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Annals of the Rheumatic Diseases Jun 2023Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target...
OBJECTIVES
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target proteinase 3 (PR3) or myeloperoxidase (MPO) found within neutrophils and monocytes. Granulomas are exclusively found in GPA and form around multinucleated giant cells (MGCs), at sites of microabscesses, containing apoptotic and necrotic neutrophils. Since patients with GPA have augmented neutrophil PR3 expression, and PR3-expressing apoptotic cells frustrate macrophage phagocytosis and cellular clearance, we investigated the role of PR3 in stimulating giant cell and granuloma formation.
METHODS
We stimulated purified monocytes and whole peripheral blood mononuclear cells (PBMCs) from patients with GPA, patients with MPA or healthy controls with PR3 or MPO and visualised MGC and granuloma-like structure formation using light, confocal and electron microscopy, as well as measuring the cell cytokine production. We investigated the expression of PR3 binding partners on monocytes and tested the impact of their inhibition. Finally, we injected zebrafish with PR3 and characterised granuloma formation in a novel animal model.
RESULTS
In vitro, PR3 promoted monocyte-derived MGC formation using cells from patients with GPA but not from patients with MPA, and this was dependent on soluble interleukin 6 (IL-6), as well as monocyte MAC-1 and protease-activated receptor-2, found to be overexpressed in the cells of patients with GPA. PBMCs stimulated by PR3 formed granuloma-like structures with central MGC surrounded by T cells. This effect of PR3 was confirmed in vivo using zebrafish and was inhibited by niclosamide, a IL-6-STAT3 pathway inhibitor.
CONCLUSIONS
These data provide a mechanistic basis for granuloma formation in GPA and a rationale for novel therapeutic approaches.
Topics: Animals; Myeloblastin; Granulomatosis with Polyangiitis; Zebrafish; Interleukin-6; Leukocytes, Mononuclear; Microscopic Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Granuloma; Giant Cells; Peroxidase
PubMed: 36801813
DOI: 10.1136/ard-2021-221800 -
Journal of Clinical and Experimental... Jan 2023Sporotrichosis is an uncommon subacute or chronic infection caused by Sporothrix spp. In some urban areas of Latin America, sporotrichosis has been considered an...
Sporotrichosis is an uncommon subacute or chronic infection caused by Sporothrix spp. In some urban areas of Latin America, sporotrichosis has been considered an emergent cosmopolitan disease of zoonotic transmission by domestic cats. There are four different clinical forms of the disease: fixed cutaneous, lymphocutaneous, multifocal or disseminated cutaneous, and extracutaneous. The oral mucosa is rarely involved, usually as unspecified chronic ulcers in the context of multifocal or disseminated cutaneous form of systemic sporotrichosis. Microscopical features include chronic granulomatous inflammation containing microabscesses and fungal hyphae positive for Periodic acid Schiff and silver-based stains. The diagnosis of sporotrichosis is usually based on culture detection and strict correlation of clinical, microscopical and laboratorial data. We herein contribute with two additional illustrative cases of oral manifestation of sporotrichosis in immunocompromised patients from an endemic urban area from Rio de Janeiro-Brazil. Sporotrichosis, ulcer, oral cavity, immunosuppression.
PubMed: 36755684
DOI: 10.4317/jced.59040 -
The Ultrasound Journal Feb 2023The spleen is frequently scanned in workup of infections. Hypoechoic splenic micro-abscesses are known signs of disseminated tuberculosis in HIV co-infected patients....
BACKGROUND
The spleen is frequently scanned in workup of infections. Hypoechoic splenic micro-abscesses are known signs of disseminated tuberculosis in HIV co-infected patients. The spleen of HIV patients is thus often scanned using high-frequency transducers.
METHODS AND FINDINGS
We describe a reticulo-nodular "sponge pattern" in the spleen of an HIV-positive patient with Hodgkin's lymphoma. Disseminated throughout the spleen, very small (1.5-2.0 mm) hypoechoic lesions having a branching reticulo-nodular distribution were seen. The lesions partly, but not entirely, follow splenic vasculature. Review of stored images of other patients identified 15 more cases showing a similar pattern. All patients were HIV positive, almost all with CD4 counts below 200 cells/mm. Seven (44%) were additionally diagnosed with HHV-8-associated diseases, but the pattern was seen with various underlying opportunistic infections.
