498 MAST-CELL DEGRANULATION IN CROHN’S DISEASE
sue
SIR,-During a large ultrastructural morphological study of Crohn’s disease we have found mast-cell degranulation to be a prominent feature. Surgically resected specimens from twelve patients with Crohn’s disease and three controls were prepared for ultrastructural analysis.’ Numerous mast cells, and fewer basophils, were preferentially located in the various diseased muscle layers, in the oedematous submucosa, and
are
Fig. I-Non-degranulated mast cell in submucosa of ileal specimen from patient with Crohn’s disease (x 6400).
substantial evidence for a role for mast-cell mediain this disease. Further trials of disodium cromoglycate
provide
tors
indicated. A. M. DVORAK
Electron
Microscopy Unit, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, U.S.A.
R. A. MONAHAN J. E. OSAGE G. R. DICKERSIN
YERSINIA ENTEROCOLITICA AND GLOMERULONEPHRITIS
SiR,—Most cases of glomerulonephritis in the Western world are of unknown aetiology, even though many cases have been described where infectious agents other than streptococci are responsible. In Malrno and Copenhagen we have seen several patients with Yersinia enterocolitica serotype 3 in whom proteinuria, haematuria, and in some cases hypertension and altered kidney function developed and in whom other causes of infection could be excluded. We have now done a consecutive study of 23 patients with acute glomerulonephritis, verified clinically and by biopsy, seen at Herlev Hospital over a 21-month period. The department serves a population of 600 000 in Copenhagen County. Cases of glomerulonephritis admitted to the county paediatric departments are not included. The patients were aged 14-72 (average 38-5). Kidney-biopsy specimens from all these patients were examined light-microscopically by Dr Claus Brun, Copenhagen Municipal Hospital, and immunofluorescence microscopy was done where there was sufficient tissue. 11 of the 23 patients had serological evidence of current or recent yersiniosis, with an increased titre for Y. enterocolitica serotype 3 (from 80 to 10240) and in most cases a clear increase or fall in titre during the observation period. Only 5 of the 11 patients showed signs of clinical yersiniosis. 1,1 None had increased antistreptolysin 0 or anti-streptococcal hyaluronidase titre and all had normal C3, C4, and C,q. Immunofluorescence microscopy was attempted on 9 of the 11 patients. In 1 case there was insufficient tissue for evaluation, but all the remaining 8 cases showed glomerular, granular, and global fluorescence of IgG, IgA, and C3, and in 3 cases for C,q and properdine also. Double-layer technique with specific anti-yersinia antibodies3 revealed clear fluorescence for yersinia antigen in 5 of the 8 cases and fluorescence was blocked specifically by a control technique (see figure). Samples from 23 other patients with glomerulonephritis but no increased yersinia 1. Hannover Larsen, J. Proc. 3rd int. Symp. Yersinia. Basle (in the 2. Winblad, S. Symp. Ser. immunobiol. Standard. 1968, 9, 133. 3. Cederberg, A. Acta path. microbiol. scand. 1967, 71, 376.
Fig. 2-Degranulated mast cell in submucosa of patient with Crohn’s disease (x6600).
of ileal
press).
specimen
adjacent to and within proliferating autonomic nervous system elements of the gut. Non-degranulated (fig. 1) and degranulated (fig. 2) mast cells were present in all specimens examined. Morphological evidence of mast-cell degranulation in Crohn’s disease suggests a role for released mast-cell mediators (histamine, platelet activation factor, slow-reacting substance of ariaphylaxis, eosinophil chemotactic factor) in the pathogenesis and symptomatology of the disease and in discussion of
possible treatments. Dr Henderson and Dr Hishon (Jan. 14, p. 109) describe a patient with Crohn’s disease who responded to disodium cromoglycate. This response, after conventional medical therapy
had failed, obviated the need for resection. This response toa
drug which inhibits the release of histamine from human mast cells2 and our finding of mast-cell degranulation in Crohn’s tis1. Dvorak, A. M., Mihm, M. C. Jr., H. F. Lab. Invest. 1976, 2. Orange, R. P., Austen, K. F. Prog. Immun. 1971, 1, 173.
