- Email: [email protected]
Churg-Strauss syndome
CORRESPONDENCE
deprivation caused by sun-downing, lack of choice in caregiving) issue. *Abhilash Desai, John T Chibnall Department of Geriatric Psychiatry, Saint Louis University School of Medicine, St Louis, MO 63104, USA. 1
Vedhara K, Cox NKM, Wilcock GK, et al. Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 1999; 353: 627–31. 2 Leproult R, Copinschi G, Buxton O, Van Cauter E. Sleep loss results in an elevation of cortisol levels the next evening. Sleep 1997; 20: 865–70. 3 Robinson-Wheelen S, Kiecolt-Glaser J. Spousal caregiving: does it matter if you have a choice? J Clin Geropsychol 1997; 3: 283–89.
Author’s reply Sir—Abhilash Desai and John Chibnall correctly observe that we did not comment on which part of caregiving or how much caregiving gives rise to the immune alterations that we report. We did collect data on a various factor relevant to this issue (eg, the average numbers of hours per day participants were engaged in the caregiving role; their self-reported quality of sleep; their social support networks and the nature and frequency of the caregiving challenges they faced). However, our main aim was to show that the task of caregiving per se was associated with immune modulation. In this context, it was not directly relevant to report on those parts of the caregiving role or the psychosocial status of the caregivers that gave rise to the psychological morbidity we observed. Clearly, these are important issues but ones that could be given adequate consideration within the context of our report. Many of the caregiving indices we examined and the ones referred to by Desai and Chibnall are not clearly defined and not, therefore, amenable to accurate measurement. For example, Desai and Chibnall suggest that the caregiving task may differ if it is undertaken voluntarily or involuntarily. It is unclear how this distinction could be made in the context of informal caregivers—ie, it is unlikely that caregivers would readily admit that they have involuntarily taken on their caregiving role. Similarly, in practice, we observed that it is difficult to obtain accurate estimates from caregivers on the intensity of their caregiving role. Such assessment difficulties further cautioned against the inclusion of these data in our report. Desai and Chibnall also remark that a control group of partners who were not the patients’ primary carers may have yielded different results, which is,
1970
indeed, possible. However, it is not clear that, in practice, such a population could be readily identified or recruited. Furthermore, even if such a group were available it is likely that their personal and social circumstances would result in a biased population which would not be comparable to our cohort of spousal caregivers (eg, individuals from higher socioeconomic groups; or individuals who had a chronic debilitating disease which prevents them from taking on the caregiving role). We agree that it is important to obtain a clearer understanding of which parts of the caregiving role resulted in the chronic stress and concomitant immune modulation observed in our cohort, but these issues were beyond the scope of the report. K Vedhara Department of Experimental Psychology, University of Bristol, Bristol BS8 1TN, UK
Churg-Strauss syndome Sir—Richard Green and Andrew Vayonis (Feb 27, p 725)1 describe two cases of Churg-Strauss syndrome (CSS) in patients treated for asthma with zarfirlukast who had not been receiving systemic corticosteroids. They compare these patients with those previously reported by us2 by stating that their patients had not been withdrawn from corticosteroids and hence did not have the forme fruste of CSS. They imply a causative role for zarfirlukast in the pathogenesis of CSS in these patients. There have been several other reports of CSS in association with zarfirlukast treatment for asthma,3,4 in which corticosteroid withdrawal was not a primary component of syndrome onset. However, in our series, in the Green and Vayonis cases, and in the other reported cases, all patients had signs consistent with incipient CSS characterised by a long course of asthma and sinusitis that required systemic or high doses of inhaled steroids for control, and the institution of new asthma therapy such as leukotriene modifiers or long-acting -agonists. Before the introduction of these therapies, Lanham and colleagues5 had described the natural course of CSS as “indolent allergic disease that evolves into asthma with multiple exacerbations that may progress to eosinophilia and finally, multi-organ eosinophilic vasculitis”. Hence we feel that all the reported cases are not directly the result of these new medications, but rather, occurred as part of the natural course of the
