Journal of the Royal Society of Medicine Volume 84 July 1991
node only. A small bowel enema showed thickened terminal ileum folds which was confirmed on CT-scan. A duodenal biopsy was negative for alpha-heavy chain positive, immunoproliferative small intestinal disorder (IPSID) or lymphoma. Colonoscopy was normal, and colonic and terminal ileum biopsies showed no evidence of tuberculosis or lymphoma. Screening tests for collagen vascular disease were negative. T-lymphocyte function was slightly impaired in keeping with a chronic infectious disease, and the HIV screens were negative. In view of the negative histology the patient was discharged to be closely followed-up as an outpatient. The patient was readmitted in July 1989 desperately ill with diarrhoea, a high swinging fever, emaciation (30 kg) and profound lassitude. Blood cultures, full blood count and bone marrow examination were negative. A repeat CT-scan of the chest carried out because of the development of signs in the left base, now showed large mediastinal nodes and left lower lobe consolidation. Bronchoscopy was unhelpful with regard to bacteriology and histology, but mediastinal lymph node biopsy revealed caseating granuloma with acidfast bacilli (AFB). Her general condition improved dramatically on anti-TB treatment within 2 weeks. Twelve weeks later her weight improved, diarrhoea stopped and a small bowel enema and CT-scan were completely normal.
diagnostic approach in such patients in whom the diagnosis remains elusive. The hallmark of diagnosis is the finding of caseating granuloma and/or AFB on histology or culture of the intestinal lesion'. These rigid criteria have been extended to include an unequivocal response to anti-TB treatment in patients with clinical, radiological and/or operative evidence of intestinal TB associated with histologically-proven TB elsewhere2. The diagnosis in our patient was made on the latter basis. The one-year delay in establishing the diagnosis in our case raises the question as to whether laparotomy should not have been undertaken during earlier admissions. Laparotomy remains the definitive investigation in many patients with intestinal TB"12. The question also arises as to whether a therapeutic trial with anti-TB therapy is warranted in some patients with suspected intestinal TB in whom the diagnosis of TB cannot be readily established2. This approach may be of both diagnostic and therapeutic value, and is practised in most endemic areas.
Discussion The case highlights several problems relating to the diagnosis of suspected intestinal TB and, indeed, the
(Accepted 18 June 1990. Correspondence to Dr Th Lingenfelser, Department of Medicine, University of Tuebingen, Division of Gastroenterology, 7400 Tuebingen, Germany)
437
References 1 Marks IN. Abdominal tuberculosis. In: Baillieres clinical and tropical medicine & communicable diseases. Vol 3/2. London: Bailliere Tindall, 1988:329-48 2 Gilinsky NH, Marks IN, Kottler RE, et al Abdominal tuberculosis: a 10-year review. S Afr Med J 1983;64:849-57
Massive lower gastrointestinal bleeding in association with the brown bowel syndrome
J P Hurley MB1 R Leary MBs C E Connolly FRCPath2 P Keeling FRCSI' Departments of 'Surgery and 2Pathology, University College Hospital, Galway, Ireland Keywords: brown bowel syndrome; vitamin E
The brown bowel syndrome (BBS), so called because of the accumulation of lipofuscin in the intestinal smooth muscle layer, is a rare condition occurring in association with vitamin E deficiency and leads to atrophy of the intestinal smooth muscle. We report a case of BBS in a coeliac presenting with massive lower gastrointestinal bleeding, a complication not previously recognized in this condition, which shows lipofuscin deposition in vascular smooth muscle may have been the predisposing factor.
