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| Vol. 28 No. 2 February 2005 |
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| David
C. Dale, MD, FACP, Editor-in-Chief Daniel
D. Federman, MD, MACP, Founding Editor Wendy Levinson, MD, FACP, Associate Editor, What's New in ACP Medicine |
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| IN THIS ISSUE |
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| PRACTICE OF MEDICINE |
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Life after Rofecoxib Shaun Ruddy, MD On September 30, 2004, when rofecoxib (Vioxx) was withdrawn from the market, two million patients were taking the drug. Aggressive direct-to-consumer marketing, funded by a $400 million annual advertising budget, had made rofecoxib the best-selling of the nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit cyclooxygenase-2 (COX-2). On October 1, 2004, many of those two million patients reached for the phone and called their doctor's office to ask, “What do we do now?” This was not an easy question to answer. Reflexively substituting one of the other selective COX-2 inhibitors—either celecoxib or valdecoxib—was probably the most common response, but perhaps not the wisest. As events unfolded and the safety of valdecoxib became an issue, simple substitution became a less attractive choice. There are theoretical reasons to believe that COX-2 inhibitors as a class may increase the rate of thrombotic events such as myocardial infarction (MI) and stroke. These agents suppress the formation of prostaglandin I2, the mediator produced by endothelium that induces vasodilation, inhibits platelet aggregation, and prevents the proliferation of vascular smooth muscle. Unlike aspirin and nonselective NSAIDs, COX-2 inhibitors do not stop platelets from making thromboxane A2, the COX-1 product that constricts blood vessels, aggregates platelets, and causes vascular proliferation. The Evidence Evidence of this risk emerged from a randomized placebo-controlled trial of rofecoxib for the prevention of adenomatous polyps; this trial showed a significant increase in cardiovascular events at 18 months in patients taking higher doses. Earlier studies had already suggested such an increase, and subsequent observational studies have supported it. As for the other COX-2 inhibitors, the initial large trial of celecoxib showed no increase in cardiovascular events at 6 months, but a retrospective analysis showed an increase at 12 months in patients who were not taking concomitant aspirin. When valdecoxib and its prodrug were used acutely to treat postoperative pain after coronary artery bypass grafting, an increase in MIs was observed. The available data indicate that there are no such increased risks for nonselective NSAIDs. These findings indicate that selective COX-2 inhibitors should be avoided in patients at high risk for thrombotic cardiovascular events. It makes little sense to add low-dose aspirin to a COX-2 inhibitor in hopes of preventing cardiovascular events, because aspirin negates the beneficial effects of COX-2 agents in preventing gastrointestinal complications such as ulcers and bleeding. Even worse, NSAIDs may interfere with the antiplatelet effects of aspirin. What about the other 95% of patients—those without cardiovascular risks—who had been taking rofecoxib? The first question should be, Why was this patient put on a COX-2 inhibitor to begin with? Possible answers include the following: (1) Some well-intentioned person in an office awash with samples of the newest COX-2 inhibitor gave them to the patient, and then the prescription was renewed—a scenario that, in my personal estimation, may account for as much as 48% of cases. (2) The patient came to the office clutching a tear-out from a newspaper advertising a COX-2 inhibitor, and it was simpler to prescribe the drug than to take the time to explain why the patient did not need it (accounting for perhaps 47% of cases). (3) The presence of risk factors, such as advanced age (the rate of serious bleeding increases steeply after age 65), a history of bleeding or peptic ulcers, or ongoing warfarin or corticosteroid treatment justified the selection of a COX-2 inhibitor despite the enormously higher cost (accounting for possibly 5% of cases). For short-term treatment of joint pain, analgesics such as acetaminophen, tramadol, or even opiates are as effective as NSAIDs. Even for the chronic pain of osteoarthritis—which is the most common indication for NSAIDs—such analgesics are effective in more than half of patients, and NSAIDs are by no means effective in all such patients. The Alternatives In patients whose joint disease has a major inflammatory component, one of the tried-and-true generic nonselective NSAIDs such as ibuprofen, naproxen, or sulindac is an appropriate choice. These agents are as effective as selective COX-2 inhibitors for controlling symptoms, at one fifth to one tenth the cost. For patients at high risk for GI complications, a selective COX-2 inhibitor used at the lowest possible effective dose (cardiovascular complications escalate rapidly with increasing doses) is one alternative. Another is to prescribe a generic nonselective NSAID plus misoprostol or a proton pump inhibitor.
