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Clinical and Experimental Dermatology May 2024Atopic dermatitis (AD) is a common inflammatory skin disease with multiple clinical manifestations. Among AD phenotypes, psoriasiform AD shows the coexisting of...
Atopic dermatitis (AD) is a common inflammatory skin disease with multiple clinical manifestations. Among AD phenotypes, psoriasiform AD shows the coexisting of eczematous itching lesions in flexural areas with psoriasiform plaques. The use of anti-IL-4 and anti-IL-13 in psoriasiform AD may lead to therapeutic failure or worsening of manifestations. A recent Delphi consensus proposed JAK inhibitors (JAKi) as a viable alternative, even in the first line, in patients with different clinical phenotypes of AD, including psoriasiform AD. A retrospective analysis of patients in our dermatology clinic with moderate-severe AD and treated with JAKi was performed. Among the 192 overall patients, 21 had psoriasiform AD. EASI, p-NRS and DLQI were the severity scores considered and their reduction was observed in all 21 patients at weeks 4, 16 and 24 of treatment. At week 16 the percentage of patients achieving EASI-75 and EASI-90 was 80.95% and 66.67%, respectively. While at week 24 95.23% of patients achieved EASI-75 and 85.71% obtained EASI-90. No adverse event lead to treatment interruption. This study confirmed the clinical effectiveness of JAKi treatment in adult patients with moderate-to-severe psoriasiform AD, with a good safety profile. These drugs are proposed as the first choice for the treatment of this form of AD, although further studies with larger cohorts are required.
PubMed: 38699956
DOI: 10.1093/ced/llae162 -
Journal of Cutaneous Pathology Apr 2024Psoriasis is an inflammatory skin disease driven by upregulation of cytokines in the Th17 pathway, including interleukin-36 (IL-36). Previous studies have highlighted...
BACKGROUND
Psoriasis is an inflammatory skin disease driven by upregulation of cytokines in the Th17 pathway, including interleukin-36 (IL-36). Previous studies have highlighted the utility of IL-36 immunostaining for psoriasis compared to spongiotic dermatitis and other psoriasiform dermatoses; however, no study has examined the role of IL-36 staining in distinguishing psoriasis from pityriasis rosea (PR) and pityriasis lichenoides (PL), known histologic mimickers of psoriasis.
METHODS
We compared the immunostaining pattern of IL-36 for 21 PR cases, 22 PL cases, and 10 psoriasis cases. We graded the immunostaining as 0, negative; 1, focal weak; 2, diffuse weak; 3, focal, strong; or 4, diffuse strong. We further categorized stains as negative (0-2 score) or positive (3-4 score) and utilized Fisher's exact test to compare the immunostaining pattern of these entities.
RESULTS
All psoriasis specimens were positive for IL-36, whereas all PR specimens were negative (p = 0.00000002). Twenty PL specimens were negative (p = 0.000001). Nine of 10 pityriasis lichenoides et varioliformis acuta cases were negative (p = 0.00012), and 11 of 12 cases of pityriasis lichenoides chronica were negative (p = 0.00003).
CONCLUSIONS
Our findings highlight the potential role of IL-36 immunostaining in distinguishing psoriasis from other psoriasiform dermatoses, including PR and PL.
PubMed: 38689501
DOI: 10.1111/cup.14633 -
Clinical Cancer Research : An Official... Jul 2024Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly...
PURPOSE
Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood.
EXPERIMENTAL DESIGN
Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays.
RESULTS
Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine-targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo.
CONCLUSIONS
Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.
Topics: Humans; Male; Female; Immune Checkpoint Inhibitors; Middle Aged; Aged; Cytokines; Skin; Adult; Drug Eruptions; Pruritus; Neoplasms; Skin Diseases; Exanthema; Aged, 80 and over; Psoriasis; Eczema
PubMed: 38652814
DOI: 10.1158/1078-0432.CCR-23-3431 -
Frontiers in Medicine 2024Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain...
Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.
PubMed: 38633304
DOI: 10.3389/fmed.2024.1363405 -
The Annals of Pharmacotherapy Apr 2024
PubMed: 38590149
DOI: 10.1177/10600280241244511 -
The Journal of Allergy and Clinical... May 2024The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread... (Review)
Review
The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread application of ICIs has unveiled a spectrum of immune-related adverse events (irAEs), most often affecting the skin. Cutaneous irAEs (cirAEs) encompass a range from common morbilliform and lichenoid rashes to more severe conditions such as bullous dermatoses and psoriasiform eruptions, each presenting distinct clinical challenges. Moreover, less common but clinically severe cutaneous reactions like toxic epidermal necrolysis have also been observed. cirAEs are frequently observed, with an incidence ranging from 37% to 70% for anti-cytotoxic T lymphocyte-associated antigen-4 antibodies and 17% to 40% for anti- programmed death-1/anti-programmed death ligand-1 antibodies. Recognizing the critical need for effective therapeutic strategies, this review carefully examines current approaches and guidelines for managing cirAEs.
Topics: Humans; Immune Checkpoint Inhibitors; Drug Eruptions; Neoplasms; Skin; Stevens-Johnson Syndrome
PubMed: 38548170
DOI: 10.1016/j.jaip.2024.03.034 -
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 -
International Immunopharmacology Mar 2024To elucidate the mechanism of Pentraxin 3 (PTX3) in the pathogenesis of psoriasiform dermatitis using Ptx3-knockout (Ptx3-KO) background mice.
