Patient-reported complications associated with Campylobacter jejuni infection.

This study aimed to investigate the occurrence of complications, especially musculoskeletal symptoms, after sporadic Campylobacter jejuni enteritis of domestic origin in Finland. This multi-centre cross-sectional study was conducted during a seasonal peak in 2002. Questionnaires were sent to Campylobacter-positive patients, representing different geographical areas, 2 months after collection of positive stool samples. Medical records were viewed in several cases. Besides antimicrobial susceptibility testing C. jejuni isolates were serotyped. A total of 235 patients (58%) returned the questionnaire and 201 C. jejuni-positive patients were finally included in the study. Musculoskeletal symptoms associated with C. jejuni enteritis were frequent (39%); joint pain was most commonly reported (81%). The incidence of reactive arthritis was 4% and that of Achilles enthesopathy and/or heel pain was 9%. Stomach ache during enteritis was associated with the later development of joint pain. Antimicrobial treatment was common but did not prevent complications.

Mast cells and IgE-containing cells in gastric mucosa of Helicobacter pylori infected and non-infected patients with chronic urticaria.

BACKGROUND: Several studies have indicated that antibiotic therapy aimed at eradication of Helicobacter pylori has effects on symptoms of chronic urticaria (CU) patients. However, the possible connections and pathomechanism by which H. pylori might be linked to CU have remained largely unknown. The IgE-mediated pathway might be a possible link between H. pylori infection and CU. We therefore clarified the role of H. pylori as an inducer of IgE response. MATERIALS AND METHODS: Gastroscopy was performed and mucosal biopsy specimens were taken to evaluate the histology, as well as the presence of H. pylori bacteria, mast cells and IgE-containing cells in the antral mucosa, in 21 CU patients. Controls (n = 48) included 19 patients with lichen planus, nine patients with atopic dermatitis and 20 patients with no skin or allergic disease. RESULTS: The mean densities of IgE-containing cells were significantly higher in H. pylori-infected patients and in patients with skin disease compared to non-H. pylori-infected patients with no skin or allergic disease. No significant difference was found in the number of IgE-containing cells between H. pylori-infected and non-infected patients with CU. There was no significant difference in the mean densities of mast cells in the different patient groups. CONCLUSIONS: Our findings suggest that H. pylori gastritis leads to increased IgE production. However, we could not show a significant difference in IgE staining between H. pylori-infected and non-infected patients with CU.

Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis.

BACKGROUND: The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial. OBJECTIVES: To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo. METHODS: Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4-7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive. RESULTS: 11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive. CONCLUSION: Analysis 4-7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.

Prevalence of Sindbis-related (Pogosta) virus infections in patients with arthritis.

OBJECTIVE: To determine the role of Pogosta virus as a triggering infection in non-specific arthritis. METHODS: Serum samples of 142 patients with acute arthritis were screened for the evidence of Pogosta virus infection. Serological tests for Chlamydia trachomatis, salmonella, parvovirus B19, and Borrelia burgdorferi were also carried out. As verified later, 78 of the patients had rheumatoid arthritis and 63 seronegative poly- or oligoarthritis, while one had systemic lupus erythematosus. RESULTS: In the early stage of the joint symptoms 4 patients with rheumatoid arthritis, 1 with seronegative polyarthritis and 1 with systemic lupus erythematosus had recent Pogosta virus infection. Four of them had probably had Pogosta disease at the time of the onset of arthritis. In 11 patients with a diagnosis of seronegative arthritis, serological evidence of preceding infection due to salmonella or Chlamydia trachomatis was found, strongly suggesting classical reactive arthritis in these cases. CONCLUSIONS: Our study suggests that also a Sindbis virus infection may be associated both to an acute joint inflammation as a part of Pogosta disease or chronic arthritis. At present, this possibility still needs further research.

Extraction of IgE-binding components of Helicobacter pylori by immunoblotting analysis in chronic urticaria patients.

