- Email: [email protected]
A significant step forward for gout
Comment
There are medicolegal implications. In the context of otherwise unexplained SUDI, an isolate of S aureus or E coli should be viewed as at least a possible explanation for death, even if the organisms are found in mixed culture. Recent evidence indicates that death in unexplained SUDI is often rapid, with transition from being well to death in less than 1 h in many cases.9,10 If bacteria have a role, this points to direct action of bacterial toxins on cardiorespiratory activity or neural control. The new science of proteomics offers techniques to recognise bacterial protein products in human body fluids, and this is the obvious next step in investigating sudden infant death.11 *James A Morris, Linda M Harrison
1 2 3
4
5
6 7 8
9
Royal Infirmary, Lancaster LA1 4RP, UK [email protected]
10
JAM has given expert testimony in cases of sudden infant death when the significance of bacterial isolates has been an issue. LMH declares that she has no conflict of interest.
11
Fleming PJ, Blair PS, Bacon C, Berry PJ. Sudden unexpected deaths in infancy: the CESDI SUDI studies 1993–1996. London: The Stationery Office, 2000. Morris JA. The common bacterial toxin hypothesis of sudden infant death syndrome. FEMS Immunol Med Microbiol 1999; 25: 11–17. Harrison LM, Morris JA, Telford DR, Brown SM, Jones K. The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position. FEMS Immunol Med Microbiol 1999; 25: 19–28. Zorgani A, Essery SD, Al Madani O, et al. Detection of pyrogenic toxins of Staphylococcus aureus in sudden infant death syndrome. FEMS Immunol Med Microbiol 1999; 25: 103–08. Gilbert R, Rudd P, Berry PJ, et al. Combined effect of infection and heavy wrapping on the risk of sudden unexpected death in infancy. Arch Dis Child 1992; 67: 171–77. Morris JA, Harrison LM, Partridge SM. Postmortem bacteriology; a re-evaluation. J Clin Pathol 2006; 59: 1–9. Morris JA, Harrison LM, Partridge SM. Practical and theoretical aspects of postmortem bacteriology. Curr Diagn Pathol 2007; 13: 65–74. Weber MA, Klein NJ, Hartley JC, Lock PE, Malone M, Sebire NJ. Infection and sudden unexpected death in infancy: a systematic retrospective case review. Lancet 2008; 371: 1848–53. Poets CF, Meny RG, Chobonian MR, Bonofiglo RE. Gasping and other cardiorespiratory patterns during sudden infant death. Pediatr Res 1999; 45: 350–54. Blair PS, Platt MW, Smith IJ, Fleming PJ. Sudden infant death syndrome and the time of death: factors associated with night-time and day-time deaths. Int J Epidemiol 2006; 35: 1563–69. Banks RE, Dunn MJ, Hochstrasser DF, et al. Proteomics: new perspectives, new biomedical opportunities. Lancet 2000; 356: 1749–56.
A significant step forward for gout See Articles page 1854
1816
Gout is an increasingly common inflammatory joint disease worldwide, with a prevalence of 1·4% in the UK and Germany.1,2 Although not life-threatening, it is extremely painful and disabling, and needs rapid, effective, and safe treatment. Traditional treatments have included colchicine and non-steroidal anti-inflammatory drugs (NSAIDs), but these are not without serious and potentially life-threatening adverse events. The use of corticosteroids in the acute phase of the illness provides an equally effective and safer method to treat gout. In a systematic review, Janssens and colleagues3 stated that there was inconclusive evidence for the effectiveness of corticosteroids in the treatment of acute gout. However, in today’s Lancet, the same group claim to provide evidence of equivalent effectiveness of oral prednisolone and naproxen in the treatment of gout arthritis.4 Their study was done in the Netherlands and adds to our recent work from Hong Kong, in which we compared oral prednisolone with NSAIDs in patients presenting to an emergency department with acute gout-like syndrome.5 Both studies provide useful and important information to front-line staff who manage patients presenting with acute joint pain.
