ClinicalRadiology(1991) 44, 62-63
Case Report: Small Bowel Histiocytosis-X B. J. P A T E L , A. J. C H I P P I N D A L E
a n d S. C. G U P T A
Department of Diagnostic Radiology, The Royal Manchester Children's Hospital, Pendlebury, Manchester A case of histiocytosis-X with gastrointestinal involvement is described in a 4-month-old child presenting with bloody diarrhoea and obstructive symptoms. Diagnosis was made following iaparotomy. The child subsequently developed classical muitisystem manifestations of the disease. Patel, B.J., C h i p p i n d a l e , A . J . & G u p t a , S.C. (1991). Clinical Radiology 44, 62 63. Case Report: Small Bowel Histiocytosis-X
I n v o l v e m e n t o f the g a s t r o i n t e s t i n a l t r a c t in g e n e r a l i z e d h i s t i o c y t o s i s - X is p r o b a b l y n o t u n c o m m o n , a l t h o u g h r e p o r t s in t h e l i t e r a t u r e a r e e x c e e d i n g l y rare ( D e p r e t t e r e et al., 1983). R a d i o l o g i c a l f i n d i n g s in g a s t r o i n t e s t i n a l i n v o l v e m e n t in this c o n d i t i o n h a v e o n l y b e e n d e s c r i b e d o n c e p r e v i o u s l y ( F e i n b e r g a n d Lester, 1958). W e r e p o r t a child w h o p r e s e n t e d at the age o f 4 m o n t h s w i t h a h i s t o r y o f b l o o d y d i a r r h o e a since birth. She w a s f o u n d to h a v e intestinal i n v o l v e m e n t w i t h h i s t i o c y t o s i s - X , a n d subseq u e n t l y d e v e l o p e d classical c u t a n e o u s , p u l m o n a r y a n d skeletal m a n i f e s t a t i o n s o f the disease. CASE REPORT A 4-month-old female child presented with a history of bloody, foul smelling, mucous diarrhoea since birth. Two weeks prior to her admission she developed intermittent effortless bile-stained vomiting. She had lost 1 kg in weight in 2 weeks and had developed oedema of her arms and legs. A red scaly rash had been noticed on her back, neck and trunk from the age of about 6 weeks. On examination there was a scaly papular rash having the above distribution. There was no lymphadenopathy. Her abdomen was soft and non-distended and there was hepatomegaly. Investigations on admission revealed a haemoglobin concentration of 9.9 g/dl and a low serum albumin of 12 g/1. The chest radiograph showed widespread reticular shadowing throughout both lung fields. The upper gastrointestinal tract was examined using water soluble non-ionic contrast medium. This showed extensive small bowel narrowing and featureless mucosa extending from the third part of the duodenum through to the jejunum (Fig. 1). Rectal and duodenal biopsies were normal and stool cultures grew no pathogens. A barium enema was normal. Subsequently, a small bowel enema was performed which confirmed the abnormalities demonstrated previously involving the distal duodenum and the jejunum. The patient underwent a diagnostic laparotomy when resected specimens of a small segment of jejunum and regional lymph nodes showed infiltration by mononuclear and multinucleated histiocytes and eosinophils. Trephine bone biopsy also showed histiocytic collections with occasional mitotic figures indicating marrow involvement. The patient was commenced on a trial of chemotherapy. She responded slowly with gradual reduction in the nasogastric aspirates. A further small bowel study showed some improvement in the appearances of the small bowel (Fig. 2). Chemotherapy was continued and she was commenced on oral feeding which was tolerated well. However, she presented after 6 months with progressive unilateral (left-sided) proptosis. Skull radiographs showed an irregular lytic lesion in the roof of the left orbit involving the lesser and greater wings of the sphenoid (Fig. 3). High resolution CT sections through the orbits showed a large mass of slightly increased attenuation involving intra- and extraconal tissues with destruction of the bony margins of the orbital roof (Fig. 4). Despite some initial improvement with further chemotherapy the proptosis progressed and required local radiotherapy. She ultimately responded well to treatment achieving full remission. Her disease remains quiescent 2 years after cessation of chemotherapy. She has slight facial asymmetry secondary to the radiotherapy, but no evidence of hypothalamic or pituitary disturbance. Correspondence to: Dr B. J. Patel, Radiology Department, Singleton Hospital, Sketty, Swansea SA2 8QA.
