700
of organising pneumonia in all cases. The main feature was a tendency for symptoms to recur annually between February and May, with increasing severity and duration of symptoms until diagnosis. This seasonal pattern of relapse was noted in both patients described by Grinblat et al in 1981,4 adding strength to the association. Symptoms and radiographic changes improved after corticosteroid therapy and patients remained well on no treatment until the following year. A puzzling feature was the development of abnormal liver function tests suggestive of intrahepatic cholestasis during bouts of active pulmonary disease. Liver biopsy specimens were examined in two cases and showed non-specific
granulomatous changes.
COP/BOOP
and SOP? Extensive have been negative in microbiological investigations most cases,3A,11 although a few patients with BOOP improve with antibiotic therapyNo particular occupational groups are at risk. There have been reports of COP in patients with oesophageal reflux and in a male patient with CREST syndrome and primary biliary cirrhosis3,12 but in most cases there is no clinical evidence of oesophageal disease or serological evidence of connective tissue disorder. The rapid response to corticosteroids supports an immunologically mediated hypersensitivity. In SOP, this is most likely to be in response to an inhaled agent present in the environment in spring. Might the other idiopathic organising pneumonias be due to an idiosyncratic reaction to a non-seasonal inhaled allergen? There is no direct evidence of this. It is also far from clear why the host lung should respond to an agent in such an unusual way. However, it seems likely that the idiopathic organising pneumonias represent a distinct clinical entity. Clinicians should be aware of this condition, especially in patients with atypical lung consolidation, since the response to treatment is rapid and gratifying. Failure of pneumonic symptoms to improve with antibiotic therapy, together with a greatly raised sedimentation rate, should alert the doctor to the correct diagnosis. Transbronchial biopsy from areas of consolidation may provide sufficient material for confirmation. If the histological appearance is unhelpful the clinician must decide between a more invasive diagnostic procedure or a closely monitored trial of corticosteroids. What
causes
1. Milne LS. Chronic pneumonia (including a discussion of two syphilis of the lung). Am J Med Sci 1911; 142: 408-38.
2.
cases
Floyd R. Organisation of pneumonic exudates. Am J Med Sci 1922;
of
163:
527-48. 3. Davidson AG, Heard 4.
BE, McAllister WAC, Turner-Warwick MEH. Cryptogenic organising pneumonitis. Q J Med 1983; 207: 382-94. Grinblat J, Mechlis S, Lewitus Z. Organizing pneumonia-like process: an unusual observation in steroid responsive cases with features of chronic
interstitial pneumonia. Chest 1981; 80: 259-63. McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med 1985; 312: 152-58. 6. Guerry-Force ML, Muller NL, Wright JL, et al. A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial 5.
Epler GR, Colby TV,
and small airways disease. Am Rev Respir Dis 1987; 135: 705-12. 7. Geddes DM. BOOP and COP. Thorax 1991; 46: 545-47. 8. Bellomo R, Finlay M, McLaughlin P, Tai E. Clinical spectrum of cryptogenic organising pneumonitis. Thorax 1991; 46: 554-58. 9. Miyagawa Y, Nagata N, Shigematsu N. Clinicopathological study of migratory lung infiltrates. Thorax 1991; 46: 233-38. 10. Cordier JF, Loire R, Burne J. Idiopathic bronchiolitis obliterans organizing pneumonia: definition of characteristic clinical profiles in a series of 16 patients. Chest 1989; 96: 999-1004. 11. Spiteri MA, Klenerman P, Sheppard MN, Padley S, Clark TJK, Newman-Taylor A. Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity. Lancet 1992; 340: 281-84. 12. Davidson AG, Epstein O. Relapsing organising pneumonitis in a man with primary biliary cirrhosis, CREST syndrome, and chronic pancreatitis. Thorax 1983; 38: 316-17.
pneumonia
Depression and suicide: preventable?
