Erupción fija por luz solar, una serie de 13 casos en Bogotá, Colombia / Fixed Sunlight Eruption: A Series of 13 Cases in Bogotá, Columbia

Desde 1975 se han publicado algunos casos que asocian la radiación ultravioleta como un desencadenante de erupciones cutáneas fijas (erupción o exantema fijo por luz solar o síndrome de fotosensibilidad localizada de amplio espectro). Describimos los casos de 13 pacientes con esta dermatosis, 4 varones (30,8%) y 9 mujeres (69,2%), con edades comprendidas entre los 28 y los 56 años, atendidos en un centro de referencia en dermatología en Bogotá, Colombia. Las lesiones se localizaron en la cara interna de los muslos, los glúteos, la región poplítea, la axilar anterior y posterior y el dorso de los pies. La prueba de fotoprovocación logró la reproducción de las lesiones en todos los casos en las áreas afectadas y la histopatología reveló cambios similares a los descritos en los eritemas fijos por medicamentos. Esta enfermedad podría corresponder a un subtipo de erupción fija, aunque no se descarta que sea una dermatosis diferente con una patogenia común.(AU)

Few reports describing an association between UV radiation and fixed skin eruptions have been published since 1975. These reactions have received various names, including fixed sunlight eruption, fixed exanthema due to UV radiation, and broad-spectrum abnormal localized photosensitivity syndrome. We present a series of 13 patients (4 men [30.8%] and 9 women [69.2%]) aged between 28 and 56 years who were evaluated for fixed eruptions induced by UV radiation at a dermatology referral hospital in Bogotá, Colombia. The lesions were located on the inner thighs, buttocks, popliteal region, anterior and posterior axilla, and dorsum of the feet. Photoprovocation reproduced lesions in all the affected areas, and histopathology showed changes similar to those seen in fixed drug eruptions. While these UV-provoked reactions may be a type of fixed skin eruption, we cannot rule out that they may also be a distinct condition that simply shares a pathogenic mechanism with fixed eruptions.(AU)

[Translated article] Fixed Sunlight Eruption: A Series of 13 Cases in Bogotá, Colombia / Erupción fija por luz solar, una serie de 13 casos en Bogotá, Colombia

Desde 1975 se han publicado algunos casos que asocian la radiación ultravioleta como un desencadenante de erupciones cutáneas fijas (erupción o exantema fijo por luz solar o síndrome de fotosensibilidad localizada de amplio espectro). Describimos los casos de 13 pacientes con esta dermatosis, 4 varones (30,8%) y 9 mujeres (69,2%), con edades comprendidas entre los 28 y los 56 años, atendidos en un centro de referencia en dermatología en Bogotá, Colombia. Las lesiones se localizaron en la cara interna de los muslos, los glúteos, la región poplítea, la axilar anterior y posterior y el dorso de los pies. La prueba de fotoprovocación logró la reproducción de las lesiones en todos los casos en las áreas afectadas y la histopatología reveló cambios similares a los descritos en los eritemas fijos por medicamentos. Esta enfermedad podría corresponder a un subtipo de erupción fija, aunque no se descarta que sea una dermatosis diferente con una patogenia común.(AU)

Few reports describing an association between UV radiation and fixed skin eruptions have been published since 1975. These reactions have received various names, including fixed sunlight eruption, fixed exanthema due to UV radiation, and broad-spectrum abnormal localized photosensitivity syndrome. We present a series of 13 patients (4 men [30.8%] and 9 women [69.2%]) aged between 28 and 56 years who were evaluated for fixed eruptions induced by UV radiation at a dermatology referral hospital in Bogotá, Colombia. The lesions were located on the inner thighs, buttocks, popliteal region, anterior and posterior axilla, and dorsum of the feet. Photoprovocation reproduced lesions in all the affected areas, and histopathology showed changes similar to those seen in fixed drug eruptions. While these UV-provoked reactions may be a type of fixed skin eruption, we cannot rule out that they may also be a distinct condition that simply shares a pathogenic mechanism with fixed eruptions.(AU)

The lived experience of young adults with Fetal Valproate Spectrum Disorder, and the perspective of their parents: A qualitative study.