Fig. 1 Water-soluble non-ionic upper GI study showing loss of mucosal pattern of the duodenal loop and the proximal jejunum. The walls show thickening with separation of bowel loops.
DISCUSSION H i s t i o c y t o s i s - X is a s p e c t r u m o f r e l a t e d d i s o r d e r s c h a r a c t e r i z e d by p r o l i f e r a t i o n o f n o n - n e o p l a s t i c histiocytes b e a r i n g L a n g e r h a n s ' g r a n u l e s a n d i n t e r d i g i t a t i n g c y t o p l a s m i c e x t e n t i o n s . C l i n i c a l m a n i f e s t a t i o n s are Lett e r e r Siwe disease, H a n d - S c h u e l l e r - C h r i s t i a n disease a n d e o s i n o p h i l i c g r a n u l o m a . R a d i o l o g i c a l f i n d i n g s in gastrointestinal involvement have only been described o n c e p r e v i o u s l y ( F e i n b e r g a n d Lester, 1958). T h e s e a u t h o r s r e p o r t e d a 2 - w e e k - o l d child w h o p r e s e n t e d w i t h v o m i t i n g a n d o b s t r u c t i v e s y m p t o m s . T h e child subseq u e n t l y d e v e l o p e d a skin r a s h a n d l y m p h a d e n o p a t h y . R a d i o l o g i c a l e x a m i n a t i o n o f the u p p e r a l i m e n t a r y t r a c t showed marked coarsening of the mucosal pattern with a c o b b l e s t o n e a p p e a r a n c e e x t e n d i n g f r o m the d u o d e n u m to the ileum. E x t e n s i v e i n f i l t r a t i o h w i t h h i s t i o c y t o s i s - X was f o u n d at a u t o p s y . T h e y also e x a m i n e d the g a s t r o i n t e s t i nal t r a c t in a p a t i e n t w i t h s u b a c u t e r e t i c u l o e n d o t h e l i o s i s without gastrointestinal symptoms and found generalized absence of a normal mucosal pattern, segmentation of intestinal loops and barium flocculation. Subsequent r e t r o s p e c t i v e r e v i e w o f 22 p r o v e n cases o f L e t t e r e r - S i w e disease a n d H a n d - S c h u e l l e r - C h r i s t i a n disease r e v e a l e d 10 p a t i e n t s w h o h a d h i s t o l o g i c a l e v i d e n c e o f intestinal
SMALL BOWEL HISTIOCYTOSIS-X
Fig. 2 - Follow-up small bowel enema. The mucosa is now recognizable, although the mucosal pattern is coarse and there is some separation of loops.
Fig. 3 PA view of the orbit, showing irregular lytic lesion of the roof of the left orbit involving the lesser and greater wings of the sphenoid (arrow).
63
and/or mesenteric involvement at autopsy. Seven of these had Letterer Siwe disease and six had gastrointestinal symptoms. Keeling and Harris (1973) described a further case of histiocytosis-X with malabsorption which was associated with histiocytic infiltration of the small intestine; they reviewed 11 other fatal cases where histiological material from the intestine was available. The ileum was most commonly affected followed by the duodenum and the jejunum. The lamina propria was most often involved, either alone or accompanied by infiltration of the other layers. Seven of these patients had developed diarrhoea and five had histological involvement of the small intestine. Tamura et al. (1980) described a child with Letterer-Siwe disease associated with protein-losing enteropathy. The mechanism of malabsorption is uncertain. Necropsy examination of the liver and the pancreas suggests that these are unlikely to be responsible. Villous architecture is normal in the majority. Mesenteric lymph node involvement may cause lymphatic obstruction and interfere with absorption of lipids. Bacterial infection in debilitated children may also cause diarrhoea. The frequent association of diarrhoea and mucosal infiltration by histiocytes suggests such cellular infiltration may itself impair intestinal function. Gastrointestinal bleeding is also known to be associated with intestinal infiltration by histiocytes in histiocytosis-X. Pops and Campbell (1968) reported an adult with gastrointestinal bleeding caused by histiocytic infiltration of the ileum with subsequent ulceration. Hyams et al. (1985) described a 5-month-old infant with a prolonged history of lower gastrointestinal bleeding which was found to be due to diffuse histiocytic involvement of the colon with ulceration. At the benign end of the spectrum eosinophilic granuloma is also known to involve the gastrointestinal tract. Toole and Moschopoulos (1959) reported two cases involving the duodenum and reviewed 47 cases available in the literature. The stomach was the commonest site being involved in 70% of the cases. These patients usually present with obstructive symptoms. Treatment is usually by surgical resection and the prognosis is good with no reported cases of recurrence in the literature. Acknowledgements.We thank Dr P. Morris-Jones for permission to publish this case.
