NEPHROGENIC ASCITES

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might imagine, with only about half the patients maintaining a strict gluten-free diet. Moreover, when abnormal histological findings in jejunal biopsy specimens are taken into account, many patients who claim to be on a strict diet are probably consuming gluten. 13--18 In general, most patients remain well, and growth and biochemical variables, on an individual basis, appear unaffected. In one study, however, the whole group overall weighed significantly less than age and sex matched controls.18 These published results strongly suggest that many patients diagnosed in childhood as having coeliac disease enter adult life in a suboptimum condition with respect to dietary compliance and jejunal morphology. What are the likely explanations for this unsatisfactory situation, and can anything be done about it? It is clear from formal gluten challenge studies that patients do not necessarily get symptoms immediately on reintroduction of gluten. In particular, it may take many years for children to relapse. 19-21 It is also well known that jejunal morphological abnormalities may be due to dietary constituents other than gluten—eg, milk or soy protein." However these results are perceived, they strongly suggest that between 40 and 60% of young coeliacs do not maintain a strict gluten-free diet.18 Since so many are apparently well, some researchers have questioned whether firm dietary compliance is really necessary.22 Jejunal morphology in childhood coeliacs sometimes improves on an entirely normal diet; this observation implies that the state of gluten sensitivity may be only transient,23 although this view is not generally accepted. than

one

What can be done to encourage adolescents to maintain a gluten-free diet? There appears to be a general consensus that failure to comply runs the risk of several serious complications of the disease and that close supervision by an interested physician or paediatrician is important. As a means of identifying those at risk, it is unlikely that many patients would accept jejunal biopsy repeated over many years. Such an approach may not be entirely helpful anyway, since

subsequent reinvestigation in adult life of some patients with supposed coeliac disease diagnosed in childhood reveals that a high proportion have entirely 14. Mortimer PE, Stewart J S, Norman AP, Booth CC Follow-up study of coeliac disease Br Med 1968; J iii. 7-9. 15. Sheldon W. Prognosis in early adult life of coeliac children treated with a gluten-free diet Br Med J 1969, ii: 401-04 16 Young WE, Pringle EM 110 children with coeliac disease, 1950-1969 Arch Dis Child

1971, 46: 421-36 17 Weir DG, Hourihane D O’B Coehac disease during the teenage period the value of serial serum folate estimations Gut 1974, 15: 450-57 18. Kumar PJ, Walker-Smith J, Milla P, Harris G, Colyer J, Halliday R The teenage coeliac follow up study of 102 patients Arch Dis Child 1988; 63: 916-20 19 Visakorpi JK Definition of coeliac disease in childhood In Hekkens WTJM, Pena AS, eds Coeliac disease. Leiden. Stenfert Kroese, 1974. 10-16 20. Shmerling DH Franckx J Childhood celiac disease a long term analysis of relapses in 91 patients J Pediatr Gastroentrol Nutr 1986, 5: 565-69 21. Egan-Mitchell B, Fottrell PF, McNicholl B Prolonged gluten tolerance in treated coeliac disease In McNicholl B, McCarthy CF, Fottrell PF, eds Perspectives in

coeliac disease Lancaster MTP, 1978 25 PJ, Harris G, Walker-Smith J, Milla P, Clark ML. The teenage coeliac. Gut

22 Kumar

1985, 26: A551 23. Schmitz J, Arnaud-Battandier F, Jos J, Rey J Long-term follow-up of childhood coeliac disease (CD ) is there a ’natural recovery’? Pediatr Res 1984; 18: 1052

normal jejunal mucosae despite eating a normal diet.24 If the criteria for diagnosis of coeliac disease in childhood, as defined by The European Society for Paediatric Gastroenterology and Nutrition,25 are strictly adhered to, results such as these will presumably be less common in the future. Rectal biopsy may be an alternative, but has received little attention.26 Weir and Hourihane17 recommended serum folate estimations as the best single indicator of dietary maintenance. Intestinal permeability testing may also be a satisfactory means of detecting those who fail to comply,27 and antigliadin antibodies may be helpful if techniques can be sufficiently refined.28 In the long-term, regular dietary counselling may well achieve the best results; it is noticeable in one study that some of the non-compliant patients admitted to their dietary lapses outside the consultation room.18 Patient education is of paramount importance and in practice it is sometimes very difficult to know what is a gluten-free diet. The Coeliac Society has been a most successful vanguard for information for many coeliac patients. As with adolescents who have diabetes or chronic renal failure, those with coeliac disease have special needs that have to be addressed. Some words of encouragement come from an enlightened teenager who wrote "the diet can never stop you doing anything you want to do". 29 Now that dietary treatment has at last been shown to reduce the most serious risks of long-term coeliac disease-intestinal lymphoma and cancers of some other sites--dietary compliance is of prime importance to all patients with this lifelong disease. 30

NEPHROGENIC ASCITES ASCITES develops in a small proportion of patients with renal failure, usually, but not always, after they have started haemodialysis. In most cases no cause can be found and they are said to have "nephrogenic ascites"-a useful term whatever its etymological shortcomings. The association between renal failure and ascites was first described in 197012 and has lately been reviewed by Gluck and Nolph.3 The reported frequency varies between 0-7 and 26%’* of patients on haemodialysis, but the higher figures are almost 24.