BACKGROUND: While research has investigated the physical and neurodevelopmental consequences following prenatal exposure to valproate, our understanding of individuals with a formal diagnosis of Fetal Valproate Spectrum Disorder (FVSD), particularly in the context of adulthood, remains limited. AIM: To investigate how symptoms and challenges of FVSD present in adulthood. METHODS: 30 people took part in the study, including 13 young adults aged between 21 and 37 years, 15 mothers, and 2 fathers. In all cases, valproate had been used for the treatment of maternal epilepsy. Data were collected using semi-structured interviews and analysed using thematic analysis. RESULTS: Six broad themes were identified: 1. Health and development, 2. Employment, 3. Daily living and independence, 4. Social skills and relationships, 5. Access to services, and 6. Impact on families. Individuals with FVSD live with an array of physical, mental, and developmental challenges that extend well beyond childhood, significantly altering their life course and that of their families. Challenges in obtaining employment, achieving independent living, and navigating social and romantic relationships become increasingly significant as individuals with FVSD age. Despite their persistent need for support, services for adults with FVSD are either limited or entirely absent. Recommendations from families were provided regarding optimized support systems. CONCLUSION: This study highlights the lifelong physical, cognitive, emotional, social and behavioural symptoms associated with FVSD. Young adults and their parents desire further research regarding the condition along with improved support and health services in adulthood.

The teratogenesis risk associated with antiseizure medication duotherapy in women with epilepsy.

PURPOSE: To investigate rates of occurrence of pregnancies associated with a foetal malformation (FM pregnancy rates) following simultaneous intrauterine exposure to two antiseizure medications in 524 pregnancies in women with epilepsy from the Australian Pregnancy Register who were treated simultaneously with various combinations and dosages of two antiseizure medications (duotherapy). RESULTS: FM pregnancy rates tended to be higher in those exposed simultaneously to two antiseizure medications, each of which was a statistically significant teratogen (valproate, topiramate, or carbamazepine), than when there was exposure to only one such teratogen. When there was exposure to only one such teratogen together with clonazepam or levetiracetam, for neither of which there was statistically significant evidence of heightened teratogenicity, the FM pregnancy rates also tended to be higher, but less so. When lamotrigine was the other component of the duotherapy with an established teratogen, FM pregnancy rates tended to be lower than that for the teratogen used as monotherapy. CONCLUSION: Leaving aside issues in relation to seizure control, our data suggest that it would be best to avoid using established teratogenic antiseizure medications (carbamazepine, valproate and topiramate) in combination with each other due to the increased FM risks. When combining an established teratogenic medication with a less teratogenic one, i.e. lamotrigine, levetiracetam or clonazepam, lamotrigine appears to be the safer option.

Use of isotretinoin among girls and women of childbearing age and occurrence of isotretinoin-exposed pregnancies in Germany: A population-based study.

BACKGROUND: Exposure to isotretinoin during pregnancy must be avoided due to its teratogenicity, but real-world data on its use are scarce. We aimed to describe (i) isotretinoin use in women of childbearing age in Germany; (ii) the occurrence of isotretinoin-exposed pregnancies; and (iii) malformations among children exposed in utero. METHODS AND FINDINGS: Using observational data from the German Pharmacoepidemiological Research Database (GePaRD, claims data from approximately 20% of the German population), we conducted annual cross-sectional analyses to determine age-standardized prevalence of isotretinoin use between 2004 and 2019 among girls and women aged 13 to 49 years. In cohort analyses, we estimated the number of exposed pregnancies by assessing whether there was prescription supply overlapping the beginning of pregnancy (estimated supply was varied in sensitivity analyses) or a dispensation within the first 8 weeks of pregnancy. Data of live-born children classified as exposed in a critical period according to these criteria were reviewed to assess the presence of congenital malformations. The age-standardized prevalence of isotretinoin use per 1,000 girls and women increased from 1.20 (95% confidence interval [CI]: 1.16, 1.24) in 2004 to 1.96 (95% CI: 1.92, 2.01) in 2019. In the base case analysis, we identified 178 pregnancies exposed to isotretinoin, with the number per year doubling during the study period, and at least 45% of exposed pregnancies ended in an induced abortion. In sensitivity analyses, the number of exposed pregnancies ranged between 172 and 375. Among live-born children, 6 had major congenital malformations. The main limitation of this study was the lack of information on the prescribed dose, i.e., the supply had to be estimated based on the dispensed amount of isotretinoin. CONCLUSIONS: Isotretinoin use among girls and women of childbearing age increased in Germany between 2004 and 2019, and there was a considerable number of pregnancies likely exposed to isotretinoin in a critical period. This highlights the importance of monitoring compliance with the existing risk minimization measures for isotretinoin in Germany.

Face-to-face: isotretinoin use and pregnancy outcome.

