Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully clarified.Recently,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(S.maltophilia)was significantly increased in both the rumen and milk microbiota.Accordingly,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary gland.Therefore,this study investigated the mechanism by which enterogenic S.maltophilia induces mastitis.Results First,S.maltophilia was labelled with superfolder GFP and administered to mice via gavage.The results showed that treatment with S.maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal leakage.Furthermore,tracking of ingested S.maltophilia revealed that S.maltophilia could migrate from the gut to the mammary gland and induce mastitis.Subsequently,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S.maltophilia.Then,using mouse mammary epithelial cells(MMECs),we verified that S.maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusions In conclusion,the results showed that enterogenic S.maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis.Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

Prevalence of Mastitis and Associated Risk Factors in Lactating Camels (Camelus Dromedarius) on Dairy Farms in Benadir Region, Somalia

The study took a comprehensive approach to understanding mastitis in lactating camels, a disease that significantly impacts milk quantity and quality. This complex and multifactorial disease poses a significant challenge to dairy camel farming, particularly in Somalia. The studys objective was to determine the prevalence of mastitis and the risk factors associated with it among lactating camels on dairy farms in Benadir, Somalia. To achieve this, a cross-sectional study was conducted from May to September 2022 in the Benadir region of Somalia. A total of 96 lactating camels underwent examination using the California Mastitis Test (CMT) to identify clinical and subclinical mastitis cases. Additionally, a questionnaire survey was conducted among 20 farm employees/owners to gather information on hygiene practices, parity, lactation stage, tick infestation, and the presence of udder/teat lesions. Data regarding parity and lactation stage were obtained through owner interviews. The data collected on specifically designed forms were recorded and entered into a Microsoft Excel spreadsheet for analysis using SPSS version 20 statistical software, ensuring a comprehensive and reliable analysis of the data. The studys findings revealed a significant prevalence of camel mastitis, with 34.4% (33/96) of lactating camels affected and clinical and subclinical cases constituting 5.2% and 29.2%, respectively. Quarter-level prevalence was 46.3%, with clinical and subclinical mastitis at 4.7% and 41.6%, respectively. The study also identified significant associations (P < 0.05) among risk factors such as stage of lactation, parity, and age, indicating a higher susceptibility to mastitis in older camels during early lactation compared to those in late lactation and younger camels. These findings underscore the crucial role of inadequate hygienic conditions on camel farms and udder tick infestations in driving the elevated prevalence of mastitis, highlighting the need for improved management practices in dairy farming in Benadir, Somalia. Effective interventions, including improved management practices and extension services, are essential to reduce the burden of mastitis in dairy camels.

Granulomatous mastitis in a 50-year-old male:A case report and review of literature

BACKGROUND Granulomatous mastitis(GM)an inflammatory disease of the breast that usually affects women of childbearing age,occurs very rarely in males.CASE SUMMARY We present a case study of a 50-year-old male patient with GM.The patient developed a breast lump following the cleaning of a previously embedded dirtfilled nipple.While an initial improvement was noted with antibiotic therapy,a recurrence occurred a year later,showing resistance to the previously effective antibiotics.Subsequently,the lesion was excised.The histopathological examination confirmed the diagnosis of GM.CONCLUSION GM should be considered a possible diagnosis of male breast masses.

Research Progress of Zhuang Medicine Combined with Nanogels in Mastitis

Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relieving pain, promoting blood circulation, removing blood stasis, and softening hardness to dissipate stagnation, and show definite curative effect in preventing and treating breast diseases. Nano-composite hydrogels have the advantages of small toxic and side effects, high bioavailability, high targeting and controllable drug release. Therefore, this paper summarized and analyzed relevant literature of Zhuang medicine in treating breast diseases and clinical research of nanogels, providing new ideas and scientific basis for the treatment of mastitis with Zhuang medicine combined with nanogels.

