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.
CONCLUSIONS: 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.

BACKGROUND: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description.
OBJECTIVE: 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: 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.

Symptomatic oral lichen planus (OLP) can be challenging to treat.
To compare the efficacy of oral acitretin plus topical triamcinolone acetonide (TAC), 0.1%, with TAC monotherapy in patients with symptomatic OLP.
This monocentric, investigator-initiated, placebo-controlled, investigator- and patient-blinded randomized clinical trial was conducted from December 2018 to June 2020 at the Postgraduate Institute of Medical Education and Research, a tertiary referral center in Chandigarh, India. Sixty-four patients 18 years or older with symptomatic OLP were recruited by consecutive sampling. Data were analyzed from July to December 2020.
The patients were randomized to receive either a combination of oral acitretin (25-35 mg/d) and TAC (treatment group) or TAC in combination with placebo (placebo group) for 28 weeks, with an additional 8 weeks of treatment-free follow-up after the end of treatment (36 weeks of total study duration).
The disease severity and treatment response were assessed using Oral Disease Severity Score (ODSS), Oral Health Impact Profile 14 (OHIP-14), and visual analog scale (VAS). The primary aim was to assess the number of patients achieving ODSS-75 (75% reduction in ODSS compared with baseline) in both groups at 28 weeks and at the end of 36 weeks.
Among 64 patients, 31 in the treatment group and 30 in the placebo group completed the study (mean [SD] age, 50.6 [15.2] years vs 49.2 [14.4] years; male-female ratio, 13:19 vs 16:16). Baseline ODSS, visual analog scale, and Oral Health Impact Profile 14 scores were comparable in both groups. In the intention-to-treat analysis, there was a statistically significant higher number of patients achieving 75% or higher reduction in ODSS in the treatment group compared with the placebo group at the end of 28 weeks (28 [88%] vs 15 [47%], a 41 [95% CI, 20-61] percentage point difference between groups; P < .001; Cramér V = 0.47) and 36 weeks (27 [84%] vs 13 [41%], a 43 [95% CI, 23-67] percentage point difference between groups; P < .001; Cramér V = 0.47). Relapses during the posttreatment follow-up of 8 weeks were low among patients in both treatment and placebo groups (1 [3%] vs 2 [6%], a 3 [95% CI, -13 to 7] percentage point difference between groups; P > .99; Cramér V = 0.07).
In this randomized clinical trial, the combination of oral acitretin and TAC was more effective than TAC monotherapy in patients with symptomatic OLP.
Clinical Trial Registry of India Identifier: CTRI/2018/11/016448.

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BACKGROUND: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics.
OBJECTIVE: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy.
METHODS: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022.
RESULTS: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1).
CONCLUSIONS: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

OBJECTIVE: To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs.
METHODS: This retrospective study used Taiwan\'s National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan-Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities.
RESULTS: The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65-1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment.
CONCLUSIONS: Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients.

UNASSIGNED: Erythrodermic psoriasis (EP) remains challenging to manage because it is rare and has complex complications. Although acitretin is recommended as an appropriate choice for EP, there is a lack of large-scale evidence.
UNASSIGNED: This study aims to assess the efficacy and safety of acitretin as systemic monotherapy in EP patients.
UNASSIGNED: We retrospectively analyzed data from patients with EP who received at least 3 months of acitretin as systemic monotherapy during hospitalization and out-patient follow-up from January 2005 to May 2021 at the Peking Union Medical College Hospital, China.
UNASSIGNED: The efficacy was clinically evaluated after 1, 2, 4, and 12 weeks of treatment, which was classified as a good response (>75% of lesions cleared), partial response (50%-75% cleared), moderate response (25-50% cleared), or no response (<25% cleared). Safety was assessed on the basis of physical examination results and significant changes in laboratory examination results after 12 weeks of treatment.
UNASSIGNED: Overall, 81 patients (79.0% men; mean age, 47.9 years) were included. The acitretin dose ranged from 20 to 60 mg/day (0.3 to 0.8 mg/kg/day). The rates of good, partial, and moderate responses were 0.0%, 2.5%, and 42.0% at 1 week; 3.7%, 34.6%, and 61.7% at 2 weeks; 29.6%, 58.0%, and 12.4% at 4 weeks; and 85.2%, 13.6%, and 1.2% at 12 weeks after treatment initiation, respectively. EP patients transformed from psoriasis vulgaris showed a higher good/partial response rate compared with that of EP patients that developed from pustular or articular psoriasis (44.6% vs. 14.3%, p = 0.035). Patients with concurrent infection showed a lower rate of good/partial response compared with that of those without concurrent infection (16.7% vs. 44.4%, p = 0.049). Adverse effects were seen in 45 (55.6%) patients in 12 weeks, and dyslipidemia (n = 31; 38.3%), xerosis (n = 24; 29.6%), and elevated liver enzymes (n = 6; 7.4%) were most commonly reported. Twenty-three patients were followed up for over 3 years, and six (26.1%) patients had EP recurrence.
UNASSIGNED: Acitretin as a systemic monotherapy showed satisfactory effectiveness for EP, especially in patients developed from psoriasis vulgaris and without infection.

BACKGROUND: Acitretin has been linked to the development of psychiatric disturbance.
OBJECTIVE: The aim of this study was to assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs).
METHODS: This is a nationwide matched cohort study. From Taiwan\'s National Health Insurance Research Database, adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs).
RESULTS: In total, 1,152 and 2,304 patients in the acitretin and the reference cohorts, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p < 0.001), mood disorders (12.81% vs. 7.67%; p < 0.001), and psychosis (7.21% vs. 4.63%; p < 0.001) in the acitretin cohort was significantly higher than that in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23-1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI: 1.56-4.33) or psoriatic arthritis (HR 3.23, 95% CI: 1.75-5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age.
CONCLUSIONS: Compared with DMARDs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients.

COVID-19 infection can have a poor prognosis, especially in patients with chronic diseases and those receiving immunosuppressive or immunomodulating therapies. This study aimed to investigate the severity of COVID-19 infection in patients with psoriasis and compare the infection severity for systemic treatments and comorbidities. We conducted a study in the dermatology clinics of five different centers in the Eastern Black Sea region of Turkey. Four hundred and eighty-eight patients were included, and 22.5% were confirmed as having COVID-19 infection. In our study, the frequency of hospitalization rates due to COVID-19 infection were similar (15.4%, 25.9% respectively) in patients receiving biological treatment and receiving non-biological systemic treatment (P=0.344). Hospitalization rates were higher in patients with hypertension, androgenetic alopecia, and acitretin use (P=0.043, P=0.028, P=0.040). In conclusion, current biologic treatments and non-biologic systemic treatments in patients with psoriasis did not appear to increase the risk of the severe form of COVID-19, except for acitretin.