REFERENCES
Fig. 4 - CT of the orbit. There is a large soft tissue mass in the roof of the left orbit displacing the globe anteriorly. The mass involves intra- and extraconal soft tissues and there is destruction of the bony margins of the orbital roof.
Deprenere, A, Aelvoet, G, Van Acker, KJ & Dockx, P (1983). Intractable diarrhoea in Histiocytosis-X. Helvetica Paediatrica Aeta, 38, 291 294. Feinberg, SB & Lester, RG (1958). Roentgen examination of the gastrointestinal tract as an aid in the diagnosis of acute and subacute reticuloendotheliosis. Radiology, 71,525-533. Hyams, JS, Haswell, JE, Gerber, MA & Berman, MM (1985). Colonic ulceration in Histiocytosis-X. Journal of Paediatrie Gastroenterology and Nutrition, 4, 286-290. Keeling, JW & Harris, JT (1973). Intestinal malabsorption in infants with Histiocytosis-X. Archives of Diseases in Childhood, 48, 350- 354. Pops, M A & Campbell, T (1968). Gastrointestinal bleeding from ileal ulceration in Histiocytosis-X. Archives of Internal Medicine, 122, 271 272. Tamura, T, Umetsu, M, Motoyo, H & Yokoyama, S (1980). Congenital Lenerer-Siwe disease associated with protein losing enteropathy. European Journal of Paediatries, 135, 77-80. Toole, HJ & Moschopoulos, AN (1959). Eosinophilic granuloma of the gastrointestinal travt. British Journal of Surgery, 46, 445 448.
Case Report: Small Bowel Histiocytosis-X B. J. P A T E L , A. J. C H I P P I N D A L E
a n d S. C. G U P T A
Department of Diagnostic Radiology, The Royal Manchester Children's Hospital, Pendlebury, Manchester A case of histiocytosis-X with gastrointestinal involvement is described in a 4-month-old child presenting with bloody diarrhoea and obstructive symptoms. Diagnosis was made following iaparotomy. The child subsequently developed classical muitisystem manifestations of the disease. Patel, B.J., C h i p p i n d a l e , A . J . & G u p t a , S.C. (1991). Clinical Radiology 44, 62 63. Case Report: Small Bowel Histiocytosis-X
I n v o l v e m e n t o f the g a s t r o i n t e s t i n a l t r a c t in g e n e r a l i z e d h i s t i o c y t o s i s - X is p r o b a b l y n o t u n c o m m o n , a l t h o u g h r e p o r t s in t h e l i t e r a t u r e a r e e x c e e d i n g l y rare ( D e p r e t t e r e et al., 1983). R a d i o l o g i c a l f i n d i n g s in g a s t r o i n t e s t i n a l i n v o l v e m e n t in this c o n d i t i o n h a v e o n l y b e e n d e s c r i b e d o n c e p r e v i o u s l y ( F e i n b e r g a n d Lester, 1958). W e r e p o r t a child w h o p r e s e n t e d at the age o f 4 m o n t h s w i t h a h i s t o r y o f b l o o d y d i a r r h o e a since birth. She w a s f o u n d to h a v e intestinal i n v o l v e m e n t w i t h h i s t i o c y t o s i s - X , a n d subseq u e n t l y d e v e l o p e d classical c u t a n e o u s , p u l m o n a r y a n d skeletal m a n i f e s t a t i o n s o f the disease. CASE REPORT A 4-month-old female child presented with a history of bloody, foul smelling, mucous diarrhoea since birth. Two weeks prior to her admission she developed intermittent effortless bile-stained vomiting. She had lost 1 kg in weight in 2 weeks and had developed oedema of her arms and legs. A red scaly rash had been noticed on her back, neck and trunk from the age of about 6 weeks. On examination there was a scaly papular rash having the above distribution. There was no lymphadenopathy. Her abdomen was soft and non-distended and there was hepatomegaly. Investigations on admission revealed a haemoglobin concentration of 9.9 g/dl and a low serum albumin of 12 g/1. The chest radiograph showed widespread reticular shadowing throughout both lung fields. The upper gastrointestinal tract was examined using water soluble non-ionic contrast medium. This showed extensive small bowel narrowing and featureless mucosa extending from the third part of the duodenum through to the jejunum (Fig. 1). Rectal and duodenal biopsies were normal and stool cultures grew no pathogens. A barium