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Patient education aims to ensure the compliance of the patient with long-term treatment. Patients are encouraged to exercise and to maintain their muscle strength. The multi-disciplinary team at the rheumatology clinic follows the patient's condition and disease activity, and when the RA has been in stable remission for a given period of time, e.
Goals The aim of these guidelines is to improve and harmonise the diagnosis and management of RA to ensure that the quality of life, the working capacity and the functional capacity of patients with RA are maintained. Target groups These guidelines are targeted at health care professionals at all levels e. RA begins as an immunological disturbance, and circulating biomarkers, e. Preclinical rheumatoid arthritis autoan Elevated rhe Early clinical symptoms are non-specific.
The epidemiology of early infl Most patients with undifferentiated arthritis do not have RA and their condition may resolve without treatment, but persisting arthritis must be followed-up and treated. Patients with arthritis who have a high risk of developing RA should be identified and treated promptly. Miten tuo EULAR recom Prevalence and The inc Prevalence and in These figures are comparable to the ones in Finland, where the overall annual incidence is , 59 among females and 30 among males «Puolakka K, Kautiainen H, Pohjolainen T ym.
The prevalence of RA is 0. Nationwide pre Low and stable pr The ris Epidemiological studies in The variation of these figures is due to variations in the criteria used to define RA as well as to differences in geographical region and timing of the studies. The global prevalence has been estimated to be 0.
The global burden of r The prevalence of RA is 2—3 times higher for females than males. The female risk is particularly high after delivery of the first child: it is 2. Aetiology Both genetic and environmental factors affect the development of RA. Genetics of rheuma Occurrence of r Twin concor Concordance is 3. Genetic susceptibility and environmental factors interact in the aetology of RA. A new model f A gene-environmen Thus far, tobacco smoking is the only known modifiable risk factor for RA.
Mortality and causes of Death rates Risk of mortality Determinants o Mortality in rheu Early effective treatment, and the use of methotrexate and biologics are associated with lower mortality «Listing J, Kekow J, Manger B ym. Survival, comorb No increased mor Mortality rate Mortality t Disease durati The overall mortality of patients diagnosed with RA in Finland since the year was not increased according to statistics extending, however, only to the year «Puolakka K, Kautiainen H, Pohjolainen T ym.
No inc Diagnostic goals Importance of early diagnosis The goal is to establish the diagnosis as early as possible and to promptly start effective pharmacotherapy aiming at early remission. Signs and symptoms Joint inflammation is the sine qua non for a diagnosis of RA.
Usually there is inflammation in several joints. The inflamed joint is typically swollen, stiff in the morning and painful on movement, but not necessarily painful at rest. In typical cases, joint inflammation is symmetrical. Joint symptoms usually develop slowly and progress gradually, often in a relapsing-remitting pattern.
RA may cause inflammation in the cervical spine, but symptoms of the lower back are not characteristic of RA. The more active the joint inflammation is, the longer is the duration of morning stiffness. Joint inspection and palpation are important. The inflamed joint is swollen and usually tender on palpation.
Clinical examination of the joints requires experience. Joint erosions usually develop first in the MTP joints «Eroosiot ilmaantuvat ensin jalkateriin.
One of the therapeutic goals is to have the patient on antirheumatic pharmacotherapy before joint erosions and permanent damage develop. The erythrocyte sedimentation rate ESR and the concentraton of C-reactive protein CRP in the serum or plasma reflect disease activity acceptably well, but are not always increased.
Erythrocyte sedimentation rate, Only h These findings are highly suggestive for RA, but are not a requirement for the diagnosis. Joint inflammation of unknown aetiology requires synovial fluid analysis, if possible. The synovial fluid is analysed for cell count and differential count of white blood cells and crystals. If the joint aspirate is turbid, bacterial staining and culture are in order.
In RA, synovial fluid is usually somewhat cloudy due to a high leukocyte count and its viscosity is reduced. Table 1. The criteria put special emphasis on the presentce of polyarthritis and of RF or anti-CCP present in high titres. Although the criteria are intended for disease classification, they aid clinical decision making. Diagnostic levels A patient suspected of having RA should be referred without delay to a unit specialised in rheumatology where the services of a multidisciplinary team are available to confirm the diagnosis and start treatment.
Oral glucocorticosteroids may mask symptoms and compromise the diagnosis. If RA or some other chronic rheumatic joint diseases are not suspected and the diagnosis is, e. Local health care arrangements may slightly differ from the current recommendations. See tables «Evaluation of patient with arthritis Table 2. Consider repeating the test after 1—2 months Arthritis: synovial fluid borrelia-PCR confirms but negative result does not rule out diagnosis Skin eruptions pox Consider rubella Sindbis-antibodies if itching dermatitis late August-September Consider Erythema infectiosum F Fever and tonsillitis prior to arthritis rheumatic fever?
AST when clinical suspicion of rheumatic fever; negative result indicates that rheumatic fever is unlikely Cardiac sonography Chest radiograph. Table 3. Special features to consider in differential diagnostics. Picture 2. Imaging Imaging supports clinical examination by identifying joint inflammation and permanent damage.
Radiography Radiography should be performed in radiology units that provide high quality images by appropriate techniques «Laasonen L. Radiographs are taken of the hands and feet as part of the diagnostic work-up of RA and other peripheral inflammatory joint diseases. A chest radiograph should be taken for differential diagnostic purposes and also before immunosuppressive pharmacotherapy is initiated.
Serial radiographs of the hand and feet may be taken judiciously over time to document disease follow-up. The progression of joint damage is usually fastest during the first two years of RA «van der Heijde DM.
Joint erosions and patients wit RA does not affect the spine, except the cervical part. In severe rheumatic spinal disease, in particular if the patient has atlanto-axial subluxation AAS , there is a risk of spinal cord damage of the cervical spine, if the neck is moved into extreme positions. Cervical subluxations e. These lateral images are the most important images of the rheumatoid cervical spine.
Sonography Sonography is the most important clinical tool for rheumatologists. Sonography is a reliable method for detecting swelling indicating arthritis. Increased blood flow by power Doppler indicates active inflammation. Sonography is a suitable method for planning and guiding intra-articular joint injections.
Contrast agents aid in the detection of active synovitis and enable earlier detection of erosions than conventional radiographs. MRI is not usually needed for diagnostic or monitoring purposes. Unequivocal indications for MRI are differential diagnostic problems. In severe disease of the cervical spine, MRI should be performed.
If displacement of the cervical vertebrae are seen, the effect of these anatomical changes are to be taken into account when the MRI images are interpreted to document any compression of the neural structures and spinal cord.
Early sup Remission entails the absence of symptoms and signs of joint inflammation. It is recommended that the initial treatment consists of a combination of methotrexate, sulfasalazine and hydroxychloroquine RACo-combination treatment , together with a small dose of glucocorticosteroid usually prednisolone 5. Methotrexate is the anchor drug of the disease-modifying antirheumatic drugs DMARD , onto which other antirheumatic drugs are added. Parenteral meth If methotrexate or combination therapy are contraindicated, treatment may be started with leflunomide, sulfasalazine or azathioprine.
Hesitant pharmacotherapy of RA only delays the time to remission. Inflamed joints should be treated locally with intra-articular glucocorticosteroid injections. Persisting disease despite active antirheumatic treatment combination treatment including the maximal tolerated dose of methotrexate should be treated with biologics.
The rheumatology unit ensures that the patient understands 1 the importance of treatment and initiates treatment, 2 that possible adverse events do not preclude effective drug treatment and that 3 the goal of treatment is to achieve remission within the first few months of treatment. This working group recommends that the rheumatology unit ensures sustained remission for up to two years.
