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In the caeco-ureterocele (see definition below) heart attack grill arizona discount 80mg exforge mastercard, the upper pole of the renal duplication is dysplastic and non-functional arteria jejunalis buy 80mg exforge overnight delivery. It can be voluminous pulse pressure 41 order exforge paypal, dissociating the trigone and slipping into the urethra blood pressure medication and exercise 80mg exforge with visa, and may prolapse through the urethral meatus (caeco-ureterocele). The ureterocele orifice is tight, and located in the bladder itself or below the neck. The ureter corresponding to the lower pole moiety is raised by the ureterocele and is frequently refluxing or compressed by the ureterocele, leading to an obstructive megaureter. Occasionally, large ureteroceles are responsible for reflux or obstruction of the contralateral upper tract. Intravesical ureteroceles are mostly combined with a single kidney system and account for about 15% of cases. In girls, the ureteral orifice may be located (13): • in the urethra, from the bladder neck to the meatus (35%) • in the vaginal vestibule (34%) • in the vagina (25%) • in the uterus and Fallopian tube (6%). In boys, the ureteral orifice may be located (13): • in the posterior urethra (47%) • in the prostatic utricle (10%) • in the seminal vesicles (33%) • in the vas deferens or ejaculatory ducts (10%). In cases with a small upper pole or a slightly obstructive ureterocele, prenatal diagnosis is difficult. If prenatal diagnosis is impossible, the following clinical symptoms, besides incidental findings, can reveal the congenital anomaly at birth or later: • At birth, a prolapsed and sometimes strangulated ureterocele may be observed in front of the urethral orifice. In a newborn boy, it might cause acute urinary retention, simulating urethral valves. In cases of prenatal diagnosis at birth, ultrasonography confirms the ureteral dilatation that ends at the upper pole of a renal duplication. It also demonstrates the presence of a ureterocele in the bladder, with a dilated ureter behind the bladder. At this point, it is important to assess the function of the upper pole using nuclear renography of the region of interest. Magnetic resonance urography may visualise the morphological status of the upper pole and lower moieties and of the contralateral kidney. Urethrocystoscopy may reveal the pathology in cases where it is difficult to make the differential diagnosis between ureterocele and ectopic megaureter. In some cases, clinical symptoms can lead to diagnosis: • In neonates: dribbling of urine, pyuria, and acute pyelonephritis. In some cases, the large ectopic ureter presses against the bladder and can look like a pseudo-ureterocele (22,23). Girls who present with lifelong minimal urinary incontinence, never being dry, normal bladder function, complete emptying, and normal ultrasound are very suspicious for ectopic ureter. Filling the bladder with methylene blue and checking for clear urine output from the vagina can give clear evidence of extrasphincteric ureteral ectopia. This test is also helpful in confirming a vesicovaginal fistula (in this case blue fluid is drained from the vagina). The choice of a therapeutic modality depends on the following criteria: clinical status of the patient. In a clinically asymptomatic child with a ureterocele and a non or hypofunctional upper pole, without significant obstruction of the lower pole and without bladder outlet obstruction, prophylactic antibiotic treatment is given until follow-up procedures are instigated. If decompression is effective and there is no reflux (~25% of cases and more often in intravesical ureterocele), the patient is followed-up conservatively. After an endoscopic incision, most of the children with an extravesical ureterocele (50-80%) need a secondary procedure, compared with only 18% of those with an intravesical ureterocele (32). Secondary surgery is necessary if decompression is not effective, significant reflux is present, or there is obstruction of the ipsi or contralateral ureters, and/or bladder neck obstruction. Surgery may vary from upper pole nephrectomy to complete unilateral bladder reconstruction (10,26,33-40). In an ectopic ureterocele with severe hydroureteronephrosis and without reflux, the primary upper tract approach without endoscopic decompression (partial upper-pole nephroureterectomy, pyelo/uretero-pyelo/ureterostomy and upper-pole ureterectomy) gives up to an 80% chance of being the definitive treatment (30,41). Obstruction is considered to be the presence of non-refluxing dilatation of non-ureterocele-bearing moieties (especially of the lower pole) or of an obstructive drainage pattern on diuretic renography. Ureteral reconstruction (ureteral reimplantation/ ureteroureterostomy/ureteropyelostomy and upper-pole ureterectomy) is a therapeutic option in cases in which the upper pole has function worth preserving. Both procedures can be performed through an open or laparoscopic approach (42-44). In