Birch pollen allergy in Europe.

Birch and other related trees of the families Betulaceae and Fagaceae (alder, hazel, oak, hornbeam, chestnut, and beech) constitute the birch homologous group. This grouping is primarily based on the extensive IgE cross-reactivity of allergen homologs to the major birch allergen Bet v 1. Birch pollen is the most dominant tree pollen in Northern and Central Europe and is a major cause of allergic rhinitis and, possibly, asthma symptoms. Over the last few decades, levels of birch pollen have risen and the period of exposure has increased due to climate changes. Subsequently, the prevalence of birch pollen sensitization has also increased. The cross-reactivity and sequential pollen seasons within the birch homologous group create a prolonged symptomatic allergy period beyond birch pollen alone. Furthermore, many plant food allergens contain homologs to Bet v 1, meaning that the majority of patients with birch pollen allergy suffer from secondary pollen food syndrome (PFS). As a result, the negative impact on health-related quality of life (HRQoL) in patients allergic to birch pollen is significant. The purpose of this manuscript was to narratively review topics of interest such as taxonomy, cross-reactivity, prevalence, clinical relevance, PFS, and HRQoL with regard to birch pollen allergy from a European perspective.

Short course of grass allergen peptides immunotherapy over 3 weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without asthma: A randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 µg LPP administered subcutaneously over 3 weeks. METHODS: In a randomized, double-blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 µg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) was assessed as secondary endpoints. RESULTS: The mean reduction in CSMS in the LPP vs placebo group was -15.5% (P = .041) during the peak period and -17.9% (P = .029) over the entire pollen season. LPP-treated group had a reduced reactivity to CPT (P < .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤30 minutes in 10.5% of LPP-treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication. CONCLUSION: Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well-tolerated.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2016 revision

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

Asthma management: A new phenotype-based approach using presence of eosinophilia and allergy.

Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy-to-use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype-targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers' comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic nonallergic asthma and noneosinophilic nonallergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype-specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalized therapy.

A randomized DBPC trial to determine the optimal effective and safe dose of a SLIT-birch pollen extract for the treatment of allergic rhinitis: results of a phase II study.

BACKGROUND: Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted. METHODS: Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10,000, 20,000 or 40,000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen-specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season). RESULTS: In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P < 0.001, respectively). For this primary endpoint, a significant linear dose-response curve was observed: the higher the dose, the better the improvement observed. Likewise, active treatment resulted in an increase in PNIF and serum IgG levels compared to placebo. The highest improvements were found in the 40,000 AUN/ml group. All active dosages resulted in more adverse reactions than placebo, which were mainly mild and well-controlled. CONCLUSIONS: A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40,000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).

Bronchial inflammation in seasonal allergic rhinitis with or without asthma in relation to natural exposure to pollen allergens.

BACKGROUND: Nasal inflammation in allergic rhinitis enhances bronchial Th2 driven inflammation and development of asthma. We assessed bronchial inflammation induced by natural allergen exposure during pollen season in patients with pollinosis with or without asthma to show the intensity of inflammation in asthma and rhinitis and possible persistence of inflammation in periods without allergen exposure. METHODS: Sputum was induced in 52 patients with seasonal allergic rhinitis without asthma, 38 patients with seasonal allergic rhinitis and seasonal asthma and 23 healthy volunteers. Sampling was performed 6-8 weeks before the expected beginning of symptoms, during symptomatic period and 6-8 weeks after the end of symptoms. Sputum ECP was measured by means of chemi-luminiscent immunometric assay and sputum cell counts were assessed by classical staining and immunocytochemistry. RESULTS: Sputum eosinophils were on the whole higher in both asthma and rhinitis compared to controls (p<0.001, p=0.003). The rise of eosinophils during pollen season compared with values out of pollen season was significant in asthma (classical staining) (p=0.014) and slightly apparent in rhinitis (immunocytochemistry) (p=0.073). The seasonal rise of sputum ECP was observed only in rhinitis (p=0.006). CONCLUSIONS: Inflammation of the lower airway in patients with allergic rhinitis with and without asthma has been confirmed by means of both sputum eosinophil count and sputum ECP level. Persistent inflammation of lower airway in periods without allergen exposure was proven in seasonal asthma. This may have implications for the therapy of seasonal allergic rhinitis with and without asthma in terms of promoting long-term anti-inflammatory treatment.

Histamine increases the level of IFNγ produced by HIV-1 specific CTLs and this production depends on total IgE level.