Case report A 58-year-old man was transferred from a peripheral hospital with a 2-day history of passing large amounts of fresh blood per rectum. There was no associated abdominal pain. He had required seven units of blood in the 24 h prior to transfer. The patient had no past history of gastrointestinal bleeding but was a known coeliac. On admission the patient was pale, pulse 110/min, blood pressure 90/60. Abdominal examination was normal, rectal examination confirmed fresh blood but no mass was felt. His haemoglobin was 8.4 g/dl, a COAG screen, plain film ofthe abdomen, chest X-ray and ECG were normal. The patient was resuscitated with a further three units of blood. Colonoscopy failed to demonstrate a bleeding point, but fresh blood was seen as far as the caecum. Emergency angiography was unavailable, and as the patient continued to bleed he had a total colectomy and ileostomy. He had no further bleeding and made a good postoperative recovery. A histological diagnosis of the brown bowel syndrome was made.
~~~~
VC
...
or
Figure 1. Section of colon showing marked smooth muscle atrophy (H & Ex24)
Discussion The BBS, a term first used to describe this condition in 19631, is characterized by a copper coloured bowel due to the accumulation of lipofuscin in the smooth muscle layer and atrophy and atony of the smooth muscle (Figure 1). The brown bowel syndrome has previously been reported in association with coeliac disease2. It is due to malabsorption and is specifically associated with a deficiency of vitamin E3. Though the precise pathophysiology is unknown it is
0141-0768/91/ 070437-02/$02.00/0 © 1991 The Royal Society of Medicine
438
Journal of the Royal Society of Medicine Volume 84 July 1991
postulated that vitamin E has an important protective role in mitochondria preventing the unsaturated lipids of the mitochondrial membrane being damaged by free radicals formed during oxidative phosphorylation4'5. Our patient was a coeliac of 11 years, a poor complier with his gluten free diet and had frequent bouts of steatorrhoea. His vitamin E level during admission was low, 5.6 ng/l (normal range 9-14 ng/l). Lower gastrointestinal haemorrhage has not been desribed as a complication of the brown bowel syndrome. Lipofuscin deposition in vascular smooth muscle has only been occasionally documented6. In this case histological sections through the mesentery revealed accumulation of lipofuscin in smooth muscle of the wall of the arteries and veins and it can be postulated that it is this defect in vascular smooth muscle that allowed massive haemorrhage to occur and continue. In conclusion, while the brown bowel syndrome is rare it may present with massive lower gastrointestinal bleeding
and therefore one must seek and treat vitamin E deficiency in conditions causing malabsorption in an effort to prevent this condition. References 1 Tosser AH, Hukill PB, Spiro HM. Brown bowel syndrome. Ann Intern Med 1963;22:872-7 2 Stamp GW, Evans DJ. Accumulation of ceroid in smooth muscle indicates severe malabsorption and vitamin E deficiency. J Clin Pathol 1987;40:798-802 3 Foster CS. The brown bowel syndrome: a possible smooth muscle mitochondrial myopathy? Histopatiology 1979;3:1-17 4 Hoster JP, Kimmel KK, Mockler DD. The 'Brown Bowel Syndrome': A case report. Am J Gastro 1982;77:854-55 5 Farrell PM, Bieri JG, Fratartoni JF, Wood RE, Di Sant Agnese PA. The )ccrence and effects of human Vitamin E deficiency. 6 Fox B. Lipofuscinosis of the gastro-intestinal tract in man. J Clin Pathol 196720:806-13 (Accepted 18 June 1990. Correspondence to JPHuriey, Department of Cardiac Surgery, Mater Hospita, Ecckes Street, Dublin 7, Ireland)
5 q- Syndrome and monoclonal gammopathy with a1 antitrypsin deficiency
C Jeandell J P Aymard2 F Penin' R L Hofmann3 M George4 F Bertrand3 M J Gregoire' G Cunyl CHU Nancy, Brabois, 54500, Vandoeuvre Las Nancy, France, 'Service of Internal Medicne B, 2Regional Blood Transfusion and HematoogjCentr, . md 8StC. 3Department of Biochemieti s Keywords: myelodysplastic.syndrome.r, dys; a, antitrypsin
We describe a patient who presented with 5 q-syidrome, monoclonal gammopathy of undetermined s ance (MGUS) and a, antitrypin (a, ATl) deficienc n di the possible relations between these three abn alites Ti-r knowledge this is the first such case-inthe tedical literatle.