DISCUSSION AND CONCLUSION
After comparison with spleen microscopic anatomy, we hypothesize that the white pulp of spleens in our patients is hyperplastic or otherwise changed in consistency to be better visible by high-frequency ultrasound. Concomitant human herpesvirus-8 infection may be another cause of this visible white pulp. While we can only speculate about the etiology of the splenic "sponge pattern," it needs to be recognized as it may be misinterpreted as splenic micro-abscesses of disseminated infections, like tuberculosis in severely immune-compromised patients.
PubMed: 36735108
DOI: 10.1186/s13089-022-00297-z -
Frontiers in Pediatrics 2022More than 400 single gene defects have been identified as inborn errors of immunity, including many arising from genes encoding proteins that affect NF-κB activity. We... (Review)
Review
More than 400 single gene defects have been identified as inborn errors of immunity, including many arising from genes encoding proteins that affect NF-κB activity. We summarise the skin phenotypes in this subset of disorders and provide an overview of pathogenic mechanisms. NF-κB acts cell-intrinsically in basal epithelial cells during differentiation of skin appendages, influences keratinocyte proliferation and survival, and both responses to and amplification of inflammation, particularly TNF. Skin phenotypes include ectodermal dysplasia, reduction and hyperproliferation of keratinocytes, and aberrant recruitment of inflammatory cells, which often occur in combination. Phenotypes conferred by these rare monogenic syndromes often resemble those observed with more common defects. This includes oral and perineal ulceration and pustular skin disease as occurs with Behcet's disease, hyperkeratosis with microabscess formation similar to psoriasis, and atopic dermatitis. Thus, these genotype-phenotype relations provide diagnostic clues for this subset of IEIs, and also provide insights into mechanisms of more common forms of skin disease.
PubMed: 36733767
DOI: 10.3389/fped.2022.1098426 -
Scientific Reports Jan 2023Staphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that...
Staphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that characterise infection can be clonal, whereby a large bacterial population is founded by a single or few organisms. Our previous work has shown that macrophages are responsible for restricting bacterial growth such that a population bottleneck occurs and clonality can emerge. A subset of phagocytes fail to control S. aureus resulting in bacterial division, escape and founding of microabscesses that can seed other host niches. Here we investigate the basis for clonal microabscess formation, using in vitro and in silico models of S. aureus macrophage infection. Macrophages that fail to control S. aureus are characterised by formation of intracellular bacterial masses, followed by cell lysis. High-resolution microscopy reveals that most macrophages had internalised only a single S. aureus, providing a conceptual framework for clonal microabscess generation, which was supported by a stochastic individual-based, mathematical model. Once a threshold of masses was reached, increasing the number of infecting bacteria did not result in greater mass numbers, despite enhanced phagocytosis. This suggests a finite number of permissive, phagocyte niches determined by macrophage associated factors. Increased understanding of the parameters of infection dynamics provides avenues for development of rational control measures.
Topics: Humans; Staphylococcus aureus; Phagocytosis; Macrophages; Staphylococcal Infections; Phagocytes; Abscess
PubMed: 36681703
DOI: 10.1038/s41598-023-27928-2 -
Journal of the National Medical... Apr 2023In this paper, we reported a 37-year-old man who developed several lymphadenopathies after using the second dose of Pfizer-BioNtech vaccination against SARS-CoV-2. The...
In this paper, we reported a 37-year-old man who developed several lymphadenopathies after using the second dose of Pfizer-BioNtech vaccination against SARS-CoV-2. The excisional lymph node biopsy showed eosinophil-rich inflammation with micro-abscesses. Although eosinophilic dermatosis and eosinophilic myocarditis have been described previously following COVID-19 vaccinations, eosinophilic lymph node abscess was not reported in the literature. In our case, all lesions were completely recovered with steroid treatment. The patient has been doing well and no recurrence has been observed for six months.
Topics: Male; Humans; Adult; Abscess; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Lymphadenopathy; Lymph Nodes
PubMed: 36681552
DOI: 10.1016/j.jnma.2023.01.003 -
Clinical, Cosmetic and Investigational... 2023Eosinophilic pustular folliculitis (EPF) is a rare, chronic, non-infectious inflammatory skin disease. Although the pathogenesis of EPF is unknown, eosinophilic pustular...