34, 179.
Section of glomerulus showing global, enterocolitica serotype 3 antigen.
granular deposits
of Y.
be seen along glomerulus basal membranes and in where IgG and complement C3 are also located. Section thickness 1 p.m (reduced to 2/5 of 850.)
Deposits mesangium
can
499 were examined by immunofluorescence microscopy; showed fluorescence for yersinia.
titre
none
HLA-B27-ASSOCIATED SPONDYLARTHRITIS IN CHRONIC BRUCELLOSIS
,
Light microscopy showed proliferative glomerulonephritis in 10 of the 11 cases. There have been
about clinical signs of and clinical done. Howin common and posat least Scandinavia, is, ever, yersiniosis about In Denmark the is 3%.6 In prevalence increasing. sibly our small series the frequency of serological evidence for Y. enterocolitica serotypeinfection was 48%, and of these tients about half showed signs of glomerular involvement of immunological origin with a specific yersinia antigen. We believe that Y. enterocolitica serotype 3 may be a common xtiological factor in the development of acute glomerulonephritis. We have started a prospective controlled study. a
few
publications
glomerulonephritis in patients with serological yersinioses,4.s but no systematic study has been
pa-
Departments of Nephrology University of Copenhagen, Herlev Hospital,
B and
Pathology, M. FRIEDBERG S. LARSEN
Copenhagen, Denmark Renal Unit,
University of Lund, T. DENNEBERG
Malmö, Sweden
SCABIES AND ACUTE GLOMERULONEPHRITIS
SIR,-Scabies with secondary infection
can
give
rise
to
glomerulonephritis,7 the association being more frequent
in tropical and subtropical zones than in temperate climates.’, 11 A severe case seen in France is reported here. A 19-year-old butcher, previously fit, presented in June, 1977, with pruritic lesions on his hands, legs, abdomen, and back. 3 weeks later he complained of weakness, loss of appetite, nausea, and vomiting. He was producing little or no urine and had ankle and palpebral cedema with a weight-loss of 3 kg. His temperature was 40 °C. He was referred to us on July 20. We found pruritic vesicular lesions on wrist, palm, and penis and impetiginous lesions of the upper part of thigh and buttock. A secondarily infected scabies was diagnosed although an acarus was not isolated. A -haemolytic streptococcus grew from a cutaneous lesion swab and not from a throat swab. His antistreptolysin 0 titre was 320 units. Blood-pressure was 100/60 mm Hg. He passed about 300 ml urine in 24 h. Laboratory investigations and the progress of the disease corroborated acute glomerulonephritis. He had haematuria and proteinuria. Serum 1C&bgr;-globulin (lCp) was below 5 mg/dl. His plasma creatinine was 12.9 mg/dl and urea 390 mg/dl. An arteriovenous shunt was placed on his right leg. Three haemodialyses were done until diuresis was restored. Cutaneous lesions recovered with benzyl benzoate and ampicillin treatment. On Aug. 26 his renal function was normal and his serum-R1C had risen to 36 mg/dl. The severity of this case is a reminder of the need to look for evidence of nephropathy in patients with scabies, especially if bacteria have invaded the skin. A short course of penicillin should be given to prevent glomerulonephritis if a R-ha’molytic streptococcus grows from a swab taken from a cutaneous lesion. J. P. CHARMES Services de Néphrologie et C.H.U. Dupuytren, 87031 Limoges, France
tations of chronic brucellosis may be neglected even by experienced rheumatologists. These manifestations include arthralgias, myalgias, recurrent arthritic episodes, and back pain, accompanied by radiological signs of sacroiliitis or reactive changes of the dorsal vertebrae. These symptoms resemble those associated with the group of rheumatic diseases known as reactive spondylarthritides, which are associated with an increased frequency of the histocompatibility antigen HLA B27.1 This antigen was sought by a lymphocytotoxicity micromethod2 in 63 male and 5 female patients with chronic brucellosis, They had a history of infection and acute febrile disease, frequent relapses, and at least three positive passive hmmagglutination and complement-fixation tests. Antigen was prepared from Brucella abortus bovis, this being the causative agent in most brucella infections in
Hungary.
