Search Results (115)

Background and Clinical Significance: Patent Blue V (PBV) is widely used for sentinel lymph node mapping but may rarely cause severe hypersensitivity reactions. These reactions can present atypically, with predominant cardiovascular collapse and minimal cutaneous manifestations, potentially delaying recognition and treatment. Case Presentation: We report the case of a 52-year-old woman who developed sudden and prolonged refractory hypotension shortly after PBV injection during melanoma surgery. The reaction initially occurred in the absence of bronchospasm or early significant cutaneous manifestations. Profound cardiovascular collapse preceded the delayed appearance of erythema and piloerection, making early recognition of perioperative anaphylaxis particularly challenging. Hemodynamic instability required aggressive fluid resuscitation and prolonged vasopressor support. Subsequent diagnostic work-up, including serum tryptase measurement and allergological evaluation, confirmed PBV-induced anaphylaxis. PBV-induced anaphylaxis may present with isolated cardiovascular collapse without typical clinical features. Conclusions: Early recognition and prompt hemodynamic support are essential to optimize outcomes in the perioperative setting. Full article

Bovine tuberculosis (bTB) remains endemic in southern Italy, particularly in Sicily, posing challenges for disease control and eradication. This study evaluated the diagnostic agreement between the intradermal tuberculin test (IDT), interferon-gamma release assay (IFN-γ), and post-mortem lesion detection in 1801 cattle from 44 herds in the province of Palermo during 2024–2025. Diagnostic agreement between IDT and IFN-γ was substantial in 2024 (κ = 0.731; 95% CI: 0.64–0.82; n = 991) and decreased to moderate in 2025 (κ = 0.453; 95% CI: 0.33–0.57; n = 572), reflecting a higher proportion of IFN-γ positive and inconclusive animals. An increase in inconclusive results for IFN-γ was observed in 2025, but the available data did not allow investigation of the factors underlying this difference. Agreement between ante-mortem tests and post-mortem lesion detection was poor in a selected subgroup of slaughtered animals, potentially subject to verification bias, highlighting the limitations of single diagnostic tools and the need for a complementary approach combining immunological and pathological methods. These findings support the interpretation of the complementary roles of IDT and IFN-γ within herd-level bTB surveillance, highlight the need for standardized protocols to manage inconclusive IFN-γ results, and underline the complementary contribution of post-mortem inspection within integrated surveillance strategies in endemic settings. Official confirmation of bovine tuberculosis relies on an integrated evaluation combining diagnostic results, post-mortem findings, and epidemiological investigations. Given the absence of a validated gold standard applicable to all animals in this observational dataset, the study was designed as a diagnostic agreement study rather than a formal accuracy assessment. Full article

Background: Staphylococcus aureus (SA) causes septicemia and arthritis, eventually resulting in substantial economic losses and health hazards in poultry. Lethal electron beam (eBeam) treatment kills bacteria while preserving surface epitopes. Methods: This study compared broiler chicken immune responses (local and systemic) after eBeam-killed (eB) or formalin-killed (FK) SA injections. The vaccine (sham) control was endotoxin-free PBS. This study contained six treatments (trt) with five chickens/trt, with vaccine trts divided into two groups, A and B. Group A received in ovo vaccine/sham treatments (phase 1) initially. At 34 d of age, the pulps of growing feathers (GFs) received intradermal (i.d.) injections of the respective trt to elicit booster and primary responses in groups A and B, respectively. Blood was collected to analyze leukocyte populations and plasma SA-specific antibody levels. Additionally, in phase 2, GFs were collected to assess leukocyte presence in GF pulps. Two-way ANOVA was conducted to test the effects of treatment, time, and their interactions, followed by Tukey’s HSD tests at p < 0.05 for statistical significance. Results: Early in phase 1, the eB group had increased SA-specific IgM, IgA, and total lymphocyte concentrations compared with FK. In phase 2, FK and eB i.d. vaccines increased total lymphocyte and T cell proportions in GF pulps compared with sham. In blood, the recall eB vaccination increased monocytes, B cells, CD8+ T cells, and total lymphocytes, while the recall FK vaccination increased heterophils (p < 0.05). Conclusions: Improved early protection at mucosal surfaces may be reflected by higher plasma levels of SA-specific IgM and IgA following in ovo eBeam-killed-SA vaccination. Additionally, both eB-SA and FK-SA vaccines stimulated robust local inflammatory responses dominated by lymphocytes in GF pulps. Full article

