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Appearance of pyoderma faciale, an extraintestinal manifestation of inflammatory bowel disease that may mimic acne. Reprinted with permission from Cutis. 2008;81:488-490. ©2008, Quadrant HealthCom Inc. (39)
Source publication
Case reports have described a possible association between isotretinoin and inflammatory bowel disease (IBD). We critically appraised the literature on this association to assess whether it supports a causal relationship.
We systematically searched for case reports, case series, and clinical trials assessing this association. We then applied the Hi...
Context in source publication
Context 1
... must also consider the possibility of reverse causation: that IBD resulted in exposure to isotretinoin. Pyoderma faciale is a dermatologic condition that may mimic severe acne, but is in fact a known extra-intestinal manifestation of IBD that may precede its diagnosis (Figure 4) (24). Neutrophilic dermatoses such as Sweet's syndrome may also associated with IBD(25). ...
Citations
... Less common adverse events, reported in less than 10% of patients, included abnormal bloodwork, vision changes, hair loss, abdominal pain, menstrual irregularities, and other miscellaneous manifestations [6,7]. Some side effects remain speculative like inflammatory bowel disease, mood changes, and changes in bone mineralization [8][9][10]. There was no report of serious adverse events [11]. ...
Oral isotretinoin remains the most effective treatment for acne. The aim of this retrospective single-center cohort study was to estimate the prevalence of adverse events with the different oral isotretinoin brands used in acne treatment. The population consisted of all patients who consulted for acne between January 2015 and January 2020. The inclusion criterion was the initiation of treatment with oral isotretinoin. The exclusion criteria were the use of two or more brands during the same course of treatment and previous treatment with oral isotretinoin. Statistical analysis was carried out using Chi-square and Mann–Whitney tests. We analyzed 468 patients of whom 68.6% were female. The median age was 21 years. The median weight was 65 kg. The treatment was Roaccutane®, Curacné®, Acnotren®, Isosupra®, Contracné®, or Acnogen® in 44.2%, 28%, 14.5%, 10.5%, 1.7% and 0.4% of cases, respectively. Xerosis was the most frequently reported side effect regardless of the brand. The highest frequencies of hypercholesterolemia (25.6%) and eczema (13%) were noted with Roaccutane®; hypertriglyceridemia (16.8%), epistaxis (9.9%) and fatigue (3.1%) with Curacné®; excessive sweating (4.1%) and headache (4.1%) with Isosupra®; and abnormal liver function tests (11%) with Acnotren®. We found a significant correlation mainly between abnormal ASAT and Acnotren® (p = 0.009), hypercholesterolemia and Roaccutane® [OR = 1.652 (95% CI 1.056–2.585)], hypertriglyceridemia and higher body weight (p = 0.004). Factors related to the drug brand and to characteristics of acne patients could explain the variability in the prevalence of some adverse events.
... Contrarily, retinoic acid, a form of vitamin A enhances the intestinal barrier function by increasing various tight junction protein expressions, such as occludin, claudin-1, claudin-4, and zonula occludens-1. Impaired intestinal barrier function has been implicated in the pathogenesis of IBD; consequently, isotretinoin might prevent IBD development instead of triggering it [17]. However, isotretinoin also provides pleiotropic effects, including natural killer T-cell stimulation, B-cell differentiation, disruption of glycoprotein synthesis and epithelial tissue growth, apoptosis, and alteration of cytokines [17]. ...
... Impaired intestinal barrier function has been implicated in the pathogenesis of IBD; consequently, isotretinoin might prevent IBD development instead of triggering it [17]. However, isotretinoin also provides pleiotropic effects, including natural killer T-cell stimulation, B-cell differentiation, disruption of glycoprotein synthesis and epithelial tissue growth, apoptosis, and alteration of cytokines [17]. ...
... Hence, the study recommended a gastroenterologist referral if a previously healthy individual developed gastrointestinal symptoms during isotretinoin treatment [24]. Similarly, Crockett et al. studied the casual association between isotretinoin usage and IBD, which concluded that there is no adequate proof to confirm or refuse whether the association between IBD and isotretinoin exists [17]. The latter was supported by Bendezú-García et al. [25]. ...
Inflammatory bowel disease (IBD) is an autoimmune inflammatory disorder that affects the gastrointestinal system with an annual increase in incidence and prevalence worldwide. While the precise cause behind IBD remains obscured, certain genetic susceptibilities, in addition to environmental factors, may trigger the stimulation of the immunoinflammatory system against the gastrointestinal system, eventually resulting in IBD. Furthermore, certain medications have been proposed to increase the risk of developing IBD, such as isotretinoin. IBD has been reported during the post-marketing phase of isotretinoin. Subsequently, IBD development was added as a potential gastrointestinal adverse effect of isotretinoin. This review article aims to evaluate the possible association between isotretinoin exposure and the development of inflammatory bowel disease. We enrolled 32 relevant studies, including case reports, case-control, and cohort studies. The results were critically analyzed and reviewed by independent authors to answer the research question and achieve the primary endpoint.
