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Topical
sensitizers and contact sensitization with squaric acid dibutylester
(SADBE)
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, are used in Europe and in Canada in the treatment
of alopecia areata patients, but the lack of specific information
on toxicity leads to uncertainty of their safety.
However, it should be borne in mind, that SADBE is not an approved
therapeutic substance. Although the median response rate of 43%
makes contact sensitizers an effective therapeutic tool for alopecia
areata, currently this mode of treatment 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.
Squaric
acid dibutylester (SADBE) as a contact sensitizer for alopecia
areata
Studies in both animal and human systems have shown SADBE to
be effective in the treatment of alopecia areata. Although negative
in the Ames test and clinically seemingly effective, SADBE is
not as commonly used as diphenylcyclopropenone (DCP) in the treatment
of alopecia areata as it is reported to be unstable in acetone
solution. Two steps are required to trigger the body’s immune
system with SADBE:
- Sensitization to SADBE is generally accomplished with
a 2% solution in acetone applied to an area on the scalp or
upper arm. 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 SADBE,
the contact dermatitis inducing chemical. The next time SADBE
is applied
to the skin, the body's immune system reacts to it, and the
affected area develops an allergic (immune) reaction.
- After
a 2-week delay to limit unnecessary irritation caused by the
addition
of the elicitation dose to the persistent sensitization one, a dilute concentration
of 0.0001% to 0.001% SADBE is applied. The dose is adjusted weekly to find
a reaction of minimal erythema without discomfort.
The first signs of hair growth are usually visible after 8-12
weeks of commencing treatment. Later the frequency of application
may be reduced from weekly doses 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, contact sensitization 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 squaric acid dibutylester (SADBE)
Response rates with respect to the use of SADBE in initiating
re-growth of hair in alopecia areata patients have varied. This
variability in success rates can be attributed at least in part
to different investigators having different parameters for what
constitutes successful re-growth. SADBE is usually used in those
patients that become tolerant to DCP. It is applied in the same
way and shows a similar rate of success. The following three factors
are found to be of negative prognostic significance in the treatment
of alopecia areata by contact sensitizers: 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 contact sensitizers. 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 of chemical that works for each person as some people are
much more sensitive to contact sensitizers 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.
Common side effects associated with the contact dermatitis induced
by the use of topical sensitizers include pruritis (severe itching),
a mild to severe dermatitis (inflammation of the skin), and regional
lymphadenopathy (abnormal enlargement of the lymph nodes). Sleep
disturbances secondary to the pruritis have also been reported.
Less common side effects include urticaria (hives), erythema (redness),
vitiligo (commonly known as leukoderma), arthralgia (severe joint
pain), and fever. "Dyschromia in confetti" -like lesions
of hypo (excessive) and hyper (diminished) pigmentation may occur.
Apart from these listed side effects, no long-term side effects
have been reported after 21 years of SADBE treatment worldwide.
Topical
sensitizers and contact sensitization with squaric acid dibutylester
(SADBE) references
- Dall'oglio F, Nasca MR, Musumeci ML, La
Torre G, Ricciardi G, Potenza C, Micali G. Related Articles,
Links Topical immunomodulator therapy with squaric acid dibutylester
(SADBE) is effective treatment for severe alopecia areata (AA):
results of an open-label, paired-comparison, clinical trial.
J Dermatolog Treat. 2005 Feb;16(1):10-4. PMID: 15897160
- Mastrolonardo M, Lopalco PL,
Diaferio A. Topical immunotherapy with
contact sensitizers: a model to study the natural history of
delayed hypersensitivity. Contact Dermatitis. 2002 Oct;47(4):210-4.
PMID: 12492519
- Morita K, Nakamura
M, Nagamachi M, Kishi T, Miyachi Y. Seventeen cases of alopecia
areata: combination of SADBE topical immunotherapy with other
therapies. J Dermatol. 2002 Oct;29(10):661-4.
PMID: 12433000
- Mastrolonardo M, Diaferio A. Topical immunotherapy with squaric
acid dibutylester: unusual hair pigmentary changes in two cases
of alopecia areata.
