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PERIARTERITIS NODOSA
973 PERIARTERITIS NODOSA SIR.—I am prornpted by your excellent and informaleader of Oct. 2 to emphasise some points in the logy of the condition, which I made some years ago.1 There would actually appear to be multiple conditions new described under the name of periarteritis nodosa, tht one common feature being the presence of widespread
rotising arteritis. condition as described by Kussmaul and Maier 2p the small and medium-sized arteries and is affects 66 marked by the naked-eye appearance of tiny white tubercleions in the acute phase, and aneurysm and thrombus tion at a later stage. Whereas there are many conditions which may give necrotising arteritis in different partg of the y it is my belief that the condition as described by Kmaul and Maier has a specific aetiology and it, and it ealy. should be given the name of periarteritis nodosa or polyarteritis nodosa acuta. In it the small artery or riole has its whole circumference involved in any part of course, but in the medium-sized artery the lesion appears This was described in 1907 by Dickson, 3 to be eccentric. who noted a slight bulge at the site and concluded that this signified early aneurysm formation ; but serial sections show that the apparently eccentric position of the lesion is due to the disease involving a branch at the point where it arises from the main vessel, the aneurysm-like bulge being the bfpnning of its lumen. In some cases where an artery divides into two branches the parent vessel is free of disease, but the branches themselves show the necrotic process, again starting at their points of origin. A similar distribution of the necrotising lesions was described in a form of rheumatic lung.’ The
true
pbly
The presence of leucocytic infiltration at the site of the lesion has led to confusion, and it was actually at one time believed because of this that the condition was of infective origin. However, serial sections show that the necrotis occurs in the first instance without any leucocytic response, which is a secondary phenomenon. Moreover, the lumen of the vessel tends to be markedly increased at the site of the necrosis, suggesting a bursting from within as the cause. It is also noteworthy that only the arteries are involved, the veins never. The true pulmonary circulation is not involved : thus a section of lung may show a normal pulmonary artery lying adjacent to a diseased bronchial artery (which belongs to the systemic
circulation). seen in a section of liver where may lie next to a normal portal vein bile-duct. Conversely, it has been shown 4 that there is type of rheumatic lung in which a necrotising arteritis ly resembling periarteritis nodosa occurs and involves pulmonary circulation to the exclusion of the systemic Sections have also shown that there may appear to be a d attack of the condition while the primary one is ing evidence of healing by fibrous proliferation, and in ’ cases the necrosis may be found in the subintimal ferating fibrous stroma and not in the remnants of the , again suggesting that the cause is pressure acting from the lumen.
A similar condition may be
crotic
-
hepatic artery
study
of the
reported
strates that in
cases
of
periarteritis
nodosa
great many of them the bloodmuch higher than normal and the heart a
ure is frequently hypertrophied.
It haa been suggested by that any rise of pressure has been due to the renal mia aasociated with the condition, but in most evidence suggests that the hypertension and " thecondition have preceded, and not followed, the is Thus it appears probable that the arterial of periarteritis nodosa is of traumatic origin and to actual of the walls of the artery, owing bursting ‘‘ rapidly rising blood-pressure. Similarly, when =_=- of necrotising arteritis are confined to the pul-
‘-
1. A. Thesis, University of Glasgow, 1938. 2. . A., Maier, R. Dtsch. Arch. klin. Med. 1866, 1, 484, , W. E. C. J. Path. Bact. 1907, 12 31. 4. A. Glasg. med. J. 1947, 28, 127. 3.
monic circulation they are probably due to an increase of pressure in that circulation due to left heart -failure, or back-pressure from niitral stenosis. The question of course arises as to which part of the arterial system will suffer damage in such a sudden rise of pressure in the systemic circulation. The larger vessels are well supported with their musculo-elastic elements, while the smallest vessels subserve a wide vascular bed so that pressure in them will be low. Thus it would appear justifiable to believe that the small and medium-sized arteries, the ones involved in periarteritis nodosa, would be the ones most likely to suffer. This view also eorresponds to the presence of the lesion at the beginning of a branch, where, of course, the pressure will be highest. Can this theory be reconciled with the work of Selye on the diseases of adaptation " ’? Ile has shown that the production of corticoids increases the body’s resistance to stress-producing agents; but where there is an excessive or unbalanced production of mineralocorticoid, the process may derail and the primarily useful generaladaptation syndrome become the cause of disease—the so-c.alled diseases, which include periarteritis nodosa. It has been found experimentally that an animal may be sensitised to the action of mineralocorticoid— for example, by a high-salt diet or unilateral nephrectomy. A significant feature of the experimental work carried out by Selye has been an associated rise in blood-pressure. Thus he mentionsthat animals overdosed with deoxycortone (a mineralocorticoid) reproduce " the experimental equivalent of certain hypertensive rheumatic and allergic diseases of man—in particular, malignant nephrosclerosis, necrotising arteritis similar to periarteritis nodosa, as well as intense and persistent rise in arterial blood pressure." There may therefore bo grounds for suggesting that Selye’s experimental work gives added that the lesions of periarteritis weight to the nodosa can be attributed to a rapid rise of blood"
eollagen
"
"
theory
pressure. The Royal Infirmary, Greenock.