are
they
One of the paradoxes of modern psychiatry is that, although the past 30 years has seen the introduction of many antidepressant drugs, the long-term outcome of depression has changed very little. For example, one of the most consistent findings in follow-up studies of depression is the very high proportion of patients who die by suicide. Guze and Robins,1 in their review of outcome studies before 1970, noted that 12-60% of deaths in such patients were due to suicide. Three reports in 1988 showed that little had changed,z-4 Lee and Murray,2 in a 16-year follow-up of patients from the Maudsley Hospital, London, reported that 45% of deaths in these patients were the result of suicide or probable suicide. Only one-third of patients were free of recurrent moderate or severe psychiatric morbidity during this time. Considerations such as these prompted a symposium at the XVIII Collegium Internationale Neuro-Psychopharmacologicum in Nice, this summer, where Angst, in a review of his 30-year follow-up of mood disorders in Zurich, reported that these conditions have a strong tendency to recur.s Bipolar illness starts at a median age of 29 and unipolar illness at 46 years. Depressive disorders recur in 82% of cases. There is a wide variation in the length of episodes, but the median is 5 months. Angst suggested that all cases of bipolar illness deserve consideration for long-term treatment. Patients who report three or more episodes of depressive disorder, especially within the past 5 years, should likewise be seriously considered for long-term treatment. What do we know about the effect of maintenance treatment in recurrent mood disorders? Frank et al6 found that imipramine at a dose of 200 mg a day, with or without additional interpersonal psychotherapy, was effective. Mean time before relapse on placebo was 45 weeks vs 131 for imipramine. For interpersonal psychotherapy alone, mean time was 82 weeks. In the further 2-year study presented at the symposium, patients on placebo showed a greater tendency to relapse (mean time 54 weeks) than patients on imipramine (mean time 99 weeks). There is also good evidence that careful long-term treatment can reduce the suicide rate of patients with
701
mood disorders. In an 11-year follow-up study of 103
colleagues7 found a low patients, Coppen mortality (standardised mortality ratio 0-6) and no suicides during that time. Coppen’s updated results presented in Nice showed that, after 15 years, there had been only 2 suicides (8% of all deaths), 1 in a patient who had decided to discontinue treatment 9 months earlier. The patients had been treated in a mood disorders clinic in which compliance with lithium was good and drop-out rate was low. In a group of patients from the same hospital who were followed for the same length of time, suicides made up 33% of the recorded deaths. Similar results have been reported from a four-nation study of long-term lithium treatment. Suicides accounted for 15 % of 40 deaths that occurred in 798 patients and the mortality was similar to that of the corresponding normal population (SMR 0-9). These studies were conducted in patients attending lithium clinics.8 Selective serotonin reuptake inhibitors such as sertraline, paroxetine, citralopam, and fluoxetine have likewise been used for maintenance therapy in depression. At the meeting, S. A. Montgomery from St Mary’s Hospital, London, noted that all these drugs have proved superior to placebo and that their relative freedom from side-effects is an advantage when they are to be used prophylactically. Their place in chronic management of bipolar illness is uncertain; for now, long-term treatment of this condition will probably remain lithium augmented when necessary and
by antidepressants or neuroleptics. Overall, although there is a substantial case for chronic treatment of mood disorders, as endorsed by a World Health Organisation consensus statement,9 psychiatrists and general practitioners seem reluctant to prescribe long-term therapy. All reports of successful long-term treatment come from mood disorders clinics, which are not universally esteemed. Psychiatrists, like other clinicians, are more used to crisis management than to a systematic long-term approach. In such clinics patients can be assessed with long-term treatment in mind, and there are better opportunities for education of patients and their families. Moreover, systematic follow-up is easier. Some critics claim that this approach requires a large diversion of resources, but this need not be so and prevention of relapse is a considerable saving in itself. There are now several options open for long-term treatment. Lithium is easy to monitor for compliance, inexpensive, and of known prophylactic efficacy. Additional antidepressant or neuroleptic drugs can be prescribed. There are many years of follow-up data on this method. Low doses, in a once daily regimen, usually present few difficulties with side-effects or toxicity.10 Long-term treatment with the tricyclic antidepressants or selective serotonin reuptake blockers can also be used in the treatment of recurrent depressive illness. In 1992 it is poor medical practice to manage these long-term illnesses with short-term treatment.
SB, Robins E. Suicide and primary affective disorders. Br J Psychiatry 1970; 117: 437-38. 2. Lee AS, Murray RM. The long-term outcome of Maudsley depressives. BrJ Psychiatry 1988; 153: 741-51. 3. Lehmann HE, Fenton FR, Deutsch M, Feldman S, Engelsmann F. An 11-year follow-up study of 110 depressed patients. Acta Psychiatr 1. Guze
Scand 1988; 78: 57-65. 4. Kiloh LG, Andrews G, Neilson M. The long-term outcome of depressive illness. Br J Psychiatry 1988; 153: 752-57. 5. Angst J, Baastrup P, Grof P, Hippius H, Poeldinger W, Weis P. The course of monopolar depression and bipolar psychoses. Psychiatr Neurol Neurochir 1973; 76: 489-500. 6. Frank E, Kupfer DJ, Perel JM, et al. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990; 17: 1093-99. 7. Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C. Does lithium reduce the mortality of recurrent mood disorders? J Affect Disord 1991; 23: 1-7. 8. Muller-Oerlinghausen B, Ahrens B, Volk J, et al. Reduced mortality of manic-depressive patients in long-term lithium treatment: an international collaborative study by IGSLI. Psychiatry Res 1991; 36: 329-31. 9. WHO Mental Health Collaborating Centres. Pharmacotherapy of depressive disorders: a consensus statement. J Affect Disord 1989; 17: 197-98. 10. Coppen A, Abou-Saleh M, Milln P, Bailey J, Wood K. Decreasing lithium dosage reduces morbidity and side-effects during prophylaxis. J Affect Disord 1983; 5: 353-62.
