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Consumer products as a cause of fragrance contact sensitisation and allergic contact dermatitis 4 symptoms syphilis order 250mg lopinavir amex. Clinical relevance Clinical relevance is a concept used to treatment 4 letter word lopinavir 250 mg without prescription describe the significance of a positive (allergic) patch test reaction for an individual patient: a reaction is deemed relevant if contact allergy to medicine 257 buy 250 mg lopinavir visa the substance is associated with previous or current episodes of allergic contact dermatitis walmart 9 medications buy discount lopinavir 250mg online. As these requirements may be met to a varying extent, the validity of relevance information as reported in clinical studies may also be variable. However, information on clinical relevance is important, in principle, because the proportion of currently relevant sensitisations reflects the amount of current exposure and resulting disease state, which may increase or decrease with time. In this way, current relevance also reflects the direct burden of a fragrance contact allergy to the individual and indirectly to society. Further important aspects of the evaluation of clinical relevance as a final step of patch testing have been discussed (92-95). Generally, clinical relevance is categorised as “current”, “previous” or “unknown”. Further differentiation has been introduced by adding information on: • Occupational versus non-occupational causation; and • the level of certainty of the relevance statement. In some cases, clinical relevance may not be established due to: • Immunological cross-reactivity with an individual allergen, diagnosed or not; • Active sensitisation by the patch testing; • Contact sensitisation not caused by the substance, but by a contaminating constituent; or • Failure to test with a true hapten. It should be noted that this statement on clinical relevance refers to the past history of a patient. This implies that a lack of, or unknown, clinical relevance does not make future allergen avoidance unnecessary. In the context of contact allergy to fragrance ingredients, a number of alternative concepts of relevance have been used, for example: • A history of intolerance to perfume or to perfumed products; • A history of intolerance to perfume actually containing the allergen diagnosed; • Detection of the culprit allergen in a perfume previously used. Elicitation with clinical symptoms/signs, current and past In case reports or small series, the clinical relevance of positive patch test reactions is usually well established and presented in detail. The studies can be subdivided into those which focus on medical history, patch testing with consumer products or detection of specific allergens in consumer products used by patients. Medical history A series of studies conducted in the 1990s showed that most individuals with contact allergy to fragrance ingredients were aware that they could not tolerate fragranced products on their skin and were able to specifically name product categories that initiated their disease (9). In this context, colognes, deodorants and lotions were named significantly more often by fragrance allergic dermatitis patients than by patients without fragrance contact allergy (3). If these conditions were not met, but skin contact to items generally containing the item was likely, “possible” was used. Table 4-11: Extract from ((62) Table 3) regarding the proportion of patients with “present clinical relevance” (see text) and “past clinical relevance” (criteria not given). Prior to the test, the history of adverse reactions to fragrances was classified as “certain” (6. The combination of the two mixes was important, as more patients with a “certain” history, but also independently from history, reacted to just one of the mixes rather than to both. Danish Contact Dermatitis Group 2005-2008 (66) In 12302 consecutive patients patch tested in seven dermatology clinics and three university hospitals, 10. Clinical relevance covered current and/or past relevance based on: 1) medical history; 2) results of patch and/or use tests; 3) ingredient labelling: or 4) chemical analysis. These proportions were higher than the average for other cosmetic allergens such as preservatives and hair dyes, which gave relevant reactions in about 50% of those positive, as did Myroxylon pereirae. Myroxylon pereirae itself is not used in cosmetics as it is banned, but sensitisation may be caused by exposures to related substances and thus relevance may be difficult to determine. Cosmetic products Fragrance formulae from cosmetic products Popular fine fragrances (5), as well as toilet soaps, shampoos, lotions, deodorants, and aftershaves have been