678 A.E., and may enhance absorption of this essential ment in normal human neonates.
trace
ele-
Department of Nutrition, Agricultural Experimental Station,
College of Agricultural and Environmental Sciences, Sciences,
University of California, Davis, California 95616, U.S.A.
LUCILLE S. HURLEY BO LÖNNERDAL ANNA G. STANISLOWSKI
POLYARTERITIS NODOSA AND HAIRY-CELL LEUKÆMIA
SIR,-Classic polyarteritis nodosa is
a systemic necrotising affecting medium and small muscular arteries. The aetiology is usually unknown, though some cases seem to be related to hepatitis-B-virus infection.’ The host factors which allow virus-antibody complexes to persist in the circulation and deposit in vessel wallsl,2 are poorly defined. The occurrence of vasculitis in patients with chronic lymphoproliferative neoplasms3 such as chronic lymphatic leukaemia, Hodgkin’s disease, and multiple myeloma may provide insight into this problem since immunological abnormalities and recurrent infections are common to all. Patients with hairy-cell leukaemia are very susceptible to infection4’ and are reported to have serum factors which impair monocyte function.6 For this reason, we believe that the coincidence of hairy-cell leuksemia and polyarteritis nodosa in the patient described in this report may have pathogenetic implications. A 36-year-old man presented with an indolent septic ulcer on the right index finger in April, 1976. He was pale and had moderate splenomegaly. He had pancytopenia with typical hairy-cells accounting for 4% of the total white-cell count. Splenectomy was done in July, 1976, after which he had bacterial pneumonia and herpes labialis. Several minor skin and oropharyngeal infections occurred after discharge from hospi-
vasculitis
2 months the patient had severe rest pain. He was admitted to hospital where he was noted to be normotensive with weak pulsations in the right dorsalis pedis and posterior tibial arteries. The ankle-occlusion pressure was 140 mm Hg on the left and 95 mm Hg on the right. The rest of the physical examination was normal apart from mild axillary and inguinal lympha-
denopathy. The Hb was 10.8 g/dl, w.B.c. 4x 109/1 (4% hairy-cells), and platelets 400x 109/1. Bone-marrow and lymph-node histology revealed extensive hairy-cell infiltration. Renal and liver function tests were normal and neither HBs antigen nor antibody were detected. Serum-IgG was raised at 38.0 g/1 but tests for rheumatoid factor, antinuclear antibody, and cryoglobulins were negative. Total serum complement (CHsa) and the early complement components were low, suggesting activation of the classical pathway. Circulating immune complexes were detected (Clq binding assay). Arteriography showed numerous microaneurysms 2-5 mm in diameter in the inferior mesenteric circulation and in the arteries of both legs (see figure). Since both polyarteritis nodosa and hairy-cell leukaemia are a chance association is highly unlikely. The susceptibility of patients with hairy-cell leuksemia to infection is largely due to neutropenia, but may also result from a profound monocytopenia and impaired monocyte function.4 The monocyte-macrophage system has a central role in the clearance of immune complexes, and any factor interfering with function of this system could result in the prolonged circulation and deposition of these complexes. Although current reviews’5 do not comment on the occurrence of vasculitic disorders in hairy-cell leukaemia, the frequent use of corticosteroids and immunosuppressive drugs may modify the nature and expression of a concurrent vasculitis. We believe this to be the first report of an association between the two conditions. More detailed studies of other patients with hairy-cell leukaemia are in progress.
rare,
tal. 1977 the patient had several episodes of arthritis of both knees which responded to short courses of prednisone. In March, 1978, intermittent claudication of the right leg developed. The claudication distance rapidly decreased and within
During
Gocke, D. J., Hsu, K., Morgan, C., Bombardieri, S., Lockshin, M., Christian, C. L. Lancet, 1970, ii, 1149. 2. Gerber, M. A., Brodin, A., Steinberg, D., Vernance, S., Yang, C. H., Paronetto, F. New Engl. J. Med. 1972, 286, 14. 3. Fauci, A. S., Haynes, B. F., Katz, P. Ann intern. Med. 1978, 89, 660 4 Golomb, H. M., Catovsky, D., Golde, D.W. ibid. 1978, 89, 677. 5. Turner, A., Kjeldsberg, C. R. Medicine, 1978, 57, 478. 6. Kjeldsberg, C. R. Ann, intern Med. 1978, 88, 268.
