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Combination
therapy for alopecia areata
So far, topical immunotherapy with contact sensitizing agents
has been defined as the best overall treatment for chronic and
severe (more than 50% hair loss) alopecia areata. The use of systemic
steroids would be more effective, but their long-term use can
result in unacceptable side effects. Recent research studies have
looked into methods of increasing the effectiveness of current
treatments and some studies suggest a combination therapy can
provide a superior result.
Combination therapy is a method of treating disease through the
simultaneous use of a variety of drugs to eliminate or control
the biochemical cause of the disease.
In some recalcitrant cases alopecia areata can be refractory
to topical immunotherapy. Also, since it is a heterogeneous disease
in the same patient, it may require multiple modalities to re-grow
hair on differing portions of the scalp. It is for this reason
that many combination therapies have been tried in alopecia areata.
Since little data exists regarding the natural evolution of alopecia
areata, assessment of the efficacy of a treatment must be considered
with care. Moreover, the condition is highly unpredictable in
presentation, evolution, and response to treatment. What is important
to remember is that the longer the victim has the disease and
the greater severity of the disease, the smaller are the chances
of successful treatment.
Clinical
studies on combination therapy for alopecia areata
In their efforts to identify a universally acceptable and effective
treatment regime for alopecia areata patients, different research
teams have weighed the efficacy of combined therapy through clinical
trials. Some of these trials involved treatment with the combination
of topical, intra1esiona1, and/or systemic steroids, and some
trials with other drug combinations. The following results have
been documented with combination therapy.
- Unger and Schemmer evaluated the advantageous use of
combination therapy with topical, intralesional, and oral corticosteroids
in 15 patients with alopecia totalis or alopecia universalis.
30 to 40 mg of prednisone daily was prescribed in combination
with 0.025% fluocinolone acetonide cream under occlusion for 12
hours per day. Seven of the 15 patients who were able to re-grow
virtually all their scalp hair were able to discontinue oral corticosteroids
without recurrence of their disease for an average follow-up of
32 months.
- In six patients with treatment-refractory alopecia
universalis, oral Prednisolone 5 mg/kg was administered for
2 months followed
by the addition of oral administration of 2.5 mg/kg of cyclosporine.
Prednisolone therapy was continued during the cyclosporine
therapy and gradually decreased after the cyclosporine therapy
was discontinued.
One month after the addition of cyclosporine, hair began to
grow in all six cases and continued for more than 6 months
after the
stoppage of cyclosporine.
- Shapiro and colleagues used oral cyclosporine 5 mg/kg
per day in combination with oral prednisone 5 mg daily for
6 months in eight patients with alopecia areata with more than
95 percent
of the scalp affected. Two of the eight patients experienced
cosmetically acceptable hair re-growth, but both relapsed
after
therapy was
discontinued.
- Olsen and colleagues examined the effect of 2% topical
minoxidil on prednisone-induced hair growth. At the end of
the trial, the authors concluded that 2% topical minoxidil appears
to limit or slow post-steroid hair loss in patients with alopecia
areata.
- In a controlled, double-blind study in patients with
severe, chronically treatment-resistant alopecia areata, comparisons
were made between twice-daily applications of 5% topical Minoxidil
followed 30 minutes later by the application of 0.05% betamethasone
dipropionate cream (Diprosone, non-optimized vehicle), either
therapy alone or placebo. Thirteen percent of patients treated
with placebo, 22 percent treated with steroid alone, 27 percent
treated with Minoxidil alone, and 56 percent treated with
the combination therapy showed a fair to good re-growth of hair
after 16 weeks of therapy. The authors hypothesized that the
simultaneous
use of topical steroid increases the local tissue concentration
of Minoxidil, probably through vasoconstriction and a secondary
reduced clearance of drug.
- The use of topical 5% Minoxidil plus 0.5% anthralin (Drithocreme)
was evaluated in an open-label study of severe alopecia areata
previously shown to be resistant to Minoxidil (orally or topically)
or topical anthralin alone. One milliliter of 5% topical Minoxidil
was applied twice a day; anthralin was applied 2 hours after
the evening Minoxidil dose and left on overnight. Terminal
hair re-growth
was seen in 39 of 50 patients after 11 weeks, with sustained
hair growth in 4 patients with continued treatment up to 84
weeks.
Side effects were mild to moderate scaling and pruritis. Although
Minoxidil blood levels increased with the combination therapy
over topical Minoxidil alone, there was no clinical evidence
of systemic Minoxidil effects.
