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Combined oral pulse and topical corticosteroid therapy for severe alopecia
areata in children: A long-term follow-up study

Article  in  Dermatologic Therapy · July 2015

DOI: 10.1111/dth.12255

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Dermatologic Therapy, Vol. 00, 2015, 00–00 C 2015 Wiley Periodicals, Inc.
V
Printed in the United States
All rights reserved
DERMATOLOGIC THERAPY
ISSN 1396-0296

ORIGINAL PAPERS

Combined oral pulse and topical

corticosteroid therapy for severe
alopecia areata in children: a
long-term follow-up study
Jovan Lalosevic*, Mirjana Gajic-Veljic*,†,
Branka Bonaci-Nikolic†,‡, & Milos Nikolic*,†
*Division of Pediatric Dermatology, Clinic of Dermatovenereology, Clinical
Center of Serbia †Faculty of Medicine, University of Belgrade and ‡Clinic of
Allergy and Clinical Immunology, Clinical Center of Serbia, Belgrade,
Serbia

ABSTRACT: There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated
65 children/adolescents with AA affecting >30% of scalp. Fourty-three percent of patients had AA
plurifocalis (AAP). Fifty-seven percent had AA subtotalis (AAS), AAP1ophiasis (AAP1OPH), and
alopecia totalis/universalis (AT/AU). Long-term follow-up (median 96 months) data were available for
69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks.
Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion
was applied 6 days a week. Hair growth was assessed on a scale ranging 0–100% of regrowth in
individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months
after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth.
61.5% of all patients were considered good responders. Significantly, higher percentage of good
responders was found in AA lasting 12 months. No patients had serious side effects. There was no
change in stability of the hair status at the long-term follow-up. Most AA patients had beneficial effects
with this protocol. Best results were in AAP and AAP1OPH. Combined topical and oral pulse
corticosteroid therapy of AA in children shows long-lasting results, without serious side effects.

KEYWORDS: alopecia therapy, clobetasol, pulse corticosteroids

Introduction nails (1). The estimated lifetime risk of AA in

general population is 1.7% (2,3). The majority of
Alopecia areata (AA) is a chronic, organ-specific
cases (60%) include patients under 20 years, but
autoimmune disease mediated by autoreactive T
AA can occur at any age (3).
cells; it affects hair follicles and sometimes the
The management of severe AA is difficult as
Address correspondence and reprint requests to: Professor the course of the disease is characterized by
Milos Nikolic, MD, PhD, Department of Dermatovenereology, extreme variability, not only in the time of initial
Faculty of Medicine, University of Belgrade, Pasterova 2, onset of hair loss but also in the duration, extent,
11000 Belgrade, Serbia, or email: [email protected]. and pattern of hair loss. Considering these factors