patients with bilateral single ectopic ureters (a very rare condition), an individual approach depending on the sex and renal and bladder function is necessary. In most cases, in young children (first years of life) diagnosis is done by ultrasonography. Management includes a conservative approach, endoscopic decompression, partial nephroureterectomy, or complete primary reconstruction. Treatment Choice of treatment will depend on symptoms, function and 3 B reflux as well on surgical and parenteral choices: observation, endoscopic decompression, ureteral reimplantation, partial nephroureterectomy, complete primary reconstruction. In half, to two-thirds of children with an extravesical ureterocele a secondary procedure is needed (compared to 20-25% of those with an intravesical ureterocele). The process of formation of cystic dilatation of the vesical end of the ureter and ofdiverticula at the ureteral ostium. Impact of prenatal diagnosis on the morbidity associated with ureterocele management. Histology of upper pole is unaffected by prenatal diagnosis in duplex system ureteroceles. How prenatal ultrasound can change the treatment of ectopic ureterocele in neonatesfi The role of 99mtechnetium dimercapto-succinic acid renal scans in the evaluation of occult ectopic ureters in girls with paradoxical incontinence. Ectopic ureteroceles in infants with prenatal hydronephrosis: use of renal cortical scintigraphy. Ureterocele eversion with vesicoureteral reflux in duplex kidneys: findings at voiding cystourethrography. Incontinence due to an infrasphincteric ectopic ureter: why the delay in diagnosis and what the radiologist can do about it. Pseudoureterocele: potential for misdiagnosis of an ectopic ureter as a ureterocele. Management of ectopic ureterocele associated with renal duplication: a comparison of partial nephrectomy and endoscopic decompression. A meta-analysis of surgical practice patterns in the endoscopic management of ureteroceles. Long-term followup of endoscopic incision of ureteroceles: intravesical versus extravesical. Long-term outcome of transurethral puncture of ectopic ureteroceles: initial success and late problems. Ectopic ureteroceles: surgical management with preservation of continence-review of 60 cases. Effectiveness of primary endoscopic incision in treatment of ectopic ureterocele associated with duplex system. Recent advances in the management of ureteroceles in infants and children: why less may be more. Partial nephroureterectomy in a duplex system in children: the need for additional bladder procedures. Clinical evolution of vesicoureteral reflux following endoscopic puncture in children with duplex system ureteroceles. Ectopic ureterocele: clinical application of classification based on renal unit jeopardy. Ureterocele associated with ureteral duplication and a nonfunctioning upper pole segment: management by partial nephroureterectomy alone. Ectopic ureter with complete ureteric duplication: conservative surgical management. Surgery for duplex kidneys with ectopic ureters: ipsilateral ureteroureterostomy versus polar nephrectomy.
Patients with fibromyalgia will continue to blood pressure medication with water pill order exforge without prescription not have opioids intended to blood pressure band trusted 80mg exforge be covered prehypertension blood pressure treatment purchase 80 mg exforge visa, although an opioid taper for patients with fibromyalgia would be newly covered blood pressure medication starting with d discount exforge 80mg overnight delivery. Create a new line for five chronic pain conditions including fibromyalgia for the 2020 Biennial Review Prioritized List as shown below b. Remove all diagnoses other than chronic fatigue syndrome and modify line title ii. All providers with primary responsibility for managing fibromyalgia, chronic pain 17 Reprioritization of Certain Chronic Pain Conditions March 2019 syndrome and related conditions patients should be trained in pain science. Rehabilitation services provided under this guideline also count towards visit totals in Guideline Note 6. Less frequent monitoring may be appropriate for certain medications after safety and efficacy are established. Tapering should be unidirectional with a shared goal set by the patient and provider, generally with a 5 10% decrease monthly, and can be paused or slowed if the prescriber believes this is medically appropriate based on the patient’s overall status. Taper plans should include nonpharmacological 19 Reprioritization of Certain Chronic Pain Conditions March 2019 treatment strategies for managing the patient’s pain. Tapering should be unidirectional with a shared goal set by the patient and provider, generally with a 5-10% decrease monthly and can be paused or slowed if the prescriber believes this is medically appropriate based on the patient’s overall status. New language (without showing changes from previous version) Transitional coverage for patients on long-term opioid therapy: For patients receiving long-term opioid therapy (>90 days) for conditions of