Department of Medicine,
acute
SIR,-The joint manifestations of acute brucella infection-i.e., acute oligoarticular purulent arthritis, spondylitis, or sacroiliitis-are well known, but the rheumatic manifes-
Dermatologie,
J. M. BONNETBLANC J. ROUX D. BENEVENT C. LEROUX-ROBERT
4. Forsström, J., Viander, M., Lehtonen, A., Ekfors, T. Scand. J. infect. Dis. 1977, 9, 253. 5. Lemo, R., Kalliomäki, J. L. Ann. intern. Med. 1974, 81, 458. 6. Hannover Larsen, J. Ugeskr. Laeg. 1977, 44, 2627. 7. Gordon W. Lancet, 1972,i, 794. 8. Svartman, M., Potter, E. V., Finklea, J. F., Poon-King, T., Earle, D. P. ibid. p. 249. 9. Allen, B. R. ibid. p. 434. 10 Moulin, G., Bouchet, B., Berthoux, F. Ann. Derm. Vener. 1977, 104, 81.
B27 was found in 12.8% of 352 healthy Hungarians, and in 25% of patients with chronic brucellosis. Patients were classified into two groups depending on the presence or absence of symptoms seen with brucellosis-associated spondylarthritis. 27 patients (39%) had a history of exudative arthritis, severe back pain, or clinical signs of arthritis or painful and limited spine movements with a tenderness of the dorsolumbar vertebrae and sacroiliac joints on physical examination. They had radiological evidence of sacroiliitis or osteochondritis of the dorsal vertebrae. The frequency of B27 was 44% in this group, and among the remaining 41 patients the frequency was 12%, almost the same as that of the normal population. The difference between the two groups was significant (P
sue
SIR,-During a large ultrastructural morphological study of Crohn’s disease we have found mast-cell degranulation to be a prominent feature. Surgically resected specimens from twelve patients with Crohn’s disease and three controls were prepared for ultrastructural analysis.’ Numerous mast cells, and fewer basophils, were preferentially located in the various diseased muscle layers, in the oedematous submucosa, and
are
Fig. I-Non-degranulated mast cell in submucosa of ileal specimen from patient with Crohn’s disease (x 6400).
substantial evidence for a role for mast-cell mediain this disease. Further trials of disodium cromoglycate
provide
tors
indicated. A. M. DVORAK
Electron
Microscopy Unit, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, U.S.A.
R. A. MONAHAN J. E. OSAGE G. R. DICKERSIN
YERSINIA ENTEROCOLITICA AND GLOMERULONEPHRITIS
SiR,—Most cases of glomerulonephritis in the Western world are of unknown aetiology, even though many cases have been described where infectious agents other than streptococci are responsible. In Malrno and Copenhagen we have seen several patients with Yersinia enterocolitica serotype 3 in whom proteinuria, haematuria, and in some cases hypertension and altered kidney function developed and in whom other causes of infection could be excluded. We have now done a consecutive study of 23 patients with acute glomerulonephritis, verified clinically and by biopsy, seen at Herlev Hospital over a 21-month period. The department serves a population of 600 000 in Copenhagen County. Cases of glomerulonephritis admitted to the county paediatric departments are not included. The patients were aged 14-72 (average 38-5). Kidney-biopsy specimens from all these patients were examined light-microscopically by Dr Claus Brun, Copenhagen Municipal Hospital, and immunofluorescence microscopy was done where there was sufficient tissue. 11 of the 23 patients had serological evidence of current or recent yersiniosis, with an increased titre for Y. enterocolitica serotype 3 (from 80 to 10240) and in most cases a clear increase or fall in titre during the observation period. Only 5 of the 11 patients showed signs of clinical yersiniosis. 1,1 None had increased antistreptolysin 0 or anti-streptococcal hyaluronidase titre and all had normal C3, C4, and C,q. Immunofluorescence microscopy was attempted on 9 of the 11 patients. In 1 case there was insufficient tissue for evaluation, but all the remaining 8 cases showed glomerular, granular, and global fluorescence of IgG, IgA, and C3, and in 3 cases for C,q and properdine also. Double-layer technique with specific anti-yersinia antibodies3 revealed clear fluorescence for yersinia antigen in 5 of the 8 cases and fluorescence was blocked specifically by a control technique (see figure). Samples from 23 other patients with glomerulonephritis but no increased yersinia 1. Hannover Larsen, J. Proc. 3rd int. Symp. Yersinia. Basle (in the 2. Winblad, S. Symp. Ser. immunobiol. Standard. 1968, 9, 133. 3. Cederberg, A. Acta path. microbiol. scand. 1967, 71, 376.
