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Iontophoresis
Iontophoresis is defined as the passing of an ionized substance
through intact skin by the application of a direct electrical
current.[134]
Tap water iontophoresis is considered by many dermatologists
to be the first line of treatment for hyperhidrosis of the
palms and soles.[7,134]
Although more cumbersome, iontophoresis can be used to treat
axillary hyperhidrosis as well.[7]
In addition to simple tap water iontophoresis, clinicians
have also used iontophoresis to deliver anticholinergics and
other drugs to areas affected by hyperhidrosis.[4]
Two iontophoresis devices currently available in the US, the Drionic and the Fischer Model MD-1a Iontophoresis unit, have received US Food and Drug Administration approval for treating hyperhidrosis.
See the following area for specific information
on iontophoresis
History
Mechanism of action
Recommended regimen
Clinical studies
Side effects
Studies of iontophoresis with anticholinergics
and other agents
History
Not long after it was discovered, electricity was tried
as treatment for human disease during the 18th century. Pivati
is reported to have used iontophoresis to treat arthritis
in 1740.[7] Research
during the late 19th century and the 20th century demonstrated that
iontophoresis is an efficient method for the delivery of drugs
into the body through the skin. Interestingly, the sweat glands
are the main portal of entry for any drugs delivered through
the skin, since electrical resistance is lowest by that route.[7,47]
Dermatologists have tried iontophoresis for a host of conditions,
including vitiligo and scleroderma.[7]
Currently hyperhidrosis is said to be the only clear indication
for iontophoresis, because use of this therapy in hyperhidrosis
has been both successful and popular.[7,131]
In 1936, Ichikasa discovered that iontophoresis of drugs
led to a reduction of sweating in the affected area.[7]
In the 1940s, Takata and Shelley independently found that
anhidrosis could be obtained by iontophoresis with tap water.
The treatment became increasingly popular after Levit published
his paper on a practical device for iontophoresis in 1968.[7,85]
Back to top
Mechanism of action
One of the physical principles of electricity is that molecules
with the same charge repel, and those with opposite charge attract,
one another. In iontophoresis, a charged molecule is delivered
across the skin, by placing it near the electrode of like
charge, while the electrode of opposite charge is placed elsewhere
on the body.[7]
This physical explanation for how drugs are transported across
skin does not explain the mechanism of action of tap water
iontophoresis in reducing sweat output, however. Although
the mechanism of action is currently not understood, there have been
several theories advanced.[7]
An early theory was that iontophoresis leads to a plugging
of sweat gland ducts. This concept was based on the development
of iatrogenic miliaria when iontophoresis was done on the
back, chest, or arms of patients. Microscopic analysis showed
keratin plugs obstructing sweat ducts. However, light and
electron microscopy of sweat glands in a patient with palmar
hyperhidrosis did not show ductal obstruction.[56]
This finding led to the theory that iontophoresis may cause
a functional impairment of the sweat gland, either by completely
blocking sympathetic nervous system transmission to the gland,
raising the threshold for transmission of sympathetic nerve
impulse, or changing the cellular secretory physiology.[7]
However, neurotransmitter levels in the eccrine gland or surrounding
microcirculation do not change after iontophoresis.[147]
Decreased pH in the sweat duct due to an increase in H+
ions during tap water iontophoresis may contribute to eccrine
gland dysfunction.[121]
Anodal current has a better inhibitory effect on sweating
than cathodal current, and this may be due to the lowering
of pH. Use of saline in iontophoresis is not as effective
as use of tap water; Sato and colleagues also found that the
pH of anodal water did not drop during saline iontophoresis.
Back to top
Recommended regimen
The regimen recommended for iontophoresis will vary with
the device used, the areas to be treated, and whether the treatment
is to be carried out in the clinic or at home.[3,7,86,134].