shown to provoke allergic contact dermatitis in patients when used for patch testing (5, 6, 97, 98). Moreover, commercially available fragrance formulae and dilutions of individual fragrance allergens were potent elicitors of allergic contact dermatitis under simulated use conditions (10, 99, 100). This was much more prevalent than those patients in whom no positive reaction to their deodorant was observed. This observation supports the notion that the respective fragrance allergens are important in contact allergy to fragrance ingredients caused by deodorants, supporting data regarding exposure (chapter 10. Table 4-13: Extract from ((105) Table 2) on the frequency of positive reactions to fragrance allergens in patients with vs. However, notable differences were: (i) the greater relative importance of Evernia prunastri (Oak moss absolute); and (ii) generally an extremely high proportion of positive reactions to various other fragrance ingredients. Elicitation in diagnostic patch tests without clinical history In a variable proportion of patients, a positive patch test reaction does not correlate with recent or past episodes of presumptive allergic contact dermatitis. Apart from particular circumstances, such as cross-reactivity or reactivity to contaminants outlined above, there are several possible explanations for this: • the patch test reaction was a false-positive (irritant). Sometimes, a repeated open application or provocative use test is employed to mimic “normal” exposure to the allergen. Moreover, the positive result supports the necessity of future allergen avoidance. Apart from the risk of developing allergic contact dermatitis in the future, sensitisation means an alteration of the immune status of the individual. Health related quality of life Skin diseases in general are known to affect quality of life significantly (106); this also applies to eczema, where most studies concern atopic dermatitis and hand eczema patients (107, 108). Hand eczema has a poor prognosis and may affect the self-image, limit social activities and lead to occupational restrictions (108, 109). The quality of life in hand eczema patients with fragrance contact allergy is affected in a similar degree as patients with other contact allergies (110). In a questionnaire study of 117 patients recently diagnosed with contact allergy to fragrance ingredients, most presented with hand or facial eczema. In response to the question if and how fragrance allergy had affected their life situation, 67. Occupational restrictions Contact allergy is known to influence severity and prognosis of hand eczema (112, 113) including risk of sick leave (110). Fragrance contact allergy is mostly of a non-occupational origin (88) related to the personal use of scented cosmetics, but may have secondary occupational consequences. This may be due to exposure to fragrance ingredients also in the work place or because hand eczema has developed. Hand eczema itself may make it impossible to remain in the trade even if protective equipment is used. In young people, fragrance allergy may limit the choice of occupations, as it will be difficult to work as a hairdresser, cosmetologist or in other occupations with a significant skin exposure to fragranced products. No specific cost estimates for fragrance allergy exist, but the yearly total costs of contact dermatitis in Western Europe was estimated to be 5. Prices were based on the Allergy White Paper (1997) and on results of investigations and extrapolations of known data for Western Europe (114). Fragrance allergy is the second most frequent cause of contact allergy after th nickel allergy and is seen in every 10 patient investigated for contact allergy. Even a modest reduction in nickel allergy has been estimated to have the value of 12 million Euro/year/million people in Denmark (Environmental Project Nr. These estimates show that the cost of contact allergy in the population may be considerable. Allergen avoidance Generally, “allergen avoidance” can be regarded as having two aspects: (i) primary prevention of the acquisition of contact allergy achieved by avoiding or limiting exposure of the general population, or certain parts of it, to allergens; and (ii) secondary prevention in terms of avoiding (re-)elicitation of allergic contact dermatitis in sensitised individuals. Primary prevention: limiting or eliminating exposure to allergens in the population the main aim of public health is the primary prevention of disease in populations. Allergic contact dermatitis (to fragrances) has the potential to have a significant impact on quality of life, including effects on fitness for work (chapter 4. Moreover, it is a common phenomenon and therefore a reduction of exposure to potential (fragrance) allergens