disease. CSS could have occurred coincidentally with these drugs in progressive disease; in unmasking of progressive disease owing to steroid withdrawal; or delayed progression of airway symptoms by the new therapies before systemic involvement. For instance, the inhaled corticosteroids that these patients were taking could have been absorbed systemically and thereby quelled some early CSS manifestations or the leukotriene modifiers could have quelled airway symptoms that would otherwise have been heralding events of the syndrome. Both Merck and Glaxo Wellcome have sent letters to health-care professionals issuing warnings of the occurrence of CSS in association with another leukotriene receptor antagonist, montelukast, and with an inhaled corticosteroid, fluticasone. Similarly, the Physician’s Desk Reference lists warn of the possibility of CSS in association with beclomethasone, flunisolide, cromolyn, and others. The fact that this syndrome is being reported with several different medications all of which have different structures makes a drug-related aetiology unlikely. Both the aetiology and incidence of CSS remain unknown. Although the number of reported cases of CSS seems to be increasing previous reports probably underestimated the incidence of CSS because many patients who had previously been perceived to have asthma were put on suppressive doses of systemic steroids or high-dose inhaled steroids, and thus never developed the full clinical manifestations of the syndrome. We therefore contest the implication that CSS was induced by zafirlukast. *Michael Wechsler, Jeffrey M Drazen Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA (e-mail: [email protected]) 1
Green RL, Vayonis AG. Churg-Strauss syndrome after zafirlukast in two patients not receiving systemic steroid treatment. Lancet 1999; 353: 725–26. 2 Wechsler ME, Garpestad E, Flier SR, et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA 1998; 279: 455–57. 3 Katz RS, Papernik M. Zariflukast and Churg-Strauss syndrome. JAMA 1998; 279: 1949. 4 Knoell DL, Lucas J, Allen JN. Churg-Strauss syndrome associated with zafirlukast. Chest 1998; 114: 332–34. 5 Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine 1983; 63: 65–81.
THE LANCET • Vol 353 • June 5, 1999
deprivation caused by sun-downing, lack of choice in caregiving) issue. *Abhilash Desai, John T Chibnall Department of Geriatric Psychiatry, Saint Louis University School of Medicine, St Louis, MO 63104, USA. 1
Vedhara K, Cox NKM, Wilcock GK, et al. Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 1999; 353: 627–31. 2 Leproult R, Copinschi G, Buxton O, Van Cauter E. Sleep loss results in an elevation of cortisol levels the next evening. Sleep 1997; 20: 865–70. 3 Robinson-Wheelen S, Kiecolt-Glaser J. Spousal caregiving: does it matter if you have a choice? J Clin Geropsychol 1997; 3: 283–89.
Author’s reply Sir—Abhilash Desai and John Chibnall correctly observe that we did not comment on which part of caregiving or how much caregiving gives rise to the immune alterations that we report. We did collect data on a various factor relevant to this issue (eg, the average numbers of hours per day participants were engaged in the caregiving role; their self-reported quality of sleep; their social support networks and the nature and frequency of the caregiving challenges they faced). However, our main aim was to show that the task of caregiving per se was associated with immune modulation. In this context, it was not directly relevant to report on those parts of the caregiving role or the psychosocial status of the caregivers that gave rise to the psychological morbidity we observed. Clearly, these are important issues but ones that could be given adequate consideration within the context of our report. Many of the caregiving indices we examined and the ones referred to by Desai and Chibnall are not clearly defined and not, therefore, amenable to accurate measurement. For example, Desai and Chibnall suggest that the caregiving task may differ if it is undertaken voluntarily or involuntarily. It is unclear how this distinction could be made in the context of informal caregivers—ie, it is unlikely that caregivers would readily admit that they have involuntarily taken on their caregiving role. Similarly, in practice, we observed that it is difficult to obtain accurate estimates from caregivers on the intensity of their caregiving role. Such assessment difficulties further cautioned against the inclusion of these data in our report. Desai and Chibnall also remark that a control group of partners who were not the patients’ primary carers may have yielded different results, which is,