1
Lalosevic et al.

and the unpredictability of numerous relapses, it lens. In every child, body weight and body height
is obvious that there is a challenge in implement- were measured at each visit. The written consent
ing a treatment protocol for AA. was obtained from the parents of the patients.
To this date, there are no widely accepted ther- For every patient the following data were sum-
apy protocols; nevertheless, corticosteroids, either marized: gender, age, family history of AA, atopy,
topical or systemic, are currently used as an effec- and autoimmune diseases (diabetes mellitus
tive and well-tolerated treatment for AA (4). type I, lupus erythematosus, autoimmune thy-
Topical corticosteroid therapy has been fre- roid gland disorders); personal history of atopy;
quently utilized for milder forms of AA, with a nail involvement, AA duration before the therapy
few publications of its use in alopecia totalis initiation (less than 6 months, 7–12, 13–24, and
(AT) and alopecia universalis (AU). (5) To avoid more than 25 months).
prolonged treatment with oral corticosteroids, Patients received oral dexamethasone solution
Burton and Shuster introduced high dose intra- (equivalent to 5 mg/kg of prednisolone), in a sin-
venous pulse methylprednisolone therapy in gle daily dose, after breakfast. Two days before
1975 (6). From that time, different protocols the pulse, on the day of the therapy and 2 days
(7–12) have been published, but few data are after the pulse, patients received oral ranitidine
available about their long-term effects in AA. 2 mg/kg, maximum 300 mg/day. The treatment
was repeated once every 4 weeks. It was planned
that all patients should receive 6 pulses. In
Objectives patients who had an incomplete response at the
6-month check-up, the therapy was continued.
The aim of this retrospective study is to deter- The therapy was initially extended to 9 months;
mine the short-term and long-term effects of if further growth was achieved, but still incom-
combined topical and oral pulse corticosteroid plete, the therapy was continued to a maximum
therapy (PCT) of AA in children. of 12 months.
Before and after each pulse cycle, cardiac
rhythm, blood pressure, serum glucose, sodium
Patients and methods and potassium levels were checked. The patients
were hospitalized for one day after the pulse
This single-center retrospective study included 65 therapy for medical observation.
AA patients, aged 2–18 (mean 10.6 6 5.0 years), All patients applied topical clobetasol propio-
treated at the Division of Pediatric Dermatology, nate 0.05% ointment under plastic wrap occlusion
Clinic of Dermatovenereology, Clinical Center of overnight, 6 days a week. After 3 weeks of treat-
Serbia, Belgrade, between 1st January 2002 and ment, a 7-day break without topical therapy was
31st December 2012. The data were obtained made to prevent side effects and tachyphylaxis.
from the medical records of the patients. The percentage of scalp hair loss was eval-
The inclusion criteria were as follows: (1) uated by photos and medical documentation at
patients younger than 18 years; (2) more than the time of pulse therapy, according to the AA
30% of scalp affected; (3) no contraindications to investigational assessment guidelines and it was
systemic corticosteroid therapy (e.g., diabetes done by a board-certified dermatologist (M
mellitus, liver dysfunction, acute or chronic Nikolic or M Gajic-Veljic) (13). Patients with mul-
infection, peptic ulcer, arterial hypertension, car- tiple patches of AA covering 30–60% of scalp sur-
diac arrhythmias). Before the inclusion in the face area (SSA) were classified as AA plurifocalis
therapy protocol, the following procedures were (AAP); those with AA covering 60–95% were clas-
performed: dermatologic and pediatric physical sified as AA subtotalis (AAS). Patients with AAP
examination, routine blood and urine laboratory concomitant with band-like hair loss in the occi-
analyses, chest X-rays (to exclude tuberculosis), pital area were classified as AAP1ophiasis
and standard ophthalmic exam. Before every (AAP1OPH); and those with 100% scalp or 100%
subsequent pulse, a complete physical examina- scalp and body hair loss were classified as AT/
tion and routine blood tests were performed AU.
(erythrocyte sedimentation rate, C-reactive pro- The statistical analysis of the obtained hair
tein, complete blood count, serum electrolytes, regrowth was performed after 3, 6, and, in cases
glycemia, and urinalysis). Once in 3 months, that received more than 6 cycles of pulse ther-
ophthalmic exam was repeated, with a special apy, after 9 and 12 months. Hair growth was
attention to the intraocular pressure and the assessed on a percentage scale ranging from 0 to