Case report An 86-year-old woman in previous good health was amitted to the hospital due to excsive f . Physical examination was unremarkable. She denied any sfiant alcohol intake and did not smoke but there was a possible to benzene. Routine blood tests disclosed a am (Hb: 9 g/dl, MCV: 113 fl), white -u,ount,:x1OtL2Q% polymorphonuclear cells, 78% 1 2%Ln cytes) and a platelet cou 9(22Ox19.PI B,1,tIte, and red cell folate were ihin t n em c concentration was 2.12-rn *Lfmi ntion tests were normal. Serum protein el showed sediment in the gammaglobulin band and a maked a, globulin band. An immunelectophoretic stu.dydetected an IgM monoclonal .protein with kappa light -chains. Quantitative immunoglobulin assays were IJgG 13.3 gll (normal, 7 to 16), IgA: 2.43 g/l (normal, 0.9 to 3.3) and IgM: 8.29 gll (normal, 0.5 to 2.5). There were no osteolytic bone lesions on roentgenograms. The bone marrow aspirate was normocellular and showed a normal granulocytic series (42%) with 3% myeloblasts. The erythroid series was decreased (G/E ratio of 5.6) with evidence of disordered maturation and dyserythropoiesis. Among Ted cells, the proportion of sideroblasts was 35% -with absence of ringed cells. A plasma-lymphocytic infiltration was apparent (lymphocytes: 40%, plasmacytes: 5%). The most striking finding was the occurrence of numerous unilobular nucleated megakaryocytes. The karyotype performed on bone marrow cells showed deletion of the long arm of chromosome
Kffylipe frXom a 48-h bone marrow culture showing de,is, of the loiW arm of chromosome no 5 without translocation of the dO1etWdseAnL This anomaly concerned about 20% of mitoses
Figure I_.
No 5[del(5Xa13;q33)] (Figure 1). No karryotypically abnormal lymphocytes were found in the peripheral blood. Serum a, antitrypsin level was 36 mg/dl (normal values: 140 to 340) and protease inhibitor typing showed the homozygous ZZ phenotype. Family history was negative- for liver and "pulmonary diseases. The patient had no significant history of pulmonary disease and no emphysema on thoracic CT scan. A liver biopsy was not performed.
Discsion 'he 5 q syndrome is a distinct myelodysplastic syndrome (MWD) with macrocytic anaemia, low to normal leukocyte count, normal or elevated platelet count, nonlobulated s, and a rather mild clinical course with only a- sll chanc of evolving into an acute nonlymphatic lo-lkIikdi- it occurs more often in women. The 5 q- anomaly occM-s preominantly in myeloproliferative disorders. Besidds aIew observations in solid tumo6us, this anomaly -has also been found in lymphoproliferative conditions2. On the ether hand, dysglobuhlinaemia associated with MDS with B q. anomaly is rarely described, except 5 q- syndrome induced by chemotherapy for the dysglobulinaemia3. Only five cases have been reported; one case of multiple myeloma3 and four cases of MGUS1"4. The absence of the deleted chromosome in the lymphocytes of the peripheral blood indicates that the anomaly is an acquired one, occurring originally in a bone marrow stem cell. The chromosomally abnormal stem cell is able to follow erthroid, myeloid, megakaryocytic and possibly B lymphocytic dilTrentiation. Thus, the acquisition of a 5 q- clone for myeloid and lymphocytic pathways could lead to simultaneous development of MDS and MGUS. We cannot rule out the possibility that benzene may have induced 5 q- anomaly. What is more, the association between a, AT deficiency - genetically determined as regards the
0141-0768/91/ 070438-09/.0/ o 1991 The Royal Society of Medicine