A comparison of these two studies draws attention to important differences in the approach to gout— one from a purist and the other from a pragmatic viewpoint. Should the clinical diagnosis of acute gout be confirmed by the presence of negatively birefringent monosodium urate crystals in joint aspirate before treatment is started? Purists will argue that such confirmation is crucial.6 However, researchers might not be facing the heavy demands from undifferentiated patients in busy primary-care clinics and emergency departments. Pragmatists make a clinical diagnosis of acute gout-like arthritis and treat it accordingly, often without definitive laboratory confirmation of disease. Arthrocentesis is not always possible because of technical difficulty, patients’ preference, and resource constraints. Pragmatists will further argue that insufficient evidence exists to suggest that such an approach leads to harm. Janssens and colleagues’ new study4 veers towards the purist point of view because a definitive diagnosis of gout was made in every case. This finding will satisfy purist researchers but will only partly convince clinicians who diagnose and treat acute gout-like syndrome in front-line settings. However, purist studies might lose relevance when applied in www.thelancet.com Vol 371 May 31, 2008
circumstances in which a definitive diagnosis of gout has not been made. Janssens and colleagues’ study is a high-quality randomised trial, comparing steroids with NSAIDs in acute gout. It is the largest trial of its type until now and is well designed, generalisable (at least to a European population), and applicable to the undifferentiated patient with acute monoarthropathy in primary care. However, some aspects of the study deserve particular attention. 381 patients were referred to the trial centre with suspected monoarthritis, of whom only 120 (32%) entered the trial. Therefore two-thirds of these potential patients with a gout-like syndrome still needed acute treatment. Should steroids be given to this group? Three of the 165 patients who were excluded because monosodium urate crystals were not identified had bacterial arthritis. This group represents 0·08% of patients with gout. Treatment of such patients with steroids can be perceived as hazardous since symptoms might be masked, time to definitive care delayed, the immune response blunted, and the risk of disseminated sepsis increased. However, there is little if any evidence that advertently or inadvertently treating bacterial arthritis with steroids produces such adverse effects. In fact, evidence is scarce that use of short courses of steroids in children with septic arthritis reduces residual joint dysfunction.7 The low incidence of adverse gastrointestinal events in the group receiving NSAIDs is surprising. This finding could be partly explained because patients with a history of upper gastrointestinal disease were excluded. However, the investigators suggest that substantial economic benefits might result from considering prednisolone as a first treatment option for gout. This notion might be correct in view of other studies8–10 showing that significant adverse events are associated with NSAIDs, but Janssens’ study shows no safety difference between the two treatments. From their data, an economic benefit seems unlikely, but a formal cost-effectiveness analysis is needed. Although there are validated methods to assess pain,11 there are no validated means to assess general or walking disability for patients with gout. Although pain might be the primary disabling factor in patients with gout, comorbid disorders can have an important role in quality of life for these patients.12 Further evidence is needed that these invalidated methods are valid for acute gout. www.thelancet.com Vol 371 May 31, 2008
T Rainer
Comment
Tophus in patient with gout
There are two main hindrances to implementation of these findings in clinical practice. First, although well designed, Janssens’ study is fairly small and was done in one centre. The general clinician might not be convinced that studies with only 120 patients should change long-established practice. Clearly this study needs to be repeated in other locales with different incidences of gastrointestinal disease. Second, changes in clinical practice often need strong marketing forces, which might not be forthcoming unless drug companies stand to benefit from newer and more expensive drugs. Nevertheless Janssens’ trial will go some way to satisfy both rheumatological purists and front-line pragmatists that short-term oral corticosteroids are as equally effective as NSAIDs in the initial treatment of acute gout and gout-like syndrome. *Timothy H Rainer, Colin A Graham Accident and Emergency Medicine Academic Unit, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR [email protected] We declare that we have no conflict of interest. 1
2 3
Annemans L, Spaepen E, Gaskin M, et al. Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005. Ann Rheum Dis 2007; published online Nov 2. DOI:10.1136/ard.2007.076232. Roddy E, Zhang W, Doherty M. The changing epidemiology of gout. Nat Clin Pract Rheumatol 2007; 3: 443–49. Janssens H, Lucassen P, van de Laar F, Janssen M, van de Lisdonk E. Systemic corticosteroids for acute gout. Cochrane Database Syst Rev 2008; 16: CD005521.