Psychological experience of breastfeeding among primiparous women with lactating mastitis:A qualitative research

Objective:The objective of this study is to comprehensively understand the psychological experience of primiparous women during breastfeeding while dealing with lactating mastitis and to establish a reliable foundation for tailored support measures.Methods:Twenty primiparous mothers from a tertiary hospital in Beijing between January and March 2023 were chosen using purposive sampling for semi-structured interviews.After conducting 20 interviews,data saturation was achieved.The Colaizzi’s seven-step analytical approach was employed to analyze,summarize,and refine the identified themes.Results:Among primiparous women afflicted by lactating mastitis,the primary themes regarding breastfeeding attitudes included three key aspects:(1)uncertainty during the initial diagnosis phase,(2)intricate emotional journey during treatment,and(3)positive psychological outlook during the recovery stage.Conclusion:Primiparous women undergoing lactating mastitis experience substantial physical and psychological strain.It is crucial for medical personnel,family caregivers,and society at large to be attuned to the emotions of these patients.Tailored support measures should be offered to enhance patients’physical and mental well-being and facilitate disease recovery.

Correlation Between Granulomatous Mastitis and Autoimmune Function and the Immuneregulating Role of Traditional Chinese Medicine

Granulomatous mastitis(GM)is a benign granulomatous condition,and its pathogenesis may be related to autoimmune disorders.Cellular immunity,humoral immunity,immunoglobulins,and complement could all play a role in the disease process,showing certain clinical patterns.Corticosteroids can quickly control disease progression,and immunosuppressants can be used for complex and refractory GM cases.In traditional Chinese medicine(TCM),“healthy qi”is similar to immune system function.For GM with deficient healthy qi,TCM treatments such as internal and external herbal applications can help regulate immune function and shorten disease duration by staged and TCM treatment,regulating viscera,reinforcing healthy qi,and eliminating pathogenic factors.

Granulomatous lobular mastitis treated by a combined internal and external treatment of traditional Chinese medicine:A case report

BACKGROUND Granulomatous lobular mastitis(GLM)is a rare benign inflammatory disease of the breast and is classified under comedo mastitis in traditional Chinese medicine(TCM).The etiology of this disease is unknown,and it mainly occurs in women of childbearing age.The diagnosis depends on histopathological biopsy.At present,there is no systematic and standardized treatment plan for GLM.In the absence of evidence supporting an infectious etiology,affected patients might continue to receive multiple courses of antibiotics and unnecessary surgery.CASE SUMMARY A 37-year-old Chinese woman with a history of coronavirus disease 2019 infection presented with swelling and pain in the left breast.She also had erythema,nodules in the lower extremities,arthritis in both knees,cough,and headache.In the early stage of GLM,the mass was not significantly reduced by conservative treatment with internal application of TCM;hence,surgical treatment was carried out.The aim of postoperative treatment was to drain the pus,eliminate the necrosed tissue,and expand the muscles;fumigation and washing using TCM was applied.CONCLUSION Combined internal and external treatment with TCM,following the principle of“Prioritize internal treatment before ulceration and emphasize external treatment after ulceration”was effective in our patient with GLM.The prognosis was good.We believe that TCM offered valuable therapeutic benefits in this disease.

Heterogeneity of Outcomes Reporting in Trials Evaluating Traditional Chinese Medicine Breast Massage for Stasis Acute Mastitis: A Methodological Review

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI,Wanfang,VIP,Sino Med,Pub Med,Web of Science,Embase,Cochrane library,JBI,CINAHL,Psyc INFO,Clinical Trials Registry Platform portal,Clinical Trials Registry,Australian New Zealand Clinical Trials Registry,Center Watch Registry from inception to May 15,2022 to find randomized controlled trials,non-randomized controlled trials,case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage,with search terms of mastitis,acute mastitis,lactation mastitis,puerperal mastitis,breast problem,breast engorgement,milk stasis,blocked ducked,breast pain,breast massage,and acupoint massage.Outcomes and the measurement schemes(measurement methods,timing of assessing outcome,frequency of assessing outcome,measurers)were extracted from the included studies.We used the Management of Otitis Media with Effusion in Children with Cleft Palate(MOMENT)to assess the quality of each study,then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials(OMERACT)Filter 2.1 framework.Results We identified 85 clinical trials,in which 54 different outcomes were reported.A total of 81.2%(69/85)of studies were assessed as medium quality with a mean score of 2.6,and 18.8%(16/85)as low quality with a mean score of 0.9.These outcomes were organized in three core areas.Lump size(89.4%,76/85)was the most frequently reported outcome,followed by breast pain(69.4%,59/85)and milk excretion(68.2%,58/85).Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous.Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.

