- Email: [email protected]
Systemic mastocytosis
CORRESPONDENCE
sodium level returned to normal. These results are being analysed. Webtable 2 (http://image.thelancet. com/extras/01art10039webtable2.pdf) records the number of children with shock and also those in whom ear infections or other infections were found. We agree that provision of vaccines alone will not improve outcome in bacterial meningitis. But there is no doubt that the addition of H influenzae type b and pneumoccocal vaccines to the expanded programme for immunisation would have an immediate and beneficial effect. Nicola Principi and Susanna Eposito note that there was a nonsignificant improvement in children with H influenzae treated with dexamethasone, compared with those who received placebo. If children who were not tested for hearing, or in whom tests were inconclusive, are excluded and all poor outcomes (death and sequelae) are combined, as they suggest, the poor outcomes are 36 (69%) of 57 in the steroid group and 52 (66%) of 78 in the placebo group. This difference is still not significant (p=0·81). The 31 cases of H influenzae treated with ceftriaxone alone are too few for analysis. The results cannot be compared with those of all cases treated with only chloramphenicol and penicillin, since they differ in many respects including cause of meningitis and mean age. Not surprisingly, children treated with ceftriaxone had better outcomes than those who received chloramphenicol and penicillin. If a larger study of the use of ceftriaxone in our setting (which we are undertaking at present) confirms this finding, then the question of adjuvant steroid therapy with ceftriaxone may need to be reviewed. Indeed, the reason we undertook our study in a developing country was because current recommendations, such as that of The American Academy of Pediatrics Committee on Infectious Diseases,1 are based only on evidence from developed countries. We agree that in developed countries, where H influenzae meningitis has become rare, the value of steroid therapy is put in question. *Elizabeth M Molyneux, G Malenga Department of Paediatrics, College of Medicine, Box 360, Blantyre, Malawi (e-mail: [email protected]) 1
American Academy of Pediatrics. Haemophilus influenzae infections. In: Pickering LK, ed. 2000 Red book: report of the committee on infectious diseases, 25th edn. Elk Grove Village, IL: American Academy of Pediatrics, 2000: 262–72.
Systemic mastocytosis Sir—T Koide and colleagues (June 15, p 2084)1 report a Japanese woman aged 58 years who presented over a 6-year period with repeated episodes of flushing, palpitations, and syncope. A diagnosis of systemic mastocytosis was made afer the identification of raised serum histamine and an increase in mast-cell numbers within the bone marrow and skin. Excellent symptom control was achieved with a combination of H1 and H2 blockers. We describe a white female patient aged 43 years who first presented at age 27 with recurrent episodes of urticaria, throbbing occipital headaches, abdominal pain, postural hypotension, and syncope. She had areas of urticaria pigmentosa that spared her head and neck. Assessment of bone marrow showed no evidence of mastocytosis and radiological studies, including bone scan, small bowel, and barium enema, were unremarkable. Her baseline plasma tryptase was raised at 19·5 ng/mL (normal range 0–20), and her plasma histamine was normal. Despite the diagnosis of cutaneous (non-systemic) mastocytosis her clinical course has been difficult to control. She is currently receiving treatment with a combination of aspirin 1800 mg daily, ranitidine 300 mg daily, neoclarityn 10 mg daily, and montelukast 20 mg daily, but still experiences systemic reactions, albeit less frequently. We agree with Koide and colleagues that plasma histamine is not a sensitive screening test in the diagnosis of mastocytosis. Plasma tryptase is a better marker of mast number and activity. It has a half life of around 2·5 h compared with 2·5 min for plasma histamine. Plasma tryptase concentrations are raised in patients with telangectasia eruptive macularis perstans (TEMP)— an indolent form of mastocytosis—and hence represents a useful screening test in patients presenting with unexplained anaphylactic reactions.2 Similarly there is a correlation between plasma tryptase concentrations and the burden of mast cells in systemic and cutaneous mastocytosis.3 There are currently no consensus guidelines in the management of systemic or cutaneous mastocytosis. Treatment is based on blocking mastcell products, including histamine, prostaglandin D2, and leukotrienes. In our patient, a combination of H1 and H2 blockers, high-dose aspirin, and leukotriene antagonists did not completely control the syncopal episodes, unlike in the systemic case reported by Koide and colleagues. Thus, a diagnosis of systemic
THE LANCET • Vol 360 • November 16, 2002 • www.thelancet.com
mastocytosis does not imply that the symptom management will be more difficult to achieve than in cutaneous mastocytosis. The major distinction is that patients with evidence of systemic disease are at greater risk from an associated haematological clonal, nonmast-cell-lineage disease.4 *Anthony Williams, Thirumala Krishna, Anthony Frew Department of Immunology and University Medical Specialties Clinical Group, Mailpoint 810, Southampton General Hospital, Southampton SO16 6YD, UK (e-mail: [email protected]) 1
2
3
4
Koide T, Nakajima T, Makifuchi T, Fukuhara N. Systemic mastocytosis and recurrent anaphylactic shock. Lancet 2002; 359: 2084. Ludolph-Hauser D, Rueff F, Fries C, Schopf P, Przybilla B. Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. Lancet 2001; 357: 361–62. Sperr WR, Jordan JH, Fiegl M, et al. Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease. Int Arch Allergy Immunol 2002; 128: 136–41. Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001; 25: 603–25.