1817
Comment
4
5
6 7
Janssens HJEM, Janssen M, van de Lisdonk EH, van Riel PLCM, van Weel C. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008; 371: 1854–60. Man CY, Cheung TF, Cameron P, Rainer TH. Comparison of oral prednisolone and oral indomethacin in the treatment of acute gout-like arthritis: a double-blind, randomised, controlled trial. Ann Emerg Med 2007; 49: 670–77. Schumacher HR Jr, Edwards LN, Perez-Ruiz F, et al. Outcome measures for acute and chronic gout. J Rheumatol 2005; 32: 2452–55. Odio CM, Ramirez T, Arias G, et al. Double blind, randomized, placebo-controlled study of dexamethasone therapy for hematogenous septic arthritis in children. Pediatr Infect Dis J 2003; 22: 883–88.
8 9
10
11 12
James DS. The multisystem adverse effects of NSAID therapy. J Am Osteopath Assoc 1999; 99: S1–7. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 769–72. Garcia Rodriguez LA, Hernandez-Diaz S. The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res 2001; 3: 98–101. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996; 27: 485–89. Roddy E, Zhang W, Doherty M. Is gout associated with reduced quality of life? A case-control study. Rheumatology (Oxford) 2007; 46: 1441–44.
Steroid and antiviral treatment for Bell’s palsy Bell’s palsy is an acute peripheral unilateral facial paralysis of unknown cause. It is the most common acute facial paralysis, with an incidence of 20–30 per 100 000 people annually. In our series of 3385 patients with acute facial paralysis over the past 30 years, Bell’s palsy accounted for 2097 cases (62%). PCR usually identifies fragments of DNA of herpes simplex virus in clinical samples from patients with Bell’s palsy. These fragments were detected more often in saliva from patients with Bell’s palsy than in saliva from healthy volunteers.1 Such DNA fragments were also identified in the endoneural fluid of the facial nerve during facial-nerve decompression surgery in 11 of 14 patients (79%) with Bell’s palsy.2 Thus we speculate that reactivation of herpes simplex virus might lead to Bell’s palsy: herpes simplex virus is involved in about 31–79% of cases of Bell’s palsy.1–3 Ramsay-Hunt syndrome is the second most common acute facial paralysis, and is caused by reactivation of latent varicella zoster virus. It is associated with zoster oticus and is often complicated by vestibulocochlear
Bell’s palsy Zoster without vesicles Herpes simplex virus 31–79% of Bell’s palsy
RamsayHunt syndrome
Varicella zoster virus 8–28% of Bell’s palsy
Figure: Involvement of herpes simplex and varicella zoster viruses in acute facial palsy
1818
dysfunction. The diagnosis of acute facial paralysis is sometimes complicated by the presence of so-called zoster without vesicles (zoster sine herpete). In the absence of vestibulocochlear dysfunction or zoster in the auricle, such cases are clinically diagnosed as Bell’s palsy. Serological and PCR studies show that the prevalence of zoster sine herpete in Bell’s palsy ranges from 8% to 28%.4,5 Therefore although herpes simplex virus is a major cause of Bell’s palsy, varicella zoster virus and other unknown causes might also be important (figure). Steroids and adjunctive antiviral drugs might improve outcome for patients with Bell’s palsy. In 2007, two randomised placebo-controlled trials assessed the role of antiviral drugs but gave conflicting findings.6,7 In a singleblind study in 296 patients, we compared valaciclovir (1000 mg a day for 5 days) plus prednisolone (60 mg for the first 3 days, tapered thereafter) with placebo plus prednisolone.6 Complete recovery was significantly higher (p=0·045, 95% CI 0·47–0·60) in the valaciclovir group than in the placebo group (110 of 114 [96·5%] patients vs 96 of 107 [89·7%] patients, respectively. By contrast, Sullivan and colleagues7 noted that 92·7% of 124 patients treated with aciclovir (2000 mg a day) plus prednisolone (50 mg a day) for 10 days had complete recovery compared with 96·1% of 127 patients treated with placebo plus prednisolone for 10 days (p=0·28, 95% CI 0·42–0·55). The researchers concluded that an antiviral was not beneficial in improving the prognosis of facial paralysis. Systematic reviews8,9 suggest that oral steroids are safe and effective in the treatment of Bell’s palsy. Steroids have many side-effects, including anti-inflammatory effects and the suppression of immune reactions. Regardless of the cause, the pathological condition underlying Bell’s www.thelancet.com Vol 371 May 31, 2008
There are medicolegal implications. In the context of otherwise unexplained SUDI, an isolate of S aureus or E coli should be viewed as at least a possible explanation for death, even if the organisms are found in mixed culture. Recent evidence indicates that death in unexplained SUDI is often rapid, with transition from being well to death in less than 1 h in many cases.9,10 If bacteria have a role, this points to direct action of bacterial toxins on cardiorespiratory activity or neural control. The new science of proteomics offers techniques to recognise bacterial protein products in human body fluids, and this is the obvious next step in investigating sudden infant death.11 *James A Morris, Linda M Harrison
1 2 3
4
5
6 7 8
9
Royal Infirmary, Lancaster LA1 4RP, UK [email protected]
10
JAM has given expert testimony in cases of sudden infant death when the significance of bacterial isolates has been an issue. LMH declares that she has no conflict of interest.
