A controlled survey of less typical long-term consequences after an extensive waterborne epidemic.

BACKGROUND: Extensive backflow of treated wastewater caused household water contamination in a Finnish town in 2007. The drinking water of 9 500 residents became heavily polluted with faecal microbes, resulting in a large gastroenteritis epidemic. Cases of reactive arthritis, milder joint symptoms and prolonged gastrointestinal symptoms were observed after the outbreak. A follow-up survey was performed to study less familiar long-term health consequences within a year from the outbreak. METHODS: The contaminated group comprised a sample of residents of the area with polluted water supply (N = 323) and the control group a sample of residents in a nearby municipality (N = 186). The presence of 20 general symptoms or complaints was inquired by a mail survey. Quarterly prevalence of each symptom or complaint was measured. Twelve of these proceeded to further analysis. RESULTS: The response rate was 53% (323/615) in the contaminated group and 54% (186/343) in the control group. Rash, eye irritation, heartburn and weight loss were more prevalent in the contaminated group during the first year quarter. In the last year quarter, only eye irritation was significantly more common in the contaminated group. CONCLUSION: The excess prevalence of four complaints at the first year quarter can be explained by acute gastroenteritis or intensive water chlorination. The excess prevalence of eye irritation at the fourth year quarter cannot be explained by chlorination anymore but might be a sign of co-existing reactive joint disease. In general, long-term consequences of the outbreak can be considered minor in terms of the surveyed symptoms or complaints.

The evolving treatment of ANCA-associated vasculitides.

Prevention of organ damage and maintenance of long-term remission are the principal goals for treatment of ANCA-associated vasculitides. This can be accomplished by early diagnosis and swift initiation of remission-inducing agents. Outcome has improved but relapses and glucocorticoid- and cyclophosphamide-related toxicity are still major concerns. For remission induction in generalized disease a combination of glucocorticoids and cyclophosphamide or rituximab is used. Rituximab is suitable especially for younger patients with fertility concerns and when cyclophosphamide avoidance otherwise is desirable. In the treatment of relapses and refractory disease, rituximab has proved effective. As maintenance treatment rituximab prevents relapses more effectively than azathioprine.

Risk factors for uveitis in a Finnish sarcoid population.

PURPOSE: To evaluate possible risk factors for uveitis among Finnish sarcoidosis patients. METHODS: Patient charts of patients with sarcoidosis, with (n = 97) or without (n = 255) uveitis, and with a comprehensive eye examination from January 2014 to January 2021 at Tays Eye Centre, Tampere University Hospital, Finland were studied. RESULTS: Sarcoidosis patients with uveitis had higher rate of lymphocytopenia (43% vs. 29%, p = 0.041) and lower serum lysozyme levels (2.0 mg/L vs. 2.3 mg/L, p = 0.049; 95% CI, -0.692 to -0.002). Lysozyme level or lymphocytopenia did not have a statistically significant effect on the probability of uveitis in a binary logistic regression analysis. No other differences in the potential risk factors with p-values ≤0.05 were found, including bilateral hilar lymphadenopathy, serum angiotensin-converting enzyme (ACE) levels, sex, age and history of smoking. CONCLUSION: Lymphocytopenia and lower serum lysozyme levels present as possible risk factors for uveitis among patients with sarcoidosis. Systematic measurement of lymphocyte and lysozyme levels in sarcoidosis is needed to further understand their role as potential risk factors.

A severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant.

A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.

Low utility of ocular screening in sarcoidosis in Finland.

PURPOSE: Systematic ocular screening is recommended in sarcoidosis, because of a high rate of ocular involvement. The purpose of this study was to determine whether ocular screening is useful in sarcoidosis in a Finnish university hospital population with 0.5 M inhabitants. METHODS: Patient charts of patients with sarcoidosis, without a history of ocular sarcoidosis, without ocular inflammatory symptoms, and with a comprehensive eye exam from January 2014 to January 2021 at Tays Eye Centre, Tampere, Finland, were studied. RESULTS: Five of 262 patients (2%) were diagnosed with asymptomatic uveitis. No other types of ocular sarcoidosis were found. Anterior uveitis without complications was present in three patients, unilaterally in two and bilaterally in one patient. Posterior uveitis was present in two patients, a unilateral choroidal granuloma requiring treatment in one and bilateral punched-out chorioretinal lesions in the other patient. CONCLUSIONS: With this low rate of ocular involvement requiring treatment in sarcoidosis, systematic screening for asymptomatic ocular sarcoidosis does not seem useful in a Finnish population. In Tays Eye Centre, systematic screening of ocular sarcoidosis was discontinued in 2021.

