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Hyperhidrosis Dr Abbas Pardakhty 2011 Kerman Faculty of Pharmacy 2

Sweat Glands The human body has 2-5 million sweat glands Two main types: 3 ECCRINE APOCRINE Source:

Eccrine Sweat Glands Approximately 3 million eccrine sweat glands Secrete a clear, odorless fluid Aid in regulating body temperature Areas of concentration: Facial, plantar, and axillae 4 Source:

Apocrine Sweat Glands Inactive until puberty Produce thick fluid Secretions come in contact with bacteria on the skin and produce characteristic “body odor” Found in axillary and genital areas 5 Source:

Sweating The hypothalamus serves as the thermoregulatory center It controls both blood flow and sweat output to the skin’s surface 6 Source:

Sweating The hypothalamus can be triggered by: 7 EXERCISE TEMPERATURE CHANGE STRESS HORMONES Source:

Sweating 8 Once triggered, the hypothalamus sends messages down the spinal cord via neurotransmitters. Source:

Sweating The neurostransmitters travel down the spine via ganglion or sympathetic nerves These ganglion travel to nerves, which reach the skin’s surface 9 Photo used with permission: The Whiteley Clinic,2007 Source:

Neurotransmitters 10 Neurotransmitters act as “vehicles,” transmitting information from the hypothalamus to the skin’s surface. Photo used with permission: The Whiteley Clinic, 2007

Neurotransmitters The neurotransmitters can “exit” at various places along the spinal cord. The “exit” determines the location of skin innervation. 11

Spinal Cord Innervations 12 T2 – T8 innervate the skin of the upper limbs T2-T4 innervate the skin of the face T4-T12 innervate the skin of the trunk T10-T12 innervate the skin of the lower limbs Source:

Neurotransmitters 13 Acetylcholine innervates Eccrine Sweat Glands Catecholamines innervate Apocrine Sweat Glands Source:

Sweating Once innervated, the apocrine and eccrine glands will produce …. SWEAT! 14 Source:

What is Hyperhidrosis? Sweating that is more than required to maintain normal thermal regulation 15

Sweating Nomenclature Areas: Focal, regional, generalized Symmetry: Symmetric or asymmetric Classification: Primary vs. secondary Type of sweating: Anhidrosis, euhydrosis, hyperhidrosis 16 Multi-specialty Working Group on Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis, 2003.

17 Hyperhidrosis

Causes of Generalized Hyperhidrosis Usually secondary in nature Drugs (Venlafaxine,...), toxins, substance abuse Cardiovascular disorders Respiratory failure Infections Malignancies Hodgkin’s, myleoproliferative disorders, cancers with increased catabolism Endocrine/metabolic disorders Thyrotoxicosis, pheochromocytoma, acromegaly, carcinoid tumor, hypoglycemia, menopause Rarely Idiopathic / Primary HH 18

Causes of Localized Hyperhidrosis Usually Idiopathic / Primary Social anxiety disorder Eccrine nevus Gustatory sweating Frey syndrome Impaired evaporation Stump hyperhidrosis after amputation 19

20 Idiopathic (Primary) Focal Hyperhidrosis

21 Mean Age of Onset

Diagnosis of Primary Focal Hyperhidrosis Focal, visible, excessive sweating of at least 6 months duration without apparent cause with at least 2 of the following characteristics: – Bilateral and relatively symmetric – Impairs daily activities – Frequency of at least one episode per week – Age of onset less than 25 years – Positive family history – Cessation of focal sweating during sleep 22 Multi-specialty Working Group on Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis, 2003.

Diagnostic Work-up History – Age of onset – Location – Trigger factors – Review of symptoms Physical exam Laboratory evaluation – Gravimetric – 1° research tool – Starch iodine – defines area of disease 23 Starch iodine test, with the darkened area showing location of excessive sweating

24 Axillary Sweat Production 1° hyperhidrosis patients healthy controls Hund et al. Arch Derm 2002;138(4):539-41

DLQI Total Scores and Ranges by Dermatological Disease/Condition Diseases with DLQI Scores 10 or Greater DiseaseDLQI Score (baseline) Hyperhidrosis palms18–8.8 Hyperhidrosis axillary17–10 Eczema (inpatient)16.2 Focal hyperhidrosis (general)15.5–9.2 Psoriasis (inpatient)13.9 Hyperhidrosis forehead12.5 Atopic eczema12.5–5.8 Psoriasis (outpatient)11.9–4.51 Contact dermatitis10.8 Pruritus10.5–10 25 Spalding et al. Value in Health 2003;6(3):242(abstract) Scores range from 0 to 30, with 30 indicating the worst quality of life.

