The hazards of living without a spleen were recognised by the paediatricians in the early 1960’s when they focussed attention on the syndrome of fulminant sepsis, often due to pneumococcal infection, occurring in young children within the first two years of splenectomy. The danger of post-splenectomy sepsis (PSS) extends into adult life and splenectomised patients remain at risk 10, 20 and even 30 years after the operation. Problems following splenectomy may just be the tip of the iceberg. It is clear that many other diseases are associated with impaired splenic function in the presence of intact spleens.peer-reviewe

Muller, Andre F.

Toghill, P. J.

English

PubMed

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Maltese Medical Journal 49 Volume VI Issue I 1994 HYPOSPLENISM IN GASTRO-INTESTINAL DISEASE P. J. Toghill, F. Muller Keywords: Hyposplenism,lnf/ammatory Bowel Disease, Coeliac Disease, Liver Disease, Sepsis INTRODUCTION The hazards of living without a spleen were recognised by the paediatricians in the early 1960's when they focussed attention on the syndrome of fulminant sepsis, often due to pneumococcal infection, occurring in young children within the fIrst two years of splenectomy 1. A child, well at breakfast, might be febrile by lunch, comatose by evening and dead by the following morning. We now recognise that this danger of post-splenectomy sepsis (PSS) extends into adult life and splenectomised patients remain at risk 10, 20 and even 30 years after the operation 2. Problems following splenectomy may just be the tip of the iceberg. What is now clear is that many other diseases are associated with impaired splenic function in the presence of intact spleens (Table I). These patients with functional hyposplenism are, like the splenectomised, also vulnerable to the syndrome of PSS. In some of these patients with diseases such as sickle cell disease and thrombocythaemia, where there is infarction of splenic tissue, the cause of the hyposplenism is obvious. It is also easy to understand the mechanics involved in infiltrative diseases such as sarcoidosis or amyloidosis. However in the gastro-intestinal disorders, including inflammatory bowel disease and coeliac disease, the reasons for the hyposplenism are obscure. To this group must now be added alcoholic liver disease in which impaired splenic function appears to be yet another factor in the known . vulnerability of the alcoholic to infection 3. INVESTIGATORY TECHNIQUES Early studies to define those patients with hyposplenism in gastrointestinal disease relied on simple haematological markers such as the presence of Howell-Jolly bodies, acanthocytes and target cells. It soon became apparent that these methods were not suffIciently sensitive to Hammersmith group in London solved this problem by measuring the clearance of isotopically labelled heated erythrocytes 4. This test is based on the fact that red cells damaged by heat become mildly spherocytic and are preferentially cleared by the spleen when re­injected. In this way they behave in a similar way to erythrocytes in hereditary spherocytosis. Impaired clearance of such labelled cells has been shown to be a reliable index of hyposplenism. While the clearance of heated red cells proved a useful experimental tool it was time consuming and needed careful calibration. A simpler method was required and this was provided by Gino Corazza who was able to exploit some earlier observations on erythrocytes from splenectomised patients 5,6. If such erythrocytes are viewed by differential interference contrast microscopy, (which gives a three dimensional view), pits or craters are seen (Figure I). The number of pits or craters can be counted in a simple and reproducible way. In health less than 2% of erythrocytes contain pits whereas after splenectomy up to 50% of cells show pits. This therefore gives a method of assessing splenic function which correlates well with the more complex methods. The true nature of these pits remains uncertain but electron microscopy suggests that they are really vacuoles containing intra-cellular debris of ferritin, haemoglobin and cell membranes 6. This method supplemented with ultrasonic measurements of spleen size provides, therefore, a relatively easy method to assess splenic size and function. P. J. Toghill, MB BS, FRCP, MRCS, LRCP Consultant Physician F. Muller, DM, MRCP (UK) Senior Registrar Queen's Medical Centre, Directorate ofMedicine, University Hospital, Nottingham, UK. pick up lesser degrees of hyposplenism. The Maltese Medical Journal 50 Volume VI Issue I 1994 system. Increased levels of circulating immune complexes have been found in untreated coeliac disease 11 and it is possible that this could lead to functional blockage of the splenic reticulo­endothelial system. However, very high levels of immune complexes in childhood are insufficient to induce splenic hypofunction in childhood coeliac disease 12. Interestingly patients with dermatitis herpetiformis, a disease linked closely to coeliac disease, may also show evidence of impaired splenic function. CHRONIC INFLAMMATORY BOWEL DISEASE Preston, a haemotologist in Sheffield, was one of the first to notice changes of hyposplenism in the peripheral blood of patients with active ulcerative colitis. Subsequent formal investigation of patients with inflammatory bowel disease using the heated red cell clearance method showed significant degrees of hyposplenism in both ulcerative colitis and Crohn's disease. The relationship with disease activity seems much clearer with ulcerative colitis where both medical and surgical treatment improves the hyposplenism which is dependent on the extent of the disease 13-15 . Pereira et aP6 using the simple measure of spleen length at laparotomy noted that patients with ulcerative colitis and Crohn's disease shown to have small spleens had more severe disease and more complications such as perforation, fistulae, abscesses, bleeding and toxic megacolon. Disseminated intravascular coagulation was also shown in hyposplenic patients with inflammatory bowel disease l5 , a complication noted previously in asplenic subjects. The association between Crohn's and hyposplenism is less well defined 17 and there are suggestions that it is colonic Crohn's disease where the link is strongest. The mechanisms, as with coeliac disease. are poorly understood but the profound enteric loss of lymphocytes in inflammatory bowel disease might contribute to the splenic hypofunction. CHRONIC LIVER DISEASE The spleen in liver disease sometimes plays a dual role in that it may contribute to haematological hypersplenism concurrently with immunological hyposplenism. Earlier I TABLE I Haematological Auto-Immune Gastrointestinal I Miscellaneous I 1 -' J .) :.:.1 FIGURE I - Erythrocytes from Splenectomised patient COELIAC DISEASE One of the first gastrointestinal diseases shown to be associated with hyposplenism was coeliac disease 7 and several groups using the clearance of isotopically