node only. A small bowel enema showed thickened terminal ileum folds which was confirmed on CT-scan. A duodenal biopsy was negative for alpha-heavy chain positive, immunoproliferative small intestinal disorder (IPSID) or lymphoma. Colonoscopy was normal, and colonic and terminal ileum biopsies showed no evidence of tuberculosis or lymphoma. Screening tests for collagen vascular disease were negative. T-lymphocyte function was slightly impaired in keeping with a chronic infectious disease, and the HIV screens were negative. In view of the negative histology the patient was discharged to be closely followed-up as an outpatient. The patient was readmitted in July 1989 desperately ill with diarrhoea, a high swinging fever, emaciation (30 kg) and profound lassitude. Blood cultures, full blood count and bone marrow examination were negative. A repeat CT-scan of the chest carried out because of the development of signs in the left base, now showed large mediastinal nodes and left lower lobe consolidation. Bronchoscopy was unhelpful with regard to bacteriology and histology, but mediastinal lymph node biopsy revealed caseating granuloma with acidfast bacilli (AFB). Her general condition improved dramatically on anti-TB treatment within 2 weeks. Twelve weeks later her weight improved, diarrhoea stopped and a small bowel enema and CT-scan were completely normal.
diagnostic approach in such patients in whom the diagnosis remains elusive. The hallmark of diagnosis is the finding of caseating granuloma and/or AFB on histology or culture of the intestinal lesion'. These rigid criteria have been extended to include an unequivocal response to anti-TB treatment in patients with clinical, radiological and/or operative evidence of intestinal TB associated with histologically-proven TB elsewhere2. The diagnosis in our patient was made on the latter basis. The one-year delay in establishing the diagnosis in our case raises the question as to whether laparotomy should not have been undertaken during earlier admissions. Laparotomy remains the definitive investigation in many patients with intestinal TB"12. The question also arises as to whether a therapeutic trial with anti-TB therapy is warranted in some patients with suspected intestinal TB in whom the diagnosis of TB cannot be readily established2. This approach may be of both diagnostic and therapeutic value, and is practised in most endemic areas.
Discussion The case highlights several problems relating to the diagnosis of suspected intestinal TB and, indeed, the
(Accepted 18 June 1990. Correspondence to Dr Th Lingenfelser, Department of Medicine, University of Tuebingen, Division of Gastroenterology, 7400 Tuebingen, Germany)
437
References 1 Marks IN. Abdominal tuberculosis. In: Baillieres clinical and tropical medicine & communicable diseases. Vol 3/2. London: Bailliere Tindall, 1988:329-48 2 Gilinsky NH, Marks IN, Kottler RE, et al Abdominal tuberculosis: a 10-year review. S Afr Med J 1983;64:849-57
Massive lower gastrointestinal bleeding in association with the brown bowel syndrome
J P Hurley MB1 R Leary MBs C E Connolly FRCPath2 P Keeling FRCSI' Departments of 'Surgery and 2Pathology, University College Hospital, Galway, Ireland Keywords: brown bowel syndrome; vitamin E
The brown bowel syndrome (BBS), so called because of the accumulation of lipofuscin in the intestinal smooth muscle layer, is a rare condition occurring in association with vitamin E deficiency and leads to atrophy of the intestinal smooth muscle. We report a case of BBS in a coeliac presenting with massive lower gastrointestinal bleeding, a complication not previously recognized in this condition, which shows lipofuscin deposition in vascular smooth muscle may have been the predisposing factor.