A. LYALL.
THE SMALL-LIST PRACTITIONER
SIR,—Why has the small-list practitioner over the age of 60 to apply for the new remuneration ? His age, the size of his list, and surely the length of his residence . in the district are known to the paying authorities. I thought the regulation was meant to put an end to " a gross injustice: instead it looks as if it is to be given as a kind of charity. Nobody applied for the Danckwerts addition. Why should we? OVER-60 SMALL-LIST PRACTITIONER. "
ISONIAZID AND P.A.S. SIR,—So many of us are groping for a satisfactory regimen of chemotherapy for prolonged treatment of tuberculosis that the paper by Dr. Joiner and his colleagues in your issue of Oct. 2 must attract attention, though the significance of the results quoted is perhaps not altogether clear. What is disappointing in this, as in some other papers, is the failure to describe clearly the dose of the drugs used. 250 mg. of isoniaid may be given as a single dose or may be divided. 10g. of p-aminosalicylic acid (P.A.S.) has been split into two doses or four in different Medical Research Council trials ; which method was used here t There is only an oblique suggestion that it may have been the former. There is much uncertainty about the value of methods other than those so far proved satisfactory by the M.R.C. trials 6 7; and those, involving daily injections, are not acceptable for very long periods. What seems probable is that the efficacy of p.A.s. is related to the peak blood concentration obtained four times, thrice, or perhaps 5. 6. 7.
Selve, H. Brit. med. J. 1950, ii, 1129 ; Ibid, 1951, i, 203. Ibid, 1952, i, 1157. Lancet, 1953, ii, 217.
rotising arteritis. condition as described by Kussmaul and Maier 2p the small and medium-sized arteries and is affects 66 marked by the naked-eye appearance of tiny white tubercleions in the acute phase, and aneurysm and thrombus tion at a later stage. Whereas there are many conditions which may give necrotising arteritis in different partg of the y it is my belief that the condition as described by Kmaul and Maier has a specific aetiology and it, and it ealy. should be given the name of periarteritis nodosa or polyarteritis nodosa acuta. In it the small artery or riole has its whole circumference involved in any part of course, but in the medium-sized artery the lesion appears This was described in 1907 by Dickson, 3 to be eccentric. who noted a slight bulge at the site and concluded that this signified early aneurysm formation ; but serial sections show that the apparently eccentric position of the lesion is due to the disease involving a branch at the point where it arises from the main vessel, the aneurysm-like bulge being the bfpnning of its lumen. In some cases where an artery divides into two branches the parent vessel is free of disease, but the branches themselves show the necrotic process, again starting at their points of origin. A similar distribution of the necrotising lesions was described in a form of rheumatic lung.’ The
true
pbly
The presence of leucocytic infiltration at the site of the lesion has led to confusion, and it was actually at one time believed because of this that the condition was of infective origin. However, serial sections show that the necrotis occurs in the first instance without any leucocytic response, which is a secondary phenomenon. Moreover, the lumen of the vessel tends to be markedly increased at the site of the necrosis, suggesting a bursting from within as the cause. It is also noteworthy that only the arteries are involved, the veins never. The true pulmonary circulation is not involved : thus a section of lung may show a normal pulmonary artery lying adjacent to a diseased bronchial artery (which belongs to the systemic
circulation). seen in a section of liver where may lie next to a normal portal vein bile-duct. Conversely, it has been shown 4 that there is type of rheumatic lung in which a necrotising arteritis ly resembling periarteritis nodosa occurs and involves pulmonary circulation to the exclusion of the systemic Sections have also shown that there may appear to be a d attack of the condition while the primary one is ing evidence of healing by fibrous proliferation, and in ’ cases the necrosis may be found in the subintimal ferating fibrous stroma and not in the remnants of the , again suggesting that the cause is pressure acting from the lumen.
