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525 and related to haemodynamic stress.’ Despite this, Pope et al. refer to the role of medial thinning in the aetiology of cerebral aneurysms, which they regard as congenital. Dr Jones (June 6, p. 1265) assumed that Pope et al. were referring to the medial defects of Forbus, yet, far from manifesting thinning of the wall, they appear to be actually a reinforcement. True thinning of the wall is an acquired early aneursymal change associated with degeneration not only of the elastica but also of the muscle cells and intercellular matrix.4 Jones disagreed with their assumption that aneurysms are congenital, and asserted that Du Boulay5 had shown the medial defects to be a physiological mechanism to maintain blood flow during vasoconstriction. The ubiquitous so-called medial defects are sometimes present at birth, but frequently develop postnatally.2 2 Their distribution in nature is completely at variance with the frequency and distribution of berry aneurysms in man and lower animals. There is no evidence to show they are loci minoris resistentiae, and study of early aneurysms formation reveals that the defects are involved fortuitously.2 2 5 Du Boulay’s explanation of medial defects is inconsistent with their distribution since some forks have no defects, and others have a defect only at the lateral angle, rather than at the apex or crotch. The most plausible explanation is that they act as a raphe between the muscle of the adjoining arterial wall at sites where the direction of vasoconstrictor effect is in two very different, or almost opposing directions. The difference in the direction of the vasoconstrictor effect of the adjacent walls of two arterial segments at either a fork or a union will be 180°, less the angle subtended by the two walls. The more acute the angle, the closer will be the direction of the vasoconstrictor effect of the adjacent walls approximate 180°, or otherwise directly oppose each other. This thesis is substantiated by the observation that the medial defects have a known predilection for acute angles, whether apical or lateral. 2 In an obtuse angle, the direction of the muscle is only gradually altered from one arterial segment to the next, but the need for a medial raphe at the acute angle would be enhanced. I suggested, therefore, that the term medial defect be abandoned, for it appears to be more in the nature of a sheet anchor for the medial muscle at the fork during vasoconstriction, and that "medial raphe" would be more appropriate. Department of Pathology, Wellington Clinical School of Medicine, University of Otago, Wellington, New Zealand W. E. STEHBENS ADVERSE REACTIONS TO DAPSONE SIR,-Your comprehensive and useful editorial (July 25, p. 184) omitted two descriptions of dapsone’s use and side-effects. In an open study6 of 71 patients with rheumatoid arthritis we suggested that dapsone was an effective treatment. We found, over periods of up to a year, few adverse effects. More recent experience over longer periods, giving 100 mg daily, has not altered our conclusions. We have had one case of agranulocytosis. Our results have since been confirmed by others in a controlled trial7 The chief limitation in treating rheumatoid arthritis is that patients are usually anaemic and dapsone tends to lower haemoglobin levels further, by about 2 g/dl. The question of balancing risks of treatment is relevant; patients, including children, who might be selected for dapsone treatment may otherwise have been given gold, penicillamine, or corticosteroids. Postgraduate Centre, Dudley Road Hospital, P O Box 293, Birmingham B18 7QH B. MCCONKEY 3 Forbus WD. On the origin of miliary aneurysms of the superficial cerebral arteries. Bull Johns Hopk Hosp 1930; 47: 239-284. 4 Stehbens WE. Ultrastructure of aneurysms. Arch Neural 1975; 32: 798-807. 5 Du Boulay GH Some observations on the natural history of intracranial aneurysms Br J Radiol 1965; 38: 721-757. 6 McConkey B, Davies P, Crockson RA, Crockson AP, Butler M, Constable TJ. Dapsone in rheumatoid arthritis. Rheumatol Rehabil 1976; 15: 230-34. 