Summary Primary Focal Hyperhidrosis is a separate and unique disease 26 Bilateral & symmetricBilateral & symmetric Axilla, palms, soles, craniofacialAxilla, palms, soles, craniofacial Onset in childhood and adolescenceOnset in childhood and adolescence Significant impact on quality of lifeSignificant impact on quality of life Effective therapiesEffective therapies

Treatment 27

Available Treatments Topical agents Iontopheresis Systemic agents – anticholnergic Botulinum toxin Surgery – Local excision/currettage – Thoracic sympathectomy 28

29 Treatment Response

Treatment Options 30 Topical Systemic Iontophoresis Botox Local Excision Thorascopic Sympathectomy Click on the first treatment option to begin!

Topical Treatment First line treatment Aluminum Chloride Hexahydrate antiperspirant of choice Most beneficial for axillary hyperhidrosis Can be used for plantar and palmar 31 Photos used with permission: Hornberger, 2004

Topical Treatment: How Does it Work? 32 The metal ions in the topical antiperspirant damage the lining of the sweat gland. As damage continues, a PLUG is formed over the sweat gland.

Topical Treatment Sweat production never ceases, the gland is simply plugged Sweating will return as the skin undergoes regeneration or shedding Therefore…topical treatment is NOT a cure! 33 Hornberger, 2004 Photo used with permission: Neurosurgical Medical Clinic, Inc

Topical Treatment: How to Use Best to apply before bedtime Allow to remain on skin for 6 – 8 hours Apply every 24 – 48 hours until sweating diminishes Maintenance applications needed every 1-3 weeks 34 Hornberger, 2004

Topical Treatment: Pros and Cons 35 Non – invasive Itching and burning of skin at application site & Time-consuming & Temporary relief Hornberger, 2004

Topical Treatment: Effectiveness % stop using due to the “CONS” Naumann, Hamm, & Lowe, % effective for Axillary Hyperhidrosis

Treatment Options 37 Topical Systemic Iontophoresis Botox Local Excision Thorascopic Sympathectomy Click on the second treatment option!

Systemic Treatment Anticholinergics can be used in treating hyperhidrosis Most effective for cranio-facial hyerhidrosis Robinul – drug of choice 38 Haider & Solish, 2004

39 Oral Glycopyrrolate (Glycopyrronium bromide)

How Does it Work? 40 Anticholinergic Blocks Acetylcholine transmission Eccrine sweat glands Eccrine sweat glands no longer stimulated Sweat production ceases! Haider & Solish, 2004

Anticholinergics Long term therapy is required Major side effects: Dry mouth Dry eyes Constipation Blurred vision Difficulty with urination 41 Thomas, Brown, & Vafaie, 2004

Anticholinergics Limited use in treating hyperhidrosis Only 21% effective 69.7% stop using due to side effects 42 Hamm, Naumann, & Kowalski, 2006

Topical anticholinergics glycopyrronium bromide as 1 and 2% cream or roll- on solution Topical hyoscine as 0.25, 1, or 3% solution or cream also gave control of sweating, but was associated with a much higher incidence of side-effects. Patients with diabetic gustatory sweating have also noted a reduction in the frequency and severity of episodes after applying glycopyrronium 0.5% cream 43

Treatment Options 44 Topical Systemic Iontophoresis Botox Local Excision Thorascopic Sympathectomy Click on the third treatment option!

Iontophoresis Used for palmar and plantar hyperhidrosis Passage of direct electrical current onto skin’s surface Device can be purchased for home use 45 Photo used with permission: Beast Psoriasis, 2006 Thomas, Brown, & Vafaie, 200 4

Iontophoresis Sit with hands or feet in shallow tray of water Allow 15 – 20 milli-amps of electrical current to pass through water Use for 10 days, 30 minutes each day Maintenance therapy needed 46 Photo used with permission: Beat Psoriasis, 2006 Thomas, Brown, & Vafaie, 2004

Iontophoresis: Mechanism of Action 47 WATER + ELECTRICTY = Thickening of skin And Blocked sweat flow

Iontophoresis Side effects: Skin irritation Skin burns Vesicle formation Time consuming treatment 80% effective for palmar and/or plantar hyperidrosis 48 Photo used with permission: Beat Psoriasis, 2006 Thomas, Brown, and Vafaie, 2004

Treatment Options 49 Topical Systemic Iontophoresis Botox Local Excision Thorascopic Sympathectomy Click on the fourth treatment option!