BACKGROUND: An association between Helicobacter pylori and chronic urticaria has been suspected previously. An IgE-mediated pathway might be a possible link between H. pylori infection and chronic urticaria, and therefore we wanted to prepare an optimal H. pylori antigen to detect H. pylori-specific IgE antibodies in chronic urticaria patients. METHODS: H. pylori antigen extracts were prepared in different ways to find the optimal antigen extract to be used in the assays. Immunoblotting was used to detect IgE-binding bands. The results were applied in an H. pylori RAST assay for specific H. pylori IgE antibodies in patient sera. RESULTS: In immunoblotting, the largest number of IgE-stained bands were visualized in the washing fluids and sonicated extracts, while strong heating and denaturing treatments destroyed the epitopes for IgE binding, suggesting that they belonged to the flagellar structures of H. pylori. However, in H. pylori-specific RAST analysis, specific IgE was found only in 1 of 25 H. pylori-infected patients. CONCLUSIONS: Our findings suggest that although IgE-binding epitopes were found in H. pylori, H. pylori-specific IgE antibodies are not common in chronic urticaria, and the clinical significance of the IgE response is unclear.

Urocanic acid isomers do not modulate intracellular calcium and cyclic AMP in human natural killer cells.

Ultraviolet irradiation influences natural killer cell function both in vitro and in vivo. The postulated ultraviolet photoreceptor in the epidermis, urocanic acid, has been reported to depress the cytotoxic activity of human natural killer cells. Therefore, this study investigated whether this would occur through specific second messengers, using a radioimmunoassay for intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and Fluo-3 staining plus flow cytometry for free calcium. Both isolated lymphocytes and enriched CD16+ cells were used. A combination of the trans- and cis-isomers of urocanic acid (200 microg/ml) induced cAMP in both CD16+ and CD16- cells, but individual, stereospecific effects were not demonstrable. Urocanic acid did not induce significant changes in calcium levels in lymphocytes, or natural killer cells alone or conjugated to K562 target cells. Evidently, the biochemistry of urocanic acid-mediated natural killer-cell modulation is complex, and the cellular receptor(s) and specific signal transduction pathway(s) mediating the biological effects of urocanic acid remain elusive.

Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis.

OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA-stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella-stool culture; for infections with Chlamydia trachomatis-culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis. RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS: Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.

Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans.

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture- or PCR-confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South-Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100,000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring-like in 31.8% and homogeneous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture-positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogeneous than ring-like. B. burgdorferi may disseminate early without generalized symptoms.

Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis.

BACKGROUND: Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA. OBJECTIVE: To evaluate the effect of a three month course of ciprofloxacin on ReA. METHODS: In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery. RESULTS: Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study. CONCLUSION: Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

The role of Borrelia burgdorferi in interstitial cystitis.

BACKGROUND/AIMS: Borrelia burgdorferi spirochete has been found both in bladder biopsies and the urine of patients with Lyme disease (LD) as well as in experimental animals. The urological symptoms in borreliosis resemble those of interstitial cystitis (IC): frequency, urgency and nocturia. The aim of this studies is to find the role of B. burgdorferi in interstitial cystitis. METHODS: We studied antibodies against B. burgdorferi from serum samples of 50 IC patients with two separate EIA tests. Patients with positive serology in both tests underwent cystoscopy and a bladder biopsy was taken. The presence of borrelia DNA was studied with borrelia-specific polymerase chain reaction (PCR), and with universal bacterial PCR. RESULTS: IgM class antibodies to B. burgdorferi were not found, but IgG antibodies were found in four samples (8%). This was higher than in the control material (2%). One patient's sample was strongly positive, whereas three samples were weakly positive. Bladder biopsies taken from the 4 patients were negative for borrelia DNA in both PCR tests. None of the seropositive patients had any symptoms consistent with LD. CONCLUSION: These results indicate that persistent infection of B. burgdorferi has no role in the etiology of IC. On the other hand a connection with a past borrelia infection and IC is not excluded.

Peptic ulcer and Helicobacter pylori in patients with lichen planus.

