Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9 / 中西医结合学报

OBJECTIVE@#To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.@*METHODS@#Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.@*RESULTS@#EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.@*CONCLUSION@#Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Herpetic whitlow in a child with AIDS: the importance of Tzanck test in the diagnosis

Abstract Herpetic whitlow is a viral infection of the fingers caused by the herpes simplex virus. The disease has a bimodal age distribution, affecting children under 10 years of age and young adults between 20 and 30 years old. It can be easily mistaken for panaritium or bacterial cellulitis. In patients with AIDS, atypical, chronic and recurrent ulcerated lesions occur. The Tzanck test allows a quick and low-cost diagnosis of herpes simplex virus infection. The authors report the case of a child with AIDS with painful finger ulcers in which the diagnosis was confirmed by the Tzanck test.

Interstitial lung disease due to anti-TNF use in the treatment of psoriasis

Abstract Psoriasis is a chronic inflammatory disease that affects the skin variably, according to genetic and environmental factors. Some patients may benefit from systemic treatment with immunobiological agents, drugs that can be accompanied by several adverse effects. A case of a 58-year-old patient undergoing treatment for psoriasis with adalimumab for five years is reported. Alterations compatible with interstitial pneumonia were detected with important regression after adalimumab discontinuation. This case is relevant due to the scarcity of reports on late pulmonary adverse effect of anti-TNF treatment of psoriasis.

Psoriasis paradójica palmoplantar secundaria al tratamiento de la colitis ulcerosa con adalimumab / Paradoxical psoriasis of the palms and soles due to treatment of ulcerative colitis with adalimumab

Los anticuerpos anti-TNF-a (tumor necrosis factor alpha) se utilizan para tratar tanto la psoriasis como la enfermedad inflamatoria intestinal (EII). Sin embargo, estos fármacos han sido implicados en la ocurrencia de la psoriasis paradójica en los pacientes sin antecedentes de psoriasis que reciben tratamiento por una colitis ulcerosa (CU) y otras enfermedades autoinmunes. Se presenta el caso de un paciente de 29 años, sin antecedentes de dermatosis, que desarrolló una psoriasis palmoplantar paradójica por el uso del adalimumab que recibía por un diagnóstico de CU. El cuadro remitió al suspender el medicamento y recurrió al reiniciarlo, motivo por el cual se rotó al ustekinumab. La CU respondió satisfactoriamente, sin nuevas lesiones dermatológicas.

Anti TNF-a (tumor necrosis factor alpha) antibodies are used to treat both psoriasis and inflammatory bowel disease (IBD). However, these drugs have been implicated in the occurrence of the so-called paradoxical psoriasis in patients with no previous history of psoriasis, who receive treatment for ulcerative colitis and other autoimmune diseases. We present a 29-year-old male patient, with no previous history of dermatosis, who developed paradoxical palmar-plantar psoriasis due to the use of adalimumab that he was receiving for a diagnosis of ulcerative colitis. The condition remitted when the drug was suspended and recurred when it was restarted, and for that reason, treatment was rotated to ustekinumab. Ulcerative colitis responded satisfactorily, with no new dermatological lesions.

Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyper-proliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. METHODS: HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. RESULTS: Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. CONCLUSIONS: Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

4'-O-ß-D-glucosyl-5-O-methylvisamminol ameliorates imiquimod-induced psoriasis-like dermatitis and inhibits inflammatory cytokines production by suppressing the NF-κB and MAPK signaling pathways

Psoriasis is a chronic inflammatory skin disorder in humans, and the inflammatory reaction plays an important role in development and onset of psoriasis. 4'-O-β-D-glucosyl-5-O-methylvisamminol (4GMV) is one of the major active chromones isolated from Saposhnikoviae divaricata (Turcz.) Schischk, which has been reported to exhibit excellent anti-inflammatory activities. However, the possible therapeutic effect on psoriasis and underlying mechanism has not been reported. Thus, the aim of this study was to investigate the protective effect of 4GMV on the imiquimod (IMQ)-induced psoriasis-like lesions in BALB/c mice and the anti-inflammatory effect on the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. The results demonstrated that 4GMV decreased IMQ-induced keratinocyte proliferation and inflammatory cell infiltration. Moreover, 4GMV treatment significantly inhibited the production of NO, PEG 2, and cytokines such as interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and IL-22 in LPS-stimulated RAW264.7 macrophages. 4GMV also suppressed the LPS-upregulated protein expressions of iNOS and COX-2 in a dose-dependent manner. Furthermore, qRT-PCR analysis showed that 4GMV down-regulated the mRNA level of IL-1β and IL-6 expression. Further studies by western blot indicated that 4GMV inhibited the activation of upstream mediator NF-κB by suppressing the expression of TLR4 and the phosphorylation of IκBα and p65. The phosphorylation of JNK, p38, and ERK were also markedly reversed by 4GMV in LPS-treated RAW264.7 macrophages. Taken together, these results demonstrated that 4GMV showed a protective effect in IMQ-induced psoriasis-like mice and inhibited inflammation through the NF-κB and MAPK signaling pathways, indicating that 4GMV might be a potential therapeutic drug for psoriasis.

L-methylfolate, a new option in psychiatric treatment, would it be linked to psoriasis relapse? / L-metilfolato, uma nova opção no tratamento psiquiátrico, estaria ligado à recaída de psoríase?

ABSTRACT We report a case of a 61-years-old woman in remission of psoriasis for 20 years. She presented recurrence of psoriasis in the form of plaques few days after taking L-methylfolate 15mg/day. The L-methylfolate was prescribed as an adjuvant for the treatment of depression in a patient with the methylenetetrahydrofolate reductase gene polymorphism (MTHFR).

