Efficacy of Low-Dose Isotretinoin in Patients With Treatment-Resistant
Isotretinoin was shown to be effective in patients with treatment-resistant
rosacea by Nikolowski and Plewig1 in 1980
for the first time. Since then, many other studies2-4
confirmed its efficacy in a daily dose of 0.5 to 1.0 mg/kg. However, it has
also been noted that adverse effects of the drug may limit its use. In this
study, we aimed to determine if low doses of isotretinoin were effective in
patients with treatment-resistant rosacea.
Patients and Methods
Eighteen female and 4 male patients with a mean age of 49.1 years and
a mean duration of illness of 6.5 years were enrolled in the study. Of these
patients, 18 had previously used topical steroids, 11 had used topical metronidazole,
and all had used systemic tetracycline and/or metronidazole. The efficacy
of these previous treatments was either incomplete or transitory. Patients
were evaluated for their degree of erythema and rhinophyma using a scale (from
+ to ++++), whereas the numbers of telangiectasias, papules, and pustules
were counted numerically. Patients were evaluated on the basis of eye examinations,
complete blood cell counts, urinalyses, liver function tests, and determinations
of serum creatinine, cholesterol, and triglyceride levels. Patients were treated
for 16 weeks with follow-up visits at weeks 3, 6, 9, 12, and 16. Patients
were evaluated clinically, photographically, and with laboratory tests. All
patients received oral isotretinoin, 10 mg/d, every morning after breakfast.
During the treatment, patients were allowed to use only topical emollient
creams if needed.
All patients completed the study. The most rapid response to treatment
was for pustular lesions. For the subjective symptoms, a burning sensation
reported by 18 patients at the beginning of the study completely diminished
by the sixth week of treatment.
The Wilcoxon matched pairs test was used for statistical analysis comparing
the clinical findings at the ninth week of treatment with the initial assessment,
and the end of the treatment with the ninth week evaluation.
Table 1 shows erythema scores
of the patients at different treatment stages. As seen in Table 1, there was a significant decline in erythema at the ninth
week when compared with the initial values (P<.001),
and at the end of the study compared with the ninth week (P<.001). Distribution of telangiectasia scores is also shown in Table 1. Telangiectasia scores significantly
decreased by the ninth week of treatment (P<.05),
showing a further significant decline at the end of the study (P<.001).
Papular lesion counts and their comparison at different treatment stages
are illustrated in Table 2. Papular
lesions were significantly reduced at the ninth week evaluation (P<.001), showing an even more pronounced decrease at the end of
the study (P<.001). Pustular lesions decreased
significantly by the ninth week of treatment (Table 2; P<.001). However, the difference
between the end of treatment and ninth week values is not significant (P=.11), which may be due to the early and complete response
of pustular lesions to isotretinoin. The mean total scores for patients at
the beginning, the ninth week, and the end of the treatment were also evaluated.
The mean total score decreased from 8.86 to 4.86 by the ninth week (P<.001) and to 2.55 by the end of the study (P<.001).
Three patients had rhinophyma, which was not sufficient for statistical
analysis. Still, their total scores regressed from 8 to 4 with treatment.
On eye examinations before treatment, 4 patients had conjunctivitis and 1
patient had corneal erosions. With topical medications and systemic isotretinoin
use, their conditions regressed by the third week. No patient became pregnant
while taking the medication. During treatment, 5 patients were detected to
have dry eyes, erythema, and a burning sensation in their eyes, effects that
were considered to be caused by isotretinoin use. All patients achieved relief
with the use of artificial tears.
During treatment, 18 patients had dry lips and 14 had facial xerosis,
which were relieved using topical emollients. Five patients had a mild to
moderate increase in serum triglyceride levels. All other results of laboratory
tests remained normal throughout the study.
The mechanism of action of isotretinoin for rosacea has not been clearly
identified. Histopathologically, isotretinoin has been shown to reduce lymphohistiocytic
perivascular infiltration edema and the number of ectatic vessels in patients
with rosacea.5 These conditions are assumed
to be due to the anti-inflammatory effects of the drug.5, 6
It has been shown that retinoid reduction of leukotriene and hydroxyeicosatetraenoic
acid products has decreased the neutrophil chemotactic effects of these compounds.7 The blockage of inflammatory response by isotretinoin
has been shown in vivo with a potassium iodide patch test as well.5, 8, 9
The adverse effects of isotretinoin use, such as cheilitis, facial dermatitis,
alopecia, epistaxis, muscle and joint pains, conjunctivitis, and cataracts,
have considerably limited patient adjustment.2-4
In addition, pronounced increases in serum triglyceride and cholesterol levels
may limit its usage.2-4, 10
In our small group, using a daily dose of 10 mg of isotretinoin, we did not
observe such adverse effects. Although we selected patients resistant to treatment
with a long history of complaints, our results confirmed the efficacy of isotretinoin
use, but whether remissions will continue after the cessation of treatment
is not addressed by our study.
F. Gülru Erdogan, MD
Konutkent 2, A7 Blok 35
06530 Ankara, Turkey
Pinar Yurtsever, MD
Demet Aksoy, MD
Fatma Eskioglu, MD
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