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Isotretinoin epiphyseal closure
Isotretinoin epiphyseal closure -
Enable All Save Settings. Bright upgrade to Internet Explorer rise 9 or download Firefox, Testing, Safari or Chrome. Black outBenzac gel is used to drive the symptoms of moderate acne vulgaris. Benzoyl snowberry acts as an antimicrobial agent and travels and peels the outermost layer of skin. Famous antibacterial active against Propionibacterium acnes, a quick involved in acne vulgaris.
❾-50%}Isotretinoin epiphyseal closure.Isotretinoin misconceptions, misinformation still thrive
Harper says that for her patient, the presence of actual scarring outweighed the theoretical risk of PTC. Next: Association between isotretinoin and IBD. Those studies, however, did not control for an underlying diagnosis of acne, or the fact that most people treated with isotretinoin also have been treated with antibiotics.
Both of these factors could act as confounding variables, she says. Related: Research indicates IBD, depression risks with isotretinoin minimal. Later epidemiologic studies have attempted to control for these variables as much as possible, she says.
J Invest Dermatol. JAMA Dermatol. FDA reports are limited on the doses of isotretinoin associated with premature fusion. A prospective study with a large population of adolescents to examine the development of growth plates while taking isotretinoin therapy would add strength to the current understanding of its effects. Isotretinoin-induced premature fusion of growth plates seems to be associated with variable doses and durations of months to years.
The growth plates of both the proximal tibia and distal femur may be affected by isotretinoin. This study increases recognition among primary care providers about the potentially harmful side effects of isotretinoin, including premature epiphyseal closure in the pediatric population. This helps providers better educate patients about the risks and benefits of isotretinoin therapy in order for them to make informed decisions. Further clinical research is needed to assess the development of growth plates in the pediatric population while utilizing isotretinoin therapy.
Author contributions: Both authors provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; both authors drafted the article or revised it critically for important intellectual content; both authors gave final approval of the version of the article to be published; and both authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. Search in Google Scholar. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol ;— Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and cis-retinoic acid. N Engl J Med ;— Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects. Dermatol Surg ;—8.
Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma. Accutane drug label of Premature epiphyseal closure in a child receiving oral cis-retinoic acid. J Am Acad Dermatol ;—6. Premature epiphyseal closure in an adolescent treated by retinoids for acne: an unusual cause of anterior knee pain.
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JAMA Dermatol ;—9. Laboratory monitoring during isotretinoin therapy for acne: a systematic review and meta-analysis. JAMA Dermatol ;— A cross-sectional magnetic resonance imaging study of factors influencing growth plate closure in adolescents and young adults. Acta Paediatr ;— The growth plate: a physiologic overview. Efort Open Rev ;— The interaction between retinoic acid and the transforming growth factors-beta in calf articular cartilage organ cultures.
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J Am Acad Dermatol ;6 2 Suppl — Food and Drug Administration. Premature epiphyseal growth plate arrest after Isotretinoin therapy for high-risk neuroblastoma: a case series and review of the literature. Pediatr Blood Canc ;e Correction osteotomy for bilateral varus knee deformity caused by premature epiphyseal closure induced by hypervitaminosis A: a case report.
BMC Muscoskel Disord ; Genu varum deformity due to premature epiphyseal closure after treatment with isotretinoin for neuroblastoma: a case report. J Orthop Surg ; Dense metaphyseal bands and growth arrest associated with isotretinoin therapy. Studies published in English between and were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing.
We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded. Results: A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin.
Procedure: We identified patients from the Children's Hospital Los Angeles CHLA database with high-risk neuroblastoma diagnosed from to who experienced premature epiphyseal growth plate arrest and compared their characteristics to other patients with high-risk neuroblastoma.
We then performed a literature review of this complication. Read the Article. Back To All News.
Context : Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients.
Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia. Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U. Food and Drug Administration FDA has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne.
It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen. JOM Analysis of the effects of isotretinoin on the premature epiphyseal closure in pediatric populations: a literature review. Read the Article.
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Background: Vitamin A-derived retinoids have been reported to cause skeletal abnormalities ranging from hypercalcemia to premature epiphyseal closure. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment. Introduction: Premature epiphyseal closure associated with isotretinoin therapy in the pediatric population has been rarely reported in the literature. Context: Oral isotretinoin, a systemic retinoid and a vitamin A derivative, epiphyseal closure in patients treated with isotretinoin. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin.Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients. Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia.
Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U. Food and Drug Administration FDA has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne.
It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen. This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure.