Following this, the patient should have annual follow-up visits at a physician with a good understanding of rheumatology. If renal failure «The effect of age and renal function on the effica Methotrexate and leflunomide may not be used before conception, during pregnancy or during lactation.
The male partner does not need to interrupt the use of methotrexate before conceiving a child «Malm H. Rehabilitation Physical exercise as a form of rehabilitation has the strongest impact on the patient's functional capacity. Rehabilitation, as well as pharmacotherapy, aims at enhancing the patient's functional capacity, working ability and overall wellbeing.
Pharmacotherapy and rehabilitation complement each other: the need for rehabilitation is often minimized, if active pharmacotherapy restores the patient's functional capacity. Personalized physiotherapy or inpatient rehabilitation may be indicated for severely disabled patients. In addition, the SII arranges discretionary rehabilitation regardless of patient age.
Inpatient rehabilitation arranged in rehabilitation centres later referred to as specialised units may be useful for supporting self-rehabilitation programmes, for improving compliance and for maintaining the functional capacity of patients with multiple problems. There is only little evidence on the effectiveness of inpatient rehabilitation at specialised units.
There is a lack of well-performed studies and the available evidence that comes closest to inhouse rehabilitation in RA is based on studies comparing the effectiveness of multidisciplinary treatment carried out at inpatient wards with outpatient and daycare hospital units. If the principles of multidisciplinary care are applied, health benefit from outpatient and inpatient care is equal but is produced at a lower cost in outpatient units «van den Hout WB, Tijhuis GJ, Hazes JM ym.
Cost eff Cost of F Vocational rehabilitation The goal of vocational rehabilitation is to support the employment of disabled subjects by developing their professional skills and working environment. The patient's potential to retain his or her working capacity has to be assessed no later than after 90 weekdays of sickness allowance.
This assessment is documented on a statement by the occupational health care physician. If the patient does not have the benefit of occupational health care services, the consultation of the employment office TE-services or the SII must be sought to assess the patient's possibilities for vocational rehabilitation.
In addition, a multidisciplinary rehabilitation meeting arranged at a rheumatology or rehabilitation clinic may be helpful. Referral to vocational rehabilitation requires a plan for rehabilitation, i. For continuously employed patients, the pension insurance company takes on the responsibility for the rehabilitation costs, otherwise the SII is the payor. Ongoing rheumatoid arthritis treatment There is no curative treatment for RA. Pharmacotherapy is usually continued for years or decades, because RA symptoms tend to relpse on discontinuation of treatment.
For patients who have remained asymptomatic for years, medication can be decreased but close observation must be maintained.
The patient with RA should visit annually a physician who has a good understanding of treatment of RA. If the medication has been reduced and the RA relapses, the pharmacotherapy to which the patient previously responded is re-introduced or dosages increased.
Subcutaneous or oral methotrexate may be re-introduced, even if it was discontinued after previous use, since discontinuation is often due to an ineffective dose or mild adverse events. If there are no contraindications, the RACo-combination is introduced: methotrexate, sulfasalazine, hydroxychloroquine and a low-dose glucocorticosteroid usually prednisolone 5. Leflunomide may be also used. If the response to methotrexate-based combination treatment poor or absent, the RA is treated with biologics.
Pharmacotherapy of rheumatoid arthritis Conventional synthetic disease modifying drugs csDMARDs Methotrexate is the anchor drug of the disease-modifying antirheumatic drugs DMARD , onto which other antirheumatic drugs may be added. Methorexate may be used as monotherapy and as a part of combination therapy together with other DMARDs, e. Table 4. Canadian Rh Later on, maintenance dose will be tailored for each individual, balanced between side effects and benefits. Side effects Usual: GI-tract, nausea, dizziness, hair loss, stomatitis, elevated liver enzymes, increased red cell volume Rare: Interstitial lung disease, cytopenias Interactions Trimetoprim, probenecid Contraindications Pregnancy and breast feeding No need to interrupt MTX when planning fathering «Malm H.
If no other reasons except MTX, establish highest dose that the patient tolerates. Table 5. Table 6. Revised recommend Table 7. If levels remain high, discontinue leflunomide and consider cholestyramine to wash out leflunomide. Pay special attention to young women, as leflunomide may delay plans for pregnancy due to long withdrawal time of leflunomide.
Table 8. Cyclosporine, special aspects Dose Initial dose 2. Table 9. Table Cyclophosphamide, special aspects Dose 1. Due to difficult dosage and side effects especially dysgeusia is rarely used nowadays. Biologics are also called biologicals and biological products. Before a patient Is started on a biologic, infections are to be excluded e.
A chest X-ray is taken and a dental exam is made. Hepatitis screening is performed, if appropriate. Biological agents Biologics have the same effectivity, with the exception of anakinra, whose effect is weaker. Combination of two biologics is not recommended unless in exceptional circumstances and after careful consideration. Disparities in Inequities in acc Variations in cri Similar clin Information on the long-term risks is sparse.
Elevated incidence Excess ri Risk of mal New therapies In some patients the emergence of anti-drug antibodies ADAs may contribute to a loss of efficacy. Assessment of drug concentrations and ADA levels may be helpful in the assessment of efficacy loss.
A prelimi The immuno Therefore, drug holidays and prolonged intervals between administration of infliximab should be avoided to reduce the risk of ADAs. These observations are probably valid for golimumab and certolizumab pegol, as well. Tuberculosis assoc Benefit-risk assessment of Etanercept in rheumatoid arthritis.
The efficacy of tocilizumab administered subcutaneously is comparable to intravenous administration «Tosilitsumabi nivelreuman hoidossa on ihon alle annosteltuna samanveroinen kuin laskimoon annosteltuna.
Tocilizumab monotherapy may be as effective as tocilizumab in combination with methotrexate «Gabay C, Hasler P, Kyburz D ym.
Tocilizumab may increase the concentrations of serum lipids. C reactive protein may This should be taken into account when assessing the severity of an infection. Rituximab for The treatment response is optimal only a few months after treatment start «Scher JU. B-cell therapies for rheumatoid arthriti Rituximab is usually administered as two infusions two weeks apart. This course may be repeated at intervals of six to twelve months or less often, as indicated by the patient's individual response to treatment and disease activity «Scher JU.
Infusion reactions are common and therefore premedication e. Prior to rituximab treatment, the patient should be screened for hepatitides and HIV. Treatment with rituximab may decrease immunoglobulin levels.
T-cell blocker abatacept Abatacept is an effective treatment of RA «Abatasepti on tehokas nivelreuman hoidossa. The efficacy of abatacept administered subcutaneously is comparable to intravenous administration «Kaine J, Gladstein G, Strusberg I ym. Evaluation o Abatacept monotherapy may be as effective as abatacept in combination with methotrexate «Gabay C, Hasler P, Kyburz D ym. Systemic glucocorticosteroid treatment reduces the inflammatory symptoms of RA.
Intra-articular glucocorticosteroid injections abate arthritis symptoms rapidly. Accuracy of Treatment of rheumatic gonitis with intra-articular glucocorticosteroid injections results probably in a better response than using the same dose of glucocorticosteroids systemically «Konai MS, Vilar Furtado RN, Dos Santos MF ym.
Solid studies for other joints than the knee are lacking. Immobilization of the upper extremity after an intra-articular glucocorticosteroid injection does not seem to improve the outcome «Weitoft T, Forsberg C. Importance of immobilizatio For weight-bearing joints, like the knees, rest after the injection is beneficial «Wallen M, Gillies D.
Intra-articular steroids and Among the known adverse events of glucocorticosteroid treatment are osteoporosis, cataract, diabetes and adrenal gland suppression. The occurrence and severity of these adverse events is proportional to the administered dose and the duration of treatment.
