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The Journal of Investigative Dermatology Mar 2017
Topics: Adjuvants, Immunologic; Aminoquinolines; Complement Activation; Complement C3; Dermatitis; Humans; Imiquimod; Immunity, Cellular; Skin
PubMed: 27876407
DOI: 10.1016/j.jid.2016.11.011 -
Dermatology Online Journal Jul 2007A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia...
A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia and pallor of the epidermis. The patient's serum zinc level was 36 mug/dl [nl. 66-144 mug/dl]. A diagnosis of acrodermatitis enteropathica was established and the patient responded well to zinc replacement therapy. Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by mutations in SLC39A4, which encodes the tissue-specific zinc transporter ZIP4.
Topics: Acrodermatitis; Adolescent; Astringents; Biopsy; Cation Transport Proteins; Diagnosis, Differential; Female; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Mutation; Skin; Zinc; Zinc Sulfate
PubMed: 18328205
DOI: No ID Found -
The Journal of Clinical Investigation Jun 2020Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2....
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2. KLK6 levels are elevated in multiple inflammatory and autoimmune conditions, but no definitive role in pathogenesis has been established. Here, we show that skin-targeted overexpression of KLK6 causes generalized, severe psoriasiform dermatitis with spontaneous development of debilitating psoriatic arthritis-like joint disease. The psoriatic skin and joint phenotypes are reversed by normalization of skin KLK6 levels and attenuated following genetic elimination of PAR1 but not PAR2. Conservation of this regulatory pathway was confirmed in human psoriasis using vorapaxar, an FDA-approved PAR1 antagonist, on explanted lesional skin from patients with psoriasis. Beyond defining a critical role for KLK6/PAR1 signaling in promoting psoriasis, our results demonstrate that KLK6/PAR1-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease. Further, we identify PAR1 as a promising cytokine-independent target in therapy of psoriasis and psoriatic arthritis.
Topics: Animals; Arthritis, Psoriatic; Dermatitis; Female; Humans; Kallikreins; Male; Mice; Mice, Transgenic; Receptor, PAR-1; Signal Transduction; Skin
PubMed: 32155135
DOI: 10.1172/JCI133159 -
Case Reports in Dermatological Medicine 2022Psoriasis is a chronic inflammatory papulosquamous disorder which affects around 2% of the world's population. A peak exacerbation in psoriatic symptoms was noted during...
Psoriasis is a chronic inflammatory papulosquamous disorder which affects around 2% of the world's population. A peak exacerbation in psoriatic symptoms was noted during COVID-19 due to lack of access to dermatological care mixed with heightened emotional stress during the pandemic. This case report describes a 52-year-old admitted male patient who sustained a diffuse rash on multiple areas of his body a week prior to testing positive for COVID-19. We explore plausible causes for the occurrence of the rash, discuss our treatment plan, include relevant clinical pictures, and review published literature to examine conditions that present similarly to the rash seen in our patient. It is crucial for dermatologists to be able to discern various systemic manifestations associated with cutaneous lesions, such as the one seen in this patient, in order to make an accurate and prompt diagnosis. A better understanding of the association between COVID-19 infection and psoriasiform lesions is needed for improving the prognostic and therapeutic outcomes in patients.
PubMed: 36567752
DOI: 10.1155/2022/1820673 -
Frontiers in Pharmacology 2022: Psoriasis is characterized by keratinocyte proliferation and massive inflammatory leukocytes infiltration, affecting 0.14%-1.99% of the world's population. Our aim was...
: Psoriasis is characterized by keratinocyte proliferation and massive inflammatory leukocytes infiltration, affecting 0.14%-1.99% of the world's population. Our aim was to identify novel potential therapeutic strategies for psoriasis. : Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules that were closely related to psoriasis based on the GSE30999 dataset, which contained expression data from 85 patients with moderate-to-severe psoriasis. Then, angiopoietin-like 4 (ANGPTL4), one of the most related hub genes, was selected for and functional assays. In our experiments, imiquimod (IMQ)-induced psoriasiform dermatitis in mice and human keratinocytes (HaCaT) cells were used to study the potential roles and mechanisms of ANGPTL4 in psoriasis. : WGCNA analysis revealed the turquoise module was most correlated with psoriasis, and ANGPTL4 is one of the most related hub genes that significantly upregulated in psoriasis lesions compared with non-lesional skin. Consistent with the bioinformatic analysis, the expression of ANGPTL4 was significantly upregulated in IMQ-induced psoriasiform skin of mice. Exogenous recombinant ANGPLT4 protein treatment could promote the proliferation and induce the expression of inflammatory cytokines in HaCaTs, whereas silencing of ANGPTL4 effectively inhibited these effects. Then we demonstrated that recombinant ANGPTL4 protein exacerbated psoriasiform inflammation and epidermal hyperproliferation . Mechanismly, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) pathways were involved in ANGPTL4-mediated regulation of proliferation and inflammation. : We found ANGPTL4 was significantly increased in IMQ-induced psoriasiform skin of mice. ANGPTL4 could promote keratinocyte proliferation and inflammatory response ERK1/2 and STAT3 dependent signaling pathways in psoriasis.
PubMed: 35860030
DOI: 10.3389/fphar.2022.850967 -
Journal of Dermatological Science Dec 2018Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is...
BACKGROUND
Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood.
OBJECTIVE
To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice.
METHODS
Following daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions.