Epidemiology on trial Sir—Haroon Ashraf’s News item of August 3,1 and your August 10 Editorial2 comment on the decision in the UK High Court of Justice in which Mr Justice Mackay found that there was no difference in risk of venous thromboembolism between secondgeneration and third-generation combined oral contraceptive pills. The judge commented that, although the result would come as a serious disappointment to the claimants, “this trial was almost certainly the most exhaustive examination that this question has yet received and that their case could not have been more effectively put forward than it was”. I fear that the same may also be said to some of those in the scientific community who have advocated the existence of the difference in risk with more than the usual scientific vigour. The case required an examination of the voluminous evidence amassed on this subject. The trial also considered the limitations of epidemiology and addressed head-on the suggestion— which is repeated in your August 3 issue1—that there is an inherent bias in studies funded by industry. Having heard all the evidence, the judge concluded that he need make no allowance when reviewing the studies
1611
For personal use. Only reproduce with permission from The Lancet Publishing Group.
sodium level returned to normal. These results are being analysed. Webtable 2 (http://image.thelancet. com/extras/01art10039webtable2.pdf) records the number of children with shock and also those in whom ear infections or other infections were found. We agree that provision of vaccines alone will not improve outcome in bacterial meningitis. But there is no doubt that the addition of H influenzae type b and pneumoccocal vaccines to the expanded programme for immunisation would have an immediate and beneficial effect. Nicola Principi and Susanna Eposito note that there was a nonsignificant improvement in children with H influenzae treated with dexamethasone, compared with those who received placebo. If children who were not tested for hearing, or in whom tests were inconclusive, are excluded and all poor outcomes (death and sequelae) are combined, as they suggest, the poor outcomes are 36 (69%) of 57 in the steroid group and 52 (66%) of 78 in the placebo group. This difference is still not significant (p=0·81). The 31 cases of H influenzae treated with ceftriaxone alone are too few for analysis. The results cannot be compared with those of all cases treated with only chloramphenicol and penicillin, since they differ in many respects including cause of meningitis and mean age. Not surprisingly, children treated with ceftriaxone had better outcomes than those who received chloramphenicol and penicillin. If a larger study of the use of ceftriaxone in our setting (which we are undertaking at present) confirms this finding, then the question of adjuvant steroid therapy with ceftriaxone may need to be reviewed. Indeed, the reason we undertook our study in a developing country was because current recommendations, such as that of The American Academy of Pediatrics Committee on Infectious Diseases,1 are based only on evidence from developed countries. We agree that in developed countries, where H influenzae meningitis has become rare, the value of steroid therapy is put in question. *Elizabeth M Molyneux, G Malenga Department of Paediatrics, College of Medicine, Box 360, Blantyre, Malawi (e-mail: [email protected]) 1
American Academy of Pediatrics. Haemophilus influenzae infections. In: Pickering LK, ed. 2000 Red book: report of the committee on infectious diseases, 25th edn. Elk Grove Village, IL: American Academy of Pediatrics, 2000: 262–72.
