- Email: [email protected]
Topical Immunotherapy in Children with Alopecia Areata
VOL.
104.
NO.
5.
SUPPLEMENT.
MAY
HAIR
1995
FOLLICLE AUTOANTmODIES
IN DEBRA RAT SERA
35S
established lesional rats had autoantibodies specific for components
autoantibodies, nine of ten prelesional DEBR rats expressed some
of the hair follicle of which one had skeletal muscle autoantibodies
form of autoantibody at a serum dilution of 1:80.
and four had antinuclear antibodies. For autoantibodies against the
Our findings clearly show that in the DEBR model, as in human
inner root sheath in some active lesional rats, sera could be titrated
AA, the immune system can be presented with a range of poten
to 1:1280 and still maintain staining intensity. Control sera from
tially stimulatory self antigens derived from hair-follicle epidermal
PVG/Ola rats showed no positive staining for hair-follicle compo
differentia. Because the production of antibody seemed to coincide
nents or other tissues.
with the development of the cellular infiltrate and there was
An earlier study by Michie, t which stimulated the current work,
variable targeting of a range of follicle dilferentia, autoantibodies in
detected autoantibody activity in DEBR serum with staining of hair
DEBR serum may be a consequence of cellular disruption by
cuticle and fiber. Using sera from AA patients Calver
a/* reported
immune cells and subsequent release of autoantigens. This presence
staining for the outer root sheath, inner root sheath, hair shaft,
of autoantibodies ahead of actual hair loss could indicate their
et
epidermis, sebaceous glands, and apocrine glands, with individual
production and possible active participation in the progression of
sera
the lesion.
exhibiting
heterogeneity in
autoantibody
specificity.
Our
findings revealed a more restricted range of epithelial targets in the DEBR rat. The autoantibodies raised in the DEBR rat were against normally expressed antigens as they were able to target epithelia in normal PVG/Ola rat tissue as well as lesional DEBR follicles. Nor were the autoantibodies species specific as they targeted the same epithelia in human scalp sections. Autoantibodies against striated muscle were particularly promi
We would like to thank Dr.
1.
Dr.
Kill
V.
Randall, Mr. N. Calver (Bradford University), and
(University of Dundee) for discussion and assista,ue in protocol
development. This work was supporled by the National Alopecia Areata Foundation (PP, RFO) and the Medical Research
Council (KJM). ------
nent in serum from prelesional rats. Cell antinuclear antibodies as found in 10 of the 30 DEBR rat sera when tested on a rat embryonic REFERENCES
epidermal cell line were further characterized as staining for nucleoli, centrosomes, centromeres, and nuclear lamina or pre
m
sented as a homogeneous nuclear stain. Autoantibodies against
1.
Zhang
odel of human alopecia areata.
Oliver RF: Immunohistological study of the development of the
cellular infiltrate in the pelage follides of the DEBR model for alopecia areata.
other tissues were not detected. When considering all types of
t Michie HJ: The DEBR rat: an animal Thesis, University of Dundee. 1989.
J-G.
Br] Dennatol130:405-414. 1994 2.
Oliver RF. Lowe JG: Oral cyclosporin A restores hair growth in the DEBR rat
3.
Tobin DJ. Orentreich N. Fenton DA. et al: Antibodies to hair follicles in alopecia
model for alopecia areata. Clj" Exp Dennatol (in press)
areata.] Invest DennatoI102:721-724.
1994
Topical Immunotherapy in Children with Alopecia Areata Giovanni Orecchia and Piergiorgio Malagoli Department of Dermatology, University of Pavia, Pavia, Italy
I
n the last decade in Europe, topical squaric acid dibutylester
complete or cosmetically acceptable regrowth was achieved and in
( SADBE) has been used in the treatment of alopecia areata
another six (21.4"Ic,) a significant hair regrowth
in the adult population. This study attempts to define this drug's effectiveness and handiness in pediatric patients suf
correlation was found between response and sex, age of onset of the illness, extent, duration, and dilferent clinical types of the disease.
fering from severe alopecia areata, who are psychologically
Fourteen of28 patients were followed up for
disturbed and resistant to other therapies.
a
appeared. No
period ranging from
18 months to 8 years: even if SADBE is not a cure for alopecia, it
Twenty-eight children (under 13 years old), suffering from
remained efficacious in relapses, too.
extensive and long-standing alopecia areata and who were not responsive to conventional therapies, were sensitized on the head with 2% of SADBE in acetone and treated with weekly applica tions. The treatment lasted 12 months. In nine patients (32.1%)
In severe forms of AA , under psycologic disturbed personal and family situations [11, treatment with SADBE seems justified for children, too. Indeed, particularly in these patients, it has many advantages compared with other therapies that are either associated with serious side effects or, in the judgment of some authors,
Reprint S.
