Dermatol. 2014;26(1):99.
64. Jung SK, Jang HW, Kim HJ, Lee SG, Lee KG, Kim SY, et al. A Prospective, Long-Term Follow-Up Study of 1,444 nm Nd:YAG Laser: A New Modality for Treating Axillary Bromhidrosis. Ann Dermatol. 2014 Mar 31;26(2):184–8.
65. Sharon VR, Garcia MS, Bagheri S. Management of recalcitrant hidradenitis suppurativa with ustekinumab. Acta Dermato Venereologica. 2012;92(3):320–1.
66. Gulliver WP, Jemec GBE, Baker KA. Experience with ustekinumab for the treatment of moderate to severe Hidradenitis suppurativa. Journal of the European Academy of Dermatology and Venereology. 2011;26(7):911–4.
67. Tzanetakou V, Kanni T, Giatrakou S, Katoulis A, Papadavid E, Netea MG, et al. Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa. JAMA Dermatology. 2016;152(1):52.
AUTHORS | Professor Rodney Sinclair and Dr William Cranwell
Prof Sinclair’s main research interests are skin cancer epidemiology, psoriasis, genetic diseases of the skin, autoimmune diseases of the skin, skin immunology and hair and skin stem cell biology. He is considered a world leader in hair disease, nail disease, psoriasis and skin cancer diagnosis and treatment.
View profile on Epworth Find a Doctor
PH | 1300 SINCLAIR WEB | www.sinclairdermatology.com.au