Efficacy of oral retinoids for keratoacanthoma centrifugum marginatum.

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma. This condition is difficult to diagnose because of its large size and expansive nature and may be diagnosed as a malignant tumor. There are various treatments such as surgery and oral retinoids; however, limited studies have verified their effectiveness. Here, we report a case of KCM on the anterior chest of a 50-year-old woman and evaluate the efficacy of oral retinoids. In this case, oral retinoids were highly effective for KCM treatment. A total of 55 cases of KCM, including 54 previously reported cases, were reviewed, and their clinical characteristics and treatment were examined. In this report, 14 of 16 patients were effectively treated with oral retinoids, resulting in a treatment rate of 87.5%. Furthermore, even low-to-medium doses were sufficient for treatment and prevention. KCM can be misdiagnosed as a malignant disease based on its clinical features. Due to its large size and expansive nature, a wide excision may be performed; however, because oral retinoids have a very high response rate, an accurate diagnosis will help avoid an unnecessary wide excision.

Keratoacanthoma centrifugum marginatum after photodynamic therapy with good response to oral retinoids and topical 5-fluorouracil.

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterized by progressive peripheral growth, and usually devoid of deep invasion. Different systemic (oral retinoids) or topical treatments have been reported, but there is not a well-defined therapeutic protocol. We report the case of a KCM developing after photodynamic therapy (PDT) on the right leg of a 64-year-old woman. It was treated successfully with oral acitretin combined with topical 5-Fluorouracil + salicylic acid for 5 months. This is the first case of KCM developing after PDT and successfully treated with oral retinoid combined with topical treatment.

Case report: Hypertrophic lichen planus initially misdiagnosed as squamous cell carcinoma.

Fewer than 26 case reports describe hypertrophic lichen planus (HLP) misdiagnosed as cutaneous squamous cell carcinoma (cSCC). It can be difficult to distinguish between HLP and cSCC, as these two conditions share many clinical and histopathological characteristics. Patients who are misdiagnosed with cSCC often undergo unnecessary medical and/or surgical interventions before receiving a diagnosis of HLP and improving on HLP-directed therapy. This case series highlights the course of three female patients, referred to a single tertiary institution between 2018 and 2022, who were initially misdiagnosed with cSCC before receiving a diagnosis of HLP. We have emphasized the clinical and histopathological distinguishing features between HLP and cSCC, the pathogenesis of HLP, and current and new HLP-directed therapy. We hope that this case series serves as a reminder to dermatologists, dermatologic surgeons, and dermatopathologists to be aware of this diagnostic challenge.

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.

The implementation of risk minimization measures to prevent teratogenic pregnancy outcomes related to oral retinoid and valproate use in Belgium.

INTRODUCTION: Both oral retinoid and valproate containing medicines are highly teratogenic. Their use by women of childbearing age is controlled by risk minimization measures (RMMs) introduced by the European Medicine Agency, including the pregnancy prevention programme (PPP). In 2018, the RMMs were revised as previous measures were insufficient to prevent the use of these medicines during pregnancies. AIM & METHODS: A cross-sectional survey was conducted among patients, physicians and pharmacists to evaluate the implementation of the revised RMMs in Belgium. The primary outcome was compliance with key aspects of the PPP. Differences in compliance between oral retinoid and valproate stakeholders were investigated. The relationship between potential determinants (population characteristics and RMM usage) and compliance was studied via multiple logistic regression. RESULTS: A total of 317 eligible patients, physicians and pharmacists participated. The majority of the studied patients fail to comply with the PPP, mainly driven by poor implementation of pregnancy testing. A large number of healthcare providers is unaware of the available educational materials. CONCLUSION: It is likely that a substantial part of Belgian women of childbearing age using oral retinoids or valproate insufficiently meet the PPP requirements. We propose to better inform healthcare providers about the mandatory PPPs and available educational materials as well as to support them with the implementation of such programmes to improve the safe use of these teratogenic medicines.

Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review.

BACKGROUND: Harlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge. CASE PRESENTATION: We describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate. CONCLUSIONS: The association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.

Enfermedad de Darier tratada con acitretina oral / Darier's disease treated with oral acitretin

La enfermedad de Darier (ED) descrita por Darier y White en 1889, es un trastorno autosómico dominante de la queratinización, causada por una mutación del gen ATP2A2, localizado en el cromosoma 12 que codifica para la bomba de calcio ATP-asa de tipo 2 del retículo sarco-endoplásmico (SERCA-2), que conduce a una queratinización anormal (disqueratosis) y pérdida de la adhesión intercelular de los queratinocitos (acantolisis), con la consecuente formación de hendiduras suprabasales. Se caracteriza por alteraciones de la queratinización de la epidermis, uñas y mucosas. Presentamos el caso de un paciente masculino de 21 años, con lesiones cutáneas e histológicas características de (ED), quien realizó tratamiento con acitretina oral a una dosis de 30 mg al día, con respuesta favorable. Se plantea una alternativa terapéutica con retinoides orales para las lesiones crónicas y resistentes.