Case report A 58-year-old man was transferred from a peripheral hospital with a 2-day history of passing large amounts of fresh blood per rectum. There was no associated abdominal pain. He had required seven units of blood in the 24 h prior to transfer. The patient had no past history of gastrointestinal bleeding but was a known coeliac. On admission the patient was pale, pulse 110/min, blood pressure 90/60. Abdominal examination was normal, rectal examination confirmed fresh blood but no mass was felt. His haemoglobin was 8.4 g/dl, a COAG screen, plain film ofthe abdomen, chest X-ray and ECG were normal. The patient was resuscitated with a further three units of blood. Colonoscopy failed to demonstrate a bleeding point, but fresh blood was seen as far as the caecum. Emergency angiography was unavailable, and as the patient continued to bleed he had a total colectomy and ileostomy. He had no further bleeding and made a good postoperative recovery. A histological diagnosis of the brown bowel syndrome was made.
~~~~
VC
...
or
Figure 1. Section of colon showing marked smooth muscle atrophy (H & Ex24)
Discussion The BBS, a term first used to describe this condition in 19631, is characterized by a copper coloured bowel due to the accumulation of lipofuscin in the smooth muscle layer and atrophy and atony of the smooth muscle (Figure 1). The brown bowel syndrome has previously been reported in association with coeliac disease2. It is due to malabsorption and is specifically associated with a deficiency of vitamin E3. Though the precise pathophysiology is unknown it is
0141-0768/91/ 070437-02/$02.00/0 © 1991 The Royal Society of Medicine
438
Journal of the Royal Society of Medicine Volume 84 July 1991
postulated that vitamin E has an important protective role in mitochondria preventing the unsaturated lipids of the mitochondrial membrane being damaged by free radicals formed during oxidative phosphorylation4'5. Our patient was a coeliac of 11 years, a poor complier with his gluten free diet and had frequent bouts of steatorrhoea. His vitamin E level during admission was low, 5.6 ng/l (normal range 9-14 ng/l). Lower gastrointestinal haemorrhage has not been desribed as a complication of the brown bowel syndrome. Lipofuscin deposition in vascular smooth muscle has only been occasionally documented6. In this case histological sections through the mesentery revealed accumulation of lipofuscin in smooth muscle of the wall of the arteries and veins and it can be postulated that it is this defect in vascular smooth muscle that allowed massive haemorrhage to occur and continue. In conclusion, while the brown bowel syndrome is rare it may present with massive lower gastrointestinal bleeding
and therefore one must seek and treat vitamin E deficiency in conditions causing malabsorption in an effort to prevent this condition. References 1 Tosser AH, Hukill PB, Spiro HM. Brown bowel syndrome. Ann Intern Med 1963;22:872-7 2 Stamp GW, Evans DJ. Accumulation of ceroid in smooth muscle indicates severe malabsorption and vitamin E deficiency. J Clin Pathol 1987;40:798-802 3 Foster CS. The brown bowel syndrome: a possible smooth muscle mitochondrial myopathy? Histopatiology 1979;3:1-17 4 Hoster JP, Kimmel KK, Mockler DD. The 'Brown Bowel Syndrome': A case report. Am J Gastro 1982;77:854-55 5 Farrell PM, Bieri JG, Fratartoni JF, Wood RE, Di Sant Agnese PA. The )ccrence and effects of human Vitamin E deficiency. 6 Fox B. Lipofuscinosis of the gastro-intestinal tract in man. J Clin Pathol 196720:806-13 (Accepted 18 June 1990. Correspondence to JPHuriey, Department of Cardiac Surgery, Mater Hospita, Ecckes Street, Dublin 7, Ireland)
5 q- Syndrome and monoclonal gammopathy with a1 antitrypsin deficiency
C Jeandell J P Aymard2 F Penin' R L Hofmann3 M George4 F Bertrand3 M J Gregoire' G Cunyl CHU Nancy, Brabois, 54500, Vandoeuvre Las Nancy, France, 'Service of Internal Medicne B, 2Regional Blood Transfusion and HematoogjCentr, . md 8StC. 3Department of Biochemieti s Keywords: myelodysplastic.syndrome.r, dys; a, antitrypsin
We describe a patient who presented with 5 q-syidrome, monoclonal gammopathy of undetermined s ance (MGUS) and a, antitrypin (a, ATl) deficienc n di the possible relations between these three abn alites Ti-r knowledge this is the first such case-inthe tedical literatle.
