Development Of Reactive Arthritis Research Articles

Lactobacillus rhamnosus GG for the prevention of reactive arthritis relapse in children

Introduction. The results of numerous studies indicating the relationship between the development of reactive arthritis (ReA) and the disturbance of the intestinal microbiocenosis give rise to interest in commensal microorganisms that make up the intestinal microbiota as potential initiators of immune-dependent inflammatory diseases of the joints. In this regard, the question of the expediency of using probiotic preparations for the correction of ReA patients intestinal microflora is of practical interest.The purpose of the study was to evaluate the effectiveness of Lactobacillus rhamnosus LGG (LGG) in the preventive treatment of children with ReA to prevent the development of relapses.Materials and methods. Clinical and microbiological study included 60 patients with ReA from 3 to 17 years old, who were divided into two groups, 30 children each. Patients of the group 1 received courses of treatment with LGG in the inactive phase of the disease. Patients of the group 2 (comparison group) were not treated with probiotic. The criteria for the effectiveness of treatment were the number of relapses of ReA during follow-up observation for 1 year; dynamics of intestinal microbiocenosis condition according to the following parameters: indicator of microbial contamination (IMC) of intestinal microsymbionts; ability to biofilm formation (BF); levels of lactoferrin and lysozyme in coprofiltrates.Results. In patients treated with LGG, relapses of arthritis were significantly less frequent during 12 months of prospective observation relative to the comparison group. Patients of the group 1 showed positive dynamics of the state of intestinal microbiocenosis: a decrease in the severity of dysbiosis, a decrease of lactoferrin and lysozyme level in coprofiltrates, IMC and BF of opportunistic microorganisms against the increase IMC and BF in bifidobacteria and lactobacilli.Conclusions. The use of LGG in the treatment of children with ReA in the inactive phase of the disease contributes to the correction of intestinal microbiocenosis disorders and reduces the number of arthritis relapses.

Прогнозирование развития реактивного артрита у детей с дисплазией соединительной ткани

Objective. To develop a model for automated prediction of the development of recurring reactive arthritis in children with symptoms of connective tissue dysplasia (CTD). Patients and methods. The work included two stages. At the first stage, in order to identify the predisposing factors to the development of reactive arthritis (ReA), two age- and sex-representative groups of children aged 3-17 years were formed: group 1 consisted of children with ReA (50 patients), group 2 – comparison group (25 conditionally healthy children from the general population). All children underwent a standard clinical examination with determination of CTD symptoms, and microbiological examination, including evaluation of the state of microbiocenosis of the distal colon by degrees; the ability of isolated microorganisms to biofilm formation (BF); levels of lactoferrin (LF) and lysozyme (LZC) in coprofiltrates of children. At the second stage, to create an automated prediction model, two additional groups of children were formed: 30 conditionally healthy children with CTD symptoms without arthritis and 30 conditionally healthy children without CTD symptoms. Stepwise discriminant analysis (DA) and the method of resultants mapping were used. Results. The factors determining the risk of ReA development in children with connective tissue dysplasia were identified. Highly informative markers associated with the development and course of ReA were established: the presence of external phenotypic symptoms and dysplasia of internal organs; dysbiotic disorders of the distal large intestine; high rates of microbial contamination and BF of intestinal microsymbionts; increased levels of LF and LZC in coprofiltrates of children. Conclusion. The diagnostic algorithm for automated prediction of the development of arthritis recurrence was developed, which allows primary care physicians to solve the problem of secondary prevention of ReA. Key words: reactive arthritis, children, connective tissue dysplasia, intestinal microbiota, prediction method

Chronic seronegative spondyloarthropathy following acute Mycoplasma pneumoniae infection in a human leukocyte antigen B27-positive patient: a case report