Royal Postgraduate Medical School, London W12
G. R. V. HUGHES K. B. ELKON R. SPILLER D. CATOVSKY
I. JAMIESON
1.
YERSINIA ENTEROCOLITICA AND THYROID DISEASES IN SPAIN
SIR,-Studies in Denmark’2 and the U.S.A.3 have revealed high incidence of anti Yersinia enterocolitica (Y.E.) antibodies in several thyroid diseases. In Denmark, the prevalence of a
anti-Y.E. antibodies in the normal population is higher than it is in U.S.A.; nevertheless the incidence of antibodies to Y.E. serotype 3 is similar in patients of both countries with thyroid diseases. We have looked for anti-Y.E. antibodies serotypes 3 and 9, in sera of 154 patients with a variety of thyroid diseases and in 44 controls. Agglutination was done in a microtitre system
(Dynatech Corporation, Cambridge, Massachusetts) using as antigen strains supplied by Dr Sten Winblad (Lund University, Mahno, Sweden). In positive cases, seroagglutination to brucella was tested by the same method to see if there was a crossreaction. Titres of 1/8 or greater were considered significant (see table). The frequency of anti-Y.E. antibodies was similar in control individuals and in patients with thyroid diseases; positive cases were serotype 9 except in 1 control and in 1 patient with multinodular goitre. In positive cases with Graves’ disease, there was no relation to functional status; none of the positive cases 1. 2.
...
Microaneurysms
in arteries of both
legs.
Bech, K., Larsen, J. H., Hansen, J. M. Lancet, 1974, ii, 951. Bech, K., Nerup, J., Larsen, J. H. Acta endocr. 1977, 84, 87. 3. Shenkman, L., Bottone, E. J. Ann. intern. Med. 1976, 85, 735.
679 FREQUENCY
OF ANTI-Y.E.
ANTIBODIES
SEROTYPES
3
AND
9
IN
PATIENTS WITH THYROID DISEASES AND IN CONTROLS
90
plasma-exchange all).
sessions each
lasting about
3 h
(270
h in
Our data suggest, however, that if plasmapheresis were restricted to patients with biopsy evidence of some relatively normal glomeruli, the demands on the unit would be much reduced and the success-rate would be significantly higher. If our conclusion that plasmapheresis is worthless in cases where all the glomeruli are badly affected is confirmed by other workers this would have implications for the provision of plasmapheresis on renal units for routine as opposed to research purposes.
had agglutinin titres to brucella, and none of these patients had any symptoms compatible with yersiniosis. The presence of anti-Y.E. antibodies in different thyroid diseases and the improbability of a single xtiology, suggest that the association reported by others is only an incidental finding. Division
If our experience is typical, a regional unit serving a population of 2 million would expect to use plasmapheresis only about five times per year, which is not adequate to maintain the high level of clinical experience in what is a potentially hazardous procedure. It would, therefore, seem preferable that each region should have a central plasmapheresis unit to deal with renal problems, myasthenia gravis, disseminated lupus, and the various hsematological conditions which can be helped
by plasma exchange. D. HARMER R. FINN
of Endocrinology
Department of Medicine, and Division of Microbiology, Ciudad Sanitaria de la Seguridad Social,
Hospitalet de Llobregat, Barcelona, Spain
T. M. GÓMEZ SÁEZ J. SOLER RAMÓN
A. CASANOVA
PLASMAPHERESIS IN FULMINATING CRESCENTIC NEPHRITIS
SiR,-Plasmapheresis has proved very effective in the treatof Goodpasture’s syndrome’ and myasthenia gravis2-4 and it may also be valuable in fulminating glomerulonephritis
epithelial crescents. of ten cases recovered (plasma-creatinine 100-300 1.13-3-39 mg/dl). We retrospectively reviewed the biopsy material to see whether there were any features which correlated with a successful outcome. The main finding was that the four patients who recovered all showed some normal or near normal glomeruli, in addition to the severely damaged glomeruli. Relatively normjl glomeruli were not seen in the six cases who did not respond. There was no control series and we cannot be certain that Four
out
PLEXUS DAMAGE
SIR,-Chronic idiopathic intestinal pseudo-obstruction (c.i.i.p.) is a rare syndrome with an obscure pathogenesis.’ At surgery, there is no identifiable organic lesion obstructing the bowel lumen, and conventional histological examination of resected specimens is unhelpful. However, detailed study of myenteric plexus with silver preparations has revealed significant damage to the neurones in the five published case-reports in which this specialised neuropathological technique has been done.2-s We have demonstrated damage to the myenteric plexus in a resected specimen of small bowel from an 18-month-old child with the C.I.I.p. syndrome.
