H2 antihistamines: May be useful for combination therapies in cancer?

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.

Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review.

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

Pruritus related to trastuzumab and pertuzumab in HER2 + breast cancer patients.

PURPOSE: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2 + breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. METHODS: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2 + breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. RESULTS: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. CONCLUSIONS: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Impact of antihistamine use on the survival outcomes of immune checkpoint inhibitors in advanced cancer patients.

Histamine and H1 receptors play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) might increase the effect of ICIs. This study aimed to evaluate the impact of antihistamines on the oncological outcomes of ICIs. This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. A total of 133 patients receiving ICIs in the metastatic setting were included. Melanoma (33.1%) was the most common tumor type. The most common ICI was nivolumab (63.2%). Fifty-five (38.4%) patients received antihistamines concomitantly with ICIs. The most common antihistamine was pheniramine (85.5%). The median progression-free survival (PFS) (8.2 vs. 5.1 months, P  = 0.016) and overall survival (OS) (16.2 vs. 7.7 months, P  = 0.002) were longer in patients receiving antihistamines concomitantly with ICIs. In multivariate analysis, PFS [hazard ratio (HR) = 0.63, 95% CI: 0.40-0.98, P  = 0.042] and OS (HR = 0.49, 95% CI: 0.29-0.81, P  = 0.006) were also better in those patients after adjusting for confounding factors, such as performance status, bone or liver metastasis, and concurrent chemotherapy. This study suggested that antihistamines may enhance the efficacy of ICIs in patients with advanced cancer. If validated in prospective trials, antihistamines and ICIs combinations might be new options to improve oncological outcomes.

Premedication strategy in cetuximab rechallenge after Grade 2 hypersensitivity reactions.

INTRODUCTION: Cetuximab, an IgG1 monoclonal antibody, is utilized in the treatment of metastatic colorectal cancer and squamous cell head and neck cancers. Due to the risk of hypersensitivity reactions, standard premedication with a histamine-1 (H-1) antagonist is recommended prior to administration, however, there is less guidance for premedication strategies to assist with rechallenge after infusion reactions. Here, we describe two cases of successful cetuximab treatment after Grade 2 reactions, in addition to risk factors and proposed premedication strategies for successful rechallenge. CASE REPORT: Two patients who experienced Grade 2 hypersensitivity reactions were both successfully rechallenged with increased premedications 1-2 weeks after initial infusions. The first patient was a 56-year-old male diagnosed with metastatic colorectal cancer receiving cetuximab as part of a clinical trial. The second patient was a 73-year-old male diagnosed with head and neck cancer receiving cetuximab as part of standard of care concurrent with radiation. MANAGEMENT AND OUTCOME: Each patient was rechallenged with an increased premedication strategy including dexamethasone, famotidine, diphenhydramine, and acetaminophen in addition to reducing the infusion rate. Both patients either continued treatment or successfully completed therapy, without any additional infusion-related reactions. DISCUSSION: We aimed to review risk factors related to cetuximab infusion reactions and propose a premedication strategy for rechallenge postreaction. Known risk factors include male sex and the accumulation of cetuximab-specific IgE. These may be mitigated by the addition of increased premedication with dexamethasone and famotidine with concurrent reduced infusion rate.

Effects of Opioids, Steroids, Benzodiazepines, Anticholinergics, and Antihistamines on the Efficacy of Antipsychotics for Treating Delirium in End-of-Life Adult Patients Undergoing Palliative Care.

The purpose of the study was to determine the effect of combination therapy involving opioids, steroids, benzodiazepines, anticholinergics, and antihistamines on antipsychotics efficacy for delirium. The study included adult inpatients receiving end-of-life palliative care and diagnosed with hyperactive delirium. Changes in delirium symptoms were assessed using the Intensive Care Delirium Screening Checklist (ICDSC). A retrospective analysis was conducted on 97 patients with ICDSC scores of ≥4, comparing the scores before and after antipsychotic administration. A mean score <4 sustained for 3 days after antipsychotics administration was considered effective. The mean days with ICDSC <4 within a 3-day period were evaluated as well. The efficacy of antipsychotics was compared between cases with and without the use of opioids, steroids, benzodiazepines, anticholinergics, and antihistamines. The results revealed no significant differences in the efficacy of antipsychotics for delirium when used in conjunction with opioids (odds ratio 0.614, 95% CI [0.179-2.105]), benzodiazepines (0.387, [0.108-1.390]), steroids (1.258, [0.276-5.746]), or anticholinergics (2.085, [0. 148-29.458]). Additionally, no significant differences were observed in the mean days with ICDSC <4 within 3-day period. Although opioids, benzodiazepines, steroids, anticholinergics, and antihistamines are recognized as delirium risk factors, their use for symptom relief in patients with delirium may not affect antipsychotic efficacy.

Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.

Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARß). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.

Updates in the diagnosis and practical management of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on the history and documentation of sensitization, such as the production of allergen-specific IgE, preferably using molecular diagnostics. Treatments are based on patient education, non-pharmacological and pharmacological remedies, allergen-specific immunotherapy (AIT), and surgery. Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. AREAS COVERED: This review discusses current and emerging management strategies for AR, covering pharmacological and non-pharmacological remedies, AIT, and biologics in selected cases with associated severe asthma. However, AIT presently remains the unique causal treatment for AR. EXPERT OPINION: The management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered in the fixed association between intranasal antihistamines and corticosteroids, probiotics and other natural substances, and new formulations (tablets) of AIT.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Abstract Objective: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. Methods: Between July 2018- February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. Results: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p<0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p>0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p< 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p>0.05). Conclusion: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. Level of evidence: 1B.

Successful treatment with Omalizumab of a child affected by Systemic Mastocytosis: clinical and biological implications.

BACKGROUND: Pediatric Mastocytosis is a rare and heterogeneous disease, characterized by accumulation of mast cells in the skin (Cutaneous Mastocytosis) and/or, less frequently, in other organs, mainly liver, spleen, bone marrow, lymph nodes and gastrointestinal tract (Systemic Mastocytosis). Patients affected by Systemic Mastocytosis show symptoms caused by  a massive release of mast cell mediators: itching, flushing, abdominal pain, generalized weakness, fatigue and neuropsychiatric disorders. Moreover, children with Systemic Mastocytosis are at greater risk of anaphylactic/anaphylactoid reactions, often poorly controlled by the conventional therapy with antihistamines, mast cells stabilizers and steroids. As a result, children affected by Systemic Mastocytosis have a poor quality of life and suffer the consequence of prolonged steroidal treatment. CASE PRESENTATION: A child with Systemic Mastocytosis and severe symptoms, refractory to symptomatic and steroidal therapy, has been successfully treated with Omalizumab, an anti-IgE monoclonal antibody usually employed in allergic patients with severe asthma and orticaria. The onset of clinical benefit of Omalizumab therapy was extraordinarily rapid, but proved to be strictly dependent on drug administration. The child has become completely and steadily asymptomatic. No other anaphylactic episodes have been reported. Steroid treatment could be definitively withdrawn after the second dose of Omalizumab, and all the other medications were later reduced. Twenty months after beginning, Omalizumab therapy is still ongoing with good symptomatology control; no side effects have been observed so far. CONCLUSIONS: In our experience, Omalizumab is an effective treatment for children affected by Systemic Mastocytosis not responding to conventional medical treatments. The main strengths of this therapy are its rapid and extraordinary efficacy to control the severe mast cells mediator-related symptoms, the lack of side effects and its steroid-sparing effect. However, more extensive and controlled studies in pediatric patients affected by Systemic Mastocytosis are needed to substantiate these promising findings.

Meclizine, a piperazine-derivative antihistamine, binds to dimerized translationally controlled tumor protein and attenuates allergic reactions in a mouse model.

Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like activity. Therefore, dTCTP is considered as a therapeutic target for allergic diseases. Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes. In this study, nine compounds listed in the literature as interacting with mTCTP were investigated for their ability to suppress the activity of extracellular dTCTP in bronchial epithelial cells. It was found that one of the nine, meclizine, a piperazine-derivative antihistamine, significantly reduced IL-8 release and suppressed the NF-κB pathway. The direct interaction of meclizine with dTCTP was confirmed by surface plasmon resonance (SPR). Also, we found that meclizine can attenuate ovalbumin (OVA)-induced airway inflammation in mice. Therefore, meclizine might be a potential anti-allergic drug as an inhibitor for dTCTP.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial.

OBJECTIVE: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. METHODS: Between July 2018-February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. RESULTS: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p < 0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p > 0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p < 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p > 0.05). CONCLUSION: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. LEVEL OF EVIDENCE: 1B.

Prevalence of polypharmacy and associated adverse outcomes and risk factors among children with asthma in the USA: a cross-sectional study.

