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Contact dermatitis inducers: Dinitrochlorobenzene (DNCB), diphenylcyclopropenone (DPCP), squaric acid dibutyl ester
(SADBE) - how they are believed to work
The difference between an irritant and a contact dermatitis inducer
is a bit vague. Clinically, the effects of an irritant are much
the same as a contact sensitizing chemical with inflammatory dermatitis
induction being the key symptom. Essentially, an irritant treatment
for alopecia areata acts by disrupting the normal cell growth and
differentiation in the skin. This physical damage then stimulates
the immune system to respond to clear up the problem and limit the
skin damage. A contact dermatitis inducer is a chemical that the
immune system is responsive (allergic) to. It may not have a direct
action on the skin cells. Rather, the skin immune system identifies
the molecules of the chemical as something it should respond to.
The resulting inflammation will cause skin dermatitis that varies
in severity with each individual depending on how allergic the person
is to the contact dermatitis inducing chemical.
The popular belief is that irritants and contact dermatitis inducers
work as antigenic competition. That is, the irritant chemical applied
to the scalp is far more interesting to the inflammatory cells than
the hair follicles. Thus the cells move away from the hair follicles
and towards the skin surface where the irritation induced skin damage
is or where the contact sensitizer chemical is present. It would
seem the cells find the skin damage or irritating chemical much
more of a threat than any hair follicle antigens.
However, this assumes that the cells responding to the irritant
or contact dermatitis inducer are the same as the cells responding
to the hair follicle antigens. I don't agree with this idea. I think
the chemical irritation/contact sensitization induces inflammation
from a mostly new group of cells and in doing so causes a change
in the cyotkine environment of the skin. Cytokines are hormone like
chemicals that are produced by inflammatory cells to communicate
with each other. Some cytokines excite immune cells to attack and
destroy, other cytokines tell immune cells to calm down and go home.
I think there might be a change in the cytokine response that encourages
cells to move away from the hair follicles and into the upper skin
layers and/or to leave the skin entirely. There is some research
to suggest irritants cause cytokine production levels to change.
Contact
dermatitis inducers: Dinitrochlorobenzene (DNCB), Diphenylcyclopropenone
(DPCP), Squaric acid dibutyl ester (SADBE) - how treatment is given.
DNCB (Dinitrochlorobenzidine), DPCP (Diphenylcyclopropenone or
Diphencyprone), and SADBE (Squaric acid dibutyl ester) are topical
contact sensitizers. They are primarily used for people with extensive
scalp hair loss as opposed to patchy hair loss. Given these treatments
are mostly used by people with long term extensive hair loss each
has a relatively good success rate in growing cosmetically acceptable
hair when treatment is given by a dermatologist experienced in their
use. Less experienced dermatologists may have a lower success rate
and possibly a higher incidence of side effects. The allergic response
the body makes to the chemical(s) results in good hair regrowth
with claims of a 38% success rate for DPCP (Shapiro 1993), 63% for
DNCB (Swanson 1981) and up to 70% for SADBE (Flowers 1982). However
different investigators report different success rates for the same
contact sensitizer. For example, in using SADBE some investigators
report only a 50% chance of response (Case 1984, Johansson 1986),
or even less (Valsecchi 1986, Caserio 1987). The variability in
success rates varies at least in part due to different investigators'
different definitions of what constitutes successful regrowth (ie
success = light fuzz?, patchy regrowth?, total recovery? etc).
DNCB is not very popular as it has been shown to be potentially
mutagenic at high doses (Krakta 1979). However, there are no
reports
of people treated with low dose DNCB for alopecia areata ever
having any side effects of this nature. DPCP and SADBE are known
not to
be mutagenic (Strobel 1980), but their is a lack of specific information
on toxicity to be sure of their true safety. DPCP and SADBE seem
to be replacing DNCB use outside of the USA (DPCP has not been
passed for official use in the US and so is not widely available
there).
DPCP and other contact sensitizers do have side effects. As a
sensitizer a chemical should have a desired effect of causing
scalp itching
and redness. This irritation is important as this is necessary
for the treatment to work. For some people this inflammation
can become
excessive and cause undesired blistering, skin peeling, and even
some skin scarring. Other patients have reported swollen lymph
nodes,
hives, and decreased/increased pigment production in the area
of application.
When sensitizing agents are used to treat alopecia areata, the
dermatologist should first apply a small dose of the chemical at
quite a high concentration to a patch of skin and monitor the reaction.
This initial application is to "sensitize" the immune
system to the compound. If you have a skin reaction then you should
be suitable for treatment.
The dermatologist should then apply a larger dose of a very dilute
solution of the chemical. If you have a reaction then that is the
concentration you will use for long term treatment. If there is
no reaction then stronger and stronger chemical concentrations will
be applied until a skin reaction is obtained. It is important to
define a minimum dose that works for each person as some people
are much more sensitive to the chemicals than others. One chemical
concentration may be good for some people but too strong for others.
Excess irritation in sensitive people may cause excessive skin blistering
and other side effects. Finding the correct dose for you may take
several visits to the dermatologist over several weeks.
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This
individual had complete scalp alopecia. They have been treated
only on one half of the scalp with DPCP. The other half was
not treated. This is one method used by some dermatologists
to make usre that the sensitizing agent can actually promote
hair growth. Once hair growth is apparent on the treated half
of the scalp, the other half is treated too.
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Once the correct dose has been found the frequency of treatment
is determined. Application may be required once a week in the initial
stages to kick start hair growth. Later the frequency of application
may be reduced to a maintenance dose. As with all forms of alopecia
areata treatment the chemicals have to continue to be applied and
continue to induce a skin reaction for hair growth to persist. If
you stop the treatment the hair will gradually fall out again.
When an irritant treatment is correctly applied you should develop
a red rash and feel itchy but nothing more. The dermatologist will
recommend you keep the irritant on your scalp for a period of time
that varies depending on how sensitive your skin is and the personal
preference of the dermatologist. You may have to avoid washing your
scalp for several hours or even a couple of days depending on your
dermatologists recommendations. You may also be directed to cover
your scalp when outside as sunlight degrades such chemicals as DPCP
and SADBE rendering them ineffective. Because DPCP and SADBE are
biodegradable they have a limited storage life and solutions have
to be made up fresh on a regular basis.
Because of the irritation from the chemicals it is important not
to touch your scalp or let any one else touch it with their bare
hands. You do not want to spread the irritant to other areas of
skin or to other people. You may have to cover your head, especially
when sleeping, to stop the irritant spreading and getting onto bedclothes
and eventually on to your face or worse, your partner.
If the treatment works and hair growth develops some dermatologists
will trust you to apply the irritant chemicals yourself as a maintenance
dose at home. Other dermatologists believe the chemicals are too
powerful, could be inappropriately applied by the patient, and will
want you to attend the dermatology clinic to ensure safe and proper
treatment.
Treatment
of alopecia areata with irritants and sensitizers references
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