the back and spine, continued coverage of opioid medications requires an individual treatment plan which includes a taper plan. Tapering should be unidirectional with a shared goal set by the patient and provider, generally with a 5 10% decrease monthly and can be paused or slowed if the prescriber believes this is medically appropriate based on the patient’s overall status. The goal of this proposal is to expand treatment options for patients with chronic pain conditions that are currently not covered in the Oregon Health Plan, with the goal of improving patient health and safety. This proposed benefit expansion includes a menu of pharmacologic and non-pharmacologic pain treatment services that are currently not covered for these conditions. The Chronic Pain Task Force met seven times between September, 2017 and December, 2018. All meetings were public, and members of the task force received extensive written and oral public input on the proposal, including testimony from national experts on pain management and opioid tapering. The new line would include: • Fibromyalgia and four broad chronic pain diagnoses (G89. March 7, 2019 1 Chronic Pain Update • Nonpharmacologic treatments including exercise therapy, acupuncture, tai chi, acupuncture, physical therapy and cognitive behavioral therapy. For the other conditions, the proposal contains some requirements for safe and effective prescribing in alignment with the Oregon Opioid Prescribing Guidelines. For patients currently receiving opioids for fibromyalgia through an exception to the Prioritized List, and for other patients receiving prescriptions for opioids which do not align with the prescribing guidelines, the proposal includes coverage of opioids during an individualized taper plan. The plan must include a goal of achieving cessation of opioids, though the taper plan may be slowed or paused if appropriate. There is also an option to not make any changes to the current prioritization of fibromyalgia and certain other chronic pain conditions due to the low level of effectiveness for various therapies and due to the other consequences of reprioritizing these diagnoses in the funded region, such as an increase in coverage for opioid medications. At no time has the proposal affected opioids being prescribed for other funded conditions under the Oregon Health Plan. For patients who are currently receiving opioids for fibromyalgia despite this guideline, the new coverage proposal may result in them being required to begin an individualized taper plan. Patients receiving opioids for the other four chronic pain conditions under consideration could be required to taper as part of Oregon Health Plan coverage, but only if their current prescriptions do not align (or cannot be adjusted to align) with safe and effective prescribing as outlined in the Oregon Opioid Prescribing Guidelines. Decisions about the pace of any taper plan would be made by prescribers, not health plans, and taper plans could be paused if needed. As has always been the case, providers may refuse to prescribe opioids, or decide to initiate a taper plan based on their clinical judgement. This leaves about 27,000 recipients who might be eligible for the new nonpharmacologic benefits, though some of these might already have access to certain benefits such as physical therapy because of other orthopedic conditions. Of the 90,000 recipients, about 40,000 had at least one opioid prescription during the time period and 13,000 had at least 120 days supply of opioids during that year. These cost adjustments assume no significant impact on pharmaceutical costs, as most of the patients receiving opioids would already be eligible to receive them due to a comorbid funded diagnosis. They assume no significant cost from increased access to pregabalin as it will be available in generic form in 2019. The Commission’s legislative mandate is to rank services “by priority, from the most important to the least important, representing the comparative benefits of each service to the population to be served. These are used to determine a score which ranks the line under consideration relative to other lines on the Prioritized List. The Commission could choose to accept the proposal as presented or to adopt a modified version. Alternately, it could decide not to create a new line for the reprioritization of these services at all. Whether or not the Commission creates the new line, the Commission will consider modifying Guideline Note 60, Opioids for Conditions of the Back and Spine, to remove the existing reference to an end date for tapering that has already passed (January 1, 2018) and to update language related to tapering in light of the work of the Chronic Pain Task Force. They decided to reprioritize back pain to the funded region of the Prioritized List which allowed access to evidence-based treatments, but also restricted opioid coverage because of a lack of evidence of benefit, and concerns given the opioid epidemic. The new suggested changes to the back and spine guidelines are to remove