Primary Thyroid Lymphoma: A Retrospective-Observational Study in a Single Institutional Center.

Background and Objectives: primary thyroid lymphoma (PTL) is a rare neoplasm, displaying a variety of histological features. It is often a challenge for pathologists to diagnose this tumor. Materials and Methods: this study is a retrospective analysis of clinical and pathological characteristics of a group of eleven patients (eight women and three men, mean age 68 years, range 50-80 years) diagnosed with PTL. Results: nine patients (81.81%) presented a tumor with progressive growth in the anterior cervical region, usually painless and accompanied by local compressive signs. Histologically, we identified six cases (55%) of diffuse large B-cell lymphoma, three cases (27%) of extranodal marginal zone lymphoma, one case (9%) of follicular lymphoma, and one case (9%) of mixed follicular-diffuse lymphoma. PTL was associated with microscopic Hashimoto autoimmune thyroiditis in ten cases (90.9%). Ten patients (90.9%) presented with localized disease (stage I-IIE). A percentage of 60% of patients survived over 5 years. We observed an overall longer survival in patients under 70 years of age. Conclusions: PTL represents a diagnosis that needs to be taken into account, especially in women with a history of Hashimoto autoimmune thyroiditis, presenting a cervical tumor with progressive growth. PTL is a lymphoid neoplasia with favorable outcome, with relatively long survival if it is diagnosed at younger ages.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

Managing Severe Adverse Reactions to Biologicals in Severe Asthma.

BACKGROUND: The use of biological agents in the treatment of various inflammatory and malignancy conditions has expanded rapidly. However, these agents can induce hypersensitivity reactions, posing significant clinical challenges. METHODS: We conducted a retrospective study that included nine patients with severe asthma who experienced hypersensitivity reactions to biological agents (omalizumab, benralizumab and dupilumab). RESULTS: Hypersensitivity reactions to biologicals in severe asthma were observed in 9 of 68 patients treated. In five cases, treatment was stopped or changed to another available biological, and for four patients administered under close surveillance, titrated provocation or desensitization was applied. Successful desensitization was achieved in three of the patients, allowing them to continue therapy without adverse reactions. Improvements in asthma control were observed post-desensitization, leading to the reduced need for systemic steroid treatments and an increase in quality of life. CONCLUSIONS: This study highlights the importance of recognizing hypersensitivity reactions to biologicals to have an appropriate approach for patients with severe asthma. As an effective approach for patients experiencing hypersensitivity reactions to biological agents, desensitization allows treatment continuation.

IL-31-Pruritus Interleukin: Serum Values and Clinical Impact in Chronic Spontaneous Urticaria-A Romanian Retrospective Study.

(1) Background: This study aimed to evaluate the implications of interleukin-31 (IL-31) in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters that were identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the accepted international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Significantly elevated serum IL-31 levels were observed in CSU patients compared to the controls (p < 0.0001). Although no direct correlations were found between IL-31 and inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)), eosinophils, or total immunoglobulins E (IgE), significant differences in IL-31 levels were identified based on CSU severity, quality of life impact, itch intensity, and response to histamine H1 receptor antagonists (H1 antihistamines) (p < 0.05 for all). (4) Conclusions: Our findings underscore that IL-31 is not directly associated with general inflammation, eosinophilic response, or atopy in CSU. Nevertheless, its expression is influenced by key disease characteristics: severity, pruritus, and H1 antihistamine response. This investigation provides essential insights into CSU pathogenesis, potentially leading to novel therapeutic interventions. An enhanced understanding of these mechanisms is crucial due to the limitations of current treatment modalities in terms of fully managing CSU symptoms.

A retrospective study regarding the influence of COVID-19 disease on asthma.