mol/1,
these were not spontaneous recoveries; we have seen a patient with extensive crescent formation who recovered without any treatment. However, a 40% recovery-rate in patients presenting in acute renal failure with extensive epithelial crescents is quite contrary to our previous experience, particularly since several of these patients had a marked diuresis within a few days of starting plasmapheresis. Our findings, therefore, support those of Lockwood et al. who concluded that plasmapheresis is valuable in this condition. Plasmapheresis, however, is costly and time-consuming. We normally treat our patients with nine 3 litre exchanges within 20 days, so the treatment of these patients over a year required 1. Lockwood, C. M., Rees, A. J., Pearson, T. A., Evans, D. J., Peters, D. K., Wilson, C. B. Lancet, 1976, i, 711. 2. Pinching, A. J., Peters, D. K., Davis, J. N ibid. 1976, ii, 1373. 3. Finn, R., Coates, P. M. ibid. i, 190 4. Dan, P. C., Lindsboun, J. M., Cassel, C. K., Denys, E. H., Shev, E. E., Spitler, L. E. NewEngl. J. Med. 1977, 297, 1134. 5 Lockwood, C. M., Pinching, A. J., Sweny, P., Rees, A. J., Pussell, B., Uff, J.,Peters, D. K. Lancet, 1977, i, 63.
A. W. FORBES
CHRONIC IDIOPATHIC INTESTINAL PSEUDO-OBSTRUCTION WITH MYENTERIC
ment
with crescent formation in the absence of anti-basement membrane antibody.5 We wish to report our experience over a period of one year of treating ten such cases with plasmapheresis combined with prednisolone, azathioprine, and cyclophosphamide. Every patient presented with acute renal failure requiring urgent dialysis, but with no evidence of previous renal disorder, and biopsy revealed severe proliferative changes with marked
H. J. GOLDSMITH J. M. BONE
Renal Unit, Sefton General Hospital, Liverpool L15 2HE
A male child
was
admitted
at
the age of 2 months for vomit-
ing and chronic diarrhoea with steatorrhoea and poor weight gain. A barium meal demonstrated spontaneous gastro-cesophageal reflux with abnormal gastric folds in the cardia and distended coils of proximal small bowel. Jejunal biopsy was normal. Pancreatic insufficiency was excluded by pancreaticfunction studies, and sweat tests were normal. There was no evidence of anaemia or thrombocytopenia. Despite medical treatment, vomiting persisted with no significant weight gain, but steatorrhoea ceased. The child was readmitted at 16 months. A further barium meal showed distension of the proximal jejunal coils followed by an obstruction which severely reduced the barium flow. At operation, a narrowed segment of small bowel 7 cm long was found at 20 cm from the duodenojejunal junction and resected with an end-toend anastomosis. Postoperative recovery was uneventful. Since his operation, the child has gained weight and he is clinically well. Macroscopically, the mucosa appeared normal with no evidence of ulceration or obstruction and the muscle coat was not 1. 2.
Faulk, D. L., Anuras, S., Christensen, J. Gastroenterology, 1978, 74, 922. Dyer, N. H., Dawson, A. M., Smith, B F., Todd, I. P. Br. med. J. 1969, i, 686. 3. Coste, T., Bernardes, P., Molas, P. Nouv. Presse méd. 1972, 1, 447. 4. Phat, V. N., Chousterman, M., Bloch, F., Petite, J. P., Camilleri, J. P. Ann. Anat. Path. 1978, 23, 131. 5. Schuffler, M. D., Bird, T. D., Sumi, S. M., Cook, A. Gastroenterology, 1978, 75, 889.
trace
ele-
Department of Nutrition, Agricultural Experimental Station,
College of Agricultural and Environmental Sciences, Sciences,
University of California, Davis, California 95616, U.S.A.