Paerregaard A, Vilien M, Krasilnikoff PA, Gudmand-Hoyer E Supposed coeliac disease during childhood and its presentation 14-38 years later Scand J

Gastroenterol 1988, 23: 65-70 AS, Harms HK, Rey J, Shmerling DH, Visakorpi JK, Walker-Smith JA The diagnosis of coeliac disease. A commentary on the current practices of members of the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) Arch Dis Child 1979; 54: 783-86. 26 Breen EG, Coughlan G, Connolly CE, Stevens FM, McCarthy CF Coeliac proctitis 25. McNeish

ScandJ Gastroenterol 1987, 22: 471-77. 27. Cobden I, Dickinson RJ, Rothwell J, Axon ATR Intestinal permeability assessed

by

of two molecules results in coeliac disease Br Med J 1978; ii: 1060 28 Falchuk ZM, Strober W Gluten-sensitive enteropathy synthesis of antigliadin antibody in vitro Gut 1974, 15: 947-52 29 Anon. The coeliac handbook 6th ed London, the Coeliac Society, 1985 26. 30. Holmes GKT, Prior P, Lane MR, Pope D, Allan R. Malignancy in coeliac disease—effect of a gluten-free diet. Gut (in press) 1 Cinque TJ, Letten J Idiopathic ascites—complication of chronic extracorporeal dialysis Am Soc Nephrol 1970, 4: 16 (abstr). 2. Mahoney JF, Gutch CF, Holmes JH Intractable ascites in chronic dialysis patients. Am Soc Nephrol 1970; 4: 51 (abstr) excretion ratios

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certainly an overestimate. The condition may be becoming less common as dialysis techniques improve. Patients present with increasing abdominal swelling; two-thirds are recognised as having serious fluid overload.33 Interdialytic weight gains are often excessive,4 and patients either admit to extreme thirst or are unable to accept their doctor’s analysis of their fluid intake. Appetite is poor and muscle loss is often pronounced. The degree of ascites may cause abdominal discomfort, anorexia, and even breathlessness.5 Investigation aims to exclude other causes of ascites since there is no specific test for the nephrogenic variety. Cardiac function should be assessed by ultrasound, which may also reveal a pericardial effusion. The ascitic fluid should be examined for occult infection, particularly tuberculosis. The fluid is straw-coloured and has a surprisingly high protein content. 3,6 Biopsy specimens of the peritoneum may occasionally reveal another cause, such as granulomas or malignancy, but usually show no more than a non-specific fibrinous reaction. Radiological examination of the inferior vena cava may show stenosis due to lymphoma or a hepatic cyst.’ Liver function should also be assessed. Laparoscopy may be helpful: in a series of nine patients, a patient with peritoneal tuberculosis and another with cirrhosis were diagnosed in this way.6 Why does the ascitic fluid accumulate? The peritoneum may be more leaky as a result of previous peritoneal dialysis; chronic fluid overload with hepatic congestion is common and may increase pressure in the hepatic and portal capillaries; and removal of peritoneal fluid by lymphatic channels may be reduced.8 It is also possible that the relatively high protein content of the fluid may be due to the concentrating effect of regular ultrafiltration; the consequent increase in osmotic pressure will lead to the formation of yet more fluid. Many forms of treatment have been tried. Attempts to remove the fluid by regular ultrafiltration are usually thwarted by the development of hypotension caused by hypovolaemia in the main extracellular fluid compartment.3.5Repeated paracentesis is a tempting therapy because it relieves the symptoms due to pressure. However, it also leads to protein loss and aggravates the cachexia found in many of these patients. Intraperitoneal steroids help in some cases by reducing the rate of reaccumulation of fluid but are not effective as long-term therapy.3,9 The success of nephrectomy in a few patients has led to the suggestion that the diseased kidneys fail to excrete a substance that increases peritoneal permeability.10 A more likely explanation is that removal of the kidneys reduces thirst in patients with increased angiotensin II generation. Furthermore, nephrogenic ascites has been described in anephric patients." A logical treatment is insertion of a 3 Gluck