BACKGROUND: During the Covid-19 pandemic patients suffering from asthma raised many concerns regarding the outcome ofthe impact of COVID-19 disease on their preexisting condition. The 2021 GINA report indicates that people with asthma do not appear to be at increased risk of a severe form of COVID-19. METHOD: This study is a retrospective study of patients (n = 163) median age = 27.8 years, M:F = 1:1.26, with asthma evaluated using ACT (asthma control test) and VAS (visual analog scale) before and after COVID-19 disease. An ACT score over 20 points placed patients in the controlled asthma group. RESULTS: The overall evaluation for COVID-19 in our asthma patients revealed that 22.7% of the studied group had the COVID-19 disease (21.5% in the controlled asthma group and 24.5% in uncontrolled asthma group). Asthma disease history was longer in the uncontroled asthma group (128 ± 96.8 months vs. 296 ± 59.7 months, p = 0.05). Asthma treatment was conducted according to the GINA guideline, and 18.4% (30 pts) of the patients were on allergen immunotherapy treatment. Significantly more uncontrolled patients were significantly more in Step 1 and 5 of treatment (p = 0.05 and p = 0.03). During the COVID-19 pandemic, patients in the GINA step 5 of treatment experienced a worsening of asthma, often twice as severe as compared to patients with asthma in GINA step 1-4. In these patients, even mild COVID-19 disease led to worsened asthma symptoms, while severe COVID-19 led to a severe asthma impairment measured by ACT score (p = 0.03) and VAS scale (p = 0.02), with increased oral corticosteroids consumption. CONCLUSION: Maintaining optimal asthma control should be able to reduce risk of severe outcomes after COVID-19 disease. Communication via phone with the specialist involved in their asthma care was very comforting for patients, thus confirming the necessity to include phone calls, smart phone's application or online evaluations and counseling in long-term care of chronic diseases.

Off-Label Benralizumab in Severe Non-Necrotizing Eosinophilic Vasculitis following Critical COVID-19 Disease and in DRESS.

Benralizumab is a humanized recombinant mAb that binds to the interleukin 5 receptor (IL-5R) expressed on eosinophils and is approved for the treatment of severe eosinophilic asthma. There are a series of severe eosinophilic disorders that may benefit from this treatment, and it could be a life-saving therapy. In this paper, we present two severe patients with eosinophil-induced diseases that had a good resolution after one dose of Benralizumab 30 mg. The first case is a severe non-necrotizing eosinophilic vasculitis following critical COVID-19 disease and the second case is a DRESS (Drug Rash with Eosinophilia and Systemic Symptoms Syndrome) due to allopurinol. Conclusions: The successful administration of Benralizumab in rare or severe eosinophilic disease could be an option for life-saving therapies when conventional treatments fail.

Follow-Up of a Rare Case of Eosinophilic Gastroenteritis Associated with Persistent Blood Eosinophilia and Multiple Food Allergies.

Eosinophilic gastroenteritis (EGE) is a subgroup of the eosinophilic gastro-intestinal disorders (EGIDs), characterized by eosinophilic infiltration and chronic inflammation of the gastrointestinal tract. These are rare diseases with still incompletely elucidated causes and mechanisms, with frequently delayed diagnosis and variable outcome. Despite increased interest in eosinophilic diseases in recent years, fewer data have been published on EGE and no standardized diagnostic and therapeutic approach exists. This paper reports the case of a young male patient diagnosed with EGE in 2017 based on clinical and histopathological criteria and constantly monitored during five years. Besides gastrointestinal eosinophilic infiltration, biopsies also revealed eosinophilic infiltration of the oesophagus, despite no declared characteristic oesophageal symptoms. We found increased specific IgE to multiple foods and progressive blood hypereosinophilia which preceded EGE diagnosis by three years. The EGE management included selective dietary restrictions and pharmacologic therapy based on daily budesonide non-enteric coated tablets, proton pumps inhibitors, antihistamines, cromoglycate, correction of iron, calcium and vitamin D deficiencies. The clinical outcome was good, while blood eosinophilia and endoscopic appearance remained almost unchanged. After one year the patient complained of respiratory symptoms suggesting asthma, needing continuous combined inhaled therapy. The reported case is illustrative for complex presentation, diagnosis and outcome of a rare case of mucosal chronic EGE associated with oesophageal involvement, peripheral eosinophilia, multiple food allergies and asthma.

Immunological signature of chronic spontaneous urticaria (Review).

Chronic urticaria (CU) is a condition characterized by intensely pruritic, edematous, erythematous papules lasting for more than 6 weeks. Over half of the cases have concomitant swelling of deeper tissues, known as angioedema. The socio-economic burden of the disease is significant. Unfortunately, patients with severe CU, refractory to conventional treatment, have limited and expensive therapeutic options. The pathogenesis of CU is not yet completely understood. Therefore, elucidating the pathophysiological mechanisms involved would potentially identify new therapeutic targets. It has been accepted in recent years that mast cells and their activation, followed by excessive degranulation represent the key pathophysiological events in chronic spontaneous urticaria (CSU). The triggering events and the complexity of the effector mechanisms, however, remain intensely debated topics with conflicting studies. One pathogenetic mechanism incriminated in chronic spontaneous urticaria is the response mediated by the high-affinity receptor for IgE (FcεRI) expressed on mast cells. Increasing recognition of chronic spontaneous urticaria as an autoimmune disease linked to the cytokine-chemokine network imbalance resulting from alteration of innate immune response is another pathogenetic explanation. It is likely that these different pathological mechanisms are more interconnected, both acting synergistically, rather than separately, to produce the clinical expression of CU. The discovery and understanding of pathogenic mechanisms represent the premise for the development of safe and effective immunomodulators and targeted biological treatment for severe, refractory CU.