Joint symptoms after a large waterborne gastroenteritis outbreak--a controlled, population-based questionnaire study.

OBJECTIVES: Waterborne outbreaks offer an opportunity to study joint symptoms after a simultaneous exposure. In November 2007, a gastroenteritis outbreak due to faecal contamination of tap water took place in a Finnish town. The purpose of this study was to evaluate the occurrence of joint symptoms after the outbreak. METHODS: The authors conducted a controlled, population-based questionnaire survey to study the occurrence of joint symptoms within 8 weeks after the exposure. The survey covered three areas: contaminated and uncontaminated parts of the town and a control town. A total of 1000 residents were randomly selected from each area, and the joint symptoms were first analysed separately and thereafter categorized as arthritis-like if joint swelling, redness, warmth or pain in movement was reported. RESULTS: A total of 2123 responses could be evaluated. The overall prevalence of joint symptoms was 13.9% in the contaminated group, 4.3% in the uncontaminated group and 1.5% among the control group, and the frequency of arthritis-like symptoms in the groups was 6.7, 2.1 and 0.5%, respectively. Gastrointestinal symptoms predicted joint complaints, diarrhoea and blood in faeces being the most significant. Residing in the contaminated area was associated with any joint symptom [odds ratio (OR) = 4.0, 95% CI 1.8, 9.0] and joint pain (OR = 7.3, 95% CI 2.1, 24.8) without preceding gastroenteritis. CONCLUSION: The frequency of joint symptoms was high in the contaminated group and also increased in the uncontaminated group. Furthermore, the risk of joint symptoms was increased in the contaminated group even without gastroenteritis.

Severe Puumala virus infection in a patient with a lymphoproliferative disease treated with icatibant.

Early identification of patients at risk of a severe course of hantaviral disease and lack of effective medication represent a global challenge in the treatment of this emerging infection. We describe a 67-year-old female patient with a history of chronic lymphoproliferative disease involving the spleen and an extremely severe acute Puumala hantavirus infection. She was treated with the bradykinin receptor antagonist icatibant and recovered. She is the second patient with a spleen abnormality and severe Puumala infection treated with icatibant in our hospital. We suggest that patients with spleen abnormalities may be more susceptible to severe hantavirus disease. The activation of the kinin-kallikrein system and the formation of bradykinin in hantavirus-infected endothelial cells indicate that the role of bradykinin receptor antagonist icatibant in the treatment of hantavirus disease is worth studying.

Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant.

We recently described a patient with very severe Puumala hantavirus infection manifested by capillary leakage syndrome and shock. He was successfully treated with the bradykinin receptor antagonist, icatibant (Antonen et al., 2013). Here we report analysis of the pathophysiology which indicated pronounced complement activation, prolonged leukocytosis, extensive fibrinolysis, circulating histones, and defects in liver function. The patient had an uncommon HLA-phenotype, which may have contributed to the severe course of the disease.

Outcome of reactive arthritis after an extensive Finnish waterborne gastroenteritis outbreak: a 1-year prospective follow-up study.

The purpose of the study was to assess the 1-year outcome of definitive reactive arthritis (ReA) after a waterborne outbreak. A cohort of 21 patients (15 females and 6 males, median age 54 years) with ReA related to an extensive waterborne outbreak in Finland was clinically followed-up by rheumatologists with visits at baseline, at 1 month and 3, 6 and 12 months. Although the outcome was in general favourable, 1/3 of the patients had chronic course; 7 (33 %) of the 21 patients needed disease-modifying anti-rheumatic drugs (DMARDs) and even 8 (38 %) of them used glucocorticoids at 12 months. Four (19 %) were using non-steroidal anti-inflammatory drugs and nine (43 %) other analgesics. Many patients had articular pain and impaired physical function still at 12 months, even though inflammatory parameters and the number of swollen joints were low. Only one patient (5 %) was human leucocyte antigen-B27-positive. She had the most severe ReA and also additional infectious arthritis caused by Salmonella serotype enteritidis leading to osteonecrosis of her hip joint with subsequent need for arthroplasty. ReA as observed in our study was overall fairly mild, but in many individuals, postinfectious arthralgia and DMARD use continued at least up to 1 year.

Effects of erythropoietin treatment on cell-mediated immune responses in predialysis patients.