Fig. 2-Degranulated mast cell in submucosa of patient with Crohn’s disease (x6600).
of ileal
press).
specimen
adjacent to and within proliferating autonomic nervous system elements of the gut. Non-degranulated (fig. 1) and degranulated (fig. 2) mast cells were present in all specimens examined. Morphological evidence of mast-cell degranulation in Crohn’s disease suggests a role for released mast-cell mediators (histamine, platelet activation factor, slow-reacting substance of ariaphylaxis, eosinophil chemotactic factor) in the pathogenesis and symptomatology of the disease and in discussion of
possible treatments. Dr Henderson and Dr Hishon (Jan. 14, p. 109) describe a patient with Crohn’s disease who responded to disodium cromoglycate. This response, after conventional medical therapy
had failed, obviated the need for resection. This response toa
drug which inhibits the release of histamine from human mast cells2 and our finding of mast-cell degranulation in Crohn’s tis1. Dvorak, A. M., Mihm, M. C. Jr., H. F. Lab. Invest. 1976, 2. Orange, R. P., Austen, K. F. Prog. Immun. 1971, 1, 173.
34, 179.
Section of glomerulus showing global, enterocolitica serotype 3 antigen.
granular deposits
of Y.
be seen along glomerulus basal membranes and in where IgG and complement C3 are also located. Section thickness 1 p.m (reduced to 2/5 of 850.)
Deposits mesangium
can
499 were examined by immunofluorescence microscopy; showed fluorescence for yersinia.
titre
none
HLA-B27-ASSOCIATED SPONDYLARTHRITIS IN CHRONIC BRUCELLOSIS
,
Light microscopy showed proliferative glomerulonephritis in 10 of the 11 cases. There have been
about clinical signs of and clinical done. Howin common and posat least Scandinavia, is, ever, yersiniosis about In Denmark the is 3%.6 In prevalence increasing. sibly our small series the frequency of serological evidence for Y. enterocolitica serotypeinfection was 48%, and of these tients about half showed signs of glomerular involvement of immunological origin with a specific yersinia antigen. We believe that Y. enterocolitica serotype 3 may be a common xtiological factor in the development of acute glomerulonephritis. We have started a prospective controlled study. a
few
publications
glomerulonephritis in patients with serological yersinioses,4.s but no systematic study has been
pa-
Departments of Nephrology University of Copenhagen, Herlev Hospital,
B and
Pathology, M. FRIEDBERG S. LARSEN
Copenhagen, Denmark Renal Unit,
University of Lund, T. DENNEBERG
Malmö, Sweden
SCABIES AND ACUTE GLOMERULONEPHRITIS
SIR,-Scabies with secondary infection
can
give
rise
to
glomerulonephritis,7 the association being more frequent
in tropical and subtropical zones than in temperate climates.’, 11 A severe case seen in France is reported here. A 19-year-old butcher, previously fit, presented in June, 1977, with pruritic lesions on his hands, legs, abdomen, and back. 3 weeks later he complained of weakness, loss of appetite, nausea, and vomiting. He was producing little or no urine and had ankle and palpebral cedema with a weight-loss of 3 kg. His temperature was 40 °C. He was referred to us on July 20. We found pruritic vesicular lesions on wrist, palm, and penis and impetiginous lesions of the upper part of thigh and buttock. A secondarily infected scabies was diagnosed although an acarus was not isolated. A -haemolytic streptococcus grew from a cutaneous lesion swab and not