X Obesity Jonathan Q. Purnell, MD
Oregon Health & Science University New Standards for Obesity Risk in Asians The World Health Organization (WHO) classification for overweight and obesity, which predominantly applies to people of European ancestry, assigns an increasing risk for comorbid conditions—including hypertension, type 2 diabetes mellitus, and cardiovascular disease—to persons with higher body mass indexes (BMIs) relative to persons of normal weight (i.e., those with a BMI between 18.5 and 25). Asian populations, however, are known to be at increased risk for diabetes and hypertension at lower BMI ranges than non-Asian groups. Consequently, the WHO has suggested lower cutoff points for consideration of therapeutic intervention in Asians: a BMI of 18.5 to 23 represents acceptable risk, 23 to 27.5 represents increased risk, and 27.5 or higher represents high risk.1 The absolute BMI cutoffs for overweight and obesity remain unchanged for Asians. 1. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. WHO Expert Consultation: Lancet 363:157, 2004 [PMID 14726171] The Transitory Effects of Low-Carb Diets Severe carbohydrate restriction (< 30 g/day) may lead to modest spontaneous weight loss without initial activation of appetite. Until recently, the ability to draw meaningful conclusions about the longer-term safety and efficacy of low-carbohydrate diets was impeded by the paucity of controlled studies and the variability of carbohydrate restriction from study to study (from < 20 to ≥ 200 g/day).1 Although methodological issues remain, recent randomized, controlled studies have shown that during the first 6 months of diet treatment, persons placed on a low-carbohydrate diet lose weight more rapidly than those placed on a low-calorie, low-fat diet.2–4 Subsequently, however, persons on the low-carbohydrate diet either stop losing weight or regain weight, and by 1 year, weight losses are the same in the two diets.2,3 The average 1-year weight loss ranged from 2.5 to 5.1 kg in these studies, and both diets had a high dropout rate (approximately 30% to 40%).3,4 Lipid levels and glucose metabolism improved with both diets, in proportion to weight loss.2–5 1. Bravata DM, Sanders L, Huang J, et al: Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA 289:1837, 2003 [PMID 12684364] 2. Brehm BJ, Seeley RJ, Daniels SR, et al: A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 88:1617, 2003 [PMID 12679447] 3. Foster GD, Wyatt HR, Hill JO, et al: A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 348:2082, 2003 [PMID 12761365] 4. Stern L, Iqbal N, Seshadri P, et al: The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med 140:778, 2004 [PMID 15148064] 5. Yancy WS, Olsen MK, Guyton JR, et al: A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 140:769, 2004 [PMID 15148063] Surgery for Obesity Surgical therapy for severe obesity results in significant, sustained weight loss in a majority of patients.1 These large weight losses bring improvements in the comorbid conditions that accompany obesity, including lowering of lipid levels and blood pressure and reduced rates of diabetes, progression to diabetes, and sleep apnea.1 In addition to these improvements in morbidity, cohort and population-based studies have demonstrated reduced mortality of, as well as reduced use of health care resources by, morbidly obese patients who have lost weight after bariatric surgery, as compared with control subjects.2,3 Bariatric operations can be classified into one of three types: restriction of food passage, malabsorption of nutrients, or a combination of the two [see Table]. With regard to total weight loss and improved disease outcomes, the gastric bypass procedure has the greatest support from published studies,1 whereas the gastric banding procedure has the lowest published rates of morbidity (11%) and mortality (0.05%).4 Because of the potential for rapid weight loss after bariatric surgery, follow-up by a nutritionist and a physician is important to ensure that patients preserve lean mass and maintain hydration and to monitor for symptomatic cholelithiasis. Lifelong alteration in dietary habits may be required to ensure the continued success of the surgery, and dietary supplements may be needed to prevent nutritional deficiencies. 1. Buchwald H, Avidor Y, Braunwald E, et al: Bariatric surgery: a systematic review and meta-analysis. JAMA 292:1724, 2004 [PMID 15479938] 2. Christou NV, Sampalis JS, Liberman M, et al: Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 240:416, 2004 [PMID 15319713] 3. Flum DR, Dellinger EP: Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 199:543, 2004 [PMID 15454136] 4. Chapman AE, Kiroff G, Game P, et al: Laparoscopic adjustable gastric banding in the treatment of obesity: a systematic literature review. Surgery 135:326, 2004 [PMID 14976485] 6 Immunology/Allergy
XI Diagnostic and Therapeutic Principles in Allergy Mitchell H. Grayson, MD
Washington University School of Medicine Phillip E. Korenblat, MD, FACP Washington University School of Medicine Using Omalizumab Omalizumab is a humanized anti-IgE monoclonal antibody that is administered subcutaneously on a biweekly to monthly schedule. It has been shown to significantly reduce symptom scores in patients with allergic rhinitis, as well as to relieve symptoms and modestly improve airway function in patients with moderate to severe asthma. Patients with low pulmonary functions, patients who have had emergency department visits within the preceding year, and patients on high-dose inhaled corticosteroids are the most likely to respond to therapy with anti-IgE.1 The appropriate end points for omalizumab therapy remain uncertain. Standard measures of allergic sensitivity are not useful in patients who are taking omalizumab: skin testing will produce negative results, and total IgE will be elevated because IgE is bound to the anti-IgE medication in circulation. Current data support continued administration for a minimum of 12 weeks. 1. Bousquet J, Wenzel S, Holgate S, et al: Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest 125:1378, 2004 [PMID 15078749] A Low-Cost Option for Asthma Although generally not viewed as a major therapeutic option because of their narrow therapeutic window and significant side effects, methylxanthines still have some usefulness in asthma care. Current asthma treatment guidelines suggest theophylline (at a serum concentration of 5 to 15 µg/ml) to be an alternative treatment in mild and moderate persistent asthma.1 The addition of low-dose theophylline (5 to 10 mg/ml) to inhaled corticosteroids has shown benefit in asthma, with a lower risk of side effects than with higher theophylline doses. As a result, methylxanthines remain worthy of consideration as part of the therapeutic regimen, especially in patients for whom cost is an issue. 1. National asthma education and prevention program expert panel report 2: guidelines for the diagnosis and management of asthma (NIH Publication No. 97-4051). National Institutes of Health, Bethesda, Maryland, 2002 http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm XV Allergic Reactions to Hymenoptera David B. K. Golden, MD, FACP Johns Hopkins University School of Medicine Diagnosing Insect-Venom Allergy The diagnosis of insect-venom allergy can be confirmed by skin tests or serologic tests. The recommended procedure for skin tests is intradermal testing with serial dilutions of the five Hymenoptera venom protein extracts or, in the case of fire-ant sensitivity, whole body extracts of imported fire ants. Most patients with a definite history of insect-sting reactions have clearly positive skin-test results; in some patients, however, the results are clearly negative. Negative skin-test results in a patient with a history of insect-sting reactions may represent the loss of sensitivity. However, to exclude false negative results, such patients should be tested for venom-specific IgE antibodies in the serum with serologic testing. If necessary, the venom skin test may be repeated after several months. A few cases of sting anaphylaxis are non-IgE mediated and may be related to subclinical mastocytosis or simply to toxic mast cell hyperreleasability. Detection of allergen-specific IgE antibodies in serum is typically done by radioallergosorbent testing (RAST). An elevation in the level of venom-specific IgE is certainly diagnostic; but the test is often qualitative and poorly standardized, and it yields negative results in 15% to 20% of patients whose skin-test results are positive. It is important to note that the degree of sensitivity as detected by skin testing or RAST does not correlate reliably with the degree of sting reaction. The strongest skin-test results often occur in patients who have had only large local reactions, and some patients who have had near-fatal anaphylactic shock show only weak sensitivity on skin testing or RAST. Because of cross-reactivity, patients allergic to yellow-jacket venom may also have positive skin tests for other vespid venoms; 95% of such patients test positive for yellow hornet and white-faced hornet venom; more than half also have positive reactions to Polistes wasp venom. It is possible to determine whether the patient has a specific or a cross-reactive sensitivity to wasp venom using a RAST-inhibition test in specialized laboratories. Selecting Patients for Venom Immunotherapy Current indications for venom immunotherapy are a history of previous systemic allergic reaction to a sting and a positive venom skin test.1 The risk of an anaphylactic reaction to a sting varies in accordance with the history of previous stings and is correlated with the results of venom skin testing or serologic testing, typically RAST. The risk declines gradually with time [see Table]. The patients at highest risk are those with a recent history of anaphylaxis and positive skin-test results; in such patients, the risk of a systemic reaction to a subsequent sting is approximately 50%. Children and adults with a history of large local reactions are at low risk for a systemic reaction (i.e., < 10%), as are children whose systemic reactions are limited to cutaneous signs and symptoms. In these low-risk persons, venom immunotherapy is not required, but some patients will still request treatment because of frequent exposure or fear of reaction. Children who experience moderate or severe systemic reactions to an insect sting have a relatively high risk of recurrence, even 10 to 20 years after the initial allergic reaction.2 Some adults may experience progressively worsening reactions, so all adults with systemic reactions are advised to undergo venom immunotherapy. There is no test that accurately predicts which patients will progress to more severe reactions and which will not. 1. Moffitt JE, Golden DB, Reisman RE, et al: Stinging insect hypersensitivity: a practice parameter update. J Allergy Clin Immunol 114:869, 2004 [PMID 15480329] 2. Golden DBK, Kagey-Sobotka A, Norman PS, et al: Outcomes of allergy to insect stings in children with and without venom immunotherapy. N Engl J Med 351:668, 2004 [PMID 15306668] When Is It Safe to Stop Venom Immunotherapy? The package inserts for the commercial venom immunotherapy products available in the United States recommend indefinite immunotherapy, and in most patients, skin-test results and RAST results remain positive after 5 to 10 years of treatment. Nevertheless, even when skin tests remain positive, venom immunotherapy can usually be stopped after 5 years. Observation of patients for 5 to 10 years after completing a 5- to 8-year course of venom treatment has shown a 5% to 10% risk of systemic symptoms after any sting but only a 2% risk of a reaction requiring epinephrine treatment. Patients who have a higher frequency of relapse include those receiving honeybee-venom therapy, those with a history of very severe pretreatment sting reactions, and those who have had a systemic reaction to a sting or an injection during the period of venom immunotherapy. Some patients prefer to continue venom treatment for their continued sense of security. Children who have had a 3- to 5-year course of venom immunotherapy show persistent tolerance, even 10 to 20 years after discontinuing treatment. VI Neoplastic Disorders Jerome B. Posner, MD Radiation Therapy for Brain Tumors Postoperative radiation therapy increases survival and improves the quality of life in patients with high-grade tumors (i.e., anaplastic astrocytomas or gliomas). However, its role in patients with low-grade tumors, particularly those that are asymptomatic, is uncertain.1 After total resection of pilocytic astrocytomas, radiation therapy is not required. In patients with low-grade astrocytomas or oligodendrogliomas whose only symptoms are well-controlled seizures, radiation therapy may safely be deferred until symptoms develop.1 High-grade gliomas should be treated with high doses of radiation (5,500 to 6,000 cGy in fractions of 180 to 200 cGy) delivered to a limited field that encompasses the tumor and its immediate surroundings. New techniques of conformal field radiation planning, such as intensity-modulated radiotherapy, decrease treatment-related morbidity and may enhance tumor control.2 Stereotactic radiosurgery, in which high doses of ionizing radiation in multiple narrow beams are directed to a precise intracranial location by stereotaxy, is used in some centers to treat metastases, schwannomas, meningiomas, and some pituitary tumors and to boost conventional radiation for gliomas; its efficacy for gliomas has not been established.3 1. Dropcho EJ: Low-grade gliomas in adults. Curr Treat Options Neurol 6:265, 2004 [PMID 15157404] 2. Teh BS, Mai WY, Grant WH, et al: Intensity modulated radiotherapy (IMRT) decreases treatment-related morbidity and potentially enhances tumor control. Cancer Invest 20:437, 2002 [PMID 12094538] 3. Souhami L, Seiferheld W, Brachman D, et al: Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 60:853, 2004 [PMID 15465203] Treating Spinal Cord Metastases Metastases to vertebral bodies cause symptoms by compressing the spinal cord.1 Epidural spinal cord compression by a metastatic tumor is a neurologic emergency. Treatment consists of high-dose dexamethasone, 100 mg by I.V. bolus, followed by 100 mg/day in divided doses for 3 days; the drug is then rapidly tapered. Some institutions use smaller doses. Definitive therapy entails irradiation with or without surgical decompression. In one study, patients treated with radical decompressive surgery plus postoperative radiation therapy regained the ability to walk more often and maintained it longer than patients treated with radiation alone.2 Surgical procedures include laminectomy or removal of a vertebral body.3 Patients who are ambulatory when treated usually remain so after treatment.1 Those who are not ambulatory may regain the ability to walk; those who are paraplegic rarely do so. 1. Byrne TN: Metastatic epidural cord compression. Curr Neurol Neurosci Rep 4:191, 2004 [PMID 15102344] 2. Patchell RA: A randomized trial of direct decompressive surgical resection in the treatment of spinal cord compression caused by metastasis. Plenary presentation, ASCO Annual Meeting, Chicago, 2003 3. Maranzano E, Trippa F, Chirico L, et al: Management of metastatic spinal cord compression. Tumori 89:469, 2003 [PMID 14870766] Prognosis in Brain Tumors Histologic grade is an important prognostic factor for patients with primary brain tumors.1 For example, the median survival of patients with glioblastoma multiforme is a little longer than 1 year, and the 5-year survival rate is less than 10%. Patients with anaplastic astrocytoma have a median survival of 2 to 3 years; for those with astrocytoma, median survival is 5 to 10 years. Patients with a pilocytic astrocytoma often have a normal life span. Many patients with meningiomas2 and pituitary tumors3 remain asymptomatic; in such patients, the tumor is often discovered incidentally when a brain image is done for another reason or at autopsy after the patient dies of another disease. Age is an important determinant of prognosis; younger patients survive longer than older patients despite having tumors that are of similar histology. Gene expression profiles may prove to be a better prognostic factor than histology.4 1. Buckner JC: Factors influencing survival in high-grade gliomas. Semin Oncol 30(6 suppl 19):10, 2003 [PMID 14765378] 2. Krampla W, Newrkla S, Pfisterer W, et al: Frequency and risk factors for meningioma in clinically healthy 75-year-old patients: results of the Transdanube Ageing Study (VITA). Cancer 100:1208, 2004 [PMID 15022288] 3. Ezzat S, Asa SL, Couldwell WT, et al: The prevalence of pituitary adenomas. Cancer 101:613, 2004 [PMID 15274075] 4. Huang H, Okamoto Y, Yokoo H, et al: Gene expression profiling and subgroup identification of oligodendrogliomas. Oncogene 23:6012, 2004 [PMID 15208679] Primary CNS Lymphoma Although primary central nervous system lymphoma (PCNSL) was once rare, the incidence of this disease continues to increase in immunocompetent persons (e.g., those who are not infected with HIV).1 PCNSL is now an important consideration in the diagnosis and treatment of brain tumors, particularly because the tumor is sometimes curable.2 PCNSL usually presents as a brain mass; less commonly, PCNSL begins in the eye, spinal cord, or leptomeninges. Leptomeningeal tumors may cause headache and hydrocephalus. If the eyes are affected, visual difficulties that suggest uveitis or vitreitis may be the first complaint. Because the mass lesions in the brain are generally deep, patients often present with behavioral and personality change rather than with the seizures that characterize gliomas. PCNSL grows rapidly and spreads widely throughout the brain and spinal cord, but it rarely metastasizes outside the CNS. Multiple lesions are common in PCNSL. Diagnosis of PCNSL can be made by identification of malignant lymphocytes obtained by vitrectomy (in cases of eye involvement), cerebrospinal fluid examination (in cases of leptomeningeal tumor), or needle biopsy of the brain. Untreated patients with PCNSL die within several months after diagnosis of the disease. Treatment consists of high-dose, methotrexate-based systemic chemotherapy with or without subsequent radiation therapy.3 Compared with radiation therapy alone, chemotherapy increases the median time to relapse; for some patients, this treatment is curative. HIV-positive patients with PCNSL are also treated with this regimen. Treatment with highly active antiretroviral therapy has been effective in some patients with AIDS. 1. Olson JE, Janney CA, Rao RD, et al: The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis. Cancer 95:1504, 2002 [PMID 12237919] 2. DeAngelis LM: Primary central nervous system lymphoma: a curable brain tumor. J Clin Oncol 21:4471, 2003 [PMID 14597745] 3. Gavrilovic IT, Abrey LE: Primary central nervous system lymphoma. Curr Oncol Rep 6:388, 2004 [PMID 15291982] XXXV Helminthic Infections Wesley C. van Voorhis, MD, PHD, FACP Diagnosing Geohelminth Infection Roundworms, hookworms, and whipworms are geohelminths, requiring a soil phase for the fecally expelled eggs to develop into their infective stages. Thus, infections from these parasites usually occur in rural areas with poor sanitation. Intestinal infections are usually easily diagnosed by finding the eggs of the responsible parasite on stool examination. During the pulmonary phase of roundworm or hookworm infections, the diagnosis is made by finding larvae in respiratory secretions. Results of stool examinations are usually negative during the pulmonary phase because this phase occurs early in infection, weeks or months before adult worms have matured sufficiently to liberate eggs into the feces. Positive stool samples during the respiratory phase indicate earlier long-standing infection. Thus, in eosinophilic pneumonitis, negative stool examination results do not exclude a parasitic etiology. Adult Ascaris lumbricoides (roundworms) can be readily detected in upper gastrointestinal series; the large (10 to 30 cm) worms are outlined by contrast material, and in late follow-up films, the parasite's alimentary tract may be defined by a thin line of ingested contrast medium. Ultrasonography can detect adult worms in the small intestine, facilitating diagnosis of Ascaris as the cause of abdominal symptoms. Worms in the biliary tract can be detected by ultrasonography or endoscopic cholangiopancreatography.1 At times, patients may note the passage of the large, smooth adult Ascaris worms in the stool or may cough up an adult worm. Adult whipworms, which are 3 to 5 cm in length, may be visualized by anoscopy or colonoscopy. Adult hookworms, which are 0.6 to 1.2 cm in length, may be visualized by endoscopy of the proximal small intestine. 1. Reddy DN, Sriram PV, Rao GV: Endoscopic diagnosis and management of tropical parasitic infections. Gastrointest Endosc Clin N Am 13:765, 2003 [PMID 14986797] The Long Reach of Strongyloidiasis Although Strongyloides stercoralis is the least prevalent of the intestinal nematodes in the United States, it is widely distributed within the tropics and subtropics. In the United States, Strongyloides infection is more prevalent in persons residing in the southern states; in persons living in institutions with poor sanitation1; and in immigrants, military veterans, and other persons who have traveled or resided in locales where Strongyloides is endemic. Strongyloides is one of the few helminths capable of internal reinfection; it can multiply in the human host without reinfection by soil-dwelling larvae. As a result of ongoing internal reinfection, strongyloidiasis may persist for decades, as has been documented in some veterans of World War II and the Vietnam War. If host immunity is suppressed, the internal reinfection cycle may become unbridled, leading to hyperinfection that can result in an overwhelming and frequently fatal illness.1 Invasion of the small intestine wall by adult S. stercoralis worms may produce abdominal pain that is often localized to the midepigastrium; the pain is similar to that of peptic ulcer but is aggravated by food consumption. Diarrhea, nausea, and vomiting often occur; less commonly, urticaria, asthma, and weight loss may occur. Patients with heavy infection may experience malabsorption, gastrointestinal bleeding, and a protein-losing enteropathy. In cases of chronic infection, symptoms may be absent or may be mild and intermittent; symptoms include diarrhea, abdominal pain, and recurring episodes of urticaria, especially on the buttocks and the wrists. Less commonly, larva currens, which is a pathognomonic serpiginous, pruritic, elevated eruption, evolves along the tract of larval migration in the skin of the perianal, gluteal, or other body areas. 1. Keiser PB, Nutman TB: Strongyloides stercoralis in the immunocompromised population. Clin Microbiol Rev 17:208, 2004 [PMID 14726461] Trichinellosis in the United States Although meat in the United States is not inspected for Trichinella larvae, laws proscribing the feeding of uncooked garbage to pigs have reduced the transmission of the disease. Most cases in the United States are attributable to noncommercial pork, bear, and cougar meat. About 15 cases of trichinellosis, occasionally leading to death, are reported annually in the United States, but more cases, especially mild ones, probably remain undiagnosed.1 The triad of periorbital edema, myalgias, and eosinophilia strongly suggests the diagnosis of trichinellosis. Most patients with trichinellosis have a history of consuming pork products or the meat of wild mammals. The development of symptomatic infection or eosinophilia in other persons who have eaten the meat incriminated in a case of trichinellosis provides epidemiologic confirmation of the diagnosis. Persons with light infections may have minimal symptoms, or the symptoms may suggest diagnoses other than trichinellosis, such as diarrheal or influenzal syndromes or polymyositis. In rare instances, central nervous system involvement may suggest aseptic meningitis or encephalitis. 1. Roy SL, Lopez AS, Schantz PM: Trichinellosis surveillance—United States, 1997–2001. MMWR Surveill Summ 52:1, 2003 [PMID 14532870] Tapeworms from Sushi Humans acquire fish tapeworm infection by ingestion of inadequately cooked fish containing the infective plerocercoid stage of parasitic Diphyllobothrium species, including D. latum.1,2 The risk of acquiring diphyllobothriasis has increased with the growing popularity of raw fish dishes, such as sushi, sashimi, seviche, and Dutch green herring. Freshwater fish, including pike and yellow perch caught in the United States, may harbor Diphyllobothrium species, as may anadromous salmon. Diphyllobothrium species other than D. latum are found in Pacific salmon and Alaskan blackfish. Adult fish tapeworms may grow up to 15 m in length and live for 20 years or longer in the small intestine. Human infections are often asymptomatic, although some patients experience anorexia, nausea, or weight loss. Because D. latum competes with the host for vitamin B12, megaloblastic anemia and neuropathy from vitamin B12 deficiency may develop. Diagnosis is made by finding the operculated eggs in the stool or by recovering proglottids in the stool after a saline purge. Therapy is with praziquantel (5 to 10 mg/kg, given once), which is investigational for this use.3 An alternative is niclosamide, in a single oral dose of 2 g; however, this drug may be difficult to obtain in the United States and may be available only from compounding pharmacies. 1. Butt AA, Aldridge KE, Sanders CV: Infections related to the ingestion of seafood. Part II: parasitic infections and food safety. Lancet Infect Dis 4:294, 2004 [PMID 15120346] 2. Raether W, Hanel H: Epidemiology, clinical manifestations and diagnosis of zoonotic cestode infections: an update. Parasitol Res 91:412, 2003 [PMID 13680371] 3. Drugs for parasitic infections. Med Lett Drugs Ther (in press)
XVI Approach to the Diagnosis of Skin Disease Robert T. Brodell, MD Diagnosing Fungal Infection with Potassium Hydroxide A potassium hydroxide (KOH) preparation test for fungal infections involves the application of KOH to the scales of skin or the hair shafts to clear the keratin so that fungal hyphae and spores can be identified. For example, scales can be lightly scraped onto a glass slide after placing the slide on the advancing margin of an annular plaque with central clearing. After a coverslip is applied, a 2.5% KOH preparation is applied to the slide next to the coverslip. The KOH preparation then spreads under the coverslip through capillary action. After being gently heated, any excess KOH is blotted away and the specimen is examined under a microscope. The following is selected from the FDA's list of recently approved products. Complete, updated information on FDA approvals and notifications is available on the FDA Web site (http://www.fda.gov). Biologic Product for Mucositis in Cancer Patients Generic Name: Palifermin Brand Name: Kepivance Manufacturer: Amgen, Inc., Thousand Oaks, California The FDA has approved a new biologic product, palifermin, to help
reduce the rate and duration of mucositis in patients with leukemia
or lymphoma who are receiving high-dose chemotherapy and radiation
treatments associated with bone marrow transplantation. Palifermin
is a recombinant version of keratinocyte growth factor (KGF).
Like endogenous KGF, palifermin stimulates the growth of cells
in the skin and in the mucosa of the mouth, stomach, and colon.
This presumably leads to faster replacement of oral mucosal cells
that are killed by cancer treatments. In a study of 212 patients
with leukemia or lymphoma who were receiving high doses of chemotherapy
and radiation treatments associated with bone marrow transplantation,
severe mucositis developed in 63% of those who received palifermin
but in 98% of placebo recipients. In patients who did experience
severe mucositis, the condition lasted an average of 3 days in
patients receiving palifermin and 9 days in patients receiving
placebo. Palifermin is given intravenously for 3 days before and
3 days after cancer treatment. The most common side effects of
palifermin are skin rash, unusual sensations in the mouth (e.g.,
tingling), and increases in blood protein that suggest pancreatic
irritation. Palifermin has not yet been shown to be safe Source: New Biotechnology Drug Approved to Treat Mucositis Associated with Cancer Treatments. FDA News. U.S. Food and Drug Administration, December 15, 2004 (http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01332.html) Spielberger R, Stiff P, Bensinger W, et al: Palifermin for oral mucositis after intensive therapy for hematologic malignancies. N Engl J Med 351:2590, 2004 [PMID 15602019]
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