Z, Nolph KD. Ascites associated with end stage renal disease Am J Kid Dis 1987; 10: 8-18. 4 Gotleib L, Servadio C. Ascites in patients undergoing maintenance hemodialysis. Am J Med 1976: 465-70. 5 Hobar PC, Turner WW, Valentine RJ. Successful use of the Denver peritoneovenous shunt in patients with nephrogenic ascites. Surgery 1987; 101: 161-63 6. Mauk PM, Schwartz JT, Lowe JE, et al Diagnosis and course of nephrogenic ascites Arch Intern Med 1988; 148: 1577-79 7 Arismendi GS, Izard MW, Hampton WR, Maher JF. The clinical spectrum of ascites associated with maintenance dialysis. Am JJ Med 1976; 60: 46-51. 8. Morgan AG, Terry SI. Impaired peritoneal fluid drainage in nephrogenic ascites. Clin Nephrol 1981; 15: 61-65 9 Jones BF, Trevillian PR, Nanra RS Idiopathic ascites of haemodialysis response to treatment. Br Med J 1976; i: 877. 10. Feingold LN, Gutman RA, Walsh FX, et al. Control of cachexia and ascites in hemodialysis patients by binephrectomy. Arch Intern Med 1974, 134: 989-97 11. Popli S, Chen WT, Nakamoto S, et al Haemodialysis ascites in anephric patients. Clin Nephrol 1981, 15: 203-05

peritoneovenous shunt. This technique has been tried with some short-term success,5,12 but obstruction of the shunt is a major longer term complication. Renal transplantation is the best treatment if the patient is fit enough and a kidney can be found.3 Alternatively, haemodialysis should be replaced by continuous ambulatory peritoneal dialysis (CAPD),13,14 which will reduce the patient’s pressure symptoms and so lead to an increase in appetite. Surprisingly, the protein losses in the dialysate are not excessive. Nephrogenic ascites is a dangerous complication of dialysis: Gluck and Nolph3found that a third of the patients reported died and mean time from detection of the ascites to death was 11 months. This poor outcome may be greatly improved by early conversion to CAPD or transplantation.

MYOCARDITIS, HISTOLOGY, AND IMMUNOSUPPRESSION INFECTIVE myocarditis, most often of viral origin, has not fired too much investigational enthusiasm; in the absence of generally usable specific antiviral agents, treatment has been largely restricted to broad measures, management of failing ventricular function, and care of arrhythmias. Within the past decade the possible benefits of immunosuppression have been a worrying responsibility-what should one do in individual cases? In 1980, Mason et all reported that patients with left ventricular dilatation and signs of chronic interstitial inflammation, shown by biopsy of the myocardium, responded favourably to corticosteroids and immunosuppressvie drugs. Because of the risks of fluid overload in an already failing heart, steroids have not always been given, and the suggestion that endomyocardial biopsy is a prerequisite for logical treatment is not easy to accommodate. Dec and his colleagues2 at Harvard Medical School and the Massachusetts General Hospital have lately reported a study of the relation between histological findings on early repeat right ventricular biopsy and ventricular function in patients with myocarditis who had been treated by immunosuppressive agents. From a very considerable bank of biopsy data, 20 patients with histological confirmation of myocarditis were marshalled. In all cases coronary arteriography excluded important stenoses and the clinician had requested cardiac biopsy for diagnostic purposes. The patients had symptomatic heart failure with reduced left ventricular ejection fraction as shown by radioventriculography. The biopsy was repeated and ventricular function reassessed after a period of immunosuppressive treatment with prednisolone and azathioprine; these procedures were done at a mean of 79 days after the initial biopsy. At repeat biopsy, 8 patients had evidence of ongoing myocarditis and in 12 the inflammation had resolved. In 8 of the 12 patients whose myocarditis had resolved, ventricular function had improved significantly. Left ventricular 12 Yen MC, Stewart EH. Pentoneo-venous shunt for ascites associated with maintenance dialysis Clin Nephrol 1977; 8: 446-48 13. Ing TS, Daugirdas JT, Popli S, et al Treatment of refractory haemodialysis ascites with maintenance pentoneal dialysis. Clin Nephrol 1981; 15: 198-202. 14. Rubin J, Kiley J, Ray R, et al. Continuous ambulatory peritoneal dialysis treatment of dialysis-related ascites Arch Intern Med 1981; 141: 1093-95 1. Mason JW, Billingham ME, Ricci DR. Treatment of acute inflammatory myocarditis assisted by endomyocardial biopsy Am J Cardiol 1980; 45: 1037-44 2 Dec WG, Fallon JT, Southern JF, Palacios IG. relation between histological findings on early repeat right ventricular biopsy and ventricular function in patients with myocarditis. Br Heart J 1988; 60: 332-37