LUCILLE S. HURLEY BO LÖNNERDAL ANNA G. STANISLOWSKI
POLYARTERITIS NODOSA AND HAIRY-CELL LEUKÆMIA
SIR,-Classic polyarteritis nodosa is
a systemic necrotising affecting medium and small muscular arteries. The aetiology is usually unknown, though some cases seem to be related to hepatitis-B-virus infection.’ The host factors which allow virus-antibody complexes to persist in the circulation and deposit in vessel wallsl,2 are poorly defined. The occurrence of vasculitis in patients with chronic lymphoproliferative neoplasms3 such as chronic lymphatic leukaemia, Hodgkin’s disease, and multiple myeloma may provide insight into this problem since immunological abnormalities and recurrent infections are common to all. Patients with hairy-cell leukaemia are very susceptible to infection4’ and are reported to have serum factors which impair monocyte function.6 For this reason, we believe that the coincidence of hairy-cell leuksemia and polyarteritis nodosa in the patient described in this report may have pathogenetic implications. A 36-year-old man presented with an indolent septic ulcer on the right index finger in April, 1976. He was pale and had moderate splenomegaly. He had pancytopenia with typical hairy-cells accounting for 4% of the total white-cell count. Splenectomy was done in July, 1976, after which he had bacterial pneumonia and herpes labialis. Several minor skin and oropharyngeal infections occurred after discharge from hospi-
vasculitis
2 months the patient had severe rest pain. He was admitted to hospital where he was noted to be normotensive with weak pulsations in the right dorsalis pedis and posterior tibial arteries. The ankle-occlusion pressure was 140 mm Hg on the left and 95 mm Hg on the right. The rest of the physical examination was normal apart from mild axillary and inguinal lympha-
denopathy. The Hb was 10.8 g/dl, w.B.c. 4x 109/1 (4% hairy-cells), and platelets 400x 109/1. Bone-marrow and lymph-node histology revealed extensive hairy-cell infiltration. Renal and liver function tests were normal and neither HBs antigen nor antibody were detected. Serum-IgG was raised at 38.0 g/1 but tests for rheumatoid factor, antinuclear antibody, and cryoglobulins were negative. Total serum complement (CHsa) and the early complement components were low, suggesting activation of the classical pathway. Circulating immune complexes were detected (Clq binding assay). Arteriography showed numerous microaneurysms 2-5 mm in diameter in the inferior mesenteric circulation and in the arteries of both legs (see figure). Since both polyarteritis nodosa and hairy-cell leukaemia are a chance association is highly unlikely. The susceptibility of patients with hairy-cell leuksemia to infection is largely due to neutropenia, but may also result from a profound monocytopenia and impaired monocyte function.4 The monocyte-macrophage system has a central role in the clearance of immune complexes, and any factor interfering with function of this system could result in the prolonged circulation and deposition of these complexes. Although current reviews’5 do not comment on the occurrence of vasculitic disorders in hairy-cell leukaemia, the frequent use of corticosteroids and immunosuppressive drugs may modify the nature and expression of a concurrent vasculitis. We believe this to be the first report of an association between the two conditions. More detailed studies of other patients with hairy-cell leukaemia are in progress.
rare,
tal. 1977 the patient had several episodes of arthritis of both knees which responded to short courses of prednisone. In March, 1978, intermittent claudication of the right leg developed. The claudication distance rapidly decreased and within
During
Gocke, D. J., Hsu, K., Morgan, C., Bombardieri, S., Lockshin, M., Christian, C. L. Lancet, 1970, ii, 1149. 2. Gerber, M. A., Brodin, A., Steinberg, D., Vernance, S., Yang, C. H., Paronetto, F. New Engl. J. Med. 1972, 286, 14. 3. Fauci, A. S., Haynes, B. F., Katz, P. Ann intern. Med. 1978, 89, 660 4 Golomb, H. M., Catovsky, D., Golde, D.W. ibid. 1978, 89, 677. 5. Turner, A., Kjeldsberg, C. R. Medicine, 1978, 57, 478. 6. Kjeldsberg, C. R. Ann, intern Med. 1978, 88, 268.