Background/Objectives: Chemotherapy drug (ChD)-induced maculopapular eruptions (MPEs) may interrupt optimal cancer treatment when no equally effective alternative therapy is available. Evidence supporting rapid drug desensitization (RDD) for delayed-type MPE remains scarce. We aimed to evaluate the feasibility and safety of RDD in patients with ChD-induced MPE. Methods: Adult patients with ChD-induced MPE who underwent RDD between January 2021 and January 2024 were evaluated. Delayed MPE recurrence was assessed until the subsequent chemotherapy cycle. Results: A total of 63 RDD procedures were performed in 10 patients with ChD-induced MPE, most commonly triggered by taxanes and platinum agents. The median onset of the index reaction was 60.0 h (24.0–336.0), and delayed intradermal tests were positive in 2 of 9 tested patients (22.2%). No delayed MPE recurrences were observed during the predefined follow-up period until the subsequent chemotherapy cycle. Immediate breakthrough reactions occurred in 3 of 10 patients (30.0%), corresponding to 17 of 63 RDD procedures (27.0%), and were limited to mild flushing and pruritus that resolved with antihistamines with or without low-dose corticosteroids. All RDD procedures were successfully completed without severe systemic reactions, and all patients were discharged on the same day. Conclusions: In carefully selected patients with delayed-type MPE, RDD appears to be a feasible and safe short-term strategy for enabling continuation of essential chemotherapy within the predefined observation period. As this pilot study includes a small and heterogeneous patient population with limited follow-up, the findings should be considered preliminary and hypothesis-generating and warrant confirmation in larger prospective studies with longer follow-up. Full article

Intradermal injections of anti-canine immunoglobulin E (IgE) in healthy dogs have been utilized in preclinical drug testing to evaluate the efficacy of anti-allergic drugs used to treat canine atopic dermatitis (AD). However, the molecular effects of established canine anti-allergic drugs on this acute canine IgE-mediated atopic model remain largely uninvestigated. The objective of this study was to characterize the effect of proactive oclacitinib and prednisolone treatments on the immune and skin barrier transcriptome of IgE-mediated late-phase reactions (LPRs) in an acute model of canine AD. Sixteen healthy adult research-bred beagles were randomized to receive either oclacitinib or prednisolone orally for six days, followed by an intradermal anti-canine IgE injection. Biopsies were collected 24 h post-injection for RNA isolation and sequencing; previously analyzed transcriptomes (healthy skin, saline-injected skin, IgE lesions without drug modulation) from the same colony of dogs served as controls. Administration of prednisolone and oclacitinib prior to intradermal anti-IgE injections reduced the number of differentially expressed genes (DEGs) in 24 h samples to 1251 and 1471, respectively. Both treatments resulted in a decrease in expression of several significantly upregulated T helper-(Th)1 (e.g., MX1, OAS1, STAT1), Th2 (e.g., CCL13, CCL8, IL13RA1, IL-33, IL5RA, OSM), chemokine and receptor (e.g., CCL19, CCL2, CCL3, CCR1, CCR3) genes in comparison to the untreated IgE-mediated lesions. Interestingly, only prednisolone treatment significantly reduced IL-13 upregulation, an important gene in the Th2 immune response. In conclusion, both prednisolone and oclacitinib reduced the transcriptomic changes observed in the acute lesions of the canine IgE-induced atopic dermatitis model, with prednisolone inducing a broader inhibitory immune response. Full article