Two databases were utilized for the literature review and were conducted at different time periods. Studies published in English between and were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors.
Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded. A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin.
The FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18 years of age. Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0. Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years.
There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment, which are much lower compared to the high doses utilized for neuroblastoma. Based on this study, isotretinoin appears to impact the growth plates of proximal tibia and distal femur.
A cause-and-effect relationship between isotretinoin and premature epiphyseal closure cannot be concluded. Isotretinoin, better known by its brand-name Accutane, is a vitamin A derivative primarily utilized for the treatment of acne in both adult and pediatric populations [ 1 ].
It works by inhibiting sebaceous gland functions. For children over 12 years of age, the recommended dose for the treatment of severe acne and moderate acne refractory to other treatment is 0. Multiple cycles of 6—8 doses may be needed depending on the evaluation of the tumor [ 3 ].
Additionally, isotretinoin has been utilized at doses of 0. Neuroblastoma and epidermolytic hyperkeratosis have sporadic prevalence, whereas acne vulgaris is common among the pediatric population.
Retinoids may also be utilized as a prophylaxis for squamous cell carcinoma and for the treatment of T-cell lymphoma [ 4 , 5 ]. Few cases of premature epiphyseal closure in patients with acne following the recommended doses of isotretinoin have been reported to the U. Clinical screenings are often performed to assess the side effects of isotretinoin on the liver, lipid profile, and other systemic symptoms, especially the risk of depression and suicide.
However, currently, there is no clinical or laboratory screening to assess the risk of growth arrest in pediatric patients on therapeutic doses of isotretinoin for the treatment of acne. During the process retinoid-induced epiphyseal closure, lab values of calcium, phosphorus, and alkaline phosphate that indicate bone health are typically normal [ 7 ]. X-ray and MRI of long bones may be useful to the findings of growth plate disruption.
In a few case reports, patients with premature epiphyseal closure complained of knee pain [ 8 , 9 ]. However, arthralgia is a common side effect of isotretinoin consumption, and it can mask the knee pain caused by growth plate fusion, potentially leading to a misdiagnosis. We will elaborate on reports of skeletal growth disruption following isotretinoin therapy exposure.
In addition to cases of premature epiphyseal closure, there are other adverse effects of isotretinoin use, including mucocutaneous effects of cheilitis chapped lips and xerosis dry skin , which are both among the most common side effects reported. Other mucocutaneous side effects include epistaxis nosebleed , desquamation skin peeling , pruritis itching , and photosensitivity.
Ocular manifestations of isotretinoin include dryness, irritation, and conjunctivitis. Musculoskeletal effects of arthralgia, myalgia, and back pain are also common. There is also a possible link between isotretinoin and depression and suicide. Other less common side effects reported include bone mineral density loss, hearing loss, pseudotumor cerebri, pancreatitis, anaphylaxis, and hematuria [ 10 ].
Additionally, isotretinoin is teratogenic and can cause severe birth defects and spontaneous abortion [ 11 ]. Females of reproductive age who are taking isotretinoin are required to comply with the iPLEDGE Program, a pregnancy prevention program for female patients on isotretinoin [ 12 ].
Laboratory testing and clinical measurements are recommended to monitor the symptoms and side effects associated with the oral intake of isotretinoin including possible elevated liver enzymes, hyperlipidemia, dry eyes, and epistaxis.
Patients are also routinely screened for depression and suicidal ideation [ 2 ]. However, growth screening of adolescents is not recommended as part of the clinical investigation for patients on therapeutic doses of isotretinoin for acne treatment [ 2 ]. Physiologic growth plate fusion varies in age among males and females. Growth plates were examined with MRI of volunteers between the ages of 14 and It is important to note that growth plate fusion due to normal physiology occurs at highly varying ages in both genders.
Thus, the developing growth plates in adolescents may be susceptible to deformities related to isotretinoin at variable ages. Puberty and adolescence also coincide with the development of acne. For this reason, many adolescents might be prescribed isotretinoin while their growth plates are still undergoing development and thus may have an increased risk of premature epiphyseal closure related to isotretinoin. To understand the impact of isotretinoin on skeletal growth, we first need to explain the physiology of skeletal growth.
Growth in height is determined by the vertical elongation of long bones, a process that is moderated by growth plates, which are also known as epiphyseal plates. The growth plate is the cartilaginous portion of the long bones, whose structure is comprised of chondrocytes suspended in a collagen matrix.