Loin Loin
pain/haematuria syndrome
pain/haematuria syndrome
diagnosis given unilateral
to
patients
with
is
a
descriptive
recurrent
attacks of
bilateral loin
pain accompanied by macroscopic haematuria in whom no cause can be identified. Fever during attacks is an occasional feature. Young women are overrepresented,12 and a disproportionate number of patients have a medical connection through their work or that of their spouse.23 Some prove, after months of observation, to be malingerers. Those in whom investigations are consistently negative, and who are labelled as having the syndrome, pose several or
microscopic
or
dilemmas. First is the absence of a reliable confirmatory test. Changes of medium and small arteries found on renal arteriography were mentioned in the original description1 and were subsequently confirmed,’ but they are subtle. Arteriolar deposits of C3, which are frequently found in biopsy specimens from these patients,5 are not specific and sometimes occur in apparently normal kidneys.6 No consistent histological changes have been identified in renal specimens. IgA nephropathy, which can present with loin pain and haematuria, is more common in men and the pain is rarely as severe. Thus the diagnosis is made by exclusion and probably includes many subgroups. Second, no one knows what causes the pain. Multiple small infarcts were proposed in 19671 and this remains the favoured hypothesis because examination of kidneys after nephrectomy has confirmed "sclerotic" changes in the arteries and small cortical infarcts.’ Minor changes in the coagulation system have been described3,8,9,1O and are thought to cause the arterial lesions, but their relevance is difficult to assess when the patients often have a heavy consumption of analgesics and the controls do not. Nor do patients with more severe
of organising pneumonia in all cases. The main feature was a tendency for symptoms to recur annually between February and May, with increasing severity and duration of symptoms until diagnosis. This seasonal pattern of relapse was noted in both patients described by Grinblat et al in 1981,4 adding strength to the association. Symptoms and radiographic changes improved after corticosteroid therapy and patients remained well on no treatment until the following year. A puzzling feature was the development of abnormal liver function tests suggestive of intrahepatic cholestasis during bouts of active pulmonary disease. Liver biopsy specimens were examined in two cases and showed non-specific
granulomatous changes.
COP/BOOP
and SOP? Extensive have been negative in microbiological investigations most cases,3A,11 although a few patients with BOOP improve with antibiotic therapyNo particular occupational groups are at risk. There have been reports of COP in patients with oesophageal reflux and in a male patient with CREST syndrome and primary biliary cirrhosis3,12 but in most cases there is no clinical evidence of oesophageal disease or serological evidence of connective tissue disorder. The rapid response to corticosteroids supports an immunologically mediated hypersensitivity. In SOP, this is most likely to be in response to an inhaled agent present in the environment in spring. Might the other idiopathic organising pneumonias be due to an idiosyncratic reaction to a non-seasonal inhaled allergen? There is no direct evidence of this. It is also far from clear why the host lung should respond to an agent in such an unusual way. However, it seems likely that the idiopathic organising pneumonias represent a distinct clinical entity. Clinicians should be aware of this condition, especially in patients with atypical lung consolidation, since the response to treatment is rapid and gratifying. Failure of pneumonic symptoms to improve with antibiotic therapy, together with a greatly raised sedimentation rate, should alert the doctor to the correct diagnosis. Transbronchial biopsy from areas of consolidation may provide sufficient material for confirmation. If the histological appearance is unhelpful the clinician must decide between a more invasive diagnostic procedure or a closely monitored trial of corticosteroids. What
causes
1. Milne LS. Chronic pneumonia (including a discussion of two syphilis of the lung). Am J Med Sci 1911; 142: 408-38.
2.
cases
Floyd R. Organisation of pneumonic exudates. Am J Med Sci 1922;
of
163:
527-48. 3. Davidson AG, Heard 4.