2
 Combined pulse and topical corticosteroid therapy

Table 1. Patient characteristics at the beginning Statistical analyses

of therapy (n 5 65)
Statistical analyses were performed using Statisti-
Age, years (mean 6 SD) 2–18 (10.6 6 5.0)
cal Package for the Social Sciences, version 20
Male/female, n 27/38
software for Macintosh. The data were tested for
AA type, n (%)
Plurifocalis 28 (43.0) normal (Gaussian) distribution using the Kolmo-
Subtotalis 7 (10.8) gorov–Smirnov test. Normally distributed contin-
Plurifocalis with ophiasis 15 (23.1) uous variables are presented as mean 6 SD (95%
Totalis and universalis 15 (23.1) confidence interval). Categorical variables are
AA duration, n (%) expressed as numbers and percentages. Differen-
6 Months 14 (21.5) ces of continuous normally distributed data were
7–12 Months 14 (21.5) tested for statistical significance using one-way
13–24 Months 11 (16.9) analysis of variance. Fisher’s exact test and Chi-
>25 Months 26 (40.0) square test was used for comparison of nonpara-
Nail involvement, n (%) 37 (56.9)
metric variables. Statistical significance was
Personal history of atopy, n (%) 8 (12.3)
defined as p < 0.05.
Family history of atopy, n (%) 5 (7.6)
Family history of autoimmune 8 (12.3)
diseases, n (%)
Family history of AA, n (%) 10 (15.4)
Results
Patient characteristics
A total of 65 children met the study criteria.
100% of regrowth in individual AA lesions. Only Their demographic and clinical data are sum-
growth of terminal hair (not vellus or intermedi- marized in Table 1. Severe forms of AA (AAS,
ate hair) from the lesions was regarded as AAP1OPH, AT/AU) were diagnosed in 37/65
regrowth. The responders were classified as 0%, (57%) patients.
1–49%, 50–74%, 75–99%, and 100% of regrowth.
More than 50% of regrowth was considered as a Short-term outcome, at the end of protocol (6–12
good response. months after the therapy initiation). Of 65 partic-
Short-term outcome was estimated at the end ipants, 4 pulses were given to 5 patients (persons
of therapy, and was assessed 3, 6, 9, and 12 that had 100% hair regrowth, where further
months after the commencement of the pulses were estimated unnecessary), 6 pulses to
protocol. 39 subjects, 9 pulses to 12 subjects, and 12
Relapse was defined as an increase of the pulses were given to 9 patients.
affected SSA by at least 10%. There was no Patients with AA that lasted >12 months
change in the treatment protocol in patients before the commencement of our protocol, sig-
who had relapses. nificantly more frequently needed 9 or 12 pulses
Long-term follow-up (median 96, range 12– (6 pulses vs. 9 p 5 0.048; and 6 pulses vs. 12,
132 months after the completion of the protocol) p 5 0.029). When comparing patients that
data were available for 45/65 (69%) of patients. received 9 and 12 pulses, no statistically signifi-
Patients that had relapses after the end of ther- cant difference was found in AA duration.
apy applied only topical clobetasol propionate At the end of therapy, 56.9% (37/65) of all
ointment. Long-term outcome assessment was patients had more than 75% of hair regrowth. Of
performed by clinical examination, between these, 73.9% (27/37) had a complete regrowth.
August and December 2013. At the long-term fol- Of AAP patients, 65.5% (18/28) had complete
low-up, we estimated the current hair status and regrowth, while in more severe AA forms, com-
compared it to the finding at the short-term fol- plete hair regrowth was registered in 21.6% (8/
low-up. Subsequently, the hair growth outcomes 37). Only 6.7% (1/15) of AT/AU patients had
were defined as stable, worse, or improved. The complete regrowth. No terminal hair regrowth
change in hair status (worse or improved) was was obtained in 32.3% (21/65) patients (FIG. 1).
defined as a decrease or increase by at least 10% Of all patients, 61.5% (40/65) were considered as
of the scalp surface covered by terminal hair. good responders (regrowth more than 50%).
In patients who achieved hair regrowth at the In our group of patients, age, gender, family
end of short-term evaluation, we registered relap- history of AA, autoimmune diseases, and atopy;
ses, if they appeared, within the following year as well as personal history of atopy, AA duration,

3
Lalosevic et al.

FIG. 1. Hair growth assessment on the 3, 6, 9, and 12-month evaluation.