Systemic mastocytosis Sir—T Koide and colleagues (June 15, p 2084)1 report a Japanese woman aged 58 years who presented over a 6-year period with repeated episodes of flushing, palpitations, and syncope. A diagnosis of systemic mastocytosis was made afer the identification of raised serum histamine and an increase in mast-cell numbers within the bone marrow and skin. Excellent symptom control was achieved with a combination of H1 and H2 blockers. We describe a white female patient aged 43 years who first presented at age 27 with recurrent episodes of urticaria, throbbing occipital headaches, abdominal pain, postural hypotension, and syncope. She had areas of urticaria pigmentosa that spared her head and neck. Assessment of bone marrow showed no evidence of mastocytosis and radiological studies, including bone scan, small bowel, and barium enema, were unremarkable. Her baseline plasma tryptase was raised at 19·5 ng/mL (normal range 0–20), and her plasma histamine was normal. Despite the diagnosis of cutaneous (non-systemic) mastocytosis her clinical course has been difficult to control. She is currently receiving treatment with a combination of aspirin 1800 mg daily, ranitidine 300 mg daily, neoclarityn 10 mg daily, and montelukast 20 mg daily, but still experiences systemic reactions, albeit less frequently. We agree with Koide and colleagues that plasma histamine is not a sensitive screening test in the diagnosis of mastocytosis. Plasma tryptase is a better marker of mast number and activity. It has a half life of around 2·5 h compared with 2·5 min for plasma histamine. Plasma tryptase concentrations are raised in patients with telangectasia eruptive macularis perstans (TEMP)— an indolent form of mastocytosis—and hence represents a useful screening test in patients presenting with unexplained anaphylactic reactions.2 Similarly there is a correlation between plasma tryptase concentrations and the burden of mast cells in systemic and cutaneous mastocytosis.3 There are currently no consensus guidelines in the management of systemic or cutaneous mastocytosis. Treatment is based on blocking mastcell products, including histamine, prostaglandin D2, and leukotrienes. In our patient, a combination of H1 and H2 blockers, high-dose aspirin, and leukotriene antagonists did not completely control the syncopal episodes, unlike in the systemic case reported by Koide and colleagues. Thus, a diagnosis of systemic
THE LANCET • Vol 360 • November 16, 2002 • www.thelancet.com
mastocytosis does not imply that the symptom management will be more difficult to achieve than in cutaneous mastocytosis. The major distinction is that patients with evidence of systemic disease are at greater risk from an associated haematological clonal, nonmast-cell-lineage disease.4 *Anthony Williams, Thirumala Krishna, Anthony Frew Department of Immunology and University Medical Specialties Clinical Group, Mailpoint 810, Southampton General Hospital, Southampton SO16 6YD, UK (e-mail: [email protected]) 1
2
3
4
Koide T, Nakajima T, Makifuchi T, Fukuhara N. Systemic mastocytosis and recurrent anaphylactic shock. Lancet 2002; 359: 2084. Ludolph-Hauser D, Rueff F, Fries C, Schopf P, Przybilla B. Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. Lancet 2001; 357: 361–62. Sperr WR, Jordan JH, Fiegl M, et al. Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease. Int Arch Allergy Immunol 2002; 128: 136–41. Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001; 25: 603–25.
Epidemiology on trial Sir—Haroon Ashraf’s News item of August 3,1 and your August 10 Editorial2 comment on the decision in the UK High Court of Justice in which Mr Justice Mackay found that there was no difference in risk of venous thromboembolism between secondgeneration and third-generation combined oral contraceptive pills. The judge commented that, although the result would come as a serious disappointment to the claimants, “this trial was almost certainly the most exhaustive examination that this question has yet received and that their case could not have been more effectively put forward than it was”. I fear that the same may also be said to some of those in the scientific community who have advocated the existence of the difference in risk with more than the usual scientific vigour. The case required an examination of the voluminous evidence amassed on this subject. The trial also considered the limitations of epidemiology and addressed head-on the suggestion— which is repeated in your August 3 issue1—that there is an inherent bias in studies funded by industry. Having heard all the evidence, the judge concluded that he need make no allowance when reviewing the studies
1611
For personal use. Only reproduce with permission from The Lancet Publishing Group.