10.5826/dpc.1303a133
Introduction: Isotretinoin is an effective drug widely used in the treatment of severe acne. In this study, we tried to evaluate the incidence of anal fissures with clinical and laboratory side effects associated with isotretinoin.
Methods: The study evaluated 210 patients who received systemic isotretinoin treatment. Especially patients with constipation and anal bleeding were evaluated by the General Surgery clinic to arrange appropriate treatments.
Results: Of 210 patients included in the study, 138 (65.7%) were female and 72 (34.3%) were male, with a mean age of 23.7 years. The most common adverse event was dry lips in 206 (98.1%) patients. The mucocutaneous side effects were constipation 36 (17.1%), anal bleeding 18 (8.6%), mucosal erosion 10 (4.7%), anal fissure 7 (3.3%). Treatment was discontinued due to elevated liver function tests in 5 patients (2.3%), and because anal bleeding could not be controlled in 1 patient.
Conclusions: Isotretinoin is the most effective acne medicine used today. Clarification of the patients about the rarely seen side effects such as dryness, erosion, fissure and bleeding in the anal mucosa in addition to the common mucocutaneous side effects will ensure that patients are more cautious and increase their tolerance to the treatment.
text/xml
2160-9381
2859
en
Zeynep Şener Bahçe
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
constipation
Evaluation of the Incidence of Anal Fissures in Patients Who Systemic Isotretinoin Therapy for Acne
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-07-31
2022-09-21
2023-07-31
2023-08-24
e2023133
Dermatol Pract Concept
Introduction: Isotretinoin is an effective drug widely used in the treatment of severe acne. In this study, we tried to evaluate the incidence of anal fissures with clinical and laboratory side effects associated with isotretinoin.
Methods: The study evaluated 210 patients who received systemic isotretinoin treatment. Especially patients with constipation and anal bleeding were evaluated by the General Surgery clinic to arrange appropriate treatments.
Results: Of 210 patients included in the study, 138 (65.7%) were female and 72 (34.3%) were male, with a mean age of 23.7 years. The most common adverse event was dry lips in 206 (98.1%) patients. The mucocutaneous side effects were constipation 36 (17.1%), anal bleeding 18 (8.6%), mucosal erosion 10 (4.7%), anal fissure 7 (3.3%). Treatment was discontinued due to elevated liver function tests in 5 patients (2.3%), and because anal bleeding could not be controlled in 1 patient.
Conclusions: Isotretinoin is the most effective acne medicine used today. Clarification of the patients about the rarely seen side effects such as dryness, erosion, fissure and bleeding in the anal mucosa in addition to the common mucocutaneous side effects will ensure that patients are more cautious and increase their tolerance to the treatment.
Zeynep Şener Bahçe
2023/07/31
10.5826/dpc.1303a133
e2023133
Private Memorial Hospital, Department of General Surgery, Diyarbakır, Turkey
2160-9381
constipation
en
e2023133
Çıkım AÇ, Muammer Seyhan M. Efficiency and side effects of isotretinoin usage in the treatment of acne vulgaris. Türkderm. 2008;42:51-55.
Evaluation of the Incidence of Anal Fissures in Patients Who Systemic Isotretinoin Therapy for Acne
https://dpcj.org/index.php/dpc/article/download/2859/2198
         Evaluation of the Incidence of Anal Fissures
        in Patients who Systemic Isotretinoin Therapy
                           for Acne
                                           Hamza Aktas1, Zeynep Şener Bahçe2


1 Private Memorial Hospital, Department of Dermatology, Diyarbakır, Turkey
2 Private Memorial Hospital, Department of General Surgery, Diyarbakır, Turkey



Key words: acne vulgaris, isotretinoin, adverse events, anal fissure, constipation
Citation: Aktaş H, Şener Bahçe Z. Evaluation of the Incidence of Anal Fissures in Patients Who Systemic Isotretinoin Therapy for Acne.