and nail involvement did not affect the short- The only side effect of oral PCT was mild
term outcomes. headache on the day after the pulse, registered
Eleven of sixty-five (16.9%) patients had relap- in 10.7% (7/65) of patients. In all patients, the
ses during the treatment period. When compar- headache resolved after one dose of paraceta-
ing hair regrowth outcomes to the occurrence of mol. Topical therapy-induced scalp skin atrophy,
relapses during the treatment period, a statisti- found only in patients with AT/AU, was regis-
cally significant difference was found (p 5 0.005). tered in 13.3% (2/15), after 2 and 3 months of
If this was analyzed as a prognostic factor, there therapy, respectively. Two months after the dis-
was a statistically higher number of nonrespond- continuation of topical clobetasol, the atrophy
ers (<50% hair regrowth) in patients who had completely regressed. There were no gastric side
relapses during the treatment period. effects, blood pressure, and serum electrolytes
We found that a higher number of good res- were unaffected. According to the growth veloc-
ponders in patients with AA lasting 6 months ity charts and the growth/height curves, no dis-
(71.4%, 10/14) in comparison with patients with turbance was found in any of our patients.
AA lasting >6 months (58.8%, 30/51) was not
statistically significant (p 5 0.296). Conversely, Comparison short-term versus long-term outcome
there was a significantly higher number of good (45 patients). For the long-term assessment, 69%
responders (p 5 0.027) in AA lasting 12 months, (45/65) of all patients were available. The
then in AA lasting >12 months: 73% (27/37) vs. median follow-up time after the end of therapy
46.4% (13/28), respectively. The AA duration was 96 months (range 12–132 months).
(more or less than 12 months; more or less than In patients with AAP, comparing the short-
6 months) did not have any significant influence term and long-term hair status, we found a stat-
on complete hair regrowth (p 5 0.212, p 5 0.069, istically significant difference (p < 0.01). Patients
respectively). who had <75% of hair regrowth at the short-

4
 Combined pulse and topical corticosteroid therapy

term assessment were stable at the long-term either as oral (8,11,18) or intravenous
follow-up. In AAP patients who had 100% of hair pulses,(9,10,19,20) to this date only a few studies
regrowth (15/22), three (20%) had a worsening of have followed their long-term effects, (10,21) and
their hair status. In the 74–99% group, 3/4 even fewer focused only on children (21).
patients had an improvement in their hair status. This study is the largest one that investigated
When we excluded patients that had an improve- oral PCT in children, with long-term follow-up,
ment, no statistically significant change in stabil- and the first to examine the effects of combined
ity was found among AAP patients. topical and systemic corticosteroid therapy on
In patients with more severe AA forms, AA.
although 2/23 patients had an improvement, Many of the previously published studies con-
there was no significant change in the stability firmed the beneficial effect of PCT in the treat-
of hair status. ment of AA. However, given that a standard
Among the patients that were lost to follow- protocol has not been reached, there have been
up after the end of protocol, the majority were discrepancies in the type of administration, dos-
good responders (12/20, 60%). In AAP group: ages, and the duration of PCT (Table 2).
four had 100% regrowth and there was one Our short-term results are in accordance with
patient in each of the 75–99%, 50–74%, and 0% the previously published studies concerning
outcome groups. In AAP1OPH: two had 100%, oral pulse therapy in children with AA (11,12),
one patient had 1–49% regrowth and 2 patients but our study has a significantly higher percent-
had no regrowth. In AAS: two had 75–99% and age of severe AA forms and a larger total num-
two had 0% of regrowth; both AT/UN patients ber of patients than previously published
were 75–99% responders. studies.
Concerning patients with AAP, we found a sig- The majority of our AAP patients (83%) had
nificantly higher percentage of good responders more than 75% of hair regrowth (improvement)
in patients who had three or less relapses within at end of therapy, while in more severe forms of
the first year of follow-up (p 5 0.012). AA, >75% improvement was noted in 35.1% of
At the one-year follow-up, AAP patients patients.
showed a significantly lower number of relapses As can be seen in the Table 2, our results are
when compared with patients with more severe comparable to the previously reported short-
forms of AA, 10/22 vs. 12/15 (p 5 0.047). Eight term effects of PCT for different types of AA in
patients with AT/UN never had any signs of hair adults and adolescents (10,19,22).
regrowth. Nevertheless, our results show a higher per-
centage of complete hair regrowth in compari-
son to all previously published studies (Table 2).
Discussion Both Luggen et al (9) and Friedli et al (7) admin-
istered methylprednisolone 500 mg i.v. for three
Alopecia areata is an esthetically disturbing dis- days only once, while Friedland et al. (20)
ease, and, if left untreated, may have profound repeated the same treatment monthly (2–10
psychological and social effects on the sufferers, months) and had better complete hair regrowth
with a negative effect on the quality of life, both outcomes. Our data show even better outcomes
in children and adolescents (14). in comparison with the previous three studies;
Different therapy protocols for extensive AA still, our results can be best compared with the
have been tried, such as topical, intralesional or data of Friedland et al (20), taking into consider-
systemic corticosteroids, psoralen and ultraviolet ation that they also examined exclusively
A, contact immunotherapy, anthralin, minoxidil, children.
topical calcineurin inhibitors, and cyclosporine. Compared with the studies that examined oral
Because of lack of evidence from randomized PCT, our data show better results than Sharma
controlled trials, up to now, only few studies give et al (11) and BinSaif et al (18) (Table 2); yet,
us guidelines for effective AA treatment (15,16). Agarwal et al (8) described an extremely high
For the time being, topical clobetasol propionate percentage (93%) of good responders (>50% of
0.05% is considered an efficacious and safe as a regrowth), in patients treated with 5 mg/kg of
first-line agent for the treatment of limited oral betamethasone twice weekly for 6 months.
patchy alopecia (17). This can be explained with a high percentage of
Although there are many publications con- moderately severe AA patients (20–50% of scalp
cerning the systemic use of corticosteroids, affection), 13/15.