Methylome and transcriptome data integration reveals potential roles of DNA methylation and candidate biomarkers of cow Streptococcus uberis subclinical mastitis

Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.

Transcriptome‑wide mapping of milk somatic cells upon subclinical mastitis infection in dairy cattle

Background Subclinical intramammary infection(IMI)represents a significant problem in maintaining dairy cows’health.Disease severity and extent depend on the interaction between the causative agent,environment,and host.To investigate the molecular mechanisms behind the host immune response,we used RNA-Seq for the milk somatic cells(SC)transcriptome profiling in healthy cows(n=9),and cows naturally affected by subclinical IMI from Proto-theca spp.(n=11)and Streptococcus agalactiae(S.agalactiae;n=11).Data Integration Analysis for Biomarker discov-ery using Latent Components(DIABLO)was used to integrate transcriptomic data and host phenotypic traits related to milk composition,SC composition,and udder health to identify hub variables for subclinical IMI detection.Results A total of 1,682 and 2,427 differentially expressed genes(DEGs)were identified when comparing Prototheca spp.and S.agalactiae to healthy animals,respectively.Pathogen-specific pathway analyses evidenced that Proto-theca’s infection upregulated antigen processing and lymphocyte proliferation pathways while S.agalactiae induced a reduction of energy-related pathways like the tricarboxylic acid cycle,and carbohydrate and lipid metabolism.The integrative analysis of commonly shared DEGs between the two pathogens(n=681)referred to the core-mastitis response genes,and phenotypic data evidenced a strong covariation between those genes and the flow cytometry immune cells(r2=0.72),followed by the udder health(r2=0.64)and milk quality parameters(r2=0.64).Variables with r≥0.90 were used to build a network in which the top 20 hub variables were identified with the Cytoscape cyto-hubba plug-in.The genes in common between DIABLO and cytohubba(n=10)were submitted to a ROC analysis which showed they had excellent predictive performances in terms of discriminating healthy and mastitis-affected animals(sensitivity>0.89,specificity>0.81,accuracy>0.87,and precision>0.69).Among these genes,CIITA could play a key role in regulating the animals’response to subclinical IMI.Conclusions Despite some differences in the enriched pathways,the two mastitis-causing pathogens seemed to induce a shared host immune-transcriptomic response.The hub variables identified with the integrative approach might be included in screening and diagnostic tools for subclinical IMI detection.

Candidate genes for mastitis resistance in dairy cattle:a data integration approach

Background Inflammation of the mammary tissue(mastitis)is one of the most detrimental health conditions in dairy ruminants and is considered the most economically important infectious disease of the dairy sector.Improving mastitis resistance is becoming an important goal in dairy ruminant breeding programmes.However,mastitis resistance is a complex trait and identification of mastitis-associated alleles in livestock is difficult.Currently,the only applicable approach to identify candidate loci for complex traits in large farm animals is to combine different information that supports the functionality of the identified genomic regions with respect to a complex trait.Methods To identify the most promising candidate loci for mastitis resistance we integrated heterogeneous data from multiple sources and compiled the information into a comprehensive database of mastitis-associated candidate loci.Mastitis-associated candidate genes reported in association,expression,and mouse model studies were collected by searching the relevant literature and databases.The collected data were integrated into a single database,screened for overlaps,and used for gene set enrichment analysis.Results The database contains candidate genes from association and expression studies and relevant transgenic mouse models.The 2448 collected candidate loci are evenly distributed across bovine chromosomes.Data integration and analysis revealed overlaps between different studies and/or with mastitis-associated QTL,revealing promising candidate genes for mastitis resistance.Conclusion Mastitis resistance is a complex trait influenced by numerous alleles.Based on the number of independent studies,we were able to prioritise candidate genes and propose a list of the 22 most promising.To our knowledge this is the most comprehensive database of mastitis associated candidate genes and could be helpful in selecting genes for functional validation studies.