RESUMO Paciente do sexo feminino, 61 anos, em remissão da psoríase por 20 anos. Apresentou recidiva de psoríase em forma de placas poucos dias após início de tratamento L-metilfolato na dose diária de 15mg. O L-metilfolato foi prescrito como terapêutica coadjuvante para tratamento de depressão em paciente portadora do polimorfismo do gene metilenotetrahidrofolato redutase.

Paradoxical psoriasis after the use of anti-TNF in a patient with rheumatoid arthritis

Abstract The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of infliximab for rheumatoid arthritis, developed psoriasis. In an attempt to switch anti-TNF class, we observed a cumulative worsening of the lesions requiring suspension of the immunobiological agent and the introduction of other drugs for clinical control. The therapeutic challenge of this paradoxical form of psoriasis is the focus of our discussion. The use of another anti-TNF in these patients is a matter of debate among experts.

Acute generalized exanthematous pustulosis x Von Zumbusch’s pustular psoriasis: A diagnostic challenge in a psoriatic patient

AbstractSevere cutaneous drug reactions include a wide spectrum of clinical manifestations ranging from mild morbilliform cutaneous rash, to severe forms of hypersensitivity. Special attention is given in this report to the acute generalized exanthematous pustulosis (AGEP), induced in 90% of cases by the use of systemic drugs, especially aminopenicillins and macrolides. The incidence of the disease is low, 1-5 cases per million patients / year. The main differential diagnosis is Von Zumbusch's Pustular Psoriasis. The prognosis is generally good and the disease self limited, after withdrawal of the triggering drug. In this report the authors describe a case of AGEP, triggered by ceftriaxone in a patient with psoriasis vulgaris.

A case of generalized ostraceous psoriasis mimicking dermatitis neglecta

Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the induction of psoriasis on previously uninvolved skin of psoriasis patients, and in the triggering of psoriasis for the first time in patients without a personal or family history. Lithium-induced psoriasis (and its resistance to treatment) is one of the major reasons for noncompliance in patients treated with lithium. We describe a male patient who developed generalized ostraceous psoriasis whose clinical appearance mimicked dermatitis neglecta, 10 months after starting therapy with lithium.

Alopecia secondary to anti-tumor necrosis factor-alpha therapy

Biologic drugs represent a substantial progress in the treatment of chronic inflammatory immunologic diseases. However, its crescent use has revealed seldom reported or unknown adverse reactions, mainly associated with anti-tumor necrosis factor (anti-TNF). Psoriasiform cutaneous reactions and few cases of alopecia can occur in some patients while taking these drugs. Two cases of alopecia were reported after anti-TNF therapy. Both also developed psoriasiform lesions on the body. This is the second report about a new entity described as 'anti-TNF therapy-related alopecia', which combines clinical and histopathological features of both alopecia areata and psoriatic alopecia. The recognition of these effects by specialists is essential for the proper management and guidance of these patients.

Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside.

Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID) mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended? / Aparecimento de psoríase durante o tratamento das doenças inflamatórias intestinais com infliximabe: a terapia biológica deve ser suspensa?

CONTEXT: Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. OBJECTIVE: To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. METHODS: A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. RESULTS: Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. CONCLUSION: As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

CONTEXTO: Inúmeros casos paradoxais de lesões psoriásicas induzidas ou exacerbadas por infliximabe têm sido descritos nos últimos anos, existindo discordância quanto à necessidade de interromper o infliximabe, para se conseguir a resolução destas reações adversas cutâneas especificamente em pacientes com doença inflamatória intestinal (DII). OBJETIVO: Revisar sistematicamente a literatura para coletar informações sobre pacientes com DII, que apresentaram essa reação adversa cutânea, focando principalmente na abordagem terapêutica. MÉTODOS: Uma revisão sistemática da literatura foi realizada utilizando as bases de dados Medline, Embase, SciELO e Lilacs. Os estudos publicados foram identificados, analisados †e os dados extraídos. RESULTADOS: Trinta e quatro estudos (69 pacientes com DII) preencheram os critérios de inclusão para a revisão, existindo inconsistência no relato de alguns aspectos clínicos e terapêuticos. A maioria dos pacientes incluídos tinha doença de Crohn (89,86%), era do sexo feminino (47,83%), tinha idade média de 27,11 anos, e sem antecedentes de psoríase (84,05%). Os pacientes desenvolveram principalmente a psoríase tipo placa (40,58%). Houve remissão completa das lesões psoriásicas em 86,96% dos pacientes com DII, existindo diferenças nas abordagens terapêuticas; interrupção do infliximabe determinou a resolução em 47,83% dos casos e 43,48% dos pacientes continuaram recebendo o tratamento com infliximabe. CONCLUSÃO: Uma vez que cresce o número de pacientes com DII com psoríase induzida ou agravada por infliximabe, os médicos devem estar cientes de suas manifestações clínicas, para que o diagnóstico e tratamento adequados sejam devidamente estabelecidos. A decisão sobre continuar ou interromper o infliximabe deve ser individualizada.

A Case of Psoriasis Induced by Infliximab Treatment for Crohn's Disease / 대한소화기학회지

Infliximab, the monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and rheumatoid arthritis. Infliximab treatment has adverse events including infusion reactions, opportunistic infections, and the potential for the event such as reactivation of latent tuberculosis. Cutaneous adverse reactions of TNF-alpha agents include skin rash, urticaria, pruritus, lupus-like eruption, and injection site reactions. Most of all, psoriasis or psoriasiform dermatitis induced by infliximab treatment for Crohn's disease is rarely reported in Korea. We report a case of psoriasis induced by infliximab treatment for Crohn's disease with a review of world literature.