BackgroundWe report a case of a 30-year-old patient who presented with acute Mycoplasma pneumoniae infection that was complicated by reactive arthritis and asymmetric proximal myopathy and progressed to chronic spondyloarthropathy. Reactive arthritis and sacroiliitis are unusual extrapulmonary manifestations of M. pneumoniae infection, which is a common condition.Case presentationA 30-year-old Greek previously healthy man presented to our emergency department with fever, progressively worsening bilateral lower limb weakness, and asymmetric oligoarthritis. Our diagnosis was based on a positive polymerase chain reaction test for M. pneumoniae using blood and cerebrospinal fluid and magnetic resonance imaging findings that suggested sacroiliitis. Our patient was also found to be human leukocyte antigen B27 positive. His infection was successfully treated with a 14-day course of doxycycline; the arthritis was treated with naproxen and corticosteroids. His arthritis, which restricted his mobility, improved progressively, and he was discharged without any neurological symptoms.ConclusionsIn our case, an acute M. pneumoniae infection eventually progressed to chronic spondyloarthropathy. In our patient, M. pneumoniae infection may represent a random event, or it might be a necessary factor for the development of reactive arthritis, asymmetric proximal myopathy, and sacroiliitis, always in combination with the appropriate genetic background. Extrapulmonary manifestations of M. pneumoniae may occur even in the complete absence of respiratory symptoms, and the diagnosis of unusual complications, such as reactive arthritis, requires high clinical suspicion and extensive investigation.

Reactive arthritis and other musculoskeletal symptoms associated with acquisition of diarrhoeagenic Escherichia coli (DEC)

ObjectivesUsing a prospective research design, we evaluated the association between acquisition of diarrhoeagenic Escherichia coli (DEC) and development of reactive arthritis (ReA) and other reactive musculoskeletal (MSK) symptoms among international...

Reactive arthritis imunopathogenesis

Introduction. It is known, that reactive arthritis is one of the widespread joints pathology. In recent years an increase in the number of patients with this pathology has been observed. Causative factors of reactive arthritis are completely unexplored today, the question of pathogenesis of reactive arthritis remains for discussions. Inflamatory diseases of joins, wich are developing due to immune disorders after urogenital, intestinal or respiratory infection belong to reactive arthritis.The aim of the study – to learn the functional activity of cells of phagocytic system (monocytes and neutrophils of peripheral blood) and detection of diagnostic value of phagocytic reactions in cases of reactive arthritis.Research Methods. The investigations were conducted on blood samples, of patients with reactive arthritis (n=20) and healthy donors (n=12). The phagocytic activity of neutrophils was determined using method based on endocytosis latex particles by phagocytes, which are visualized in cytoplasm of cells in form of round granules with blue color. Test with nitro blue tetrazolium (NBT-test) was carried out according to the change of color NBT in presents of reactive oxygen species. The counting of neutrophils with blue color granules allows to determine fraction of neutrophils with reactive oxygen species.Results and Discussion. Trigger factor causing development of reactive arthritis mostly is Chlamidia trachomatis (36 %). Patients with this pathology have statistically significant changes of functional metabolic activity of neutrophils and monocytes of blood. By such indicators as amount of white blood cells, monocytes and neutrophils in peripheral blood and phagocytic activity in cases of reactive arthritis signs of inflammation have been detected.Conclusion. Received data testify about decreased phagocytic activity of neutrophils and monocytes of blood with the development of reactive arthritis.

Видовий склад інфекційних чинників, що спричиняють розвиток реактивного артриту та їх вплив на аргіназно-NО-синтазну регуляторну систему лімфоцитів периферичної крові

The own observations results of urogenital, gastrointestinal and nasopharyngeal infectious factors that cause the development of reactive arthritis (PeA) are being presented. The greatest contribution to the development of this disease make Chlamidia trachomatis (36%), Streptococcus haemolyticus (pyogenes) (19%) and hepatitis viruses B and C (10%). As a result of the research a number of kinetic parameters of arginase and NO-synthase reactions in peripheral blood lymphocytes of patients with reactive arthritis was identified. The authentic increase of arginase activity in 3.3 times and eNO-synthase activity decrease by 1,9 times in peripheral blood lymphocytes of patients with PeA, compared to practically healthy donors were determined. Increased activity of arginase and iNO-synthase of lymphocytes indicates changes in immune cells functional activity, which may be due to impaired metabolic and regulatory processes in these cells caused by a bacterial or viral infection.

