The molecular mechanism of the adverse effects of the biological and small molecular drugs in the therapy of inflammatory skin diseases - psoriasis and atopic dermatitis

Lemiesz P, Nowowiejska-Purpurowicz J, Flisiak I. Ann Med. 2026 Dec;58(1):2611461. doi: 10.1080/07853890.2025.2611461.

Abstract

The summary of pathogenesis and comparison between
psoriasis and atopic dermatitis.

Patients with the most common chronic inflammatory dermatoses, namely psoriasis and atopic dermatitis, gained access to state-of-the-art therapeutic options providing spectacular improvement of skin lesions. Although generally safe, biological agents and small molecular drugs have also side effects which may be mild and irrelevant to the therapy course, but sometimes, of a greater extent and influencing further therapeutic decisions. In this review, we summarize the molecular explanation for the most common adverse effects of drugs used in the treatment of psoriasis and atopic dermatitis. Biologics used in psoriasis predominantly target TNFα, IL-17, 23, while in AD inhibit IL-4,13,31. Janus kinase (JAK) inhibitors represent small-molecule therapies effective in both conditions, although more prominently in AD.

Five-Grass-Pollen Sublingual Immunotherapy Drops Are Efficacious and Well Tolerated in Adults: The RHAPSODY Phase III Trial

Didier A, Juhl RG, Dalgaard T et al. Allergy. 2025 Dec 24. doi: 10.1111/all.70191.

ABSTRACT

Background

Tablet formulations of allergen extracts are widely recommended over other formulations for the sublingual immunotherapy (SLIT) of respiratory allergies. However, with adequate clinical trial evidence, SLIT (liquid) drop formulations may be a relevant allergy treatment option.

Methods

Graphical Abstract

The RHAPSODY multinational, Phase III, parallel-group, double-blind, placebo-controlled, randomised clinical study of adults with moderate-to-severe, grass-pollen-induced allergic rhinoconjunctivitis (ARC) with or without asthma was conducted at 45 investigating centres in six European countries. Participants received 26 months of continuous treatment with active 5-grass-pollen SLIT drops or placebo. The primary efficacy endpoint was the average daily total combined score (TCS, comprising a symptom score and a rescue medication score) during the second peak grass pollen season (PGPS).

Results

Of the 445 randomised patients (mean ± standard deviation (range) age: 32.6 ± 9.9 (18–63); males: 55.1%), 389 completed the trial.

Baseline Monocyte Count Predicts Complete Response to Omalizumab in Chronic Spontaneous Urticaria: A Retrospective Analysis

Turhan İ D, Solak B (January 01, 2026) Cureus 18(1): e100556. doi:10.7759/cureus.100556

Abstract

Introduction: Chronic spontaneous urticaria (CSU) is a distressing skin condition characterized by wheals and angioedema. While omalizumab is an effective biologic therapy for antihistamine-refractory CSU, a subset of patients shows partial or no response. Identifying reliable biomarkers to predict treatment outcomes remains a significant clinical need. This study aimed to investigate the relationship between systemic inflammatory parameters, specifically monocyte counts, and the clinical response to omalizumab.

Methods: This retrospective study included 52 patients with CSU treated with omalizumab (300 mg/four weeks) for at least 12 weeks at a tertiary referral center. Patients were stratified into two groups based on their response at week 12: "Complete Response" (Urticaria Activity Score over seven days (UAS7) = 0) and "Non-Complete Response." Baseline and post-treatment complete blood count (CBC) parameters, C-reactive protein (CRP), and total IgE levels were analyzed. Binary logistic regression was performed to identify independent predictors of response.

Binary logistic regression analysis for independent
predictors of complete response to omalizumab

Results: Eleven patients (21.15%) achieved a complete response. The complete responder group exhibited significantly higher baseline median monocyte counts (0.68 vs. 0.40 K/µL, p = 0.001) and basophil counts (p = 0.032), but significantly lower baseline CRP levels (p = 0.003) compared to non-responders.

Rebound Pruritus and Urticaria Post-discontinuation of Chronic Cetirizine Use: A Case Report.