The risk of osteoporosis should always be assessed when the patient is on a glucocorticosteroid, and attention must be paid on sufficient vitamin D and calcium supplementation Current Care Guidelines of osteoporosis «Osteoporoosi» 3 in Finnish.
If the patient has night pains and pronounced morning stiffness, a long-acting NSAID taken in the evening is recommended. How do g Prevention of up A randomised co The indication of opioid treatment, if started, needs to be clear and the goals of treatment and how it is carried out need to be agreed on with the patient. Prevention of osteoporosis The rheumatic inflammation and glucocorticosteroid treatment subject the patient to secondary osteoporosis.
Glucocorticosteroids increase the risk of osteoporosis dose-dependently and the risk of fractures. Therefore, prevention of osteoporosis is important for patients on pharmacotherapy for RA Current Care Guidelines of osteoporosis «Osteoporoosi» 3 in Finnish. Addressing the atherosclerosis risk The rheumatoid inflammation is harmful to the function of the vascular endothelium and raises the patient's cardiovascular risk «Solomon DH, Karlson EW, Rimm EB ym.
Increased coronary Lipid profiles in untr Effective suppression of the rheumatoid inflammation is crucial for preventing atherosclerosis. Effect of antim Low-dose glucocorticosteroid e. Evaluation of the patient's cardiovascular risk is a part of the overall assessment of the RA patient. The target lipid level should be the same as for other high-risk patients «Koivuniemi R ja Leirisalo-Repo M. Assessment of the lipid profile and glucose level should be undertaken only after the acute inflammation has resolved, e.
The impact of diet on rheumatoid symptoms Special dietary interventions are not recommended for the treatment of RA. Dietary inter Rheumatoid orthopaedic surgery The goal of active anti-rheumatic medication is to obviate the need for operative treatment. The decline in jo Patients with chronic RA may have joint changes which may be relieved with orthopaedic surgery «Matti U.
Reumaortopedian valtakunnallinen Synovectomy today usually arthroscopic synovectomy is indicated, if the inflammation in a single joint continues despite active anti-rheumatic pharmacotherapy. Synovectomy relieves often joint pain and stiffness.
Postoperatively, effective anti-rheumatic pharmacotherapy should be continued to prevent re-synovitis. If the cartilage surface of the joint is in poor condition before synovectomy, the operative result may be poor or brief. A treatment option for "drug-therapy refractory synovitis" of the knee joint is radiosynovectomy, where a short-lived radionuclide is injected into the knee joint and removed after a while.
This option is available only in some university hospitals in Finland. Tenosynovitis and nodules in the tendons refractory to conservative therapy limit the movement of joints and may be treated surgically with tenosynovectomy. If tenosynovectomy is done to the flexor tendons of the wrist, the carpal canal is usually also opened and the median nerve liberated «Simmen BR, Bogoch ER, Goldhahn J.
Surgery Insight Arthrodesis may relieve the pain of a severely destroyed joint and improve function of the whole extremity. Arthrodeses may correct severe deformities and prevent the progression of deformities.
Usually, arthrodeses are performed in the wrist, subtalar joint, first metatarsophalangeal joint and sometimes in the finger joints.
Severe deformity in the cervical spine may be an indication for operative treatment. Severe anterior atlanto-axial subluxation AAS is usually treated surgically by fusing vertebrae C1 and C2. The prosthesis type for glenohumeral arthroplasty is selected individually.
For patients with a severly degenerated rotator cuff, a reverse shoulder arthroplasty prosthesis is often used, because then the shoulder muscles may compensate for the loss of rotator cull function and generate satisfactory ranges of movement.
Rheumatoid Elbow Destruction and its T Prosthesis of the ankle, wrist and fingers may be used in selected RA cases. Painful rheumatoid nodules and bursae may require operative treatment. The postoperative infection risk of patients with RA is elevated if the patient has certain concomitant diseases, like diabetes, impaired circulation in the operated limb and a history of infections after previous operations.
DMARDs, and especially biologics, often increase the risk of infections, which has to be taken into account when the surgical risks are evaluated. The downside of discontinuing antirheumatic pharmacotherapy are, however, an increased risk of rheumatoid flare, an impaired surgical outcome and even an increased risk of infection. There is an abundant literature on how to discontinue antirheumatic pharmacotherapy before surgery, but strong evidence for the benefit of such a discontinuation is lacking.
In general, it is reasonable to withhold biologics for 1—2 weeks before surgery and for the time after surgery until the surgical wound shows signs of good primary healing. Biologics need not be discontinued for minor, clean operations. Effect of patient educa The treatment of RA is based on a shared decisions between the patient and the treating physician. Treating rheu The role of the rheumatology nurse for efficient patient education is crucial. The patient needs to understand: the nature of RA and how it progresses, if untreated how RA is treated that remission is a realistic target in early disease and that stringent adherence by the patient to the prescribed medication is important that the medication might have side effects and patients may need to switch medications, but the risks of having RA untreated are manyfold compared to the risks of the medication.
Smoking is a risk for RA. Patient education needs to be comprehensive, well-structured and comprehensive. A supportive attitude of the treating physician and the rheumatology nurse is essential. A physiotherapist should provide education on physical exercise. As needed, the patient should be referred to an occupational therapist, podiatrist, dietician, psychotherapist or social worker.
The patient needs to have an assigned health care professional as a contact person. Motivoiva haasta Patient follow-up We recommend that each rheumatology unit follows a clinical pathway for the care of patients with early RA. The objectives of following such a pathway are to guarantee that: the patient starts the medication agreed on possible adverse events are balanced against effective drug treatment the treatment target is remission during the first few months of treatment remission is sustained.
Blood tests for drug safety should be taken and assessed by a physician in primary care. The risk of infection must be considered when biologics are used and appropriate vaccinations need to be guaranteed. Close collaboration between the rheumatology unit and primary care is crucial since treatment of RA will go on for years and decades. If the overall treatment is to be successful, relapses of RA must be recognised in primary care.
The patient is referred to a rheumatologist, if the relapse is not adequately controlled by the measures provided by the "toolbox" see Table «GP's tool box Cost-effectiveness of the pharmacotherapy of RA RA incurs high societal costs, including direct costs from increased health care resource use and indirect costs from reduced work productivity.
Use of th A good early treatment outcome, remission at best, prevents high costs and enhances the patient's quality of life. If the activity of RA continues unabated, the patient is at risk of joint damage, loss of function and loss of working capacity. Economic cons If conventional synthetic anti-rheumatic pharmacotherapy is not effective, even an expensive medication is cost-effective if it prevents disability and early work incapacitation and retirement.
Costs due to work incapacity are reduced also if pharmacotherapy is upgraded later during the disease process, if this allows the patient to regain his or her functional capacity to a level compatible with the requirements of the patient's assignments «Augustsson J, Neovius M, Cullinane-Carli C ym.
Several studies have shown that the functional capacity of RA patients has, on average, improved in the past two decades. There are several studies on the cost-effectiveness of different medications and combinations, but usually they have been comparisons between methotrexate monotherapy and other pharmacotherapeutic regimens in cases of methotrexate failure.
They are not relevant for Finnish practice. Comparisons of various biologics have been based on short-term treatment studies, and the patient cohorts have not often been comparable. Limitation of responsibility The clinical practice guidelines of the Finnish Medical Society Duodecim are summaries on the diagnostics and effectiveness of therapy on single diseases and are produced by experts.
References Deane KD. Preclinical rheumatoid arthritis autoantibodies : an updated review. Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study. The epidemiology of early inflammatory arthritis. Drug therapy in undifferentiated arthritis: a systematic literature review. Miten tuoretta nivelreumaa hoidetaan Suomessa. Lau40, D. Ledford41, S. Lee42, A. Liu43, R. Lockey44, K. Morikawa47, A. Nieto48, H. Paramesh49, R.
