1. hyperhidrosis dr abbas pardakhty 2011 kerman faculty of pharmacy 2

Hyperhidrosis

Dr Abbas Pardakhty2011

Kerman Faculty of Pharmacy

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Sweat Glands

The human body has 2-5 million sweat glandsTwo main types:

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ECCRINEAPOCRINE

Source: www.sweathelp.org

Eccrine Sweat Glands

Approximately 3 million eccrine sweat glands

Secrete a clear, odorless fluidAid in regulating body

temperatureAreas of concentration:

Facial, plantar, and axillae

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Apocrine Sweat Glands

Inactive until pubertyProduce thick fluid

Secretions come in contact with bacteria on the skin

and produce characteristic “body odor”

Found in axillary and genital areas

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Sweating

The hypothalamus serves as the thermoregulatory center

It controls both blood flow and sweat output to the skin’s surface

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Sweating

The hypothalamus can be triggered by:

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EXERCISE

TEMPERATURE CHANGE

STRESS

HORMONESSource: www.sweathelp.org

Sweating

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Once triggered, the hypothalamus sends messages down the

spinal cordvia neurotransmitters.


SweatingThe neurostransmitters travel down the spine

via ganglion or sympathetic nerves

These ganglion travel to nerves, which reach the skin’s surface

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Photo used with permission: The Whiteley Clinic,2007


Neurotransmitters

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Neurotransmitters act as “vehicles,” transmittinginformation from the hypothalamus to the skin’s surface.

Photo used with permission: The Whiteley Clinic, 2007

NeurotransmittersThe neurotransmitters can “exit” at various

places along the spinal cord.

The “exit” determines the location of skin innervation.

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Spinal Cord Innervations

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T2 – T8 innervate the skin of the upper limbs

T2-T4 innervatethe skin of the face

T4-T12 innervate theskin of the trunk T10-T12 innervate the skin

of the lower limbs


Neurotransmitters

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Acetylcholine innervates

Eccrine Sweat Glands

Catecholaminesinnervate

Apocrine Sweat Glands


Sweating

Once innervated, the apocrine and eccrine glands will produce.…

SWEAT!

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What is Hyperhidrosis?

•Sweating that is more than required to maintain normal thermal regulation

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Sweating Nomenclature

•Areas: Focal, regional, generalized•Symmetry: Symmetric or asymmetric•Classification: Primary vs. secondary•Type of sweating: Anhidrosis, euhydrosis,

hyperhidrosis

16Multi-specialty Working Group on Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis, 2003.

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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

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Causes of Localized Hyperhidrosis

•Usually Idiopathic / Primary•Social anxiety disorder•Eccrine nevus•Gustatory sweating•Frey syndrome•Impaired evaporation•Stump hyperhidrosis after amputation

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Idiopathic (Primary) Focal Hyperhidrosis

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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

22Multi-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

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Starch iodine test, with the darkened area showing location of excessive sweating

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Axillary Sweat Production

1° hyperhidrosis patients healthy controls

346.0

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 palms18–8.8Hyperhidrosis axillary17–10

Eczema (inpatient)16.2Focal hyperhidrosis (general)15.5–9.2

Psoriasis (inpatient)13.9Hyperhidrosis forehead12.5

Atopic eczema12.5–5.8Psoriasis (outpatient)11.9–4.51

Contact dermatitis10.8Pruritus10.5–10

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

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•Bilateral & symmetricBilateral & symmetric•Axilla, palms, soles, craniofacialAxilla, palms, soles, craniofacial•Onset in childhood and Onset in childhood and adolescenceadolescence•Significant impact on quality of Significant impact on quality of lifelife•Effective therapiesEffective therapies

TreatmentTreatment

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Available Treatments

•Topical agents•Iontopheresis•Systemic agents

–anticholnergic

•Botulinum toxin•Surgery

–Local excision/currettage–Thoracic sympathectomy

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Treatment Response

Treatment Options

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Topical

Systemic

Iontophoresis

Botox

Local Excision

Thorascopic Sympathectomy

Click on the first treatmentoption to begin!

Topical TreatmentFirst line treatment

Aluminum Chloride Hexahydrate antiperspirant of choice

Most beneficial for axillary hyperhidrosis

Can be used for plantar and palmar

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Photos used with permission:www.feelbest.com

Hornberger, 2004

Topical Treatment:How Does it Work?

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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.

www.sweathelp.org

Topical TreatmentSweat 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!

33Hornberger, 2004

Photo used with permission:Neurosurgical Medical Clinic, Inc

Topical Treatment:How to Use

Best to apply before bedtimeAllow to remain on skin for 6 – 8 hours

Apply every 24 – 48 hours until sweating diminishes

Maintenance applications needed every 1-3 weeks

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Hornberger, 2004

Topical Treatment: Pros and Cons

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Non – invasiveItching and burning of skin

at application site&Time-consuming&Temporary reliefHornberger, 2004

Topical Treatment:Effectiveness

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66.6% stop using dueto the “CONS”

Naumann, Hamm, & Lowe, 2002

88% effective forAxillary Hyperhidrosis

Treatment Options

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Topical

Systemic

Iontophoresis

Botox

Local Excision


Click on the second treatmentoption!