1970
indeed, possible. However, it is not clear that, in practice, such a population could be readily identified or recruited. Furthermore, even if such a group were available it is likely that their personal and social circumstances would result in a biased population which would not be comparable to our cohort of spousal caregivers (eg, individuals from higher socioeconomic groups; or individuals who had a chronic debilitating disease which prevents them from taking on the caregiving role). We agree that it is important to obtain a clearer understanding of which parts of the caregiving role resulted in the chronic stress and concomitant immune modulation observed in our cohort, but these issues were beyond the scope of the report. K Vedhara Department of Experimental Psychology, University of Bristol, Bristol BS8 1TN, UK
Churg-Strauss syndome Sir—Richard Green and Andrew Vayonis (Feb 27, p 725)1 describe two cases of Churg-Strauss syndrome (CSS) in patients treated for asthma with zarfirlukast who had not been receiving systemic corticosteroids. They compare these patients with those previously reported by us2 by stating that their patients had not been withdrawn from corticosteroids and hence did not have the forme fruste of CSS. They imply a causative role for zarfirlukast in the pathogenesis of CSS in these patients. There have been several other reports of CSS in association with zarfirlukast treatment for asthma,3,4 in which corticosteroid withdrawal was not a primary component of syndrome onset. However, in our series, in the Green and Vayonis cases, and in the other reported cases, all patients had signs consistent with incipient CSS characterised by a long course of asthma and sinusitis that required systemic or high doses of inhaled steroids for control, and the institution of new asthma therapy such as leukotriene modifiers or long-acting -agonists. Before the introduction of these therapies, Lanham and colleagues5 had described the natural course of CSS as “indolent allergic disease that evolves into asthma with multiple exacerbations that may progress to eosinophilia and finally, multi-organ eosinophilic vasculitis”. Hence we feel that all the reported cases are not directly the result of these new medications, but rather, occurred as part of the natural course of the
disease. CSS could have occurred coincidentally with these drugs in progressive disease; in unmasking of progressive disease owing to steroid withdrawal; or delayed progression of airway symptoms by the new therapies before systemic involvement. For instance, the inhaled corticosteroids that these patients were taking could have been absorbed systemically and thereby quelled some early CSS manifestations or the leukotriene modifiers could have quelled airway symptoms that would otherwise have been heralding events of the syndrome. Both Merck and Glaxo Wellcome have sent letters to health-care professionals issuing warnings of the occurrence of CSS in association with another leukotriene receptor antagonist, montelukast, and with an inhaled corticosteroid, fluticasone. Similarly, the Physician’s Desk Reference lists warn of the possibility of CSS in association with beclomethasone, flunisolide, cromolyn, and others. The fact that this syndrome is being reported with several different medications all of which have different structures makes a drug-related aetiology unlikely. Both the aetiology and incidence of CSS remain unknown. Although the number of reported cases of CSS seems to be increasing previous reports probably underestimated the incidence of CSS because many patients who had previously been perceived to have asthma were put on suppressive doses of systemic steroids or high-dose inhaled steroids, and thus never developed the full clinical manifestations of the syndrome. We therefore contest the implication that CSS was induced by zafirlukast. *Michael Wechsler, Jeffrey M Drazen Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA (e-mail: [email protected]) 1
Green RL, Vayonis AG. Churg-Strauss syndrome after zafirlukast in two patients not receiving systemic steroid treatment. Lancet 1999; 353: 725–26. 2 Wechsler ME, Garpestad E, Flier SR, et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA 1998; 279: 455–57. 3 Katz RS, Papernik M. Zariflukast and Churg-Strauss syndrome. JAMA 1998; 279: 1949. 4 Knoell DL, Lucas J, Allen JN. Churg-Strauss syndrome associated with zafirlukast. Chest 1998; 114: 332–34. 5 Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine 1983; 63: 65–81.
THE LANCET • Vol 353 • June 5, 1999