must be an objective of effective Public Health measures. Means of limiting or eliminating exposure to fragrance allergens include the following: • Prohibition by regulatory measures or other means. Substitution by a component which is chemically different, but effectively not different in terms of allergenicity or cross-reactivity, is not adequate. One difficulty with this approach is that sometimes no sensitisation data exist for those components of a fragrance formula which are used to replace a “known sensitiser”. Secondary prevention: avoiding re-exposure to (a) specific sensitiser(s) in clinically diagnosed individuals In clinical dermatology, avoidance of re-exposure to an allergen is central to the care of sensitised patients. Contact sensitisation, as a latent condition, persists life-long, and therefore allergen avoidance is the only means of avoiding potentially severe and/or handicapping disease, which affects quality of life and may affect fitness for work, i. In this context, the valid diagnosis of sensitisation, by patch testing (95) with standardised materials, is a prerequisite of successful allergen avoidance.
It provides contnuous informaton on the progress being made to medicine keeper buy generic lopinavir 250mg on line achieve goals and alerts staf and managers to chapter 9 medications that affect coagulation lopinavir 250 mg for sale problems medications for schizophrenia 250 mg lopinavir, providing an opportunity for these to medicine bg cheap 250 mg lopinavir otc be resolved early. Efectve monitoring relies on accurate records being maintained for all patents and periodic, regular reportng of actvites. It relies on data generated through routne informaton as well as from other sources such as research studies. There are various types of evaluaton; Process evaluaton measures the quality of programme implementaton and assesses coverage. Regular evaluaton is required not simply for surveillance purposes but is necessary for efcient management of the programme. Data may be collected through seroprevalence surveys or through the routne reportng of cases seen by health facilites. Although surveillance data is an important source for M&E, surveillance should not be confused with, or substtuted for, actual programme monitoring. It provides an overview of all registered patents and should be used as a clinical and programme management tool at facility level. This will help to identfy leakages or gaps in patent management within the facility and enable the facility to implement strategies to address them early preventng adverse treatment outcomes. The informaton submited to the sub/district is entered into the electronic register and data validaton and analysis is done using this tool. Reportng on quarterly cohorts does not mean that data is collated on a quarterly; monthly data collaton is required at the lowest level of care (facility, sub-district or district level). This will ensure that meaningful acton is taken resultng in sub/ districts and provinces and ensure tmeous reportng. In each instance, sub-district data should be submited to the district within 3 weeks, district data submited to the province a week later and provincial data submited to the natonal ofce 1 week later. Yellow sheets – as soon as all the smear conversion sputum results at the end of the intensive phase (2 or 3 months) have been captured Green sheets – as soon as all outcomes have been recorded (the correct outcome as well as the outcome date). Data needs to be collated and analysed at facility level because this is the level at which quality improvements have to be made. It is recommended that on a quarterly basis standard Natonal Tuberculosis Management Guidelines 2014 89 facility reports are generated and tracked over tme. An analysis of the facility data should answer the following questons: What does the data show Informaton from additonal sporadic evaluaton can be extremely useful in providing insights into the factors contributng to the facility’s performance. This informaton may come from diferent sources such as the Facility Supervisory Checklist. Trying to identfy the underlying practces that contribute to poor programme performance is a challenge. All too frequently staf and managers become defensive and provide explanatons for programme performance that are not borne out by the data available. Building data analysis skills and instlling the practce of self-refecton is necessary at all levels in the health system in working towards systematc improvements. Treatment of Tuberculosis: Guidelines for Natonal Programmes, 3rd Editon, World Health Organisaton, 2003. A Tuberculosis Guide for Specialist Physicians, Internatonal Union Against Tuberculosis and Lung Disease, 2003. Guidance for natonal