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This article discusses the rare neutrophilic dermatosis pustular pyoderma gangrenosum (PG), characterized by necrotizing skin lesions. It highlights the importance of thorough histological examination in diagnosing this variation, which resembles other pustular dermatoses. The case study of a 54-year-old female highlights the unique histological aspects of PG, including epidermal erosion, neutrophilic infiltration, sterile abscesses, and no vasculitis. The article emphasizes the need for differential diagnosis and clinical correlation, emphasizing the importance of collaboration between physicians and pathologists for accurate diagnosis.

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Neutrophilic figurate erythema (NFE) is a rarely reported figurate erythema that clinically presents similarly to erythema annulare centrifugum (EAC) with neutrophil-predominant perivascular and interstitial infiltrate in the dermis on histopathology. We present the case of a 32-year-old active-duty military male who presented with a chronic treatment-resistant skin rash. The rash began on his thighs five years previously and was treated with topical and oral antifungals repeatedly without improvement. The patient was deployed overseas during the rash onset, but the rash persisted upon his return stateside. No triggers were identified. His persistent skin eruption consisted of erythematous polycyclic annular plaques with a "trailing edge" scale. Histologic examination revealed perivascular neutrophils and perivascular and interstitial eosinophils without signs of vasculitis or infection. With only 15 reported cases, it can be difficult to recognize leading to long delays in diagnosis and treatment. Despite having a clinical course similar to EAC, NFE may require anti-neutrophil therapy to resolve completely.

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OBJECTIVE: We describe the demographics, clinical presentation, imaging findings, and treatment response among 235 cases of biopsy-proven idiopathic granulomatous mastitis (IGM) at a single institution. METHODS: An institutional review board-approved retrospective search of the breast imaging database was performed to select patients with biopsy-proven IGM between 2017 and 2022. Retrospective review evaluated clinical presentation, imaging findings with US and mammography, and treatment recommendations (antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], warm compresses, or observation only). Response to treatment was evaluated on follow-up US. A favorable treatment response was a decrease in size or resolution of disease on follow-up imaging. Statistical analysis using Poisson regression was performed to evaluate the clinical outcomes associated with each treatment. RESULTS: A total of 235 patients met the selection criteria with a mean age of 38 years (18 to 68). The majority of patients were Hispanic (95%, 223/235). Of all patients, 75.3% (177/235) received treatment (consisting of 1 or any combination of antibiotics, NSAIDs, warm compresses), 24.7% (58/235) were treated with observation, 78.7% (185/235) returned for follow-up imaging, and 21.3% (50/235) were lost to follow-up. Of those with follow-up imaging, disease improvement was seen in 70.3% (102/145) of patients who received treatment compared with 72.5% (29/40) of patients treated by observation alone. Multivariate analysis further showed no difference in clinical outcomes among the treatment of unifocal, multifocal, or recurrent IGM. CONCLUSION: Nonsteroidal treatment of IGM showed no significant improvement on follow-up imaging compared to treatment with observation alone in a predominantly Hispanic patient population.

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Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that characteristically presents with progressive ulcerative lesions. The association of PG with hematological malignancies remains unclear due to its varied clinical presentation. Herein, we report the unusual case of PG in a 75-year-old male with stage III follicular diffuse large B-cell lymphoma. Seven days subsequent to his first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) therapy, he presented to the emergency department with generalized malaise, bilateral lower extremity edema, and ecchymoses with ulcerative wounds on the dorsal of his feet. Due to the rapid progression of the patient's dermatological manifestations and declining clinical status, he required serial surgical wound debridement and a biopsy, which revealed an occlusive vasculopathy with dermal and epidermal necrosis. These pathological findings, along with the patient's clinical presentation, led to the diagnosis of PG. The patient was treated with negative pressure wound therapy, steroids, and tacrolimus ointment, which led to a marked improvement in the appearance of the patient's dermatological features and clinical status.

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Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an inflammatory cutaneous disorder of unknown etiology that typically occurs in association with systemic disease. Rheumatoid arthritis and systemic lupus erythematosus are the most common associated diseases. PNGD manifests as skin-colored to erythematous papules and plaques, mainly on the extremities. However, to the best of our knowledge, no cases of PNGD in the vulva have been reported in foreign literature to date. Herein, we report the first case of a 31-year-old female with systemic lupus erythematosus disease who presented multiple plaques and a pigmented, rough, mamillated skin surface affecting the vulva, leading to disfigurement of the vulva and interfering with sexual intercourse due to severe pain, irritation, and frequent infection. Surgical excision of the whole lesion with reconstruction of the vulva was done in two sessions and histologically diagnosed as PNGD.