references to dates that have passed and to consider adding language allowing for a more individualized taper plan. Materials for the March 14th meetings will be posted on Thursday, March 7th at. You can attend the meetings, which are open to the public, and speak during time set aside for public comment. You can listen to the meetings by dialing 1-888-204 5984, participant code 801373 and also register for the meeting webinar at attendee. What is the comparative effectiveness of newer interventions for the treatment of osteoarthritis of the kneesfi Does the comparative effectiveness of newer interventions for the treatment of osteoarthritis of the knees vary by: a. What are the harms of newer interventions for the treatment of osteoarthritis of the kneesfi Whole body vibration appears to be popular based on its widespread availability for home purchase, but the physical experience of doing this intervention might not be universally appealing. Resource Allocation the machines for home use range from $100 to $250 to thousands of dollars. Clinic-based treatments would be low to moderate expense depending on what is charged and the frequency of treatments. Balance of Benefits and Harms We have low confidence that whole body vibration improves intermediate-term function but not to a clinically significant degree, and it is similar to exercise and strength-training programs in terms of pain. Some patients have preferences for or against nonallopathic treatments, which leads to moderate variability in values and preferences. It is a strong recommendation because available evidence supports inefficacy rather than clinical benefit. A daily supplement would likely be acceptable to many patients, so we would expect low variability of values and preferences. Resource Allocation Glucosamine and chondroitin are inexpensive daily supplements. Individual patient data meta-analysis showed that glucosamine alone has no effect. Because these are over-the-counter supplements, product quality may vary significantly. Balance of Benefits and Harms We have low to moderate confidence that glucosamine, chondroitin, or the combination has no effect on long-term pain or function. We have low confidence that chondroitin or the combination with glucosamine may improve intermediate-term pain and function. We make a weak recommendation against coverage for chondroitin and glucosamine-chondroitin because evidence supports intermediate term improvements in pain and function. Evidence suggests glucosamine alone is an ineffective intervention, so we make a strong recommendation against coverage. However, a single minimally invasive intervention would likely be appealing if it offered long-term relief and had few risks.
Purchase exforge with american express. Using the Omron Blood Pressure Monitor.
False negatives occur soon after acute hepatitis C onsets arrhythmia kidney function quality exforge 80mg, and in association with immunosuppression or renal failure 5 cheap exforge 80mg online. This information guides the management of chronic hepatitis C infection including the response to blood pressure medication liver disease exforge 80mg low price treatment arrhythmia lyrics exforge 80 mg. Treatment Acute hepatitis C infection may be clinically self-limited but commonly leads to chronic infection and liver damage. A combination of antiviral agents is necessary: pegalated interferon plus ribavirin. Chronic hepatitis C requires surveillance for progression to cirrhosis, liver failure and the development of hepatocellular hepatoma. Super-infection tends to result in a more severe hepatitis than hepatitis B alone; further, 80% go on to chronic infection. Co-infection with both B and D viruses causes chronic hepatitis D infection in less than 5% of persons. Hepatitis D infection has the highest morbidity and mortality rate of all the hepatitis infections. The presentation is that of acute hepatitis or a flare of hepatitis, and the disease can rapidly evolve into cirrhosis, liver failure or hepatocellular carcinoma. Domestic animals are a common reservoir for the hepatitis E virus; some surveys indicate infection rates exceeding 95% among domestic pigs in endemic countries. These patients may also experience malaise, fever, nausea, vomiting, anorexia, abdomen discomfort, headaches and fatigue. It is not clear if acquisition of an acute infection will provide lifelong immunity. It is not clear if the immune globulin from developing countries would be more effective. Travelers to endemic countries should be advised not to consume any uncooked food or untreated water. Safe practices, such as hand washing prior to eating and no swimming in First Principles of Gastroenterology and Hepatology A. An experimental vaccine based on recombinant viral proteins has been developed and tested in a population of military personnel working in a developing country. Unclear is if the vaccine offers long-term protection or is cost-effective for this generally mild disease. About 90-95% of the North American population is seropositive, most after