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The Journal of International Medical... Apr 2024Generalized pustular psoriasis (GPP) is characterized by painful and occasionally disfiguring cutaneous manifestations with sepsis-like systemic symptoms, and is a rare... (Review)
Review
Generalized pustular psoriasis (GPP) is characterized by painful and occasionally disfiguring cutaneous manifestations with sepsis-like systemic symptoms, and is a rare severe variant of psoriasis. Currently, there is no standard treatment for GPP. Here, we report a case of a female patient with ankylosing spondylitis (AS) and mild scalp psoriasis, who developed GPP and alopecia following three courses of adalimumab therapy. The patient's condition gradually improved following cessation of adalimumab and treatment with secukinumab and acitretin. After eight weeks of treatment, the patient achieved almost complete clearance of her psoriasis, her alopecia improved, and her AS was relieved. Therefore, we believe that a combination of secukinumab with acitretin may be a rational approach for the treatment of severe GPP.
Topics: Female; Humans; Acitretin; Antibodies, Monoclonal, Humanized; Drug Therapy, Combination; Psoriasis; Spondylitis, Ankylosing; Treatment Outcome; Middle Aged
PubMed: 38661102
DOI: 10.1177/03000605241247702 -
AIDS (London, England) Jul 2024Some drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or Simian...
OBJECTIVES
Some drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or Simian Immunodeficiency Virus (SIV), but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses.
DESIGN
To investigate this hypothesis, drugs were tested ex vivo on peripheral blood mononuclear cells (PBMC) from nine antiretroviral therapy (ART)-suppressed individuals.
METHODS
We tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant [inhibitor of apoptosis proteins (IAP) inhibitor], bortezomib (proteasome inhibitor), and INK128/sapanisertib [mammalian target of rapamycin mTOR] [c]1/2 inhibitor). After 6 days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay).
RESULTS
Obatoclax reduced intact HIV DNA [median = 27-30% of dimethyl sulfoxide control (DMSO)] but not defective or total HIV DNA. Other drugs showed no statistically significant effects.
CONCLUSION
Obatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.
Topics: Humans; Indoles; HIV Infections; Pyrroles; Leukocytes, Mononuclear; Proviruses
PubMed: 38626436
DOI: 10.1097/QAD.0000000000003908 -
Dermatology Reports Mar 2024The development of flares or new-onset of immune-mediated dermatologic diseases, including psoriasis, has occurred with the worldwide spreading of the COVID-19 pandemic....
The development of flares or new-onset of immune-mediated dermatologic diseases, including psoriasis, has occurred with the worldwide spreading of the COVID-19 pandemic. We report the case of a 38-year-old woman who came to our department with a severe flare of plaque psoriasis four weeks after SARS-CoV-2 infection. Her Psoriasis Area Severity Index was 25, and her Dermatology Life Quality Index was 18. Our initial decision was to prescribe acitretin, but the patients reported adverse events. For this reason, we started risankizumab with complete skin clearance after 16 weeks. The patient is still on treatment, and no adverse events have been reported to date.
PubMed: 38623366
DOI: 10.4081/dr.2023.9722 -
Clinical and Experimental Dermatology Apr 2024Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end stage renal...
Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end stage renal disease on hemodialysis. However, these patients often lack medication choices and in certain clinical scenarios, the benefits of acitretin may outweigh the potential risks. We identified 24 end stage renal disease patients on HD taking acitretin from Duke and Vanderbilt University Medical Centers. While adverse effects were common, patients did not frequently discontinue the medication due to them. We also found no association between acitretin with hospital admissions or mortality. We lastly found statistically significant increases in ALP and total bilirubin when on acitretin and dialysis compared to baseline. However, there was no dose-dependency or temporal association with acitretin or hemodialysis initiation. Based off these preliminary findings, we find that acitretin may safely be used in patients receiving HD with close monitoring of ALP and bilirubin.
PubMed: 38620055
DOI: 10.1093/ced/llae093 -
Tobacco Induced Diseases 2024Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and...
Tobacco smoking negatively influences the achievement of greater than three-quarters reduction in psoriasis area and severity index after eight weeks of treatment among patients with psoriasis: Findings from a prospective study.
INTRODUCTION
Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China.