5
 Table 2. Studies on the administration of PCT for alopecia areata
Relapse after
Number of No Regrowth Regrowth Regrowth Complete Follow-up, the therapy

6
Author, year of participants Treatment regrowth <50%, %, >50%, 50–99%, >75%, %, regrowth, median (%, n of
publication Type of pulse therapy (adults/children) protocol %, (n) (n of patients) %, (n) (n) %, (n) (months) responders)
Luggen (9), 2008 Methylprednisolone, 25 once 52% 56%, 44% NR 28%, 12 73%,
500 mg i.v. 3 days (25/0) (13) (14) (16), (7) 8/11
11% (4)
Lalosevic et al.

Friedland (20), Methylprednisolone, 24 once monthly, 33%, NR NR NR 38%, 25 81%,

2013 500 mg i.v. 3 days (0/24) (2–10 (8) (9) (1-68) 13/16
treatments)
Friedli (7), 1998 Methylprednisolone, 2 45 once 47%, 69%, 31% NR 24%, 7 25%,
3 250 mg i.v. 3 days (38/7) (21) (31) (20), (11) (1.5-11) 4/16
14% (9)
Nakajima (19), Methylprednisolone, 139 once 22%, 41%, 59%, 48%, NR 15.3 NR
2007 500 mg i.v. 3 days (NR*) (30) (57) (82) (66) (6-70)
Bin Saif (18), Methylprednisolone, 42 1–3 days every 2 NR NR NR 29%, NR 12-48 58%,
2012 15 mg/kg, oral (NR†) weeks, 24 (12) 21/36
weeks
Staumont-Salle Methylprednisolone, 30 once monthly, NR 67%, 33%, NR NR 12.3 years 90%,
(10), 2012 500–1000 (22/8) (up to 3 (20) (10) (10-15.8) 9/10
(a)/10–20 mg/kg treatments)
(c) mg i.v. 3 days
Seiter (22), 2001 Methylprednisolone, 30 once every 28 47%, 60%, 40%, NR 30%, 12 38%,
8 mg/kg i.v. 3 days (26/4) days, (3 (14) (18) (12) (9) 6/16
treatments)
Agarwal (8), Betamethasone, 0.5 15 2 days a week, 6 7%, 7%, 93%, 67%, NR 12 NR
2006 (<12yr) or 5 mg/kg, (NR‡) months (1) (1) (14) (10)
oral
Sharma (11), Prednisolone 300 mg, 16 once monthly, 19%, 38%, 62%, 56%, 32%, 18 25%,
1998 (<11yr prednisolone (0/16) minimum of (3) (6) (10) (9) (5) (6-36) 4/16
5 mg/kg), oral 3 treatments
Lenane (17), Topical clobetasol pro- 20 2x/day, 2 cycles NR 15%, 85%, NR NR NR NR
2014 pionate 0.05% (0/20) of 6 weeks on, (3) (17)
then 6 weeks
off
(total of 24
weeks)
Tosti (5), 2003 Topical clobetasol pro- 28 once daily, 6 NR NR NR 29%, 11%, 6 38%,
pionate 0.05% (NR§) days a week, (8) (3) 3/8
for 6 months
This study, 2015 Dexamethasone 65 once every 28 32%, 35%, 65 57%, 42%, 96 59%,
(eq to prednisolone (0/65) days, (21) (23) (20)%, (37) (27) (12-132) 22/37
5 mg/kg), oral 1 top- (up to 12 42 (13)
ical 0.05% clobetasol treatments) 1
propionate (once daily 6
days a week)