Some general advice:
- Scratches and cuts on the surface to be treated should
be covered with a thin layer of petro-
latum.[86,134]
Coat the skin around the axilla with petrolatum if treating
that area.[7]
- Use nondeionized tap water (from the faucet).[7]
- Fill the trays with just enough water to cover the hands
(or feet).[134]
- After placing the body part in the device tray, or after
applying the device or wet pads attached to an electrode
to the axilla, turn the machine on. Slowly increase the
amperage until a tingling that is not unpleasant is felt in the affected area,[86,145]
or to a maximum of 20 mA.[4,134,145]
- Treat for 20 minutes a session every two to three days[134]
or for ten minutes three to five times a week.[7]
- Halfway through the 20-minute session, reverse current
flow to switch anode site to opposite side,[134]
or keep one side in anodal pan each session until euhidrosis
is reached and then switch sides.[7]
- Can do hands and feet simultaneously, with hands and feet
going into separate trays.[7]
- Maintenance treatment frequency will vary, but one to three times
a week is usually necessary.[7,86]
If mineral content of tap water is low, insufficient current
flow may occur. This can be corrected by adding a teaspoon
of baking soda to each tray.[134]
- Do not treat pregnant patients or those with pacemakers
or arrhythmias.[86,134]
- If patient fails to respond to tap water iontophoresis
alone, one can add an anticholinergic. Glycopyrrolate 2-mg
tablets can be crushed and added to each tray (see
section on use of anticholinergics in iontophoresis).[134]
- Irritation developing along the water line can be treated
with 1% hydrocortisone cream.[134]
- Children can be treated with iontophoresis, but some
may not be able to tolerate the same current levels used
by adults.[86,130]
Back to top
Clinical studies
Observational studies in palmar sweating
Using different current configurations
Controlled studies in palmar sweating
Study of portable device for home use
Study with gravimetric follow-up
Observational studies in palmar sweating
An early observational study of iontophoresis in 113 patients
with palmoplantar hyperhidrosis published in 1952 demonstrated
a response rate of 91% for palmoplantar hyperhidrosis and
showed that adding ionizable agents to the water did not improve
the results.[22]
Using different current configurations
In another study, 30 patients with palmoplantar hyperhidrosis
were successfully treated, using different pan and electrode
configurations, current, and duration of sessions.[130]
Treated 6 days a week until sweating stopped, patients required
2 to 3 weeks to reach that endpoint and remained in remission
for an average 6.3 months. Observing that some patients could
not tolerate the usual current level when the electrodes were
placed in separate pans, one group of patients was treated
with both electrodes in the same pans. This configuration
required longer times to reach anhidrosis despite higher current
levels.
A group of 18 patients with palmar hyperhidrosis had iontophoresis
of one hand with the other serving as control.[133]
Patients were treated with 12 to 20 mA for 20 minutes 3
times a week for 3 weeks. Fifteen of 18 had markedly reduced
sweat production in their treated hands.
Controlled studies in palmar sweating
A double-blind study of 11 patients with palmar hyperhidrosis
used a sham treatment of one involved hand as placebo.[31]
After a median of 10 treatments using current from 2 to 10
mA, sweat production was measured by gravimetry and compared
to baseline. A median reduction of 38% from baseline was found
for the treated hands. After maintenance treatment every other
week for 3 months, there was an 81% median reduction of sweat
production (P<0.05).
Study of portable device for home use
A portable iontophoretic device, the Drionic unit (General Medical
Company, Los Angeles, California), has been on the market since 1984.
This battery-operated device allows patients to treat their
hyperhidrosis at home. A study of the device’s efficacy
was carried out on 27 treatment sites in 22 patients: 10 palms,
9 feet, and 8 axillae.[3] Patients used the device on the involved
area, using the opposite side as control, for 30 minutes twice
a day for 5 days followed by 30 minutes daily. Sweat production
was assessed using a computerized image analysis of chemically
treated paper applied to the involved area. Two axillae and
one foot did not respond to treatment. It took 2 weeks for 80%
of palms to respond, and by 20 days 100% of hands, 78% of feet,
and 75% of axillae responded. Of the 24 sites that had at least
a 50% improvement in subjective symptoms, there was a statistically
significant decrease in mean sweat production after 1 month
of treatment compared to controls (P<0.001 for palms and
soles and P<0.01 for axillae). Follow-up 1 month after therapy
was stopped found a continued statistically significant difference
in sweat production only for palms. The authors concluded that
the device has a role in treating hyperhidrosis but may require
twice-daily treatment for more than 2 weeks for some patients
and that retreatment is necessary 2 weeks after stopping treatment.
Study with gravimetric follow-up
To investigate whether a current other than the standard
direct current (DC) would lessen side effects of iontophoresis,
25 patients with palmar hyperhidrosis were treated in a double-blind
manner with standard DC, alternating current (AC), or an alternating
current with a DC offset (AC/DC).[110] Patients were treated
4 times a week until resolution, and then once weekly as maintenance.
Gravimetric measurement of sweat production was done. Those
treated with standard DC had improvement in hyperhidrosis
after an average of 11 treatments, as well as the usual side effects,
including the occasional mild shock with incorrect technique (ie, moving hands in or out of the bath too quickly). Those on AC
treatments had no resolution of hyperhidrosis after a total
of 25 treatments. Those on the AC/DC protocol improved at
the same rate as those on DC, but there were no signs of skin
irritation or discomfort. The authors concluded that the AC
with a DC offset “should become the treatment of choice.”
A recent study of 112 patients with palmoplantar symptoms
had treatment of their hands with the standard direct current
tap water iontophoresis method.[70]
Sweat production was measured by gravimetry at baseline and
20 days after the last of 8 treatments. The final sweat
production was significantly reduced compared to baseline
(P<0.001) for 81.2% of the patients. The mean time to return
of symptoms was 35 days. Longer periods of remission were
seen after a second period of treatment. Interestingly, in
65 of the responders, plantar symptoms also decreased
without undergoing iontophoresis in that area. The authors
speculate that a biofeedback process may be involved in this
unexpected response.
