The advent of biologic agents within the past two decades has dramatically improved the treatment of psoriasis and psoriatic arthritis. Given that there now exists 11 FDA approved biologic options available for psoriasis, with more in the pipeline, the therapeutic armamentarium has been greatly enhanced. However, the fact that there are so many available options has also caused confusion for providers. Therefore, this manuscript deliberately focuses on the most clinically useful facts (such as efficacy and safety data) about each and every FDA approved biologic agent (including pipeline agents) for psoriasis. Moreover, among the clinically relevant facts, this manuscript purposely emphasizes the unique merits and demerits of each agent to make it easier for the provider to select which one of these many options is the best for the particular patient on hand. The goal of this manuscript is to aid the busy practicing dermatologist in becoming more adept at using these agents with the ultimate aim of improving patient care.
The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 Ϯ 1.4 ng/ml; n ϭ 12) and ACTHstimulated (94.0 Ϯ 9.4 ng/ml; n ϭ 14) corticosterone levels compared with normoxic controls (basal ϭ 8.3 Ϯ 0.5 ng/ml; n ϭ 11; stimulated ϭ 51.3 Ϯ 3.8 ng/ml; n ϭ 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 Ϯ 4 vs. 78 Ϯ 8 pg/ml) or after (481 Ϯ 73 vs. 498 Ϯ 52 pg/ml) porcine ACTH injection (20 g/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1␣ mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate. adrenocorticotropin; aldosterone; newborn; steroidogenic acute regulatory protein; peripheral-type benzodiazepine receptor; hypoxia-inducible factor HYPOXIA is one of the most common causes of neonatal morbidity and mortality (10, 17). Considerable attention has been paid to the short-and long-term neurological, cardiopulmonary, and renal consequences of neonatal hypoxia (3,8,14,34,36). In comparison, the adrenal adaptation in vivo to prolonged neonatal hypoxia has not been extensively studied. One pertinent study in human infants with hypoxemia due to bronchiolitis demonstrated an augmented cortisol, but not aldosterone, response to ACTH (12). This suggests a zone-specific adrenal adaptation to hypoxia.We have extensively examined dispersed adrenal cells in vitro removed from suckling rats exposed to hypoxia from birth (28). We have found that, as opposed to adult rats (29), steroidogenesis in vitro is augmented in adrenal cells from hypoxic neonatal rats despite no changes in steroidogenic enzy...
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The scalp is one of the most commonly affected regions in psoriasis. However, scalp psoriasis can be difficult to treat because of challenges in the delivery of therapy. Effective therapeutic regimens for scalp psoriasis are essential to improving the quality of life of patients. Recent data on topical therapies, phototherapy, systemic agents, and complementary therapy have demonstrated that it is possible to achieve and maintain significant improvement in scalp psoriasis. In this review, efficacy data for these modalities and an algorithm for the practical management of scalp psoriasis are presented.
Background Psoriasis is a common disorder of the skin, immune system, and joints that is influenced by genetic and environmental factors. It can be aggravated or induced by drugs. Objectives To identify the major drugs implicated in inducing or exacerbating psoriasis and to discuss their characteristics. Methods We performed a PubMed literature search for reviews and case reports on drugs that exacerbate or induce psoriasis. Articles were screened by title and abstract and then examined for their findings and references. Results Drugs most often reported to exacerbate or induce psoriasis were β-blockers, lithium, synthetic antimalarials, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, interferons, tetracyclines, tumor necrosis factor-α inhibitors, and steroid withdrawal. Conclusions Characterizing drugs that induce or exacerbate psoriasis by latency and type of psoriatic eruption can help guide clinical reasoning. Although a relatively uncommon occurrence, psoriatic lesions can be caused by drugs, allowing astute physicians to recognize and change their management plans accordingly.
Nail psoriasis has a prevalence that ranges from 10 to 82% and can significantly impact the quality of life of patients. Nail psoriasis is one of the most challenging areas to treat, and multiple therapies have been explored. Topical and injectable therapies are recommended for fewnail disease. Systemic therapies, including biologics, can be considered for patients with multiple and resistant nail disease, impaired quality of life, and severe skin and joint involvement, due to their long-term efficacy. Although outcome data are difficult to compare, interleukin (IL)-17 inhibitors may have superior short-term efficacy when compared to IL-23 inhibitors and tumor necrosis factor (TNF)-alpha inhibitors, although long-term efficacy is similar to TNF-alpha inhibitors. IL-23 inhibitors and TNF-alpha inhibitors have a similar efficacy for nail psoriasis.
Heterogeneous genetic and environmental factors contribute to the psoriasis phenotype, resulting in a wide range of patient response to targeted therapies. Here, we investigate genetic factors associated with response to the IL-12/23 inhibitor ustekinumab in psoriasis. To date, only HLA-C*06:02 has been consistently reported to associate with ustekinumab response in psoriasis. Genome-wide association testing was performed on the continuous outcome of percent change in Psoriasis Area Severity Index (PASI) at 12 weeks of ustekinumab therapy relative to baseline. A total of 439 European ancestry individuals with psoriasis were included [mean age, 46.6 years; 277 men (63.1%)]. 310 (70.6%) of the participants comprised the discovery cohort and the remaining 129 (29.4%) individuals comprised the validation cohort. Chromosome 4 variant rs35569429 was significantly associated with ustekinumab response at 12 weeks at a genome-wide significant level in the discovery cohort and replicated in the validation cohort. Of psoriasis subjects with at least one copy of the deletion allele of rs35569429, 44% achieved PASI75 (75% improvement in PASI from baseline) at week 12 of ustekinumab treatment, while for subjects without the deletion allele, 75% achieved PASI75 at week 12. We found that differences in treatment response increased when rs35569429 was considered alongside HLA-C*06:02. Psoriasis patients with the deletion allele of rs35569429 who were HLA-C*06:02 negative had a PASI75 response rate of 35% at week 12, while those without the deletion allele who were HLA-C*06:02 positive had a PASI75 response rate of 82% at week 12. Through GWAS, we identified a novel SNP that is potentially associated with response to ustekinumab in psoriasis.
Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder that primarily affects the axial skeleton, especially the sacroiliac joints and spine. This results in chronic back pain and, in extreme cases, ankylosis of the spine. Despite its debilitating effects, the pathogenesis of AS remains to be further elucidated. This study used single cell CITE-seq technology to analyze peripheral blood mononuclear cells (PBMCs) in AS and in healthy controls. We identified a number of molecular features associated with AS. CD52 was found to be overexpressed in both RNA and surface protein expression across several cell types in patients with AS. CD16+ monocytes overexpressed TNFSF10 and IL-18Rα in AS, while CD8+ TEM cells and natural killer cells overexpressed genes linked with cytotoxicity, including GZMH, GZMB, and NKG7. Tregs underexpressed CD39 in AS, suggesting reduced functionality. We identified an overrepresented NK cell subset in AS that overexpressed CD16, CD161, and CD38, as well as cytotoxic genes and pathways. Finally, we developed machine learning models derived from CITE-seq data for the classification of AS and achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of > 0.95. In summary, CITE-seq identification of AS-associated genes and surface proteins in specific cell subsets informs our understanding of pathogenesis and potential new therapeutic targets, while providing new approaches for diagnosis via machine learning.
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