NR, not reported

*- 35.1 (15–71) years
†
- 19.5 67.4 years
‡
- range 8–45 years
§
- 22 (17–42) years
 Combined pulse and topical corticosteroid therapy

Tosti et al. (5) used the identical topical proto- adult patients, while others (20,23) defined good
col as we did, and showed more favorable results hair regrowth outcomes differently from us. Our
(>75% of regrowth) in adult AT/UN patients data that show that the previous AA duration
(28.5% vs. 14% at the 6 months follow-up). How- does not influence the complete hair regrowth in
ever, she reported that one third of those children, and differ from those of Friendland
patients experienced severe relapses with return et al. (20), which might be due to the differences
to pretreatment state despite application of the in the therapy protocol (Table 2).
treatment, resulting in 19% of stable responders. According to our data, in AA lasting >12
These better results could be explained by the months, one should initially expect slower hair
fact that Tosti’s study was a prospective on, and growth response, necessitating more than six
the patients had an exact amount of clobetasol pulses.
prescribed to them, giving a better adherence None of our patients had serious therapy side
and compliance to the treatment protocol. effects, including infections and asthenia. Gas-
Lenane et al. (17) (patients treated only with trointestinal side effects were absent in all of our
topical 0.05% clobetasol cream) reported a patients. In studies that investigated the treat-
higher percentage of patients that had more ment of AA with PCT, only Friedli et al. (7) men-
than 50% of hair regrowth. This could be due to tioned gastroprotective measures (ranitidine
milder inclusion criteria (they included patients 300mg/d 2 days before treatment, continued for
with more than 10% of SSA affected, rather than 1 week), while other authors (10,11,20,22,23) did
>30% as we and other authors did). not declare such medication.
As expected, we had the most satisfactory In our AAP patients, the long-term results
results in patients with AAP. Our patients with were not significantly worse than the short-term
AAP had higher percentage of good responders results, which is in line with a French study (10).
in comparison with studies that used only i.v. In patients with more severe forms of AA, our
PCT (without topical therapy) in children and results show stable hair status at the long-term
adults: 89.7% (our study) vs., 50.0% (9), vs. 70.0% assessment, with a minimal, but still noticeable
(7), vs. 72.2% (22). Conversely, in AAP1OPH and percentage of subsequent hair regrowth in com-
AT/UN patients, our results were comparable or parison to the short-term assessment. This dif-
better in comparison with other studies – in fers from the data published by Staumont (10)
AAP1OPH: 60.0% (our study) vs. 55.5% (9), vs. and Hubiche (21), which showed a worsening of
0% (7), vs. 10.0% (22); and in AT/UN: 14.3% (our hair growth status at the long-term follow-up.
study) vs. 16.7% (9), vs. 0% (7), vs. 20% (22). This could be due to the smaller number of
Similar to other authors, we analyzed several patients in the two previous studies (12 and 30,
prognostic factors that might influence the ther- respectively). In our study, the slight hair
apy outcomes in AA patients. Among general regrowth after completion of the protocol could
prognostic factors of AA, such as family history be explained by the effects of subsequent topi-
of autoimmune diseases and atopy, gender, age, cal treatment or potential spontaneous AA
personal history of atopy, and nail affection, we regrowth. Also, our results show more promising
found that none influenced hair growth out- outcomes for patients that had three or less
comes at the end of the therapy. Our results are relapses in the first year after the end of the
in accordance with the data published by Im therapy.
et al. (23) In some studies, atopy has been found We are aware of the limitations of our study,
to be a bad prognostic factor for AA treated topi- taking into consideration that it was not a pro-
cally (24,25). spective one, that the hair growth assessment
Several authors (19,20,23), reported a 6 was not performed blinded, and that 31% of our
months AA duration as a good prognostic factor. patients were lost to follow-up. Nevertheless, our
Even though our results show a higher percent- study provides unique data on the effects of a
age of good responders in the 6 month’s group, new combination therapy protocol for AA, and
the difference was not significant. Our results also gives an insight in the long-term effects of
show that the AA duration can be referred as a this therapy for different AA subtypes.
prognostic factor, but the duration 12 months We found that the combination of oral PCT
might be a better cutoff, at least when children and topical 0.05% clobetasol propionate is a safe
are concerned. Our findings differ from the data and efficient method for the treatment of severe
of previous authors (19,20,23), probably due to AA forms in children and adolescents. Our com-
the fact that some of them (19) investigated only bination protocol showed excellent and long-

