Acne recurrence after treatment with oral isotretinoin: 5-year follow-up

Received on: 10/05/2011
Approved on: 01/09/2011

This study was carried out at the Instituto
Lauro de Souza Lima (ILSL) - Bauru (SP),
Brazil.

Conflicts of interests: none
Financial support: none

Abstract

Introduction: Isotretinoin was initially used to treat severe inflammatory acne and is now widely recognized as an effective therapy for acne vulgaris. Many factors are associated with the recurrence of this condition, which ranges from 5.6-65.4%. There is much con- troversy regarding the importance and contribution of each factor.
Objectives: To determine the recurrence rate in patients who underwent full treatment with oral isotretinoin (dose between 120 and 150 mg/kg) and risk factors.
Methods: Retrospective study of data from 276 patients treated with isotretinoin. The analysis was carried out after a minimum of 30 months after the end of the treatment. Recurrence was defined as the appearance of new active lesions that required retreatment.
Results: While the recurrence rate in patients who underwent the full dose was 25.53%, it reached 81.03% in those who received an incomplete dose. The other studied factors presented no statistical significance.
Conclusion: Oral isotretinoin therapy is effective in producing a significant and long- term reduction of acne. Nevertheless, it is important to note that recurrence can occur, especially when recommended doses are not reached.

Keywords: ACNE VULGARIS, ISOTRETINOIN, RECURRENCE

INTRODUCTION

Acne, one of the most prevalent dermatologic disorders 1 , can affect patients'''''''' quality of life and cause relevant psychoso- cial impacts. Isotretinoin (13-cis-retinoic acid) was first used to treat serious inflammatory acne in Europe in 1976 and in the US in 1982. Its use transformed the therapeutics of serious and resistant acne, and it is now widely recognized as an effective treatment for acne vulgaris 2,4 .

This retinoid is known to have many action mechanisms through connections to specific receptors. It reduces the size of the sebaceous glands and inhibits their activity and lipidic pro- duction; modulates epithelium proliferation and differentiation; decreases the proliferation of Proprionibacterium acnes in the hair follicles; and has other immunological and anti-inflammatory effects 4,6 .

It is considered to be the most effective treatment for acne due to its capacity to induce complete and prolonged remission in all degrees of severity of the condition; recommended daily doses range between 0.5 and 2.0 mg/kg, with a total recom- mended dose between 120 and 150 mg/kg 78 . Nevertheless, notwithstanding fully completed treatments, recurrence is fre- quently seen in the literature and in daily practice. The condi- tion reappears in 5.6% to 65.4% of cases; 2 this great variation relates to diverse factors and their interaction such as; daily aver- age dose, cumulative dose, treatment duration, variations in patient characteristics (e.g., gender, age, degree and location). There is much controversy over the importance and contribu- tion of each factor in the rates of recurrence 9 .

METHODS

A retrospective study was conducted to determine the recurrence rate and potential risk factors linked to recurrence in patients who completed a treatment regimen of oral isotretinoin (accumulated dose of 120-150 mg/kg) in a public health service in Brazil (Instituto Lauro de Souza Lima/Bauru, SP, Brazil). The medical records of patients (n = 1,167) diag- nosed with and treated for acne from 01/01/2005 to 31/12/2006 in a general dermatology outpatient clinic were analyzed. During that period, 276 patients used free isotretinoin supplied by the Brazilian Health Ministry s exceptional medica- tions program. This study was carried out in compliance with the ethical rules of the Declaration of Helsinki.

More than half (n = 188) of the patients completed the treatment regimen, while 58 abandoned the treatment after at least 3 months of use. Patients were excluded from the analysis if they used the medication for less than 3 months or if they could not be contacted after the follow-up period.

Data was available on gender, age, severity, location, total dose of isotretinoin, and treatment duration. A treatment was considered to be complete at accumulated doses between 120 and 150 mg/kg. After a minimum of 30 months after the end of treatment, patients answered a telephone questionnaire about whether or not the acne reappeared and about their use of maintenance treatments and oral contraceptives during that period. Recurrence was defined as the emergence of active lesions that, in the patient''''''''s opinion, needed treatment.

The Chi-square Test and Fisher s Exact Test (5% signifi- cance level) were used in the statistical comparison between dif- ferent factors and the recurrence event.

RESULTS

Of a total of 188 who completed the treatment, 145 (77.12%) were male and 43 were female (22.87%). The average of age at the beginning of the treatment was 18.1 (17.4 for men and 20.2 for women).