labelled erythrocytes or pitted cell counts have confirmed that from 25% to 75% of patients with coeliac disease have hyposplenism. Much depends, of course, on the sensitivity of the methods used. The severity of the hyposplenism increases with age at diagnosis and the duration of exposure to gluten 7.8. Although in most patients hyposplenism improves with gluten withdrawal, some investigators have shown it to progress inspite of apparently strict dietary control 9. The dreaded complication of gut lymphoma does not seem to be influenced by whether or not hypospleni'sm is present 10. No single mechanism has been put forward to explain the hyposplenism of coeliac disease. In some patients the hyposplenism is associated with generalised lymph node atrophy and it has been suggested that this is all part of a more widespread atrophy of the lympho-reticular Sickle Cell Disease Throm bocythaeplia Systemic Lupus Erythematosus Thyroid Disease Coeliac Disease Ulcerative Colitis Crohn's Disease Whipple's Disease Idiopathic Ulcerative Enteritis Tropical Sprue Intestinal Lymphangiectasia Alcoholic Cirrhosis Sarcoidosis Amyloidosis Old Age Long Ternl Parenteral Nutrition L____________________________~ suggestions of immunological hyposplenism in Maltese Medical Journal 51 Volume VI Issue I 1994 immune chronic active hepatitis and primary biliary cirrhosis have not been confIrmed 18 but there are now clear indications that immunological hyposplenism frequently complicates alcoholic cirrhosis 3. The alcohol itself seems to be more important than the cirrhosis since abstinence reverts the hyposplenic changes. MISCELLANEOUS GASTROENTEROLOGICAL CONDITIONS Hyposplenism has been described in several other gut diseases though they have been less extensively investigated. Low spleen weights, between 5 and 75 g, have been reported from autopsies in tropical sprue though no formal studies of splenic function have been undertaken19. Splenic atrophy and/or Howell­Jolly bodies are often features of chronic idiopathic ulcerative enteritis though of course these fIndings may be primarily related to the pre-existing gluten enteropathy. Increased pitted References 1. 	 Horan M, Colebatch JH. The relation between splenectomy and subsequent infection. Arch of Dis of Childhood 1962; 37:398-414 2. 	 Zarrabi MN, Rosner F. Serious infections in adults following splenectomy for trauma. Arch ofInt Med 1984; 144:1421-4. 3. 	 Muller AF, Toghill PJ. Splenic function in alcoholic liver disease. Gut 1992; 33: 1836 ­9. 4. 	 Marsh GW, Stewart JS. The use of chromium labelled heat-damaged red cells to study splenic function. Br J of Haemat 1966; 12: 161-6. 5. 	 Corazza GR, Bullen AW, Hall R, Losowsky MS. A simple method of assessing splenic function in coeliac disease. Clih Sc 1981; 60:109-13. 6. 	 Holroyde CP, Gardner FH. Acquisition of autophagic vacuoles by human erythrocytes: physiological role of the spleen. Blood 1970; 36:566-75. 7. 	 Martin JB, Bell HE. The association of splenic atrophy and malabsorption. Canadian Med Assoc J 1965; 62:875-8. cell counts with other confIrmatory evidence of hyposplenism have been noted in Whipple's ,jisease 20 and intestinal lymphangiectasia 21. IS HYPOSPLENISM IMPORTANT IN GASTROINTESTINAL DISEASE? Recent arguments have been put forward that the risks of PSS have been over-stressed22. Nevertheless, the majority of paediatricians, haematologists and physicians regard PSS as a very real and much feared entity. The Sheffield group have reported high rates of post-operative infections after surgery for ulcerative colitis in patients with defective splenic function 13-15 and overwhelming pneumococcal septicaemia has been reported in both ulcerative colitis and coeliac disease23,24. Wyke25 has offered several explanations why alcoholics get infections which include impaired humoral and cellular host defences and defective reticulo-endothelial phagocytic function. Now hyposplenism must be added to this list. 8. 	 O'Grady JG, Stevens FM, Harding B, O'Gorman TA, McNichol B, McCarthy CF. Hyposplenism and gluten senSItIve enteropathy. Gastroent 1985; 87:1326-31. 9. 	 Trewby PN, Chipping PM, Palmer SJ, Roberts PO, Lewis SM, Stewart JS. Splenic atrophy in adult coeliac disease: is it reversible? Gut 1981; 22:628-32. 10. 	 Robertson OAF, Swinson CM, Hall R, Losowsky MS et al. Coeliac disease, splenic function and malignancy. Gut 1982; 23:666-9. 11. 	 Doe WF, Booth CC, Brown DL. Evidence for compliment-binding immune complexes in adult coeliac disease, Crohn's disease and ulcerative colitis. Lancet 1973; i: 402-3. 12. Corazza GR, 	Lazzari R, Frisoni M. Clq binding activity in childhood coeliac disease. Ital J of Gastroent 1983; 15: 14-6. 13. 	 Ryan FP, Smart RC, Preston FE, Holdsworth CD. Hyposplenism in ulcerative colitis. Lancet 1974; ii:318-20. 14. 	 Ryan FP, Smart RC, Holdsworth CD, Preston FE. Hyposplenism in inflammatory bowel disease. Gut 1978; 19:50-5. Maltese Medical Journal 52 Volume VI Issue I 1994 15. 	 Palmer, KR, Sherrif SB, Holdsworth CD, Ryan FP. Further experience of hyposplenism in inflammatory bowel disease. Quart J of Med 1981; 200:463-71. 16. 	 Pereira JLR, Hughes LE, Young HL. Spleen size in patients with inflammatory bowel disease. Does it have any clinical significance? Dis of the Colon & Rectum 1987; 30:403-9. 17. 	 Muller AF, Comford E, Toghill PJ. Splenic function in inflammatory bowel disease: assessment by differential interference microscopy and splenic ultrasound. Quar J of Med (in press). 18. 	 Marcus HS, Muller AF, Toghill PJ. Splenic function assessed by quantification of erythrocyte pits is normal in chronic active hepatitis and primary biliary cirrhosis. J of Hepatol 1993; 18: 106-11. 19. 	 Suarez RM, Spies TO, Suares RM (Jnr). The use of folic acid in sprue. Annals of Int Med 1947; 26:643-77. 20. 	 Corazza GR, Lazzari R, Fasoni M, Gasbarrini G. Splenic function in childhood disease. Gut 1982; 23:415-6. 21. 	 Foster PN, Bullen AW, Robertson OAF, Chalmers AM, Losowsky MS. Development of impaired splenic function in intestinal lymphangiectasia. Gut 1985; 26:861-4. 22. 	 Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis and its mortality rate: actual versus perceived risks. Br J of Surg 1991; 78:1031-8. 23. 	 Foster KJ, Devitt N, Gallagher PJ, Abbott PM. Overwhelming pneumococcal septicaemia in a patient with ulcerative colitis and splenic atrophy. Gut 1983; 23:630-2. 24. 	 O'Donoghue DJ. Fatal pneumococcal septicaemia in coeliac disease. Postgrad Med J 1986; 62:229-30. 25. 	 Wyke RJ. Probelms of bacterial infection in patients with liver disease. Gut 1987; 28:623-41. The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. Users may access this full-text article and can make use of the information contained in accordance with the Copyright Act provided that the author must be properly acknowledged.  Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. This article has been reproduced with the authorization of the editor of the Malta Medical Journal (Ref. No 000001)  