Clinical efficacy of external treatment with Zi Cao Yang He Tang combined with hormone therapy for granulomatous mastitis and its effect on cellular pyroptosis proteins

Objective:To observe the clinical effect of external application of Zi Cao Yang He Tang combined with dexamethasone ointment in the treatment of granulomatous lobular mastitis in the mass stage and the effect on cellular pyroptosis-related proteins.Methods:Forty patients with granulomatous lobular mastitis were randomly divided into 20 cases in the observation group and 20 cases in the control group.Both groups were given dexamethasone ointment for treatment,and the observation group was treated with external application of Zi Cao Yang He Tang on the basis of the control group.Breast lump vol-ume changes,breast pain and pus symptoms,pathology and histology and immunohistochemistry,cellular death-related indicators expression were compared between the two groups.Results:After treatment,the difference in mass volume of the observation group was significantly greater than that of the control group(16.7±21.5 in the control group and 32.9±27.4 in the experimental group)and the difference between the two groups was statistically significant(P<0.05);the objective remission rate of the patients in the observation group(ORR=85%)was significantly higher than that of the treatment group(ORR=50%,P<0.05).In terms of pus formation rate and pain level,the breast pain score of the observation group was significantly lower than that of the control group after two weeks or three weeks of treatment(P<0.05);the pus formation rate of the observation group was 30%,and the pus formation rate of the control group was 20%,and the difference was not statistically significant(P>0.05).The immunohistochemical expression levels of caspase-1 and GSDMD in the observation group were significantly lower than those in the control group(P<0.05);and in terms of the expression of cellular pyroptosis-related indexes,the expression of GSDMD,cas-pase-1,and NLRP3 in the observation group was significantly lower compared with that in the control group(P<0.05).Conclusion:The efficacy of external application of Zi Cao Yang He Tang combined with dexamethasone ointment in treating granulomatous lobular mastitis in the mass stage is remarkable,which can effectively reduce breast pain,reduce the size of the mass,de-crease the expression of cellular pyroptosisrelated indexes,and have a good anti-inflammatory effect.

Exploring the pathogenesis of idiopathic granulomatous mastitis based on the prolactin theory

Prolactin(PRL),as a cytokine,plays a variety of multidirectional roles in immunity and inflammation.An autoimmune condition known as idiopathic granulomatous mastitis(IGM)involves many inflammatory cells and cytokines.PRL links neuroendocrine and immune systems and plays an active role in the inflammatory and immune processes.Based on the theory of PRL and combined with the latest research review at home and abroad,this paper aims to review the mechanism of action of PRL on IGM from the aspects of various inflammatory cells,cytokines and pathways,revealing the influence of PRL theory on IGM and the mechanism of action,so as to effectively control inflammation in the long-term.

Value of identifying and diagnosing mammary carcinoma and non-lactation mastitis lump by color Doppler ultrasonography

Objective: To evaluate the value of identifying and diagnosing mammary carcinoma and non-lactation mastitis lump (NLM) by multicolor Doppler ultrasonography. Methods: We compared and analyzed the examination results of 69 cases of mammary carcinoma proved by surgical pathology and 22 cases of NLM before surgery by multicolor Doppler ultra-sonography. Results: The detection rates of mammary carcinoma and NLM focus by ultrasonic examining were 100%. The shape, envelope, foul line, blood stream between sound and image of two diseases were similar. Of the two diseases, the representation with slight calcification in lump, lower echo in low echo, bloodstream distribution and resistance were different. Conclusion: By analyzing the sound and image representation of mammary lump, we find color Doppler ultrasonography has significant value in identifying and diagnosing mammary carcinoma and non-lactation mastitis lump.