subclinical infection. Symptomatic infections present with infectious mononucleosis characterized by fatigue, headache, pharyngitis, fever, posterior cervical chain adenopathy, splenomegaly and lymphocytosis. Mild hepatitis is a common presentation, but jaundice, hepatomegaly and severe hepatitis are rare presentations. Herpes simplex and yellow fever) account for less than 1% of all acute viral hepatitis in North America. Complications of Acute Viral Hepatitis Most patients with viral hepatitis recover completely. The most important complication is the development of chronicity, which may follow hepatitis B, C and D. This complicates acute hepatitis B infrequently in adults but occurs in acute hepatitis C in over 70% of cases. Chronic hepatitis is suspect if symptoms and/or elevated serum aminotransferase levels persist beyond six months. Fulminant Liver Failure Fulminant liver failure is the development of acute liver cell injury proceeding to liver failure and hepatic encephalopathy within 8 weeks in a patient without any known previous liver disease. Clinically, the patient deteriorates with development of deep jaundice, confusion and drowsiness. At this stage, the mortality rate exceeds 50% unless a liver transplant can be performed rapidly. Death may occur from infection, hypoglycemia, increased intracranial pressure with cerebral edema, or renal failure. Massive hepatic necrosis leads to a shrunken liver in which the architecture collapses histologically. Usually a liver biopsy is not required; the procedure is associated with considerable bleeding risk unless done by the transjugular route. Cholestasis Occasionally, acute viral hepatitis exhibits a cholestatic phase, in which the patient becomes intensely pruritic and jaundiced. Relapsing (Biphasic) Hepatitis Clinically, these patients begin improving, only to have a recurrence of the signs and symptoms of their hepatitis. Hepatitis C is characterized by repeated and wide fluctuations in liver aminotransferase values, but a true biphasic clinical course is uncommon. This is due to circulating immune complexes of viral proteins and antibody, with complement activation. Extrahepatic manifestations in acute hepatitis A are uncommon, but include arthritis, vasculitis, thrombocytopenia and aplastic anemia. In both hepatitis B and C, about 5-10% of cases initially develop a serum-sickness-like syndrome characterized by skin rash, angioedema and arthritis. Other immunologic manifestations include pericarditis, aplastic anemia or neurologic abnormalities such as Guillain Barre syndrome. The extraintestinal manifestations associated with chronic hepatitis will be discussed in the next chapter. Summary Acute viral hepatitis is usually a self-limited disease and in most cases requires supportive care only. For the few patients who develop fulminant liver failure, liver transplantation will be the only treatment option. Introduction the term chronic hepatitis means active, ongoing inflammation of the liver that persists for more than six months, being detected by biochemical and histologic means. Typically, biochemical tests are used to identify and follow patients with chronic hepatitis. Liver biopsies serve to define more precisely the nature of the chronic hepatitis, and to provide useful information regarding the extent of damage and prognosis. Histologically, chronic hepatitis is characterized by infiltration of the portal tracts by inflammatory cells. These cells are predominantly mononuclear, and include lymphocytes, monocytes and plasma cells. Liver biopsy is the gold standard to evaluate the grade (degree of inflammation) and stage (degree of fibrosis/cirrhosis) of chronic viral hepatitis. Histologic or inflammatory activity (A score) is determined by an algorithm incorporating the amount of portal and lobular inflammation and necrosis into a score from A0 A3. The degree of fibrosis (F score) is evaluated separately to obtain the stage of disease and ranges from F0-F4 (Figure 1-4). Other causes include autoimmune hepatitis, drug-induced hepatitis, Wilson’s disease, 1-antitrypsin deficiency, and steatohepatitis. Primary biliary cirrhosis and primary sclerosing cholangitis may occasionally mimic chronic hepatitis, but are not usually classified as such. Table 2 summarizes an approach to help determine the etiology of chronic hepatitis. A careful assessment of risk factors is helpful in determining the cause of chronic hepatitis (Table 2). The rate of transmission via needle stick injury varies with the type of virus exposure, bore size of the needle, and whether the needle is hollow or not (Table 3). In most cases, selected laboratory tests will provide confirmation of the diagnosis. This portal tract contains a chronic inflammatory infiltrate that is confined to the portal triad and does not extend past the limiting plate (arrowheads). Inflammatory cells are shown infiltrating and destroying the periportal hepatocytes (arrow) and disrupting the limiting plate (interface necrosis) (arrowheads). F1= Minimal fibrosis without bridging; F2/3= Bridging fibrosis in which fibrous tissue connects the joining triads; F4= Cirrhosis. The slide on the bottom right represents chronic hepatitis and a hepatocellular carcinoma. The histologic activity is dependent primarily on the degree of interface necrosis but lobular necroinflammatory foci are also included in grading.