enema was normal. Subsequently, a small bowel enema was performed which confirmed the abnormalities demonstrated previously involving the distal duodenum and the jejunum. The patient underwent a diagnostic laparotomy when resected specimens of a small segment of jejunum and regional lymph nodes showed infiltration by mononuclear and multinucleated histiocytes and eosinophils. Trephine bone biopsy also showed histiocytic collections with occasional mitotic figures indicating marrow involvement. The patient was commenced on a trial of chemotherapy. She responded slowly with gradual reduction in the nasogastric aspirates. A further small bowel study showed some improvement in the appearances of the small bowel (Fig. 2). Chemotherapy was continued and she was commenced on oral feeding which was tolerated well. However, she presented after 6 months with progressive unilateral (left-sided) proptosis. Skull radiographs showed an irregular lytic lesion in the roof of the left orbit involving the lesser and greater wings of the sphenoid (Fig. 3). High resolution CT sections through the orbits showed a large mass of slightly increased attenuation involving intra- and extraconal tissues with destruction of the bony margins of the orbital roof (Fig. 4). Despite some initial improvement with further chemotherapy the proptosis progressed and required local radiotherapy. She ultimately responded well to treatment achieving full remission. Her disease remains quiescent 2 years after cessation of chemotherapy. She has slight facial asymmetry secondary to the radiotherapy, but no evidence of hypothalamic or pituitary disturbance. Correspondence to: Dr B. J. Patel, Radiology Department, Singleton Hospital, Sketty, Swansea SA2 8QA.
Fig. 1 Water-soluble non-ionic upper GI study showing loss of mucosal pattern of the duodenal loop and the proximal jejunum. The walls show thickening with separation of bowel loops.
DISCUSSION H i s t i o c y t o s i s - X is a s p e c t r u m o f r e l a t e d d i s o r d e r s c h a r a c t e r i z e d by p r o l i f e r a t i o n o f n o n - n e o p l a s t i c histiocytes b e a r i n g L a n g e r h a n s ' g r a n u l e s a n d i n t e r d i g i t a t i n g c y t o p l a s m i c e x t e n t i o n s . C l i n i c a l m a n i f e s t a t i o n s are Lett e r e r Siwe disease, H a n d - S c h u e l l e r - C h r i s t i a n disease a n d e o s i n o p h i l i c g r a n u l o m a . R a d i o l o g i c a l f i n d i n g s in gastrointestinal involvement have only been described o n c e p r e v i o u s l y ( F e i n b e r g a n d Lester, 1958). T h e s e a u t h o r s r e p o r t e d a 2 - w e e k - o l d child w h o p r e s e n t e d w i t h v o m i t i n g a n d o b s t r u c t i v e s y m p t o m s . T h e child subseq u e n t l y d e v e l o p e d a skin r a s h a n d l y m p h a d e n o p a t h y . R a d i o l o g i c a l e x a m i n a t i o n o f the u p p e r a l i m e n t a r y t r a c t showed marked coarsening of the mucosal pattern with a c o b b l e s t o n e a p p e a r a n c e e x t e n d i n g f r o m the d u o d e n u m to the ileum. E x t e n s i v e i n f i l t r a t i o h w i t h h i s t i o c y t o s i s - X was f o u n d at a u t o p s y . T h e y also e x a m i n e d the g a s t r o i n t e s t i nal t r a c t in a p a t i e n t w i t h s u b a c u t e r e t i c u l o e n d o t h e l i o s i s without gastrointestinal symptoms and found generalized absence of a normal mucosal pattern, segmentation of intestinal loops and barium flocculation. Subsequent r e t r o s p e c t i v e r e v i e w o f 22 p r o v e n cases o f L e t t e r e r - S i w e disease a n d H a n d - S c h u e l l e r - C h r i s t i a n disease r e v e a l e d 10 p a t i e n t s w h o h a d h i s t o l o g i c a l e v i d e n c e o f intestinal
SMALL BOWEL HISTIOCYTOSIS-X
Fig. 2 - Follow-up small bowel enema. The mucosa is now recognizable, although the mucosal pattern is coarse and there is some separation of loops.