Observations on Chlamydia trachomatis and other microbes in reactive arthritis.

There are problems in attributing causality in inflammatory arthritis. So far as C. trachomatis and sexually acquired reactive arthritis are concerned, there is much in favour of a causal relationship, although there are important caveats which need to be explored before it is possible to say unreservedly that C. trachomatis plays a causative role in reactive arthritis. For example, micro-organisms have never been cultured from synovial effusions in early disease, and only once has substantial benefit of antimicrobial treatment been reported. The claim that ocular strains of C. trachomatis are of over-riding importance in pathogenesis needs confirmation before it can be accepted. No conclusion can be made about the possibility of other small intracellular bacteria in joints having a role in causing disease. However, if it can be shown that eradication of the micro-organism, which may be difficult to prove, coincides with clinical recovery, it would go some way to recognising causality. In spite of the recognised difficulties, antibiotic studies have an important role in identifying aetiology. They need to focus on very early disease and on eradication of intra-articular bacteria. Treatment of established disease is likely to be less informative. Although a combination of antibiotics might have a future in treating established disease, diagnosing and treating non-gonococcal urethritis as soon as possible should be the aim in order to prevent the development of reactive arthritis.

Seroprevalence of campylobacteriosis and relevant post-infectious sequelae

Post-infectious sequelea such as Guillain Barré syndrome (GBS), reactive arthritis (RA), and inflammatory bowel disease (IBD) may arise as a consequence of acute Campylobacter-enteritis (AE). However, reliable seroprevalence data of Campylobacter-associated sequelae has not been established. The objectives of this study were, first, to identify the most specific and sensitive test antigen in an optimized ELISA assay for diagnosing a previous Campylobacter-infection and, second, to compare the prevalence of anti-Campylobacter antibodies in cohorts of healthy blood donors (BD), AE, GBS, RA, and IBD patients with antibodies against known GBS, RA and IBD triggering pathogens. Optimized ELISAs of single and combined Campylobacter-proteins OMP18 and P39 as antigens were prepared and sera from AE, GBS, RA and IBD patients and BD were tested for Campylobcter-specific IgA and IgG antibodies. The results were compared with MIKROGEN™-recomLine Campylobacter IgA/IgG and whole cell lysate-immunoblot. Antibodies specific for Helicobacter pylori, Mycoplasma pneumoniae, Yersinia enterocolitica, and Borrelia afzelii were tested with commercial immunoblots. ROC plot analysis revealed AUC maxima in the combination of OMP18 and P39 for IgA and in the P39-antigen for IgG. As a result, 34–49 % GBS cases, 44–62 % RA cases and 23–40 % IBD cases were associated with Campylobacter-infection. These data show that Campylobcater-seropositivity in these patient groups is significantly higher than other triggering pathogens suggesting that it plays an important role in development of GBS and RA, and supports the hypothesis that recurrent acute campylobacteriosis triggers IBD.

Lack of TNFR p55 Results in Heightened Expression of IFN-γ and IL-17 during the Development of Reactive Arthritis

Reactive arthritis (ReA) is a type of arthritis originating from certain gastrointestinal or genitourinary infections. In previous studies, we reported the development of progressive Yersinia enterocolitica-induced ReA in mice lacking TNFR p55; however, the mechanisms underlying this effect are still uncertain. In this study, we investigated the impact of TNFR p55 deficiency in modulating Ag-specific Th1 and Th17 responses during this arthritogenic process. We found more severe ReA in TNFRp55(-/-) mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed greater amounts of IFN-γ and IL-17 in arthritic joints of TNFRp55(-/-) mice compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55(-/-) mice, as well as in spleen cells obtained from infected mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine secretion were associated with a greater frequency of CD4(+)IL-17(+), CD4(+)IFN-γ(+), and IL-17(+)IFN-γ(+) cells in TNFRp55(-/-) mice compared with WT mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-γ resulted in reduced joint histological scores in TNFRp55(-/-) mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23, in the generation of augmented IFN-γ and IL-17 production under TNFR p55 deficiency. Taken together, these data indicate that, in the absence of TNFR p55 signaling, Th1 and Th17 effector cells may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.