Matteo,
requests to: Dr. G. Pavia, Italy.
Orecchia. Clinica Dermatologica, Policlinico
Abbreviation: SADBE. squaric
acid
0022-202X/95/$09.50
•
and furthermore it is readily accepted because it is a clean therapy (unlike topical anthralin). In addition it is not time consuming (there is
dibutylester.
SSDI0022-202X(95)00127-7
ineffective: it is a topical treatment, it is easy to apply (home therapy),
•
Copyright
©
1995 by The Society for Investigative Dermatology,
Inc.
36S
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
ORECCHIA AND MALAGOLI
a check-up every 2 months) and it is neither painful (unlike intrale
REFERENCES
sional infiltration with triamcinolone) nor risky [2] (unlike some potent topical corticosteroids, which may cause systemic absorption,
1.
Verri AP, Orecchia G, Cerru ti G, Ron chi G, Rabbiosi G: Alop ecia arcata in p e diatric patien ts : psychological aspects. Fifth International Congress of Pedi
adrenal suppression, and retardation of bone growth). This work demonstrates also that any adverse effect of this therapy can be avoided as applications are carried out weekly, with very low
atric Dermatology, July 11-15, 1989
2.
Capdli E, Orecchia G: Mutagenic evaluation of SADBE in human lymphocites.
International Symposium on Human Hair Follicles in Bio medical Research.
concentrations, over less than 5% of the body area, in a site, the head,
Bruxelles 5-6/2/88. Reported in: Van Neste DJ, La Chapelle JM, Antoine JL
which is quite tolerant to topical allergens. Because irritation is not a
(eds. ) . TreHds it,
prerequisite of recovery, we believe that SADBE is a suitable treatment
Publishers, 1989
even for children resistant to other therapies [3-5]. Therefore, considering the advantages due to its easy application and to the absence of side effects, we attest to the validity of SADBE as a suitable treatment particularly apt in children resistant to
Human Hair Groll't" and Alopecia Research. Kluwer Academic
3.
MacDonald Hull S, Pepall L, Cunliffe W]: Alopecia areata in children: response to
4.
Orecchia G, Rabbiosi G: Squ aric acid dibutylester in alopecia arcata: is discomfort
5.
Orecchia G. Perfetti L: Alopecia areata and topical sensitizers: all ergic response is
treatment with diphencyprone. Br] Dermatof 125:164-168, 1991 really necessary?] Am Acad Dernlf,tof 16:876-879, 1987
conventional therapies.
necessary but irritation is not.
BrJ Dentlatof
124:509-512, 1991
Treatment of Severe Alopecia Areata with Topical Diphenylcyclopropenone and 50/0 Minoxidil: A Clinical and Immunopathologic Evaluation Jerry Shapiro, Jerry Tan, Vincent Ho, and Victor Tron University
of British Columbia Hair Clinic, Research, Treatment and Transplant
T
Center,
Vancouver,
Canada
opical diphenylcyclopropenone and minoxidil have
weeks of treatment with DPCP. The addition of topical 5%
been used in the treatment of alopecia areata with
minoxidil did not produce any significant clinical benefit in this 24-week
variable results [1-5]. This study was designed to evaluate the efficacy of diphenylcyclopropenone alone or in combination
ences
trial. Immunophenotypic analysis
between
responders
and
showed no differ
nonresponders
at
baseline.
During treatment, Leu-4, Leu-2, and Leu-3 and keratinocyte
with topical 5% minoxidil for the treatment of chronic severe
intercellular
alopecia areata. The effect of therapy on cutuaneous T-cell and
cantly reduced in biopsy specimens of responders versus non
adhesion
molecule
Langerhans cell subpopulations and intercellular adhesions molc
responders.