Baja California is the second-highest state in Mexico for hospital discharges attributed to coccidioidomycosis (CM), yet epidemiological information on exposure patterns in affected communities remains limited. To estimate exposure to Coccidioides and assess its association with environmental factors, we conducted intradermal coccidioidin skin testing among 416 residents across nine regions of Baja California. We analyzed 24 environmental variables, including bioclimatic, topographic, and land use indicators. Overall, 31.9% of participants tested positive. Higher odds of exposure were observed in Valle de las Palmas and La Morita. Exploratory comparisons of environmental variables showed that, in unadjusted analyses, annual precipitation, precipitation during the wettest month, and elevation differed between high- and low-positivity localities. However, after applying the Benjamini–Hochberg false discovery rate correction, none of the evaluated continuous environmental variables remained statistically significant. These findings should therefore be interpreted as exploratory and hypothesis-generating rather than as evidence of an independently defined environmental profile. Overall, the results indicate heterogeneous exposure to Coccidioides across Baja California and suggest exploratory spatial variability in exposure across sampled localities. Because participants were recruited through nonprobability community-based sampling, these findings should be interpreted as exploratory rather than population-representative estimates. Full article

Objective: This study aimed to evaluate patients who developed hypersensitivity reactions (HSRs) during rituximab treatment and report the outcomes of desensitization protocols implemented to allow treatment continuation. Methods: We retrospectively reviewed the institutional data of 76 patients who received rituximab therapy at the Adult Hematology Department between January 2022 and September 2023. Among these, 11 patients who experienced immediate hypersensitivity reactions during infusion were analyzed. The overall frequency of rituximab-associated HSRs was 14.47% (11 out of 76 patients). Demographic data, underlying diseases, timing and type of HSRs, and details of the desensitization protocols were recorded. Results: The overall frequency of rituximab-associated HSRs was 14.47% (11 out of 76 patients). Among the 11 patients, eight were male and three were female, with a median age of 56 years (range: 19–72). Eight patients had CD20-positive non-Hodgkin lymphoma (NHL) and three had acute B-lymphoblastic leukemia (B-ALL). HSRs occurred during the first rituximab exposure in nine patients, at the fourth dose in one patient, and at the eighth dose in another. Symptoms included widespread rash, pruritus, flushing, chills, shivering, dyspnea, dysphagia, back pain, dizziness, syncope, and throat discomfort. All the patients were consulted by the Allergy and Immunology Clinic. Based on prick and intradermal test (IDT) results and the planned rituximab dose, desensitization protocols consisting of a three-dilution/12-step and a four-dilution/16-step regimen were prepared. Overall, 46 desensitization procedures were successfully completed in 11 patients. Notably, no severe anaphylactic events or treatment discontinuations due to drug toxicity occurred during the implementation of the protocols. Conclusions: Although the number of patients was limited, our findings indicate that in patients with hematologic malignancies receiving rituximab who develop early HSRs, desensitization represents a safe and effective strategy before considering treatment modification. These results support that, in appropriately selected patients, desensitization protocols are an important approach to continue therapy without interruption while minimizing adverse reactions. Full article

Canine atopic dermatitis (AD) is a common allergic skin disease for which identifying allergen sensitization via IgE serological or intradermal testing is necessary to implement allergen-specific immunotherapy. Because serum IgE has a short half-life and circulating levels fluctuate with environmental allergen exposure, the timing of blood sampling may influence serological test outcomes. This cross-sectional study assessed seasonal variation in allergen-specific IgE concentrations and seropositivity rates across pollen and mite allergen categories in Scandinavian dogs suspected of allergic disease. PAX multiplex macroarray results from 5014 canine sera submitted by veterinarians across Denmark, Norway, and Sweden over one full year were retrospectively analyzed for 17 allergens, including tree, grass, and weed pollens, house dust mites, and storage mites. Mean sIgE levels showed statistically significant but relatively small seasonal variation. Seropositivity rates, however, showed clearer patterns: seropositivity for tree and weed pollen was highest in spring and summer, and that for house dust mite peaked in autumn and winter, while storage mite sensitization rates showed the opposite trend. These results confirm that IgE serological test results in dogs are affected by the sampling season and emphasize the importance of considering timing when collecting and interpreting IgE serological tests in atopic dogs. Full article