Isotretinoin has been used to treat severe acne for more than 40 years. There are no accurate data on the absolute risk of potential teratogenicity to all fetuses exposed to isotretinoin. According to current guidelines, isotretinoin should be discontinued at least 1 month before pregnancy. This study enrolled pregnant women who contacted the Clinical Pharmacology and Toxicology Unit for individual drug risk assessment between 2016 and 2020. Data on maternal characteristics and isotretinoin exposures were obtained at first consultation. After delivery, follow-up calls were conducted using a structured questionnaire. Of 2,323 pregnant women consulted, 1.3% (31/2,323) had systemic isotretinoin exposure during and before pregnancy. Of 31 prospectively followed pregnancies, eight terminated electively. Most elective terminations (7/8) were performed because of the fear of fetal malformation. The majority of continued pregnancies (16/23) resulted in healthy live birth. There were no major birth defects. In six pregnancies, intrauterine deaths (three first trimester, three second trimester) were reported. Cesarean section was performed in 70.5% (12/17) of all deliveries. The median gestational age at birth was 39, and no preterm births were reported. Local isotretinoin treatments in six cases were evaluated and presented additionally, and all babies were born healthy. Based on the results of this study, there was no evidence of major birth defect, mental disorder, or retinoid embryopathy associated with the use of isotretinoin in pregnancy. Not local use, but systemic exposure to isotretinoin is of great concern that results in pregnancy termination.

A new perspective on isotretinoin in pregnancy: Pregnancy outcomes, evaluation of complex phenotypes, and importance of teratological counselling.

OBJECTIVES: Teratogens are responsible for 5% of all known causes of congenital anomalies. Isotretinoin, a retinoic acid-derived agent, leads to congenital anomalies in 21-52% of cases when exposure occurs during pregnancy according to studies conducted before 2006. However, rates of congenital anomalies were much lower in later studies. The purpose of this study was to investigate the rates of congenital anomalies in isotretinoin exposure during pregnancy, isotretinoin exposure before pregnancy, and a control group unexposed to any teratogenic agents. STUDY DESIGN: In this cohort study, we divided pregnant women admitted to our center between 2009 and 2020 into two groups: isotretinoin exposure before and during the pregnancy (n = 77) and isotretinoin exposure before the pregnancy (n = 75). We selected the control group from among the non-teratogen exposed pregnant women with a simple random sampling method. Obstetricians calculated the ages of all pregnancies via ultrasound (USG) (crown-rump diameter for the first trimester; biparietal diameter and femur length for the second trimester). After birth, a pediatric genetics specialist examined all babies. Whole-exome sequencing (WES) was conducted on the babies who displayed complex phenotypes. RESULTS: Among the isotretinoin exposure before and during the pregnancy, isotretinoin exposure before the pregnancy, and the control groups, there were statistically significant differences in live births (respectively, 64.3 %, 88 %, 93.3 %), congenital anomalies (respectively, 28.6 %, 6.1 %, 1.4 %), miscarriages (respectively, 13 %, 2.7 %, 4 %), terminations (respectively, 32.5 %, 9.3 %, 2.7 %), and premature births (11.9 %, 16.7 %, 2.9 %) (respectively, p < 0.001, p < 0.001, p = 0.014, p < 0.001). We detected novel phenotypical features in five patients. CONCLUSIONS: Our study demonstrated that study design, long-term follow-up, teratological counseling, and implementation of advanced molecular analysis in complex phenotypes with novel phenotypical features are beneficial for understanding the association of congenital anomalies with isotretinoin exposure. While evaluating congenital anomalies, we detected statistically significant differences between isotretinoin exposure before and during the pregnancy vs control, but we did not detect any statistically significant differences between isotretinoin exposure before the pregnancy and controls. Another finding of the study is that WES might be an efficient way to evaluate complex phenotypes in isotretinoin-exposed babies; however, further research is required.

Use of Acitretin Among Girls and Women of Childbearing Age and Occurrence of Acitretin-Exposed Pregnancies in Germany.