7 Swinson DR, Zlosnick J, Jackson L Double-blind trial of dapsone against placebo in the treatment of rheumatoid arthritis. Ann Rheum Dis 1981; 40: 235-39. PRIMARY BILIARY CIRRHOSIS, PENICILLAMINE, AND LICHEN PLANUS SIR,-Epstein and co-workers mention that 9 of the 55 patients treated with penicillamine for primary biliary cirrhosis (PBC) acquired rashes requiring cessation of therapy-but they do not specify the type of eruption. We wish to draw attention to a report by Seehafer et a1.2 of lichen-planus-like lesions caused by penicillamine in primary biliary cirrhosis and to record two cases in which pre-existing lichen planus was exacerbated by penicillamine. Case 1 A woman aged 47 was seen in 1973 with xanthelasma, hepatomegaly, raised alkaline phosphatase, strongly positive antimitochondrial antibody (AMA), and liver histology consistent with PBC. In 1977 she was noted to have oral lichen planus. She was started on penicillamine in May, 1979. In August, 1979, the lichen planus involved her lips, and by October, 1979, there was extensive oral involvement with scattered lesions on the wrists, trunk, and legs. Biopsy of a leg lesion was consistent with hypertrophic lichen planus. The lesions resolved gradually with a reduction of penicillamine dosage and with use of topical cortisone. Case 2 A 44-year-old woman was diagnosed as having oral and vaginal lichen planus in 1976. In 1978 PBC developed with raised alkaline phosphatase, positive AMA, and hepatic histology consistent with this diagnosis. In March, 1980, generalised cutaneous lesions of lichen planus developed. The penicillamine was continued but by March, 1981, widespread erosive and disabling lichen planus necessitated admission to hospital, where biopsy of the skin lesions showed bullous lichen planus. The penicillamine was discontinued and she recovered over the next three months. The relation of lichen planus to PBC is unclear. Penicillamine may precipitate a lichen-planus-like eruption or exacerbate existing lichen planus PBC. We are aware of only one report of lichen- planus like eruptions due to penicillamine in a patient who did not have PBC.3 3 Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, U.S.A. FRANK C. POWELL ROY S. ROGERS, III PET-LINKED SALMONELLOSIS SIR,-We were interested in your editorial on reptilian salmonellosis (July 18, p. 130) because we have the same problem. In Japan, reports of terrapin-linked salmonellosis began in 1976,4 4 and we saw our first case in 1977. A little girl had salmonella gastroenteritis and her brother’s red-eared terrapin proved to be a car- rier of Salmonella typhimurium. Since then we have seen 24 children with salmonellosis at hospitals affiliated to Asahikawa Medical College and the number of patients in on the increase. Usually their family or a friend kept pets such as the red-eared terrapin, a tortoise, or a crayfish. S. typhimurium was common (two-thirds of isolates) and other serotypes were S. java, S. saintpaul, S. heidelberg, and S. hartford Children usually get the pets at street stalls opened for local shrine and summer festivals, so the problem is nationwide. There is much to be said for a ban on the sale of small freshwater turtles, since the severe cases we have seen, with bacteraemia or acute hemiplegia, have all been in young infants. Families with small children should not keep these dangerous pets. Department of Paediatrics, Dohoku-Byoin National Sanatorium, Asahikawa 070, Japan Department of Paediatrics, Asahikawa Medical College, Asahikawa 078-11 KOZO FUJITA KO-ICHI MURONO HAJIME YOSHIOKA 1. Epstein O, Jain S, Lee RG, et al. D-penicillamine treatment improves survival in primary biliary cirrhosis. Lancet 1981; i: 1275-77. 2. Seehafer JR, Rogers RS, Fleming CR, Dickson ER. Lichen planus-like lesions caused by penicillamine in primary biliary cirrhosis. Arch Dermatol 1981; 117: 140-42. 3. Van de Staak WJBM, Cotton DWK, Jonckheer-Venneste MMH, et al. Lichenoid eruption following penicillamine. Dermatologica 1975; 150: 372-4. 4. Nakamon J, Miyazaki K, Nishio T, et al. Pet terrapin-linked salmonellosis; first proved cases in Japan and its epidemiology (in Japanese) Rinsho-to-Saikin 1976, 3: 88-94.
