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Journal of Clinical and Investigative... Jul 2023Seborrheic dermatitis (SD) is an inflammatory disease that has a papulosquamous morphology in areas rich in sebaceous glands such as the scalp, face, and body folds....
BACKGROUND
Seborrheic dermatitis (SD) is an inflammatory disease that has a papulosquamous morphology in areas rich in sebaceous glands such as the scalp, face, and body folds. Petaloid SD is an uncommon presentation found in patients with dark skin (Fitzpatrick Skin type V-VI). This form of SD can appear as pink or hypopigmented polycyclic coalescing rings or scaly macules and patches in the typical areas SD appears, which can mimic other conditions including lupus erythematosus. There is significant disproportion in the representation of darker skin types in dermatological textbooks and scarce literature on petaloid SD. This case demonstrates the presentation of the petaloid SD in an African American patient to contribute to the limited literature on dermatological conditions within this population.
CASE REPORT
A 25-year-old African American female with a history of mild hidradenitis suppurativa and asthma who presented with asymptomatic hypopigmented rashes throughout her face, scalp, and chest. She was diagnosed with the petaloid form SD and treated with ketoconazole shampoo once weekly, ketoconazole cream 1-2x daily, and hydrocortisone 2.5% ointment twice daily as needed. At six-week post-treatment follow-up, the patient's rashes significantly improved.
CONCLUSIONS
The petaloid form of SD is commonly experienced in dark-skinned patients. While common treatments for SD are effective in this form of SD, special consideration of skin types, skincare habits, and haircare in the African American population should be explored. This case report demonstrates how this uncommon skin condition presents in patients of Fitzpatrick skin type V-VI and a successful treatment course.
PubMed: 38249156
DOI: 10.13188/2373-1044.1000086 -
Proceedings of the National Academy of... Dec 2023Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over...
Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over extracellular localization of therapeutic proteins. A critical gap therefore remains the need to develop and incorporate methodologies that allow for posttranslational control over expression dynamics, localization, and stability of nucleic acid-generated protein therapeutics. To address this, we explored how the body's endogenous machinery controls protein localization through signal peptides (SPs), including how these motifs could be incorporated modularly into therapeutics. SPs serve as a virtual zip code for mRNA transcripts that direct the cell where to send completed proteins within the cell and the body. Utilizing this signaling biology, we incorporated secretory SP sequences upstream of mRNA transcripts coding for reporter, natural, and therapeutic proteins to induce secretion of the proteins into systemic circulation. SP sequences generated secretion of various engineered proteins into the bloodstream following intravenous, intramuscular, and subcutaneous SP mRNA delivery by lipid, polymer, and ionizable phospholipid delivery carriers. SP-engineered etanercept/TNF-α inhibitor proteins demonstrated therapeutic efficacy in an imiquimod-induced psoriasis model by reducing hyperkeratosis and inflammation. An SP-engineered anti-PD-L1 construct mediated mRNA encoded proteins with longer serum half-lives that reduced tumor burden and extended survival in MC38 and B16F10 cancer models. The modular nature of SP platform should enable intracellular and extracellular localization control of various functional proteins for diverse therapeutic applications.
Topics: Humans; Animals; Melanoma; Psoriasis; Inflammation; Protein Sorting Signals; Dermatitis; RNA, Messenger; Disease Models, Animal
PubMed: 38109533
DOI: 10.1073/pnas.2313009120 -
Cureus Nov 2023Bloch-Sulzberger Syndrome, also known as Incontinence Pigmentosa (IP), is a rare genodermatosis in which skin involvement occurs in almost all patients. Additionally,...
Bloch-Sulzberger Syndrome, also known as Incontinence Pigmentosa (IP), is a rare genodermatosis in which skin involvement occurs in almost all patients. Additionally, other ectodermal tissues like the central nervous system, eyes, hair, nails, and teeth may also be impacted. An X-linked dominant inheritance pattern characterizes the condition. But in our situation, IP caused a mutation in the body cells. There are four steps to the dermatological results. We describe the case of a 12-day-old female who had cutaneous features. It is crucial to make an early diagnosis using criteria like cutaneous symptoms so that quick diagnoses and interventions for other organs can be made to control more deadly complications in the future.
PubMed: 38106755
DOI: 10.7759/cureus.48823 -
Pharmaceuticals (Basel, Switzerland) Nov 2023: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is...