OBJECTIVE: To estimate the prevalence of polypharmacy, identify risk factors and examine related adverse outcomes in the US children with asthma. DESIGN, SETTING AND PARTICIPANTS: This population-based, cross-sectional study included 1776 children with asthma from the 2011-2020 National Health and Nutrition Examination Surveys. EXPOSURES: Polypharmacy is defined as taking ≥2 medications concurrently for ≥1 day over the past 30 days. MAIN OUTCOMES AND MEASURES: (1) Weighted prevalence estimates of polypharmacy in children with asthma; (2) asthma attacks and emergency department (ED) visits. RESULTS: The estimated prevalence of polypharmacy in the US children with asthma was 33.49% (95% CI 31.81% to 35.17%). 15.53% (95% CI 14.31% to 16.75%), 12.63% (95% CI 11.37% to 13.88%) and 5.33% (95% CI) of participants were taking 2, 3-4, and 5 prescription medications, respectively. In addition to asthma medications, the most common sources of polypharmacy included antihistamines (20.17%, 95% CI 16.07% to 24.28%), glucocorticoids (16.67%, 95% 12.57% to 20.78%), and anti-infectives (14.28%, 95% CI 10.29 to 18.28). Risk factors for the increased number of medications included age 5-11 years old (vs 1-4 years: adjusted incidence rate ratio (aIRR) 1.38, 95% CI 1.10 to 1.72), fair-to-poor health (vs excellent or very good: aIRR 1.42, 95% CI 1.05 to 1.92), or ≥6 healthcare utilisation encounters over the last year (vs 0-5 encounters: aIRR 1.45, 95% CI 1.26 to 1.66). Polypharmacy increased the odds of an asthma attack (adjusted OR (aOR) 2.80, 95% CI 1.99 to 3.93) and ED visit (aOR 2.41, 95%1.59-3.63) after adjusting for demographics, insurance and health status. CONCLUSIONS: Every one in three US children with asthma experienced polypharmacy. Although it may reflect the treatment guidelines that various asthma medications are needed for maintenance therapy, our results suggested that polypharmacy increased the odds of asthma attacks or ED visits. This may be due to the concurrent use with other non-asthma medications indicating that there is an opportunity to improve medication management in children with asthma.

Factors Associated With Refractoriness to an Up to Fourfold Dosage of Antihistamines in Isolated Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease and has a significant impact on patients' quality of life. The aim of treatment is complete symptom control. AIM: To identify potential factors associated with antihistamine-refractory isolated CSU and to determine the factors that predict response to second-generation H1 antihistamines at dosages from one- to fourfold. METHODS: We conducted a retrospective cohort study, which included adult patients diagnosed with isolated CSU and had complete symptom control. Clinical and laboratory findings were compared between the patients who were responsive to second-generation H1 antihistamines (< fourfold) and those who were refractory to a fourfold dose. Clinical and laboratory data were compared by dosage in the antihistamine-responsive group. RESULTS: There were 182 isolated CSU patients who met the study criteria, of whom 150 (82.4%) were responsive to treatment with up to a fourfold dose of second-generation H1 antihistamines, while 32 (17.6%) were refractory. In univariate analysis, age at onset, body mass index, baseline Urticaria Activity Score-7 (UAS7), white blood cell count, total neutrophil count, neutrophil-lymphocyte ratio, platelet count, and new generation antihistamines were significantly higher in the antihistamine-refractory group. According to multivariate analysis, baseline UAS7 was the only independent factor associated with antihistamine-refractory isolated CSU (odds ratio 1.14, 95% CI 1.01-1.28, P = .03). In the antihistamine-responsive group, white blood cell count tended to predict response to antihistamine treatment (P < .001, 0.04, 0.34 between onefold and twofold, twofold and threefold, and threefold and fourfold, respectively). CONCLUSION: Baseline UAS7 was an independent factor associated with antihistamine-refractory isolated CSU.

Efficacy of cationic amphiphilic antihistamines on outcomes of patients treated with immune checkpoint inhibitors.