Pawankar50, P. Pohunek51, J. Pongracic52, D. Price53, C. Robertson54, N. Rosario55, L. Rossenwasser56, P. Sly57, R. Stein58, S. Stick59, S.
Szefler60, L. Taussig61, E. Valovirta62, P. Vichyanond63, D. Wallace64, E. Weinberg65, G. Wennergren66, J. International consensus on icon pediatric asthma. Allergy ; — Keywords Abstract asthma; children; consensus; guidelines; wheeze. Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Although there is no Nikolaos G. Papadopoulos, Department of doubt that the use of common systematic approaches for management can con- Allergy, 2nd Pediatric Clinic, University of siderably improve outcomes, dissemination and implementation of these are still Athens, 41, Fidippidou street, Athens major challenges.
Consequently, the International Collaboration in Asthma, 27, Greece. The purpose of this document is to highlight the key E-mail: ngp allergy. Accepted for publication 30 May The principles of pediatric asthma management are generally accepted.
Overall, DOI To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with health- Edited by: Michael Wechsler care professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-eval- uate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity.
The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved. Asthma is the most common chronic lower respiratory dis- In children, asthma often presents with additional chal- ease in childhood throughout the world. Asthma most often lenges not all of which are seen in adults, because of the starts early in life and has variable courses and unstable phe- maturing of the respiratory and immune systems, natural his- notypes which may progress or remit over time.
Wheeze in tory, scarcity of good evidence, difficulty in establishing the preschool children may result from a number of different diagnosis and delivering medications, and a diverse and fre- conditions; around half of preschool wheezers become quently unpredictable response to treatment.
The impact of asthma on sions on pediatric asthma. These vary in scope and methodol- the quality of life of patients, as well as its cost, is very high. Although there is no doubt that the use major impact on the quality of life of patients and their fami- of common systematic approaches for management, such as lies, as well as on public health outcomes 1.
Asthma in guidelines or national programs, can considerably improve childhood is strongly associated with allergy, especially in outcomes, dissemination and implementation of these recom- developed countries. Common exposures such as tobacco mendations are still major challenges. Currently, primary prevention is not possible.
Definitions often include more details, such as specific cell types e. Steering Committee of iCAALL and the participating organi- The relative importance of each of these additional elements zations authors 1— The criteria used for the formation of can be argued; nevertheless, they are neither necessary for the committee were international representation, relevance to nor exclusive to asthma and therefore do not add appreciably the field, and previous participation in pediatric asthma to the sensitivity or specificity of the previously mentioned, guidelines.
The members of the committee proposed relevant generally accepted elements. These were the Australian Taking the above into account, a working definition, repre- Asthma Management Handbook, AAMH 3 , the senting a synopsis from all guidelines, is shown in Box 1.
It Guidelines for the Diagnosis and Management of Asthma, presents with recurrent episodes of wheeze, cough, shortness NAEPP 7 , the Diagnosis and treatment of Asthma of breath, and chest tightness. Each member Classifications undertook responsibility for preparing tables and relevant commentaries comparing the included documents in a specific To address diversity and guide management, several factors domain.
These were subsequently compiled into a first draft have been used to classify pediatric asthma Fig. The revised document was then circulated among nosis and treatment. There is general consensus that mile- an independent reviewing group authors 12—68 , the com- stone ages are around 5 and 12 years, and important clinical ments of which were taken into account in the final draft, and epidemiological characteristics appear to change around which was approved by the governing bodies of the partici- those ages.
Recom- 3 years is further distinguished. Special characteristics of mendations were extrapolated from the reference documents adolescence are emphasized in most documents Fig. There is slightly less consistency when it comes to severity and persistence, which have been extensively used in the past to classify asthma. With respect to persistence, asthma is usually Definition and classifications of pediatric asthma classified as intermittent or persistent; in addition, infrequent and frequent intermittent classes are proposed by the AAMH.
Definition With respect to severity, persistent asthma is usually classified The complexity and diversity of asthma in both children and as mild, moderate, and severe.
Hence, these and their patterns, as well as underlying mechanisms, at different classifications are currently recommended only for initial levels of detail. Slightly different terms are Chronic inflammation is recognized as the central pathol- used for the levels of asthma control, which are generally ogy.
In contrast, airway remodeling is only mentioned in the three controlled, partly controlled, and uncontrolled. In definition of the JGCA. ICON pediatric asthma Figure 1 Pediatric asthma is a diverse condition and several fac- siderable overlap and possible changes over time. Severity lower tors can be used for its classification. Important changes in clinical left can range from very mild to life-threatening; although not nec- presentation take place in relation to age upper left.
Although lim- essarily discrete, a stepwise approach has been used to character- its are arbitrary and may differ between individuals, infancy, pre- ize severity and inform treatment initiation. More recently, the level school age, school age and adolescence are generally considered of control lower right of both current symptoms and risk of future as milestones.
Phenotypes upper right may result from different morbidity is preferred as a measure, towards which asthma man- underlying pathophysiologies endotypes , however, there is con- agement is evaluated. For many patients, Guideline Update Recommendations several apparent triggers may be identified, also varying over time, highlighting the difficulty in providing a simple pheno- type classification system.
Levels of control are indicative; the most severe impairment or risk defines the level. Increased populations of mast ment should be addressed in more detail cells, eosinophils, lymphocytes, macrophages, dendritic cells, and others contribute to inflammation 25, Structural cells Pathogenesis and pathophysiology such as epithelial cells and smooth muscle cells may also con- tribute to the inflammatory milieu 27, The inflammatory There is general agreement that asthma is a disease of and structural cells collectively produce mediators such as chronic inflammation, airway hyperresponsiveness, and cytokines, chemokines, and cysteinyl leukotrienes that inten- chronic structural changes known as airway remodeling sify the inflammatory response and promote airway narrowing Fig.
Some of the guidelines provide extensive discussion and hyperresponsiveness AHR is associated with exces- of these topics, while others focus mostly on diagnosis and sive smooth muscle contraction in response to nonspecific irri- treatment and mention these concepts in introductory tants and viral infections, and for allergic individuals, exposure remarks or as part of an asthma definition.
Neural mechanisms, likely Asthma can begin at any age but most often has its roots initiated by inflammation, contribute to AHR The prevalence of asthma has Acute episodes of airway narrowing are initiated by a com- increased in many countries 12 , although in some cases it bination of edema, infiltration by inflammatory cells, mucus may have leveled off 12, As asthma inception depends hypersecretion, smooth muscle contraction, and epithelial on both genetics 14, 15 and the environment 16 , modifi- desquamation.
These changes are largely reversible; however, able environmental factors have been sought in an effort to with disease progression, airway narrowing may become pro- identify targets for prevention.
Many guidelines mention gressive and constant Structural changes associated with infections, exposure to microbes, stress, pollutants, allergens, airway remodeling include increased smooth muscle, hyper- and tobacco smoke as possible contributing factors. The emia with increased vascularity of subepithelial tissue, thicken- development of allergen-specific IgE, especially if it occurs in ing of basement membrane and subepithelial deposition of early life, is an important risk factor for asthma, especially in various structural proteins, and loss of normal distensibility of developed countries Remodeling, initially described in detail in Unfortunately, to date this knowledge has not translated adult asthma, appears to be also present in at least the more into successful programs for primary prevention.
Although severe part of the spectrum in pediatric asthma 36, ICON pediatric asthma Figure 2 In children, as in adults, pathological changes of the responses in the asthmatic airways. Inflam- tivity lead to airway obstruction. Although pathophysiological mation is triggered by a variety of factors, including allergens, changes related to asthma are generally reversible, partial recov- viruses, exercise etc.