Background: Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a major zoonotic disease in West Africa. In Africa, bTB is endemic in cattle with a prevalence ranging from 2% up to 18%. The disease causes significant public health risks due to unpasteurized milk and milk product consumption. In the context of the EU-PRISMA project, which promotes research and innovation for productive, resilient, and healthy agropastoral systems in West Africa, a cross-sectional survey was conducted in dairy herds from Mali and Niger to assess animal, herd, and within-herd bTB prevalence, as well as to identify animal risk factors and predictors of bTB herd status. Method and principal findings: A random cross-sectional survey on dairy cattle farms using comparative intradermal tuberculin test and epidemiological inquiry was performed in four regions of Mali (Bamako, Koulikoro, Mopti, and Sikasso) and three regions of Niger (Tahoua, Dosso, and Tillabéry). Herd and animal prevalence of bTB and within-herd prevalence were significantly higher in Mali (especially in Bamako and Koulikoro) than in Niger. Several risk factors were significantly associated with animals positive to bTB, i.e., the region where animals live, the age range from 3 to 7 years old, and female animals. In addition, in regions with higher bTB prevalence, the herd with slaughtering of animals in the farm and the herd with the presence of an animal assembly area were associated with the most unfavorable status of a herd with regards to bTB. Moreover, the average and the median annual economic losses of bTB at animal level were estimated at €262 and €137 respectively, with large variability depending on the farm (between €46 and €838). Conclusion and significance: This survey provides useful data on bTB epidemiology and economical losses in Mali and Niger and urges for improvement of surveillance systems and prevention and control strategies. Cost-benefit, return of investment, or similar analyses are strongly recommended to help with decision making. Full article

Hypersensitivity reactions to iodinated contrast media (ICM) are traditionally categorized as immediate or delayed reactions, involving IgE-mediated pathways, non–IgE-dependent mast cell or complement activation, or T cell–mediated immune mechanisms. However, we observed that some individuals develop systemic inflammatory responses that do not fit these established categories. We describe here a case series of three patients who developed cytokine release syndrome (CRS)-like reactions following iodinated contrast administration, which were initially difficult to distinguish from sepsis and were only recognized after recurrent episodes. Clinical presentation, laboratory findings, cytokine profiles, allergy investigations, and treatment outcomes were reviewed. All patients developed fever, rigors, and hypotension within 5 to 70 h after exposure, accompanied by leukocytosis and markedly elevated inflammatory markers despite negative microbiological investigations. Serum tryptase levels remained within the normal range with no significant rise, while cytokine analyses demonstrated elevations of pro-inflammatory interleukin-6 and other cytokines in patients 1 and 3 where samples were available. Standard corticosteroid premedication did not prevent recurrence, and one patient developed systemic symptoms following intradermal testing. All patients improved with high-dose systemic corticosteroids and supportive care. These findings suggest that ICM may induce a cytokine-mediated inflammatory phenotype distinct from classical hypersensitivity reactions, highlighting the importance of early clinical recognition to guide diagnosis and management. Full article

Bovine purified protein derivative (PPD-B), a crude protein extract from Mycobacterium bovis cultures, has been the standard reagent for delayed-type hypersensitivity (DTH) testing in cattle, but its undefined composition and variability compromise reproducibility and specificity. To address these limitations, we developed and evaluated RRbTB-E, a recombinant fusion protein comprising ESAT-6, as a defined alternative for skin testing. RRbTB-E was produced in Escherichia coli, purified by affinity chromatography, and characterized by SDS-PAGE and Western blot. In M. bovis-sensitized guinea pigs, RRbTB-E induced robust DTH reactions comparable to PPD-B, with consistent performance across six independent experiments and long-term stability after storage at 4–8 °C for more than 900 days. Furthermore, RRbTB-E did not induce significant reactions in non-sensitized or Mycobacterium avium–sensitized animals, confirming antigenic specificity. RRbTB-E also elicited DTH responses in Mycobacterium tuberculosis–sensitized guinea pigs. In naturally infected cattle, it triggered responses similar in magnitude to PPD-B, while remaining negative in non-infected animals. These findings support RRbTB-E as a stable, reproducible, and specific candidate for standardized intradermal testing in bovine tuberculosis diagnosis. Full article