The aetiology of lichen planus is unknown, but it is often connected with infections. In recent years peptic ulcer disease has also been closely linked with an infectious agent, Helicobacter pylori. A case-control study was conducted in 78 patients with lichen planus to find out a previous history of peptic ulcer disease, using a questionnaire and a medical record review. Patients were also asked about family history in first- and second-degree relatives. Fifty-seven patients with other skin diseases were interviewed as controls. The prevalence of H. pylori infection in patients with lichen planus was compared to that of 39 patients with other skin diseases and to the overall prevalence rates of H. pylori infection in Finland. Our findings are consistent with an approximately three-fold increased risk of peptic ulcer in patients with chronic/repeating lichen planus, when compared to the control patients (p = 0.04) and also to the overall peptic ulcer prevalence rates in Finland. Forty-one percent of the patients with chronic/repeating lichen planus had a first- or second-degree family member with a peptic ulcer, while the corresponding rate in the control group was only 12% (p=0.003). The prevalence of H. pylori infection in patients with chronic/repeating lichen planus and transient lichen planus was not significantly different from that in patients with other skin diseases.

[Population study of antibodies to some potential pathogens of spondyloarthopathies: the study of the Chukotka population]. / Populiatsionnoe issledovanie antitel k nekotorym potentsial'nym agentam spondiloartropatii: izuchenie populiatsii Chukotki.

The paper presents the results of the study of specific immune response stimulated by some enterobacteria in populations with high incidence of HLA-B27. A, M and G antibodies to Yersinia, Clebsiella, Salmonella and Campilobacter were studied on 292 plasma samples. The levels of the antibodies varied with anthropological parameters of the examinees (gender, age, nationality). The presence of the gene HLA-B27 in the genotype levels gender dimorphism of the specific humoral immune response. This may be of importance in pathogenesis of spondyloarthropathies which occur more frequently in men.

No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Etiologic aspects of chronic urticaria.

BACKGROUND: Urticaria is a common disease that is always a challenge to the dermatologist due to its evasive etiology. PATIENTS AND METHODS: One hundred and seven chronic urticaria patients were studied. Routine laboratory investigations were performed and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody determinations, autoimmune reactivity, infections, allergies, and hyperreactivities were investigated. RESULTS: Pathologic findings were seen in 92 patients. Concomitant diseases suggesting autoimmune reactivity were detected in nine patients and, in 16 patients, infections including maxillary sinusitis, streptococcal tonsillitis, and tooth infection were found. Elevated total IgE level was detected in 37 out of 75 patients and positive skin prick test results in 47 out of 91 patients. Fifty-five patients had a history of recent dyspeptic symptoms. A diagnosis of adult celiac disease was made in two patients and, additionally, IgA antigliadin antibodies were seen in four patients. H. pylori IgG antibodies were found in 40 out of 107 patients. Active gastritis was verified by esophagogastroduodenoscopy in 30 out of 32 patients with positive Helicobacter staining in 24 samples. An elevated IgE level was detected in 64% of H. pylori-positive and in 39% of H. pylori-negative patients. CONCLUSIONS: In this study, several findings suggesting aberrant immunologic activation were detected in chronic urticaria patients. Inflammation in the gastrointestinal tract, e.g. caused by H. pylori infection, may have an important role in the etiology of chronic urticaria.

Enterobacterial antibodies in Chinese patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To study the role of microbial infection in rheumatic diseases. METHODS: Sera from 39 Chinese patients with rheumatoid arthritis (RA), 52 patients with ankylosing spondylitis (AS) and 51 healthy subjects (HS) were examined for IgG, IgA, and IgM class antibodies against Proteus mirabilis, Escherichia coli, Campylobacter jejuni, Salmonella typhimurium and enteritidis, Yersinia enterocolitica, and Klebsiella pneumoniae (capsular serotypes 31 and 43), using an enzyme-linked immunosorbent assay. RESULTS: In patients with RA, IgA class antibodies against all bacterial strains used as the antigen were increased when compared to healthy controls. In patients with AS, significantly elevated IgA levels were observed against Campylobacter and Klebsiella K43. IgM class antibodies were less frequently elevated in RA and in AS than IgA class antibodies. In RA patients, IgG antibodies against Klebsiella K43 and Proteus were significantly increased. No differences were observed in IgG class antibodies between AS patients and healthy controls. CONCLUSION: Increases in serum bacterial antibodies in RA and AS suggest that in both diseases stimulation of the intestinal immune system by enterobacteria may have a role. However, the question whether this phenomenon is due to increased intestinal permeability and/or represents cross reactions between different enterobacteria remains open.

Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous psoriasis.

OBJECTIVE: To evaluate the possible role of streptococcal cell wall antigens in the development of psoriatic arthritis. METHODS: IgM, IgA and IgG class serum antibodies against peptidoglycan-polysaccharide (PG-PS) and peptidoglycan (PG), both from group A streptococcus, were measured in patients with psoriatic arthritis (PA), non-arthritic psoriasis (NAP), rheumatoid arthritis (RA) and in healthy controls, using ELISA. RESULTS: Both groups of psoriatic patients had elevated IgA levels specific to streptococcal PG-PS. No association with the severity of the skin disease or with the different subsets of PA was detected. Higher concentrations of IgG against the two streptococcal preparations was observed in PA than in RA. Analysis of antibody levels in patients with recent onset arthritis showed lower concentrations of IgM antibodies against streptococcal as well as control antigens in early than in late PA, whereas an overall increase of specific IgA and IgG antibodies was observed in early RA. CONCLUSION: The results suggest chronic mucosal stimulation of lymphocytes by long-lived streptococcal antigens in patients with psoriasis, without any difference observed between PA and NAP. The differences between recent onset versus established PA and RA could reflect a distinct immunopathology in the two arthritides.

Function of lymphocyte homing-associated adhesion molecules on human natural killer and lymphokine-activated killer cells.

We have analyzed the ability of fresh and rIL-2-activated human NK cells to interact with high endothelial venules (HEV) that are known to support physiologic lymphocyte extravasation, and examined the role of different adhesion molecules in this process. In in vitro HEV-binding assays, NK cells bound to both peripheral lymph node (pLN) and mucosal HEV. Activation by rIL-2 slightly decreased adherence to pLN HEV, but increased adherence to mucosal high endothelium. Markedly fewer NK cells than PBL expressed L-selectin, and the expression was diminished further upon treatment with rIL-2. Inhibition studies showed, however, that L-selectin was the most important single molecule to mediate adhesion to pLN HEV. Binding to mucosal HEV was mediated mainly by CD44 and alpha 4 integrin, and the expression level of these molecules was increased by rIL-2, paralleling the results in HEV-binding assays. Higher m.w. forms of CD44, representing differentially glycosylated/variant forms of CD44, were more abundant on large granular lymphocytes than on unseparated PBL. We conclude that, despite weak recirculatory capacity, NK cells or a subpopulation of NK cells with the correct adhesion molecules can interact with and bind to high endothelial cells. Lymphokines can modulate the expression of adhesion molecules that NK cells utilize for HEV binding. Our results suggest that activation of NK cells with IL-2 may facilitate the extravasation of lymphokine-activated killer cells, especially to mucosal sites, whereas homing to peripheral lymphoid tissues may be diminished. This should be taken into consideration when procedures for lymphokine-activated killer cell immunotherapy are planned.

Expression of CD80 (B7/BB-1) and CD28 in human white blood cells treated with urocanic acid.

Urocanic acid (UCA) is formed in the epidermis where it accumulates to be converted from trans- to cis-UCA by ultraviolet (UV) radiation. The two isomers modulate immune functions in several experimental systems. In particular, cis-UCA has been shown to induce antigen-specific immune tolerance, but the molecular mechanism of this effect is unknown. The present investigation was instituted to disclose any effect of UCA isomers on the cellular expression of the costimulatory antigens CD80 (B7/BB-1) and CD28. CD80 expression was efficiently induced in monocytic (CD14+) cells by human interferon-gamma, while CD28 levels on lymphocytes remained unchanged, as detected by flow cytometry. Neither UCA isomer showed any effect on the expression patterns of these costimulatory molecules. The results obtained suggest that the mode of action for epidermal UCA-induced tolerogenesis may not involve modulation of CD80 (B7/BB-1) or CD28 expression.