Dermatol Pract Concept. 2023;13(3):e2023133. DOI: https://doi.org/10.5826/dpc.1303a133
Accepted: January 11, 2023; Published: July 2023
Copyright: ©2023 Aktaş et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Hamza Aktaş, Private Memorial Hospital, Department of Dermatology, Fırat Bulvarı Peyas Mahallesi no:12, 21080
Kayapınar/Diyarbakır, Turkey. Tel: 0505 6685239 Fax: +90 0412 314 66 17 E-mail: drhamzaaktas21@gmail.com




  ABSTRACT              Introduction: Isotretinoin is an effective drug widely used in the treatment of severe acne. In this
                        study, we tried to evaluate the incidence of anal fissures with clinical and laboratory side effects asso-
                        ciated with isotretinoin.
                        Methods: The study evaluated 210 patients who received systemic isotretinoin treatment. Especially
                        patients with constipation and anal bleeding were evaluated by the General Surgery clinic to arrange
                        appropriate treatments.
                        Results: Of 210 patients included in the study, 138 (65.7%) were female and 72 (34.3%) were male,
                        with a mean age of 23.7 years. The most common adverse event was dry lips in 206 (98.1%) patients.
                        The mucocutaneous side effects were constipation 36 (17.1%), anal bleeding 18 (8.6%), mucosal ero-
                        sion 10 (4.7%), anal fissure 7 (3.3%). Treatment was discontinued due to elevated liver function tests
                        in 5 patients (2.3%), and because anal bleeding could not be controlled in 1 patient.
                        Conclusions: Isotretinoin is the most effective acne medicine used today. Clarification of the patients
                        about the rarely seen side effects such as dryness, erosion, fissure and bleeding in the anal mucosa in
                        addition to the common mucocutaneous side effects will ensure that patients are more cautious and
                        increase their tolerance to the treatment.




Original Article | Dermatol Pract Concept. 2023;13(3):e2023133                                                                           1
Introduction                                                      Objectives
Acne vulgaris is a multifactorial disease of the pilosebaceous    Isotretinoin can also dry the anal mucosa, triggering fissure
unit that affects millions of people around the world to vary-    formation. In this study, we evaluated the side effects and
ing degrees. It affects about 85% of the young population.        especially the development of anal fissures, mucosal damage
Although it is primarily a disease of the adolescent period,      and rectal bleeding in patients receiving systemic isotretinoin
we observe it in neonatal and infancy periods, as well as pre-    therapy.
pubertal period and advanced age patients [1-3].
    Primary pathogenic factors of acne are increased sebum
                                                                  Methods
production, changes in keratinization process, follicular col-
onization with the natural immune activation of Propion-          The study included all patients who applied to dermatology
ibacterium Acnes and increased inflammation. Lesions of           clinic between 2018-2019 and received systemic isotretinoin
various variations such as come done, papule, pustule, nod-       therapy. The data were evaluated retrospectively (the local
ule and rarely cyst, characterize acne [4].                       ethics committee confirmed that formal approval was not re-
    The distribution of acne lesions is often the face, back,     quired for this retrospective audit of practice). Patients with
chest and shoulder areas where sebaceous glands are densely       missing data were excluded from the study. Participants were
located. Treatment of acne vulgaris varies based on the type,     informed about the study. Adolescents who agreed to partic-
extent and severity of the lesions. While topical antibiotics     ipate in the study provided signed informed consent forms.
and retinoid are the first choice in the treatment of mild           Before treatment, all patients and their families were
acne, systemic antibiotics and anti-androgenic agents are         questioned for hyperlipidemia and atherosclerosis. Patients’
used in moderate to severe acne [5,6].                            demographic data such as age and gender as well as body
    The most effective treatment method for severe acne is        weight, duration of the disease and the medications used
systemic isotretinoin. Isotretinoin is an agent that suppresses   were recorded. Before treatment, after treatment and at in-
sebum production and is effective on all pathogenic factors       tervals during treatment, the following laboratory values
that play a role in the formation of acne and has been used       were examined: hemoglobin, hematocrit, leukocyte, plate-
in the USA since 1982 in the treatment of severe nodulocys-       let count, erythrocyte sedimentation rate (ESR), alkaline
tic and persistent acne. However, as antibiotic resistance is     phosphatase (ALP), lactate dehydrogenase (LDH), aspartate
increasing worldwide, antibiotic monotherapy has begun to         aminotransferase (AST), alanine aminotransferase (ALT),
be used less frequently in acne treatment. Classically used       cholesterol (low density cholesterol (LDL) high density cho-
for nodulocystic acne, isotretinoin has become the drug of        lesterol (HDL), very low density cholesterol (VLDL), tri-
choice by dermatologists for moderate acne. It can also be        glyceride, creatine kinase (CK), and monthly beta-human
used in seborrheic dermatitis, acne rosacea, and perioral der-    chorionic gonadotropin (B-HCG) in female patients.