1
expression
were
signifi
Diphenylcyclopropenone treatment showed a 38% success rate in
cule-1 expression was also examined. Fifteen patients with chronic (more than 2 years), severe (more than 50% scalp involvement) alopecia areata participated in a
producing
cosmetically
acceptable
regrowth
in
patients
with
chronic severe alopecia.
24-week trial. Half of the scalp was treated with diphenylcyclopro penone once weekly and with either 5% minoxidil solution or a vehicle solution twice daily in a randomized double-blind design.
REFERENCES
Skin biopsy specimens from each half of the scalp were obtained before therapy and after 12 and 24 weeks of therapy for histologic
1.
Perret C, Happle R: Treatment of alop e cia areata. In: O rf.m os C, Happle R (eds.).
2.
Van cler Steen p. Van Baar H, Perret C, et al: Treatment of alopecia areata with
3.
Shapiro J: Topical immunotherapy in the treatment of chronic severe alopecia
4.
Shapiro J: Treatment of chronic severe alopecia ar ea t a with topical diphenylcy
Hair and Hair Diseases. S p ringer Verlag, 1990
immunophenotypic analysis. Thirteen patients completed the study. Five of the 13 patients (38%) showed marked regrowth of coarse terminal hair after 24
diphenylcyclopropenone.] Am Acad Demtato/24:2S3-257, 1991 areata. Dermatof eli,., 11:611-617, 1993
Reprint
requests
to: Dr. Jerry Shapiro, University of
British
Columbia
cloprop en one and 5% minoxidil:
Hair Clinic, 855 West 10th Avenue, Vancouver, British Columbia, Canada V5Z IL7.
•
SSDIO022-202X(95)00128-8
•
clinic al and immunopatholo gi c evaluation.
Shapiro]: Alopecia areata, Update on Thera py. Derillatol elin 11:35-46, 1993
5.
0022-202X/95/$09.50
a
] Am Acad Dermatal 29:729 -735, 1993
Copyright
©
1995 by The Society for Investigative
Dermatology,
Inc.
104.
NO.
5.
SUPPLEMENT.
MAY
HAIR
1995
FOLLICLE AUTOANTmODIES
IN DEBRA RAT SERA
35S
established lesional rats had autoantibodies specific for components
autoantibodies, nine of ten prelesional DEBR rats expressed some
of the hair follicle of which one had skeletal muscle autoantibodies
form of autoantibody at a serum dilution of 1:80.
and four had antinuclear antibodies. For autoantibodies against the
Our findings clearly show that in the DEBR model, as in human
inner root sheath in some active lesional rats, sera could be titrated
AA, the immune system can be presented with a range of poten
to 1:1280 and still maintain staining intensity. Control sera from
tially stimulatory self antigens derived from hair-follicle epidermal
PVG/Ola rats showed no positive staining for hair-follicle compo
differentia. Because the production of antibody seemed to coincide
nents or other tissues.
with the development of the cellular infiltrate and there was
An earlier study by Michie, t which stimulated the current work,
variable targeting of a range of follicle dilferentia, autoantibodies in
detected autoantibody activity in DEBR serum with staining of hair
DEBR serum may be a consequence of cellular disruption by
cuticle and fiber. Using sera from AA patients Calver
a/* reported
immune cells and subsequent release of autoantigens. This presence
staining for the outer root sheath, inner root sheath, hair shaft,
of autoantibodies ahead of actual hair loss could indicate their
et
epidermis, sebaceous glands, and apocrine glands, with individual
production and possible active participation in the progression of
sera
the lesion.
exhibiting
heterogeneity in
autoantibody
specificity.
Our
findings revealed a more restricted range of epithelial targets in the DEBR rat. The autoantibodies raised in the DEBR rat were against normally expressed antigens as they were able to target epithelia in normal PVG/Ola rat tissue as well as lesional DEBR follicles. Nor were the autoantibodies species specific as they targeted the same epithelia in human scalp sections. Autoantibodies against striated muscle were particularly promi
We would like to thank Dr.
1.
Dr.
Kill
V.