BACKGROUND: Cationic amphiphilic antihistamines have been shown to improve patient outcomes in immunogenic tumours, but whether they can augment and improve response to immunotherapy is unknown. We aim to evaluate the effect of cationic amphiphilic antihistamines in patients receiving immune checkpoint inhibitors (ICIs). METHODS: We conducted a retrospective propensity score-matched cohort study at two tertiary referral centres in Taiwan between January 2015 and December 2021. Patients who received desloratadine, cyproheptadine, and ebastine were classified as cationic amphiphilic antihistamine users. The primary outcome was overall survival, and the secondary outcomes were progression-free survival and clinical benefit rate. Patients treated with cationic amphiphilic antihistamines were matched to patients who received non-cationic amphiphilic antihistamines based on variables including age, cancer type, stage, and history of allergic diseases. RESULTS: A total of 734 ICI-treated patients were included. After matching, 68 cationic amphiphilic antihistamine and non-cationic amphiphilic antihistamine users remained for analysis. Compared with non-cationic amphiphilic antihistamine users, patients who received cationic amphiphilic antihistamines had a significantly longer median overall survival (24.8 versus 10.4 months; Log-rank, p = 0.018) and progression-free survival (10.6 versus 4.93 months; Log-rank, p = 0.004). The use of cationic amphiphilic antihistamines was associated with an approximately 50% lower risk of all-cause mortality (HR, 0.55 [95% CI: 0.34-0.91]). Survival benefits were not seen in patients who received cationic amphiphilic antihistamines before immune checkpoint blockade. These survival benefits were observed regardless of the generation of cationic amphiphilic antihistamines. CONCLUSION: The use of cationic amphiphilic antihistamines was associated with improved survival among patients treated with immunotherapy.

Chronic Nodular Prurigo: A Retrospective Study of 74 Cases. / Prurigo crónico nodular: Estudio retrospectivo de 74 casos.

BACKGROUND AND OBJECTIVE: Chronic nodular prurigo (CNPG) is a recently defined and currently underdiagnosed disease with a variety of causes. It is associated with multiple comorbidities, and its management and treatment have improved with a better understanding of its pathogenesis. The aim of this study was to describe our experience with a series of patients with CNPG. MATERIAL AND METHODS: Single-center, observational, retrospective study of the sociodemographic and clinical characteristics of patients with CNPG seen at the dermatology department of a tertiary care hospital between 2009 and 2021. RESULTS: We included 74 patients, mostly women (63.5%), with a mean age of 57 years. Overall, 39.2% of patients had a concomitant skin condition, mainly atopic dermatitis (62%). Other comorbidities included endocrine disorders (54.1%), cardiovascular disease (44.4%), and psychiatric disorders (36.5%). Skin biopsy helped confirm the clinical diagnosis in 70% of cases. The mean immunoglobulin E level was higher than normal (516 IU/mL), regardless of atopic predisposition. On average, patients received 3 treatments, the most common choices being methotrexate, antihistamines, and topical and oral corticosteroids. Methotrexate was among the most effective options. CONCLUSIONS: CNPG is a complex disease associated with multiple comorbidities. It requires a multidisciplinary approach, with the dermatologist at the center. Classical treatment approaches are probably insufficient.

Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice.

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.

Successful desensitization under antihistamine suppression in a case with urticaria due to osimertinib.

INTRODUCTION: Osimertinib is an approved therapy for patients with a Thr790met (T790M) mutation diagnosed with non-small cell lung cancer (NSCLC) that progresses during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. However, in 7-13% of patients, drug-related side effects lead to discontinuation of osimertinib treatment. In such cases, osimertinib desensitization is a treatment option that can be considered. CASE REPORT: A 59-year-old female patient, who was followed up with the diagnosis of stage 4 NSCLC, was consulted to the allergy clinic because of urticaria. The patient developed urticaria plaques 20 h after the third dose of osimertinib tablet. MANAGEMENT & OUTCOME: With the diagnosis of osimertinib-induced urticaria, desensitization was planned for the patient. Treatment was started with a dose of 0.1 mg/day osimertinib. The procedure was completed in approximately 50 days, and a dose of 80 mg/day was reached with antihistamine suppression. DISCUSSION: Here, a successful osimertinib desensitization in a patient with a history of osimertinib-related type 1 allergic reaction is reported. Osimertinib desensitization is a treatment option that should be considered in cases where treatment has to be ceased due to drug-related side effects.