11
Fleming PJ, Blair PS, Bacon C, Berry PJ. Sudden unexpected deaths in infancy: the CESDI SUDI studies 1993–1996. London: The Stationery Office, 2000. Morris JA. The common bacterial toxin hypothesis of sudden infant death syndrome. FEMS Immunol Med Microbiol 1999; 25: 11–17. Harrison LM, Morris JA, Telford DR, Brown SM, Jones K. The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position. FEMS Immunol Med Microbiol 1999; 25: 19–28. Zorgani A, Essery SD, Al Madani O, et al. Detection of pyrogenic toxins of Staphylococcus aureus in sudden infant death syndrome. FEMS Immunol Med Microbiol 1999; 25: 103–08. Gilbert R, Rudd P, Berry PJ, et al. Combined effect of infection and heavy wrapping on the risk of sudden unexpected death in infancy. Arch Dis Child 1992; 67: 171–77. Morris JA, Harrison LM, Partridge SM. Postmortem bacteriology; a re-evaluation. J Clin Pathol 2006; 59: 1–9. Morris JA, Harrison LM, Partridge SM. Practical and theoretical aspects of postmortem bacteriology. Curr Diagn Pathol 2007; 13: 65–74. Weber MA, Klein NJ, Hartley JC, Lock PE, Malone M, Sebire NJ. Infection and sudden unexpected death in infancy: a systematic retrospective case review. Lancet 2008; 371: 1848–53. Poets CF, Meny RG, Chobonian MR, Bonofiglo RE. Gasping and other cardiorespiratory patterns during sudden infant death. Pediatr Res 1999; 45: 350–54. Blair PS, Platt MW, Smith IJ, Fleming PJ. Sudden infant death syndrome and the time of death: factors associated with night-time and day-time deaths. Int J Epidemiol 2006; 35: 1563–69. Banks RE, Dunn MJ, Hochstrasser DF, et al. Proteomics: new perspectives, new biomedical opportunities. Lancet 2000; 356: 1749–56.
A significant step forward for gout See Articles page 1854
1816
Gout is an increasingly common inflammatory joint disease worldwide, with a prevalence of 1·4% in the UK and Germany.1,2 Although not life-threatening, it is extremely painful and disabling, and needs rapid, effective, and safe treatment. Traditional treatments have included colchicine and non-steroidal anti-inflammatory drugs (NSAIDs), but these are not without serious and potentially life-threatening adverse events. The use of corticosteroids in the acute phase of the illness provides an equally effective and safer method to treat gout. In a systematic review, Janssens and colleagues3 stated that there was inconclusive evidence for the effectiveness of corticosteroids in the treatment of acute gout. However, in today’s Lancet, the same group claim to provide evidence of equivalent effectiveness of oral prednisolone and naproxen in the treatment of gout arthritis.4 Their study was done in the Netherlands and adds to our recent work from Hong Kong, in which we compared oral prednisolone with NSAIDs in patients presenting to an emergency department with acute gout-like syndrome.5 Both studies provide useful and important information to front-line staff who manage patients presenting with acute joint pain.