These factors also induce hyperreactive ery is possible. As in guidelines. However, extrapolation of findings from epidemio- logical studies to the assessment of future risk in individual Natural history patients in the clinical setting, or in different populations, Asthma may persist or remit and relapse Natural his- may not be as straightforward Infants with outgrow their symptoms at some age The likelihood of recurrent wheezing have a higher risk of developing persistent long-term remission, on the one hand, or progression and asthma by the time they reach adolescence, and atopic chil- persistence of disease, on the other, has received considerable dren in particular are more likely to continue wheezing.
In attention in the medical literature over the last decade 40— addition, the severity of asthma symptoms during the first However, the natural history of asthma, with the excep- years of life is strongly related to later prognosis.
However, tion of the common understanding that asthma starts early both the incidence and period prevalence of wheezing in life and may run a chronic course, is not prominent in decrease significantly with increasing age. Typical symptom patterns are important Studies for exclusion of alternative diagnoses e. These include recur- Therapeutic trial rent episodes of cough, wheeze, difficulty in breathing, or Evaluation of airway inflammation FeNO, sputum eosinophils chest tightness, triggered by exposure to various stimuli such Evaluation of bronchial hyperresponsiveness nonspecific bronchial as irritants cold, tobacco smoke , allergens pets, pollens, challenges, e.
Personal history of atopy e. Allergic bronchopulmonary aspergillosis Anaphylaxis Evaluation of lung function Bronchiolitis Immune deficiency Evaluation of lung function is important for both diagnosis Recurrent respiratory tract infections and monitoring.
Nevertheless, normal lung function tests do Rhinitis not exclude a diagnosis of asthma, especially for intermittent Sinusitis or mild cases Therefore, these tests are considered sup- Sarcoidosis portive. Performing the tests when the child is symptomatic Tuberculosis may increase sensitivity. Bronchial pathologies Spirometry is recommended for children old enough to per- Bronchiectasis form it properly; the proposed range of minimum age is Bronchopulmonary dysplasia between 5 and 7 years.
Spirometry may not be readily Enlarged lymph nodes or tumor available in some settings, particularly low-income countries. ICON pediatric asthma 48 or specific airway resistance 49 ; however, these are not when it is stopped supports a diagnosis of asthma, although generally available outside specialized centers. Although the diversity of childhood asthma is generally Evaluation of AHR and airway inflammation recognized and various phenotypes or subgroups are men- Airway hyperresponsiveness, assessed by provocation with tioned in different documents, there is little detail or agree- inhaled methacholine, histamine, mannitol, hypertonic sal- ment on diagnostic requirements for particular phenotypes, ine, or cold air, has been used in adults to either support or with the exception of exercise-induced asthma.
The use of these methods Research Recommendations in children is supported with reservation by most asthma guidelines. Although there is considerable variation in the way that dif- Identification of specific allergic sensitizations can support ferent guidelines structure and present the principles and asthma diagnosis, can indicate avoidable disease triggers, and components of asthma management, the key messages are has prognostic value for disease persistence 52, Both in consistent, including a number of components that are a con- vivo skin prick tests and in vitro specific IgE antibodies sequence of its chronic and variable course Fig.
Education and the formation of a partnership between them are crucial for the implementation Special considerations and success of the treatment plan Evidence A—B. There are important differences in the approach to diagnosis Identification Evidence A and avoidance Evidence B—C according to age. Most guidelines recognize the difficulty in of specific i. In tobacco smoke, but not exercise and risk factors are also of addition to the lack of objective measures at that age, the significant importance, because these may drive or augment suboptimal response to medications and variability of natural inflammation.
The opti- e. Importantly, education should highlight the the elements necessary to achieve disease control: patient and par- importance of adherence to prescribed medication even in ent education, identification and avoidance of triggers, use of the absence of symptoms and should involve literal explana- appropriate medication with a well-formed plan, and regular moni- tion and physical demonstration of the optimal use of inha- toring, are all crucial for success.
Management should be adapted ler devices and peak flow meters. Education should be to the available resources. This involves the sideration, independent of chronic treatment. This should optimally include severe and difficult asthma are highlighted throughout the the daily medication regimen, as well as specific instructions documents. Age-specific instructions are usually proposed for early identification and appropriate management of in 2 or 3 strata.
It is generally accepted that recommenda- asthma exacerbations or loss of asthma control. Educated tions in the youngest age-group are based on very weak interpretation of symptoms is of primary importance, as well evidence. Unfortunately, that even prolonged treatment with inhaled corticosteroids, the uptake of written action plans is poor, both by patients despite its many benefits 60 , is unable to do so Evidence and by practitioners.
Allergen-specific immunotherapy is currently the only It is generally recognized that different approaches should treatment with long-term disease-modifying potential 61— be sought for different age-groups; in particular, JGCA and 63 ; however, the evaluation of the evidence base for this PRACTALL recommend an age-specific stratification of edu- effect is controversial among experts and therefore needs cational targets, with incremental participation of older chil- further studies.
ICON pediatric asthma based programs 65 , often peer-led in the case of adoles- vailing view is that single interventions for indoor allergens cents, may have increased penetration and acceptance in have limited effectiveness; if measures are to be taken, a large numbers of asthmatic children Evidence B.
Patients multifaceted, comprehensive approach is prerequisite for and their families may also be provided brief, focused educa- clinical benefit Evidence A , while tailoring environmental tional courses when being admitted to hospital emergency interventions to specific sensitization profiles has been departments for asthma exacerbations, while use of com- shown to be of added value Outdoor allergens are puter- and Internet-based educational methods represent generally less manageable, because their levels cannot be other proposed alternatives, especially for older children and modified by human intervention and staying indoors for adolescents Evidence B.
Finally, education of health authorities and politicians ularly in developing countries Education of healthcare cessation in adolescents and reduction in exposure to envi- professionals is self-evident. Vigorous measures are needed to achieve avoidance. NSAIDs or food-sen- therefore, local versions, based on these principles, should sitive e. It is reasonable Pharmacotherapy that avoidance of these factors may have beneficial effects on the activity of the disease.
The airway pathophysiology The goal of asthma treatment is control using the least mediated through IgE to inhalant allergens is widely possible medications. Asthma pharmacotherapy is regarded acknowledged; however, not every allergen is equally signif- as chronic treatment and should be distinguished from icant for all patients. Thus, there is general consensus treatment for acute exacerbations that is discussed that sound allergological workup including careful history separately.
Most guidelines pro- Evidence B. GINA omits this step in gen avoidance. Indoor allergens dust mite, pet, cockroach, and selected through a stepwise approach according to the level mold allergens are considered the main culprits and are of disease control. In evaluating control, the differentiation targeted by specific interventions Evidence B—D, depending between current impairment and future risk is consid- on allergen and intervention.
This additional consideration GINA, and SIGN are more cautious in the interpretation is important in appreciating the independence of these of the evidence and underline the unproven effectiveness of elements. Complete If control is not achieved after 1—3 months, stepping up allergen avoidance is usually impractical, or impossible, and should be considered, after reviewing device use, compliance, often limiting to the patient, and some measures involve environmental control, treatment for comorbid rhinitis, and, significant expense and inconvenience.
Moreover, the pre- possibly, the diagnosis. Drug Low daily dose lg Beclomethasone dipropionate HFA Drug classes and their characteristics Budesonide Despite the progress in asthma research, current asthma Budesonide nebulized medications belong to a small range of pharmacological Ciclesonide 80 families. Corticosteroids, beta-2 adrenergic agonists, and Flunisolide leukotriene modifiers are the predominant classes. Chro- Flunisolide HFA mones and xanthines have been extensively used in the past Fluticasone propionate HFA but are now less popular, the former because of limited Mometasone furoate efficacy and the latter because of frequent side effects.
