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July 1998

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Patients and Methods

Results

Comment

INDEX OF FIGURES AND TABLES


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Patients and Methods

Results

Comment

INDEX OF FIGURES AND TABLES


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to TOP

Patients and Methods

Results

Comment

INDEX OF FIGURES AND TABLES


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to TOP

Patients and Methods

Results

Comment

INDEX OF FIGURES AND TABLES


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Vignettes  
 
Efficacy of Low-Dose Isotretinoin in Patients With Treatment-Resistant Rosacea  
 

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.


 

Results


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.


 

Comment


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
Ankara
 
 

1. Nikolowski J, Plewig G. Rosazea: Orale Behandlung mit 13-cis Retinsaure. Hautarzt. 1980;31:660-661. MEDLINE

2. Schmidt JB, Gebhart W, Raff M, Spona J. 13-cis Retinoic acid in rosacea: clinical and laboratory findings. Acta Derm Venereol. 1984;64:15-21. MEDLINE

3. Mahrle G, Bauermeister-Jasso K, Enderer K. Roaccutan bei Akne und Rosacea. Z Hautkr. 1985;60:120-124. MEDLINE

4. Dicken CH. Retinoids: a review. J Am Acad Dermatol. 1984;11:541-552. MEDLINE

5. Plewig G, Nikolowski J, Wolff HH. Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol. 1982;6:766-785. MEDLINE

6. Nikolowski J, Hofmann C, Plewig G. In vivo tests to study antiinflammatory mechanisms of 13-cis retinoic acid. J Invest Dermatol. 1981;76:416-417.

7. Peck GL, DiGiovanna JJ. Retinoids. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in General Medicine. Philadelphia, Pa: JB Lippincott; 1987:2582-2609.

8. Plewig G, Wagner A. Anti-inflammatory effects of 13-cis retinoic acid: an in vivo study. Arch Dermatol Res. 1981;270:89-94. MEDLINE

9. Plewig G, Wagner A, Nikolowski J, et al. Effects of two retinoids in animal experiments and after application in acne patients: 13-cis-retinoic acid Ro 4-3780 and aromatic retinoid Ro 10-9359. In: Orfanos CE, ed. Retinoids: Advances in Basic Research and Therapy. Berlin, Germany: Springer-Verlag; 1981:219-235.

10. Hoting E, Paul E, Plewig G. Treatment of rosacea with isotretinoin. Int J Dermatol. 1986;25:660-663. MEDLINE
 
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