Hypersensitivity vasculitis associated with 2-deoxycoformycin and allopuri nol therapy blood pressure medication causes nightmares buy 80 mg exforge free shipping. S Diagnostic methods No in vivo or in vitro method is currently available for diagnosis other than re-challenge blood pressure chart 40 year old male cheap exforge master card, which is hazardous due to blood pressure chart adolescent order exforge 80mg on line life-threatening pneumonitis (published) hypertension impact factor purchase exforge 80mg otc. Subungual splinter hemorrhage: multiple, painless, more frequent with sorafenib (60% to 70%), than sunitinib (30%). Periorbital edema (5 to 10% with sunitinib), facial eruption (seborrheic derma titis like, with periorbital aspect), 50% with sorafenib; 1 to 2 weeks after beginning treatment; may be associated to scalp erythema, scalp dysesthesia (sorafenib), frequent in the first three weeks; disappears spontaneously, flushing (sorafenib), bullous dermatitis (sunitinib), stomatitis (sorafenib, sunitinib), yellow skin discoloration (sunitinib), hair depigmentation (sunitinib), hair modification and alopecia (sorafenib), kystic, hyperkeratosic papules, keratoacanthoma (sorafenib). S Management When possible, switch to non calcineurin inhibitor everolimus (mammalian target of rapamycin). S Diagnostic methods One case with a positive lymphocyte stimulation test and challenge test in allergic liver injury. Used in the treatment of ovarian, breast cancer and bladder tumors (intravesical instillation). S Diagnostic methods One case of positive leukocyte migration test to vincristine. Hand-foot syndrome associated with short infusions of combination che motherapy with gemcitabine and vinorelbine. Incidence and syndrome of acute shortness of breath following vinca alka loids in patients receiving mitomycin. Maculopapular rash, occuring within the first weeks of treatment, often transitory, rarely a cause of discontinuation of treatment; pityriasis-rosea like rash, toxic erythema, exfoliative dermatitis, purpuric rash. Others: erythroderma, linear IgA bullous disease, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (rare), lichen planus eruption (sometimes with photosensitive distribu tion), lichen planus pemphigoides, psoriasis (induction, exacerbation), palmo plantaris pustulosis, lupus erythematosus, photosensitive eruption, pemphigus, bullous pemphigoid, lymphomatoid drug eruption, vasculitis, Henoch-Schonlein purpura • Respiratory: dry, non-productive tickling cough. S Diagnostic methods Skin tests (anaphylactic or cutaneous reactions) Intradermal: 0. Conversely, bradykinin could increase the formation of prostaglandins and leukotrienes. In addition, a decrease in bradykinin degradation increases the synthesis of bradykinin and/or related kinins. Potential role of vasomotor effects of fibrinogen in bradykinin-induced angioedema. Acute adverse reactions associated with angiotensin-converting enzyme inhibi tors: genetic factors and therapeutic implications. Angioedema associated with angiotensin-converting enzyme inhi bitor use: outcome after switching to a different treatment. Biochemical basis of angioedema associated with recombinant tissue plasmino gen activator treatment: an in vitro experimental approach. Amiodarone-induced vasculitis and a review of the cutaneous side effects of amiodarone. S Management Switch to ticlopidine but serious side effects may occur (diarrhea, neutropenia, thrombocytopenic purpura); cross-reactivity has been documented rarely between these two thienopyridines. Coumarin derivatives: warfarin, phenprocoumon, acenocoumarol the drugs are the therapeutic of choice for maintenance anticoagulation therapy. Skin tests and re-exposure contrain dicated Drug Allergy chapter v • 219 Skin tests: not available Specific IgE assay: assay not available S Mechanism In the pathogenesis of cutaneous necrosis, recent hypotheses favour the combined role of local fac tors and a transient imbalance of coagulation mechanisms leading to a hypercoagulable state. Contrary to phenindione, which is also an indanedione derivative, very few cases of immunologic reactions have been described. S Risk Factors Delayed allergic skin reactions: Female gender, obesity, and repetitive or long-lasting treatment. Hormonal factors, longer persistence of heparins in subcutaneous adipose tissue or a relationship to the lipase activity of heparins have been proposed to explain the gender difference. Often complicated by disseminated thrombosis of vessels in the skin and in other organs. Challenge test: Performed with increasing doses up to one daily defined dose and should be followed from day 1 up to day 5-7, as a positive reaction may occur only after several