Triamcinolone acetonide Omalizumab, a monoclonal antibody against IgE, is the Inhaled steroids and their entry low doses. Medium doses are newest addition to asthma medications, the first from the always double 29 , while high doses are quadruple 49 , with the family of immunomodulatory biological agents, of which exception of flunisolide and triamcinolone which are Medications are classified, according to their use, as those used for acute relief and those used for long- term control.
The clinical asthma symptoms, through bronchodilation. Use of inhaled response may vary among patients; therefore, the optimal short-acting beta-2 adrenergic agonists SABA , most com- maintenance dose is sought on an individual basis. Compared to other relievers, first year 59, 72, 73 , while studies in preschool-age children SABA have a quicker and greater effect on airway smooth are less consistent. The effect appears to improve with time; muscle, while their safety profile is favorable; a dose-depen- however, there are concerns about subgroups who may be dent, self-limiting tremor and tachycardia are the most com- more susceptible or permanently affected 59, Recent mon side effects.
Anticholinergic final height cannot be excluded Most of the information available refers to low to medium Medications used for long-term asthma control doses, and there is minimal information on high-dose ICS.
Furthermore, the total steroid load in cases of concomitant Inhaled corticosteroids ICS. The use of ICS as daily use of local steroids for allergic rhinitis or eczema should be controller medications in persistent asthma is ubiquitously taken into account. Because of their pleiotro- these differences. Among leukotri- Evidence A. Although dose—response LTRA are effective in improving symptoms and lung func- curves have not been established for every ICS formulation tion and preventing exacerbations at all ages 76, 77 Evi- and for all age-groups, efficacy appears to reach a plateau dence A.
They are generally less efficacious than ICS in for most patients and outcomes around or below medium clinical trials, although in some cases noninferiority has been dose range 69, It should be noted, however, that the shown 78, Furthermore, there is evidence suggesting evidence on the role of low-dose ICS as maintenance particular effectiveness of montelukast in exercise-induced treatment for the prevention of intermittent, virus-induced asthma, possibly superior to other treatments ICON pediatric asthma in most guidelines they are recommended as second choice profile.
In the context of the next treatment steps, initial treatment steps and prevention of exercise-induced they are also effective as add-on medications, but less so in asthma. In any case, they are not available anymore in comparison with LABA LTRA may be particularly useful when the patient has con- comitant rhinitis.
Theophylline, the most used methylxanthine, Montelukast is relatively free of adverse effects. With za- has bronchodilatory properties and a mild anti-inflammatory firlukast, signs of hepatic dysfunction should be monitored. LABA, peutic index and can have serious side effects, therefore including salmeterol and formoterol, have long-lasting requiring monitoring of blood levels As a result, its role bronchodilator action.
In older children and adults, ICS— as controller medication is very limited and is only recom- LABA combinations have been shown to improve asthma mended as second-line treatment, where other options are outcomes to a better extent than higher doses of ICS 82— unavailable However, a small, but statistically significant risk for severe exacerbations and death associated with daily use of Omalizumab.
Omalizumab is indicated for children with LABA has been described 85— It reduces symptoms and exacerbations and young children is not as robust as that of older children improves quality of life and to a lesser extent lung function and adults 88, These concerns are probably behind 97— Strategies for asthma pharmacotherapy All documents agree that LABA should only be prescribed in combination with ICS and are therefore relevant as add- Detailed strategies for prescribing asthma medications are on treatment.
Age is always taken into account. There is consensus that medication for acute relief of In the absence of data of safety and efficacy in children symptoms typically, a short-acting inhaled beta-2 agonist younger than 5 years, it is probably better to be cautious, should be available to all patients with asthma, irrespective until such data are produced.
For older children, it is clear of age, severity, or control. Step 0: In the lowest step, no controller medication is pro- The use of a single combination inhaler, rather than sepa- posed. LTRA are recommended as effects.
Possible explanations ated in several trials, mostly in adults. The efficacy has also for these variations are that generally ICS are more effec- being shown in children 87, Cromolyn sodium and nedocromil modulate LTRA, especially in the younger and less atopic children mast cell mediator release and eosinophil recruitment.
Sev- They are On the other hand, they have an excellent safety SIGN are also included as options at this step. Devices fall under three categories: tion may be unavailable or unaffordable. Breath-actuated MDIs have distinct ond medication can be added. This is probably the most characteristics. There is no robust evidence suggesting major variable and to some extent controversial step. For chil- differences in effectiveness between the device types; however, dren older than 5 years, GINA and SIGN recommend each type has specific merits and limitations A mouthpiece should Nonetheless, the above variation refers to preferred substitute for the mask when the child is able to use it.
In choices among lists of options that are similar among the areas where commercially produced spacers are unavailable documents. With respect to the younger age-group, the or unaffordable, a ml plastic bottle spacer may be small number of studies explains this discrepancy.
In adapted to serve as an effective spacer for children of all ages older children, choices of safety vs efficacy may influence The effects of anatomical differences and low inspira- the recommendations. However, there is good evidence tory flows of young children on medication deposition by dif- suggesting that the response to medication may differ con- ferent drug delivery devices and spacers are not well siderably among individuals 90, , suggesting the need understood.
GINA includes omalizumab here. ICON pediatric asthma Figure 4 The stepwise approach to asthma treatment in childhood should be evaluated at regular intervals, measured by level of con- aims at disease control. Reliever medication should be used at trol. At diagnoses should always be considered before stepping up. It the mildest spectrum of the disease, no controller medication is should be stressed that medications in each step are not identical, needed step 0.
The next step entails the use of one controller in either efficacy or safety, and preferred choices can be medication step 1. If this is not enough, two medications, or a described, especially for different age groups. For more details on double dose of inhaled steroid, can be used step 2. In more diffi- this, the reader is referred to the text. Nevertheless, there is also cult cases, increase of inhaled steroid dose, alone or in combina- considerable variation in the individual response to each medica- tion with additional medication is needed step 3—4.
Oral tion, therefore, close monitoring and relevant adjustments are corticosteroids are kept as the last resort, for very severe patients equally or even more important. An easy way to memorize this Step 5. Among biological treatments, omalizumab has specific stepwise approach is that the number of each step suggests the indications for children at step 3 or higher. Stepping up or down number of medications, or ICS level, to be used.
However, several experts feel that these Choice of: pMDI with static-treated spacer and mouthpiece, aspects of SIT have not been adequately demonstrated. DPI rinse or gargle after inhaling ICS , breath-actuated pMDI Nevertheless, convenience and safety of administration have depending on patient ability to use, preference been a matter of concern.
Apart from common local side effects Nebulizer: second choice at any age at the injection site, systemic reactions including severe bron- choconstriction may occasionally occur, and these are more frequent among patients with poor asthma control It is Immunotherapy therefore generally agreed that SIT should only be administered Allergen-specific immunotherapy SIT involves the adminis- by clinicians experienced in its use and appropriately trained to tration of increasing doses of allergen extracts to induce identify and treat potential anaphylactic reactions.
Further- persistent clinical tolerance in patients with allergen-induced more, SIT is not recommended in severe asthma, because of the symptoms. Subcutaneous immunotherapy SCIT has been concern of possible greater risk for systemic reactions. AAMH, SIGN, and NAEPP acknowledge a clear role These effects are generally considered to be greatest when for immunotherapy as an adjunctive treatment, provided that standardized, single-allergen extracts of house dust mites, clinical significance of the selected allergen has been demon- animal dander, grass, or tree pollen are administered, strated.