tuberculosis programmes on the management of tuberculosis in children, World Health Organisaton, Geneva. Tuberculosis Treatment Support and Adherence Guidelines, Natonal Department of Health South Africa, 2006. Interventons for Tuberculosis Control and Eliminaton, Internatonal Union Against Tuberculosis and Lung Disease, 2002. Natonal Antretroviral Treatment Guidelines, Department of Health, South Africa, 2013. Guidelines for the Preventon of Tuberculosis in Health Care Facilites in Resources Limited Setngs, World Health Organisaton, 1999. The Alcohol Use Disorders Identfcaton Test Guidelines for Use in Primary Care, 2nd Editon. Tobacco smoke, indoor air polluton and tuberculosis: a systematc review and meta-analysis. Internatonally recognized guidelines for “sensible” alcohol consumpton: is exceeding them actually detrimental to health and social circumstances Treatment of Tuberculosis guidelines, 4th Editon, World Health Organisaton, 2009 25. Recommendatons for investgatng contacts of persons with infectous Tuberculosis in low and middle income countries, World Health Organisaton, Geneva. Systematc screening for actve tuberculosis: Principles and recommendatons, World Health Organisaton, Geneva. Previous exposure results in a local delayed type hypersensitvity reacton within 24-72 hours. Keep the needle almost parallel to the skin, with the bevel pointng upwards during inserton. Isoniazid Group: antmycobacterial agent Tablet: 100mg, 300mg Injecton: 25 mg/ ml (in 2-ml ampoule) General informaton Isoniazid, the hydrazide of isonicotnic acid is highly bactericidal against replicatng tubercle bacilli. The plasma half-life, which is genetcally determined, varies from less than one hour in fast acetylators to more than three hours in slow acetylators. It is largely excreted in the urine within 24 hours, mostly as inactve metabolites. Where the standard of health in the community is low, this should be ofered routnely. It may be necessary to reduce the dosage of these drugs during treatment with isoniazid. Systemic or cutaneous hypersensitvity reactons occasionally occur during the frst weeks of treatment. Other less common forms of neurological disturbance, including optc neurits, toxic psychosis arid generalized convulsions, can develop in susceptble individuals, partcularly in the later stages of treatment and occasionally necessitate the withdrawal of isoniazid. More ofen, however, a sharp rise in serum concentratons of hepatc transaminases at the outset of treatment is not of clinical signifcance, and usually resolves spontaneously during contnuaton of treatment. Drug interactons • Isoniazid tends to raise plasma concentratons of phenytoin and carbamazepine by inhibitng their metabolism in the liver. Overdosage • Nausea, vomitng, dizziness, blurred vision and slurring of speech occur within 30 minutes to three hours of overdosage. Soluton of injecton should be stored in ampoules protected from light 2 Rifampicin Group: antmycobacterial agent Capsule or tablet: 150 mg, 300 mg General informaton A semi synthetc derivatve of rifamycin, a complex macrocyclic antbiotc, inhibits ribonucleic acid synthesis in a broad range of microbial pathogens. It has bactericidal acton and a potent sterilizing efect against tubercle bacilli in both cellular and extra cellular locatons. Following oral administraton, it is rapidly absorbed and distributed throughout the cellular tssues and body fuids; if the meninges are infamed, signifcant amounts enter the cerebrospinal fuid. A single dose of 600 mg produces a peak serum concentraton of about 10 micrograms/ml in two to four hours, which subsequently decays with a half-life of two to three hours. It is extensively recycled in the enterohepatc circulaton, and metabolites formed by deacetylaton in the liver are eventually excreted in the faeces. Since resistance readily develops, rifampicin must always be administered in combinaton with other efectve antmycobacterial agents. Natonal Tuberculosis Management Guidelines 2014 101 Dosage and administraton Rifampicin should preferably be given at least 30 minutes before meals, since absorpton is reduced when it is taken with food. This however may not be clinically signifcant and food can reduce intolerance to drugs. Adults and children: 10 mg/kg (8-12 mg/kg) daily, maximum 600mg daily, two or three tmes weekly. Contra-indicatons • Known hypersensitvity to rifamycins • Hepatc dysfuncton Precautons • Serious immunological reactons resultng in renal impairment, haemolysis or thrombocytopenia are on record in patents who resume taking rifampicin afer a prolonged lapse of treatment. Patents should be warned that treatment may produce reddish coloraton of urine, tears, saliva and sputum, and that contact lenses may be irreversibly stained. Use in pregnancy Whenever possible, the six-month regimen based upon isoniazid, rifampicin and pyrazinamide should be used. Vitamin K should be administered at birth to the infant of a mother taking rifampicin because there is a risk of postnatal haemorrhage. Adverse efects • Rifampicin is well tolerated by most patents at currently recommended doses, although gastrointestnal intolerance can be unacceptably severe. These reactons usually subside if the regimen is changed to one with daily dosage.