: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. : Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. : Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. : Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.
PubMed: 38004414
DOI: 10.3390/ph16111548 -
Clinical, Cosmetic and Investigational... 2023Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic...
PURPOSE
Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic pathways. However, the expression of HK2 and its potential therapeutic effects in psoriasis remains unclear. This study aimed to investigate the expression pattern of HK2 and evaluate its therapeutic effects in psoriasis.
PATIENTS AND METHODS
A gene expression dataset (GSE121212) downloaded from the Gene Expression Omnibus (GEO) database was used to examine the expression of HK2 in psoriasis. HK2 RNA and protein expression were investigated in psoriasis vulgaris (n=5) and healthy (n=5) samples. Immunohistochemistry for HK2 was performed on psoriasis vulgaris (n=22) and healthy skin (n=10) samples. Additionally, HaCaT cells were treated with M5 (interleukin [IL]-17A, tumor necrosis factor-α, IL-1α, IL-22, and Oncostatin-M) to induce a psoriatic inflammation cell model. A mouse model of psoriatic inflammation was established using topical 5% imiquimod cream. Psoriasis-like cells and mouse models were treated with the HK2 inhibitor 3-bromopyruvate (3-BrPA). Cell proliferation, glucose consumption, and lactate production were assessed. Furthermore, the activation of nuclear factor-kappa B (NF-Kb) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was investigated using Western blot analysis.
RESULTS
According to the GEO dataset, HK2 expression was significantly elevated in psoriasis. Upregulation of HK2 in psoriatic tissues was confirmed by quantitative real-time polymerase chain reaction and Western blotting. The immunohistochemistry score for HK2 was higher in psoriatic lesions than in healthy skin. 3-BrPA inhibited the proliferation and glycolysis of M5-stimulated HaCaT cells. Topical 3-BrPA ameliorated imiquimod-induced psoriasis-like dermatitis. Activation of NF-kB and NLRP3 was downregulated by 3-BrPA treatment.
CONCLUSION
Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models.
PubMed: 37965102
DOI: 10.2147/CCID.S435624 -
Journal of Taibah University Medical... Feb 2024Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory...
UNLABELLED
Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory cytokines are produced when immune system imbalances are driven by genetic and environmental triggers. Vinpocetine (VNP), a man-made analogue of the compound vincamine found in the dwarf periwinkle herb, has robust anti-inflammatory, immunomodulatory, and anti-oxidative effects; alleviates the epidermal penetration of immune cells, such as eosinophils and neutrophils; and abolishes the generation of pro-inflammatory molecules.
OBJECTIVE
This study was aimed at exploring the effects of long-term topical VNP, both alone and co-administered with clobetasol propionate, in an imiquimod-induced mouse model of psoriasiform dermatitis.
METHODS
The study protocol consisted of 48 Swiss albino mice, randomly divided into six groups of eight mice each. In group I, petroleum jelly was administered daily for 8 days. In group II, imiquimod was administered topically at 62.5 mg daily for 8 days. In groups III, VI, V, and VI, 0.05% clobetasol propionate, 1% VNP, 3% VNP, and 3% VNP plus 0.05% clobetasol were administered topically for an additional 8 days after the induction, thus resulting in a total trial length of 16 days.
RESULTS
Topical VNP at various doses alleviated the severity of imiquimod-induced psoriatic lesions-including erythema, silvery-white scaling, and thickening-and reversed the histopathological abnormalities. Moreover, imiquimod-exposed animals treated with VNP showed markedly diminished concentrations of inflammatory biomarkers, including tumour necrosis factor-α, interleukin (IL)-8, IL-17A, IL-23, IL-37, nuclear factor-kappa B (NF-κB), and transforming growth factor-β1.
CONCLUSION
This research provides new evidence that VNP, alone and in combination with clobetasol, may serve as a potential adjuvant for long-term management of autoimmune and autoinflammatory skin diseases, particularly psoriasis, by attenuating psoriatic lesion severity, suppressing cytokine generation, and limiting NF-κB-mediated inflammation.
PubMed: 37868105
DOI: 10.1016/j.jtumed.2023.09.002 -
Australian Journal of General Practice Oct 2023It is important to be able to manage patients regardless of ethnicities. The understanding of skin diseases, including atopic dermatitis, in patients with skin of colour...
