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IMPROVEMENT IN HYPERTROPHIC HEPATIC OSTEOARTHROPATHY AFTER LIVER TRANSPLANTATION
968 IMPROVEMENT IN HYPERTROPHIC HEPATIC OSTEOARTHROPATHY AFTER LIVER
TRANSPLANTATION
SiR,—Hypertrophic osteoarthropathy, a rare symptom in patients with liver disease, is seen more often in those with chronic cholestasis. It manifests as painful extremities with arthritis1 and digital clubbing. The syndrome has been reported in chronic rejection of the liver following transplantation.2 A growth-factormediated effect is probably involved leading to elevation of the periosteum with oedema and hyperaemia, new bone deposition, and oedema with increased vascularity of the surrounding soft tissues and ligaments. Dickinson and Martin3postulated that the clubbing may be mediated by a paracrine effect of platelet-derived growth factor. We report two patients with chronic liver disease who had disabling limb pain from hypertrophic osteoarthropathy. Symptoms resolved within a week of successful liver transplantation. A 28-year-old woman with biliary obstruction and chronic graft rejection (vanishing bileduct syndrome) after transplantation (the second attempt) 9 months earlier for fulminant viral hepatitis had intense pruritus and a serum bilirubin of 466 )mol/l. Crippling joint pain had immobilised her in the month before her third transplant. The long bones were exquisitely tender to gentle pressure and small bilateral knee effusions were present. Finger clubbing had developed. X-rays confirmed hypertrophic periostitis. The second patient was a 24-year-old woman with cryptogenic cirrhosis, referred for transplantation because of resistant ascites and lethargy. She had pain in the extremities, especially when walking or writing. No arthritis was present but tenderness over the distal radius, ulna, and tibia were elicited. Finger clubbing was present. Radiographs of the wrist and ankle joints showed the changes of hypertrophic periostitis. Post-transplant immunosuppression was with prednisone 20 mg daily, cyclosporin, and azathioprine. The first patient had been on maintenance cyclosporin before surgery. Both patients had rapid resolution of bony tenderness after transplantation, striking improvement occurring by the third post-operative day with complete loss of pressure tenderness after one week. Vagotomy had not been done in either case at the transplant operation. Radiographs after 3 months in both patients, by then well and discharged from hospital, showed that the periosteal new bone had still not resorbed, although the digital clubbing had regressed. Although we cannot rule out immunosuppression as an explanation for the rapid improvement, this seems unlikely because the first patient had symptoms whilst taking cyclosporin, and prednisone is rarely of benefit in patients with osteoarthropathy from other causes. The stimulus to periosteal reaction and new bone formation may have been a factor which accumulated due to impaired hepatic clearance or was produced in excess by the liver as part of its response to disease. Two growth factors, interleukin-1 and transforming growth factor B, have been shown to modulate bone growth in vitro.4,5 Future cases may provide a good clinical model to evaluate such a liver-derived growth factor, both in vivo and in cultured bone cell lines.
Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH
C. VICKERS A. HERBERT J. NEUBERGER E. ELIAS
1. Epstein O, Ajdukiewicz AB, Dick R, Sherlock S. Hypertrophic, hepatic osteoarthopathy: clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature. Am J Med 1979; 67: 88-97. 2. Wolfe, SM, Aelion JA, Gupta RC. Hepatic osteoarthropathy associated with a rejected liver transplant. J Rheumatol 1987; 14: 147-51. 3. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987; ii: 1434-35. 4. Beresford JN, Gallagher JA, Gowen M, et al. The effects of monocyte-conditioned medium and interleukin 1 on the synthesis of collagenous and non-collagenous proteins by mouse bone and human bone cells in vitro Biochim Biophys Acta 1984; 801: 58-65
AH, Voelkel EF, Lazzaro M, et al. Alpha and beta transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc Natl Acad Sci USA 1985; 82: 4535-38.
5. Tashjian
IS CAMPYLOBACTER PYLORI A ZOONOSIS?