Darier's disease (DD) described by Darier and White in 1889 is an autosomic dominant disorder of keratinization, caused by a mutation of gen ATP2A2, located in the chromosome 12 encoding for calcium ATPase pump of sarcoplasmic reticulum type 2 (SERCA-2) leading to abnormal keratinization (dyskeratosis) and loss of intercellular adhesion of keratinocytes (acantholysis), with the consequent formation of suprabasal clefts. Characterized for abnormal keratinization in the epidermis, nails and mucosae. We present the case of a 21-year-old, male patient, with clinically and histologically confirmed (DD) treated with oral acitretin 30 mg for day with good response. We recommend an optional therapeutic treatment for chronic, itchy, recalcitrant lesions with oral retinoids.

Enfermedad de Darier tratada con acitretina oral / Dariers disease treated with oral acitretin

La enfermedad de Darier (ED) descrita por Darier y White en 1889, es un trastorno autosómico dominante de la queratinización, causada por una mutación del gen ATP2A2, localizado en el cromosoma 12 que codifica para la bomba de calcio ATP-asa de tipo 2 del retículo sarco-endoplásmico (SERCA-2), que conduce a una queratinización anormal (disqueratosis) y pérdida de la adhesión intercelular de los queratinocitos (acantolisis), con la consecuente formación de hendiduras suprabasales. Se caracteriza por alteraciones de la queratinización de la epidermis, uñas y mucosas. Presentamos el caso de un paciente masculino de 21 años, con lesiones cutáneas e histológicas características de (ED), quien realizó tratamiento con acitretina oral a una dosis de 30 mg al día, con respuesta favorable. Se plantea una alternativa terapéutica con retinoides orales para las lesiones crónicas y resistentes.(AU)

Dariers disease (DD) described by Darier and White in 1889 is an autosomic dominant disorder of keratinization, caused by a mutation of gen ATP2A2, located in the chromosome 12 encoding for calcium ATPase pump of sarcoplasmic reticulum type 2 (SERCA-2) leading to abnormal keratinization (dyskeratosis) and loss of intercellular adhesion of keratinocytes (acantholysis), with the consequent formation of suprabasal clefts. Characterized for abnormal keratinization in the epidermis, nails and mucosae. We present the case of a 21-year-old, male patient, with clinically and histologically confirmed (DD) treated with oral acitretin 30 mg for day with good response. We recommend an optional therapeutic treatment for chronic, itchy, recalcitrant lesions with oral retinoids.(AU)

Enfermedad de Darier-White tratada con isotretinoína oral / Darier-White disease treated with oral isotretinoin

La enfermedad de Darier-White (EDW) es un trastorno autosómico dominante; descrita por Darier y White en 1889, se caracteriza por alteraciones de la queratinización de la epidermis, uñas y mucosas. Presentamos el caso de un paciente masculino de 16 años con lesiones cutáneas e histológicas características de la EDW, que realizó tratamiento con isotretinoína oral a una dosis de 0,7 mg/kg/día por seis meses, con respuesta favorable. Se plantea una alternativa terapéutica con retinoides orales para las lesiones fjas, resistentes, crónicas y pruriginosas.

Darier-White Disease (DWD) is an autosomal dominant disorder, described by Darier and White in 1889, characterized by abnormal keratinization in the epidermis, nails and mucosae. We present the case of a 16-year-old, male patient, with clinically and histologically confrmed DWD treated with oral isotretinoin (0.7 mg/kg/day) for six months, with good response. We recommend an optional therapeutic treatment for chronic, itchy, recalcitrant lesions with oral retinoids.

Lamellar ichthyosis

Lamellar ichthyosis is an inherited autosomal recessive disorder characterized by non-bullous erythroderma and scaling at birth. We report a patient born encased in a collodion membrane, who later developed generalized, brownish, plate-like scales, anhidrotic skin, scarring alopecia, bilateral ectropion, with a family history of similar-looking skin condition. Skin biopsy demonstrated marked lamellated orthohyperkeratosis and areas of hypergranulosis. Therapeutic trial of four topical agents (extravirgin coconut oil, urea lotion, mineral oil and petroleum jelly) was done which gave minimal improvement of scaling and dryness. Oral retinoids (Acitretin) was then initiated and yielded better results.