BACKGROUND: The HIV (human immunodeficiency virus) population remains a global concern whose treatment is effective, though not yet optimal. Immune based therapies have thus far been disappointing and still need to be explored further. Based on published data suggesting that the functions of cytotoxic CD8+ T lymphocytes (CTL) can be improved by histamine, we investigated the effect of histamine in vitro on HIV-1 specific CD8+ T lymphocytes in HIV+ subjects. RESULTS: 60 HIV+ subjects were included in the study. We evaluated CTL function by IFNγ (interferon gamma) production (using the enzyme-linked immunospot assay (Elispot), BD Bioscience). Changes in the production of IFNγ after incubation with histamine were compared with the levels of total IgE (immunoglobulin E, measured using a Dade Behring analyzer), because histamine is endogenously released through IgE. Activation of HIV-specific CTL by histamine occurs via H2R (histamine receptors). Thus we attempted to block this activation using cimetidine (antagonist H2R). CONCLUSIONS: We found an increase in IFNγ production after the activation of HIV-1 specific CD8+ T lymphocytes by histamine (this elevation was blocked by cimetidine), furthermore, we demonstrated a negative correlation between the production of IFNγ and levels of total IgE.

Practical guide to skin prick tests in allergy to aeroallergens.

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review.

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.

BACKGROUND: The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. OBJECTIVE: The aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic to grass pollen. METHODS: Different subgroups could be identified regarding comorbidities (with or without asthma during the grass-pollen season), sensitization (mono/polysensitization) and symptom severity. An additional exploratory analysis was performed within four subgroups based on pre-treatment assessment: Group 1=high specific IgE; Group 2=high symptom scores; Group 3=high skin sensitivity; Group 4=any of Group 1, 2 or 3. RESULTS: Asthma and sensitization status were not significant covariates as the average Rhinoconjunctivitis Total Symptom Score (RTSS) was identical for patients with and without grass-pollen asthma, as well as for mono- and polysensitized patients. Across the four subgroups, average RTSSs (+/- SD) for the optimal dosage (300 IR) were 3.91 +/- 3.16, 3.83 +/- 3.14, 2.55 +/- 2.13 and 3.61 +/- 2.97, for subgroups 1, 2, 3 and 4, respectively. ANCOVA showed that in Group 1 average RTSS did not differ significantly with different doses of SLIT. In Groups 2, 3 and 4, doses of 300 IR and 500 IR were significantly more effective than 100 IR and placebo (P< or =0.035). All doses of SLIT administered in this study can be considered safe in the patients investigated. CONCLUSIONS: The risk-benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma.

Double-blind, placebo-controlled evaluation of grass pollen specific immunotherapy with oral drops administered sublingually or supralingually.

Forty-one patients suffering from grass pollen allergy underwent specific immunotherapy with standardized allergen extract consisting of six grass pollens (H-Al per os) administered either sublingually or supralingually for one year. In order to investigate clinical and immunological changes induced by the administration of allergens via the oral mucosa, the double-blind, placebo-controlled, randomized design of the trial with 30 other patients enrolled in placebo groups was applied. Specific immunotherapy with oral drops administered sublingually or supralingually was performed in the same way, keeping the drops under or on the tongue, respectively, for 1-2 min before swallowing them; at the end of the trial the cumulative dose of the allergen was almost 20 times higher than that of the subcutaneous therapy with corresponding allergen preparation. Data about symptoms scores and drugs intake during grass pollen season, as well as skin reactivity, levels of specific IgG and IgE antibodies, before the study and after the study's completion, were obtained. It was found that both routes of administration are effective according to subjective clinical parameters and drug consumption, with a highly significant reduction of symptoms and drug intake favoring sublingual administration where a reduction of more than 60% was achieved. Only sublingual active group showed a significant increase in Dactylis glomerata-specific IgG serum levels. Adverse effects were limited to a small number of generally mild local and/or systemic reactions. The results suggest that the administration of allergens via the oral mucosa is safe and clinically effective, favoring the sublingual rather than supralingual route.

A critical appraisal of methods used in early clinical development of novel drugs for the treatment of asthma.

Asthma is a heterogeneous disorder characterized by chronic airway inflammation, hyperresponsiveness and remodeling. Being the hallmark of asthma, airway inflammation has become the most important target for therapeutic agents. Consequently, during the past decade various semi-and non-invasive methods have been explored to sample the airway inflammation in asthma. In this review, we provide a practical overview of the current status of various sampling techniques including sputum induction, exhaled breath analysis, and bronchoprovocation tests (BPTs). We focus on their applicability for monitoring in clinical practice and in intervention trials in asthma.

[Serum antibodies against annexin V and other phospholipids in women with fertility failure]. / Sérové protilátky proti annexinu V a jiným fosfolipidum m u zen s poruchou plodnosti.