Royal Postgraduate Medical School, London W12
G. R. V. HUGHES K. B. ELKON R. SPILLER D. CATOVSKY
I. JAMIESON
1.
YERSINIA ENTEROCOLITICA AND THYROID DISEASES IN SPAIN
SIR,-Studies in Denmark’2 and the U.S.A.3 have revealed high incidence of anti Yersinia enterocolitica (Y.E.) antibodies in several thyroid diseases. In Denmark, the prevalence of a
anti-Y.E. antibodies in the normal population is higher than it is in U.S.A.; nevertheless the incidence of antibodies to Y.E. serotype 3 is similar in patients of both countries with thyroid diseases. We have looked for anti-Y.E. antibodies serotypes 3 and 9, in sera of 154 patients with a variety of thyroid diseases and in 44 controls. Agglutination was done in a microtitre system
(Dynatech Corporation, Cambridge, Massachusetts) using as antigen strains supplied by Dr Sten Winblad (Lund University, Mahno, Sweden). In positive cases, seroagglutination to brucella was tested by the same method to see if there was a crossreaction. Titres of 1/8 or greater were considered significant (see table). The frequency of anti-Y.E. antibodies was similar in control individuals and in patients with thyroid diseases; positive cases were serotype 9 except in 1 control and in 1 patient with multinodular goitre. In positive cases with Graves’ disease, there was no relation to functional status; none of the positive cases 1. 2.
...
Microaneurysms
in arteries of both
legs.
Bech, K., Larsen, J. H., Hansen, J. M. Lancet, 1974, ii, 951. Bech, K., Nerup, J., Larsen, J. H. Acta endocr. 1977, 84, 87. 3. Shenkman, L., Bottone, E. J. Ann. intern. Med. 1976, 85, 735.
679 FREQUENCY
OF ANTI-Y.E.
ANTIBODIES
SEROTYPES
3
AND
9
IN
PATIENTS WITH THYROID DISEASES AND IN CONTROLS
90
plasma-exchange all).
sessions each
lasting about
3 h
(270
h in
Our data suggest, however, that if plasmapheresis were restricted to patients with biopsy evidence of some relatively normal glomeruli, the demands on the unit would be much reduced and the success-rate would be significantly higher. If our conclusion that plasmapheresis is worthless in cases where all the glomeruli are badly affected is confirmed by other workers this would have implications for the provision of plasmapheresis on renal units for routine as opposed to research purposes.
had agglutinin titres to brucella, and none of these patients had any symptoms compatible with yersiniosis. The presence of anti-Y.E. antibodies in different thyroid diseases and the improbability of a single xtiology, suggest that the association reported by others is only an incidental finding. Division
If our experience is typical, a regional unit serving a population of 2 million would expect to use plasmapheresis only about five times per year, which is not adequate to maintain the high level of clinical experience in what is a potentially hazardous procedure. It would, therefore, seem preferable that each region should have a central plasmapheresis unit to deal with renal problems, myasthenia gravis, disseminated lupus, and the various hsematological conditions which can be helped
by plasma exchange. D. HARMER R. FINN
of Endocrinology
Department of Medicine, and Division of Microbiology, Ciudad Sanitaria de la Seguridad Social,
Hospitalet de Llobregat, Barcelona, Spain
T. M. GÓMEZ SÁEZ J. SOLER RAMÓN
A. CASANOVA
PLASMAPHERESIS IN FULMINATING CRESCENTIC NEPHRITIS
SiR,-Plasmapheresis has proved very effective in the treatof Goodpasture’s syndrome’ and myasthenia gravis2-4 and it may also be valuable in fulminating glomerulonephritis
epithelial crescents. of ten cases recovered (plasma-creatinine 100-300 1.13-3-39 mg/dl). We retrospectively reviewed the biopsy material to see whether there were any features which correlated with a successful outcome. The main finding was that the four patients who recovered all showed some normal or near normal glomeruli, in addition to the severely damaged glomeruli. Relatively normjl glomeruli were not seen in the six cases who did not respond. There was no control series and we cannot be certain that Four
out
PLEXUS DAMAGE
SIR,-Chronic idiopathic intestinal pseudo-obstruction (c.i.i.p.) is a rare syndrome with an obscure pathogenesis.’ At surgery, there is no identifiable organic lesion obstructing the bowel lumen, and conventional histological examination of resected specimens is unhelpful. However, detailed study of myenteric plexus with silver preparations has revealed significant damage to the neurones in the five published case-reports in which this specialised neuropathological technique has been done.2-s We have demonstrated damage to the myenteric plexus in a resected specimen of small bowel from an 18-month-old child with the C.I.I.p. syndrome.