Randall, Mr. N. Calver (Bradford University), and
(University of Dundee) for discussion and assista,ue in protocol
development. This work was supporled by the National Alopecia Areata Foundation (PP, RFO) and the Medical Research
Council (KJM). ------
nent in serum from prelesional rats. Cell antinuclear antibodies as found in 10 of the 30 DEBR rat sera when tested on a rat embryonic REFERENCES
epidermal cell line were further characterized as staining for nucleoli, centrosomes, centromeres, and nuclear lamina or pre
m
sented as a homogeneous nuclear stain. Autoantibodies against
1.
Zhang
odel of human alopecia areata.
Oliver RF: Immunohistological study of the development of the
cellular infiltrate in the pelage follides of the DEBR model for alopecia areata.
other tissues were not detected. When considering all types of
t Michie HJ: The DEBR rat: an animal Thesis, University of Dundee. 1989.
J-G.
Br] Dennatol130:405-414. 1994 2.
Oliver RF. Lowe JG: Oral cyclosporin A restores hair growth in the DEBR rat
3.
Tobin DJ. Orentreich N. Fenton DA. et al: Antibodies to hair follicles in alopecia
model for alopecia areata. Clj" Exp Dennatol (in press)
areata.] Invest DennatoI102:721-724.
1994
Topical Immunotherapy in Children with Alopecia Areata Giovanni Orecchia and Piergiorgio Malagoli Department of Dermatology, University of Pavia, Pavia, Italy
I
n the last decade in Europe, topical squaric acid dibutylester
complete or cosmetically acceptable regrowth was achieved and in
( SADBE) has been used in the treatment of alopecia areata
another six (21.4"Ic,) a significant hair regrowth
in the adult population. This study attempts to define this drug's effectiveness and handiness in pediatric patients suf
correlation was found between response and sex, age of onset of the illness, extent, duration, and dilferent clinical types of the disease.
fering from severe alopecia areata, who are psychologically
Fourteen of28 patients were followed up for
disturbed and resistant to other therapies.
a
appeared. No
period ranging from
18 months to 8 years: even if SADBE is not a cure for alopecia, it
Twenty-eight children (under 13 years old), suffering from
remained efficacious in relapses, too.
extensive and long-standing alopecia areata and who were not responsive to conventional therapies, were sensitized on the head with 2% of SADBE in acetone and treated with weekly applica tions. The treatment lasted 12 months. In nine patients (32.1%)
In severe forms of AA , under psycologic disturbed personal and family situations [11, treatment with SADBE seems justified for children, too. Indeed, particularly in these patients, it has many advantages compared with other therapies that are either associated with serious side effects or, in the judgment of some authors,
Reprint S.
Matteo,
requests to: Dr. G. Pavia, Italy.
Orecchia. Clinica Dermatologica, Policlinico
Abbreviation: SADBE. squaric
acid
0022-202X/95/$09.50
•
and furthermore it is readily accepted because it is a clean therapy (unlike topical anthralin). In addition it is not time consuming (there is
dibutylester.
SSDI0022-202X(95)00127-7
ineffective: it is a topical treatment, it is easy to apply (home therapy),
•
Copyright
©
1995 by The Society for Investigative Dermatology,
Inc.
36S
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
ORECCHIA AND MALAGOLI
a check-up every 2 months) and it is neither painful (unlike intrale
REFERENCES
sional infiltration with triamcinolone) nor risky [2] (unlike some potent topical corticosteroids, which may cause systemic absorption,
1.
Verri AP, Orecchia G, Cerru ti G, Ron chi G, Rabbiosi G: Alop ecia arcata in p e diatric patien ts : psychological aspects. Fifth International Congress of Pedi
adrenal suppression, and retardation of bone growth). This work demonstrates also that any adverse effect of this therapy can be avoided as applications are carried out weekly, with very low
atric Dermatology, July 11-15, 1989
2.
Capdli E, Orecchia G: Mutagenic evaluation of SADBE in human lymphocites.