Microarray Analysis of Response of Salmonella during Infection of HLA-B27- Transfected Human Macrophage-Like U937 Cells

BackgroundHuman leukocyte antigen (HLA)-B27 is strongly associated with the development of reactive arthritis (ReA) in humans after salmonellosis. Human monocytic U937 cells transfected with HLA-B27 are less able to eliminate intracellular Salmonella enterica serovar Enteritidis than those transfected with control HLA antigens (e.g. HLA-A2). To investigate further the mechanisms by which HLA-B27-transfected cells allow increased replication of these bacteria, a DNA-based microarray was used for comparative genomic analysis of S. Enteritidis grown in HLA-B27- or HLA-A2-transfected cells. The microarray consisted of 5080 oligonucleotides from different serovars of Salmonella including S. Enteritidis PT4-specific genes. Bacterial RNA was isolated from the infected HLA-B27- or HLA-A2-transfected cells, reverse-transcribed to cDNA, and hybridized with the oligonucleotides on the microarrays. Some microarray results were confirmed by RT-PCR.ResultsWhen gene expression was compared between Salmonella grown in HLA-B27 cells and in HLA-A2 cells, 118 of the 4610 S. Enteritidis-related genes differed in expression at 8 h after infection, but no significant difference was detectable at 2 h after infection. These differentially expressed genes are mainly involved in Salmonella virulence, DNA replication, energy conversion and metabolism, and uptake and metabolism of nutrient substances, etc. The difference suggests HLA-B27-dependent modulation of Salmonella gene expression, resulting in increased Salmonella replication in HLA-B27-positive cells. Among the up-regulated genes were those located in Salmonella pathogenicity island (SPI)-2, which play a central role in intracellular survival and replication of Salmonella.ConclusionsThis is the first report to show the regulation of Salmonella gene expression by HLA-B27 during infection of host cells. This regulation probably leads to increased Salmonella survival and replication in HLA-B27-positive cells. SPI-2 genes seem to contribute significantly to the increased replication.

Solute Carrier Family 11 Member A1 Gene Polymorphisms in Reactive Arthritis

To investigate the role of SLC 11A1 polymorphisms in the development of reactive arthritis, 91 patients with reactive arthritis and 163 healthy controls were enrolled in this study. The SLC 11A1 polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. The genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were significantly different between the patients with reactive arthritis and controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the SLC 11A1 274C/T showed a significant association with reactive arthritis. The patients with reactive arthritis have a significantly higher frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was resistant to the development of reactive arthritis. The allele frequencies of SLC 11A1 274T and 823C were significantly increased in the patients with reactive arthritis in comparison with those of the controls, independent of HLA-B27. On the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly decreased in the patients with reactive arthritis. The estimated haplotype frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are associated with susceptibility to reactive arthritis independently of HLA-B27 in Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1 274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.

Reactive arthritis following BCG immunotherapy for urinary bladder carcinoma: a systematic review

Intravesical instillation of Bacillus Calmette-Guerin (BCG) is used with efficacy and safety in the treatment of patients with intermediate and high-risk superficial bladder carcinoma. Arthralgia and/or arthritis is one of the rare severe complications following intravesical BCG immunotherapy. We searched MEDLINE in order to analyze the frequency of this clinical complication, its pathogenesis and outcome. The electronic search was conducted using the following key words: "BCG immunotherapy" and "Arthritis, arthralgias and BCG immunotherapy". At the end of a process of abstract analysis, 48 papers were included in the systematic review. All the selected papers, except one that was a clinical review, described at least one case of arthritis after BCG therapy. The BCG immunotherapy resulted to be safe and efficacious in the treatment of bladder cancer; the development of reactive arthritis is rare and can evolve in a chronic process. The review of the literature highlighted that reactive arthritis following BCG intravesical instillation is a complication usually well controlled with the discontinuation of the immunotherapy and nonsteroidal anti-inflammatory drugs (NSAIDs) treatment. Only a small portion of patients with a particular genetic background will develop a chronic process.

