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Cureus Jan 2023Darier disease (DD) is an autosomal-dominant genodermatosis in which mutations in the ATP2A2 gene result in impaired intercellular adhesion and epidermal blistering....
Darier disease (DD) is an autosomal-dominant genodermatosis in which mutations in the ATP2A2 gene result in impaired intercellular adhesion and epidermal blistering. Treatment options usually rely on systemic retinoids, but a refractory disease is still a therapeutical challenge. Given the similarity of DD pathogenesis with Hailey-Hailey disease, concomitant treatment with low-dose-naltrexone (LDN) has been proposed. We present the case of a 34-year-old woman with a 20-year history of severe, biopsy-proven DD, previously treated with several unsuccessful topical and systemic treatments, including oral isotretinoin, cyclosporine, doxycycline, methotrexate, acitretin, and subcutaneous adalimumab. At presentation, she had widespread keratotic, crusted, brown papules on her trunk and proximal extremities. Treatment with oral LDN (4.5 mg/day in manipulated tablets) was then initiated while maintaining the current isotretinoin therapy. After three months, there was a nearly complete clearance of the lesions, and no adverse effects were reported.
PubMed: 36741607
DOI: 10.7759/cureus.33321 -
Advances in Therapy Jun 2024The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB),... (Review)
Review
The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.
Topics: Humans; Psoriasis; COVID-19; Hepatitis B; Tuberculosis; SARS-CoV-2; HIV Infections; Hepatitis C
PubMed: 38709397
DOI: 10.1007/s12325-024-02873-2 -
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 -
Clinical Drug Investigation Nov 2023Acitretin has long-lasting teratogenic properties. Therefore, pregnancies must be avoided during and within 3 years after acitretin treatment. We aimed to describe (i)...
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.
Topics: Pregnancy; Child; Humans; Female; Acitretin; Abnormalities, Drug-Induced; Germany
PubMed: 37906397
DOI: 10.1007/s40261-023-01314-2 -
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 -
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 -
Journal of Virology Jul 2021Small-molecule drugs inhibiting BK polyomavirus (BKPyV) represent a significant unmet clinical need in view of polyomavirus-associated nephropathy or hemorrhagic...
Small-molecule drugs inhibiting BK polyomavirus (BKPyV) represent a significant unmet clinical need in view of polyomavirus-associated nephropathy or hemorrhagic cystitis, which complicate 5% to 25% of kidney and hematopoietic cell transplantations. We characterized the inhibitory activity of acitretin on BKPyV replication in primary human renal proximal tubular epithelial cells (RPTECs). Effective inhibitory concentrations of 50% (EC) and 90% (EC) were determined in dilution series measuring BKPyV loads, transcripts, and protein expression, using cell proliferation, metabolic activity, and viability to estimate cytotoxic concentrations and selectivity indices (SI). The acitretin EC and EC in RPTECs were 0.64 (SI, 250) and 3.25 μM (SI, 49.2), respectively. Acitretin effectively inhibited BKPyV replication until 72 h postinfection when added 24 h before infection until 12 h after infection, but decreased to <50% at later time points. Acitretin did not interfere with nuclear delivery of BKPyV genomes, but it decreased large T-antigen transcription and protein expression. Acitretin did not inhibit the initial round of BKPyV replication following transfection of full-length viral genomes, but it affected subsequent rounds of reinfection. Acitretin also inhibited BKPyV replication in human urothelial cells and in Vero cells, but not in COS-7 cells constitutively expressing Simian virus 40 (SV40) large T antigen. Retinoic acid agonists (all- retinoic acid, 9- retinoic acid [9--RA], 13--RA, bexarotene, and tamibarotene) and the RAR/RXR antagonist RO41-5253 also inhibited BKPyV replication, pointing to an as-yet-undefined mechanism. Acitretin selectively inhibits BKPyV replication in primary human cell culture models of nephropathy and hemorrhagic cystitis. Since acitretin is an approved drug in clinical use reaching BKPyV-inhibiting concentrations in systemically treated patients, further studies are warranted to provide data for clinical repurposing of retinoids for treatment and prevention of replicative BKPyV-diseases.
