BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established...BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.展开更多
Psoriatic arthritis(PsA)is a type of chronic inflammatory arthritis which is associated with psoriasis.The early recognition and treatment for PsA are of critical importance.Janus kinase(JAK)inhibitors,as a kind of or...Psoriatic arthritis(PsA)is a type of chronic inflammatory arthritis which is associated with psoriasis.The early recognition and treatment for PsA are of critical importance.Janus kinase(JAK)inhibitors,as a kind of orally small molecules,have emerged as an encouraging class of drug in PsA treatment.This review provides a discussion of the role and current status of JAK inhibitors in the control of PsA.There are three JAK inhibitors approved for use in autoimmune diseases,for example,tofacitinib,baricitinib,and upadacitinib,and only tofacitinib has been approved in PsA treatment.The clinical trials of upadacitinib and filgotinib in PsA patients are undergoing.The efficacy and safety of these agents were briefly discussed.Although there are still issues in terms of their efficacy and safety currently,JAK inhibitors are expected to benefit more PsA patients in future.展开更多
Psoriatic arthritis(PsA)is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints,and tailoring specific treatment strategies for simultaneously delivering different drugs to di...Psoriatic arthritis(PsA)is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints,and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging.We developed a need-based layered dissolving microneedle(MN)system loading immunosuppressant tacrolimus(TAC)and antiinflammatory diclofenac(DIC)in different layers of MNs,i.e.,TD-MN,which aims to specifically deliver TAC and DIC to skin and articular cavity,achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA.In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of~100μm,while the tip-layer delivered DIC up to~300μm into the articular cavity.TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling,muscle atrophy,and cartilage destruction.Importantly,TD-MN significantly inhibited the serum TNF-αand IL-17 A in psoriatic and arthritic rats.The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity,providing a convenient and effective strategy for meeting the requirements of PsA treatment.展开更多
文摘BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.
基金This project was supported by grants from the National Natural Science Foundation of China(No.81771746 and No.81900795)。
文摘Psoriatic arthritis(PsA)is a type of chronic inflammatory arthritis which is associated with psoriasis.The early recognition and treatment for PsA are of critical importance.Janus kinase(JAK)inhibitors,as a kind of orally small molecules,have emerged as an encouraging class of drug in PsA treatment.This review provides a discussion of the role and current status of JAK inhibitors in the control of PsA.There are three JAK inhibitors approved for use in autoimmune diseases,for example,tofacitinib,baricitinib,and upadacitinib,and only tofacitinib has been approved in PsA treatment.The clinical trials of upadacitinib and filgotinib in PsA patients are undergoing.The efficacy and safety of these agents were briefly discussed.Although there are still issues in terms of their efficacy and safety currently,JAK inhibitors are expected to benefit more PsA patients in future.
基金financially supported by the National Natural Science Foundation of China(Nos.81973491 and 81473358,China)the Guangdong Basic and Applied Basic Research Foundation(2019A1515011161,China)
文摘Psoriatic arthritis(PsA)is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints,and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging.We developed a need-based layered dissolving microneedle(MN)system loading immunosuppressant tacrolimus(TAC)and antiinflammatory diclofenac(DIC)in different layers of MNs,i.e.,TD-MN,which aims to specifically deliver TAC and DIC to skin and articular cavity,achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA.In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of~100μm,while the tip-layer delivered DIC up to~300μm into the articular cavity.TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling,muscle atrophy,and cartilage destruction.Importantly,TD-MN significantly inhibited the serum TNF-αand IL-17 A in psoriatic and arthritic rats.The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity,providing a convenient and effective strategy for meeting the requirements of PsA treatment.