Predictive Factors for Oral Immune Modulation in Cow Milk Allergy.

Aim: The present study analyzed clinical and biological factors that might predict achievement of tolerance in patients with IgE-mediated cow milk allergy (CMA). Method: Seventy patients with IgE-mediated CMA (44.24 ± 24.16 months) were included in the study. The patients were evaluated clinically through skin prick test and sIgE to whole milk, casein, beta-lactoglobulin and alpha-lactalbumin. An eviction diet of 6 months was established, followed by oral food challenge test (OFC) and oral immunotherapy (OIT) with baked milk for 6 months. The tolerance was assessed after 2 years follow up. Results: Thirty percent of patients presented anaphylaxis of different degrees of severity as first manifestation of CMA. Sixty-two patients followed OIT or an accelerated reintroduction of milk. Ten patients (14.28%) did not obtain tolerance to milk within 2 years. A larger wheal in SPT and higher sIgE to milk, casein and betalactoglobulin were noted in patients with positive OFC. A basal level of <2.5 kU/l for sIgE to milk and <11.73 kU/l for sIgE to caseins predicted the occurrence of tolerance in patients with all types of clinical manifestations, including anaphylaxis. Conclusion: Basal levels of sIgE to milk and casein may help to identify patients that could become tolerant to milk.

Alliance with the School Personnel Is Crucial for the Management of Food Allergy and Anaphylaxis in School Children.

BACKGROUND: School nurses play an important role in coping with food allergy (FA) in schoolchildren, but in schools with no school nurse, the school personnel should be prepared to manage health emergencies. This study aimed to evaluate allergy management competences in primary schools in Cyprus. METHODS: The study was conducted September 2016 to May 2017 in 11/13 primary schools, selected by stratified random sampling. Information was collected from a principal/designated teacher using a questionnaire from the EuroPrevall Project, adapted for Cypriot teachers. RESULTS: An average of six children with FA per school was reported in the preceding three years. Protocols for the management of chronic diseases, including allergies, were in place in 8/11 schools. Regarding recognition of FA, 8/11 respondents knew some of the signs and symptoms. In an allergic emergency, 9/11 would call the child's parent/caregiver first and 2/11 emergency medical support. Epinephrine auto-injector (EIA) was reported by 2/11 respondents to be available in the school, but only one reported training in its use. CONCLUSIONS: The preparedness of primary schools in Cyprus did not meet safety standards regarding the preparedness of school personnel to cope with an allergic reaction in children with FA, including the use of EIA.

COVID-19 Disease Leading to Chronic Spontaneous Urticaria Exacerbation: A Romanian Retrospective Study.

(1) Background: The COVID-19 pandemic has resulted in the exacerbation of various chronic diseases. Due to the potential impact of SARS-CoV-2 on mast cells, we aimed to analyze the relevance of COVID-19 disease on chronic spontaneous urticaria (CSU) clinical presentation and biological profile. (2) Methods: This study is a retrospective case series of patients with CSU diagnosed and treated in the Allergy Department of the Professor Doctor Octavian Fodor RIGH, (Cluj-Napoca, Romania). Patients were assessed for disease activity and level of control with the weekly urticaria activity score and the visual analogue scale. Results were correlated with COVID-19 severity and with nonspecific markers of inflammation during and after the SARS-CoV-2 infection. (3) Results: SARS-CoV-2 impacted a significant proportion (33%) of the CSU patients, of which 71% developed a moderate-severe form of COVID-19. Most of the patients (68%) had moderate-severe forms of CSU and 65% took AH1 treatment (one dose, two-fold dose or four-fold dose). The rest of them (35%) received the second-line treatment (40.3% Omalizumab, 53% Prednisolone and 4.8% Cyclosporine). In Omalizumab treated group of UCS patients we observed that COVID-19 disease was not severe. We established a positive correlation between the severity of the infection and that of the CSU clinical presentation, with most bothersome symptoms of urticaria being experienced by moderate to severe COVID-19 CSU patients (47%). Inflammatory markers were positively correlated (p = 0.01) with a more severe clinical profile of CSU, in accordance with our hypothesis that the level of inflammation triggered by COVID-19 disease has a role in CSU exacerbation. The non-specific inflammatory markers, such as CRP, were positively associated with the UAS7 score (R2 = 0.363; p = 0.001). An increased rate of exacerbation of CSU was observed in moderate-severe COVID-19 infection. (4) Conclusions: COVID-19 disease can result in the exacerbation of chronic spontaneous urticaria, more likely in moderate to severe forms of infection.

Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. MATERIAL AND METHODS: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. RESULTS: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients' quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. CONCLUSIONS: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy.

Bilateral anatomical variations in the extensor compartment of forearm and hand.

An unusual variation of the extensor muscles was found during the routine dissection of the posterior compartment of the forearm. The left forearm presented an extensor medii proprius muscle, the tendon of which had an unusual trajectory. It passed through the second extensor compartment between the tendons of the extensor carpi radialis longus and extensor carpi radialis brevis muscles. The right forearm presented two muscles for the index finger: one, the extensor indicis et medius communis, the tendon of which was split into three tendons, one radial and one ulnar for the index finger and a rudimentary tendon for the middle finger; the second muscle for the index finger had an unusual origin, common with the extensor carpi radialis brevis, and its tendon ran superficially to the tendon of the extensor indicis et medius communis muscle. Knowledge goes tendon variations can be significant not only for clinicians to misdiagnose a debilitating wrist extensor pain syndrome but also for surgeons to avoid iatrogenic injuries in hand surgery.

Could FeNO Predict Asthma in Patients with House Dust Mites Allergic Rhinitis?

Background and Objectives: The evolution of allergic rhinitis to asthma is a part of "atopic march". The aim of this study was to analyze possible predictive markers for asthma occurrence in patients with allergic rhinitis to house dust mites (HDM). Materials and Methods: Fifty-eight patients with persistent allergic rhinitis (PAR) were included. The clinical, biological evaluation and fractionated exhaled nitric oxide (FeNO) measurement were performed at enrolment. The patients were clinically evaluated after one year to determine asthma occurrence. Results: The severity of rhinitis symptoms, levels of total immunoglobulin E (IgE), ICAM-1, VCAM-1, E-selectin and IL-6, but not IL-8 and TNF-α were higher in patients with allergic rhinitis who developed asthma compared to non-asthmatics, but the differences were not significant to considered them as predictive factors for asthma occurrence. The risk of asthma was independently influenced by patients aged over 30 years ((OR-3.74; CI95% 0.86-16.31; p = 0.07), a duration of allergic rhinitis over 12 months ((OR-4.20; CI95% 0.88-20; p = 0.07) and a basal FeNO over 28 parts per billion (pbb) ((OR-18.68; CI95% 3.79-92.05; p < 0.001). Conclusion: Clinical and biological parameters may predict asthma occurrence in patients with persistent allergic rhinitis to HDM. Adult patients with a longer duration of rhinitis symptoms and a high level of FeNO have a greater risk to develop asthma.

Characterization of Patients with Allergic Rhinitis to Ragweed Pollen in Two Distinct Regions of Romania.

Background and objectives: Ragweed pollen is a major source of allergen, which has rarely been observed in Romania until now. In this study, we evaluated the symptoms and associated factors in patients with allergic rhinitis to ragweed pollen in two distinct regions of Romania. Materials and Methods: We evaluated the records of patients newly diagnosed with allergic rhinitis induced by ragweed pollen in two allergological centers from North-West (NW) and Central parts of Romania between 2013 and 2015. The patients were clinically evaluated regarding disease length, presence, and severity of the allergic rhinitis symptoms and the association with other allergic manifestations (asthma and conjunctivitis). Results: The sensitization to ragweed was significantly higher in the NW part compared to the Central part (18.27% vs 4.1%, p < 0.001). More patients with monosensitization to ragweed pollen were observed in the NE center (27%) compared to the Central one (20.7%). Patients with monosensitization to ragweed pollen presented more severe forms of rhinitis (70% vs 31.5%, p = 0.02) in the NW part compared to polysensitized patients. The total symptoms score was significantly higher in patients from the Central part compared to the NW part (9.21 ± 2.01 vs 5.76 ±1.96, p < 0.001). Bronchial asthma was associated at a similar frequency to allergic rhinitis in both centers, but it was more frequently observed in monosensitized patients in the NW center. Allergic conjunctivitis was more frequently reported by patients from the Central part (75.86 vs 41.9, p = 0.02), while in the NW region it was noticed more commonly in monosensitized patients (65% vs 33.33, p = 0.02). Conclusions: Allergic rhinitis to ragweed pollen has been more frequently reported in the NW part of Romania. Patients with severe forms of rhinitis were observed in the central part, while in the NW the severe forms of disease were reported by patients with monosensitization. Ragweed pollen is intensely allergogenic and determines association of ocular and asthma symptoms. Co-sensitization increases the risk of asthma association.