THE AIM: To study serum antibodies against annexin V and against other phospholipids in women with fertility failure. DESIGN: Prospective study. SETTING: Department of Gynecology and Obstetrics, Institute of Imunology and Alergology, Institute of Forensic Medicine, Charles University and Faculty Hospital, Pilsen, Czech Republic. PATIENTS AND METHODS: We investigated sera from a total of 1550 women aged 26-41 years who attended the Division for Infertility and Reproductive imunology, in the Department of Obstetrics and Gynecology, Charles University, and Faculty Hospital, Pilsen, Czech Republic. ELISA was used for detection of antibodies against annexin V, phosphatidic (ph)-acid, ph-ethanolamine, D-L glycerol, ph-inositol, L-serine, cardiolipine, beta-glycoprotein, and prothrombine), antibodies against zona pellucida by passive hemmagglutination. Antibodies against annexin V in ovulatory cervical mucus were studied only in 47, and in follicular fluid in 168 women. Eighty-four fertile healthy women were included in the control group. RESULTS: Antibodies against annexin V were found in 13% (in 170 infertile women). Anamnestic data showed two or more unexplained pregnancy losses in 48 (28.2%), 108 (63.5%) patients had two or more unsuccessfull in vitro fertilization, polycystic ovaries (PCO) was diagnosed in 3 (1.7%), and endometriosis in 11 (6.6%) of them. The increased levels of antibodies against ph-inositole (28.8%), and L-serine (19.4%) were detected. 353% of patients had positive levels against zona pellucida. In ovulatory cervical mucus only in six (6/47) antibodies against annexin V were detected, in 5.55% in follicular fluid (6/108). CONCLUSION: Our study also demonstrated serum positivity against annexin V as a significant risk factor mainly in patiens with repeated reproductive failure.

[Inhibin B and intraacrosomal proteins in men from the couples with fertility disorders]. / Inhibin B a intraakrozomální proteiny u muzu z páru s poruchou fertility.

THE AIM: To monitor the basic andrologic and immunologic sperm factors and the levels of inhibin B in serum and in seminal plasma in men from the couples with infertility disorders. SETTING: Department of Gynecology and Obstetrics, Medical School, Charles University and University Hospital, Plzen, Institute of Molecular Genetics, AV CR, Prague, Institute of Clinical Immunology and Allergology, LF UK a FN, Plzen. METHODS: We used conventional methods for estimation of sperm quality according to WHO and we detected the intra-acrosomal proteins by monoclonal antibodies (Hs8 and Hs14, immunofluorescent method), spermantibodies by direct mixed antiimunoglobulin reaction (MAR) test, and we examined inhibin B in serum (< or =400 pg/ml= A) and in seminal plasma (< or = 600 pg/ml= N) by ELISA in 355 men aged 21-52 years (ø 34 years) with normal levels of FSH, LH and testosterone. The control group was created by 56 health sperm donors. RESULTS: We found 65% normospermatics in the group of 355 patients, 34.9% men with various kind of pathologies. Predominance of spermagglutinating antibodies was found in 15.77% in IgG, in 19.44% in IgA, in 8.44% in IgA and IgG together. Normal intraacrosomal proteins were reached in 74.65% for Hs8, in 20.85% pathologic, in 86.2% normal findings for Hs14, in 4.23% pathologic. The immunological results in control group were completaly negative. Pathological levels of inhibin B in seminal plasma was found in 37.2% (152 men), in 25% in serum, and in 5.6% in serum and in seminal plasma together. In 54.7% of patients we found physiological levels of inhibin B in both biological fluids. We also compared physiological 109/152 (71.71%), and pathological spermiogrammes 43/152 (28.29%) with abnormal levels of inhibin B in seminal plasma, with intraacrosomal proteins to levels of inhibin B in serum. Our detailed study shows high interidividual results, which must be studied in complex with diagnosis of decreased fertility in man. CONCLUSION: Andrologic and immunologic analysis in the group of 355 men showed normal parameters of spermiogrammes in 231 patients (65%), in the rest of men the immunologic profil was in various parts pathologic. Only 105 men have got excellent spermiogrammes. Inhibin B as hormon regulates in back the secretion of FSH, and serves as good indicator in male reproductive failures.

[Free radicals in immunology and infectious diseases]. / Volné radikály v imunologii a u infekcních chorob.

Free radicals contribute significantly in modification of immune processes and inflammatory reactions. They are produced by activated phagocytes which use them for killing microorganisms. Free radicals facilitate production of cytokines, which are important as modifiers of inflammatory reactions. Formation of free radicals is influenced by antioxidants which can thus modify the intensity of inflammatory reaction and immune response. The authors describe in detail the contribution of free radicals in etiology and pathogenesis of autoimmune diseases including rheumatoid arthritis, multiple sclerosis or amyotrophic lateral sclerosis. The role of free radicals and modifying influence of antioxidants in viral, bacterial, parasitic and mycotic diseases is described in the second part of the review. Finally, influence of free radicals and antioxidants on immunity changes in patients with malignant tumours, during aging and physical exercise is discussed.

