Immune-enhancing agents in autoimmune skin diseases – A review

Immunosuppressive drugs are the main stay of treatment for autoimmune dermatoses. The main disadvantage of these drugs is the increased susceptibility to life-threatening infections. Hence, in recent years, there has been an enthusiastic search for newer groups of drugs that can reduce this risk. Immune enhancing agents are considered as the key players of future. Immune enhancers function by activating various elements of the immune system and thereby amplifying the immune responses. They can be specific or non-specific in action. The main autoimmune dermatoses where the benefits of these drugs have so far been utilized include alopecia areata, vitiligo, psoriasis, lichen planus, and discoid lupus erythematosus. Immunostimulants are available in both topical and systemic forms. Topical immune- enhancing agents include contact sensitizers (diphenylcyclopropenone, dinitrochlorobenzene, and squaric acid dibutyl ester), anthralin, topical zinc, and interferons. Systemic agents include levamisole, zinc, probiotics, and so on. The exact mechanism of action of some of these drugs and other autoimmune conditions where they can be benefited is not completely understood. Another therapeutic agent that may come up in the future is individualized vaccines. Let us look forward to the days when individualized vaccines work wonders in the management of autoimmune diseases.

Immune Response to Locoregional Therapy

The immune response to cancer is an ongoing area of interest and is the focus of newer systemic agents. Liver-directed therapy has been the standard treatment for primary and metastatic disease limited to the liver. It is increasingly being recognized that these therapies may influence a broader systemic response and immune activation. The clinical and translational data supporting this phenomenon are reviewed herein. The findings and potential impact of the immune response to liver-directed therapies are summarized in this article.

Prurigo excoriée treated with low dose naltrexone

A 53-year-old woman presented with a 25-year history of acne excoriée and prurigo excoriée. Her symptoms began in 1988 coinciding with her husband’s death from a brain tumour when she was 27. The pruritus affected her quality of life and disturbed her sleep. She had scarring on her face and body resulting from persistent scratching. The pruritus proved refractory to treatment despite a multi-modal treatment approach including multiple topicals, phototherapy and systemic agents such as isotretinoin, antibiotics, anxiolytic agents and neuromodulators. She was extremely frustrated that various treatments had been ineffective at controlling the itch-scratch cycle. She was commenced on low dose naltrexone (LDN), 3 mg nocte, and she became itch free within a few weeks. She reports that the LDN has had a beneficial impact on her quality of life.

Effects of Pain From Atopic Dermatitis: Interview and Focus Group Study With Patients and Their Families

Background Pain is an underappreciated symptom of atopic dermatitis that can affect the health-related quality of life (HRQL) of patients. Objective The aim of this study is to understand the effect of pain on patients with atopic dermatitis and their family members and to recognize how this symptom affects HRQL. Methods We conducted focus groups and interviews with patients with atopic dermatitis and their family members. Researchers independently coded the transcripts and reached a consensus on the major themes. Results A total of 33 adult participants, consisting of 21 patients with atopic dermatitis (median age 47 years, range 22-77) and 12 family members (median age 50, range 22-72), attended either focus groups (23/33, 70%) or interviews (10/33, 30%), where we assessed their experiences of pain. Four themes emerged in our study. Itchiness and pain can be intertwined: pain was often caused by or otherwise associated with itchiness and could result from open sores and excoriated skin. Characteristics of pain: pain was most often described as burning. Other descriptors included mild, persistent discomfort; stinging; and stabbing. Effects of pain: pain negatively affected various aspects of daily life, including choice of clothing, sleep, social activities, and relationships. The location of painful areas could also limit physical activity, including sex. Pain management: pain from atopic dermatitis could be managed to varying degrees with different over-the-counter and prescription treatments. Systemic agents that cleared the skin also resolved the pain associated with atopic dermatitis. Conclusions Pain can be a significant factor in the HRQL of patients with atopic dermatitis and should be considered by clinicians when caring for patients with atopic dermatitis.

Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment

Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

Risk of Developing Melanoma With Systemic Agents Used to Treat Psoriasis: A Review of the Literature

Background Psoriasis is a chronic inflammatory skin disease induced by autoimmune-like dysregulation of the immune system. Treatment options have drastically evolved in recent years, and treatment advances that target specific cytokines and other molecules involved in dysregulation have had a profound effect in controlling the disease. Objective We reviewed the literature to assess the risk of developing melanoma with conventional therapies and newer agents used to treat psoriasis. Methods A comprehensive literature search using Medline (via Ovid) and Embase was conducted. Results The majority of studies reviewed reported insignificant results. Potential risk for melanoma was identified for only 3 out of 15 anti-psoriatic treatments analyzed: adalimumab (relative risk 1.8, 95% CI 1.06-3.00), etanercept (relative risk 2.35, 95% CI 1.46-3.77) and infliximab (Empirical Bayes Geometric Mean 7.90, 95% CI 7.13-8.60). The confidence intervals provided are from prior studies. There are not enough collective data on newer agents to make any conclusions on risk. Conclusions We were unable to identify any substantial risk for developing melanoma due to the use of anti-psoriatic treatments. Until additional long-term registry data become available, it would be prudent to continue screening patients with psoriasis at baseline and periodically for melanoma when these agents are used.