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Botox Botox injections can be used to treat axillary, palmar, and plantar hyperhidrosis Analgesic applied prior to injection Nerve block applied to ulnar or radial nerve prior to palmar injection 51 Haider & Solish, 2004

Botox 52 Botox blocks the release of acetylcholine at the site of the neuromuscular junction. Sweat glands are not stimulated, and sweat production ceases Site of blockage Photo used with permission: Whiteley Clinic, 2007 Haider & Solish, 2004

BIOCHEMICAL PROCESS OF VESCICULAR FUSION BLOCKAGE 53

Botox Starch Iodine test done prior to injection Delineates areas of excess sweating with black-purple discoloration of the skin 54 Photo used with permission: Eisenach, Atkinson, & Fealey, 2005 Haider & Solish, 2004

Botox Cons: Very painful to the palms and soles of feet Expensive: $1400- $1600 per treatment 55 Pros: Lasts 6-7 months 90% effective Thomas, Brown, & Vafaie, 2004

Treatment Options 56 Topical Systemic Iontophoresis Botox Local Excision Thorascopic Sympathectomy Click on the fourth treatment option!

Local Excision Used only for axillary hyperhidrosis Starch Iodine test done prior to excision Performed under local anesthesia Vasoconstrictor applied to axillary region Small incisions made 57 Eisenach, Atkinson, Foley, 2005 Photo used with permission: Gasparri, 2006

Local Excision Eccrine sweat glands removed through: Liposuction – suctioned out Curettage – scraped out Excision – cut out Incisions sutured Pain and bruising to excision site 58 Eisenach, Atkinson, & Fealey, 2005 Photo used with permission: Gasparri, 2006

Local Excision Starch Iodine tests done post excision show 80% - 90% decrease in sweating Has a potential for scarring 59 Eisenach, Atkinson, & Fealey, 2005

Treatment Options 60 Topical Systemic Iontophoresis Botox Local Excision Thorascopic Sympathectomy Click on the fourth treatment option!

Endoscopic Thoracic Sympathectomy (ETS) Last treatment option PERMANENT Surgery performed under general anesthesia 61 Haider & Solish, 2004

ETS Goal of surgery is to excise or ablate the ganglion that innervate the sweat glands Performed most frequently for palmar hyperhidrosis Performed through thorascope or video Minimally invasive 62 Photo used with permission: Neurosurgical Medical Clinic, Inc Han, Oren, & Gottfried, 2002

ETS Small incision made laterally under each axilla Incision made through intercostal space Surgery can be performed on outpatient basis However, some patients remain in hospital for one night 63 Han, Oren, & Gottfried, 2002

ETS Ganglion located along the sympathetic chain Ganglion formed below each rib Ganglion can be divided = sympathicotomy Ganglion can be removed = sympathectomy 64 Photo used with permission: Neurosurgical Medical Clinic, Inc

ETS Ganglion at T2 and T3 = palmar hyperhidrosis Ganglion at T3 and T4 = axillary hyperhidrosis Ganglion at L2-L4 = plantar hyperhidrosis 65 Photos used with permission: Neurosurgical Medical Clinic, Inc

ETS Cannot surgically excise or ablate L2-L4 for plantar hyperhidrosis due to sexual side effects 95% success rate in curing palmar hyperhidrosis Success rates slightly lower for axillary hyperhidrosis 66 Eisenach, Atkinson, & Fealey, 2005

ETS Plantar hyperhidrosis resolves in 50% - 75% of cases when T2 and T3 are excised, though L2- L4 ganglion are never surgically treated Mechanism is unknown! 67 Eisenach, Atkinson & Fealey, 2005

ETS: Side Effects Surgical complications: Hemo-pneumothorax requiring chest tube placement – 1% Atelectasis (collapse of the lung) Intercostal neuralgia – 1% Horner’s Syndrome – 1% Compensatory Sweating – 60% 68 Eisenach, Atkinson, & Fealey, 2005

Horner’s Syndrome Stellate ganglion – fusion of C8 and T1 Innervates the face If Stellate ganglion is damaged, Horner’s Syndrome will occur May be mistaken for T2 and T3 May receive electrical current from cautery of T2 and T3 69

Horner’s Syndrome Signs and Symptoms Unilateral upper eyelid ptosis Pupil constriction Facial anhidrosis 70

Treatment Option Review 71 Hyperhidrosis Topical Treatment Botox Iontophoresis Local Excision Iontophoresis Botox ETS AXILLARY PALMOPLANTAR Hornberger, 2004

Treatment Option Review 72 Photo used with permission: The Whiteley Clinic, 2007 Systemic – blocks acetylcholine