Transcript of PRIMARY BILIARY CIRRHOSIS, PENICILLAMINE, AND LICHEN PLANUS
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and related to haemodynamic stress.’ Despite this, Pope et al. referto the role of medial thinning in the aetiology of cerebral aneurysms,which they regard as congenital. Dr Jones (June 6, p. 1265) assumedthat Pope et al. were referring to the medial defects of Forbus, yet,far from manifesting thinning of the wall, they appear to be actuallya reinforcement. True thinning of the wall is an acquired earlyaneursymal change associated with degeneration not only of theelastica but also of the muscle cells and intercellular matrix.4 Jonesdisagreed with their assumption that aneurysms are congenital, andasserted that Du Boulay5 had shown the medial defects to be aphysiological mechanism to maintain blood flow duringvasoconstriction. The ubiquitous so-called medial defects are
sometimes present at birth, but frequently develop postnatally.2 2Their distribution in nature is completely at variance with thefrequency and distribution of berry aneurysms in man and loweranimals. There is no evidence to show they are loci minoris
resistentiae, and study of early aneurysms formation reveals that thedefects are involved fortuitously.2 2
5Du Boulay’s explanation of medial defects is inconsistent withtheir distribution since some forks have no defects, and others have adefect only at the lateral angle, rather than at the apex or crotch. Themost plausible explanation is that they act as a raphe between themuscle of the adjoining arterial wall at sites where the direction ofvasoconstrictor effect is in two very different, or almost opposingdirections. The difference in the direction of the vasoconstrictoreffect of the adjacent walls of two arterial segments at either a fork ora union will be 180°, less the angle subtended by the two walls. Themore acute the angle, the closer will be the direction of thevasoconstrictor effect of the adjacent walls approximate 180°, orotherwise directly oppose each other. This thesis is substantiated bythe observation that the medial defects have a known predilectionfor acute angles, whether apical or lateral. 2 In an obtuse angle, thedirection of the muscle is only gradually altered from one arterialsegment to the next, but the need for a medial raphe at the acuteangle would be enhanced. I suggested, therefore, that the termmedial defect be abandoned, for it appears to be more in the natureof a sheet anchor for the medial muscle at the fork duringvasoconstriction, and that "medial raphe" would be more
appropriate.
Department of Pathology,Wellington Clinical School of Medicine,University of Otago,Wellington, New Zealand W. E. STEHBENS
ADVERSE REACTIONS TO DAPSONE
SIR,-Your comprehensive and useful editorial (July 25, p. 184)omitted two descriptions of dapsone’s use and side-effects.In an open study6 of 71 patients with rheumatoid arthritis we
suggested that dapsone was an effective treatment. We found, overperiods of up to a year, few adverse effects. More recent experienceover longer periods, giving 100 mg daily, has not altered ourconclusions. We have had one case of agranulocytosis. Our resultshave since been confirmed by others in a controlled trial7 The chieflimitation in treating rheumatoid arthritis is that patients areusually anaemic and dapsone tends to lower haemoglobin levelsfurther, by about 2 g/dl. The question of balancing risks oftreatment is relevant; patients, including children, who might beselected for dapsone treatment may otherwise have been given gold,penicillamine, or corticosteroids.
Postgraduate Centre,Dudley Road Hospital,P O Box 293,Birmingham B18 7QH B. MCCONKEY
3 Forbus WD. On the origin of miliary aneurysms of the superficial cerebral arteries. BullJohns Hopk Hosp 1930; 47: 239-284.
4 Stehbens WE. Ultrastructure of aneurysms. Arch Neural 1975; 32: 798-807.5 Du Boulay GH Some observations on the natural history of intracranial aneurysms Br
J Radiol 1965; 38: 721-757.6 McConkey B, Davies P, Crockson RA, Crockson AP, Butler M, Constable TJ.
Dapsone in rheumatoid arthritis. Rheumatol Rehabil 1976; 15: 230-34.7 Swinson DR, Zlosnick J, Jackson L Double-blind trial of dapsone against placebo in
the treatment of rheumatoid arthritis. Ann Rheum Dis 1981; 40: 235-39.