Seng J, Cai M, Oka P (December 27, 2025) Cureus 17(12): e100214. doi:10.7759/cureus.100214

Abstract

Timeline of events

Cetirizine is a common over-the-counter antihistamine used to treat allergic rhinitis, eczema, and urticaria. There have been increasing reports showing increased risk of rebound pruritus following discontinuation of long-term antihistamine use in the United States and the Netherlands. However, evidence on this condition and its management among Asian populations remains limited. We report the case of a Chinese male in his 50s with a background of hypertension, hyperlipidaemia, and chronic urticaria who had been regularly taking over-the-counter cetirizine for the past two years.

Abstracts of the 14th C1-inhibitor Deficiency and Angioedema Workshop

 Allergy Asthma Clin Immunol 21 (Suppl 2), 55 (2025). https://doi.org/10.1186/s13223-025-00992-1

Preface

We are pleased to welcome all participants to the 14th C1-inhibitor Deficiency & Angioedema Workshop.

The aim of the Workshop is to present new research findings related to rare bradykinin-mediated angioedema disorders. These include conditions caused by hereditary or acquired C1-inhibitor deficiency, as well as those with a hereditary background but normal C1-inhibitor levels. This year, a record number of abstracts will be presented over the four-day program, including 49 oral and 58 poster presentations. In addition to previously unpublished findings, five outstanding keynote lectures will also be delivered.

On the opening afternoon, Nobel Laureate Katalin Karikó will give a special lecture on the development of the mRNA vaccine, sharing all the insights gained from the long and persistent journey that led to the production of life-saving mRNA-based vaccines.

COVID-19 mRNA Vaccination and 4-Year All-Cause Mortality Among Adults Aged 18 to 59 Years in France

Semenzato L, Le Vu S, Botton J, et al.  JAMA Netw Open. 2025;8(12):e2546822. doi:10.1001/jamanetworkopen.2025.4682

Key Points

Question  Are COVID-19 mRNA vaccines associated with the long-term risk of all-cause mortality?

Findings  In this cohort study including 22.7 million vaccinated individuals and 5.9 million unvaccinated individuals, vaccinated individuals had a 74% lower risk of death from severe COVID-19 and no increased risk of all-cause mortality over a median follow-up of 45 months.

Meaning  These national-level results found no increased risk of 4-year all-cause mortality in individuals aged 18 to 59 years vaccinated against COVID-19, further supporting the safety of the mRNA vaccines that are being widely used worldwide.

Abstract

Importance  While several studies have assessed the impact of COVID-19 vaccination on short-term mortality, none have compared long-term mortality by vaccination status, particularly in young individuals who are less likely to experience severe disease following SARS-CoV-2 infection.

TZ1391: a computationally designed circular mRNA multi-epitope vaccine candidate against Mycobacterium tuberculosis via TLR3 immunomodulation

Ali, A., Alamri, A., Mishra, V.K. et al.  BMC Immunol (2026). https://doi.org/10.1186/s12865-025-00795-4

Abstract

Graphical Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health burden due to latent infection, multidrug resistance, and the limited efficacy of the BCG vaccine. To address this challenge, we computationally designed and evaluated a circular mRNA-based multi-epitope vaccine candidate, TZ1391. Five experimentally validated M. tuberculosis antigens (ESAT-6, CFP-10, Ag85B, PPE18, and HspX) were used to predict immunodominant cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes.

Peanut Oral Immunotherapy Using 30 and 300 mg Maintenance Doses

Upton JEM, Toscano-Rivero D, Ke D, Berenjy A et al.  J Allergy Clin Immunol Pract. 2025 Oct 16:S2213-2198(25)00958-4. doi: 10.1016/j.jaip.2025.10.007. 

Abstract

Background

The lowest dose of peanut oral immunotherapy (P-OIT) has not been determined.

Objective

To evaluate whether very low-dose oral immunotherapy (30 mg) may safely and effectively increase tolerated doses and induce immunologic changes.

Methods

Visual Summary

We prospectively enrolled peanut-allergic children reactive to 444 mg peanut protein (PP) or less in double-blind placebo-controlled food challenges (DBPCFC) and randomly assigned them to three groups. Two were double-blinded P-OIT groups escalating to 30 mg (Group 30 mg) or 300 mg (Group 300 mg) PP maintenance doses. A third group followed open-label avoidance (Group Avoid). Cumulative tolerated doses of 443 mg or greater and 1,043 mg or greater PP were compared with Group Avoid by DBPCFC planned at 1 year.