A variety of humoral factors, including growth hormone, parathyroid hormone, estrogen, cytokines, and various signaling pathways, coordinate the process of endochondral ossification [ 15 ]. One study suggested that the retinoic acid may impact growth plate closure through the degradation of the cartilage matrix component [ 16 ].
In vitro , retinoic acid was added to calf cartilage cultures and demonstrated reduction in cartilage matrix synthesis and enhancement of the catabolism of cartilage proteoglycans [ 16 ]. On the other hand, the dosing of systemic retinoids may be important in determining the fate of the epiphyseal plate. In one study of guinea pigs treated with various doses of vitamin A, the frequency of growth plate disruption increased at higher doses of vitamin A [ 17 ].
In this study, we investigate how isotretinoin at various doses and durations affects growth plates in pediatric populations through a literature review of case reports and FDA reports. We also aim to understand which parts of the growth plates are affected. Excluding duplicates, we identified studies in our initial search. Of these 32 studies, 28 were selected and four were excluded.
We included in our selection reports of patients worldwide under 18 years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin, and we limited our selection to articles published in the English language between and We further narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors.
Alazawi designed the study and conducted the initial search, review, and analysis of the data. Hendriksz conducted a further literature review, and both authors reviewed the results together. Studies that followed the inclusion criteria were utilized. Alazawi and Hendriksz agreed to include patients under 18 years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. Additionally, both authors agreed on the exclusion criteria. In total, 32 items were found, of which 28 were included and four were excluded based on the foregoing criteria.
Two case reports of patients on retinoid therapy with a history of growth hormone deficiency and premature epiphyseal closure were excluded. Case reports of growth plate abnormalities associated with other retinoid derivatives, such as fenretinide and etretinate, were also excluded because of their different pharmacokinetic profiles compared to isotretinoin [ 18 , 19 ].
We also excluded studies of premature epiphyseal closure due to trauma and fractures. Eventually, a total of 28 items were selected, including: one FDA Drug Label of Accutane brand-name for isotretinoin , one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin.
Premature epiphyseal closure and growth plate abnormalities were associated with various durations and doses of isotretinoin ranging from the lowest dose of 0. Between and , the FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18 years of age. Of those 41 reports, 22 reports were for the treatment of acne, one report was for the treatment of epidermolysis bullosa, and 18 reports had unspecified reasons for utilizing isotretinoin [ 20 ].
The data were extracted from the FDA Adverse Event Reporting System database and reorganized to highlight the key elements of the study [ 20 ]. Table 1 shows the results of the FDA reports. We omitted any duplicate reports and those with adult patients over 18 years of age. In the review of six case reports and one case series selected, nine patients were found to have growth plate abnormalities related to isotretinoin therapy.
Table 2 highlights the pertinent findings of the case reports and case series. In the Duvalyan et al. In the case reported by Matsuoka et al. Park et al. From the Milstone et al. Marini et al. In two other case reports of patients being treated for acne, unilateral knee epiphyseal deformities were associated with isotretinoin therapy at doses of 0.
Nineteen supplemental articles were selected: four articles with uses of isotretinoin, two articles with dosing guidelines for isotretinoin, four articles relating to the side effects of isotretinoin, one article about laboratory monitoring during isotretinoin therapy, three studies regarding the physiology of growth plate in adolescents, two articles about how isotretinoin impacts animals growth plates in vivo , two articles about the differences between isotretinoin and other retinoid derivatives such as fenretinide and etretinate, one article relating to acne and puberty, and one article looking at the incidence of isotretinoin prescriptions among adolescents.
Growth plate arrest has been reported in doses between 0. Most cases of growth failure are reported secondary to high-dose isotretinoin use for prolonged periods and are usually seen in the treatment of neuroblastoma.
In one study, three out of pediatric neuroblastoma patients developed premature epiphyseal closure after isotretinoin exposure with an incidence rate of 1. In another case report, a year-old female developed epiphyseal fusion secondary to isotretinoin therapy. She had a history of metastatic neuroblastoma, sparing the growth plates, and was diagnosed at 3 months old. She was evaluated by orthopedic surgeons for knee pain and deformity caused by tibial and femoral growth plate fusion, with the diagnosis supported by X-ray images and pathology findings [ 22 ].
The irreversible degradation of the cartilage matrix was most likely secondary to isotretinoin [ 22 ]. The patient was diagnosed with metastatic neuroblastoma to the left proximal humerus at the age of 6 years, for which he underwent chemotherapy and radiation. Furthermore, an MRI showed focal closure of the left humeral growth plate, which is the area where the metastatic neuroblastoma was located and on which radiation therapy was focused [ 23 ].
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