Background and Objectives: Hyaluronic acid (HA) is extensively used in dermo-aesthetic medicine for its hydrating and tissue-repairing properties. Beyond cosmetic use, HA has shown therapeutic effects in inflammatory skin diseases such as seborrheic, radiation-induced, and atopic dermatitis (AD). However, HA-based aesthetic formulations such as Profhilo^®, a hybrid complex of high- and low-molecular weight HA, have not been tested in immunologically driven models of AD. This study aimed to investigate the therapeutic effects of intradermal Profhilo^® injections in a recently developed ovalbumin (OVA)-induced murine model of AD. Specific objectives included assessing changes in skin inflammation, pain sensitivity, and spinal cord pathology. Materials and Methods: Twenty-eight adult female ICR-CD1 mice were sensitized and exposed to OVA via intraperitoneal, subcutaneous, and topical routes over 49 days to induce AD-like lesions. Control animals received saline. On day 50, mice were subdivided into four groups receiving intradermal injections of Profhilo^® or saline. Skin inflammation was evaluated using the SCORAD index on days 49 and 57, and nociceptive responses were measured using the plantar thermal hyperalgesia test. On day 57, dorsal skin and thoracic spinal cord samples were collected for histological and immunohistochemical analysis, including assessments of epidermal and dermal thickness, mast cell density, collagen content, CGRP immunoreactivity, and microglial activation. Results: OVA-treated mice developed significant skin inflammation (p < 0.0001) and thermal hyperalgesia. Intradermal HA injection significantly reduced SCORAD scores (p < 0.01) and mast cell density (p < 0.05) while increasing dermal thickness (p < 0.05). In the spinal cord, HA treatment reduced CGRP immunoreactivity and microglial activation (p < 0.01 and p < 0.05, respectively), especially in OVA-treated animals. Conclusions: Intradermal Profhilo^® alleviated both cutaneous inflammation and neurogenic pain in an OVA-induced AD model. These findings suggest that HA not only improves local skin pathology but also modulates central neuroimmune responses, supporting its therapeutic potential for inflammatory skin conditions involving peripheral and central sensitization. Full article

Background/Objectives: Antigen presenting cells (APCs) and immune cells have unique properties to drive or suppress immune responses. They are therefore key targets for the expression of vaccine antigens or transgene proteins. To better determine the utility of different molecular therapies to modify these cells, mRNA and DNA-based molecular therapy vectors were compared for their ability to genetically modify immune cells after intradermal injections in mice. DNA-based vectors included naked plasmid DNA, plasmid packaged in lipid nanoparticles (LNPs), and replication-defective adenovirus (Ad) vectors. mRNA delivery was mediated by packaging into LNPs like those used in COVID-19 vaccines. Methods: Each vector was used to deliver Cre recombinase into Cre reporter mice whose cells were activated to express green fluorescent protein (GFP) and firefly luciferase after Cre recombination. The mice were injected intradermally (ID) near the base of their tail at a site that drains into the inguinal lymph node. Luciferase activity was imaged in the living mice 1 or 4 days after vector injection. The animals were then euthanized, and luciferase activity was imaged in the draining inguinal lymph node. Cells were prepared from the intradermal injection site and from the draining lymph node to determine which immune cells were genetically modified by phenotyping CD45, CD3, and CD11b GFP-positive cells by flow cytometry. Given that the skin uniquely contains Langerhans dendritic cells, these CD207⁺ cells were also phenotyped in skin samples and in the draining lymph node. Results: In both the skin and in the draining lymph node, the rank order of luciferase and GFP activation by the vectors were: (1) Ad; (2) mRNA-LNP; (3) DNA-LNP; and (4) naked DNA. Only mRNA-LNP and Ad vectors mediated obvious luciferase activity in the living animals and in the draining lymph nodes by imaging. Notably, both vectors appeared to leak from the ID injection site and not only modify the draining lymph node but also strongly modify the livers of the mice. Naked DNA and DNA-LNP mediated detectable GFP activation in the skin and draining lymph node in some mice, but this activity was low and did not reach statistical significance when compared to PBS-treated animals. mRNA-LNPs and Ad both mediated significant Cre delivery in CD45⁺, CD3⁺, CD11b⁺, and CD207⁺ immune cells in the skin and in the lymph node, with adenovirus mediating consistently higher levels of expression in all of the tested cells. Conclusions: These data indicate that mRNA-LNP and Ad vectors mediate stronger modification of skin and lymph node immune cells after intradermal injections. Naked DNA and DNA-LNPs were markedly less potent at this activity than the other vectors. These data are consistent with the higher vaccine potency of mRNA-LNP and Ad vectors and suggest that approaches that increase targeting of immune cell subsets may have utility to increase efficacy while also reducing off-target modification of tissues like the liver. Full article