OBJECTIVE
To elucidate the mechanism of Pentraxin 3 (PTX3) in the pathogenesis of psoriasiform dermatitis using Ptx3-knockout (Ptx3-KO) background mice.
METHODS
An Imiquimod (IMQ)-induced murine psoriatic model was created using Ptx3-KO (Ptx3) and wild-type (Ptx3) mice. Skin lesion severity and expression of inflammatory mediators (IL-6 and TNFα) were assessed using PASI score and ELISA, respectively. Cutaneous tissues from the two mice groups were subjected to histological analyses, including HE staining, Masson staining, and Immunohistochemistry (IHC). The PTX3, iNOS, COX2, and Arg1 expressions were quantified and compared between the two groups. We used RNA-seq to clarify the underlying mechanisms of the disease. Flow cytometry was used to analyze systemic Th17 cell differentiation and macrophage polarization.
RESULT
The psoriatic region exhibited a higher PTX3 expression than the normal cutaneous area. Moreover, PTX3 was upregulated in HaCaT cells post-TNFα stimulation. Upon IMQ stimulation, Ptx3 mice displayed a lower degree of the psoriasiform dermatitis phenotype compared to Ptx3 mice. Consistent with the RNA-seq results, further experiments confirmed that compared to the wild-type group, the PTX3-KO group exhibited a generally lower IL-6, TNFα, iNOS, and COX2 expression and a contrasting trend in macrophage polarization. However, no significant difference in Th17 cell activation was observed between the two groups.
CONCLUSIONS
This study revealed that PTX3 was upregulated in psoriatic skin tissues and TNFα-stimulated HaCaT cells. We also discovered that PTX3 deficiency in mice ameliorated the psoriasiform dermatitis phenotype upon IMQ stimulation. Mechanistically, PTX3 exacerbates psoriasiform dermatitis by regulating macrophage polarization rather than Th17 cell differentiation.
Topics: Animals; Mice; C-Reactive Protein; Cyclooxygenase 2; Dermatitis; Disease Models, Animal; Imiquimod; Interleukin-6; Macrophages; Psoriasis; Serum Amyloid P-Component; Tumor Necrosis Factor-alpha; Humans; Disease Progression; Mice, Knockout; Mice, Inbred C57BL
PubMed: 38457930
DOI: 10.1016/j.intimp.2024.111805 -
Multiple Sclerosis (Houndmills,... Jun 2024We present a case of a 30-year-old man with relapsing-remitting multiple sclerosis who developed psoriasiform dermatitis following his second course of ocrelizumab. This... (Review)
Review
We present a case of a 30-year-old man with relapsing-remitting multiple sclerosis who developed psoriasiform dermatitis following his second course of ocrelizumab. This resolved with topical therapies and discontinuation of treatment. Cases of psoriasiform rashes have been increasingly reported in the use of ocrelizumab and are possibly due to B-cell (CD20) depletion and T-cell overregulation. Nevertheless, skin-related adverse reactions are not yet considered in the risk management plans of anti-CD20 treatments in multiple sclerosis.
Topics: Humans; Multiple Sclerosis, Relapsing-Remitting; Antibodies, Monoclonal, Humanized; Male; Adult; Psoriasis; Immunologic Factors; Drug Eruptions
PubMed: 38385208
DOI: 10.1177/13524585241232277 -
Molecules (Basel, Switzerland) Jan 2024The status of parsley as a well-known folk medicine noted for its nutritional and medicinal properties prompted the exploration of its potential as a functional food and...
Exploring the Therapeutic Efficacy of Parsley ( Mill.) as a Functional Food: Implications in Immunological Tolerability, Reduction of Muscle Cramps, and Treatment of Dermatitis.
The status of parsley as a well-known folk medicine noted for its nutritional and medicinal properties prompted the exploration of its potential as a functional food and natural remedy. The paper aims to investigate the potential of parsley to enhance muscle function and alleviate psoriasiform dermatitis, eventually establishing it as a natural, well-tolerated alternative with specific benefits for both muscles and skin. This study examines the tolerability of parsley in a cohort of 937 participants by assessing immunoglobulin G (IgG) reactions. The findings reveal high tolerability, as 96.26% of participants experienced no adverse effects. Among the 902 individuals lacking hypersensitivity, 37.02% reported muscle cramps, with a notable 15.02% reduction observed in the subgroup consuming parsley juice. In the subset of 32 subjects with dermatitis, the application of parsley extract ointment led to a significant decrease in dermatological parameters (redness, thickness, scaling). While the control group exhibited improvements, statistical significance was not observed. Notably, four categories of affected area reduction were identified, with scaling demonstrating the most pronounced impact. The results propose that parsley holds promise for favorable tolerability, contributing to the alleviation of muscle cramps and presenting an effective alternative in dermatitis treatment. Nonetheless, sustained validation through long-term studies is imperative to substantiate these preliminary findings.
Topics: Humans; Functional Food; Petroselinum; Muscle Cramp; Plant Extracts; Dermatitis
PubMed: 38338356
DOI: 10.3390/molecules29030608