Topics: Acitretin; Animals; Antigens, Viral, Tumor; Antiviral Agents; BK Virus; COS Cells; Cell Line; Chlorocebus aethiops; Cystitis; Genome, Viral; HEK293 Cells; Humans; Kidney Diseases; Microbial Sensitivity Tests; Polyomavirus Infections; Retinoids; Tretinoin; Tumor Virus Infections; Vero Cells; Virus Replication
PubMed: 34011542
DOI: 10.1128/JVI.00127-21 -
Archives of Dermatological Research May 2024Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Humans; Psoriasis; Male; Female; Adult; Nerve Tissue Proteins; Middle Aged; Severity of Illness Index; Acitretin; Ultraviolet Therapy; Single-Blind Method; Polymorphism, Single Nucleotide; Young Adult; Skin; Receptors, Immunologic; Treatment Outcome; Receptors, Cell Surface; Keratolytic Agents; Combined Modality Therapy
PubMed: 38734848
DOI: 10.1007/s00403-024-02880-x -
Neurochemical Research Jan 2023Acitretin is an oral drug approved by the Food and Drug Administration that is commonly used to treat psoriasis. In recent years, acitretin has been identified as a...
Acitretin is an oral drug approved by the Food and Drug Administration that is commonly used to treat psoriasis. In recent years, acitretin has been identified as a candidate drug for the treatment of Alzheimer's disease, but its role in neuronal development is still unclear. In this study, the human neuroblastoma cell line SH-SY5Y was used as a model to study neuronal differentiation. We found that acitretin effectively promoted the differentiation of SH-SY5Y cells into neuronal cells and upregulated the expression of the neuronal marker β-III tubulin and the mature neuronal marker NFH. Differentially expressed genes were identified by RNA sequencing and analyzed by bioinformatics approaches. The results showed that genes associated with neuron development-related pathways, such as SSPO and KCNT1, had significant changes in expression. Analysis showed that PRKCA and CAMK2B may play important roles in the process by which acitretin promotes neurodevelopment. Through whole-cell patch clamping and a microelectrode array assay, we found that acitretin-treated neurons generated electrical spikes similar to those generated by mature neurons. This study provided evidence to support an accessible and safe model of neuron-like cells and verified that acitretin can promote the differentiation of neurons and has the potential to treat brain tumors and neurodevelopmental and neurodegenerative diseases.
Topics: Humans; Acitretin; Cell Line, Tumor; Neuroblastoma; Neurons; Cell Differentiation; Potassium Channels, Sodium-Activated; Nerve Tissue Proteins
PubMed: 35987975
DOI: 10.1007/s11064-022-03716-8 -
Computational and Mathematical Methods... 2022Psoriasis is a chronic noncommunicable dermatological condition, and psoriasis vulgaris is the most common phenotype. Acitretin is the most widely used systemic retinoid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is a chronic noncommunicable dermatological condition, and psoriasis vulgaris is the most common phenotype. Acitretin is the most widely used systemic retinoid in the treatment of psoriasis. This review evaluates the clinical therapeutic effects of Xiaoyin granule, a Chinese herbal medicine, combined with acitretin capsule in the treatment of psoriasis vulgaris.
METHODS
Six databases including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wan Fang, and China Biology Medicine disc (CBM) were searched for published studies on Xiaoyin granule and/or acitretin capsule in psoriasis vulgaris. The Cochrane Collaboration risk-of-bias instrument was used to assess the quality of the included RCTs. STATA 14.0 was used to conduct the statistical analysis.
RESULTS
Twenty-eight trials with 3281 patients were included in this meta-analysis. The results of this study show that the combined treatment of Xiaoyin granule and acitretin capsule could improve the total effective rate (TER) and cure rate (CR) when compared with acitretin capsule (TER: RR = 1.15, 95% CI (1.10, 1.21); CR: RR = 1.8, 95% CI (1.62, 2.00)) or Xiaoyin granule (TER: RR = 1.24, 95% CI (1.11, 1.39); CR: RR = 1.75, 95% CI (1.54, 1.98)) alone. The combined therapy could decrease the PASI score (mean difference = -1.45, 95% CI (-2.09, -0.80)) and inhibit inflammation (IL-10: mean difference = 1.16, 95% CI (0.94, 1.38); IL-17: mean difference = -2.06, 95% CI (-2.60, -1.51)) in psoriasis vulgaris patients.
CONCLUSIONS
The combination of Xiaoyin granule and acitretin capsules could be a novel therapeutic strategy in the treatment of psoriasis vulgaris. However, the quality of trials in this study limited the conclusion, and more high-quality RCTs are needed for further evaluation.
Topics: Acitretin; Chronic Disease; Combined Modality Therapy; Drugs, Chinese Herbal; Humans; Psoriasis
PubMed: 35936361
DOI: 10.1155/2022/7360975