SIR,-Dr Vaira and colleagues (Sept 24, p 725) report that antibodies to both Campylobacter pylori and C }ejunz in abattoir workers were higher than in clerical workers, but did endoscopy in only 28 of 78 non-clerical workers. They do not say whether their serological test was validated originally by endoscopy, because many people with low titres have C pylori in the stomach.’ Alternatively, since Cjejuni is a zoonosis, one reason for some of the low titres of C pylori antibodies could have been partial serological crossreactions between C pylori and C jejuni.1 To substantiate that C pylori is a zoonosis, the organism must be cultured from animals slaughtered in abattoirs. Jones and Curry2 reported that Professor Percival isolated a C pylori-like organism (CPLO) from one pig. Others have failed despite repeated attempts. In Perth we have isolated CPLOs from macaque monkeys, baboons, and ferrets. DNA hybridisation showed that there was less than 100% hybridisation between human C pylori and these animal CPLOs, indicating that they are not identical. In Seattle, USA, two types of CPLO have been isolated from Macaca nemestrina with DNA compositions different from that of C pylori, which is 36-37 mol % G + C. The "nemestrina type A" CPLO has 44 mol % G + C, and "nemestrina type B" CPLO has 24 mol % G + C. We have also found differences in their cellular fatty acids, outer membrane proteins, and menaquinones. The ferret CPLO lacks the fatty acid 3-OH-18:0 typical of C pylori and primate CPLOs. However, these animal CPLOs have some serological crossreactivity with C pylori, and they are all urease positive. Besides the one pig isolate, there is no evidence yet that human-type C pylori exists in abattoir animals, so we should not conclude it is a zoonosis. Stomach bacteria will prove to be a complicated story. Apart from CPLOs, we have seen in animal gastric specimens three different types of spiral and "corkscrew" bacteria distinguishable by special staining of their ultrastructure. Departments of Microbiology and Electronmicroscopy, Royal Perth Hospital,
STEWART GOODWIN
Western Australia 6001
JOHN ARMSTRONG
Regional Primate Research Centre, University of Washington, Seattle, USA
MELINDA BRONSDON
University of Queensland, Brisbane, Australia
LINDSAY SLY
1 Goodwin CS, Blincow E, Peterson G, et al. Enzyme-linked immunosorbent assay for Campylobacter pyloridis: correlation with presence of C pyloridis in the gastric mucosa. J Infect Dis 1987; 155: 488-94. 2. Jones EM, Curry A. Ultrastructural study of gastnc Campylobacter-like organisms (GCLO) from man, baboon, pig and ferret. In: Kaijser B, Falsen E, eds. Campylobacter IV. Proceedings of the fourth international workshop on Campylobacter infections, Goteborg, Sweden. Sweden. University of Gothenburg, 1988: 109.
ENTEROVIRUS INFECTION IN PERIPARTUM CARDIOMYOPATHY
SIR,-In peripartum cardiomyopathy (PPCM) congestive heart failure develops during the third trimester of pregnancy or in the first 6 months postpartum. The aetiology is unknown but myocarditis has been histologically proven in a few cases. One hypothesis is a viral infection of cardiac muscle. We have studied epidemiologically the relation between PPCM and enterovirus infection. The diagnosis of PPCM was made on clinical, radiographic, and echographic signs: dilated heart with low ventricular contractility, normal ventricular thickness, and heart failure first developing during the third trimester of pregnancy or in the first 6 months postpartum.3 38 black African women with PPCM (mean age 30-33 [SD 7-7] years) living in western Niger were included in the study. Controls were 37 breastfeeding African women without cardiac disease who presented at a dispensary on behalf of their children. Age, parity, social profile, and geographical and ethnic origin were similar in the two groups. For every woman a sample was taken by venepuncture into a sterile tube with anticoagulant and immediately separated by centrifugation; plasma was frozen at - 20’C.
TRANSPLANTATION
SiR,—Hypertrophic osteoarthropathy, a rare symptom in patients with liver disease, is seen more often in those with chronic cholestasis. It manifests as painful extremities with arthritis1 and digital clubbing. The syndrome has been reported in chronic rejection of the liver following transplantation.2 A growth-factormediated effect is probably involved leading to elevation of the periosteum with oedema and hyperaemia, new bone deposition, and oedema with increased vascularity of the surrounding soft tissues and ligaments. Dickinson and Martin3postulated that the clubbing may be mediated by a paracrine effect of platelet-derived growth factor. We report two patients with chronic liver disease who had disabling limb pain from hypertrophic osteoarthropathy. Symptoms resolved within a week of successful liver transplantation. A 28-year-old woman with biliary obstruction and chronic graft rejection (vanishing bileduct syndrome) after transplantation (the second attempt) 9 months earlier for fulminant viral hepatitis had intense pruritus and a serum bilirubin of 466 )mol/l. Crippling joint pain had immobilised her in the month before her third transplant. The long bones were exquisitely tender to gentle pressure and small bilateral knee effusions were present. Finger clubbing had developed. X-rays confirmed hypertrophic periostitis. The second patient was a 24-year-old woman with cryptogenic cirrhosis, referred for transplantation because of resistant ascites and lethargy. She had pain in the extremities, especially when walking or writing. No arthritis was present but tenderness over the distal radius, ulna, and tibia were elicited. Finger clubbing was present. Radiographs of the wrist and ankle joints showed the changes of hypertrophic periostitis. Post-transplant immunosuppression was with prednisone 20 mg daily, cyclosporin, and azathioprine. The first patient had been on maintenance cyclosporin before surgery. Both patients had rapid resolution of bony tenderness after transplantation, striking improvement occurring by the third post-operative day with complete loss of pressure tenderness after one week. Vagotomy had not been done in either case at the transplant operation. Radiographs after 3 months in both patients, by then well and discharged from hospital, showed that the periosteal new bone had still not resorbed, although the digital clubbing had regressed. Although we cannot rule out immunosuppression as an explanation for the rapid improvement, this seems unlikely because the first patient had symptoms whilst taking cyclosporin, and prednisone is rarely of benefit in patients with osteoarthropathy from other causes. The stimulus to periosteal reaction and new bone formation may have been a factor which accumulated due to impaired hepatic clearance or was produced in excess by the liver as part of its response to disease. Two growth factors, interleukin-1 and transforming growth factor B, have been shown to modulate bone growth in vitro.4,5 Future cases may provide a good clinical model to evaluate such a liver-derived growth factor, both in vivo and in cultured bone cell lines.
Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH
C. VICKERS A. HERBERT J. NEUBERGER E. ELIAS
1. Epstein O, Ajdukiewicz AB, Dick R, Sherlock S. Hypertrophic, hepatic osteoarthopathy: clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature. Am J Med 1979; 67: 88-97. 2. Wolfe, SM, Aelion JA, Gupta RC. Hepatic osteoarthropathy associated with a rejected liver transplant. J Rheumatol 1987; 14: 147-51. 3. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987; ii: 1434-35. 4. Beresford JN, Gallagher JA, Gowen M, et al. The effects of monocyte-conditioned medium and interleukin 1 on the synthesis of collagenous and non-collagenous proteins by mouse bone and human bone cells in vitro Biochim Biophys Acta 1984; 801: 58-65
AH, Voelkel EF, Lazzaro M, et al. Alpha and beta transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc Natl Acad Sci USA 1985; 82: 4535-38.
5. Tashjian
IS CAMPYLOBACTER PYLORI A ZOONOSIS?
SIR,-Dr Vaira and colleagues (Sept 24, p 725) report that antibodies to both Campylobacter pylori and C }ejunz in abattoir workers were higher than in clerical workers, but did endoscopy in only 28 of 78 non-clerical workers. They do not say whether their serological test was validated originally by endoscopy, because many people with low titres have C pylori in the stomach.’ Alternatively, since Cjejuni is a zoonosis, one reason for some of the low titres of C pylori antibodies could have been partial serological crossreactions between C pylori and C jejuni.1 To substantiate that C pylori is a zoonosis, the organism must be cultured from animals slaughtered in abattoirs. Jones and Curry2 reported that Professor Percival isolated a C pylori-like organism (CPLO) from one pig. Others have failed despite repeated attempts. In Perth we have isolated CPLOs from macaque monkeys, baboons, and ferrets. DNA hybridisation showed that there was less than 100% hybridisation between human C pylori and these animal CPLOs, indicating that they are not identical. In Seattle, USA, two types of CPLO have been isolated from Macaca nemestrina with DNA compositions different from that of C pylori, which is 36-37 mol % G + C. The "nemestrina type A" CPLO has 44 mol % G + C, and "nemestrina type B" CPLO has 24 mol % G + C. We have also found differences in their cellular fatty acids, outer membrane proteins, and menaquinones. The ferret CPLO lacks the fatty acid 3-OH-18:0 typical of C pylori and primate CPLOs. However, these animal CPLOs have some serological crossreactivity with C pylori, and they are all urease positive. Besides the one pig isolate, there is no evidence yet that human-type C pylori exists in abattoir animals, so we should not conclude it is a zoonosis. Stomach bacteria will prove to be a complicated story. Apart from CPLOs, we have seen in animal gastric specimens three different types of spiral and "corkscrew" bacteria distinguishable by special staining of their ultrastructure. Departments of Microbiology and Electronmicroscopy, Royal Perth Hospital,
STEWART GOODWIN
Western Australia 6001
JOHN ARMSTRONG
Regional Primate Research Centre, University of Washington, Seattle, USA
MELINDA BRONSDON
University of Queensland, Brisbane, Australia
LINDSAY SLY
1 Goodwin CS, Blincow E, Peterson G, et al. Enzyme-linked immunosorbent assay for Campylobacter pyloridis: correlation with presence of C pyloridis in the gastric mucosa. J Infect Dis 1987; 155: 488-94. 2. Jones EM, Curry A. Ultrastructural study of gastnc Campylobacter-like organisms (GCLO) from man, baboon, pig and ferret. In: Kaijser B, Falsen E, eds. Campylobacter IV. Proceedings of the fourth international workshop on Campylobacter infections, Goteborg, Sweden. Sweden. University of Gothenburg, 1988: 109.
ENTEROVIRUS INFECTION IN PERIPARTUM CARDIOMYOPATHY
SIR,-In peripartum cardiomyopathy (PPCM) congestive heart failure develops during the third trimester of pregnancy or in the first 6 months postpartum. The aetiology is unknown but myocarditis has been histologically proven in a few cases. One hypothesis is a viral infection of cardiac muscle. We have studied epidemiologically the relation between PPCM and enterovirus infection. The diagnosis of PPCM was made on clinical, radiographic, and echographic signs: dilated heart with low ventricular contractility, normal ventricular thickness, and heart failure first developing during the third trimester of pregnancy or in the first 6 months postpartum.3 38 black African women with PPCM (mean age 30-33 [SD 7-7] years) living in western Niger were included in the study. Controls were 37 breastfeeding African women without cardiac disease who presented at a dispensary on behalf of their children. Age, parity, social profile, and geographical and ethnic origin were similar in the two groups. For every woman a sample was taken by venepuncture into a sterile tube with anticoagulant and immediately separated by centrifugation; plasma was frozen at - 20’C.