Therapeutic Effect of Daphnetin on Mastitis Induced by Staphylococcus aureus in Mice

[Objectives]To observe the effects of daphnetin on mastitis induced by Staphylococcus aureus in mice.[Methods]18 postpartum ICR female mice were used to establish mastitis animal model,and were randomly divided into three groups(A,B,and C)with 6 mice in each group.Group A:blank control group;group B:S.Aureus model group;group C:S.Aureus model+daphnetin group.The experimental groups were injected 1 mL of 1.0×104 CFU/100μL of S.aureus of along the nipple catheter.The suspension was placed in the 3 rd and 4 th pairs of mammary glands,and the control group was injected with the same dose of normal saline.On the second day after infection,the rats in group A,B and C were given drugs by gavage,while the rats in group A and B were given normal saline and the rats in group C were given daphnetin once a day for 6 consecutive days.Blood samples were collected from living eyeballs,and blood cells were analyzed by automatic flow cytometer after anticoagulation.[Results]The NLR and Systemie Immune Inflammati-on Index(SII)in the blood of mastitis mice induced by S.aureus were significantly higher than those in the control group(P<0.01),suggesting that neutrophil to lymphocyte ratio(NLR)and SII can be used as diagnostic indicators of mastitis,and the levels of NLR and SII decreased significantly after daphnetin intervention.[Conclusions]NLR and SII showed high levels in mastitis mice,which are valuable for the diagnosis of mastitis and the evaluation of its prognosis.After the intervention of daphnetin,both of them decreased significantly,indicating that daphnetin has a good prognosis trend in mastitis mice induced by S.aureus.

Genetic Polymorphism of TLR4 Gene and Correlation with Mastitis in Cattle

Toll-like receptor 4 （TLR4） recognizes pathogen ligands and mediates signaling to initiate innate and adaptive immune responses. In this experiment, a 316 bp and 382 bp fragments of TLR4 gene named T4CRBR1 and T4CRBR2, of Chinese Holstein, Sanhe cattle, and Chinese Simmental was amplified by polymerase chain reaction （PCR）, respectively. The genetic polymorphisms in the three populations were detected by Single-Strand Conformational Polymorphism （SSCP） in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results showed that both alleles （A and B） of two loci were found in all the three populations and the value of polymorphism information content （PIC） indicated that these were a moderate polymorphism. Statistical results of X^2 test indicated that two polymorphism sites in the three populations fitted with Hardy-Weinberg equilibrium （P 〉 0.05）. After sequencing, A-G single nucleotide polymorphism （SNP） was identified at nucleotide 4,525 in intron 1 of TLR4 gene and C-T SNP was identified at nucleotide 1,397 in exon 3 of TLR4 gene. Meanwhile, the effect of polymorphism of TLR4 gene on somatic cell score （SCS） was analyzed, the results indicated that the cattle with allele A in T4CRBR1 showed lower somatic cell score than that of allele B （P 〈 0.05）. In short, the allele A might play an important role in mastiffs resistance in bovine.

Drug Sensitive Test on Main Pathogenic Bacteria of Cow Recessiveness Mastitis Using Traditional Chinese Medicine Preparation “Zengrujianniusan”

According to the theory of Chinese veterinary medicine and characteristics of Chinese herbal medicine, four different preparations of compound Chinese medicine ＂Zengrujianniusan＂ were composed, and the prepared water decoction was used to carry on the bacteriostatic test on main pathogens of cow recessiveness mastitis. The results showed that the four different prescriptions of water decoction all had antibacterial effects. The prescription 3 was sensitive to Staphylococcus aureus and Streptococcus agalactiae, while the other three prescriptions showed high sensitivity, and the prescription 3 had the strongest bacteriostatic effects.

Diagnosis and Treatment of Yeast Mastitis in Dairy Cattle

[Objective] Study on the yeast mastitis in dairy cattle cases which have been ineffectively treated by multiple antibiotics through traditional Chinese medicine prescription. [ Method] The isolated pathogenic fungi from milk were used for drug sensitivity testing and the ones proved were clinically treated by self-made traditional Chinese medicine prescription ＂Ruxiaotang＂. [ Result] 19 cases of 20 selected dairy cattle cases were diagnosed as yeast mastitis and cured with the except of a Candida tropicalis case. [ Conclusion] The results provide a new reference for curing yeast mastitis.

Aetiology of idiopathic granulomatous mastitis

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail.

Management of granulomatous lobular mastitis: an international multidisciplinary consensus(2021 edition)

Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.