... 3,5,18,19 A possible association between isotretinoin and in ammatory bowel disease has been reported, but current evidence is insu cient to support causality. 20,21 Recommended laboratory monitoring may include cholesterol and triglyceride levels and standard liver function tests .5 Per American Academy of Dermatology guidelines, oral isotretinoin is a rst-line choice for treatment of severe recalcitrant nodular acne . 5 The recommended daily dosing regimen and treatment duration vary among di erent populations. ...
Background:
Isotretinoin is a widely used and effective drug in the treatment of severe, recalcitrant, nodular acne. However, its poor aqueous solubility limits oral bioavailability and requires administration with a high-fat, high-calorie meal (HF/HC) for optimal absorption; poor patient adherence may decrease effective dosing and treatment efficacy.
Objective:
This review covers the properties of the lidose isotretinoin and micronized isotretinoin formulations and their use in acne therapy.
Method of literature search:
PubMed was searched using the terms acne, isotretinoin, formulations, isotretinoin efficacy, and safety. Additional articles were searched using reference lists from the obtained results.
Results:
Our review discusses pathology and approved treatment options for acne; provides mechanism of action of isotretinoin; presents clinical challenges associated with isotretinoin safety; and summarizes implications in clinical practice. Newer formulations show enhanced bioavailability in both fed and fasting states.
Limitations:
Few published studies of real-world use of the identified formulations were available.
Conclusion:
Newer drug delivery technologies can simplify isotretinoin use while maximizing bioavailability and efficacy. Based on our analysis, lidose isotretinoin and micronized isotretinoin improve oral bioavailability, pharmacological bioactivity, and increase therapeutic efficacy in patients who are unwilling or unable to consistently take the medication with an HF/HC meal. Healthcare providers should consider these formulations as tools to optimize treatment based on each patient's individual needs.
... (34) There is no obvious biological mechanism for an association between inflammatory bowel disease and isotretinoin, although several possible mechanisms have been speculated. (35) On the other hand the anti-inflammatory properties of all-trans-retinoic acid and its ability to enhance gut barrier function would suggest a possible beneficial effect of isotretinoin on inflammatory bowel disease. (35) The studies examining the association between isotretinoin and inflammatory bowel disease are summarised in Table 3. ...
... (35) On the other hand the anti-inflammatory properties of all-trans-retinoic acid and its ability to enhance gut barrier function would suggest a possible beneficial effect of isotretinoin on inflammatory bowel disease. (35) The studies examining the association between isotretinoin and inflammatory bowel disease are summarised in Table 3. A large French case control study, that included 7593 cases of inflammatory bowel disease and 30 372 controls, found that isotretinoin exposure was not associated with an increased risk for ulcerative colitis, whereas it was associated with a decreased risk for Crohn disease. ...
A significant barrier to the usage of isotretinoin has been concerns regarding its adverse effect profile. The dose-dependent mucocutaneous side effects of isotretinoin are well recognised and easily managed, particularly if a lower dose is used. A possible association with depression has gained widespread media attention and is a source of concern for many patients and their carers, but data from prospective studies and recent meta-analyses has been reassuring. Furthermore, there has been much confusion amongst both patients and physicians regarding a possible association with inflammatory bowel disease, as well the ocular and rheumatological adverse effects of isotretinoin. We provide an update on the evidence surrounding the adverse effects of isotretinoin, and discuss practical strategies to prevent and manage these adverse effects. We also discuss appropriate laboratory monitoring for patients taking isotretinoin.
... Nevertheless, individual idiosyncratic psychological adverse response to the drug cannot be excluded [209] . Similarly, the current evidence is insufficient to establish a causal association between isotretinoin and inflammatory bowel disease [210] . ...
Non-biologic therapies are useful in psoriasis for intermittent, rotational or combination treatment and in managing "difficult to treat" psoriasis, patients with minimal lesions, or who have achieved recommended cumulative dose or developed side effects/intolerance to conventional drugs, or where co-morbidities pose unusual challenges. Methotrexate, cyclosporine, acitretin, tar, anthralin, corticosteroids or calcipotriol ointments, and phototherapy are well established in psoriasis treatment. Hydroxycarbamide, azathioprine, leflunomide, mycophenolate mofetil, isotretinoin, fumarates, calcineurin inhibitors, peroxisome proliferator-activated receptor agonists, statins, pentoxifylline, sulfasalazine, colchicine, or various physical modalities often mentioned as non-standard therapies. They will remain important until an affordable, safe, effective, and remittiv therapy becomes available.
... Reddy et al. concluded that in a subgroup of patients, isotretinoin might serve as a trigger for IBD (15). Crockett et al. in their first study in 2009 mentioned that evidence was insufficient to confirm or refute a causal association, while in their second study they claimed that ulcerative colitis but not Crohn disease was associated with previous isotretinoin exposure (16,17). Unlike the former studies, Bernstein et al. concluded that isotretinoin exposure was not associated with an increased risk of developing IBD (18). ...
Background/aim:
Systemic isotretinoin treatment is an effective treatment modality for nodulocystic acne, the clinical use of which has been associated with reports of adverse events. We conducted a prospective study with the aim of determining the possible gastrointestinal and laboratory findings of nodulocystic acne patients during systemic isotretinoin treatment.