7
Lalosevic et al.

lasting results in the treatment of AAP. In the 3. Price VH. Alopecia areata: clinical aspects. J Invest Der-
majority of AA patients, six PCT were sufficient, matol 1991: 96: 68S.
4. Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J
and gave satisfactory results. Conversely, in AA
Med 2012: 366: 1515–25.
lasting >12 months, one could anticipate more 5. Tosti A, Piraccini BM, Pazzaglia M, Vincenzi C. Clobetasol
resistant disease, necessitating the administra- propionate 0.05% under occlusion in the treatment of
tion of additional corticosteroid pulses, with a alopecia totalis/universalis. J Am Acad Dermatol 2003:
lesser chance of a successful outcome. 49: 96–98.
Our study showed that every patient with wide- 6. Burton JL, Shuster S. Large doses of glucocorticoid in the
treatment of alopecia areata. Acta Derm Venereol 1975:
spread AA might be considered as a potential can-
55: 493–96.
didate for combined oral PCT 1 topical clobetasol 7. Friedli A, Labarthe MP, Engelhardt E, Feldmann R,
therapy, but a poorer response can be expected in Salomon D, Saurat JH. Pulse methylprednisolone therapy
more severe forms of AA in comparison with AAP. for severe alopecia areata: an open prospective study of
In conclusion, most patients with AA had ben- 45 patients. J Am Acad Dermatol 1998: 39: 597–602.
eficial effects with our therapy protocol. Com- 8. Agarwal A, Nath J, Barua KN. Twice weekly 5 mg beta-
methasone oral pulse therapy in the treatment of alope-
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This study was supported by the Ministry of Delaporte E. Pulse corticosteroid therapy for alopecia
areata: long-term outcome after 10 years. Dermatology
Education and Science of the Republic of Serbia, 2012: 225: 81–87.
Grant No 175065 (M Nikolic and M Gajic-Veljic). 11. Sharma VK, Muralidhar S. Treatment of widespread alo-
The Ministry of Education and Science of the pecia areata in young patients with monthly oral cortico-
Republic of Serbia had no role in the design and steroid pulse. Pediatr Dermatol 1998: 15: 313–317.
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analysis, and interpretation of the data; and oral pulse prednisolone therapy in alopecia areata. J Am
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preparation, review, or approval of the manu-
13. Olsen EA. Investigative guidelines for alopecia areata.
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Financial Disclosure J Eur Acad Dermatol Venereol 2014: 28: 1463–1468.
15. Brzezin  ska-Wcisło L, Bergler-Czop B, Wcisło-Dziadecka
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D, Lis-Swie
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Acknowledgements or without 2% topical minoxidil in the treatment of alo-
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For the help in the statistical analysis we are 17. Lenane P, Macarthur C, Parkin PC, Krafchik B, DeGroot
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