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Side effects
Several side effects are seen during tap water iontophoresis
but usually are not severe enough to lead to discontinuation
of treatment.[3,133]
Some effects can be prevented by proper preparation. Open
wounds (cuts, abrasions, hangnails) on the treated surface
can be covered with petrolatum to minimize discomfort during
the procedure.[133]
Proper education in use of the device will prevent mild shocks
from occurring. For instance, moving the hands out of the
tray or touching the electrodes can lead to a small shock.[134]
In series of patients treated with iontophoresis, a few side
effects were commonly reported. Vesiculation in the effected
area has been reported, but is usually transient.[133]
Eight of 112 patients reported vesiculation in a recently
published series.[70]
Redness of the skin, often along the water line, is also commonly
reported.[133]
Twelve of 122 patients reported erythema.[70]
Discomfort, either as a burning sensation or “pins and
needles,” is also common.[70,133]
All patients in one series complained of “pins and needles,”
and 20 of 112 complained of the burning sensation.
Both erythema and vesiculation can be treated with 1% hydrocortisone
cream should these symptoms persist.[134]
Sometimes the skin becomes dry and cracked or fissured, necessitating
the use of moisturizers or decreasing the frequency of iontophoresis
sessions.[134]
Back to top
Studies of iontophoresis and other agents
Since sweat glands are the main route for absorption of drugs
delivered by iontophoresis, using this method to deliver agents
to treat hyperhidrosis is a logical approach. Several studies
compared tap water iontophoresis to iontophoresis of anticholinergic
medication, and another compared combined iontophoresis of
aluminum chloride and an anticholinergic to tap water iontophoresis.
Poldine methylsulfate
Glycopyrronium bromide
Glycopyrrolate and aluminum chloride
Poldine methylsulfate
The anticholinergic agent poldine methylsulfate or tap water
was delivered by iontophoresis to the palms, soles, and axillae
of 13 patients, using one side either as placebo control or for
the other treatment.[47]
Poldine was more effective than tap water overall, and two
patients with sweating unresponsive to tap water had an excellent
response to poldine iontophoresis. The greatest effect of
poldine was on the palms, and the worst response was in the
axillae, where only 2 of 5 patients had a response. Systemic
side effects were seen, most commonly dry mouth. Similar to
tap water iontophoresis, continued treatment once or twice
weekly with poldine was needed, as only a few patients had
longer remissions.
Glycopyrronium bromide
Another study evaluated the use of a 0.1% solution of glycopyrronium
bromide delivered by iontophoresis to 27 patients with various
combinations of palmar, plantar, and axillary hyperhidrosis.[1]
Treatment results for tap water iontophoresis in 26 other
patients were reported for comparison. The group treated with
tap water all responded after a variable number of treatments,
but most required continued weekly or twice-weekly treatment
to maintain dryness. Patients with planter and axillary symptoms
required more treatments to reach sufficient dryness. Those
treated with glycopyrronium fared better, however. Except
for those with axillary hyperhidrosis, a prolonged period
of hypohidrosis was achieved—an average of 33.7 and 47.2
days between treatments for palmar and plantar hyperhidrosis,
respectively. Axillary patients continued to need treatment
about once per week. All patients had signs of systemic absorption
of the anticholinergic. Dryness of the mouth usually persisted
for 6 to 24 hours after therapy. Occasional visual, GI, and
urinary difficulties were reported. The reason for the prolonged
effect with glycopyrronium is unknown, and the author speculated
that the drug is held in the epidermis and slowly released.
Back to top
Glycopyrrolate and aluminum chloride
In a third study, the combination of 0.01% glycopyrrolate
and 2% aluminum chloride was delivered by iontophoresis to
patients with palmar hyperhidrosis.[129]
One group had the opposite hand treated with tap water in
a double-blind study, and a second group received the combined
treatment to both hands. Combined iontophoresis used changing
periods of time for delivery of glycopyrrolate and aluminum
chloride over 4 days: on the first day the anticholinergic alone
was given over 30 minutes, and on the second day 20 minutes were
used for delivery of glycopyrrolate and 10 minutes for aluminum
chloride. This ratio was reversed for the third day, and on
the fourth day the patients received aluminum chloride alone.
Using this approach, the investigators hoped to suppress sweating
with the anticholinergic in order to enhance the absorption
of aluminum chloride into the sweat gland. Each day the treatment
was repeated with reversed polarity, leading to an overall
treatment duration of 1 hour. In the double-blind study, the
decrease in severity as measured by iodine-starch paper patterns
was higher in the palms treated with combination therapy (P=0.084).
The mean remission duration after the 4-day treatment was
3.5 days for tap water iontophoresis and 20 days for combination
therapy (P=0.098). In the observational study, 87% of patients
responded to the treatment and had a mean remission duration
of 32 days. Only 1 patient complained of mouth dryness.
Although no specific data on treatment of the axillae by this
method are reported, the authors state that the axillary hyperhidrosis
responded as well as palmar symptoms. Two patients had 5 months
of remission of axillary sweating after a single 4-day treatment.
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