Each agency of the Department routinely conducts evaluations designed to symptoms 7dpiui cheap lopinavir 250 mg mastercard assess the process treatment varicose veins purchase lopinavir uk, outcomes treatment zap discount lopinavir 250 mg on-line, and effectiveness of its own programs based on what aspects of disparity are targeted symptoms 7 weeks pregnant lopinavir 250mg low price. Efforts are made to ensure all programs have measurable objectives that can be used to direct program activities and measure the benefts accruing to the target populations. To this end, the agency may directly collect data in the process of administering the program relating to performance. It may also conduct special evaluation studies to assess program outcomes and impacts. All monitoring and evaluation is designed in full recognition that in addition to actions outlined in the plan, changes in disparities are also related to ongoing efforts at various levels in government and private sector organizations, including efforts that address social determinants of health. The Affordable Care Act represents the most signifcant federal effort to reduce disparities in the country’s history. By building on the Affordable Care Act and shaping the Department’s health disparities reduction activities around the Secretary’s priorities, the Department will lead by example. Through the release of this Action Plan, the Department commits to the vision of a nation free from disparities in health and health care for racial and ethnic minority populations. Health Care Reform in Massachusetts: Implementation of Coverage Expansions and a Health Insurance Mandate. Patient Protection and Affordable Care Act of 2010: Advancing Health Equity for Racially and Ethnically Diverse Populations. Census Bureau, Current Population Reports, P60 238, Income, Poverty, and Health Insurance Coverage in the United States: 2009, U. Department of Health and Human Services, Health Resources and Services Administration, Uniform Data System, 2009. Subcommittee on Standardized Collection of Race/Ethnicity Data for Healthcare Quality. Race, Ethnicity, and Language Data: Standardization for Health Care Quality Improvement. In the Nation’s Compelling Interest: Ensuring Diversity in the Health Care Workforce. Optimizing Medicaid enrollment: Perspectives on strengthening Medicaid’s reach under healthcare reform. The Medicaid program provided services to an average of 50 million people in 2009; with the expected expansion (2014), the number could potentially increase by 16 million by 2019. Health Insurance Exchanges and new private competitive health insurance markets will help individuals and small employers select and enroll in high-quality, affordable private health plans. Special efforts should be made to reach target populations and put greater choice in the hands of individuals and small businesses. Additionally, the Affordable Care Act requires health plans and encourages state Medicaid programs to place a strong emphasis on prevention, specifcally by encouraging coverage for: i) any clinical preventive service recommended with a grade A or B by the U. Nondiscrimination: Section 1557 of the Affordable Care Act extends the application of existing federal civil rights laws prohibiting discrimination on the basis of race, color or national origin, gender, disability, or age to any health program or activity receiving federal fnancial assistance; any program or activity administered by an executive agency; or any entity established under Title 1 of the Act or its amendments. Data: Section 4302 of the Affordable Care Act contains provisions to strengthen federal data collection efforts by requiring that all federally funded programs to collect data on race, ethnicity, primary language, disability status, and gender. Additional funding of up to $335 million will be available this year for expanded services in existing health centers and $10 million for 125 planning grants to help communities without a health center to develop one. The Community Health Center program provides care to vulnerable populations by assuring access to comprehensive, culturally competent, quality primary healthcare services. Maternal, Infant, and Early Childhood Home Visitation Program: the Affordable Care Act provides support for the Maternal, Infant, and Early Childhood Visitation Program. Home visiting is an effective and relatively low-cost strategy used by public health and human services programs to foster child development and improve prenatal and postnatal health outcomes. The families that beneft from these visits are in communities with concentrations of premature births, low birth-weight infants, infant mortality, poverty, crime and domestic violence, high rates of high school dropouts, substance abuse, and unemployment. Promotoras, also known as peer leaders, community ambassadors, patient navigators or health advocates: the Affordable Care Act authorizes promotion of these community health workers uniquely skilled in providing culturally and linguistically appropriate services, particularly in diverse, underserved areas. Community health workers can play a critical role in providing enrollment assistance to racial and ethnic minorities. S Department of Health and Human Services the following healthcare initiatives and prevention programs present a unique opportunity to use innovative approaches to improve and change healthcare practices and policies across the public health system to sharply reduce disparities among racial and ethnic minority populations. The Standards are meant to be inclusive of all populations, but are specifcally designed to meet the needs of racial, ethnic, and linguistic populations that experience unequal access to healthcare services. The learning collaboratives have shown promise for improving the quality of care and clinical outcomes of underserved populations in community-based settings. Head Start programs promote school readiness by enhancing the social and cognitive development of children. Efforts include the provision of educational, health, nutritional, social, and other services to enrolled children and families. The Head Start program engages parents in their children’s learning and helps them in making progress toward their educational, literacy, and employment goals. Regional Extension Centers serve local communities around the country, focusing on those healthcare settings that provide primary care services to those who lack adequate coverage or medical care. The Steering Committee has identifed asthma disparities, chemical exposures, and healthy settings (where children live, learn, and play) as the three initial priorities for improving coordination of federal efforts and developing interagency collaborations to address environmental health risks and safety risks to children. Chloroform is a man-made by-product formed when chlorine is used to disinfect water. It is a colorless liquid with a pleasant, non-irritating smell and a slightly sweet taste. Low levels of chloroform are found in the air and in coastal waters, inland rivers, lakes and groundwater. Levels can be higher in industrial areas as well as in the air above swimming pools containing chlorine. Chloroform is used as a solvent, a substance that helps other substances dissolve. Also, it is used in the building, paper and board industries, and in pesticide and film production. It is used as a solvent for lacquers, floor polishes, resins, adhesives, alkaloids, fats, oils and rubber. Until the mid-1900s, chloroform was used as an anesthetic to reduce pain during medical procedures. You could be exposed to chloroform through: Breathing air with chloroform for a short time causes headache, fatigue and dizziness. Breathing air with chloroform for a long period damages the brain, liver and kidneys. Eating food with chloroform in it over a long period damages the liver and kidneys. Chloroform damages the liver, causing hepatitis, and it can also harm the kidneys, brain, heart and bone marrow. Respiratory injuries from chloroform exposure include respiratory depression, pneumonitis and pulmonary edema. Chloroform, which is toxic to the central nervous system, can cause a person to become unconsciousness and even be fatal at high doses. Anyone who may have been exposed to high levels of chloroform should be removed from the source of exposure immediately. Clothing that has come into contact with chloroform should be removed and discarded. Most of the population is exposed to very low levels of chloroform every day in the air, food and water we take in every day. Exposure to higher levels of chloroform is very unlikely for anyone outside industries using or manufacturing chloroform. Tests can determine the level of chloroform in blood, tissue and the air you exhale. These tests must be done a short time after exposure because chloroform leaves the body quickly. Chloroform (Environmental Health Criteria 163), Geneva, International Programme on Chemical Safety. However, there may be situations that require hospice interventions at night or weekends.