Directrices para el diagnóstico clínico y el tratamiento del Dengue, el Chikunguña y el Zika / Guidelines for the clinical diagnosis and treatment of Dengue, Chikungunya, and Zika

En la actualidad, las guías basadas en la evidencia constituyen una de las herramientas más útiles para mejorar la salud pública y la práctica clínica. Su finalidad es formular intervenciones con sólidas pruebas de eficacia, evitar riesgos innecesarios, utilizar los recursos de forma eficiente, disminuir la variabilidad clínica y, en esencia, mejorar la salud y garantizar una atención de calidad, razón de ser de los sistemas y servicios de salud. Las presentes directrices se elaboraron siguiendo la metodología GRADE con el apoyo de un panel de expertos clínicos de distintos países, todos ellos convocados por la Organización Panamericana de la Salud. Por medio de la respuesta a doce preguntas clave sobre el diagnóstico clínico y el tratamiento del dengue, el chikunguña y el zika, se formulan recomendaciones basadas en evidencia para pacientes pediátricos, jóvenes, adultos, personas mayores y embarazadas expuestos a estas enfermedades o con sospecha o diagnóstico confirmado de infección. La finalidad de las directrices es evitar la progresión a las formas graves y a los eventos mortales que puedan causar. Las recomendaciones están dirigidas a profesionales de la salud, incluidos el personal médico general, residente y especialista; y los profesionales de enfermería, así como a estudiantes de medicina y enfermería, quienes de una u otra forma participan en la atención de pacientes con sospecha de dengue, chikunguña o zika. También se dirige a los administradores de las unidades de salud y a los equipos directivos de los programas nacionales de prevención y control de enfermedades arbovirales, quienes tienen la responsabilidad de facilitar el proceso de aplicación de estas directrices. Esperamos que esta publicación beneficie no solo al personal de salud, que dispondrá de información científica actualizada y de la mejor calidad posible, sino a los menores, los adultos, las embarazadas, las personas mayores y la población en general, quienes recibirán una mejor atención de salud prestada por personal médico debidamente capacitado.

Evidence-based guidelines are one of the most useful tools for improving public health and clinical practice. Their purpose is to formulate interventions based on strong evidence of efficacy, avoid unnecessary risks, use resources efficiently, reduce clinical variability and, in essence, improve health and ensure quality care, which is the purpose of health systems and services. These guidelines were developed following the GRADE methodology, with the support of a panel of clinical experts from different countries, all convened by the Pan American Health Organization. By responding to twelve key questions about the clinical diagnosis and treatment of dengue, chikungunya, and Zika, evidence-based recommendations were formulated for pediatric, youth, adult, older adult, and pregnant patients who are exposed to these diseases or have a suspected or confirmed diagnosis of infection. The purpose of the guidelines is to prevent progression to severe forms of these diseases and the fatal events they may cause. The recommendations are intended for health professionals, including general, resident, and specialist physicians, nursing professionals, and medical and nursing students, who participate in caring for patients with suspected dengue, chikungunya, or Zika. They are also intended for health unit managers and the executive teams of national arboviral disease prevention and control programs, who are responsible for facilitating the process of implementing these guidelines.

Antihistamines-refractory chronic pruritus in psoriatic patients undergoing biologics: aprepitant vs antihistamine double dosage, a real-world data.

BACKGROUND: Psoriasis-related pruritus (PRP) in patients under systemic treatment is challenging. The risk to switch anti-psoriatic drugs and to lose response to previous therapy is high, thus dermatologists prefer to add an anti-pruritic agent. OBJECTIVES: To evaluate the effect of anti-histamines and aprepitant in treating PPR of psoriatic patients undergoing systemic anti-psoriatic therapies. METHODS: A pilot observational open-label study was performed on responsive psoriatic patients with PPR under treatment. Initial therapy included oral rupatadine (10 mg/day for 30 days). In case of the Epworth Sleepiness Scale (ESS) was above 14, patients were switched to aprepitant (80 mg/day for 7 days), otherwise, rupatadine dosage was increased (20 mg/day for 7 days). Clinical evaluation was performed at the baseline (T0) and after 7 days (T7). RESULTS: We enrolled 40 patients with PPR, 20 in each group. Age, gender, Psoriatic arthritis (PsA) and the itch - VAS, were matched. At T7, aprepitant displayed higher improvements than rupatadine (itch - VAS = 4 [3-5] vs 8.5 [8-9], p < .01, DLQI = 14 [13-16] vs. 18 [16-21], p < .01 and ESS = 5 [4-7] vs 15 [14-16], p < .01). Doubling the rupatadine dosage from 10 mg to 20 mg/day only slightly improve itch (itch - VAS = 9 [8-10] vs 9 [8-9], p = .03), conversely no modifications in the quality of life (DLQI = 18 [17-20] vs 18 [17-21], p = .73) and increased sleepiness (ESS = 10 [9-11] vs 15 [14-16], p < .01). CONCLUSIONS: Aprepitant may be a valid alternative in PPR patients with ESS >14 under antihistamines.