BACKGROUND
It is important to be able to manage patients regardless of ethnicities. The understanding of skin diseases, including atopic dermatitis, in patients with skin of colour (SOC) is lagging compared with that in patients with lighter skin and has been identified as an educational gap among medical practitioners.
OBJECTIVE
This paper synthesises the latest literature on the diagnosis, assessment, treatment outcomes and cultural considerations for managing atopic dermatitis in children with SOC in the general practice setting.
DISCUSSION
Atopic dermatitis in children with SOC can vary from traditional descriptions and appear psoriasiform, lichenoid, scaly, papular, hypopigmented or violaceous. It can be misdiagnosed and its severity underestimated. Complications from atopic dermatitis, as well as the treatments provided, might result in inadequate treatment unless the treating doctor is aware of specific nuances in children with SOC.
Topics: Humans; Child; Dermatitis, Atopic; Skin Pigmentation; Skin; Treatment Outcome; Psoriasis
PubMed: 37788687
DOI: 10.31128/AJGP-01-23-6684 -
World Journal of Clinical Cases Sep 2023Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation, at least in the initial stages, of T helper (Th)-2...
BACKGROUND
Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation, at least in the initial stages, of T helper (Th)-2 Lymphocytes, the related cytokine axis, and B lymphocytes with antibody production. Psoriasis is conversely a pathology resulting from a recruitment of Th-17 and Th-1 lymphocytes, after an initial role of innate immunity. Mepolizumab is a humanized monoclonal antibody directed against interleukin (IL)-5, a central cytokine in the Th-2 axis, therefore involved in the pathogenesis of asthma. Several authors have described the appearance of psoriatic lesions in patients with asthma or atopic dermatitis following the therapy with dupilumab, a monoclonal antibody that blocks the interleukin (IL)-4, another Th-2 cytokine.
CASE SUMMARY
We present the case of a 59-year-old patient who developed psoriasiform lesions on the palms after mepolizumab therapy for asthma, for the activation of the parallel cytokine cascade after the blockade of IL-5. We successfully treated the patient with a topical calcipotriol and betamethasone ointment.
CONCLUSION
We should investigate with further attention the possible impact on the human immunological ecosystem put in place by the inhibition of the activity of individual inflammatory mediators, so as to be able to recognize the initial adverse effects early.
PubMed: 37731552
DOI: 10.12998/wjcc.v11.i26.6154 -
The Journal of Dermatological Treatment Dec 2023Although psoriasis and atopic dermatitis (AD) were for decades considered to be opposing diseases, it is now known that these skin conditions can coexist or even...
Although psoriasis and atopic dermatitis (AD) were for decades considered to be opposing diseases, it is now known that these skin conditions can coexist or even overlap in the same individual. Especially when using modern drugs with targeted IL inhibition, the balance between Th1 and Th2 immunity can be disturbed. In line with it, numerous clinical cases of AD have been induced by antipsoriatic biologics (e.g., TNF-alpha, IL-23, or IL-17 inhibitors), and IL-4-/IL-13 inhibition by dupilumab also resulted in paradoxical psoriasis in patients with AD. Herein, we describe a case of psoriasis vulgaris in a patient with intrinsic AD after systemic treatment with the anti-IL-13 antibody tralokinumab. We present a 36-years-old male patient with a severe course of an intrinsic atopic dermatitis and dyshidrotic hand eczema. He responded well to the therapy with tralokinumab. However, about 7 months after the start of anti-IL-13 treatment the patient developed psoriasiform lesions. The drug was then discontinued. Currently, the patient is receiving topical therapy with topical corticosteroids and calcineurin inhibitors with stable course of psoriasis and AD. This case suggests, that not only a dual IL-4-/IL-13-blockade, but also a selective IL-13-inhibition is able to skew immune responses toward IL-17 cytokine pathway-related disease. However, no clinical scores exist to predict the development of paradoxical psoriasis in patients with AD during therapy with biologics.
Topics: Humans; Male; Adult; Interleukin-17; Dermatitis, Atopic; Interleukin-4; Psoriasis; Interleukin-13; Biological Products
PubMed: 37705378
DOI: 10.1080/09546634.2023.2258240 -
The Journal of Dermatological Treatment Dec 2023Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous... (Review)
Review
Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.
Topics: Humans; Dermatitis, Atopic; Expert Testimony; Qatar; Quality of Life; Eczema; Pruritus
PubMed: 37700510
DOI: 10.1080/09546634.2023.2251622