Clq binding activity in childhood coeliac disease.

Coeliac disease, splenic function and malignancy. Gut

Development of impaired splenic function in intestinal lymphangiectasia. Gut

Evidence for compliment-binding immune complexes in adult coeliac disease, Crohn's disease and ulcerative colitis. Lancet

Fatal pneumococcal septicaemia in coeliac disease.

Further experience of hyposplenism in inflammatory bowel disease.

Hyposplenism and gluten senSItIve enteropathy. Gastroent

Hyposplenism in inflammatory bowel disease. Gut

Hyposplenism in ulcerative colitis. Lancet

Overwhelming pneumococcal septicaemia in a patient with ulcerative colitis and splenic atrophy. Gut

Postsplenectomy sepsis and its mortality rate: actual versus perceived risks.

Spleen size in patients with inflammatory bowel disease. Does it have any clinical significance? Dis of the Colon & Rectum

Splenic atrophy in adult coeliac disease: is it reversible? Gut

Splenic function assessed by quantification of erythrocyte pits is normal in chronic active hepatitis and primary biliary cirrhosis.

Splenic function in childhood disease. Gut

Splenic function in inflammatory bowel disease: assessment by differential interference microscopy and splenic ultrasound.

The use of folic acid in sprue. Annals of Int Med

Hyposplenism in gastro-intestinal disease

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Hyposplenism in gastro-intestinal disease

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