Eosinophilic pustular folliculitis (EPF) is a rare, chronic, non-infectious inflammatory skin disease. Although the pathogenesis of EPF is unknown, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection, malignancies or syphilis. Here, we report the first case of EPF associated with syphilis, indicating that syphilis and EPF are correlated with T-helper type 2 immune responses. A 48-year-old man gradually developed erythema and pustules on the face, neck. Physical examination revealed multiple infiltrative red patches and plaques on the face, neck with tiny pustules. Skin biopsy results revealed that the dermal follicular sebaceous gland unit was infiltrated by a large number of neutrophils and eosinophils, forming eosinophilic microabscesses. Therefore, the patient was diagnosed with EPF associated with syphilis and received drug treatment. After the treatment, the pustules markedly decreased, leaving behind pigmentation. Furthermore, the patient is still being followed up.
PubMed: 36647541
DOI: 10.2147/CCID.S393841 -
BMC Neurology Jan 2023Granulomatous hypophysitis is a rare disease that presents with chronic inflammation of the pituitary gland. In this study, we reported a case of granulomatous...
BACKGROUND
Granulomatous hypophysitis is a rare disease that presents with chronic inflammation of the pituitary gland. In this study, we reported a case of granulomatous hypophysitis associated with a pituitary abscess.
CASE PRESENTATION
A 39-year-old woman presented with a 2-year history of infertility. For the past six months, she has suffered from amenorrhea, decreased libido, headaches, and vertigo. She was referred to our hospital with a suspected diagnosis of nonfunctioning pituitary adenoma based on her presentation and brain MRI findings. She underwent trans-sphenoidal surgery (TSS). Direct observation during surgery revealed drainage of malodor pus and pituitary gland abscess. The histopathological evaluation also showed granulomatous hypophysitis and neutrophilic microabscess formation. The patient was initially treated with high doses of ceftriaxone (2 g twice daily) and metronidazole (500 mg (mg) four times per day). Also, the patient received cortisol replacement therapy after the operation. After obtaining the antibiogram and culture results, the treatment regimen was continued for 4 weeks postoperatively, followed by amoxicillin-clavulanate (500/125 mg three times daily) for a total duration of 12 weeks.
CONCLUSION
The patient recovered uneventfully and the postoperative MRI was normal without any remnant lesions.
Topics: Humans; Female; Adult; Abscess; Pituitary Diseases; Pituitary Neoplasms; Hypophysitis; Pituitary Gland; Magnetic Resonance Imaging
PubMed: 36631799
DOI: 10.1186/s12883-023-03060-6 -
Frontiers in Medicine 2022Chronic disseminated candidiasis (CDC) classically occurs after profound and prolonged neutropenia. The aim of the CANHPARI study was to assess the clinical value of...
BACKGROUND
Chronic disseminated candidiasis (CDC) classically occurs after profound and prolonged neutropenia. The aim of the CANHPARI study was to assess the clinical value of adding F-fluorodeoxyglucose PET/CT to conventional radiology for initial and subsequent evaluations of CDC.
MATERIALS AND METHODS
A pilot prospective study was conducted in 23 French onco-hematological centers from 2013 to 2017 (NCT01916057). Patients ≥ 18 y.o. suspected for CDC on abdominal conventional imaging (CT or MRI) were included. PET/CT and conventional imaging were performed at baseline and month 3 (M3). Follow-up was assessed until M12. The primary outcome measure was the global response at M3, i.e., apyrexia and complete response to PET/CT. The secondary outcome measure consists in comparison between responses to PET/CT and conventional imaging at diagnosis and M3.
RESULTS
Among 52 included patients, 44 were evaluable (20 probable and 24 possible CDC); 86% had acute leukemia, 55% were male (median age 47 years). At diagnosis, 34% had fever and conventional imaging was always abnormal with microabscesses on liver and spleen in 66%, liver in 25%, spleen in 9%. Baseline PET/CT showed metabolic uptake on liver and/or spleen in 84% but did not match with lesion localizations on conventional imaging in 32%. M3 PET/CT showed no metabolic uptake in 13 (34%) patients, 11 still having pathological conventional imaging. Global response at M3 was observed in eight patients.
CONCLUSION
Baseline PET/CT does not replace conventional imaging for initial staging of CDC lesions but should be performed after 3 months of antifungal therapy.
CLINICAL TRIAL REGISTRATION
[www.clinicaltrials.gov], identifier [NCT01916057].
PubMed: 36606049
DOI: 10.3389/fmed.2022.1026067 -
Frontiers in Immunology 2022Munro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA...
INTRODUCTION
Munro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.
METHODS
Performed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.
RESULTS
We observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.
DISCUSSION
In conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Psoriasis; Skin; Abscess; Sirtuins
PubMed: 36569916
DOI: 10.3389/fimmu.2022.1057839