Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. CONCLUSION: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Pityriasis Rubra Pilaris - a difficult path to optimal treatment. Case report.

Pityriasis Rubra Pilaris is a rare, chronic inflammatory dermatosis of unknown etiology, presenting with erythema and papular eruptions. Treatment is difficult due to the lack of causal therapy, guidelines and requires an individualized approach. The most common treatments are systemic retinoids, immunosuppressants, phototherapy and biological therapy. This article presents the case of a 73-year-old man suffering from type 1 pityriasis rubra pilaris. The patient was initially treated with acitretin, which was discontinued due to hypogammaglobulinemia. This rare side effect of acitretin has not been previously published. As a second-line treatment, the patient received methotrexate, but with no clinical improvement after 3 months and an increase in skin pruritus. Finally, the use of isotretinoin resulted in significant clinical improvement and was well tolerated.

Acitretin induced primary hypothyroidism in Darier's disease: A rare case report.

ABSTRACT: Acitretin is a synthetic, second-generation retinoid mainly used for the treatment of Darier's disease (DD), which impacts biological processes by binding to a nuclear receptor from the corticosteroid/thyroid receptor superfamily, thereby altering gene expression. Our report outlines the case of a 41-year-old male patient who has received a clinical diagnosis of DD and does not exhibit any other coexisting comorbidities, who developed hypothyroidism posttreatment with acitretin, an unusual and rare side effect of the drug. His baseline routine investigations fell within normal limits before the initiation of acitretin. Acitretin-induced hypothyroidism was treated with thyroxine. Although a good therapeutic response was seen with acitretin, it could not be continued due to the development of side effects and was continued on topical therapy. This case emphasizes the likelihood of adverse effects linked to therapeutic levels of acitretin in patients without any prior history and signifies the critical importance of consistent blood monitoring throughout drug therapy.

Oral Psoriasis Therapies.

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.

Plexin B2 tissue expression and related gene polymorphisms in psoriasis and their relation to NB-UVB and Acitretin therapy.

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.

Combination of secukinumab and acitretin for generalized pustular psoriasis: A case report and review of literature.

Generalized pustular psoriasis (GPP) is characterized by painful and occasionally disfiguring cutaneous manifestations with sepsis-like systemic symptoms, and is a rare severe variant of psoriasis. Currently, there is no standard treatment for GPP. Here, we report a case of a female patient with ankylosing spondylitis (AS) and mild scalp psoriasis, who developed GPP and alopecia following three courses of adalimumab therapy. The patient's condition gradually improved following cessation of adalimumab and treatment with secukinumab and acitretin. After eight weeks of treatment, the patient achieved almost complete clearance of her psoriasis, her alopecia improved, and her AS was relieved. Therefore, we believe that a combination of secukinumab with acitretin may be a rational approach for the treatment of severe GPP.

Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 HRAS-positive variant patients.

BACKGROUND: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. OBJECTIVES: To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. METHODS: We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). CONCLUSIONS AND RELEVANCE: This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.

A report on the safety of acitretin use in patients with renal failure on haemodialysis.

Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end-stage renal disease (ESRD) on haemodialysis (HD). However, these patients often lack medication choices and in certain clinical scenarios the benefits of acitretin may outweigh the potential risks. We identified 24 patients with ESRD on HD undergoing acitretin treatment from the Duke and Vanderbilt University Medical Centers. While adverse effects were common, they were not a frequent cause of treatment discontinuation among patients. We also found no association between acitretin treatment and hospital admissions or mortality. Lastly, we found statistically significant increases in alkaline phosphatase (ALP; P = 0.03) and total bilirubin (P < 0.001) when patients were receiving acitretin and HD compared with baseline. However, there was no dose dependency or temporal association with acitretin or HD initiation. Based on these preliminary findings, we find that acitretin may safely be used in patients receiving HD, with close monitoring of ALP and bilirubin.

Multiple Keratoacanthoma-like Syndromes: Case Report and Literature Review.

Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic syndromes. Syndromes with multiple keratoacanthoma-like lesions have been documented as multiple self-healing squamous epithelioma (Ferguson-Smith syndrome), eruptive keratoacanthoma of Grzybowski, multiple familial keratoacanthoma of Witten and Zak Muir-Torre syndrome, and incontinentia pigmenti. The treatment approach of those entities is challenging due to the numerous lesions, the lesions' undefined nature, and the co-existence of other malignant skin tumors. Herein, we report a case of a 40-year-old woman who developed multiple treatment-resistant Ferguson-Smith-like keratoacanthomas with a co-existing large and ulcerated invasive squamous cell carcinoma and microcystic adnexal carcinoma on the scalp. Multiple keratoacanthomas on her extremities were successfully treated with oral acitretin (0.5 mg/kg/day) in combination with topical Fluorouracil (5-FU) 5%, while excision and plastic surgery restoration were performed to treat the ulcerated cancer lesion on her scalp. Due to the interesting nature of this rare syndrome, we performed a literature review including case reports and case series on multiple-KA-like lesions syndromes and focusing on diagnosis and therapy approaches. We also conducted a comparison of patient reports, which included assessing the clinical appearance of the lesions and evaluating the success and progress or the failure of various treatment approaches that were implemented.

Successful treatment of generalized pustular psoriasis with guselkumab.

The purpose of the article: Generalized pustular psoriasis (GPP) is a rare auto-inflammatory disease. Patients with GPP may develop life-threatening complications, including sepsis, acute renal failure, neutrophilic cholangitis, high-output congestive heart failure, acute respiratory distress syndrome and death. The therapy of GPP is very limited and the course of the disease is unpredictable.Materials and methods: We report a 60-year-old woman presenting with widespread and confluent erythematous-desquamative plaques with numerous small pustules covering almost 70% of the body surface area. Over the past years patient had undergone different types of conservative treatment regimens including topical therapy, acitretin, cyclosporin, methotrexate and long-term treatment with systemic corticosteroids. Considering the patient's overall clinical condition, we proceed to initiate the biologic therapy with guselkumab.Results: Guselkumab (anti-IL-23) in the standard dose of 100 mg was administered subcutaneously at weeks 0, 4 and followed by a maintenance dose every 8 weeks. The remission of GPP was observed already after 12 weeks of treatment. The maintenance treatment in the period of 18 months shows stable clinical response.Conclusions: Our results support the evidence that guselkumab could provide an effective therapeutic approach in the treatment of GPP.

A retrospective analysis of 65 patients with acrodermatitis continua of Hallopeau.

There are limited data on acrodermatitis continua of Hallopeau (ACH), particularly among Asian populations. The primary aim was to evaluate the clinical features of ACH and treatment approaches in a sizeable multicentre Asian cohort. We analysed data from adult patients diagnosed with ACH. Of 65 patients with ACH, seven patients had ACH with GPP. Females were more frequently affected in both conditions. Five (71.4%) developed GPP 5-33 years after ACH onset, while two (28.6%) developed GPP concurrently with ACH. The onset age for ACH with GPP (27.9 ± 13.6 years) was earlier than that of isolated ACH (39.8 ± 17.3 years). Metabolic comorbidities were common. ACH exhibited a chronic persistent course. Among systemic non-biologics, acitretin was the most frequently prescribed, followed by ciclosporin and methotrexate. Acitretin and ciclosporin demonstrated similar marked response rates, which surpassed that of methotrexate. Regarding biologics, a marked response was more commonly observed with interleukin-17 inhibitors than with tumour necrosis factor inhibitors. Females are predominant in both conditions. The onset age for ACH among Asian patients is earlier (late 30s) than that for Caucasian patients (late 40s). Interleukin-17 inhibitors may be more effective than tumour necrosis factor inhibitors in managing ACH.

Advances in treatment for lipoid proteinosis (Urbach-Wiethe disease): a case report and systematic review.

BACKGROUND: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis, caused by mutations in the ECM1 gene. This results in the deposition of periodic acid-Schiff (PAS)-positive, hyaline-like material on the skin, mucosae and internal organs. OBJECTIVES: To present a case report of LP and a systematic review to synthesize the scientific literature on the management of this uncommon and frequently missed diagnosis. METHODS: We present a case report of a 48-year-old man with LP who exhibited significant improvement after oral acitretin therapy. To address the lack of large case-control studies on LP treatment, we performed a systematic review of the literature following the PRISMA 2020 criteria. The search was conducted in PubMed, Web of Science, Cochrane and Scopus databases from inception until June 2023. To assess the methodological quality of case reports and case series, we used the Joanna Briggs Collaboration critical appraisal tool. RESULTS: We included 25 studies that met eligibility criteria. Data from 44 patients with a histopathologically confirmed diagnosis were analysed. Treatment ranged from systemic therapies (acitretin, etretinate, dimethyl sulfoxide, corticosteroids, penicillamine) to surgical or laser procedures. Regarding methodological quality, the main discrepancies arose in the reporting of participant characteristics and treatment interventions. CONCLUSIONS: Low-dose oral acitretin could have potential in managing LP, exhibiting fewer side-effects compared with other therapeutic agents. Further research is needed to establish more comprehensive and evidence-based treatment guidelines.

Efficacy of alitretinoin in the treatment of Darier disease: a case report.

Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a seborrheic and intertriginous distribution. The absence of specific targeted medications complicates the treatment process, and managing resistant cases can prove challenging due to recurrent exacerbations that may result in serious complications such as secondary bacterial and viral infections. Treatments of choice include antiseptics, topical corticosteroids, and systemic retinoids, mainly acitretin and isotretinoin. We report the case of a female patient with Darier disease that was unsuccessfully treated with acitretin and isotretinoin but showed significant improvement with alitretinoin. Previous reports on the efficacy of alitretinoin in Darier disease are reviewed.

Case for diagnosis. A pruritic eruption of keratotic papules over the face and neck

Abstract Generalized eruptive keratoacanthoma of Grzybowski is a rare variant of multiple keratoacanthomas counting with about 40 cases reported. It is a chronic and progressive disease for which none of the described therapeutic options has been entirely satisfactory. We report a case of an 83-year-old female who presented with a 3-month history of extremely pruritic, multiple, skin-coloured to erythematous to brownish, millimetric papules, with a keratotic centre. Histological examination of an incisional biopsy was consistent with the diagnosis of keratoacanthoma. The patient started acitretin 25 milligrams daily with a complete resolution of pruritus and regression of numerous lesions.

Eritrodermia ictiosiforme congénita ampollosa: a propósito de un caso / Congenital bullous ichthyosiform erythroderma

La eritrodermia ictiosiforme congénita ampollosa es una entidad poco frecuente, con herencia autosómica dominante, pero un 50% se presenta por mutaciones de novo; se caracteriza en su fase inicial por eritrodermia y aparición espontánea de ampollas. Posteriormente las ampollas disminuyen en frecuencia y aparece una descamación que compromete toda la superficie corporal. No suele haber afectación palmoplantar ni de las mucosas. Su tratamiento de primera línea son los retinoides sistémicos junto a los cuidados de la piel

Congenital bullous ichthyosiform erythroderma is a rare entity, with autosomal dominant inheritance, but in 50% of cases it is presented by de novo mutations; is characterized in its initial phase by erythroderma and spontaneous appearance of blisters. Subsequently the blisters decrease in frequency and appears a scaling that compromises the entire body surface. There is usually no palmoplantar or mucosal involvement. Its first-line treatment is systemic retinoids along with skin care