-
Expert Review of Clinical Immunology May 2023Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease belonging to the localized form of pustular psoriasis. It is characterized by sterile pustule... (Review)
Review
INTRODUCTION
Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease belonging to the localized form of pustular psoriasis. It is characterized by sterile pustule formation in palms and soles and a recurrent disease course. Although we have many treatments for PPP, there is no authoritative guidance.
AREAS COVERED
A thorough search of PubMed was conducted to identify studies in PPP from 1973 onwards, with additional references to specific articles. Any treatment methods were outcomes of interest, including topical treatment, systemic treatment, biologics, other targeted treatments, phototherapy, and tonsillectomy.
EXPERT OPINION
Topical corticosteroids are suggested as first-line therapy. Oral acitretin has become the most applied systemic retinoid recommended in PPP without joint involvement. For patients with arthritis, immunosuppressants like cyclosporin A and methotrexate are more recommended. UVA1, NB-UVB, and 308-nm excimer laser are effective phototherapy options. The combinations of topical or systemic agents and phototherapy may enhance the efficacy, particularly in recalcitrant cases. Secukinumab, ustekinumab, and apremilast are the most investigated targeted therapies. However, heterogeneous reported outcomes in clinical trials provided low-to-moderate quality evidence of their efficacy. Future studies are required to address these evidence gaps. We suggest managing PPP based on the acute phase, maintenance phase, and comorbidities.
Topics: Humans; Psoriasis; Cyclosporine; Acitretin; Immunosuppressive Agents; Dermatologic Agents; Chronic Disease
PubMed: 36970858
DOI: 10.1080/1744666X.2023.2185775 -
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 -
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 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 -
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 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss,... (Review)
Review
Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.
Topics: Animals; Humans; Acitretin; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; MicroRNAs; Stem Cell Transplantation; Stem Cells; Disease Susceptibility
PubMed: 37212107
DOI: 10.3233/JAD-221298 -
Expert Opinion on Drug Metabolism &... Apr 2024Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The... (Review)
Review
INTRODUCTION
Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of these therapies establish drug efficacy, toxicity, and optimal dosing to ensure therapeutic drug levels are sustained and adverse effects are minimized.
AREAS COVERED
A literature search was performed on PubMed, Google Scholar, and Ovid MEDLINE for PK and PD, efficacy, and safety data regarding oral systemic nonbiologic therapies utilized for moderate-to-severe plaque psoriasis. The findings were organized into sections for each drug: oral acitretin, methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib.
EXPERT OPINION
Some psoriasis patients may not respond to initial therapy. Ongoing research is evaluating genetic polymorphisms that may predict an improved response to specific medications. However, financial and insurance barriers, as well as limited genetic polymorphisms correlated with treatment response, may restrict the implementation of genetic testing necessary to personalize treatments. How well psoriasis patients adhere to treatment may contribute greatly to variation in response. Therapeutic drug monitoring may help patients adhere to treatment, improve clinical response, and sustain disease control.
Topics: Humans; Administration, Oral; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Monitoring; Polymorphism, Genetic; Precision Medicine; Psoriasis; Severity of Illness Index
PubMed: 38529623
DOI: 10.1080/17425255.2024.2335310 -
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 -
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 -
International Journal of Dermatology Nov 2022Acquired epidermodysplasia verruciformis (AEV) is a form of epidermodysplasia verruciformis (EV) that is most commonly found in immunocompromised or immunosuppressed... (Review)
Review
Acquired epidermodysplasia verruciformis (AEV) is a form of epidermodysplasia verruciformis (EV) that is most commonly found in immunocompromised or immunosuppressed patients. EV is commonly associated with human papillomavirus (HPV), which is often found in EV and AEV lesions. Clinical presentation of AEV in patients with organ transplantation, HIV+, congenital HIV+, hematological diseases, and other iatrogenic immunosuppression are reviewed. Treatment options include topical cidofovir, topical retinoids, topical imiquimod, topical glycolic acid, HPV 9-valent vaccine, acitretin, improving cellular immunity, and changing transplant medication to mycophenolate mofetil.
Topics: Acitretin; Cidofovir; Epidermodysplasia Verruciformis; HIV Infections; Humans; Imiquimod; Mycophenolic Acid; Papillomaviridae; Papillomavirus Infections; Vaccines
PubMed: 34403500
DOI: 10.1111/ijd.15857