Materials and methods:
Seventy patients with nodulocystic acne completed the study. During the monthly follow-up visits, liver function tests and lipid profiles of the patients were evaluated and gastrointestinal system complaints were examined.
Results:
We recorded a significant elevation in liver function tests and lipid profiles of the patients, the most prominent elevation being in plasma triglyceride concentrations. We observed that nausea, dyspepsia, abdominal pain, and diarrhea were the rare gastrointestinal symptoms encountered during systemic isotretinoin therapy. Constipation and anorectal bleeding were relatively more common symptoms and there seemed to be a relation between these two symptoms.
Conclusion:
Our study is the first to analyze the gastrointestinal findings of patients during systemic isotretinoin treatment. Dermatologists and gastroenterologists must keep in mind that, as well as known laboratory findings like hypertriglyceridemia and elevated liver function tests, systemic isotretinoin therapy may also cause significant clinical gastrointestinal findings.
... Nevertheless, individual idiosyncratic psychological adverse response to the drug cannot be excluded [185] . Similarly, the current evidence is insufficient to establish a causal association between isotretinoin and inflammatory bowel disease [186] . ...
... Several retrospective analyses have been performed to determine whether there is an association between isotretinoin intake and IBD. [122][123][124][125][126]281,282 While 2 studies 123,282 have shown a potential relationship, more recent analyses 122,125,283 suggest no association between IBD and isotretinoin ingestion. The most convincing article suggesting an association between isotretinoin and UC 124 was directly refuted by a later analysis of the same database. ...
Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.
... However, case reports rarely provide proof of an association or causality as observations of case reports could have resulted from chance, uncontrolled confounding, recall bias, publication bias, and subjective presentation of case details (Crockett et al., 2009;Popescu and Bigby, 2013). Uncontrolled confounding by age is a possibility as the peak age of inflammatory bowel disease occurrence is in early adulthood and the peak age of isotretinoin use is ages 13 to 24 years (Crockett et al., 2009). ...
... However, case reports rarely provide proof of an association or causality as observations of case reports could have resulted from chance, uncontrolled confounding, recall bias, publication bias, and subjective presentation of case details (Crockett et al., 2009;Popescu and Bigby, 2013). Uncontrolled confounding by age is a possibility as the peak age of inflammatory bowel disease occurrence is in early adulthood and the peak age of isotretinoin use is ages 13 to 24 years (Crockett et al., 2009). Case reports of inflammatory bowel disease occurring among patients who received treatment for severe acne with isoretinoin do not rule out other causes (Popescu and Bigby, 2013). ...
... Of 2,214 cases of inflammatory bowel disease with isotretinoin use, 1,944 (87.8% were reported by attorneys, 132 (6.0%) were reported by physicians, and 112 (5.1%) were reported by consumers. In a review of published case reports and one case series on the use of isotretinoin and inflammatory bowel disease, Crockett et al. (2009) found that the results did not meet the Bradford Hill ...
Isotretinoin was approved by the Food and Drug Administration (FDA) in 1982 and revolutionized acne therapy. Soon afterwards, case reports appeared suggesting a link between inflammatory bowel disease and use of isotretinoin. As reviewed in this article, an increasing number of case-control and prospective (cohort) studies have been reported that examined associations between use of isotretinoin and inflammatory bowel disease. Published epidemiologic studies of the use of isotretinoin and risk of Crohn's disease and ulcerative colitis vary according to whether the design was a case-control study or cohort study and by other important design differences. The strengths and limitations of the studies, such as their ability to control for important confounding variables (e.g., the severity of acne and use of antibiotics), also differ widely. Results across epidemiologic studies have been inconsistent and most studies have not found a strong association or a dose-response relationship. Based upon results from laboratory studies, several biological mechanisms have been proposed to account for either a positive (pathogenic) or inverse (protective) association between isotretinoin and inflammatory bowel disease. Although epidemiologic study findings are generally consistent with a correct temporal relationship (i.e., exposure to isotretinoin preceded the onset of inflammatory bowel disease), Crohn's disease and ulcerative colitis often have an insidious onset with some symptoms occurring well before a clinical diagnosis of inflammatory bowel disease is made. Taken overall, results from epidemiologic (case-control and cohort) studies completed to date do not show a consistent association between isotretinoin use and risk of inflammatory bowel disease. There is no clear evidence of a causal link.
... [1][2][3][4][5] Other challenges have included reports of potential associations with depression, suicidal ideation, and inflammatory bowel disease. 1,2,[6][7][8][9][10][11][12][13][14][15][16][17][18] However, continued pharmacovigilance has demonstrated that these alleged risks have not been definitively associated with ISO as the causative factor and are not common enough to take away the accessability of ISO to the millions of patients with severe acne who have experienced major improvements in their quality of life after ISO treatment. 2,9,10,11,15,18 Continued vigilance and assessments of outcomes related to how ISO is utilized allows for frequent re-evaluation of how efficacy and safety can be optimized both in terms of clearance upon completion of the initial ISO treatment course and achieving prolonged remission without the need for retreatment. ...