BE, McAllister WAC, Turner-Warwick MEH. Cryptogenic organising pneumonitis. Q J Med 1983; 207: 382-94. Grinblat J, Mechlis S, Lewitus Z. Organizing pneumonia-like process: an unusual observation in steroid responsive cases with features of chronic
interstitial pneumonia. Chest 1981; 80: 259-63. McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med 1985; 312: 152-58. 6. Guerry-Force ML, Muller NL, Wright JL, et al. A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial 5.
Epler GR, Colby TV,
and small airways disease. Am Rev Respir Dis 1987; 135: 705-12. 7. Geddes DM. BOOP and COP. Thorax 1991; 46: 545-47. 8. Bellomo R, Finlay M, McLaughlin P, Tai E. Clinical spectrum of cryptogenic organising pneumonitis. Thorax 1991; 46: 554-58. 9. Miyagawa Y, Nagata N, Shigematsu N. Clinicopathological study of migratory lung infiltrates. Thorax 1991; 46: 233-38. 10. Cordier JF, Loire R, Burne J. Idiopathic bronchiolitis obliterans organizing pneumonia: definition of characteristic clinical profiles in a series of 16 patients. Chest 1989; 96: 999-1004. 11. Spiteri MA, Klenerman P, Sheppard MN, Padley S, Clark TJK, Newman-Taylor A. Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity. Lancet 1992; 340: 281-84. 12. Davidson AG, Epstein O. Relapsing organising pneumonitis in a man with primary biliary cirrhosis, CREST syndrome, and chronic pancreatitis. Thorax 1983; 38: 316-17.
pneumonia
Depression and suicide: preventable?
are
they
One of the paradoxes of modern psychiatry is that, although the past 30 years has seen the introduction of many antidepressant drugs, the long-term outcome of depression has changed very little. For example, one of the most consistent findings in follow-up studies of depression is the very high proportion of patients who die by suicide. Guze and Robins,1 in their review of outcome studies before 1970, noted that 12-60% of deaths in such patients were due to suicide. Three reports in 1988 showed that little had changed,z-4 Lee and Murray,2 in a 16-year follow-up of patients from the Maudsley Hospital, London, reported that 45% of deaths in these patients were the result of suicide or probable suicide. Only one-third of patients were free of recurrent moderate or severe psychiatric morbidity during this time. Considerations such as these prompted a symposium at the XVIII Collegium Internationale Neuro-Psychopharmacologicum in Nice, this summer, where Angst, in a review of his 30-year follow-up of mood disorders in Zurich, reported that these conditions have a strong tendency to recur.s Bipolar illness starts at a median age of 29 and unipolar illness at 46 years. Depressive disorders recur in 82% of cases. There is a wide variation in the length of episodes, but the median is 5 months. Angst suggested that all cases of bipolar illness deserve consideration for long-term treatment. Patients who report three or more episodes of depressive disorder, especially within the past 5 years, should likewise be seriously considered for long-term treatment. What do we know about the effect of maintenance treatment in recurrent mood disorders? Frank et al6 found that imipramine at a dose of 200 mg a day, with or without additional interpersonal psychotherapy, was effective. Mean time before relapse on placebo was 45 weeks vs 131 for imipramine. For interpersonal psychotherapy alone, mean time was 82 weeks. In the further 2-year study presented at the symposium, patients on placebo showed a greater tendency to relapse (mean time 54 weeks) than patients on imipramine (mean time 99 weeks). There is also good evidence that careful long-term treatment can reduce the suicide rate of patients with
701
mood disorders. In an 11-year follow-up study of 103
colleagues7 found a low patients, Coppen mortality (standardised mortality ratio 0-6) and no suicides during that time. Coppen’s updated results presented in Nice showed that, after 15 years, there had been only 2 suicides (8% of all deaths), 1 in a patient who had decided to discontinue treatment 9 months earlier. The patients had been treated in a mood disorders clinic in which compliance with lithium was good and drop-out rate was low. In a group of patients from the same hospital who were followed for the same length of time, suicides made up 33% of the recorded deaths. Similar results have been reported from a four-nation study of long-term lithium treatment. Suicides accounted for 15 % of 40 deaths that occurred in 798 patients and the mortality was similar to that of the corresponding normal population (SMR 0-9). These studies were conducted in patients attending lithium clinics.8 Selective serotonin reuptake inhibitors such as sertraline, paroxetine, citralopam, and fluoxetine have likewise been used for maintenance therapy in depression. At the meeting, S. A. Montgomery from St Mary’s Hospital, London, noted that all these drugs have proved superior to placebo and that their relative freedom from side-effects is an advantage when they are to be used prophylactically. Their place in chronic management of bipolar illness is uncertain; for now, long-term treatment of this condition will probably remain lithium augmented when necessary and
by antidepressants or neuroleptics. Overall, although there is a substantial case for chronic treatment of mood disorders, as endorsed by a World Health Organisation consensus statement,9 psychiatrists and general practitioners seem reluctant to prescribe long-term therapy. All reports of successful long-term treatment come from mood disorders clinics, which are not universally esteemed. Psychiatrists, like other clinicians, are more used to crisis management than to a systematic long-term approach. In such clinics patients can be assessed with long-term treatment in mind, and there are better opportunities for education of patients and their families. Moreover, systematic follow-up is easier. Some critics claim that this approach requires a large diversion of resources, but this need not be so and prevention of relapse is a considerable saving in itself. There are now several options open for long-term treatment. Lithium is easy to monitor for compliance, inexpensive, and of known prophylactic efficacy. Additional antidepressant or neuroleptic drugs can be prescribed. There are many years of follow-up data on this method. Low doses, in a once daily regimen, usually present few difficulties with side-effects or toxicity.10 Long-term treatment with the tricyclic antidepressants or selective serotonin reuptake blockers can also be used in the treatment of recurrent depressive illness. In 1992 it is poor medical practice to manage these long-term illnesses with short-term treatment.