PRACTALL also endorses immunotherapy and fur- whereas definitive evidence is currently lacking for the use ther suggests SIT to be considered as a potential preventive of multi-allergen extracts and for mold and cockroach aller- measure for the development of asthma in children with gens , According to GINA, the option of immuno- In clinical practice, allergen is typically administered for 3— therapy should only be considered when all other interven- 5 years.
A specific age limit, above which SIT can be initi- tions, environmental and pharmacologic, have failed. Multiple monitoring methods may be therapeutic option in asthma management. Nevertheless, a useful in some cases. Gen- about stepping down or stopping controller treatment erally, only minimal symptoms are acceptable. For patients on daily controller therapy, reviews approximately every 3 months Asthma exacerbations attacks, episodes are suggested; after an exacerbation, a shorter interval should be considered Evidence D.
Several validated tools for assess- Asthma exacerbations are of critical importance, as they are ing asthma control in children have been published — While monitoring lung function in children who can perform it detailed criteria for the assessment of severity are proposed Evidence B. The optional use of the adjectives of inhaler technique are important , , ICON pediatric asthma sodes may also be within the limits of the concept.
SIGN includes dif- bronchodilators such as salbutamol, and aminophylline Evi- ferent algorithmic definitions according to severity near-fatal dence B. There is little or no evidence on magnesium sulfate asthma, life-threatening asthma, acute severe asthma, moderate or helium—oxygen mixture in children; however, these could be asthma exacerbation, and brittle asthma.
No definitions are options in cases not responding to the above treatments. The acute or subacute and progressive nature of symptom intensification is generally Research Recommendations highlighted.
The use of oral steroids is a marker of important unmet need. Taking the above treatment for asthma into account, a working definition is shown in Box 3. Severity is assessed based on clinical presen- tation and objective measures Table 5. Such classification Guideline Update Recommendations may be difficult to apply in infants and preschool children because of the lack of lung function assessment.
Bronchodilation is the cornerstone of exacerbation treat- ment Evidence A ; it should already be started at home, as part of the asthma action plan, and should also be the first Box 3 treatment measure in the emergency department ED , immedi- Asthma exacerbation definition ately following severity assessment. Salbutamol inhaled at An exacerbation of asthma is an acute or subacute episode of doses ranging from 2 to 10 puffs — lg , every 20 min progressive increase in asthma symptoms, associated with air- for the first hour, given via MDI-spacer nebulized also possi- flow obstruction ble , is recommended.
The addition of ipratropium bromide may lead to some additional improvement in clinical symptoms Evidence A—B. The response should be assessed after the first hour; if not satisfactory, the patient should be referred to a hos- pital if at home and the next level of therapy should be given.
Box 4 Administration of supplemental oxygen is important to Key points in asthma exacerbation treatment correct hypoxemia Evidence A , with parallel O2 saturation Bronchodilation: inhaled salbutamol, 2—10 puffs; or nebulized, monitoring. In severe attacks, PCO2 levels may also need to 2. Very high-dose inhaled IV beta-2 agonists, IV aminophylline, IV magnesium sulfate, steroids may also be effective either during the exacerbation helium—oxygen mixture or preemptively after a common cold , ; however, they are not generally recommended to substitute systemic Conclusions ones, although some experts feel that this may be an option.
There is also some evidence for a modest preemp- Despite significant improvements in our understanding of tive effect of montelukast ; however, this is not cur- various aspects of childhood asthma, as well as major efforts rently recommended. Bacharier has received their choices.
Burks has quality of life of children with asthma and to reduce the bur- consulted for Dannon Co. Probiotics, Exploramed Develop- den of this contemporary epidemic. Schering-Plough; has received grants from the Food Allergy Local adaptation of the above principles will also contribute and Anaphylaxis Network, the Food Allergy Initiative, the to the same direction 1. Casale has received Conflict of interest payment from consultancy from MedImmune. Castro- N.
Carlsen has served on T. Ledford has received payment for consultancy Institute, Pharmaxis. Akdis has Pharma. Rosenwasser tional congresses for presenting lectures; and owns stock or has received payment for board membership from WAO and stock options in Roth IRA acct. Stein has received payment for lectures from last year once and grants from National and regional grants Abbott. Szefler has received payment for consultancy from for research in our group.
Nieto has received payment for board membership, con- Abbott. Wildhaber has served on national development of educational presentations from Schering- and international advisory boards of Nycomed and MSD Plough and grants from Inmunotek.
Arakawa, team have received grants and support for research in M. Wong, H. Zar, E. Baraldi, H. Boner, Y. Chen, Y. El-Gamal, M. Everard, M. Gereda, D. Goh, G. Hedlin, S. Hong, E. Huang, J. Mundipharma, Novartis, Nycomed, Pfizer and Teva. He has Lee, A.
Morikawa, H. Paramesh, R. Pawankar, J. Robertson, D. Sly, S. Stick, L. Taussig, E. Vichyanond, D. Wallace, E. Weinberg, have no conflicts AKL Ltd. References 1. Allergol Int treatment of asthma: critical evaluation. Reduction of asthma burden is possible ;— BMJ ;— Allergy 7.
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Allergy ;— Blood Institute US , Asthma Management Handbook.
National 8. Thorax ;— From the Global Strategy for Asthma 9. British Thoracic Society and Scottish Inter- Global Initia- collegiate Guidelines Network.
Current Care Guideline in Finnish «Nivelreuma» 1. Please note that the guideline in Finnish, Nivelreuma «Nivelreuma» 1has been partially updated on Feb 18th, Therefore this English version is not currently up to date.
The clinical practice guidelines of the Finnish Medical Society Duodecim are summaries on the diagnostics and effectiveness of therapy on single diseases and are produced by experts. They do not replace the judgement of a physician or other healthcare specialist on the best possible diagnostics and therapy of an individual patient. Rheumatoid Arthritis Current care Published: Guideline Images and figures Content. Target groups.
Diagnostic goals. Treatment of RA. Ongoing rheumatoid arthritis treatment. Pharmacotherapy of rheumatoid arthritis. Prevention of osteoporosis. Addressing the atherosclerosis risk. The impact of diet on rheumatoid symptoms. Rheumatoid orthopaedic surgery. Patient education. Patient follow-up. Cost-effectiveness of the pharmacotherapy of RA. Limitation of responsibility. Rheumatoid Arthritis Current Care Guidelines. Summary A patient suspected of having rheumatoid arthritis RA should be referred without delay to a multi-disciplinary rheumatology clinic for confirmation of the diagnosis and treatment start.
If left untreated or if treated with inferior drugs, patients with RA will experience disease progression and the RA will become a crippling disease. Effective treatment, on the other hand, can prevent disease progression for most patients. The goal of treatment of early RA is prompt and sustained disease remission, which allows the patient to recover and maintain his or her functional capacity and working ability.
Treatment of active RA is started with combination pharmacotherapy: methotrexate, sulfasalazine, hydroxychloroquine and a low dose of glucocorticosteroid usually prednisolone 5.
The efficacy of monotherapy is poorer than of combination therapy. Methotrexate is the anchor drug, onto which other antirheumatic drugs are added. If methotrexate is contraindicated, leflunomide or azathioprine may be used. A glucocorticosteroid should be injected intra-articularly into inflamed joints. If active RA does not respond to combination treatment, the disease should be treated with biologics. Since RA is associated with an increased risk of bone fractures, prevention of osteoporosis is important.
The patient's risk for cardiovascular disease should be assessed as a part of overall disease assessment. Patient education aims to ensure the compliance of the patient with long-term treatment. Patients are encouraged to exercise and to maintain their muscle strength. The multi-disciplinary team at the rheumatology clinic follows the patient's condition and disease activity, and when the RA has been in stable remission for a given period of time, e. Goals The aim of these guidelines is to improve and harmonise the diagnosis and management of RA to ensure that the quality of life, the working capacity and the functional capacity of patients with RA are maintained.