PRIMARY BILIARY CIRRHOSIS, PENICILLAMINE,AND LICHEN PLANUS
SIR,-Epstein and co-workers mention that 9 of the 55 patientstreated with penicillamine for primary biliary cirrhosis (PBC)acquired rashes requiring cessation of therapy-but they do notspecify the type of eruption. We wish to draw attention to a reportby Seehafer et a1.2 of lichen-planus-like lesions caused bypenicillamine in primary biliary cirrhosis and to record two cases inwhich pre-existing lichen planus was exacerbated by penicillamine.Case 1A woman aged 47 was seen in 1973 with xanthelasma,
hepatomegaly, raised alkaline phosphatase, strongly positiveantimitochondrial antibody (AMA), and liver histology consistentwith PBC. In 1977 she was noted to have oral lichen planus. She wasstarted on penicillamine in May, 1979. In August, 1979, the lichenplanus involved her lips, and by October, 1979, there was extensiveoral involvement with scattered lesions on the wrists, trunk, andlegs. Biopsy of a leg lesion was consistent with hypertrophic lichenplanus. The lesions resolved gradually with a reduction of
penicillamine dosage and with use of topical cortisone.Case 2A 44-year-old woman was diagnosed as having oral and vaginal
lichen planus in 1976. In 1978 PBC developed with raised alkalinephosphatase, positive AMA, and hepatic histology consistent withthis diagnosis. In March, 1980, generalised cutaneous lesions oflichen planus developed. The penicillamine was continued but byMarch, 1981, widespread erosive and disabling lichen planusnecessitated admission to hospital, where biopsy of the skin lesionsshowed bullous lichen planus. The penicillamine was discontinuedand she recovered over the next three months.The relation of lichen planus to PBC is unclear. Penicillamine
may precipitate a lichen-planus-like eruption or exacerbate existinglichen planus PBC. We are aware of only one report of lichen-planus like eruptions due to penicillamine in a patient who did nothave PBC.3 3
Department of Dermatology,Mayo Clinic and Mayo Foundation,Rochester, Minnesota 55905, U.S.A.
FRANK C. POWELLROY S. ROGERS, III
PET-LINKED SALMONELLOSIS
SIR,-We were interested in your editorial on reptiliansalmonellosis (July 18, p. 130) because we have the same problem.In Japan, reports of terrapin-linked salmonellosis began in 1976,4 4and we saw our first case in 1977. A little girl had salmonellagastroenteritis and her brother’s red-eared terrapin proved to be a car-rier of Salmonella typhimurium. Since then we have seen 24 childrenwith salmonellosis at hospitals affiliated to Asahikawa MedicalCollege and the number of patients in on the increase. Usually theirfamily or a friend kept pets such as the red-eared terrapin, a tortoise,or a crayfish. S. typhimurium was common (two-thirds of isolates)and other serotypes were S. java, S. saintpaul, S. heidelberg, and S.hartford Children usually get the pets at street stalls opened forlocal shrine and summer festivals, so the problem is nationwide.There is much to be said for a ban on the sale of small freshwaterturtles, since the severe cases we have seen, with bacteraemia oracute hemiplegia, have all been in young infants. Families withsmall children should not keep these dangerous pets.
Department of Paediatrics,Dohoku-Byoin National Sanatorium,Asahikawa 070, JapanDepartment of Paediatrics,Asahikawa Medical College,Asahikawa 078-11
KOZO FUJITAKO-ICHI MURONO
HAJIME YOSHIOKA
1. Epstein O, Jain S, Lee RG, et al. D-penicillamine treatment improves survival inprimary biliary cirrhosis. Lancet 1981; i: 1275-77.
2. Seehafer JR, Rogers RS, Fleming CR, Dickson ER. Lichen planus-like lesions causedby penicillamine in primary biliary cirrhosis. Arch Dermatol 1981; 117: 140-42.
3. Van de Staak WJBM, Cotton DWK, Jonckheer-Venneste MMH, et al. Lichenoid
eruption following penicillamine. Dermatologica 1975; 150: 372-4.4. Nakamon J, Miyazaki K, Nishio T, et al. Pet terrapin-linked salmonellosis; first proved
cases in Japan and its epidemiology (in Japanese) Rinsho-to-Saikin 1976, 3: 88-94.