International Symposium on Human Hair Follicles in Bio medical Research.
concentrations, over less than 5% of the body area, in a site, the head,
Bruxelles 5-6/2/88. Reported in: Van Neste DJ, La Chapelle JM, Antoine JL
which is quite tolerant to topical allergens. Because irritation is not a
(eds. ) . TreHds it,
prerequisite of recovery, we believe that SADBE is a suitable treatment
Publishers, 1989
even for children resistant to other therapies [3-5]. Therefore, considering the advantages due to its easy application and to the absence of side effects, we attest to the validity of SADBE as a suitable treatment particularly apt in children resistant to
Human Hair Groll't" and Alopecia Research. Kluwer Academic
3.
MacDonald Hull S, Pepall L, Cunliffe W]: Alopecia areata in children: response to
4.
Orecchia G, Rabbiosi G: Squ aric acid dibutylester in alopecia arcata: is discomfort
5.
Orecchia G. Perfetti L: Alopecia areata and topical sensitizers: all ergic response is
treatment with diphencyprone. Br] Dermatof 125:164-168, 1991 really necessary?] Am Acad Dernlf,tof 16:876-879, 1987
conventional therapies.
necessary but irritation is not.
BrJ Dentlatof
124:509-512, 1991
Treatment of Severe Alopecia Areata with Topical Diphenylcyclopropenone and 50/0 Minoxidil: A Clinical and Immunopathologic Evaluation Jerry Shapiro, Jerry Tan, Vincent Ho, and Victor Tron University
of British Columbia Hair Clinic, Research, Treatment and Transplant
T
Center,
Vancouver,
Canada
opical diphenylcyclopropenone and minoxidil have
weeks of treatment with DPCP. The addition of topical 5%
been used in the treatment of alopecia areata with
minoxidil did not produce any significant clinical benefit in this 24-week
variable results [1-5]. This study was designed to evaluate the efficacy of diphenylcyclopropenone alone or in combination
ences
trial. Immunophenotypic analysis
between
responders
and
showed no differ
nonresponders
at
baseline.
During treatment, Leu-4, Leu-2, and Leu-3 and keratinocyte
with topical 5% minoxidil for the treatment of chronic severe
intercellular
alopecia areata. The effect of therapy on cutuaneous T-cell and
cantly reduced in biopsy specimens of responders versus non
adhesion
molecule
Langerhans cell subpopulations and intercellular adhesions molc
responders.
1
expression
were
signifi
Diphenylcyclopropenone treatment showed a 38% success rate in
cule-1 expression was also examined. Fifteen patients with chronic (more than 2 years), severe (more than 50% scalp involvement) alopecia areata participated in a
producing
cosmetically
acceptable
regrowth
in
patients
with
chronic severe alopecia.
24-week trial. Half of the scalp was treated with diphenylcyclopro penone once weekly and with either 5% minoxidil solution or a vehicle solution twice daily in a randomized double-blind design.
REFERENCES
Skin biopsy specimens from each half of the scalp were obtained before therapy and after 12 and 24 weeks of therapy for histologic
1.
Perret C, Happle R: Treatment of alop e cia areata. In: O rf.m os C, Happle R (eds.).
2.
Van cler Steen p. Van Baar H, Perret C, et al: Treatment of alopecia areata with
3.
Shapiro J: Topical immunotherapy in the treatment of chronic severe alopecia
4.
Shapiro J: Treatment of chronic severe alopecia ar ea t a with topical diphenylcy
Hair and Hair Diseases. S p ringer Verlag, 1990
immunophenotypic analysis. Thirteen patients completed the study. Five of the 13 patients (38%) showed marked regrowth of coarse terminal hair after 24
diphenylcyclopropenone.] Am Acad Demtato/24:2S3-257, 1991 areata. Dermatof eli,., 11:611-617, 1993
Reprint
requests
to: Dr. Jerry Shapiro, University of
British
Columbia
cloprop en one and 5% minoxidil:
Hair Clinic, 855 West 10th Avenue, Vancouver, British Columbia, Canada V5Z IL7.
•
SSDIO022-202X(95)00128-8
•
clinic al and immunopatholo gi c evaluation.
Shapiro]: Alopecia areata, Update on Thera py. Derillatol elin 11:35-46, 1993
5.
0022-202X/95/$09.50
a
] Am Acad Dermatal 29:729 -735, 1993
Copyright
©
1995 by The Society for Investigative
Dermatology,
Inc.