RESULTS
Compared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45 leukocytes, mast cells as well as CD3 T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice.
CONCLUSIONS
In summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.
Topics: Animals; Cytokines; Disease Models, Animal; Epidermis; Female; Humans; Hyperplasia; Imiquimod; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Psoriasis; TRPV Cation Channels; Water Loss, Insensible
PubMed: 30527377
DOI: 10.1016/j.jdermsci.2018.11.009 -
Allergy Mar 2022Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth...
BACKGROUND
Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations.
METHODS
The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cT ) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape.
RESULTS
Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV-related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4 T cells, Treg, and cT cells. Memory B and NK cells were also decreased. CARMIL2-deficient T cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3-17 years).
CONCLUSION
This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency.
Topics: Humans; Inflammatory Bowel Diseases; Microfilament Proteins; Mutation; Phenotype; Primary Immunodeficiency Diseases
PubMed: 34287962
DOI: 10.1111/all.15010 -
Cureus Nov 2021Lichen planus is a chronic papulosquamous eruption of the skin, scalp, nails, and mucous membranes. "Pruritic, purple, polygonal, planar, papules, plaques" are the...
Lichen planus is a chronic papulosquamous eruption of the skin, scalp, nails, and mucous membranes. "Pruritic, purple, polygonal, planar, papules, plaques" are the traditional six "P's" of lichen planus. We describe an unusual case of lichen planus presenting as cellulitis. A 64-year-old lady with a past medical history of pyoderma gangrenosum, inclusion body myositis, and chronic kidney disease presented with a two-week history of swelling, erythema, tenderness, hyperkeratotic plaques, and blisters on the medial aspect of both thighs. She had a previous history of pyoderma gangrenosum exacerbations with similar presentations; however, current lesions were different from prior presentations. We considered the differential diagnoses of bacterial cellulitis versus pyoderma gangrenosum exacerbation. Due to the difference in these lesions from previous episodes, the patient was empirically treated for bacterial cellulitis with intravenous cefepime and linezolid. The infectious diseases team was consulted and valacyclovir was added to cover for possible herpes infection, with no improvement in symptomatology. Dermatology was then consulted, and a clinical diagnosis of psoriasiform dermatitis was made. A skin biopsy was obtained and the patient was started on prednisone. There was an immediate improvement in the papules within 24 hours. The papules cleared, leaving behind violaceous flat plaques, clinically diagnosed as lichen planus. The affected area was shrinking as compared to previous examinations. The skin biopsy was reported as chronic psoriasiform dermatitis with the main differential of lichen planus. The patient was discharged home on a tapering dose of oral prednisone, topical clobetasol, and oral moxifloxacin. This case demonstrates the importance of familiarity with rare clinical subtypes as a suspicion for lichen planus. The vesiculobullous subtype of lichen planus, as seen in this patient, tends to present as blisters and cellulitis from infection of the bullae. Treatment of the infection alone is not enough and steroids are essential. This knowledge helps change management, allows for earlier improvement and better patient outcomes.
PubMed: 34900481
DOI: 10.7759/cureus.19304 -
Cureus Sep 2016Tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab, adalimumab, and certolizumab pegol are effective agents in the treatment of inflammatory bowel disease....
BACKGROUND
Tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab, adalimumab, and certolizumab pegol are effective agents in the treatment of inflammatory bowel disease. Some individuals undergoing anti-TNF-α therapy for Crohn's disease or ulcerative colitis develop psoriasiform lesions. This is a paradoxical finding, as classical psoriasis is known to respond to these agents.
PURPOSE
The clinical features of anti-TNF-α-induced psoriatic dermatitis are described.
METHOD
A 60-year-old man with Crohn's disease treated with infliximab, who developed anti-TNF-α-induced psoriasiform dermatitis, is described.
RESULTS
The man developed erythematous skin lesions in the bilateral axillae two years after beginning infliximab treatment for Crohn's disease. Biopsy revealed psoriasiform dermatitis, consistent with a diagnosis of anti-TNF-α-induced psoriasiform dermatitis. He was treated with clobetasol 0.05% ointment twice daily for two weeks and had significant improvement. Subsequently, he used the corticosteroid ointment two days per week and calcipotriene 0.005% ointment twice daily for five days per week to achieve and maintain clear skin.
CONCLUSIONS
Anti-TNF-α-induced psoriasiform dermatitis is an infrequent complication of infliximab therapy. However, the condition may require discontinuation of the anti-TNF-α agent. Anti-TNF-α-induced psoriasiform dermatitis should be considered in the differential diagnosis when evaluating a new erythematous skin condition in an individual with a history of inflammatory bowel disease who is being treated with a TNF-α inhibitor.
PubMed: 27738572
DOI: 10.7759/cureus.773 -
Skin Appendage Disorders Aug 2017We report a case of acute psoriasiform contact dermatitis of the forehead and scalp related to the use of a low-laser light cap. The patient had a positive patch test to...
We report a case of acute psoriasiform contact dermatitis of the forehead and scalp related to the use of a low-laser light cap. The patient had a positive patch test to dimethylol dihydroxyethyleneurea (DMDE), methylisothiazolinone, kathon CG, and cobalt. We believe that DMDE in the fabric of the cap was responsible for the allergic contact dermatitis in this case as the lesions resolved with cessation of cap use.
PubMed: 28879194
DOI: 10.1159/000466703