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The mucosa has intense infiltration of the colonic crypts with polymorphonuclear cells and surrounding accumulations of lymphocytes and plasma cells medications that cause hyponatremia best lopinavir 250mg. The diagnosis of ulcerative colitis is based on exclusion of infections and subsequent visualization of the rectal and colonic mucosa by flexible 62 Clinical Expression of Human Autoimmune Diseases sigmoidoscopy and biopsy and either total colonoscopy or double contrast barium enema examination treatment 4 ulcer generic 250 mg lopinavir with amex. Environmental factors medications just like thorazine buy lopinavir 250mg with amex, in particular factors that trigger detrimental mucosal immune responses to medicine in french buy lopinavir with american express enteric bacteria, are considered more important than genetic factors in the pathogenesis of ulcerative colitis (Farrell & Peppercorn, 2002). Of all environmental factors, the protective effect of cigarette smoking remains the most con sistent. Nicotine is probably the main active ingredient in this association, but the mechanisms remain unknown. In patients with long-standing disease, there is an increased risk of colonic dysplasia and adenocarcinoma. The prevalence of the disease is approximately 60 cases per 100 000, and the incidence is 3 cases per 100 000 per year (Jacobson et al. The most apparent clinical presentation of multiple sclerosis includes chronic or relapsing paralysis and problems of vision, sensation, strength, and coordination. Several disease patterns can be distinguished: relapsing-remitting (60–70%), primary progressive (10–20%), and secondary progressive multiple sclerosis (15–25%), all resulting in the accumulation of significant neurological disability (Compston & Coles, 2002). Multiple sclerosis is diagnosed based on the objective demonstration of dissemination of lesions in both time and space, and diagnosis incorporates evidence from magnetic resonance imaging (McDonald et al. Further analysis of the demyelinating lesions may reveal, besides a T cell and macrophage-dominated immune response, immunoglobulin and complement deposition, myelin protein loss, and distinct patterns of oligodendrocyte degeneration. On the basis of these findings, four patterns of demyelination have been identified, suggesting that there exist distinct pathogenetic mechanisms (Kornek & Lassmann, 2003). The primary injury is directed at the myelin itself or its cell of origin, the oligodendrocyte, being responsible for synthesis and maintenance of the myelin sheath of nerve axons. The main concept holds activated auto reactive T cells responsible for driving chronic inflammation and macrophage/microglia activation in the lesions. The presence of antibodies against myelin proteins may add to the immunopathogenetic mechanism. The estimated prevalence of disease varies between 5 and 15 cases per 100 000 (Jacobson et al. There are two peak disease incidences with different male/female ratios: before age 40, women are 3 times more commonly affected, whereas in the older age group, males predominate. The prominent clinical feature of myasthenia gravis is painless, fatigable weakness of selected muscle groups. Anti-acetylcholine receptor antibodies are present in about 85–90% of patients and, when identified in the appropriate clinical setting, are diagnostic for myasthenia gravis. Furthermore, a similar syndrome, Lambert-Eaton syndrome, is associated with antibodies against the presynaptic, voltage-gated calcium channels. Rever sibility of clinical symptoms with anticholinesterase inhibitors in myasthenia gravis is another hallmark of diagnosis. Once a diagnosis has been made, computed tomography or magnetic resonance imaging of the chest should be done to exclude an associated thymoma, which is apparent in about 10% of the patients. Myas thenia gravis is a prototypic autoimmune disease, since its antibody mediated pathogenesis is exclusively directed to the postsynaptic membrane of the neuromuscular junction. Antibodies directed to the acetylcholine receptor lower the number of functional receptors, leading to an impaired neuromuscular signal transduction, resulting in the characteristic fatigable skeletal muscle weakness. Indeed, in muscle biopsy specimens from myasthenia gravis patients, antibodies are attached to the postsynaptic membrane, receptors are lost, and postsynaptic folds are sparse and shallow. The immunopathogenetic role of the autoantibodies is further established by the occurrence of neonatal myasthenia gravis in babies born to women with the disease. In these cases, spontaneous resolution usually occurs