METHODS
Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4.
RESULTS
A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9-16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91-18.89), 14.14 (95% CI: 8.27-24.20), and 3.05 (95% CI: 1.20-7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI achievement.
CONCLUSIONS
Tobacco smoking was negatively associated with PASI achievement both in current and former smokers, and former smokers had higher PASI achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses.
PubMed: 38605857
DOI: 10.18332/tid/184143 -
Journal of the European Academy of... Apr 2024Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description.
BACKGROUND
Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description.
OBJECTIVES
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 AND RELEVANCE
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.
PubMed: 38595321
DOI: 10.1111/jdv.19996 -
Cureus Feb 2024We report the case of a 77-year-old man affected by a poorly differentiated metastatic pulmonary adenocarcinoma who, after the first course of therapy with...
We report the case of a 77-year-old man affected by a poorly differentiated metastatic pulmonary adenocarcinoma who, after the first course of therapy with cisplatin-pemetrexed-pembrolizumab treatment, developed rupioid psoriasis. We decided to discontinue pembrolizumab for four weeks until lesions improved and to start therapy with apremilast (an oral small molecule phosphodiesterase (PDE)4 inhibitor) in combination with systemic methylprednisolone 16 mg/day with consequent tapering until discontinuation in a few weeks. After accomplishing three months of treatment with apremilast, the patient gained complete remission of the rupioid lesions. Pembrolizumab therapy was reintroduced, and cycles were carried out without exacerbating the clinical picture. During the fourth month of therapy with apremilast, it was attempted to stop the treatment despite continuing the therapy with pembrolizumab. As a result, there was a relapse of the erythematous scaling plaques. After the subsequent reintroduction of apremilast, a new remission of the clinical picture occurred despite the absence of interruption of pembrolizumab. As far as we know, this is the second case of rupioid psoriasis induced by immunotherapy with pembrolizumab. Still, while the previous case was undergoing therapy with acitretin and methylprednisone, our patient is the first case treated with apremilast with excellent and rapid remission even after discontinuation and re-administration of pembrolizumab without exacerbation of dermatitis. In addition, the appearance of psoriasis during immunotherapy can be properly treated, which does not contraindicate the continuation of the antineoplastic treatment.
PubMed: 38558625
DOI: 10.7759/cureus.55249 -
Medicina (Kaunas, Lithuania) Feb 2024: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are... (Review)
Review
: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. : We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. : As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.
Topics: Humans; Immune Checkpoint Inhibitors; Arthritis, Psoriatic; Quality of Life; Psoriasis; Neoplasms
PubMed: 38541099
DOI: 10.3390/medicina60030373 -
Medicina (Kaunas, Lithuania) Feb 2024Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic... (Review)
Review
Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic syndromes. Syndromes with multiple keratoacanthoma-like lesions have been documented as multiple self-healing squamous epithelioma (Ferguson-Smith syndrome), eruptive keratoacanthoma of Grzybowski, multiple familial keratoacanthoma of Witten and Zak Muir-Torre syndrome, and incontinentia pigmenti. The treatment approach of those entities is challenging due to the numerous lesions, the lesions' undefined nature, and the co-existence of other malignant skin tumors. Herein, we report a case of a 40-year-old woman who developed multiple treatment-resistant Ferguson-Smith-like keratoacanthomas with a co-existing large and ulcerated invasive squamous cell carcinoma and microcystic adnexal carcinoma on the scalp. Multiple keratoacanthomas on her extremities were successfully treated with oral acitretin (0.5 mg/kg/day) in combination with topical Fluorouracil (5-FU) 5%, while excision and plastic surgery restoration were performed to treat the ulcerated cancer lesion on her scalp. Due to the interesting nature of this rare syndrome, we performed a literature review including case reports and case series on multiple-KA-like lesions syndromes and focusing on diagnosis and therapy approaches. We also conducted a comparison of patient reports, which included assessing the clinical appearance of the lesions and evaluating the success and progress or the failure of various treatment approaches that were implemented.
Topics: Humans; Female; Adult; Keratoacanthoma; Skin Neoplasms; Carcinoma, Squamous Cell; Acitretin; Fluorouracil
PubMed: 38541097
DOI: 10.3390/medicina60030371 -
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