matitis resistant to classical treatment [7-9]. Treatment pro-       In the monthly follow-ups, all side effects were ques-
tocol recommended in clinical applications is the use of 0.5-1    tioned in detail. Especially, patients with gastrointestinal sys-
mg/kg/day over a period of 4-12 months to reach a total           tem complaints were referred to the General Surgery clinic.
dose of 120-150 mg/kg [10]. The most common side effects          The data of the patients, whose detailed examinations were
observed during isotretinoin use are mucocutaneous side           performed here, were recorded on the follow-up form. The
effects. Mucocutaneous side effects develop secondary to a        treatment of patients who could not tolerate side effects and
decrease in sebum production, thinning of the stratum cor-        had abnormal laboratory findings was terminated.
neum and changes in skin barrier functions, among which              The data obtained were statistically analyzed using the
the most common side effect observed is cheilitis. Almost all     software program SPSS 22.0. Continuous variables were
patients have cheilitis with varying severity. Other common       expressed as mean ± standard deviation, and variables in-
side effects of systemic isotretinoin are nosebleeds, general-    dicated by count were expressed as percentages. Chi-square
ized muscle aches, malaise, and dry eyes. The most important      tests were used in comparisons.
side effect of the drug is its teratogenic effect [11,12].
    Another system in which side effects of isotretinoin are
                                                                  Results
seen is the gastrointestinal system (GIS). Regarding the side
effects of GIS, Martin et al. have been the first to report a     Of 210 patients included in the study, 138 (65.7%) were female
case of proctosigmoiditis in 1987. Afterwards, a few more         and 72 (34.3%) were male, with a mean age of 23.7 (16-59).
cases have been reported on isotretinoin-related inflamma-        Mean body weight of the patients was 62.1 (38-105) kg.
tory bowel disease (IBD) [13,14].                                 The dose of isotretinoin ranged from 20 to 70 mg/day.




2                                                                     Original Article | Dermatol Pract Concept. 2023;13(3):e2023133
The treatment was regulated in such a way that 59.2%             7 patients (3.3%) had triglycerides and 3 patients had high
of our patients received 30 mg/kg/day and 36% received           cholesterol (1.4%). Treatment was discontinued due to ele-
40/mg/kg/day. The average duration of drug use by patients       vated liver function tests in 5 patients (2.3%), and because
was detected to be 5.36 months.                                  anal bleeding could not be controlled in 1 patient.
    The most common adverse event of isotretinoin was                 Patients with constipation and anal bleeding were ex-
dry lips in 206 (98.1%) patients. Then, dry eye 87 (41.4%),      amined in detail by the general surgery clinic. Medical
nosebleed 73 (34.7%), muscle pain 58 (27.6%), malaise 56         treatment, topical moisturizers and appropriate diet were
(26.6%), facial erythema 39 (18.5%), itching 36 (17.1%),         recommended to patients with fissure and mucosal erosion.
constipation 36 (17.1%), Xerosis 30 (14.2%), sun sensitivity     The dose of isotretinoin was reduced in three patients. In
21 (10%), joint pain 17 (8.9%), anal bleeding 18 (8.6%),         the controls, symptoms were observed to improve except for
headache 18 (8.6%), hair loss 15 (7.1% ), mucosal erosion        one patient.
10 (4.7%), mental change 9 (4.2%), menstrual irregularity 8
(3.8%) and anal fissure 7 (3.3%) were observed, respectively     Conclusions
(Table 1). No patient experienced abdominal pain. Five of
the patients who developed anal fissure were female and 2        Acne vulgaris is a chronic inflammatory disease that pri-
were male, and all had fissure with constipation and anal        marily concerns adolescents. This condition, which affects
bleeding. Only 2 of 10 patients with mucosal erosion had         85% of people, is mostly seen in young girls and boys aged
constipation. In patients with fissure and mucosal erosion,      [15,16]. Acne vulgaris is treated with the use of topical treat-
the isotretinoin dose ranged from 30-70 mg/day. It was de-       ments alone or topical and systemic treatments in combina-
termined that 8 of 36 cases with constipation already had        tion, depending on the severity of the disease [5,6,16,17].