[Use of cryopreserved sperm in the microagglutination test]. / Vyuzití kryokonzervovaných spermií v mikroaglutinacním testu.

OBJECTIVE: The aim of this study was to find out the behavior of sperm cryopreserved in microagglutination test (TAT). METHODS: TAT using native sperm pertains to the screening methods in spermagglutinating antibodies. Spermatozoa cryopreserved in egg-yolk medium, just in seminal plasma or in the commercial made medium--Medi-Cult (Denmark) were used in this study. SETTING: Department of Gynaecology and Obstetrics, Institute of Clinical Immunology and Allergology Medical Faculty of Charles University, Pilsen. RESULTS: 367 tests were performed together. It includes 108 examinations with native spermatozoa, 59 with spermcryopreserved in egg-yolk medium, 109 with spermcryopreserved just in seminal plasma and 91 in Medi-Cult medium. The correspondance of results with native and cryopreserved sperm was found in 24% for egg-yolk medium, in 69% for seminal plasma and in 77% for commercial medium Medi-Cult. CONCLUSION: The results show that spermcryopreservation in Medi-Cult medium or just in the seminal plasma are able to be used in TAT for detection of spermagglutinating antibodies.

[Profile of antiphospholipid antibodies in various diagnoses associated with reproduction]. / Profil antifosfolipidových protilátek u ruzných diagnóz vázajících se k reprodukci.

The authors investigated antiphospholipid antibodies (APA) against phosphatidic acid, ph-ethanolamine, ph-DL-glycerol, ph-inositol, ph-L-serine and cardiolipine in isotypes IgG and IgM in various diagnoses associated with reproduction. They found that the most varied pattern of high levels of these antibodies is in particular in patients with the diagnosis of intractable infertility (in 26.5% women IgG against cardiolipine, in 24.5% patients IgG against ph-inositol and ph-DL-glycerol, in 17.6% women IgG against ph-ethanolamine, in 20.6% women IgG against phosphatidic acid antigens). Intractable infertility, repeated failures of IVF and patients with a basic autoaggressive disease were followed up and their antiphospholipid antibodies were assessed. In one patient follow up of APA revealed SLE before the patient developed clinical symptoms of the disease.

[Levels of endogenous plasma cortisol in patients with rheumatoid arthritis and other diffuse connective tissue diseases]. / Hladiny plazmatického endogenního kortizolu u nemocných s revmatoidní artritidou a jinými difuzními chorobami pojiva.

The authors tried to obtain information on levels of endogenous plasma cortisol in patients with rheumatoid arthritis and other diffuse connective tissue diseases, in particular systemic lupus erythematosus. Endogenous cortisol was assessed by radioimmunoanalysis at 8 a.m. and 4 p.m. If the sum of the morning and afternoon values reached the level of 280 nmol/l (sum of the lowest still normal values), they considered the daily cortisol secretion still normal. In a group of 30 patients who did not have glucocorticoid therapy the authors found only in one patient a lower daily endogenous cortisol secretion. In 117 patients with a relatively severe course of rheumatoid arthritis where small doses of corticoids (equivalents of 5-10 mg Prednisone) were administered for prolonged periods, a reduced daily secretion of endogenous plasma cortisol was recorded in almost 40%. Repeated examinations made in 13 subjects with rheumatoid arthritis revealed relatively frequent differences in values of endogenous plasma cortisol. In rare instances extremely low plasma levels of endogenous cortisol were found. Similar results as in rheumatoid arthritis, although assessed in a relatively small number of probands, were obtained by the authors also in patients with other diffuse connective tissue diseases, in particular those with systemic lupus erythematosus. Those patients had for prolonged periods roughly double doses of corticoids as compared with patients with rheumatoid arthritis. During repeated examinations the endogenous plasma cortisol levels varied also. The authors are aware that from the assembled results it is so far not possible to draw any definite conclusions and that further investigations are needed which will test the impact of endogenously produced corticoid.

[Rheumatoid arthritis--a diffuse connective tissue disease]. / Revmatoidní artritida--difuzní choroba pojiva.

The authors describe in a group of 100 patients, mostly with a severe form of rheumatoid arthritis, subjects with so-called "severe" extraarticular affections which can threaten the patients' lives or cause substantial deterioration of its quality, and those subjects where rheumatoid arthritis was the cause of death. These affections were associated--directly or indirectly--with the basic disease. From the absolute number of revealed affections the authors do not want to draw any conclusions as they are aware of various factors which could influence them. They assume, however, that the assembled data provide evidence that the American Rheumatological Association was right to include rheumatoid arthritis among diffuse connective tissue diseases and that it must be considered not only a disease of the locomotor apparatus but a potential disease of the organism as a whole.