Characterization of the IL-12 family of cytokines in human dendritic cells infected with live Chlamydia trachomatis

Chlamydia trachomatis (CT) is a clinically important pathogen. In 2–5% of cases, infection results in the development of reactive arthritis. We have previously shown that human dendritic cells (DC) can be readily infected with live CT following in vitro exposure [1]. Infected DC efficiently process chlamydia and present chlamydial antigens to both CD4+ [1] and CD8+ T cells [1,2]. Infected DC also produce a number of cytokines including IL-12 and tumour necrosis factor alpha but not IL-10 [1]. The production of IL-12 following infection gives DC the ability to stimulate Th1 responses to chlamydia. Here we have investigated production of another two cytokines from the IL-12 family – IL-23 and IL-27 – by DC infected with live CT. The results were compared with those obtained following DC activation with other inflammatory stimuli. IL-23 is a heterodimer composed of p19 and p40 subunits, where the p40 subunit is shared between IL-23 and IL-12. IL-27 is a heterodimer composed of p28 and Epstein–Barr virus-induced protein 3 (EBI3) subunits. The main function of both of these cytokines is to stimulate interferon gamma (IFN-γ) production in T cells. However, whereas IL-27 activity primarily affects naive T cells, IL-23 stimulates both primed and memory cells.

Microbial factors in spondyloarthropathies: insights from population studies.

Infections and genetics play a role in the development of reactive arthritis. The clinical manifestations and severity of the features depend on the triggering infections and the epidemiologic setting. Reports from hospital-based series show the lowest frequency of reactive arthritis, but often, patients have severe arthritis associated with a high frequency of HLA-B27. At the population level, reactive arthritis occur in 7 to 15% of the infected subjects. The disease is usually mild, affects small joints, can be polyarticular, often rapidly disappears, and has a low association with HLA-B27. There also seems to be a change in the spectrum of triggering infections. Reports of Yersinia arthritis are less common, whereas arthritis in association with Campylobacter or Salmonella infections seems to be increasing. The role of early antimicrobial chemotherapy for the prevention of reactive arthritis needs to be studied.

IL10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients

IL10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients

IL10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients.

To investigate the association of microsatellites and single-nucleotide promoter polymorphisms (SNPs) in the gene for the cytokine interleukin-10 (IL-10) with susceptibility to and outcome of reactive arthritis (ReA). From genomic DNA, IL-10 microsatellites G and R and IL-10 promoter polymorphisms at positions -1087 and -524 were typed by polymerase chain reaction, automated fragment length analysis, and restriction fragment digestion in 85 Finnish patients with ReA and 62 HLA-B27-positive Finnish controls. ReA patients had been followed up for 20 years. Genotypes and haplotypes of IL-10 were correlated with distinct features of the disease course, such as triggering agent, chronic arthritis, development of ankylosing spondylitis, and other chronic features. There was a significant decrease in the promoter alleles G12 (allele frequency 0.206 versus 0.033; corrected P < 0.001, odds ratio 0.14) and G10 (0.183 versus 0.092; P < 0.05, odds ratio 0.44) in the ReA group compared with the HLA-B27-positive controls. Chronic arthritis developed significantly more frequently in the B27-positive subjects than in the B27-negative subjects (P < 0.05) as well as in patients with [corrected] the IL10.G8 allele. No associations were observed for either SNP or for the IL10.R microsatellite polymorphism. IL10.G12 and G10 microsatellite alleles show a strong protective effect against the development of ReA in Finnish subjects. Since these polymorphic markers themselves do not have direct functional implications, they most likely mark promoter haplotypes with distinct functional properties, suggesting that differential production of IL-10 is an important susceptibility factor for the development of ReA.