OBJECTIVE: The effects of erythropoietin (EPO) treatment on the immune functions of dialysis patients have been shown to be controversial and there are only limited data concerning predialysis patients. MATERIAL AND METHODS: Twenty-four predialysis patients with renal anemia were assigned to subcutaneous EPO treatment, and those in need (n=19) were additionally treated with i.v. iron every other week. We analyzed the effect of the start of EPO treatment on (i) lymphocyte and lymphocyte subclass counts, (ii) lymphocyte stimulation functions and (iii) persisting IgG-class antibody levels to the viral antigens of Epstein-Barr virus and cytomegalovirus. RESULTS: Our main findings were a decrease in the absolute lymphocyte count, combined with decreases in all the main lymphocyte subclass counts. The absolute number of cells with activation and memory markers remained constant, and therefore their proportion slightly increased. The proliferation responses to phytohemagglutinin, tuberculin and tetanus declined significantly, while the amount of IgG-class viral antibodies remained unchanged, meaning that the humoral side of immunity was not affected by the start of the EPO treatment. Similarly, the proliferation response to pokeweed mitogen, a B-cell mitogen, was unchanged. CONCLUSIONS: EPO treatment has a suppressive effect on cellular immune functions of predialysis patients. This suppression does not correlate with erythropoiesis, kidney function or iron status.

Immunoglobulin KM and GM gene polymorphisms modify the clinical presentation of primary Sjögren's syndrome.

OBJECTIVE: To investigate whether polymorphism of immunoglobulin (Ig) genes affects susceptibility to or severity of primary Sjogren's syndrome (pSS). METHODS: Ig gene kappa (KM) and gamma (GM) polymorphisms were analyzed by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) based method in 65 Finnish Caucasian patients with pSS and in 66 healthy controls matched for sex, ethnic origin, and area of residence. Clinical and immunological data on the pSS patients were analyzed in relation to Ig genotypes. RESULTS: The genotype frequencies of Ig KM and GM genes did not differ between pSS patients and controls. Anti-SSB antibodies were encountered significantly more frequently in pSS patients carrying the KM1 allele than in those without (100% vs 48%, p = 0.016). The pSS patients with the KM1 allele had several signs of immunologically active disease: they had significantly higher erythrocyte sedimentation rate, serum IgA, serum beta2-microglobulin (beta2-m), and plasma IgG1 concentrations than patients without this allele. The pSS patients carrying the GM z allele had a milder form of pSS than those without this determinant. They had less severe labial salivary gland histological findings (grade 3-4 in 60% vs 93%, p = 0.004) and lower plasma IgG3 and serum beta2-m concentrations than those without GM z allele. CONCLUSIONS: Ig KM and GM genes do not contribute to susceptibility to pSS. The Ig KM1 allele is associated with several markers of immunologically active disease, whereas the Ig GM z allele is associated with milder pSS.

Influenza vaccination of dialysis patients: cross-reactivity of induced haemagglutination-inhibiting antibodies to H3N2 subtype antigenic variants is comparable with the response of naturally infected young healthy adults.

BACKGROUND: Annual influenza vaccination is recommended for patients with chronic renal failure, although vaccination responses in haemodialysis (HD) patients may be suboptimal. Typically, the seroreactivity has been analysed against the vaccine virus or the corresponding year's epidemic virus. No studies analysing cross-reactivity against subsequent years' viruses have been presented. METHODS: Twenty-three chronic HD patients and 26 cardiac patients were, in autumn 1995, vaccinated with a trivalent influenza vaccine. The cross-reacting haemagglutination-inhibiting antibodies to five consecutive years' (the last season 1999-2000) drift variants of H3N2 subtype influenza A virus were measured and compared with those of vaccinated cardiac patients and with those of 26 healthy military conscripts who suffered a serologically confirmed influenza A infection in the season 1995-1996. RESULTS: The influenza vaccination in HD patients resulted in comparable cross-reacting antibodies to the antibodies induced both by vaccination in cardiac patients and by natural infection in military conscripts. After a steady decline, the cross-reactivity to the latest epidemic virus improved in all the groups. This may be due to two reverted amino acid changes in the HA1 domain of the virus haemagglutinin. CONCLUSIONS: Influenza vaccination in HD patients is as effective as the vaccination of cardiac patients with normal kidney function. The cross-reactivity of vaccination-induced antibodies is even as good as that of antibodies induced by natural infection of young healthy males. Additionally, vaccination seems to prime the individual beneficially against subsequent years' influenza viruses.