A comparison of these two studies draws attention to important differences in the approach to gout— one from a purist and the other from a pragmatic viewpoint. Should the clinical diagnosis of acute gout be confirmed by the presence of negatively birefringent monosodium urate crystals in joint aspirate before treatment is started? Purists will argue that such confirmation is crucial.6 However, researchers might not be facing the heavy demands from undifferentiated patients in busy primary-care clinics and emergency departments. Pragmatists make a clinical diagnosis of acute gout-like arthritis and treat it accordingly, often without definitive laboratory confirmation of disease. Arthrocentesis is not always possible because of technical difficulty, patients’ preference, and resource constraints. Pragmatists will further argue that insufficient evidence exists to suggest that such an approach leads to harm. Janssens and colleagues’ new study4 veers towards the purist point of view because a definitive diagnosis of gout was made in every case. This finding will satisfy purist researchers but will only partly convince clinicians who diagnose and treat acute gout-like syndrome in front-line settings. However, purist studies might lose relevance when applied in www.thelancet.com Vol 371 May 31, 2008
circumstances in which a definitive diagnosis of gout has not been made. Janssens and colleagues’ study is a high-quality randomised trial, comparing steroids with NSAIDs in acute gout. It is the largest trial of its type until now and is well designed, generalisable (at least to a European population), and applicable to the undifferentiated patient with acute monoarthropathy in primary care. However, some aspects of the study deserve particular attention. 381 patients were referred to the trial centre with suspected monoarthritis, of whom only 120 (32%) entered the trial. Therefore two-thirds of these potential patients with a gout-like syndrome still needed acute treatment. Should steroids be given to this group? Three of the 165 patients who were excluded because monosodium urate crystals were not identified had bacterial arthritis. This group represents 0·08% of patients with gout. Treatment of such patients with steroids can be perceived as hazardous since symptoms might be masked, time to definitive care delayed, the immune response blunted, and the risk of disseminated sepsis increased. However, there is little if any evidence that advertently or inadvertently treating bacterial arthritis with steroids produces such adverse effects. In fact, evidence is scarce that use of short courses of steroids in children with septic arthritis reduces residual joint dysfunction.7 The low incidence of adverse gastrointestinal events in the group receiving NSAIDs is surprising. This finding could be partly explained because patients with a history of upper gastrointestinal disease were excluded. However, the investigators suggest that substantial economic benefits might result from considering prednisolone as a first treatment option for gout. This notion might be correct in view of other studies8–10 showing that significant adverse events are associated with NSAIDs, but Janssens’ study shows no safety difference between the two treatments. From their data, an economic benefit seems unlikely, but a formal cost-effectiveness analysis is needed. Although there are validated methods to assess pain,11 there are no validated means to assess general or walking disability for patients with gout. Although pain might be the primary disabling factor in patients with gout, comorbid disorders can have an important role in quality of life for these patients.12 Further evidence is needed that these invalidated methods are valid for acute gout. www.thelancet.com Vol 371 May 31, 2008
T Rainer
Comment
Tophus in patient with gout
There are two main hindrances to implementation of these findings in clinical practice. First, although well designed, Janssens’ study is fairly small and was done in one centre. The general clinician might not be convinced that studies with only 120 patients should change long-established practice. Clearly this study needs to be repeated in other locales with different incidences of gastrointestinal disease. Second, changes in clinical practice often need strong marketing forces, which might not be forthcoming unless drug companies stand to benefit from newer and more expensive drugs. Nevertheless Janssens’ trial will go some way to satisfy both rheumatological purists and front-line pragmatists that short-term oral corticosteroids are as equally effective as NSAIDs in the initial treatment of acute gout and gout-like syndrome. *Timothy H Rainer, Colin A Graham Accident and Emergency Medicine Academic Unit, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR [email protected] We declare that we have no conflict of interest. 1
2 3
Annemans L, Spaepen E, Gaskin M, et al. Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005. Ann Rheum Dis 2007; published online Nov 2. DOI:10.1136/ard.2007.076232. Roddy E, Zhang W, Doherty M. The changing epidemiology of gout. Nat Clin Pract Rheumatol 2007; 3: 443–49. Janssens H, Lucassen P, van de Laar F, Janssen M, van de Lisdonk E. Systemic corticosteroids for acute gout. Cochrane Database Syst Rev 2008; 16: CD005521.
