-
Pediatric Investigation Sep 2023Keratinopathic ichthyosis (KPI) represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the , , or genes. In KPI, the...
IMPORTANCE
Keratinopathic ichthyosis (KPI) represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the , , or genes. In KPI, the relationship between genotype and phenotype is complex.
OBJECTIVE
To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.
METHODS
Clinical data were collected from 13 children diagnosed with KPI, and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel, and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.
RESULTS
Genetic analysis identified missense mutations in either or in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis. A missense hotspot mutation in was identified in one patient with superficial epidermolytic ichthyosis. Additionally, two truncation mutations in were detected, leading to the development of generalized ichthyosiform erythroderma. Ear malformation and ectropion at birth, scalp involvement, and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.
INTERPRETATION
We analyzed the genotype-phenotype correlations in KPI, revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics. Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.
PubMed: 37736367
DOI: 10.1002/ped4.12391 -
Actas Dermo-sifiliograficas Apr 2024
Topics: Humans; Acitretin; Hair Diseases; Hair
PubMed: 37709132
DOI: 10.1016/j.ad.2023.01.022 -
Dermatology and Therapy Oct 2023Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease that affects men and women of all ages, including children. PRP is characterized by follicular and...
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease that affects men and women of all ages, including children. PRP is characterized by follicular and palmoplantar hyperkeratosis and salmon-colored scaling plaques. The exact pathogenesis of PRP is still unknown; most PRP cases are acquired, but some cases may show a familial occurrence, often associated with a mutation in the CARD14 gene. Due to the rarity of PRP, treatment recommendations are based mainly on case reports, small case series and expert opinions and still represent a major therapeutic challenge, especially in children. A growing number of reports on treatment with biologicals, particularly anti-TNFα, has been published. However, an involvement of the IL-23/Th17 axis in both psoriasis and PRP pathogenesis may suggest that this pathway may be a potential therapeutic target. Here, we present three pediatric patients with PRP successfully treated with risankizumab. All patients exhibited a severe course of PRP and lack of response to conventional therapy, including acitretin, cyclosporine and phototherapy. A single dose of 75 mg risankizumab resulted in almost complete clearance of skin lesions in case 1 and 2 at week 4. In patient 3, clear skin was achieved after the second administration of risankizumab (150 mg). All patients continue the treatment with risankizumab, and no adverse effects have been reported up to the present time. Our study demonstrates that risankizumab, an IL-23 blocker, shows good efficacy and safety among pediatric patients with PRP.
PubMed: 37704911
DOI: 10.1007/s13555-023-01005-y -
Acta Orthopaedica Et Traumatologica... Jul 2023This study aimed to determine whether isotretinoin and acitretin have beneficial effects on neural tissue damage following acute spinal cord injury.
OBJECTIVE
This study aimed to determine whether isotretinoin and acitretin have beneficial effects on neural tissue damage following acute spinal cord injury.
METHODS
Thirty-six rats were randomly divided into 6 groups: control, sham spinal cord injury, spinal cord injury with isotretinoin 15 mg/kg for 14 days, spinal cord injury with isotretinoin 15 mg/kg for 28 days, spinal cord injury with acitretin 10 mg/kg for 14 days, and spinal cord injury with acitretin 10 mg/kg for 28 days. The damage to the spinal cord was formed by the clip compression technique. A neurological evaluation was conducted on days 1, 14, and 28. All rats were sacrificed following the treatment period, and samples of their spinal cords were collected for histopathological analysis.
RESULTS
The inclined plane angle was significantly increased on the 14th and 28th days in the isotretinoin 15 mg and acitretin 10 mg groups, compared to the spinal injury group (P=.049 and P=.009, respectively). The Drummond-Moore criterion was significantly higher in the acitretin 10 mg group than in the injury group (P=.026). Cleaved Caspase-3 expression was similar in the isotretinoin 15 mg day 28 group and the control group (P > .05), but significantly decreased in the acitretin 10 mg 14th-day and acitretin 10 mg 28th-day groups compared to spinal injury isotretinoin 15 mg 14th-day and isotretinoin 15 mg 28th-day groups (P < .05).
CONCLUSION
This was the first study elaborating that isotretinoin and acitretin reduced neuronal apoptosis and improved functional recovery after spinal cord injury. These neuroprotective effects might open a window of opportunity for patients.
Topics: Animals; Rats; Acitretin; Isotretinoin; Spinal Cord Injuries; Spinal Injuries; Nerve Regeneration
PubMed: 37670445
DOI: 10.5152/j.aott.2023.22128 -
Dermatology (Basel, Switzerland) 2024Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive... (Review)
Review
BACKGROUND
Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during 3 years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe 1 month after discontinuation.
OBJECTIVES
The aim of this study was to provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature.
METHODS
Nine women of childbearing age (19-31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30 mg alitretinoin during 2-28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin," "skin diseases, genetic" and "ichthyosis" was performed.
RESULTS
Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling, and IASI-total was seen. Seven patients are still being treated, 1 patient stopped to become pregnant, 1 patient discontinued due to financial reasons. Observed side effects were reversible headache (n = 6), asteatotic eczema (n = 1), "not feeling well" temporarily (n = 1), and easier blistering of the feet (n = 1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority of articles (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n = 16) were relatively mild, except for benign intracranial hypertension (n = 1) and autoimmune hypothyroidism (n = 1).