How Could We Influence Systemic Inflammation in Allergic Rhinitis? The Role of H1 Antihistamines.

The aim of the study was the analysis of adhesion molecules' profile (ICAM-1, VCAM-1, and E-selectin) in patients with allergic rhinitis and the influence of H1 antihistamines on those markers. Seventy-nine patients with persistent allergic rhinitis (PAR) and 30 healthy volunteers were included in the study. The patients with PAR were treated with desloratadine 5 mg/day or levocetirizine 5 mg/day for 4 weeks. The clinical (rhinitis symptoms and total symptoms score (TSS), type of sensitization) and biological evaluation (total IgE, eosinophils, ICAM-1, VCAM-1, and E-selectin) as well as fractionate nitric oxide in exhaled air (FeNO) measurement was performed before and after treatment. The plasmatic levels of ICAM-1, VCAM-1, total IgE, and eosinophils and FeNO were significantly increased in patients with PAR compared to healthy volunteers. H1 antihistamines significantly improved TSS, with no differences between the investigated drugs. There was a significant decrease of eosinophils, total IgE, and FeNO after treatment. H1 antihistamines significantly decreased the plasmatic levels of ICAM-1 and E-selectin but not VCAM-1 compared to basal values. There is no difference between levocetirizine and desloratadine in the reduction of CAMs. A systemic inflammation characterized by increased levels of CAMs is present in patients with PAR. H1 antihistamines improve symptoms and reduce CAMs and FeNO levels after 1 month of treatment. H1 antihistamines might reduce the systemic inflammation which could be responsible to asthma occurrence in patients with PAR.

Oral Immunotherapy to Wheat in Allergic Asthmatic Female: A Case Report.

Wheat is the most commonly grown cereal. Immunological reaction to wheat may be IgE or T-cell- mediated. Asthma could be induced by inhaled flour or by exposure to allergens present in bakery products. In patients with IgE-mediated allergy to wheat proteins there is no specific therapy, except oral immunotherapy (OIT). There are few data regarding OIT with wheat protein in allergic patients. We present a case of a 32-yearold female patient, who worked for 5 years in wheat and bakery products industry, who developed an occupational asthma and chronic urticaria after flour inhalation or ingestion of foods that containit. The patient underwent wheat  OIT, that  was well-tolerated with no severe reaction during treatment. We may conclude that wheat OIT is a safe therapy and may induce symptoms improvement in allergic asthma and urticaria in patients with wheat allergy. Wheat OIT may induce tolerance to allergic patients.

The significance of angiogenesis and tumoral proliferation in renal cell carcinoma.

Angiogenesis represents one of the most important factors of the tumor proliferation. Renal carcinoma with clear cells is highly vascularized. Knowing numerous quantification systems of tumor angiogenesis, we used a simple one, the evaluation of the relative vascular density. We studied 61 cases with partial or total nephrectomy performed in the Urology Department of Timisoara County Hospital. We correlated the intensity of angiogenesis with a tumor proliferation factor PCNA (proliferating cell nuclear antigen) and with the monoclonal antibody PC10. Correlation of the two immunohistochemical methods with the degree of the tumor differentiation suggested an inverse ratio between vascular density and tumor proliferation degree.

Anorectal melanoma. Case report and review of the literature.

We report a case of primary anorectal melanoma, a very rare malignant tumor in this localization. The patient, a 57-year-old female, complained for one year of symptoms, which were attributed to hemorrhoids. An abdomino-perineal resection was performed. Pathologic examination revealed an anorectal melanoma with numerous lymph node metastases and an unusual metastatic deposit in a uterine leiomyoma. The pathogenesis, pathology, principles of treatment and prognosis of this entity are briefly discussed.