1817
Comment
4
5
6 7
Janssens HJEM, Janssen M, van de Lisdonk EH, van Riel PLCM, van Weel C. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008; 371: 1854–60. Man CY, Cheung TF, Cameron P, Rainer TH. Comparison of oral prednisolone and oral indomethacin in the treatment of acute gout-like arthritis: a double-blind, randomised, controlled trial. Ann Emerg Med 2007; 49: 670–77. Schumacher HR Jr, Edwards LN, Perez-Ruiz F, et al. Outcome measures for acute and chronic gout. J Rheumatol 2005; 32: 2452–55. Odio CM, Ramirez T, Arias G, et al. Double blind, randomized, placebo-controlled study of dexamethasone therapy for hematogenous septic arthritis in children. Pediatr Infect Dis J 2003; 22: 883–88.
8 9
10
11 12
James DS. The multisystem adverse effects of NSAID therapy. J Am Osteopath Assoc 1999; 99: S1–7. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 769–72. Garcia Rodriguez LA, Hernandez-Diaz S. The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res 2001; 3: 98–101. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996; 27: 485–89. Roddy E, Zhang W, Doherty M. Is gout associated with reduced quality of life? A case-control study. Rheumatology (Oxford) 2007; 46: 1441–44.
Steroid and antiviral treatment for Bell’s palsy Bell’s palsy is an acute peripheral unilateral facial paralysis of unknown cause. It is the most common acute facial paralysis, with an incidence of 20–30 per 100 000 people annually. In our series of 3385 patients with acute facial paralysis over the past 30 years, Bell’s palsy accounted for 2097 cases (62%). PCR usually identifies fragments of DNA of herpes simplex virus in clinical samples from patients with Bell’s palsy. These fragments were detected more often in saliva from patients with Bell’s palsy than in saliva from healthy volunteers.1 Such DNA fragments were also identified in the endoneural fluid of the facial nerve during facial-nerve decompression surgery in 11 of 14 patients (79%) with Bell’s palsy.2 Thus we speculate that reactivation of herpes simplex virus might lead to Bell’s palsy: herpes simplex virus is involved in about 31–79% of cases of Bell’s palsy.1–3 Ramsay-Hunt syndrome is the second most common acute facial paralysis, and is caused by reactivation of latent varicella zoster virus. It is associated with zoster oticus and is often complicated by vestibulocochlear
Bell’s palsy Zoster without vesicles Herpes simplex virus 31–79% of Bell’s palsy
RamsayHunt syndrome
Varicella zoster virus 8–28% of Bell’s palsy
Figure: Involvement of herpes simplex and varicella zoster viruses in acute facial palsy
1818
dysfunction. The diagnosis of acute facial paralysis is sometimes complicated by the presence of so-called zoster without vesicles (zoster sine herpete). In the absence of vestibulocochlear dysfunction or zoster in the auricle, such cases are clinically diagnosed as Bell’s palsy. Serological and PCR studies show that the prevalence of zoster sine herpete in Bell’s palsy ranges from 8% to 28%.4,5 Therefore although herpes simplex virus is a major cause of Bell’s palsy, varicella zoster virus and other unknown causes might also be important (figure). Steroids and adjunctive antiviral drugs might improve outcome for patients with Bell’s palsy. In 2007, two randomised placebo-controlled trials assessed the role of antiviral drugs but gave conflicting findings.6,7 In a singleblind study in 296 patients, we compared valaciclovir (1000 mg a day for 5 days) plus prednisolone (60 mg for the first 3 days, tapered thereafter) with placebo plus prednisolone.6 Complete recovery was significantly higher (p=0·045, 95% CI 0·47–0·60) in the valaciclovir group than in the placebo group (110 of 114 [96·5%] patients vs 96 of 107 [89·7%] patients, respectively. By contrast, Sullivan and colleagues7 noted that 92·7% of 124 patients treated with aciclovir (2000 mg a day) plus prednisolone (50 mg a day) for 10 days had complete recovery compared with 96·1% of 127 patients treated with placebo plus prednisolone for 10 days (p=0·28, 95% CI 0·42–0·55). The researchers concluded that an antiviral was not beneficial in improving the prognosis of facial paralysis. Systematic reviews8,9 suggest that oral steroids are safe and effective in the treatment of Bell’s palsy. Steroids have many side-effects, including anti-inflammatory effects and the suppression of immune reactions. Regardless of the cause, the pathological condition underlying Bell’s www.thelancet.com Vol 371 May 31, 2008