Regarding acne severity, 22 patients (11.7%) were diag- nosed as Grade 2 (with papules and pustules), 146 (77.65%) as Grade 3 (with nodules and cysts) and 20 (10.63%) as Grade 4 (conglobata). Regarding location, 29 patients (15.42%) had lesions only on the face and 159 on the face and trunk (84.57%). No patients presented lesions only on the trunk. When studying the correlation between location and recur- rence, we found that those with acne only on the face had a 13.79% rate of recurrence, while those with lesions on the face and back had a rate of recurrence of 27. 67% (Table 1).

The average duration of isotretinoin use was 8.6 months (range 4-15 months). Treatments lasting 4-8 months presented a 23.16% recurrence rate, while treatments lasting longer than 8 months had a recurrence rate of 27.96% (Table 2).

Of the 58 women who used isotretinoin, only 43 complet- ed the treatment regimen and were included in the analysis. Of these, 17 continued using oral contraceptives after the end of the treatment. In this group, the recurrence rate was 29.41%, while among those that didn''''''''t use oral contraceptives after treatment the recurrence rate was 15.38% (Table 3).No use Only 26 patients (13.82%) used topical treatments during the observation period. Of these, 11 presented recurrence (42.31%), while of the 162 who did not use such treatments, 37 experienced a reappearance of lesions (22.8%) (Table 4).

Among female and male patients, there were 9 (20.93%) and 39 (26.89%) cases of recurrence, respectively. After the analysis of these variables regarding the presence of recurrence, none showed statistical significance.

On the other hand, when comparing the use of complete and incomplete doses of isotretinoin, there was a statistically significant difference regarding recurrence. Recurrence was ver- ified in 48 patients (25.53%) who received a complete dose. Of the 58 patients who did not use a complete dose but used the medication for more than 3 months, 47 (81.03%) presented recurrence (Table 5).

DISCUSSION

During more than 30 years of isotretinoin use, many authors have found great variability in recurrence rates. That is due to differences in criteria for including patients in studies, in the definition of recurrence, in daily doses and, in particular, in the cumulative dose and in the duration of the follow-up peri- od. Rates varying from 23.2% to 65.3% 10,12 illustrate this diffi- culty. In the present study, the recurrence rate after a complete treatment regimen was 25.53%.

Consistent with findings in the literature, the recurrence rate found in the present study for patients who had a total dose less than 120 mg/kg was 81.03%. This finding demonstrates that reaching the minimum recommended dose is the main factor linked to a long-term maintenance of the treatment effects.

The present study did not succeed in demonstrating significant correlations of individual factors (such as gender, age at the beginning of the treatment, acne severity and loca- tion of lesions) with the total risk of recurrence. There is no consensus in the literature regarding the location of the lesions; some authors have found more frequent recurrence in patients who presented lesions only on the face, while others found more frequent recurrence in patients with lesions on the back. Additionally, some authors found greater recurrence in women older than 25, while others found this trend in younger men 3 . Such findings can be due to differences in the studied populations.

It is inferred that the number of men who used isotretinoin in the study period was much greater than that of women due to the drug''''''''s teratogenic risks and the fact that many women can present significant improvement by using oral contra - ceptives. In addition, the average age at the beginning of treat- ment was 17.4 for men and 20.2 for women. This difference might be explained by the fact that the women tried other med- ications for longer due to the teratogenic risks.

Although the rate of recurrence was slightly greater in patients who took longer to reach the full dose, when they did so this fact was not statistically significant. Therefore, there seems to be no difference between reaching the full dose in a shorter period with higher daily doses and implementing gradual increases of the daily dose until the full dose is reached.

Contrary to the authors'''''''' expectations, the use of oral con- traceptives following a completed treatment regimen did not reduce recurrence rates. Even when analyzing all female participants (both incomplete and full doses), there was no sta- tistically significant difference regarding the use of oral contra- ceptives. This might be explained by the small size of the sam- ple of women studied.

The high recurrence rate verified in patients who used topical medications after their treatment was complete (42.31%) compared to participants who did not use such substances (22.84%) suggests the existence of a bias, given that patients who begin to present new lesions are more likely to use topical med- ications. Furthermore, the number of topical medication users was very small. Even so, the variable for using topical medica- tions after a successful outcome did not significantly affect the rate of recurrence.

CONCLUSION

Oral isotretinoin is an effective treatment that produces a relevant and long-lasting reduction of acne. Nevertheless, it is important to note that the condition frequently recurs, especially when recommended doses are not reached.

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