mol/1,
these were not spontaneous recoveries; we have seen a patient with extensive crescent formation who recovered without any treatment. However, a 40% recovery-rate in patients presenting in acute renal failure with extensive epithelial crescents is quite contrary to our previous experience, particularly since several of these patients had a marked diuresis within a few days of starting plasmapheresis. Our findings, therefore, support those of Lockwood et al. who concluded that plasmapheresis is valuable in this condition. Plasmapheresis, however, is costly and time-consuming. We normally treat our patients with nine 3 litre exchanges within 20 days, so the treatment of these patients over a year required 1. Lockwood, C. M., Rees, A. J., Pearson, T. A., Evans, D. J., Peters, D. K., Wilson, C. B. Lancet, 1976, i, 711. 2. Pinching, A. J., Peters, D. K., Davis, J. N ibid. 1976, ii, 1373. 3. Finn, R., Coates, P. M. ibid. i, 190 4. Dan, P. C., Lindsboun, J. M., Cassel, C. K., Denys, E. H., Shev, E. E., Spitler, L. E. NewEngl. J. Med. 1977, 297, 1134. 5 Lockwood, C. M., Pinching, A. J., Sweny, P., Rees, A. J., Pussell, B., Uff, J.,Peters, D. K. Lancet, 1977, i, 63.
A. W. FORBES
CHRONIC IDIOPATHIC INTESTINAL PSEUDO-OBSTRUCTION WITH MYENTERIC
ment
with crescent formation in the absence of anti-basement membrane antibody.5 We wish to report our experience over a period of one year of treating ten such cases with plasmapheresis combined with prednisolone, azathioprine, and cyclophosphamide. Every patient presented with acute renal failure requiring urgent dialysis, but with no evidence of previous renal disorder, and biopsy revealed severe proliferative changes with marked
H. J. GOLDSMITH J. M. BONE
Renal Unit, Sefton General Hospital, Liverpool L15 2HE
A male child
was
admitted
at
the age of 2 months for vomit-
ing and chronic diarrhoea with steatorrhoea and poor weight gain. A barium meal demonstrated spontaneous gastro-cesophageal reflux with abnormal gastric folds in the cardia and distended coils of proximal small bowel. Jejunal biopsy was normal. Pancreatic insufficiency was excluded by pancreaticfunction studies, and sweat tests were normal. There was no evidence of anaemia or thrombocytopenia. Despite medical treatment, vomiting persisted with no significant weight gain, but steatorrhoea ceased. The child was readmitted at 16 months. A further barium meal showed distension of the proximal jejunal coils followed by an obstruction which severely reduced the barium flow. At operation, a narrowed segment of small bowel 7 cm long was found at 20 cm from the duodenojejunal junction and resected with an end-toend anastomosis. Postoperative recovery was uneventful. Since his operation, the child has gained weight and he is clinically well. Macroscopically, the mucosa appeared normal with no evidence of ulceration or obstruction and the muscle coat was not 1. 2.
Faulk, D. L., Anuras, S., Christensen, J. Gastroenterology, 1978, 74, 922. Dyer, N. H., Dawson, A. M., Smith, B F., Todd, I. P. Br. med. J. 1969, i, 686. 3. Coste, T., Bernardes, P., Molas, P. Nouv. Presse méd. 1972, 1, 447. 4. Phat, V. N., Chousterman, M., Bloch, F., Petite, J. P., Camilleri, J. P. Ann. Anat. Path. 1978, 23, 131. 5. Schuffler, M. D., Bird, T. D., Sumi, S. M., Cook, A. Gastroenterology, 1978, 75, 889.