A similar condition may be
crotic
-
hepatic artery
study
of the
reported
strates that in
cases
of
periarteritis
nodosa
great many of them the bloodmuch higher than normal and the heart a
ure is frequently hypertrophied.
It haa been suggested by that any rise of pressure has been due to the renal mia aasociated with the condition, but in most evidence suggests that the hypertension and " thecondition have preceded, and not followed, the is Thus it appears probable that the arterial of periarteritis nodosa is of traumatic origin and to actual of the walls of the artery, owing bursting ‘‘ rapidly rising blood-pressure. Similarly, when =_=- of necrotising arteritis are confined to the pul-
‘-
1. A. Thesis, University of Glasgow, 1938. 2. . A., Maier, R. Dtsch. Arch. klin. Med. 1866, 1, 484, , W. E. C. J. Path. Bact. 1907, 12 31. 4. A. Glasg. med. J. 1947, 28, 127. 3.
monic circulation they are probably due to an increase of pressure in that circulation due to left heart -failure, or back-pressure from niitral stenosis. The question of course arises as to which part of the arterial system will suffer damage in such a sudden rise of pressure in the systemic circulation. The larger vessels are well supported with their musculo-elastic elements, while the smallest vessels subserve a wide vascular bed so that pressure in them will be low. Thus it would appear justifiable to believe that the small and medium-sized arteries, the ones involved in periarteritis nodosa, would be the ones most likely to suffer. This view also eorresponds to the presence of the lesion at the beginning of a branch, where, of course, the pressure will be highest. Can this theory be reconciled with the work of Selye on the diseases of adaptation " ’? Ile has shown that the production of corticoids increases the body’s resistance to stress-producing agents; but where there is an excessive or unbalanced production of mineralocorticoid, the process may derail and the primarily useful generaladaptation syndrome become the cause of disease—the so-c.alled diseases, which include periarteritis nodosa. It has been found experimentally that an animal may be sensitised to the action of mineralocorticoid— for example, by a high-salt diet or unilateral nephrectomy. A significant feature of the experimental work carried out by Selye has been an associated rise in blood-pressure. Thus he mentionsthat animals overdosed with deoxycortone (a mineralocorticoid) reproduce " the experimental equivalent of certain hypertensive rheumatic and allergic diseases of man—in particular, malignant nephrosclerosis, necrotising arteritis similar to periarteritis nodosa, as well as intense and persistent rise in arterial blood pressure." There may therefore bo grounds for suggesting that Selye’s experimental work gives added that the lesions of periarteritis weight to the nodosa can be attributed to a rapid rise of blood"
eollagen
"
"
theory
pressure. The Royal Infirmary, Greenock.
A. LYALL.
THE SMALL-LIST PRACTITIONER
SIR,—Why has the small-list practitioner over the age of 60 to apply for the new remuneration ? His age, the size of his list, and surely the length of his residence . in the district are known to the paying authorities. I thought the regulation was meant to put an end to " a gross injustice: instead it looks as if it is to be given as a kind of charity. Nobody applied for the Danckwerts addition. Why should we? OVER-60 SMALL-LIST PRACTITIONER. "
ISONIAZID AND P.A.S. SIR,—So many of us are groping for a satisfactory regimen of chemotherapy for prolonged treatment of tuberculosis that the paper by Dr. Joiner and his colleagues in your issue of Oct. 2 must attract attention, though the significance of the results quoted is perhaps not altogether clear. What is disappointing in this, as in some other papers, is the failure to describe clearly the dose of the drugs used. 250 mg. of isoniaid may be given as a single dose or may be divided. 10g. of p-aminosalicylic acid (P.A.S.) has been split into two doses or four in different Medical Research Council trials ; which method was used here t There is only an oblique suggestion that it may have been the former. There is much uncertainty about the value of methods other than those so far proved satisfactory by the M.R.C. trials 6 7; and those, involving daily injections, are not acceptable for very long periods. What seems probable is that the efficacy of p.A.s. is related to the peak blood concentration obtained four times, thrice, or perhaps 5. 6. 7.
Selve, H. Brit. med. J. 1950, ii, 1129 ; Ibid, 1951, i, 203. Ibid, 1952, i, 1157. Lancet, 1953, ii, 217.