BACKGROUND AND OBJECTIVE: Acitretin has long-lasting teratogenic properties. Therefore, pregnancies must be avoided during and within 3 years after acitretin treatment. We aimed to describe (i) acitretin use in women of childbearing age in Germany, (ii) the occurrence of acitretin-exposed pregnancies, and (iii) malformations among children exposed in utero. METHODS: Using 2004-2019 data from the German Pharmacoepidemiological Research Database (GePaRD-claims data from ~ 20% of the German population), we determined annual age-standardized prevalence of acitretin use among girls and women aged 13-49 years. In longitudinal analyses, we estimated the number of exposed pregnancies by assessing whether the exposure window assigned to the last dispensation before pregnancy (days covered by dispensation plus 3 years) overlapped the onset of pregnancy or whether there was a dispensation in the first eight weeks of pregnancy. Data of live-born children with in utero exposure to acitretin were reviewed to assess the presence of congenital malformations. RESULTS: The age-standardized prevalence of acitretin use per 1000 girls and women was 0.04 in 2019. We identified 35 acitretin-exposed pregnancies; 94.3% of these pregnancies were classified as exposed because they occurred within 3 years after stopping acitretin treatment. Among 18 live-born children linked to their mother, four children (22.2%) had congenital malformations (three children with a major malformation). CONCLUSIONS: We observed 35 acitretin-exposed pregnancies mainly because treatment ended too late before pregnancy. Approximately one in five children born from these pregnancies had malformations, highlighting the importance of drawing more attention to the long-lasting teratogenicity of this drug.

Prescription of sodium valproate to women of childbearing potential in Southern District Mental Health Services in New Zealand.

OBJECTIVE: This study aimed to assess the adherence to guidelines in the prescription of sodium valproate (SV) to women of childbearing potential (WOCP) in Southern District Mental Health Services (SMHS) in New Zealand (NZ). METHODS: Electronic records of women aged 18-54 who were newly prescribed SV by SMHS between the 1st of January 2018 and the 31st of December 2019, were retrospectively reviewed. Documentation of the following criteria was examined: pre-commencement pregnancy test, education education on the teratogenic potential of SV and/or the importance of avoiding unplanned pregnancy, information on contraception, and the rationale for prescribing SV over alternative treatments. RESULTS: Among the 3065 WOCP who had contact with SMHS during the study period, 51 women were newly prescribed SV and at risk of pregnancy. Twenty-one women (41%) had a recorded reason for prescribing SV over alternative treatments, four women (8%) underwent a pre-commencement pregnancy test, 10 women (20%) received information about the teratogenic potential of SV and/or the importance of avoiding unplanned pregnancy, and 21 women (41%) had documentation regarding contraception. CONCLUSION: The study findings indicate heterogeneous and suboptimal documentation of specific risks associated with SV use in WOCP in SMHS. Interventions are needed to improve prescribing and documentation practices.

Congenital malformations and preeclampsia associated with integrase inhibitor use in pregnancy: A single-center analysis.

BACKGROUND: Antiretroviral therapy (ART) decreases perinatal HIV transmission, but concerns exist regarding maternal and infant safety. We compared the incidence of congenital malformations and other adverse outcomes in pregnancies exposed to integrase inhibitor (INSTI) versus non-INSTI ART. SETTING: Single-site review of all pregnancies among women living with HIV between 2008 and 2018. METHODS: We used binomial family generalized estimating equations to model the relationship of congenital anomalies and pregnancy outcomes with exposure to INSTI or dolutegravir (DTG) versus non-INSTI ART. RESULTS: Among 257 pregnancies, 77 women received ≥1 INSTI (54 DTG, 14 elvitegravir, 15 raltegravir), 167 received non-INSTI, and 3 had missing data. Fifty congenital anomalies were identified in 36 infants. Infants with first-trimester DTG or any first-trimester INSTI exposure had higher odds of congenital anomalies than infants with first-trimester non-INSTI exposure (OR = 2.55; 95%CI = 1.07-6.10; OR = 2.61; 95%CI = 1.15-5.94, respectively). Infants with INSTI exposure after the second trimester had no increased odds of anomalies. Women with INSTI exposure had higher odds of preeclampsia (OR = 4.73; 95%CI = 1.70-13.19). Among women who received INSTI, grade ≥3 laboratory abnormalities were noted in 2.6% while receiving the INSTI and 3.9% while not receiving the INSTI, versus 16.2% in women who received non-INSTI. There was no association between INSTI exposure and other pregnancy outcomes. CONCLUSION: In our cohort, first-trimester INSTI exposure was associated with increased rates of congenital anomalies and use of INSTI during pregnancy was associated with preeclampsia. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy.

Metformin Versus Insulin and Risk of Major Congenital Malformations in Pregnancies With Type 2 Diabetes: A Nordic Register-Based Cohort Study.

