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Topical sensitizers and contact sensitization with diphenylcyclopropenone (DCP)
Topical sensitizers are medications that, when applied to the
scalp, provoke an allergic reaction that leads to itching, scaling
and eventually hair growth. If the medication works, new hair
growth is usually established in 3 to 12 months. Contact sensitization
is a form of immunotherapy directed at initiating re-growth of
hair. The disadvantage of this approach is the potential for a
vigorous allergic response.
Alopecia areata has been treated by contact sensitizers for more
than 20 years. The agent used is one that the patient is unlikely
to come in contact with except in the context of clinical treatment
Although Dinitrochlorobenzene (DNCB) was the first sensitizer
that was used for the treatment of alopecia areata, it is no longer
used as it has been found to be mutagenic in the Ames test. The
Ames test is a biological assay used in genetic toxicology, to
test for mutagenic properties of a chemical compound. A compound
is said to be mutagenic if it causes a change in the DNA (deoxyriboneucleic
acid) of a living cell or organism. Today diphenylcyclopropenone
(DCP) and squaric acid dibutylester (SADBE), that are not mutagenic
in the Ames test, have been used in Europe and in Canada in
the treatment of alopecia areata patients for the last 20 years,
but the lack of specific information on toxicity gives some uncertainty
of
their
safety.
It should be borne in mind, that DCP is not an approved
therapeutic substance in the USA. Although the median response
rate of 43% makes contact sensitizers an effective therapeutic
tool for alopecia areata, currently the treatment with DCP is
still regarded as being experimental as its long-term safety profile
remains to be fully evaluated. Treatment is based on criteria
like age and extent of disease, and there is no strong evidence
to suggest that such drug-induced therapy alters the course of
alopecia areata. Potentially everyone with alopecia areata is
capable of re-growing hair even after many years of hair loss.
However, there is no permanent cure for alopecia areata and there
is no universally proven therapy for inducing remission.
Diphenylcyclopropenone (DCP) as a contact sensitizer for alopecia areata
Diphenylcyclopropenone is currently the most commonly used contact
sensitizer in the treatment of alopecia areata. Although DCP is
also non-mutagenic, it is sensitive to ultraviolet light degradation
and so needs to be hidden from light to maintain its effectiveness.
Two steps are required to trigger the body’s immune system
with DCP as a contact sensitizer:
- The contact sensitizer DCP as a 2% solution is applied
on a small area of the scalp. The skin becomes red, swollen,
itchy, or blistered. This kind of skin reaction is a sign that
the contact
sensitizer will work. The resulting inflammation varies in severity
with each individual depending on how allergic the person is
to DCP, the contact dermatitis inducing chemical. The next time
DCP
is applied to the skin, the body's immune system reacts to it,
and the affected area develops an allergic (immune) reaction.
- Two
weeks later, 0.001% solution of the same sensitizer is applied
to the bald patches. Repeat treatments with increasingly concentrated
DCP are
made every week to induce a mild eczematous reaction that is characterized
by itching
and erythema, without blistering or oozing. Two days after the application
the scalp can be washed.
The first signs of hair growth are usually visible after 8-12
weeks of commencing treatment. Treatment has to be continued once
weekly to kick start the hair growth. Later the frequency of application
may be reduced to a maintenance dose until complete hair re-growth
is obtained, and eventually treatment may be discontinued. However,
if a relapse occurs after discontinuation of therapy, treatment
can be restarted immediately to stop further progression of Alopecia
areata and induce renewed hair growth.
As a rule, treatment is initially always applied on one half
of the scalp and the other side left untreated. Treating only
one half of the head allows the physician to use the untreated
half as a control. Once re-growth occurs on the treated half,
treatment can be applied to the entire scalp. If re-growth initially
occurs on both sides, spontaneous remission is likely, although
treatment cannot be excluded as the cause.
Although the exact mechanism of how contact sensitizers work
remains to be fully elucidated, modification of the immune response
at the sites of allergic contact dermatitis probably plays a major
role. One current proposed mechanism is a local alteration in
the helper-suppressor T-lymphocyte cell ratio. However, 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 appears the cells find the skin damage or irritating chemical
much more of a threat than any hair follicle antigens.
Success rates and side effects of diphenylcyclopropenone (DCP)
Response rates with respect to the use of DCP in initiating re-growth
of hair in alopecia areata patients have varied. The reported
success rate from several published clinical trials is 40 to 60
percent in patients who had 50 to 99 percent loss of scalp hair.
DCP has also been used to treat childhood alopecia areata. The
following three factors are found to be of negative prognostic
significance in the treatment of alopecia areata by DCP: degree
of scalp involvement prior to treatment, duration of alopecia
areata before commencement of therapy, and the presence of nail
changes.
A mild eczematous reaction and enlargement of retroauricular
lymph nodes are desired reactions and inherent to treatment of
alopecia by DCP. These reactions are usually well tolerated if
the patients are aware that they are required for the therapy
to be effective. It is important to define a minimum dose that
works for each person as some people are much more sensitive to
DCP than others. One particular 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,
and therefore determining the correct dose for each patient is
crucial to the success of the treatment regime. Finding the correct
dose may take several visits to the dermatologist over several
weeks.
Undesired side effects have been noted in 2%-5% of patients treated
with DCP. Vesicular or bullous reactions sometimes occur at the
beginning of treatment before the individual appropriate concentration
has been determined. Dissemination of allergic contact dermatitis,
urticaria (hives) and erythema-like reactions may occur, but can
be successfully treated with topical corticosteroids. Pigment
disturbances like post-inflammatory hyperpigmentation (excessive
pigmentation) and spotty hypopigmentation (diminished pigmentation)
have been observed, but have been resolved within 1 year after
discontinuation of treatment in most cases. This is also known
as “dyschromia in confetti”. Apart from these listed
side effects, no long-term side effects have been reported after
18 years of DCP treatment use worldwide on about 10000 patients,
including children.
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