Pulmonary tumor thrombotic microangiopathy successfully treated with corticosteroids: a case report

Pulmonary tumor thrombotic microangiopathy is a special type of tumor thromboembolism. We report the case of a patient who developed pulmonary tumor thrombotic microangiopathy with alveolar hemorrhage. Almost ...

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Phosphorylation of intracellular signaling molecules in peripheral blood cells from psoriasis patients on originator or biosimilar infliximab

Abstract

Background

Psoriasis vulgaris is a chronic, inflammatory skin disease characterized by a dysregulated immune response and it is associated with substantial systemic comorbidities. Biological drugs like tumor necrosis factor (TNF) inhibitors can ameliorate the disease but are expensive. Biosimilar drugs have the same amino acid sequence as the originator, but differences in manufacturing can affect biological activity, efficacy and tolerability.

Objectives

We aimed to explore potential differences in intracellular phosphorylation of signaling molecules in peripheral blood cells from TNF inhibitor infliximab treated psoriasis patients compared to healthy controls, and to investigate if the phosphorylation pattern was influenced by switching from originator infliximab to biosimilar CT-P13.

Methods

By flow cytometry, we measured phosphorylation of NF-κB, ERK1/2, p38 MAPK and STAT3 before and after TNF stimulation in monocytes and T, B, natural killer and CD3⁺CD56⁺ cells from 25 psoriasis patients treated with infliximab and 19 healthy controls.

Results

At inclusion, phosphorylation levels of peripheral blood mononuclear cells were increased in psoriasis patients compared to healthy controls, even though clinical remission had already been achieved. Phosphorylation levels declined in both patients on originator and biosimilar infliximab during continued treatment. No significant differences were detected between the two medications after 12 months.

Conclusions

Psoriasis patients on infliximab have higher activation levels of PBMC than healthy controls, possibly reflecting systemic inflammation. Switching from originator infliximab to biosimilar CT-P13 did not affect phosphorylation levels or clinical parameters, suggesting that CT-P13 is a non-inferior treatment alternative to originator infliximab.

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Illuminating the covert mission of mononuclear phagocytes in their regional niches

Publication date: February 2018
Source:Current Opinion in Immunology, Volume 50
Author(s): Shu Zhen Chong, Maximilien Evrard, Chi Ching Goh, Lai Guan Ng
Monocytes, dendritic cells (DCs) and macrophages have been classically categorized into the mononuclear phagocyte system (MPS) based on their similar functional and phenotypic characteristics. While an increasing amount of research has revealed substantial ontogenic and functional differences among these cells, the reasons behind their heterogeneity and strategic positioning in specific niches throughout the body are yet to be fully elucidated. In this review, we outline how recent advances in intravital imaging studies have dissected this phenomenon and have allowed us to appreciate how MPS cells exploit their regional niches to specialize and maximize their functional properties. Understanding their cellular behavior in each of their specialized microenvironment will eventually allow us to target specific cells and their behavioral patterns for improved vaccine and therapeutic purposes.



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The role of adult attachment orientation and coping in psychological adjustment to living with skin conditions

Abstract

Background

Skin conditions can be associated with significant psychological distress. Investigation of attachment orientation and associated use of coping strategies is a promising perspective from which to investigate psychological adjustment to skin conditions.

Objectives

To examine the role of adult attachment orientation, conceptualised as two dimensions: attachment avoidance and attachment anxiety, in psychological adjustment (appearance related distress and skin related quality of life) and the mediating role of two coping strategies: defeatism and activity.

Methods

Attachment avoidance and attachment anxiety (ECR), use of coping strategies (COPE), appearance related distress (DAS 24) and skin related quality of life (Skindex-16) were assessed through a cross-sectional online survey in 207 adults with skin conditions. Multiple mediation analyses were performed using PROCESS path analysis.

Results

Overall, higher attachment avoidance and higher attachment anxiety were associated with higher appearance related distress and greater impact on emotions and functioning aspects of quality of life. For attachment anxiety, the relationship was fully explained by more frequent use of defeatism coping. For attachment avoidance, the relationship was partially explained by more frequent use of defeatism coping (and in the case of appearance related distress also more frequent use of activity coping), and higher attachment avoidance was also associated with poorer psychological adjustment in a way that could not be explained by use of assessed coping strategies.

Conclusions

Insecure attachment orientation (high attachment avoidance or high attachment anxiety) is linked to poorer adjustment. People with insecure attachment might benefit from psychological interventions that target underlying attachment orientation.

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Lymphoedema in Lentigo Maligna patients treated with imiquimod, a long term adverse effect

Abstract

Lentigo Maligna (LM) is a potential precursor lesion of Lentigo Maligna Melanoma (LMM). It is treated to prevent progression to LMM. A recent epidemiological study reports a progression rate of 2.0-2.6% over a course of 25 years¹. The gold standard of treatment is surgical excision with 5 mm margin². Topical application of imiquimod cream is an off-label alternative.

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Efficacy of anti-PD-1 on skin carcinomas and melanoma metastases in an Xeroderma Pigmentosum patient

Abstract

Xeroderma pigmentosum is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-PD-1 antibody on both melanoma and skin carcinoma in a xeroderma pigmentosum patient.

A 17-year old patient presented with metastatic melanoma and multiple non melanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at the dose of 2mg/Kg 3 weeks apart. Parallel therapeutic efficacy of anti-PD1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24.

This observation suggests anti-PD1 may be considered in patients with XP and metastatic melanoma as well as advanced non melanoma skin cancer.

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Novel POFUT1 mutation associated with hidradenitis suppurativa-Dowling Degos Disease firm up a role for Notch signalling in the pathogenesis of this disorder

Abstract

We read with great interest the article by Pavlovsky et al;¹ describing PSENEN mutations associated with hidradenitis suppurativa-Dowling Degos Disease (HS-DDD) and suggesting a role for Notch signalling in the pathogenesis of this disorder. The literature also describes mutations in the POFUT1 gene as causative genetic defects in Dowling Degos Disease.² Decreased Notch activity is associated with mutations in POFUT1.

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