Fig. 3 PA view of the orbit, showing irregular lytic lesion of the roof of the left orbit involving the lesser and greater wings of the sphenoid (arrow).
63
and/or mesenteric involvement at autopsy. Seven of these had Letterer Siwe disease and six had gastrointestinal symptoms. Keeling and Harris (1973) described a further case of histiocytosis-X with malabsorption which was associated with histiocytic infiltration of the small intestine; they reviewed 11 other fatal cases where histiological material from the intestine was available. The ileum was most commonly affected followed by the duodenum and the jejunum. The lamina propria was most often involved, either alone or accompanied by infiltration of the other layers. Seven of these patients had developed diarrhoea and five had histological involvement of the small intestine. Tamura et al. (1980) described a child with Letterer-Siwe disease associated with protein-losing enteropathy. The mechanism of malabsorption is uncertain. Necropsy examination of the liver and the pancreas suggests that these are unlikely to be responsible. Villous architecture is normal in the majority. Mesenteric lymph node involvement may cause lymphatic obstruction and interfere with absorption of lipids. Bacterial infection in debilitated children may also cause diarrhoea. The frequent association of diarrhoea and mucosal infiltration by histiocytes suggests such cellular infiltration may itself impair intestinal function. Gastrointestinal bleeding is also known to be associated with intestinal infiltration by histiocytes in histiocytosis-X. Pops and Campbell (1968) reported an adult with gastrointestinal bleeding caused by histiocytic infiltration of the ileum with subsequent ulceration. Hyams et al. (1985) described a 5-month-old infant with a prolonged history of lower gastrointestinal bleeding which was found to be due to diffuse histiocytic involvement of the colon with ulceration. At the benign end of the spectrum eosinophilic granuloma is also known to involve the gastrointestinal tract. Toole and Moschopoulos (1959) reported two cases involving the duodenum and reviewed 47 cases available in the literature. The stomach was the commonest site being involved in 70% of the cases. These patients usually present with obstructive symptoms. Treatment is usually by surgical resection and the prognosis is good with no reported cases of recurrence in the literature. Acknowledgements.We thank Dr P. Morris-Jones for permission to publish this case.
REFERENCES
Fig. 4 - CT of the orbit. There is a large soft tissue mass in the roof of the left orbit displacing the globe anteriorly. The mass involves intra- and extraconal soft tissues and there is destruction of the bony margins of the orbital roof.
Deprenere, A, Aelvoet, G, Van Acker, KJ & Dockx, P (1983). Intractable diarrhoea in Histiocytosis-X. Helvetica Paediatrica Aeta, 38, 291 294. Feinberg, SB & Lester, RG (1958). Roentgen examination of the gastrointestinal tract as an aid in the diagnosis of acute and subacute reticuloendotheliosis. Radiology, 71,525-533. Hyams, JS, Haswell, JE, Gerber, MA & Berman, MM (1985). Colonic ulceration in Histiocytosis-X. Journal of Paediatrie Gastroenterology and Nutrition, 4, 286-290. Keeling, JW & Harris, JT (1973). Intestinal malabsorption in infants with Histiocytosis-X. Archives of Diseases in Childhood, 48, 350- 354. Pops, M A & Campbell, T (1968). Gastrointestinal bleeding from ileal ulceration in Histiocytosis-X. Archives of Internal Medicine, 122, 271 272. Tamura, T, Umetsu, M, Motoyo, H & Yokoyama, S (1980). Congenital Lenerer-Siwe disease associated with protein losing enteropathy. European Journal of Paediatries, 135, 77-80. Toole, HJ & Moschopoulos, AN (1959). Eosinophilic granuloma of the gastrointestinal travt. British Journal of Surgery, 46, 445 448.