Yersinia enterocolitica O:8 and O:5 lipopolysaccharide arthritogenicity in hamsters.

To assess the arthritogenicity of Yersinia enterocolitica O:8 and O:5 lipopolysaccharide (LPS) administered separately as single antigens in hamsters. Male hamsters of the Syria strain were intramuscularly injected into each of the hind paws with two doses of Y. enterocolitica LPS O:8 or O:5. The measurement of swelling using a plethysmometer, the analysis of histological changes by routine techniques and the kinetics of LPS-specific antibodies and autoantibodies evaluated by enzyme-linked immunosorbent assay (ELISA) were performed. LPS O:8 was demonstrated to be more arthritogenic than LPS O:5, inducing acute arthritis on day 3 post-injection as well as more significant and longer lasting joint swelling after a second dose. LPS O:8 caused severe histopathological changes in the joints. Important LPS O:8-specific IgG responses and antibodies against type I and II collagen were observed. LPS O:8 administered alone has arthritogenic power and induces activation of autoreactive clones. This study supports the key role of LPS in the development of reactive arthritis.

LOCAL EXPRESSION OF CYTOKINE mRNA IN SPLEEN AND PEYER'S PATCHES OF RATS IS INVOLVED IN RESISTANCE AGAINST INFECTION WITHYERSINIA ENTEROCOLITICA

The immune-response against infection withYersinia enterocoliticawas studied in a rat model which resembles yersiniosis in human. Lewis, Fischer and Brown Norway rats were inoculated withY. enterocoliticaand the cytokine mRNA expression in spleen and Peyer's patches was determined. In Brown Norway rats the infection was mild andYersinia enterocoliticawas fully cleared. In these rats the highest anti-inflammatory cytokine expression was found probably resulting in a protective host defence against the infection. In both the Lewis and Fischer ratsY. enterocoliticapersisted. The anti-inflammatory cytokine expression was less pronounced in these two rat strains. The authors conclude that progression of disease, persistence of infection and development of reactive arthritis, may be related to the local expression of specific cytokines.

Suppurative and reactive arthritis in children

Suppurative infections of the joints in children often pose a challenge to the clinician because of difficulties in early recognition of the disease process and subsequent medical and surgical management. A prompt diagnosis is important to institute effective antibiotic therapy and to perform timely surgical procedures to prevent disabling sequelae. Reactive arthritis is a joint inflammation that develops soon after or during an infection elsewhere in the body. A strong association between development of reactive arthritis and HLA-B27 has been known for a long time, but the mechanisms by which this antigen determines the appearance of joint complications remain unclear. This article discusses the microbiological, pathophysiological, clinical, diagnostic, therapeutic, and prognostic aspects of suppurative and reactive arthritis in children.

Persistent Yersinia enterocolitica infection in three rat strains

Yersinia enterocoliticamay persist for prolonged periods of time in humans sometimes resulting in the development of reactive arthritis. To elucidate factors predisposing for persistence we developed animal models. In Lewis and Fischer rats, viable bacteria could be demonstrated for prolonged time and abscesses could be found in the liver, spleen and lungs. Splenic abscesses were observed for more than 20 weeks.Yersinia enterocoliticapersisted in Lewis and Fischer rats, but only Lewis rats developed reactive arthritis. In Brown Norway rats abscesses developed early during infection but in contrast to the other strains disappeared after 3 weeks. Culture of homogenized abscess-containing tissue of all three rat strains yieldedYersiniae. Immunofluorescence studies of the abscesses showed diffuse staining inside the abscesses only, indicating the presence ofYersinia enterocoliticaantigen. Brown Norway rats, in contrast to Lewis and Fischer rats, developed a different serological reaction pattern againstYersinia enterocoliticaantigens and this correlated with the disappearance of the abscesses.