CONCLUSION
Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin.
Topics: Pregnancy; Humans; Female; Young Adult; Adult; Alitretinoin; Acitretin; Hyperkeratosis, Epidermolytic; Ichthyosis; Immunoglobulin A
PubMed: 37666225
DOI: 10.1159/000533934 -
Frontiers in Pharmacology 2023In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their...
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.
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. 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. 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. 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. 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.
PubMed: 37663263
DOI: 10.3389/fphar.2023.1207976 -
JMIR Dermatology Jun 2023The use of risk evaluation and mitigation strategy (REMS) programs is frequently required for prescriptions with potentially teratogenic effects, especially in the field...
The use of risk evaluation and mitigation strategy (REMS) programs is frequently required for prescriptions with potentially teratogenic effects, especially in the field of dermatology. Among these REMS programs, the most well-known example is isotretinoin, an oral retinoid that uses the iPLEDGE system. iPLEDGE has strict regulations and a lengthy approval process, and until recently, patients were grouped into 3 categories: male, female, or female of reproductive potential. This strict grouping has posed problems in the medical community, especially for gender-diverse individuals where their perceived gender conflates with their assigned grouping causing patient-specific distress. The distinction between gender-a multifactorial perception of identity-and biological sex is addressed under new iPLEDGE guidelines. Dermatologists now register patients under one of 2 categories: patients who can become pregnant and those who cannot become pregnant. This change simultaneously improves the accessibility to isotretinoin among gender-diverse individuals, while limiting prescription barriers. Despite initial success being limited due to lengthy system conversions, a registration process based on reproductive potential ultimately enhances iPLEDGE's goal to prevent potential birth defects. We propose that other REMS programs follow the standard set by the iPLEDGE system, including those for the medications thalidomide, acitretin, and mycophenolate mofetil, all of which currently have a similar taxonomy to that of the old iPLEDGE system. Implementing the standardization of gender-neutral terminology can maximize enrollment and minimize distress. Current and ongoing refinement of iPLEDGE and other REMS is needed to build protocols solely around the prevention of birth defects without regard to sex or gender.
PubMed: 37632908
DOI: 10.2196/45329 -
Vaccines Jul 2023From the beginning of public vaccinations until the relaxation of COVID-19 measures, many case reports, case series and case-control studies have been published... (Review)
Review
From the beginning of public vaccinations until the relaxation of COVID-19 measures, many case reports, case series and case-control studies have been published indicating cutaneous side effects of COVID-19 vaccination. Post-vaccination pustular eruption was reported as well, with a challenging differential diagnosis between pustular psoriasis, AGEP (acute generalized exanthematous pustulosis) and neutrophil pustular eruptions. We report a case of 56-year-old woman presented with acute generalized pustular flare up culminated 5 days after the second dose of BNT162b2(Pfizer) vaccination. She was diagnosed with pustular psoriasis flare and due to the regulating role of IL-1 in pustular psoriasis and in the cytokine storm observed in cases of COVID-19 postvaccination inflammation; we decided to treat the patient with an IL-1 antagonist, subcutaneous anakinra (100 mg daily) along with acitretin. One week later, after anakinra withdrawal, she presented a pustular psoriasis flare and a 7-day anakinra re-administration led to a satisfactory improvement in the skin lesions. We also reviewed the medical literature and found 28 case reports with pustular eruption after the COVID-19 vaccination. We compared the patients reported, regarding sex, age, number of doses, post-vaccination period and vaccine brand, and compared those results with our patient. Finally, as indicated by our case and other cases with similarly treated pustular eruptions. targeted therapy to this cytokine imbalance such as anakinra (IL-1) antagonist can improve the clinical course of the patient.
PubMed: 37631866
DOI: 10.3390/vaccines11081298 -
Postepy Dermatologii I Alergologii Jun 2023
PubMed: 37545819
DOI: 10.5114/ada.2023.128984 -
Clinical, Cosmetic and Investigational... 2023Erythrodermic psoriasis (EP) is a rare and severe type of psoriasis. Common systemic therapies for children with EP include treatment with glucocorticoids, cyclosporine,...
Erythrodermic psoriasis (EP) is a rare and severe type of psoriasis. Common systemic therapies for children with EP include treatment with glucocorticoids, cyclosporine, acitretin, and methotrexate. Although these drugs are effective, they may cause serious side effects to children. Secukinumab has recently demonstrated efficacy in treating plaque psoriasis, but its efficacy in EP children remains unknown. We report a case of a seven-year-old patient who transitioned from generalized pustular psoriasis (GPP) to EP after routine systemic drug treatment. The patient was then treated with secukinumab. The patient's condition improved noticeably within 48 hours after the first injection. After the fifth injection, she almost completely cleared her skin lesions and achieved Psoriasis Area and Severity Index 90 (PASI 90) scores. During this period, she experienced only one respiratory infection. She completed all 11 doses of secukinumab by October 14, 2022, with no new rash (PASI 100) and no adverse drug reactions. Follow-up observation on March 15, 2023, showed no new rash (PASI 100) and no adverse reactions after medication withdrawal. This case suggests that it may also be effective in treating children with EP.
PubMed: 37539023
DOI: 10.2147/CCID.S420812