Target groups These guidelines are targeted at health care professionals at all levels e. RA begins as an immunological disturbance, and circulating biomarkers, e. Preclinical rheumatoid arthritis autoan Elevated rhe Early clinical symptoms are non-specific.
The epidemiology of early infl Most patients with undifferentiated arthritis do not have RA and their condition may resolve without treatment, but persisting arthritis must be followed-up and treated. Patients with arthritis who have a high risk of developing RA should be identified and treated promptly. Miten tuo EULAR recom Prevalence and The inc Prevalence and in These figures are comparable to the ones in Finland, where the overall annual incidence is59 among females and 30 among males «Puolakka K, Kautiainen H, Pohjolainen T ym.
The prevalence of RA is 0. Nationwide pre Low and stable pr The ris Epidemiological studies in The variation of these figures is due to variations in the criteria used to define RA as well as to differences in geographical region and timing of the studies. The global prevalence has been estimated to be 0. The global burden of r The prevalence of RA is 2—3 times higher for females than males.
The female risk is particularly high after delivery of the first child: it is 2. Aetiology Both genetic and environmental factors affect the development of RA. Genetics of rheuma Occurrence of r Twin concor Concordance is 3.
Genetic susceptibility and environmental factors interact in the aetology of RA. A new model f A gene-environmen Thus far, tobacco smoking is the only known modifiable risk factor for RA. Mortality and causes of Death rates Risk of mortality Determinants o Mortality in rheu Early effective treatment, and the use of methotrexate and biologics are associated with lower mortality «Listing J, Kekow J, Manger B ym.
Survival, comorb No increased mor Mortality rate Mortality t Disease durati The overall mortality of patients diagnosed with RA in Finland since the year was not increased according to statistics extending, however, only to the year «Puolakka K, Kautiainen H, Pohjolainen T ym.
No inc Diagnostic goals Importance of early diagnosis The goal is to establish the diagnosis as early as possible and to promptly start effective pharmacotherapy aiming at early remission. Signs and symptoms Joint inflammation is the sine qua non for a diagnosis of RA. Usually there is inflammation in several joints. The inflamed joint is typically swollen, stiff in the morning and painful on movement, but not necessarily painful at rest. In typical cases, joint inflammation is symmetrical.
Joint symptoms usually develop slowly and progress gradually, often in a relapsing-remitting pattern. RA may cause inflammation in the cervical spine, but symptoms of the lower back are not characteristic of RA.
The more active the joint inflammation is, the longer is the duration of morning stiffness. Joint inspection and palpation are important. The inflamed joint is swollen and usually tender on palpation. Clinical examination of the joints requires experience. Joint erosions usually develop first in the MTP joints «Eroosiot ilmaantuvat ensin jalkateriin. One of the therapeutic goals is to have the patient on antirheumatic pharmacotherapy before joint erosions and permanent damage develop.
The erythrocyte sedimentation rate ESR and the concentraton of C-reactive protein CRP in the serum or plasma reflect disease activity acceptably well, but are not always increased.
Erythrocyte sedimentation rate, Only h
The dosage regime for Kela hexacetonide intraarticular injection for JIA in children is 1 mg/kg for large joints (knees, hips. 15 g x 1's; g x 1's;5 g x 1's. /thailand/image/info/kela cream percent/ Form. Kela lotion %. Packing/Price. 30 mL x 1's;60 mL x 1's. very common (more than 1 in 10 animals displaying adverse reactions during Initial treatment is a single dose of mg meloxicam/kg body weight on the. clinically effective doses of inhaled FP, or oral prednisolone, but not inhaled Evaluation of the amount of ELF using the urea method Authors: Vilegzhanina TG1; Affiliations: mucolytics, steroids, and cromoglicate acid drugs as well. Lähelmä S., Kirjavainen M., Kela M. et al. If this is not enough, two medications, or a described, especially for different age groups. Inpatient rehabilitation arranged in rehabilitation centres later referred to as specialised units may be useful for supporting self-rehabilitation programmes, for improving compliance and for maintaining the functional capacity of patients with multiple problems. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Pay special attention to young women, as leflunomide may delay plans for pregnancy due to long withdrawal time of leflunomide. Management should be adapted ler devices and peak flow meters.To browse Academia. Nikolaos Papadopoulos. Despite the availability of several formulations of inhaled corticosteroids ICS and delivery devices for treatment of childhood asthma and despite the development of evidence-based guidelines, childhood asthma control remains suboptimal.
Improving uptake of asthma management plans, both by families and practitioners, is needed. Adherence to daily ICS therapy is a key determinant of asthma control and this mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices.
The potential adverse effects of ICS need to be weighed against the benefit of these drugs to control persistent asthma especially that its safety profile is markedly better than oral glucocorticoids. This article reviews the key mechanisms of inhaled corticosteroid action; recommendations on dosage and therapeutic regimens; potential optimization of effectiveness by addressing inhaler technique and adherence to therapy; and updated knowledge on the real magnitude of adverse events.
Kian Chung. Adnan Custovic. Karen Primero. Canadian respiratory journal : journal of the Canadian Thoracic Society. Francine Ducharme. Stefan Zielen. Xingnan Li. Andrew Harver , Jan Warren-Findlow.
David Carmona. Eric Bateman. Kenneth Bautista. Adam Atherly. Gandy Sudirgouw. Thomas Casale. Charles Feldman. Mario Castro. Jose Emparanza. Ha Nguyen. Alessandra Scaparrotta , Daniele Rapino. Bhupendrasinh Chauhan. Alessandra Scaparrotta. Karen Rance. David Montani , C. Riccardo Polosa , Pasquale Caponnetto. Delgado , Franchek Drobnic. Jose Valverde-Molina. Riccardo Castagnoli , Amelia Licari.
Jan Raaijmakers. Log in with Facebook Log in with Google. Remember me on this computer. Enter the email address you signed up with and we'll email you a reset link. Need an account? Click here to sign up. Download Free PDF. International consensus on ICON pediatric asthma. Elham Hossny. Related Papers. Expert Review of Respiratory Medicine Acute asthma exacerbations in childhood: risk factors, prevention and treatment. The use of inhaled corticosteroids in pediatric asthma: update.
Adolescent Health, Medicine and Therapeutics Asthma control in adolescents: role of leukotriene inhibitors. Canadian respiratory journal : journal of the Canadian Thoracic Society Canadian Thoracic Society guideline update: Diagnosis and management of asthma in preschoolers, children and adults: executive summary.
Journal of Allergy and Clinical Immunology Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: A randomized controlled trial. Papadopoulos1, H. Arakawa2, K. Carlsen3, A. Custovic4, J. Gern5, R.
Lemanske6, P. Le Souef7, M. Roberts9, G. Wong10, H. Zar11, C. Akdis12, L. Bacharier13, E. Baraldi14, H. Boner17, W. Burks18, T. Casale19, J. Castro-Rodriguez20, Y. Chen21, Y. El-Gamal22, M. Everard23, T. Frischer24, M. Geller25, J. Gereda26, D. Goh27, T. Guilbert28, G. Hedlin29, P. Heymann30, S. Hong31, E. Hossny32, J. Huang33, D. Jackson34, J. Kalayci36, N.
Kling38, P. Kuna39, S. Lau40, D. Ledford41, S. Lee42, A. Liu43, R. Lockey44, K. Morikawa47, A. Nieto48, H. Paramesh49, R. Pawankar50, P. Pohunek51, J. Pongracic52, D. Price53, C. Robertson54, N. Rosario55, L. Rossenwasser56, P. Sly57, R.
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