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BACKGROUND: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). METHODS: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. RESULTS: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1ß, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. CONCLUSION: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

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INTRODUCTION: Probiotics provide therapeutic benefits not only in the gut but also other mucosal organs, including the lungs. OBJECTIVE AND DESIGN: To evaluate the effects of the probiotic strain L. delbrueckii UFV-H2b20 oral administration in an experimental murine model of A. fumigatus pulmonary infection. BALB/c mice were associated with L. delbrueckii and infected with Aspergillus fumigatus and compared with non-associated group. METHODS: We investigated survival, respiratory mechanics, histopathology, colony forming units, cytokines in bronchoalveolar lavage, IgA in feces, efferocytosis, production of reactive oxygen species and the cell population in the mesenteric lymph nodes. RESULTS: L. delbrueckii induces tolerogenic dendritic cells, IL-10+macrophages and FoxP3+regulatory T cells in mesenteric lymph nodes and increased IgA levels in feces; after infection with A. fumigatus, increased survival and decreased fungal burden. There was decreased lung vascular permeability without changes in the leukocyte profile. There was enhanced neutrophilic response and increased macrophage efferocytosis. L. delbrueckii-treated mice displayed more of FoxP3+Treg cells, TGF-ß and IL-10 levels in lungs, and concomitant decreased IL-1ß, IL-17 A, and CXCL1 production. CONCLUSION: Uur results indicate that L. delbrueckii UFV H2b20 ingestion improves immune responses, controlling pulmonary A. fumigatus infection. L. delbrueckii seems to play a role in pathogenesis control by promoting immune regulation.

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Facial neutrophilic dermatosis is a relatively recent and rare entity. Herein, we report an original case with a clinical appearance of crusty pyoderma gangrenosum and limited face involvement, classifying it as neutrophilic dermatosis (ND) of the face. The latter is an infrequent entity and forms part of the ND spectrum. The few reported cases in the literature are characterized by a restricted distribution on the face, as in our case. Nevertheless, this entity remains controversial: some consider it a variant of Sweet's syndrome; others see it as a truly independent entity. Matthews et al. reported an association between ND of the face, as in the case of our patient with a crusty appearance, and ulcerative colitis. Our observation and that of Matthews et al. underline the wide and varied potential for the clinical presentation of this entity.

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Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Half of the cases are associated with an immune dysfunction and are frequently triggered by pathergy such as a tissular aggression via surgery or burn wounds. A patient with ulcerative colitis presented a PG at the site of an iontophoresis patch for tendinopathy. Treatment in a specialized burn center, corticosteroid therapy and adapted local care contributed to a favourable evolution. PG remains a diagnosis of exclusion and inflammatory phenomena must be differentiated from infectious causes such as necrotizing fasciitis to initiate immunosuppressive treatment. Being rare and difficult to diagnose and to treat as well as associated with potentially severe sequelae, a multidisciplinary team is required for the management of PG.

Le Pyoderma gangrenosum (PG) est une dermatose neutrophilique rare. Il est, dans la moitié des cas, associé à une maladie dysimmunitaire et il est fréquemment déclenché par un phénomène de pathergie, défini comme une agression tissulaire par une intervention chirurgicale ou encore une brûlure. Une patiente avec une rectocolite ulcéro-hémorragique a développé un PG sur le site d'application d'un patch d'ionophorèse pour une tendinopathie. Un traitement par une corticothérapie, un traitement immunosuppresseur local et des soins locaux adaptés ont permis une évolution favorable. Le PG reste un diagnostic d'exclusion et les phénomènes inflammatoires doivent être différenciés de phénomènes infectieux, comme la fasciite nécrosante, afin d'initier rapidement des immunosuppresseurs. Comme il s'agit d'une pathologie rare avec un diagnostic difficile, que des séquelles peuvent être catastrophiques et qu'un traitement immunosuppresseur complexe doit être instauré, une équipe pluridisciplinaire est requise pour la prise en charge de cette pathologie.

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The rising prevalence of obesity-related illnesses, such as metabolic steatotic liver disease (MASLD), represents a significant global public health concern. This disease affects approximately 30 % of the adult population and is the result of metabolic abnormalities rather than alcohol consumption. Additionally, MASLD is associated with an increased risk of cardiovascular disease (CVD), chronic liver disease, and a variety of cancers, particularly gastrointestinal cancers. Clonal hematopoiesis (CH) is a biological state characterized by the expansion of a population of blood cells derived from a single mutated hematopoietic stem cell. The presence of CH in the absence of a diagnosed blood disorder or cytopenia is known as clonal hematopoiesis of indeterminate potential (CHIP), which itself increases the risk of hematological malignancies and CVD. Steatotic liver disease may also complicate the clinical course of cancer patients receiving antineoplastic agents, a condition referred to as chemotherapy induced steatohepatitis (CASH). This review will present an outline of the various aspects of MASLD, including complications. Furthermore, it will summarize the existing knowledge on the emerging association between CHIP and MASLD and present the available data on patient cases with concurrent MASLD and hematological neoplasms. Finally, it will provide a brief overview of the chemotherapeutic drugs associated with CASH, the underlying pathophysiologic mechanisms and their clinical implications.