SB, Robins E. Suicide and primary affective disorders. Br J Psychiatry 1970; 117: 437-38. 2. Lee AS, Murray RM. The long-term outcome of Maudsley depressives. BrJ Psychiatry 1988; 153: 741-51. 3. Lehmann HE, Fenton FR, Deutsch M, Feldman S, Engelsmann F. An 11-year follow-up study of 110 depressed patients. Acta Psychiatr 1. Guze
Scand 1988; 78: 57-65. 4. Kiloh LG, Andrews G, Neilson M. The long-term outcome of depressive illness. Br J Psychiatry 1988; 153: 752-57. 5. Angst J, Baastrup P, Grof P, Hippius H, Poeldinger W, Weis P. The course of monopolar depression and bipolar psychoses. Psychiatr Neurol Neurochir 1973; 76: 489-500. 6. Frank E, Kupfer DJ, Perel JM, et al. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990; 17: 1093-99. 7. Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C. Does lithium reduce the mortality of recurrent mood disorders? J Affect Disord 1991; 23: 1-7. 8. Muller-Oerlinghausen B, Ahrens B, Volk J, et al. Reduced mortality of manic-depressive patients in long-term lithium treatment: an international collaborative study by IGSLI. Psychiatry Res 1991; 36: 329-31. 9. WHO Mental Health Collaborating Centres. Pharmacotherapy of depressive disorders: a consensus statement. J Affect Disord 1989; 17: 197-98. 10. Coppen A, Abou-Saleh M, Milln P, Bailey J, Wood K. Decreasing lithium dosage reduces morbidity and side-effects during prophylaxis. J Affect Disord 1983; 5: 353-62.
Loin Loin
pain/haematuria syndrome
pain/haematuria syndrome
diagnosis given unilateral
to
patients
with
is
a
descriptive
recurrent
attacks of
bilateral loin
pain accompanied by macroscopic haematuria in whom no cause can be identified. Fever during attacks is an occasional feature. Young women are overrepresented,12 and a disproportionate number of patients have a medical connection through their work or that of their spouse.23 Some prove, after months of observation, to be malingerers. Those in whom investigations are consistently negative, and who are labelled as having the syndrome, pose several or
microscopic
or
dilemmas. First is the absence of a reliable confirmatory test. Changes of medium and small arteries found on renal arteriography were mentioned in the original description1 and were subsequently confirmed,’ but they are subtle. Arteriolar deposits of C3, which are frequently found in biopsy specimens from these patients,5 are not specific and sometimes occur in apparently normal kidneys.6 No consistent histological changes have been identified in renal specimens. IgA nephropathy, which can present with loin pain and haematuria, is more common in men and the pain is rarely as severe. Thus the diagnosis is made by exclusion and probably includes many subgroups. Second, no one knows what causes the pain. Multiple small infarcts were proposed in 19671 and this remains the favoured hypothesis because examination of kidneys after nephrectomy has confirmed "sclerotic" changes in the arteries and small cortical infarcts.’ Minor changes in the coagulation system have been described3,8,9,1O and are thought to cause the arterial lesions, but their relevance is difficult to assess when the patients often have a heavy consumption of analgesics and the controls do not. Nor do patients with more severe