Case report An 86-year-old woman in previous good health was amitted to the hospital due to excsive f . Physical examination was unremarkable. She denied any sfiant alcohol intake and did not smoke but there was a possible to benzene. Routine blood tests disclosed a am (Hb: 9 g/dl, MCV: 113 fl), white -u,ount,:x1OtL2Q% polymorphonuclear cells, 78% 1 2%Ln cytes) and a platelet cou 9(22Ox19.PI B,1,tIte, and red cell folate were ihin t n em c concentration was 2.12-rn *Lfmi ntion tests were normal. Serum protein el showed sediment in the gammaglobulin band and a maked a, globulin band. An immunelectophoretic stu.dydetected an IgM monoclonal .protein with kappa light -chains. Quantitative immunoglobulin assays were IJgG 13.3 gll (normal, 7 to 16), IgA: 2.43 g/l (normal, 0.9 to 3.3) and IgM: 8.29 gll (normal, 0.5 to 2.5). There were no osteolytic bone lesions on roentgenograms. The bone marrow aspirate was normocellular and showed a normal granulocytic series (42%) with 3% myeloblasts. The erythroid series was decreased (G/E ratio of 5.6) with evidence of disordered maturation and dyserythropoiesis. Among Ted cells, the proportion of sideroblasts was 35% -with absence of ringed cells. A plasma-lymphocytic infiltration was apparent (lymphocytes: 40%, plasmacytes: 5%). The most striking finding was the occurrence of numerous unilobular nucleated megakaryocytes. The karyotype performed on bone marrow cells showed deletion of the long arm of chromosome
Kffylipe frXom a 48-h bone marrow culture showing de,is, of the loiW arm of chromosome no 5 without translocation of the dO1etWdseAnL This anomaly concerned about 20% of mitoses
Figure I_.
No 5[del(5Xa13;q33)] (Figure 1). No karryotypically abnormal lymphocytes were found in the peripheral blood. Serum a, antitrypsin level was 36 mg/dl (normal values: 140 to 340) and protease inhibitor typing showed the homozygous ZZ phenotype. Family history was negative- for liver and "pulmonary diseases. The patient had no significant history of pulmonary disease and no emphysema on thoracic CT scan. A liver biopsy was not performed.
Discsion 'he 5 q syndrome is a distinct myelodysplastic syndrome (MWD) with macrocytic anaemia, low to normal leukocyte count, normal or elevated platelet count, nonlobulated s, and a rather mild clinical course with only a- sll chanc of evolving into an acute nonlymphatic lo-lkIikdi- it occurs more often in women. The 5 q- anomaly occM-s preominantly in myeloproliferative disorders. Besidds aIew observations in solid tumo6us, this anomaly -has also been found in lymphoproliferative conditions2. On the ether hand, dysglobuhlinaemia associated with MDS with B q. anomaly is rarely described, except 5 q- syndrome induced by chemotherapy for the dysglobulinaemia3. Only five cases have been reported; one case of multiple myeloma3 and four cases of MGUS1"4. The absence of the deleted chromosome in the lymphocytes of the peripheral blood indicates that the anomaly is an acquired one, occurring originally in a bone marrow stem cell. The chromosomally abnormal stem cell is able to follow erthroid, myeloid, megakaryocytic and possibly B lymphocytic dilTrentiation. Thus, the acquisition of a 5 q- clone for myeloid and lymphocytic pathways could lead to simultaneous development of MDS and MGUS. We cannot rule out the possibility that benzene may have induced 5 q- anomaly. What is more, the association between a, AT deficiency - genetically determined as regards the
0141-0768/91/ 070438-09/.0/ o 1991 The Royal Society of Medicine