Candidatus Rickettsia colombiensis is a new candidate species of Rickettsiae spotted fever group that have been isolated only from ticks. The pathogenicity of Ca. R. colombiensis to human and animals is unknown. This study evaluated the pathogenic potential of Ca. R. colombiensis in Syrian hamsters and assessed the cross-reactivity between Ca. R. colombiensis and other Rickettsia in human and hamster sera. Shell vial technique was employed to isolate Ca. R. colombiensis. Subsequently, five male Syrian hamsters were inoculated intraperitoneally (IP) and five intradermally (ID) with 1 × 10⁶ Vero cells infected with Ca. R. colombiensis. One control hamster was used in each group. The health status was assessed daily, and necropsies were performed. Serum samples were tested by indirect immunofluorescence and tissues were processed by qPCR and histological stains. All Syrian hamsters remained healthy during the trial. No histopathological damages associated with rickettsial infection were observed. No Rickettsial DNA was detected in tissues. Syrian hamsters showed IgG antibody titers ranging from 1:64 to 1:1024. Control hamsters were negative. Regarding human sera, 56% (84/150) had IgG cross-reactivity antibodies against Ca. R. colombiensis. Subsequently, in a selected subset of 30 sera with moderate to high titers, all samples reacted with Ca. R. colombiensis antigen. Under specific conditions of this study, Ca. R. colombiensis did not behave as a highly virulent pathogen in the hamster model, although all infected Syrian hamsters developed IgG antibodies responses. Regarding cross-reactivity, it is possible to serologically diagnose rickettsial infection using Ca. R. colombiensis as an antigen. Full article

Tinea is a superficial fungal infection of keratinized structures caused by specific filamentous fungi called dermatophytes. Terbinafine, a drug used to treat tinea, is poorly soluble in water, and its delivery into the skin via nanoparticle formulation usingpoly(lactic-co-glycolic acid) (PLGA) has been demonstrated. In this study, we investigated the preparation conditions for nanoparticles (NPs) to achieve efficient intradermal delivery of terbinafine. Terbinafine-loaded PLGA NPs were prepared using the nanoprecipitation method, and the particle size distribution and average particle size were measured using dynamic light scattering. Skin permeability tests were conducted using mouse dorsal skin, and the amount of terbinafine delivered into the skin was measured to evaluate the release behavior in the skin. In the preparation of terbinafine-loaded PLGA NPs, under conditions where the external solution was purified water, the mean volume diameter was 40.49 ± 15.63 nm, the terbinafine-loaded content was 3.31 ± 0.29%, and the entrapment efficiency was 55.08 ± 4.88%. Under conditions of an external solution containing 1.0 × 10⁻³ w/v% arginine(Arg) aq. solution, the mean volume diameter was 41.71 ± 16.08 nm, the terbinafine-loaded content was 5.17 ± 0.37%, and the entrapment efficiency was 86.48 ± 6.01%. The entrapment efficiency and content were higher under the condition using 1.0 × 10⁻³ w/v% Arg aq. solution compared to purified water. In addition, in the skin permeability test, no drug was detected in the receptor solution sampled from both the NPs suspension group and the simple solution group, and no drug was detected in the intradermal solution in the simple solution group. The intradermal drug concentration was 77.94 ± 10.66 µg/g under conditions where purified water was used as the dialysate, and 96.42 ± 61.62 µg/g under conditions using 1.0 × 10⁻³ w/v% arginine, exceeding the reported minimum inhibitory concentration (MIC) of 8.87 µg/g, suggesting the efficacy of terbinafine-loaded PLGA NPs for the treatment of tinea versicolor. Since tinea treatment is a long-term process, it is desirable to deliver a stable amount of drug to the treatment site at all times. Therefore, the nanoparticle preparation conditions using purified water as the external solution, where the intradermal drug concentration exceeded the MIC and remained stable in the skin permeability test, were suggested to be suitable for tinea treatment. Full article