within a few weeks due to disappearance of maternal antibodies. This haplotype has also been involved in other human autoimmune diseases, including systemic lupus erythematosus, coeliac disease, insulin-dependent diabetes mellitus, and autoimmune thyroiditis, suggesting that the respective genes could determine non-antigen specific immune dysregulation rather than specify a particular “self” target to the immune system (Garchon, 2003). This may also explain why myasthenia gravis is often associated with other autoimmune diseases, such as insulin-dependent diabetes mellitus and autoimmune thyroiditis. Clinical features of the disease are unexplained con gestive heart failure, chest pain mimicking myocardial infarction, arrhythmias, syncope, and sudden death. Early and definite diag nosis of myocarditis depends on the detection of inflammatory infil trates in endomyocardial biopsy specimens according to the Dallas criteria. Histopathology reveals lymphocytic infiltrates, interstitial oedema, myocardial necrosis, and fibrosis. These antibodies are directed against a multitude of autoantigens, such as the 1-adreno receptor and I-myosin, and have only limited sensitivity (Caforio et al. For some of these autoantibodies, there is in vitro evi dence for a functional role. On the whole, myocarditis is considered a progressive disease with three distinct, chronologically successive stages. Depending on the genetic makeup of the patient, this initiating infection may go unnoticed or may trigger an autoimmune reaction that causes further myocardial injury, eventually resulting in the typical picture of dilated cardiomyopathy (Mason, 2003). These diseases affect skeletal muscle and/or skin, leading to profound tissue modification. The prevalence of these diseases is approximately 5 cases per 100 000 (Jacobson et al. Dermatomyositis, affecting both children and adults, is more common than polymyositis, which strongly predominates in adults. Women are 66 Clinical Expression of Human Autoimmune Diseases affected twice as commonly as men. Both dermatomyositis and polymyositis present with insidious onset of symmetrical muscle weakness. The proximal muscles of the extremities are most often affected, usually progressing from the lower to the upper limbs. In the case of dermatomyositis, a characteristic erythematous rash over bony prominences of the extremities is observed. The clinical diagnosis of dermatomyositis and polymyositis is confirmed by elevation of muscle enzymes in the serum, electromyographic findings of myopathy, and biopsy evidence of myositis. The muscle fibres undergo phagocytosis and necrosis, eventually resulting in perifascicular atrophy. These effects are possibly the result of vascular damage mediated by antibodies and complement. Dermatomyositis is associated with autoantibodies directed to the nuclear antigen Mi-2, but these antibodies are of low sensitivity. Associations of environmental factors with myositis onset have been identified — for instance, intake of drugs such as penicillamine, tiopronine, and pyritinol and the old anticonvulsant trimethadione. Also, the ingestion of contaminated L-tryptophan preparations may be implicated in the development of myositis. However, the neurological symptoms are characteristic of certain types of cancer and often precede the identification of the underlying malignancy. Therefore, proper identification of the neurological disorder will be of help in finding the cancer that causes the neurological disability. Most of these disorders are immune-mediated and characterized by the presence of autoantibodies. The presence of these antibodies warrants a search for small-cell lung cancer, neuroblas toma, and prostate cancer. In paraneoplastic cerebellar degeneration, patients present with slurred speech, gait instability, and tremor. Anti-Yo antibodies, reacting with a cytoplasmic component of Purkinje cells, may be found, and these antibodies are indicative of the presence of ovarian, breast, or lung cancer. Other antibodies associated with cerebellar degeneration, such as anti-Tr and anti mGluR1 antibodies, are a sign of Hodgkin lymphoma. Ataxia with or without opsoclonus-myoclonus syndrome is related to anti-Ri antibodies, which recognize neuronal nuclei, and these antibodies have been associated with breast, gynaecological, lung, and bladder cancers. Finally, the Lambert-Eaton myasthenic syndrome is caused by antibodies to voltage-gated calcium channels, which are indica tive of a small-cell lung cancer. Overall, the paraneoplastic neuro logical syndromes are rare, affecting perhaps only 0. The pathogenetic mechanism is based on the ectopic expression of a nervous system-specific antigen by a tumour.
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