- The combination of diphencyprone and inosiplex therapy
was evaluated for the treatment of alopecia totalis. Three
groups matched for age and sex were studied. One group received
inosiplex
50 mg/kg per day, another group was treated with diphencyprone
topically, and the third group received both treatments. The
duration of therapy was 6 months. None of the 22 patients
treated with
inosiplex responded, and only 2 of 22 patients responded to
diphencyprone alone.
- Shapiro and colleagues sensitized 15 patients with chronic
and severe (more than 50 percent scalp involvement) alopecia
areata to diphencyprone and then treated one-half of the scalps
of each
patient weekly. Therapy with either 5% topical Minoxidil or
placebo twice daily to the diphencyprone-treated half of the
scalp was
randomly assigned. After 24 weeks, 5 of the 15 patients showed
significant unilateral regrowth, including 3 of 5 on diphencyprone
and vehicle and 2 of 5 on diphencyprone and 5%topical Minoxidil.
The use of topical Minoxidil did not appear to add to the success
rate of diphencyprone alone.
Combination
treatment
approach alopecia areata
As a rough guideline, patients with alopecia areata are given
the combination treatment options below. They are shown in the
approximate sequence they will be offered. If the first treatment
approach fails then the xclinic may suggest the second treatment
approach. If that fails they may suggest the third approach and
so on until a hair growth response is obtained or there are no
more options.
Patients with less than 50% hair loss are given the following
options:
- Intralesional cortisone injections into the
scalp, beard area, or eyebrow area.
- Minoxidil solution.
- Combination therapy: Minoxidil and
cortisone cream
- Combination therapy: Minoxidil and anthralin
- Topical
immunotherapy
Patients with more than 50% hair loss are given the following
options:
- Topical immunotherapy with diphencyprone, SADBE
or PUVA
- Combination therapy: Minoxidil
and cortisone cream
- Combination therapy: Minoxidil and anthralin cream
- Systemic pulse steroids
At present, treatment for severe alopecia areata is very non-specific
and has considerable side effects. Treatments used are believed
to stimulate hair growth, but no evidence exists that they ultimately
influence the natural course of the disease. A lot of work is
going into researching normal hair biology in an effort to ascertain
the events that control the hair cycle. Hopefully, once the trigger
for alopecia areata is identified, more specific, more effective
and better tolerated treatments will be developed. Due to the
heterogeneous nature of alopecia areata, many dermatologists find
that combination treatments utilizing more than one treatment
approach increase the success rates in treating alopecia areata.
Combination
therapy for alopecia areata references
- Hajheydari Z, Jamshidi M, Akbari J, Mohammadpour
R.
Combination of topical garlic gel and betamethasone valerate cream in the treatment
of localized alopecia areata: a double-blind randomized controlled
study. Indian J Dermatol Venereol Leprol. 2007 Jan-Feb;73(1):29-32.
PMID: 17314444
- Joly P. The use of methotrexate alone or in combination with
low doses of oral corticosteroids in the treatment of alopecia
totalis or universalis. J Am Acad Dermatol. 2006 Oct;55(4):632-6.
PMID: 17010743
- Ross EK, Shapiro J. Management of hair loss. Dermatol Clin.
2005 Apr;23(2):227-43. PMID: 15837153
- 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
- Shapiro J, Price VH. Hair regrowth. Therapeutic agents. Dermatol
Clin. 1998 Apr;16(2):341-56. PMID: 9589208
- Shapiro J, Tan J, Ho V, Tron V.
Treatment of severe alopecia areata with topical diphenylcyclopropenone
and 5% minoxidil: a clinical and immunopathologic evaluation.
J Invest Dermatol. 1995 May;104(5 Suppl):36S. PMID: 7738390
- Shapiro J, Tan J, Ho V, Abbott F, Tron V. Treatment of chronic
severe alopecia areata with topical diphenylcyclopropenone and
5% minoxidil: a clinical and immunopathologic evaluation. J
Am Acad Dermatol. 1993 Nov;29(5 Pt 1):729-35.
PMID: 7901248
- Olsen EA, Carson SC, Turney EA.
Systemic steroids with or without 2% topical minoxidil in
the treatment of alopecia areata.
Arch Dermatol. 1992 Nov;128(11):1467-73.
PMID: 1444500
- Berth-Jones J, Hutchinson PE. Treatment of alopecia totalis
with a combination of inosine pranobex and diphencyprone compared
to each treatment alone. Clin Exp Dermatol. 1991 May;16(3):172-5.
PMID: 1718636
- Fiedler VC, Wendrow A, Szpunar GJ, Metzler C, DeVillez RL.
Treatment-resistant alopecia areata. Response to combination
therapy with minoxidil plus anthralin.
Arch Dermatol. 1990 Jun;126(6):756-9.
PMID: 2140670
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