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This clinical case series presents descriptions of 3 patients with familial Mediterranean fever (FMF) who have atypical manifestations and abnormal inheritance mechanisms in terms of Gregor Mendel's laws. Although molecular genetic testing can help with disease diagnosis, it is not always conclusive. The primary need for genetic testing in atypical cases is to explain the mechanism of inflammation and to select the optimal therapy. These clinical observations demonstrate the changes in the spectrum of phenotypic manifestations of FMF in the context of the widespread introduction of molecular genetic methods.

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Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.

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Pyoderma gangrenosum (PG) is an uncommon inflammatory disorder that exhibits a range of clinical manifestations and levels of severity. It frequently occurs alongside an underlying condition, most often inflammatory bowel disease. PG, Sweet syndrome, palisaded neutrophilic granulomatous dermatitis (PNGD), interstitial granulomatous dermatitis (IGD) and rheumatoid neutrophilic dermatitis may be associated with rheumatoid arthritis (RA). We present a case of a 65-year-old woman with disseminated dermatosis to the hands, abdomen, buttocks, and lower limbs. The dermatosis presented with numerous ulcers of varying shapes, featuring clean bases, undermined edges, and a purplish erythematous appearance. Further investigations, including imaging studies and RA factor and anti-cyclic citrullinated peptide (anti-CCP) levels, led us to the diagnosis of RA. This case indicates that RA may be frequently undiagnosed and untreated in other patients with PG, as ulcers on the lower extremities can often be the main reason for seeking medical attention.

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BACKGROUND: Neutrophilic myocarditis often stems from bacterial or fungal infections, and it is typically detectable through blood cultures or analyses of the primary infection site. However, research specifically addressing the morphological features of acute myocarditis in complex sepsis cases is scarce, with existing studies primarily dating back to the pre-antibiotic era. METHODS: This study constitutes a retrospective and descriptive analysis encompassing 22 forensic cases. We collected data from forensic reports emphasising clinical details, disease history, gross observations, and histopathological findings. RESULTS: The results show that using positive-air-pressure ventilation could be related to cardiac inflammation (45.45%, 10/22). Despite large-spectrum antibiotic therapy, the blood samples were positive for Staphylococcus aureus (MRSA strain), Klebsiella pneumoniae (ESBL strain), Acinetobacter baumannii, and Pseudomonas aeruginosa. Colonies developed in the myocardium of 36% of the patients (8/22), where 4 of them had septic emboli. Fungal myocarditis accompanied bacterial infections (2/8) and were unsuspected clinically. Background changes, such as interstitial fibrosis and arteriosclerosis, were associated with a greater degree of inflammation and septic embolism. CONCLUSION: Neutrophilic myocarditis in patients with emerging sepsis is linked to fatal virulent infections, where bacteria and/or fungi contaminate and impair the myocardium syncytium. Prolonged hospitalisation and positive-air-pressure ventilation may be a risk factor for this condition and needs further research.

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Asthma is a heterogeneous disease that can be broadly classified into type 2, which is primarily steroid-sensitive and eosinophilic, and non-type 2, which is primarily steroid-resistant and neutrophilic. While the mechanisms leading to the development of molecular-targeted therapies for type 2 asthma are being elucidated, much remains to be learned about non-type 2 asthma. To investigate the role of oxidative stress in refractory allergic airway inflammation, we compared asthma models generated by immunizing wild-type and nuclear factor erythroid-2-related factor 2 (Nrf2)-deficient mice with the house dust mite antigen. Both asthma models had similar levels of airway inflammation and hyperresponsiveness, but the Nrf2-deficient mice had increased oxidative stress and exacerbated neutrophilic airway inflammation compared with the wild-type mice. Type 2 cytokines and the expression of GATA3, a transcription factor that is important for Th2 cell differentiation, had decreased in Nrf2-deficient mice compared with the wild-type mice, whereas helper T (Th) 17 cytokines and the expression of RORγt, which is important for Th17 cell differentiation, had increased. Furthermore, the neutrophilic airway inflammation caused by Nrf2 deficiency was ameliorated by interleukin (IL)-17 neutralization. We have concluded that the disruption of the Nrf2-mediated antioxidant defense system contributed to the induction of Th17 differentiation and exacerbated allergic neutrophilic airway inflammation.

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BACKGROUND: Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi-omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development. OBJECTIVES: To determine whether multi-omics integration of sputum leads to improved granularity of the molecular classification of severe asthma. METHODS: We analyzed six -omics data blocks-microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing-from induced sputum samples of 57 severe asthma patients, 15 mild-moderate asthma patients, and 13 healthy volunteers in the U-BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi-omics datasets of the 72 asthmatics. RESULTS: Five stable omics-associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL-22 cytokine activation, with the prediction of therapeutic response to anti-IL22 antibody therapy. CONCLUSION: Multi-omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high-dimensional interactions will contribute to a more comprehensive understanding of complex endotypes. KEY POINTS: Unsupervised clustering on sputum multi-omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma. One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia. One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL-22.

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OBJECTIVE: Biomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD. METHODS: Consecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines. RESULTS: 107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection. CONCLUSION: nCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD.