|
 |
|
| Vol. 30 No. 4 April 2007 |
 |
| 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 |
 |
| IN THIS ISSUE |
|
| PRACTICE OF MEDICINE |
|
The Gap between Evidence and Practice in Gout Treatment Shaun Ruddy, MD During the past 2 decades, much effort has been expended in collecting and analyzing the scientific evidence underlying the practice of medicine and in developing practice guidelines and measures of quality of care that are based, where possible, on this evidence. Implicitly driving these efforts has been the notion that if useful models or rules for excellence in the practice of medicine were developed, they would be adopted by physicians, thereby improving patient care. Scientists have begun to examine just how well the actual practice of medicine conforms to recommended standards. The results for the diagnosis and treatment of gout show that there is much room for improvement. Gout is not a difficult disease to diagnose, and its treatment is both straightforward and very effective. Yet errors in management are common. In one study, 23% of patients with recurrent gout attacks had inappropriate therapy.1 In another study, in 18 of 46 patients, doses of allopurinol were judged to be excessive. There is very little modern scientific evidence on which to base judgments about gout treatment, probably be cause the mainstay of therapy, allopurinol, was approved in 1964, when randomized controlled trials were not prevalent. Despite this, two groups have developed recommendations for the management of gout.2,3 Both groups used a combination of a careful and exhaustive review of the literature with opinions from a panel of experts. Not surprisingly, the results were similar. Several recommendations concern the use of allopurinol in treating the hyperuricemia associated with gouty arthritis. For example, the initial dose should be reduced for patients with impaired renal function because the frequency of severe adverse reactions is increased. Too often, this precaution is not observed: one study found that only 48 of 185 patients with renal disease received a lowered dose.4 In the same study, 13 of 52 patients who were taking azathioprine did not have their doses of this agent reduced when allopurinol was begun and were therefore at high risk for severe neutropenia. A third quality indicator, that patients with asymptomatic elevations of serum uric acid should not be treated, was violated more than half the time. Dose adjustment is critical to successful lowering of serum urate with allopurinol. Although this agent is compounded in a 300 mg pill, the “one size fits all” approach definitely does not work. Indeed, in the original study of allopurinol, only 9 of 49 patients taking 300 mg daily achieved target serum urate levels.5 Similarly, in a recent trial of the new xanthine oxidase inhibitor febuxostat, only 21% of control subjects arbitrarily treated with 300 mg allopurinol daily achieved appropriate serum urate levels.6 The dose of allopurinol must be titrated by monitoring serum urate levels every few weeks and adjusting the dose, if necessary, to bring the serum urate level to less than 6.0 mg/dl. This level, below the saturating concentration of monosodium urate, nearly eliminates future gouty attacks, dissolves tophi, and sometimes improves renal function. Daily allopurinol doses of 400 mg, 500 mg, or more are often required to achieve the target level. One quality of care indicator stipulates that the serum urate level should be measured within 6 months of starting allopurinol. Unfortunately, data indicate that only one third to one half of patients have such a measurement made. The remainder presumably are left on a 300 mg daily dose, thus condemning most of them to continuing elevated serum urate levels. When gouty attacks recur or tophi fail to melt away in such patients, the allopurinol treatment is typically judged a failure. This very disappointing record of adherence to a simple regimen for an easily treated disease is chastening. How to improve the performance? Continuing medical education seems appropriate, but those who work in this field are painfully aware of the limited lasting effects their efforts have on physician behavior. The only group that has succeeded in altering physician behavior to an appreciable extent is the pharmaceutical companies. Perhaps if there were an army of drug representatives providing morning doughnuts, free lunches, educational dinners at upscale restaurants, and other perks while simultaneously flogging the appropriate dosing of allopurinol, things would improve. The advent of febuxostat, which seems likely to be approved for use soon, promises to increase attention to the treatment of gout. Perhaps this will provide some collateral benefit for the old, but still very effective, agents. References1. Neogi T, Hunter DJ, Chaisson CE, et al: Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study. J Rheumatol 33:104, 2006 [PMID 16267879] 2. Zhang W, Doherty M, Bardin T, et al: EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 65:1312, 2006 [PMID 16707532] 3. Mikuls TR, MacLean CH, Olivieri J, et al: Quality of care indicators for gout management. Arthritis Rheum 50:937, 2004 [PMID 15022337] 4. Mikuls TR, Farrar JT, Bilker WB, et al: Suboptimal physician adherence to quality indicators for the management of gout and asymptomatic hyperuricaemia: results from the UK General Practice Research Database (GPRD). Rheumatology (Oxford) 44:1038, 2005 [PMID 15870145] 5. Yu TF: The effect of allopurinol in primary and secondary gout. Arthritis Rheum 1965 8:905, 1965 [PMID 5323683] 6. Becker MA, Schumacher HR, Wortmann RL, et al: Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 353:2450, 2005 [PMID 16339094]
XX Diagnosis and Treatment of Cough J. Mark Madison, MD Cough and the Common Cold Clinical experience suggests that upper respiratory tract infection, especially the common cold, is the most common cause of acute cough. In immunocompetent patients with characteristic clinical findings, diagnostic testing has a low yield; for example, chest roentgenograms will be normal in greater than 97% of cases. However, with acute cough in immunocompromised patients, especially those with AIDS or at risk of AIDS (particularly if the patient's CD4+ T cell count is less than 200/mm3), the clinician should address pneumonia secondary to Pneumocystis jiroveci and Mycobacterium tuberculosis early in the workup, even if the physical examination and chest roentgenogram are normal.1 1. Rosen MJ: Cough in the immunocompromised host: ACCP evidence-based clinical practice guidelines. Chest 129(1 suppl):204S, 2006 [PMID 16428712] From Drip to Cough Upper airway cough syndrome (UACS) is the result of rhinosinus conditions that may cause cough by direct mechanical stimulation or by causing irritation and inflammation of tissues in the pharynx and larynx.1 Why cough develops in only a minority of patients with rhinosinus disease is not known. Typically, patients with UACS describe the sensation of fluid dripping down into their throats, nasal discharge, or the need to frequently clear their throats—other persons in the patient's vicinity may also notice frequent throat clearing by the patient—and physical examination of the nasopharynx and oropharynx reveals mucoid or mucopurulent secretions or a cobblestoned appearance of the mucosa. Unfortunately, none of these criteria, by themselves, is very sensitive or specific. Moreover, in some patients, chronic cough may be the only symptom of UACS (so-called silent UACS). Therefore, the diagnosis of UACS is often made on the basis of response to empirical therapeutic trials.2 Indeed, because postnasal drip and throat clearing are common complaints in the general population and in patients with chronic cough from other conditions, cough can be definitively ascribed to UACS only when it responds to specific therapy for UACS. 1. Pratter MR: Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines. Chest 129(1 suppl):63S, 2006 [PMID 16428694] 2. Irwin RS, Baumann MH, Boulet LP, et al: Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 129(1 suppl):1S, 2006 [PMID 16428686] Causes of Chronic Cough When evaluating a patient whose cough has persisted for more than 8 weeks, the clinician should recognize that in at least 25% of such patients, there are multiple causes contributing to the cough. In a small percentage of patients, as many as five concomitant causes have been found. In nonsmokers who are not taking an angiotensin-converting enzyme (ACE) inhibitor and who have a normal or near-normal chest roentgenogram, relatively few conditions account for most instances of chronic cough. Asthma, upper airway cough syndrome (UACS) from rhinosinus conditions, and gastroesophageal reflux disease (GERD) are the three most common causes of chronic cough in adults in the United States. In nonsmokers, chronic cough is almost uniformly caused by these three conditions, alone or in combination. In prospective studies of adults that included smokers, 91% to 94% of chronic coughs were caused by UACS (formerly called postnasal drip syndrome), asthma, GERD, or chronic bronchitis. Another common cause of chronic cough is nonasthmatic eosinophilic bronchitis (NAEB), an eosinophilic inflammatory disorder of the airways distinct from asthma. Although NAEB has been more commonly reported outside of the United States, this disorder may be responsible for as many as 10% to 30% of chronic cough cases. GERD and Chronic Cough GERD should be suspected as the cause of chronic cough whenever a patient complains of frequent episodes of typical gastrointestinal symptoms such as daily heartburn and regurgitation, especially when the chest radiograph or clinical picture suggests an aspiration syndrome. Alternatively, cough may be the only symptom of GERD; in prospective studies, such so-called silent GERD has accounted for 43% to 75% of cases. In the absence of gastrointestinal symptoms, chronic cough can be confidently attributed to GERD if the patient is a nonsmoker, is not taking an ACE inhibitor, and has a normal or near-normal chest radiograph, and asthma, upper airway cough syndrome, and nonallergic eosinophilic bronchitis have been ruled out; 92% of patients with silent GERD fit this clinical profile. Failure to obtain a history of nocturnal coughing does not exclude GERD as a cause of cough. When the chest radiograph is normal, cough from GERD most commonly occurs while the patient is awake and upright and it usually does not occur or is not noted at all during sleep. The use of 24-hour esophageal pH monitoring can help confirm that GERD is causing a cough.1 Correlation of cough and reflux events is possible when patients keep a symptom diary during the esophageal pH monitoring session. The monitoring session findings can be considered consistent with GERD as the cause of chronic cough when reflux events (acid or alkaline) appear to trigger cough or when any reflux parameter falls out of the normal range. However, the conventional diagnostic indices of GERD (e.g., percentage of time that pH is less than 4.0) that gastroenterologists use to diagnose reflux esophagitis can be misleadingly normal in patients with cough from GERD. The test should be interpreted as normal only when conventional indices for acid reflux are within the normal range and no reflux-induced coughs are identified during the 24-hour monitoring study.1 1. Irwin RS: Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest 129(1 suppl):80S, 2006 [PMID 16428697] 15 RheumatologyX Osteoarthritis Christopher Wise, MD, FACP A Cushion against Knee Damage A history of specific joint injury, usually related to sports and recreational activities, is an important risk factor for knee and hip osteoarthritis. In the knee in particular, studies showing an association of osteoarthritis with total meniscectomy and meniscal pathology in general highlight the importance of an intact meniscus in preserving the structural integrity of the surface cartilage in this joint.1 1. Hunter DJ, Zhang YQ, Niu JB, et al: The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum 54:795, 2006 [PMID 16508930] Lifestyle Treatments in Concert The role of obesity as an etiologic factor in osteoarthritis of the knee is well established, and some data suggest that weight loss may reduce the risk of development of symptoms in patients predisposed to osteoarthritis. A 2004 study demonstrated that a program of weight loss combined with exercise was more effective than either intervention alone. 1. Messier SP, Loeser RF, Miller GD, et al: Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the arthritis, diet, and activity promotion trial. Arthritis Rheum 50:1501, 2004 [PMID 15146420] In the Absence of a Cure There is no cure for osteoarthritis, and no therapy is known to prevent or retard the degenerative biologic process in articular cartilage. Thus, the treatment of osteoarthritis is focused primarily on relieving symptoms and improving function.1–4 Treatment decisions should be based on the severity and distribution of joint involvement, considered in the light of the patient's other medical problems that might affect the safety and effectiveness of any chosen therapy [see Table]. 1. Felson DT: Clinical practice: osteoarthritis of the knee. N Engl J Med 354:841, 2006 [PMID 16495396] 2. Ge A, Hu Y, Heng BC, et al: Osteoarthritis and therapy. Arthritis Rheum 55:493, 2006 [PMID 16739189] 3. Dieppe PA, Lohmander LS: Pathogenesis and management of pain in osteoarthritis. Lancet 365:965, 2005 [PMID 15766999] 4. Zhang W, Doherty M, Arden N: EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 64:669, 2005 [PMID 15471891] Acupuncture and Osteoarthritis A number of alternative or complementary therapies for osteoarthritis have been investigated. These studies have been poorly controlled or limited, however, and little evidence supports the widespread use of most integrative therapies at present. Recent studies of acupuncture for pain relief in patients with osteoarthritis have shown variable levels of improvement, including some benefit compared with no therapy, sham procedure, or minimal acupuncture, but the magnitude of improvement in these trials has been small.1–3 1. Witt C, Brinkhaus B, Jena S: Acupuncture in patients with osteoarthritis of the knee: a randomized trial. Lancet 366:136, 2005 [PMID 16005336] 2. Witt CM, Jena S, Brinkhhaus B, et al: Acupuncture in patients with osteoarthritis of the knee or hip: a randomized, controlled trial with an additional nonrandomized arm. Arthritis Rheum 54:3485, 2006 [PMID 17075849] 3. Scharf HP, Manmann U, Streitberger K, et al: Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med 145:12, 2006 [PMID 16818924]
VIII Acute Myocardial Infarction Peter B. Berger, MD Duke University School of Medicine James L. Orford, MB, CHB, MPH Mayday University Hospital, London Choices in Acute Intervention The 2004 American College of Cardiology/American Heart Association (ACC/AHA) guidelines gave a class I recommendation to the use of percutaneous coronary intervention (PCI) for any patient with an acute ST-segment elevation myocardial infarction (STEMI) who presents within 12 hours of symptom onset and who can undergo the procedure within 90 minutes of presentation by clinicians skilled in the procedure.1 When primary PCI is not available or its implementation is delayed, use of thrombolytic therapy is recommended. The ACC/AHA task force gave a class I recommendation to the use of thrombolytic therapy for any patient with an acute STEMI without contraindications for thrombolysis, who presents to a facility without the capability for expert, prompt intervention with primary PCI within 90 minutes of first medical contact.1 The delay from patient arrival to administration of thrombolytics should be less than 30 minutes.1 Reperfusion therapy, whether PCI or thrombolytics, should not await the availability of results of cardiac biomarkers. The immediate implementation of reperfusion therapy without awaiting biomarker data was given a class I recommendation.1 1. Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 110:588, 2004 [PMID 15289388] Antiplatelet Drugs in MI Aspirin should be given to patients with suspected STEMI as early as possible and continued indefinitely. True aspirin allergy is the only exception to this recommendation.1 The 2004 American College of Cardiology/American Heart Association guidelines gave a class I recommendation to the use of clopidogrel in all patients treated with primary percutaneous coronary intervention.1 Clopidogrel may be given in a loading dose of 300 mg or 600 mg; limited trial data suggest that 600 mg works within 2 to 3 hours and that outcomes may be better than with 300 mg. There are no data available regarding the combination of fibrinolytic agents and clopidogrel, but ongoing trials will provide this information. However, clopidogrel is probably indicated in patients receiving fibrinolytic therapy who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance. 1. Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 110:588, 2004 [PMID 15289388] Stat Statins? Statin therapy in the early management of acute myocardial infarction (MI) is under investigation; current evidence indicates such therapy may be beneficial. A study of more than 300,000 patients in the National Registry of Myocardial Infarction found that statin use within the first 24 hours of admission for acute MI was associated with a significantly lower rate of early complications and in-hospital mortality.1 Statin therapy in the follow-up management of acute MI is recommended.2 The 2004 American College of Cardiology/American Heart Association guidelines give a class I recommendation to starting therapy before hospital discharge in all patients with ST segment elevation MI.2,3 1. Fonarow GD, Wright RS, Spencer FA, et al: Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol 96:611, 2005 [PMID 16125480] 2. Cannon CP, Braunwald E, McCabe CH, et al: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350:1495, 2004 [PMID 15007110] 3. Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 110:588, 2004 [PMID 15289388] VII Breast Cancer Nancy E. Davidson, MD Protection for Both Bone and Breast? Raloxifene, a selective estrogen receptor modulator, is approved for use in the prevention of osteoporosis in postmenopausal women. A prospective, double-blind, randomized trial targeted 19,747 postmenopausal women at increased risk for breast cancer in a comparison of tamoxifen and raloxifene.1 The study found raloxifene to be as effective as tamoxifen in reducing the risk of invasive breast cancer.1 In addition, raloxifene was associated with a lower risk of thromboembolic events and cataracts than tamoxifen, which may make it preferable as a cancer-preventive agent. 1. Vogel VG, Costantino JP, Wickerham DL, et al: Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295:2727, 2006 [PMID 16754727] Adjuvant Chemotherapy for Early-Stage Breast Cancer In patients at risk of harboring micrometastatic disease, adjuvant chemotherapy improves 15-year survival.1 The best sequence of administering adjuvant chemotherapy and radiotherapy for early-stage breast cancer is unclear, but evidence suggests that different sequences of administration have no major effect on survival or recurrence.2 HER-2/neu protein is overexpressed in 20% to 30% of breast cancers; such overexpression may be associated with poorer prognosis and resistance to certain therapies. The monoclonal antibody trastuzumab (Herceptin), which is active against the transmembrane HER-2/neu protein, was approved by the Food and Drug Administration in 2006 for use as adjuvant therapy in HER-2 positive, early-stage breast cancer. Previously, its approved use was in stage IV breast cancer. The studies leading to this newly approved indication showed that women who received trastuzumab combined with chemotherapy had fewer relapses for up to 3 years after surgery.3,4 The most serious side effect of trastuzumab is heart failure; patients with heart disease should not receive this drug. 1. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival; an overview of the randomised trials. Lancet 365:1687, 2005 2. Hickey BE, Francis D, Lehman MH: Sequencing of chemotherapy and radiation therapy for early breast cancer. Cochrane Database Syst Rev (4):CD005212, 2006 [PMID 17054248] 3. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659, 2005 [PMID 16236737] 4. Romond EH, Perez EA, Bryant J, et al: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673, 2005 [PMID 16236738] Radiation after Surgery Many radiation oncologists recommend postmastectomy radiotherapy for women with more than three involved lymph nodes and discuss its use with younger women who have one to three positive lymph nodes. Postmastectomy radiotherapy in women with larger (³5 cm) tumors or axillary node-positive disease reduces the risk of local and regional recurrence, increases disease-free survival, and reduces a woman's risk of dying from breast cancer.1 1. Clarke M, Collins R, Darby S, et al: Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087, 2005 [PMID 16360786] XV Chronic Lymphoid Leukemias and Plasma Cell Disorders Bruce D. Cheson, MD, FACP Alternatives for Troublesome CLL The anti-CD52 monoclonal antibody alemtuzumab has been approved for use in refractory and relapsed chronic lymphoid leukemia (CLL), based on a 33% response rate and acceptable toxicity. Treatment with a combination of alemtuzumab and fludarabine may produce a response even in patients with CLL that has been refractory to each of the two agents.1 Other approaches showing promise include combined therapy with alemtuzumab and rituximab, and use of lenalidomide, an immunomodulatory drug related to thalidomide, with or without rituximab.2 1. Elter T, Borchmann P, Schulz H, et al: Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial. J Clin Oncol 23:7024, 2005 [PMID 16145065] 2. Chanan-Khan A, Miller KC, Musial L, et al: Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol 24:5343, 2006 [PMID 17088571] Initial Regimens in Multiple Myeloma Once it has been decided that treatment is indicated in a patient with multiple myeloma, there are limited effective therapeutic options. Primary agents include corticosteroids, alkylating agents, and thalidomide. The choice of regimen depends on whether the patient is considered to be a candidate for autologous hematopoietic cell transplantation (HCT). Because peripheral stem cells are best collected before the patient is exposed to alkylating agents, nonalkylator regimens (e.g., thalidomide plus dexamethasone, or dexamethasone alone) are recommended in such cases. In patients with overt, symptomatic multiple myeloma who are not considered candidates for HCT, melphalan with prednisone or melphalan, prednisone, and thalidomide are most often used for initial therapy. Treatment is generally continued until the paraprotein concentration decreases to a stable value in serum and urine, with no evidence of disease progression (plateau phase); continuing therapy beyond this point does not prolong survival but increases complications (e.g., infections). Other alkylating agents are also active but have no advantage over melphalan. A New Backup for Multiple Myeloma Bortezomib, the first in a new class of agents, proteasome inhibitors, was recently approved as a second-line agent in multiple myeloma. Used alone or in combination with other chemotherapeutic agents, bortezomib has produced improved response rates in relapsed and refractory disease.1 Data on survival and durability of response await longer follow-up. 1. Richardson PG, Sonneveld P, Schuster MW, et al: Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487, 2005 [PMID 15958804] XII Acne Vulgaris and Rosacea James Q. del Rosso, DO
University of Nevada School of Medicine Treating Truncal Acne A 1% foam formulation of topical clindamycin, which is highly adaptable for widespread application because of easy spreadability and lack of residue or bleaching of fabric, may be used in combination with a benzoyl peroxide wash for mild or moderate truncal acne vulgaris; severe truncal involvement warrants the addition of an oral antibiotic to the topical regimen. A commonly used regimen includes antibiotic-benzoyl peroxide combination gel in the morning and topical retinoid in the evening. Light on Acne A number of light sources have been tested for the treatment of acne.1,2 Photodynamic therapy using topical aminolevulinic acid (ALA-PDT) has demonstrated efficacy for acne vulgaris. A blue light administered twice weekly for 4 consecutive weeks has demonstrated efficacy for acne vulgaris exclusive of nodular lesions. The 1,064 nm Q-switched neodynium:yttrium-aluminum-garnet (Nd:YAG) laser has proved useful for the treatment of acne scarring. 1. Nestor MS: The use of photodynamic therapy for treatment of acne vulgaris. Dermatol Clin 25:47, 2007 [PMID 17126741] 2. Nestor M, Gold M, Kauvar A, et al: The use of photodynamic therapy in dermatology: results of a consensus conference. J Drugs Dermatol 5:140, 2006 [PMID 16485882] Antibiotics for Rosacea Systemic therapy for rosacea has conventionally utilized oral antibiotics, especially tetracycline derivatives (e.g., tetracycline, doxycycline, minocycline). Although there is no definitive evidence that the antimicrobial action of these agents contributes to their efficacy against rosacea, tetracyclines also have several anti-inflammatory effects unrelated to antimicrobial activity, and these effects may provide much of the therapeutic benefit in rosacea. Doxycycline in an anti-inflammatory dose, formulated as a 40 mg controlled-release doxycycline monohydrate capsule taken once daily, is approved by the Food and Drug Administration for the treatment of inflammatory rosacea, including long-term use.1 This formulation differs from other available tetracycline formulations, including doxycycline, in that it results in blood levels below those required for antibiotic activity without loss of anti-inflammatory activity, as long as it is administered no more than once daily. Both short-term (16 weeks' efficacy data) and long-term (safety data over 9 months and microbiologic data up to 18 months) treatment with doxycycline in an anti-inflammatory dose have produced therapeutic benefit without production of antibiotic-resistant bacterial flora.1 In large-scale clinical trials, no women treated with anti-inflammatory-dose doxycycline developed vaginal candidiasis.1 1. Del Rosso JQ, Webster GF, Jackson M, et al: Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline monohydrate controlled-release capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol in press
XIV Diseases of the Nail James Q. del Rosso, DO
University of Nevada School of Medicine C. Ralph Daniel, III, MD University of Mississippi School of Medicine Confirming Fungal Nail Infections The most characteristic clinical features of dermatophyte onychomycosis (the most common type of fungal nail infection) are distal onycholysis, subungual hyperkeratosis, and a dystrophic, discolored nail plate. Because this combination of features is also seen in persons with nail psoriasis, accurate diagnosis may require performance of a potassium hydroxide (KOH) preparation and fungal culture. It is important that specimens be obtained from the nail bed and that culture specimens be transported and plated appropriately, because different culture media are required for identification of dermatophyte and nondermatophyte fungal nail pathogens. Dermatophyte test medium (DTM) may be used as an in-office culture technique that has no special incubation requirements. DTM is inexpensive and accurate in the diagnosis of dermatophyte onychomycosis. Another method used to diagnose onychomycosis involves histologic examination of a nail plate specimen obtained from the distal free edge of the plate at its attachment to the nail bed.1 The nail-plate sample is sent to the histology laboratory, where it is thinly sectioned and stained with periodic acid-Schiff (PAS) stain. Under microscopic examination, fungi appear red, because the PAS stain highlights glycogen and mucoprotein in the cell walls of hyphae.1 1. Gupta AK, Ricci MJ: Diagnosing onychomycosis. Dermatol Clin 24:365, 2006 [PMID 16798434] Treatment beyond Antifungals Pharmacologic therapy alone may be inadequate in some cases of onychomycosis. A very thick mycotic nail plate, marked onycholysis, and cases presenting as lateral infection may warrant adjunctive debridement.1 In addition, the presence of a dermatophytoma has been shown to reduce the response to medical therapy, including oral antifungal agents. A dermatophyoma presents as a visible, walled-off column or spike that contains multiple, thick-walled hyphae. When a dermatophytoma is present, response to oral antifungal therapy is maximized by physical removal of the loculated mass through either surgical or chemical debridement.1 In some cases, the use of more prolonged oral antifungal therapy (beyond standard recommendations) may be needed to clear the infection, especially in immunocompromised patients, elderly patients with slow-growing nails, and in more severe cases of onychomycosis. 1. Gupta AK, Linh QT: Onychomycosis therapies: strategies to improve efficacy. Dermatol Clin 24:381, 2006 [PMID 16798437] XV Disorders of Pigmentation Pearl E. Grimes, MD
University of California, Los Angeles, School of Medicine The Feds Eye a Melasma Treatment Of the topical agents used to treat melasma, maximal efficacy has been reported with combination agents such as the triple-combination bleach containing hydroquinone 4%, tretinoin 0.05%, and fluocinoline acetonide 0.01% (TriLuma).1 In addition, hydroquinone 4% combined with retinol in a microsponge formulation has demonstrated significant efficacy in patients with melasma. Since January 2001, hydroquinone has been banned from cosmetic skin-lightening formulations in the European Union. In the United States, the Food and Drug Administration has raised the possibility that manufacturers of older hydroquinone preparations might be required to file new drug applications, effectively removing those preparations from the market. The FDA is concerned about potential side effects such as exogenous ochronosis and theoretical risks of carcinogenicity.2 Most of the cases of exogenous ochronosis in the United States are due to 2% hydroquinone, while in Africa, they are usually caused by higher concentrations or excessive quantities of the product. Concerns about carcinogenicity have been raised because hydroquinone is a derivative of benzene. Nevertheless, there has not been a single documented case of malignancy associated with topical application of hydroquinones.2,3 Carcinogenicity assays have not sufficiently demonstrated the carcinogenic potential of hydroquinone, and epidemiologic studies of workers exposed extensively to hydroquinones have not shown any negative systemic health effects.4 Similarly, developmental and reproductive studies in animals have not shown negative effects, and dermal toxicity studies in animals have failed to show any systemic toxicity.4 A study of women in Africa found no differences in pregnancy outcomes between users and nonusers of hydroquinone.5 Nevertheless, the FDA continues to scrutinize hydroquinone preparations closely. 1. Grimes PE, Kelly PA, Torok H, et al: Community-based trial of a triple combination agent for the treatment of facial melasma. Cutis 77:177, 2006 [PMID 16610738] 2. Westerhof W, Kooyers TJ: Hydroquinone and its analogues in dermatology: a potential health risk. J Cosmet Dermatol 4:55, 2005 [PMID 17166200] 3. Nordlund JJ, Grimes PE, Ortonne JP: The safety of hydroquinone. J Eur Acad Dermatol Venereol 20:781, 2006 [PMID 16898897] 4. O'donoghue JL: Hydroquinone and its analogues in dermatology: a risk-benefit viewpoint. J Cosmet Dermatol 5:196, 2006 [PMID 17177740] 5. Mahe A, Perret JL, Ly F, et al: The cosmetic use of skin-lightening products during pregnancy in Dakar, Senegal: a common and potentially hazardous practice. Trans R Soc Trop Med Hyg 101:183, 2007 [PMID 17023012] Lightening after Inflammation Therapies for postinflammatory hyperpigmentation include over-the-counter and prescription hydroquinone preparations. Other treatments are azelaic acid, kojic acid, and retinoic acid. Maximal results are achieved with hydroquinone formulations. A recent study reported significant efficacy of tazarotene 0.1% cream for treatment of postinflammatory hyperpigmentation caused by acne vulgaris.1 1. Grimes PE, Callendar V: Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis 77:45, 2006 [PMID 16475496]
Special Alerts
For more information, see Section 11, Chapter XV Parkinson Disease and Other Movement Disorders.
For more information, see Section 13, Chapter II Depression and Bipolar Disorder. Clinical Practice Guidelines
For more information, see Section 11, Chapter VIII Headache.
New Treatment of Schizophrenia The FDA has approved paliperidone extended-release tablets for the treatment of schizophrenia. Paliperidone is the principal active metabolite of the currently approved antipsychotic drug risperidone. The effectiveness of paliperadone in the acute treatment of schizophrenia was established in three 6-week, placebo-controlled trials in 1,665 patients in North America, Europe, and Asia. In all three studies, paliperadone was superior to placebo in relieving symptoms of schizophrenia. Patients in the studies received 3 to 12 mg a day of paliperadone, which is the dosage range recommended for clinical use. Among the commonly reported adverse events were restlessness, extrapyramidal symptoms, tachycardia, and sleepiness. Other atypical antipsychotics are associated with increased mortality in elderly patients with dementia-related psychosis, and paliperadone is not approved for dementia-related psychosis. The effectiveness of paliperadone has not been evaluated in placebo-controlled trials for longer than 6 weeks, and patients who use the drug for extended periods should be periodically reevaluated by a physician. Generic Name: Paliperidone Brand Name: Invega Manufacturer: ALZA Corp., Mountain View, California Source: FDA Approves New Drug for Schizophrenia. FDA News. U.S. Food and Drug Administration, December 20, 2006 (http://www.fda.gov/bbs/topics/NEWS/2006/NEW01534.html) Spot an error, have a question? Email us at whatsnew@webmd.net |
Valvular regurgitation associated
with use of dopamine agonists for Parkinson disease 
Prevention of Migraine
Headache and Management of Acute Migraine Attacks 