days. However, the allergenic epitopes causing the different hypersensitivity reactions are still unknown. In one study, 81% of patients with delayed heparin allergy showed cross-reactivity to danaparoid and 45% showed cross-reactivity to pentosanpolysulfate. Use low molecular weight heparin or heparinoids (beware of cross-reactivity) Use hirudin. Hypersensitivity reactions to anticoagulant drugs: diagnosis and manage ment options. Tolerance to intravenous heparin in patients with delayed-type hypersensitivity to heparins: a prospective study. Delayed-type hypersensitivity to the ultra-low-molecular weight heparin fon daparinux. Tolerance of recombinant hirudins and of the new synthetic anticoagulant fondaparinux. Delayed-type hypersensitivity skin reactions caused by subcutaneous unfractionated and low-molecular-weight heparins: tolerance of a new recombinant hirudin. S Management Alternative therapy: Argatroban, a synthetic thrombin inhibitor, was successfully used in patients with intolerance to heparin and hirudin. Anaphylactic and anaphylactoid reaction associated with lepirudin in patients with heparin-induced thrombocytopenia. S Management Clopidogrel is nowadays the first-line platelet aggregation inhibitor. Rash with both clopidogrel and ticlopidine in two patients following percutaneous coronary intervention with drug-eluting stents. Beta-blockers decrease endogenous adrenaline secretion by blocking beta-2-receptors at synapses, and inhibit beta 1 effects of exogenous and endogenous adrenaline on the heart. Association between beta-blockers, other antihypertensive drugs and psoria sis: population-based case-control study. Epidermal necrolysis secondary to timolol, dorzolamide and latanoprost eye drops. Drug AllergyDrug Allergy - chapter vchapter v •• 235235 Bosentan An endothelin receptor antagonist approved for the treatment of pulmonary arterial hyper tension. Drug Allergy chapter v • 237 Calcium channel blockers Used in cardiology to manage ischemic heart disease or high blood pressure. S Clinical manifestations • Cutaneous: pruritus, urticaria, angioedema (rare), maculo-papular rash, exfoliative dermatitis, erythroderma, peripheral edema, flush (pharmacodynamic effect), erythema multiforme (someti mes severe), Stevens -Johnson syndrome, toxic epidermal necrolysis (exceptional), photosensitivity and pigmentation (frequent), acute generalized exanthematous pustulosis (usual with diltiazem), lupus erythematosus-like lesions, hypersensitivity syndrome, psoriasiform eruption, vasculitis (rare), gingival hypertrophia, alopecia. S Incidence Allergic contact dermatitis in 14-38% after transdermal clonidine patch. S Clinical manifestations • Cutaneous: xerostomia (frequent), rash, pruritus, urticaria, angioedema (less frequent), Raynaud’s phenomen (rare), psoriasis exacerbation (rare), lupus erythematosus (rare). Results of a French nationwide survey of cutaneous side effects of ketopro fen gel reported between September 1996 and August 2000 (Article in French). Intradermal skin tests (1%): positive for furosemide as well as for chlorothiazide, bumetanide and sulfamethoxazole-trimethoprim (in one patient). S Clinical manifestations • Cutaneous: lupus erythematosus (+++), one-to-two years after initiation (musculo-skeletal com plaints, fever, weight loss); Sweet’s syndrome, rash, pruritus, angioedema, (rare), fixed drug erup tion, vasculitis, contact dermatitis (occupational). The two main hypotheses are: 1) Stimulation of T cells by the drug leading to reactivation of herpes virus harbored in T cells. The virus-stimulated T cells show subs tantial cross-reactivity with certain drugs; administration of the drugs leads to an expansion of these specific T cells, which continues after cessation of the drug due to the persistance of the viral anti gens. Drug Allergy chapter v • 249 Pentoxyfylline A purine derivative used as vasodilatator to relieve symptoms in some cases of intermittent claudication. S Clinical manifestations • General: anaphylactic shock • Cutaneous: urticaria, angioedema, pruritus, peripheral edema. Seroconversion is associated with male gender and insulin-dependent mellitus; these patients may be at increased risk on subsequent exposure. Complement activation (by heparin-protamine complexes or by interaction with protamine-antipro Drug Allergy chapter v • 253 tamine IgG antibody complexes leading to generation of C3a, C4a, C5a). Premedication with antihistamines and steroids reduces the severity of an allergic reaction (contro versial) References Rapp U, Liekenbrocker T, Kappa A, et al. Delayed-type hypersensitivity to protamine as a complication of insu line therapy. Single doses of intravenous protamine result in the formation of protamine-specific IgE and IgG antibodies. A biological approach in a patient with psoriasis and bullous pemphi goid associated with associated with losartan therapy. S Clinical manifestations • General: hypersensitivity syndrome: hypotension, angioedema, polymyalgia syndrome, myopathy, dermatomyositis, eosinophilia, elevated IgE levels.