OBJECTIVE: To assess the risk of major congenital malformations with metformin versus insulin in pregnancies with type 2 diabetes. RESEARCH DESIGN AND METHODS: This cohort study used four Nordic countries' nationwide registers of live and stillborn infants exposed to metformin or insulin during first trimester organogenesis. Main exclusion criteria were type 1 diabetes, polycystic ovary syndrome, fertility treatment, and exposure to other diabetes drugs. Adjusted risk ratios (RRs) and 95% CIs were estimated for any and cardiac malformations. RESULTS: Of 3,734,125 infants in the source population, 25,956 were exposed to metformin or insulin in the first trimester, and 4,023 singleton infants were included. A malformation was diagnosed in 147 (4.7%) of 3,145 infants with exposure to any metformin (alone or in addition to insulin) and 50 (5.7%) of 878 infants with exposure to insulin alone (RR 0.84, 95% CI 0.46-1.54). Among 2,852 infants exposed to metformin alone and 293 infants exposed to metformin in addition to insulin 127 (4.4%) and 20 (6.8%), respectively, had a malformation. The adjusted risk was not increased for either metformin alone (0.83, 0.44-1.58) or both metformin and insulin (0.98, 0.56-1.69) versus insulin alone. Corresponding RRs for cardiac malformations were 1.01 (0.55-1.84) for any metformin, 0.92 (0.47-1.81) for metformin alone, and 1.72 (0.76-3.91) for both metformin and insulin. CONCLUSIONS: No evidence of an increased malformation risk with metformin versus insulin in the first trimester was found. Results should be interpreted with caution since information on glycemic control was missing.

Absence of maternal-fetal adverse effects of Alternanthera littoralis P. Beauv. following treatment during pregnancy in mice.

Alternanthera littoralis P. Beauv is a plant native to Brazil that exhibits various beneficial activities including antioxidant, antibacterial, antifungal, antiprotozoal, anti-hyperalgesic, and anti-inflammatory properties. The aim of this study was to assess the impact of the ethanol extract of Alternanthera littoralis (EEAl) on reproductive outcomes, embryofetal development, and DNA integrity of pregnant female mice. Pregnant Swiss female mice were randomly assigned to three experimental groups (n = 10): controls were administered either 1% Tween 80 (vehicle), EEAl 100 mg/kg or EEAl 1000 mg/kg. Treatment was administered through gavage during the gestational period until day 18. On gestational days 16, 17, and 18, a peripheral blood sample from the tail vein was obtained for DNA integrity analysis (micronucleus test). After the last collection, animals were euthanized by cervical dislocation. Maternal organs and fetuses were collected, weighed, and subsequently analyzed. Reproductive outcome parameters were assessed by measurement of number of implants, live fetuses, and resorptions. Embryonic development was determined by adequacy of weight for gestational age as well as determination of external, visceral, and skeletal malformations. Data demonstrated that EEAl did not produce maternal toxicity at either dose associated with no marked alterations in any of the reproductive outcome parameters including implantation sites, live/dead fetuses ratio, fetal viability, post-implantation losses, resorptions, and resorption rate. However, EEAl 1000 group reduced embryofetal development by lowering placental weight. In addition, there was an increase in the frequency of external and skeletal malformations in the EEAl 1000 group, which could not be attributed to extract exposure as these values were within control levels. Based upon our findings, evidence indicates that the EEAl at the concentrations employed in our study may be considered safe for use during pregnancy and extracts of this plant show potential for development of phytomedicines to be used in pregnancy.

Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study.

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

Specific fetal malformations following intrauterine exposure to antiseizure medication.

OBJECTIVE: To investigate in the Australian Pregnancy Register of Antiepileptic Drugs patterns of fetal malformation associated with intrauterine exposure to particular currently available antiseizure medications taken by women with epilepsy. RESULTS: There was statistically significant evidence (P < 0.05) of an increased hazard of fetal malformation associated with exposure to valproate, carbamazepine, topiramate, zonisamide, and with conception after assisted fertilization, but a reduced hazard in the offspring of women who continued to smoke during pregnancy. Valproate exposure was associated with malformations in a wide range of organs and organ systems, carbamazepine and topiramate with hydronephrosis, topiramate also with hypospadias, zonisamide with spina bifida and assisted fertilization with heart and great vessel maldevelopment. CONCLUSIONS: Prenatal valproate exposure appears to interfere with the development of many if not all, fetal tissues. It seems likely that prenatal exposure to carbamazepine and topiramate, and possibly exposure to zonisamide, but also some process related to in vitro fertilization, may more selectively affect the normal development of particular fetal tissues or organs.