from a throat swab. His antistreptolysin 0 titre was 320 units. Blood-pressure was 100/60 mm Hg. He passed about 300 ml urine in 24 h. Laboratory investigations and the progress of the disease corroborated acute glomerulonephritis. He had haematuria and proteinuria. Serum 1C&bgr;-globulin (lCp) was below 5 mg/dl. His plasma creatinine was 12.9 mg/dl and urea 390 mg/dl. An arteriovenous shunt was placed on his right leg. Three haemodialyses were done until diuresis was restored. Cutaneous lesions recovered with benzyl benzoate and ampicillin treatment. On Aug. 26 his renal function was normal and his serum-R1C had risen to 36 mg/dl. The severity of this case is a reminder of the need to look for evidence of nephropathy in patients with scabies, especially if bacteria have invaded the skin. A short course of penicillin should be given to prevent glomerulonephritis if a R-ha’molytic streptococcus grows from a swab taken from a cutaneous lesion. J. P. CHARMES Services de Néphrologie et C.H.U. Dupuytren, 87031 Limoges, France
tations of chronic brucellosis may be neglected even by experienced rheumatologists. These manifestations include arthralgias, myalgias, recurrent arthritic episodes, and back pain, accompanied by radiological signs of sacroiliitis or reactive changes of the dorsal vertebrae. These symptoms resemble those associated with the group of rheumatic diseases known as reactive spondylarthritides, which are associated with an increased frequency of the histocompatibility antigen HLA B27.1 This antigen was sought by a lymphocytotoxicity micromethod2 in 63 male and 5 female patients with chronic brucellosis, They had a history of infection and acute febrile disease, frequent relapses, and at least three positive passive hmmagglutination and complement-fixation tests. Antigen was prepared from Brucella abortus bovis, this being the causative agent in most brucella infections in
Hungary.
Department of Medicine,
acute
SIR,-The joint manifestations of acute brucella infection-i.e., acute oligoarticular purulent arthritis, spondylitis, or sacroiliitis-are well known, but the rheumatic manifes-
Dermatologie,
J. M. BONNETBLANC J. ROUX D. BENEVENT C. LEROUX-ROBERT
4. Forsström, J., Viander, M., Lehtonen, A., Ekfors, T. Scand. J. infect. Dis. 1977, 9, 253. 5. Lemo, R., Kalliomäki, J. L. Ann. intern. Med. 1974, 81, 458. 6. Hannover Larsen, J. Ugeskr. Laeg. 1977, 44, 2627. 7. Gordon W. Lancet, 1972,i, 794. 8. Svartman, M., Potter, E. V., Finklea, J. F., Poon-King, T., Earle, D. P. ibid. p. 249. 9. Allen, B. R. ibid. p. 434. 10 Moulin, G., Bouchet, B., Berthoux, F. Ann. Derm. Vener. 1977, 104, 81.
B27 was found in 12.8% of 352 healthy Hungarians, and in 25% of patients with chronic brucellosis. Patients were classified into two groups depending on the presence or absence of symptoms seen with brucellosis-associated spondylarthritis. 27 patients (39%) had a history of exudative arthritis, severe back pain, or clinical signs of arthritis or painful and limited spine movements with a tenderness of the dorsolumbar vertebrae and sacroiliac joints on physical examination. They had radiological evidence of sacroiliitis or osteochondritis of the dorsal vertebrae. The frequency of B27 was 44% in this group, and among the remaining 41 patients the frequency was 12%, almost the same as that of the normal population. The difference between the two groups was significant (P