constipation before treatment. The comparison between gen-            Isotretinoin, which is a synthetic retinoid, has been used
der and anal bleeding revealed that anal bleeding was more       for many years to treat nodulocystic acne. Today, it is used in
common in women (P = 0.029). In addition, no statistically       the treatment of moderate to severe acne, severe seborrheic
significant difference was observed between gender and           dermatitis, pyoderma faciale and gram-negative folliculitis,
constipation (P = 0.226), drug dose given and constipation       unresponsive to other treatments, including oral antibiotics.
(P = 0.067), drug dose given and anal bleeding (P = 0.290)       Isotretinoin is the only drug effective on all factors involved
and drug dose given and fissure formation (P = 0.835). There     in the pathogenesis of acne vulgaris and is the most effective
was no history of IBD in patients or their families.             treatment tool in the treatment of acne vulgaris with a remis-
    In 12 of the 210 patients (5.7%) enrolled in the study,      sion rate of up to 70%-89% [18-20].
elevations in liver function tests were identified, while             The most common side effects related to the use
                                                                 of   isotretinoin   have    mucocutaneous      characteristics.
                                                                 Many of these symptoms are tolerable, treatable, and
       Table 1. Prevalence of adverse effects.                   dose-dependent [19]. Cheilitis, dry nasal, dry eyes are the
 Adverse effect                       Patients, N (%)            most common finding and occurs in almost all patients.
 Dry lip                               206 (98.1%)               Apart from these side effects, facial erythema, muscle aches,
 Dry eyes                              87 (41.4%)                itching, malaise, joint pain and headache are other common
 Nose bleeds (epistaxis)               73 (34.7%)                side effects [21-25].
 Muscle aches (myalgias)               58 (27.6%)                     Many studies have been conducted on GIS side effects of
 Tiredness                             56 (26.6%)                systemic isotretinoin. First, Martin et al reported a case of
 Facial erythema                       39 (18.5%)
                                                                 isotretinoin-related proctosigmoiditis in 1987 [13]. Several
 Itching of the skin                   36 (17.1%)
 Constipation                          36 (17.1%)                other cases of isotretinoin-related IBD have been reported
 Xerosis                               30 (14.2%)                afterwards. This suggests that isotretinoin affects the intes-
 Sun sensitivity                       21 (10%)                  tinal mucosa [13,14,17,26]. Passier et al thought that three
 Headaches                             18 (8.6%)                 patients receiving isotretinoin with gastrointestinal system
 Anal bleeding                         18 (8.6%)                 complaints might have IBD, and in the colonoscopy exam-
 Joint aches (arthralgias)             17 (8.1%)
                                                                 ination, ulcerative colitis was detected in two patients and
 Hair loss                             15 (7.1%)
 Mood change                           9 (4.2%)                  Crohn disease in one [27].
 Heavy menstrual periods               8 (3.8%)                       However, in recent large-scale studies, no relationship be-
 Anal fissure                          7 (3.3%)                  tween isotretinoin and IBD could be demonstrated [28-31].
 Herpes simplex                        2 (1%)                    Among the rarer GIS, side effects of isotretinoin include ap-
 Abdominal pain                        0 (0%)
                                                                 pendicitis, esophagitis, anorexia and weight loss [32].




Original Article | Dermatol Pract Concept. 2023;13(3):e2023133                                                                 3
    Isotretinoin can affect the anal mucosa, and this can          develop accordingly can be prevented. However, further
promote mucous dryness, leading to mucosal erosion and             case-controlled studies with low dose or fixed-dose are
fissure formation. Anal fissure is a tear in the anoderm distal    needed in order to clarify the relationship between systemic
to the dentate line. The diagnosis of an anal fissure is made      isotretinoin therapy and anal mucosal dryness, constipa-
with the evaluation of the medical history, preferably on the      tion, anal fissure, and rectal bleeding.
proctology table, and basically through inspection. With a
thorough assessment of pain in the anal fissure, diagnosis
can be made with approximately 100% accuracy as early as
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Original Article | Dermatol Pract Concept. 2023;13(3):e2023133                                                                                   5