Systemic TreatmentAnticholinergics can be used in treating

hyperhidrosisMost effective for cranio-facial hyerhidrosis

Robinul – drug of choice

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Haider & Solish, 2004

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Oral Glycopyrrolate (Glycopyrronium bromide)

How Does it Work?

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Anticholinergic

Blocks Acetylcholine transmission

Eccrine sweat glands no longer stimulated

Sweat production ceases!


Anticholinergics

Long term therapy is requiredMajor side effects:

Dry mouthDry eyes

Constipation Blurred vision

Difficulty with urination

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Thomas, Brown, & Vafaie, 2004

Anticholinergics

Limited use in treating hyperhidrosis

Only 21% effective

69.7% stop using due to side effects

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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

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Treatment Options

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Topical

Systemic

Iontophoresis

Botox

Local Excision


Click on the third treatmentoption!

Iontophoresis•Used for palmar and

plantar hyperhidrosis

•Passage of direct electrical current onto skin’s surface

•Device can be purchased for home use

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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 waterUse for 10 days, 30 minutes

each dayMaintenance therapy needed

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Photo used with permission: Beat Psoriasis, 2006


Iontophoresis:Mechanism of Action

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WATER

+

ELECTRICTY

= Thickening of skinAnd

Blocked sweat flow

www.sweathelp.org

Iontophoresis

Side effects:Skin irritation

Skin burnsVesicle formation

Time consuming treatment

80% effective for palmar and/or plantar hyperidrosis

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Photo used with permission: Beat Psoriasis, 2006

Thomas, Brown, and Vafaie, 2004

Treatment Options

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Topical

Systemic

Iontophoresis

Botox

Local Excision


Click on the fourth treatmentoption!

Botox

Botox injections can be used to treat axillary, palmar, and plantar hyperhidrosis

Analgesic applied prior to injectionNerve block applied to ulnar or radial nerve

prior to palmar injection

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Botox

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Botox blocks the release of acetylcholine at the site of the neuromuscular junction.

Sweat glands are not stimulated, and sweat production ceases

Site of blockagePhoto used with permission: Whiteley Clinic, 2007


BIOCHEMICAL PROCESS OF VESCICULAR FUSION BLOCKAGE

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Botox

Starch Iodine test done prior to injection

Delineates areas of excess sweating with

black-purple discoloration of the skin

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Photo used with permission: Eisenach, Atkinson, & Fealey, 2005


Botox

Cons:Very painful to the

palms and soles of feetExpensive: $1400-$1600

per treatment

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Pros: Lasts 6-7 months 90% effective


Treatment Options

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Topical

Systemic

Iontophoresis

Botox

Local Excision



Local ExcisionUsed only for axillary hyperhidrosis

Starch Iodine test done prior to excision

Performed under local anesthesia Vasoconstrictor applied to axillary

regionSmall incisions made

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Eisenach, Atkinson, Foley, 2005

Photo used with permission:Gasparri, 2006

Local Excision

Eccrine sweat glands removed through:Liposuction – suctioned out

Curettage – scraped outExcision – cut out

Incisions suturedPain and bruising to excision site

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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

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Treatment Options

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Topical

Systemic

Iontophoresis

Botox

Local Excision



Endoscopic Thoracic Sympathectomy (ETS)

Last treatment option

PERMANENT

Surgery performed under general anesthesia

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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

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Han, Oren, & Gottfried, 2002

ETS

Small incision made laterally under each axillaIncision made through intercostal space

Surgery can be performed on outpatient basis However, some patients remain in hospital for

one night

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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

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www.sweathelp.org


ETSGanglion at T2 and T3 = palmar hyperhidrosisGanglion at T3 and T4 = axillary hyperhidrosis

Ganglion at L2-L4 = plantar hyperhidrosis

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www.sweathelp.org

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

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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!

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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%

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Horner’s Syndrome

Stellate ganglion – fusion of C8 and T1Innervates 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

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www.sweathelp.org

Horner’s Syndrome

Signs and SymptomsUnilateral upper eyelid ptosis

Pupil constrictionFacial anhidrosis

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www.sweathelp.org

Treatment Option Review

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Hyperhidrosis

Topical Treatment

Botox

Iontophoresis

Local Excision

Iontophoresis

Botox

ETS

AXILLARY PALMOPLANTAR

Hornberger, 2004

Treatment Option Review

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Photo used with permission: The Whiteley Clinic, 2007

Systemic – blocks acetylcholine

1. hyperhidrosis dr abbas pardakhty 2011 kerman faculty of pharmacy 2

Documents

sweat glandsinactive

sweat output

sweat glandsapproximately

eccrine sweat glandssecrete

sweat glandsthe human

idiopathic primary hh

sweat glandstwo main

skins surface