Theophylline as `add-on' therapy to cetirizine in patients with chronic idiopathic urticaria - A randomized, double-blind, placebo-controlled pilot study

Background: Chronic urticaria is a prevalent condition associated with substantial disability. Its pathogenesis is not clearly understood and is divided into autoimmune and chronic idiopathic urticaria (CIU). We investigated if the non-specific phosphodiesterase inhibitor theophylline could provide additional benefit to the histamine-1 receptor (H-1R) antagonist cetirizine in CIU. Methods: This was a double-blind, placebo-controlled, parallel study. Patients were randomized to receive either cetirizine and theophylline (200 mg twice daily; group A, 67 subjects) or cetirizine and placebo for 6 months (group B, 67 subjects). Group A patients took theophylline for 6 more months. Response was assessed by visual analog scale ( VAS) and treatment effectiveness score (TES). Blood theophylline levels were also determined at visit t = 1 and t = 7. Results: The study was completed by 54 of the 67 patients (80.6%) in group A and 51 of the 67 patients (76.1%) in group B. The physician VAS values for group A were lower after t = 3, while the patient VAS values were decreased after t = 2. The physician and patient TES values in group A were statistically higher (p < 0.05) at all time points except for t = 1. At least 1 month of theophylline addition was necessary to obtain statistically significant benefit over cetirizine, and reducing theophylline by 50% during phase 2 did not alter this benefit. Pruritus values were reduced, but not statistically significant. Conclusions: Addition of theophylline to conventional H-1R antagonists was well tolerated without any adverse effects and provided considerable additional benefit in the management of CIU. Copyright (C) 2006 S. Karger AG, Basel

Chronic Ocular Complications of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: The Role of Systemic Immunomodulatory Therapy

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially blinding diseases that affect the skin and mucous membranes. Although the cutaneous manifestations tend to be self-limited and resolve without sequelae, the chronic ocular complications associated with SJS/TEN can persist despite local therapy. Poor understanding of the underlying pathophysiology and lack of a standardized clinical approach have resulted in a paucity of data in regards to suitable treatment options. Inflammatory cellular infiltration and elevated levels of ocular surface cytokines in the conjunctival specimens of affected patients give credence to an underlying immunogenic etiology. Furthermore, the presence of ongoing ocular surface inflammation and progressive conjunctival fibrosis in the absence of exogenous aggravating factors suggest a possible role for systemic immunomodulatory therapy (IMT). We review in detail the proposed immunogenesis underlying chronic ocular SJS/TEN and the possible utility of systemic IMT

Primary central nervous system lymphoma: Inter‐compartmental progression

Abstract There is limited understanding of the inter‐compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18–92]; median follow‐up 35 months [0.1–237.0]) from 2000 till 2018 were divided into group 1 (ocular, 44 patients): 1A and 1B without and with CNS progression and group 2 (CNS, 190 patients): 2A and 2B without and with ocular progression, respectively. In group 1 (44 patients), 33 patients received local treatment, and 11 patients received systemic treatment. In group 2 (15 patients), six patients received combination treatment, while seven patients received only systemic treatment. A complete response was observed in 19 (43%) and 91 (48%) patients in groups 1 and 2, respectively. The 2‐year progression‐free survival (PFS) was 35% (95% CI: 0.23, 0.54) and 56% (95% CI: 0.49, 0.63) for groups 1 and 2, respectively (p < 0.0001). Age < 60 years was significantly associated with longer PFS (median PFS 48 vs. 24 months, p = 0.01). The overall survival (OS) at 2‐year was similar among groups 1 and 2 (83% and 67%), respectively (p = 0.06). Thus, Initial compartment of involvement does not influence local response rate or OS

Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process

Many skin disorders are associated with increased numbers of activated mast cells and are worsened by stress; however, the mechanism underlying these processes is not understood. Corticotropin-releasing hormone (CRH) is secreted under stress from the hypothalamus, but also in the skin, where it induces mast cell activation and vascular permeability. We investigated the effect of CRH in a number of animal models by using i.v. Evans blue extravasation as a marker of vascular permeability. Intradermal CRH is among the most potent peptides at 100 nM, its effect being nearly comparable to that of neurotensin (NT). Pretreatment of skin injection sites with the NT receptor antagonist SR48692 blocks CRH-induced vascular permeability, which is diminished in NT−/− mice, implying that NT is necessary for the effect of CRH. CRH and NT precursor mRNA are shown to be expressed in both dorsal root ganglia and skin, whereas the latter also expresses mRNA for prohormone convertase 5, an enzyme that cleaves pro-NT into its active form. We also show that the effect of both CRH and NT is absent in W/W(v) mast cell-deficient mice; however, only a fraction of skin mast cells express CRH receptors, as shown by FACS analysis of CRH receptor (CRHR) and c-kit double-positive disaggregated mouse skin mast cells. These findings suggest that CRH induces skin vascular permeability through NT acting on mast cells and that both peptides should be considered in the pathogenesis of skin disorders exacerbated by stress