J Eur Acad Dermatol Venereol. 2002 Mar;16(2):186. PMID: 12046838
- Pardasani AG, Turner E, McMichael AJ. Squaric acid dibutylester:
indications for use and efficacy in alopecia areata. Arch Dermatol.
2001 Jul;137(7):970-2. PMID: 11453831
- Freyschmidt-Paul P, Hoffmann R, Levine E, Sundberg JP, Happle
R, McElwee KJ. Current and potential
agents for the treatment of alopecia areata. Curr Pharm Des.
2001 Feb;7(3):213-30. PMID: 11311114
- Rokhsar CK, Shupack JL, Vafai JJ,
Washenik K. Efficacy of topical sensitizers
in the treatment of alopecia areata. J Am Acad Dermatol. 1998
Nov;39(5 Pt 1):751-61. PMID: 9810892
- Nasca MR, Micali G, Pulvirenti N, Licastro
Cicero R. Transient leucoderma appearing
in an untreated area following contact immunotherapy for
alopecia areata. Eur J Dermatol. 1998 Mar;8(2):125-6. PMID:
9649675
- Iijima S, Otsuka F. Prognostic factors for clinical response
of alopecia areata to topical immunotherapy with squaric acid
dibutylester.
Arch Dermatol. 1997 Apr;133(4):539-40. PMID:
9126022
- Chua SH, Goh
CL, Ang CB. Topical squaric acid
dibutylester therapy for alopecia areata: a double-sided patient-controlled
study. Ann Acad Med Singapore. 1996 Nov;25(6):842-7.
PMID:
9055014
- Micali
G,
Cicero RL, Nasca MR, Sapuppo A.
Treatment of alopecia areata with squaric acid dibutylester.
Int
J Dermatol. 1996 Jan;35(1):52-6. PMID: 8838932
- Orecchia G, Malagoli P, Santagostino L. Treatment of severe
alopecia areata with squaric acid dibutylester in pediatric
patients. Pediatr Dermatol.
1994
Mar;11(1):65-8. PMID: 8170854
- van der Steen PH, Boezeman JB, Happle R. Topical immunotherapy
for alopecia areata: re-evaluation of 139 cases after an additional
follow-up period of 19 months.
Dermatology. 1992;184(3):198-201. PMID: 1392112
- Naldi L, Parazzini F, Cainelli T. Role of topical immunotherapy
in the treatment of alopecia areata. Quality analysis of articles
published between January 1977
and January 1988 about three treatments. Reading Group. J Am
Acad Dermatol. 1990 Apr;22(4):654-6. PMID: 2138637
- Caserio RJ.
Treatment of alopecia areata with squaric
acid dibutylester. Arch Dermatol. 1987 Aug;123(8):1036-41. PMID:
3307636
- Johansson E, Ranki A, Reunala T, Kianto U,
Niemi KM. Immunohistological evaluation
of alopecia areata treated with squaric acid dibutylester (SADBE).
Acta Derm Venereol. 1986;66(6):485-90. PMID: 2433867
- Valsecchi R, Cainelli T, Foiadelli
L, Rossi A. Topical immunotherapy of
alopecia areata. A follow-up study. Acta Derm Venereol. 1986;66(3):269-72.
PMID: 2426909
- Case PC, Mitchell AJ, Swanson NA, Vanderveen EE, Ellis
CN, Headington JT. Topical therapy
of alopecia
areata with squaric acid dibutylester. J Am Acad Dermatol.
1984 Mar;10(3):447-50. PMID: 6725657
- Flowers FP, Slazinski L, Fenske NA, Pullara TJ. Topical squaric
acid dibutylester therapy for alopecia areata. Cutis. 1982 Dec;30(6):733-6.
PMID: 6756800
- Happle R, Kalveram
KJ, Buchner U, Echternacht-Happle K, Goggelmann W, Summer
KH. Contact allergy as a therapeutic
tool
for alopecia areata: application of squaric acid dibutylester.
Dermatologica. 1980;161(5):289-97.
PMID: 7439477
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