LC Steven, CP Driver
Department of Paediatric Surgery, Royal Aberdeen Children’s Hospital, Foresterhill, Aberdeen
Correspondence to:
Mr CP Driver, Consultant Paediatric Surgeon, Royal Aberdeen Children’s Hospital, Foresterhill, Aberdeen, AB25 2ZG
Email: Chris.Driver@nhs.grampian.scot.nhs.uk
SMJ 2005 50(2): 80-81
Abstract
A five year old girl with Neimann-Pick disease type C subsequently developed Crohn’s Disease. This association has only been presented once previously in the literature. This report discusses the options for managing one chronic disease in the presence of another life limiting condition.
Key words: Neimann-Pick Disease; Crohn’s Disease
Case report
This female child was the second child of healthy, unrelated caucasian parents. She was born at term by uncomplicated vaginal delivery and there were no neonatal complications. Parental concern first arose when the child was three years old and prone to falling and in turning of the left foot. At five years of age she was referred to the community paediatric team after developing difficulties during physical education classes with poor balance, frequent falls and an awkward running style. Her fine motors skills had regressed and she was having problems dressing and feeding herself. She was prone to drooling and had abnormal tongue and conjugate eye movements.
Initial investigations showed a normal chromosomal pattern, electroencephalogram and magnetic resonance imaging of the brain. Four months after presentation Neimann-Pick disease type C was confirmed on bone marrow aspirate with the appearances of foamy storage cells and histiocytes with pale blue vacuolated cytoplasm on Glemsa stain.
At the age of seven years she began passing fresh blood per rectum with frequency of loose stools and severe pain on defaecation. Perianal examination revealed florid skin tags and fissuring but no visible fistulae. Endoscopic biopsies confirmed acute on chronic inflammation with granuloma identified at multiple levels from the transverse colon to rectum. The opinion of the gastrointestinal pathologist was that this was highly suggestive of Crohn’s disease. Biochemical blood tests, full blood count, auto- antibodies and a barium small bowel study were within normal limits.
Initial medical management of her Crohn’s disease included prednisolone, sulphasalazine and metronidazole. Early improvements were short-lived and she became increasingly steroid dependant. Despite increasing steroid dosing, her initial perianal disease progressed with painful fistulae formation and increasing difficulty with perineal cleanliness. After multiple discussions with the parents over a period of several weeks outlining all the available options, she proceeded to formation of an end colostomy with distal mucous fistula. The principle reason for choosing this option was the significant and repeated distress caused by the need for regular perineal cleaning required to minimise perianal excoriation. The parents were increasingly concerned about the impact this was having on quality of life, particularly with the limited life expectancy associated with Neimann-Pick and the difficulty in being able to explain the need for interventions several times a day.
As oral feeding was deteriorating, a percutaneous endoscopic gastrostomy was placed during the same anaesthetic. The procedures were both uncomplicated and she made a satisfactory recovery. Initial results were encouraging and her quality of life improved dramatically. Unfortunately, eight months after surgery cutaneous fistulae developed around the stomas with bleeding and subsequent abscess formation. She was commenced on an elemental diet, metronidazole, azathioprine and salazopyrin which resulted in partial healing of the fistulas but it became increasingly difficult to step down her immunosuppressant therapy. By this stage her neurological dysfunction was progressing steadily. As her Crohn’s disease had become refractory to maximal medical therapy and she was started on the monoclonal antibody infliximab infusions at a dose of 5mg/kg. These were well tolerated and after the second infusion there was a marked clinical improvement.
At the age of 10 years, 21 months after surgery and three months after the first infliximab infusion, she died of a lower respiratory tract infection. The parents and community nursing staff felt that faecal diversion had been of significant benefit to her quality of life, despite the subsequent fistula formation.
Discussion
Neimann-Pick disease covers a heterogeneous group of lipid transport disorders affecting children and young adults. In type C disease children may present with splenomegaly in isolation,1 neonatal cholestatic hepatitis 2 or invariably progressive neurological impairment.
Neimann- Pick disease type C is inherited in an autosomal recessive manner with the majority of patients having mutations of the NPC 1 gene, mapped to chromosome 18. Lipid transport is deranged due to an abnormality of intracellular lysosomal acid-sphingomyelinase but actual sphingomyelinase levels are normal.
The association between Neimann-Pick disease type C and Crohn’s disease has only been reported once previously in the literature.3 This male child presented at age 12 with abnormal mental development, perianal abscesses and skin tags. Papules and nodules were present over the lower anterior abdominal wall and confirmed to be Crohn’s disease on biopsy.
The decision to perform a colostomy for our patient was considered due to her painful perianal disease and difficulties with hygiene and the deteriorating skin condition in this area. Whilst there are no set guidelines for palliative surgery in children, an improvement in quality of life primarily for the child and as a secondary and subservient consideration for family must always be the priority. Radical excisional surgery was considered inappropriate with the limited life expectancy of this child. It must be remembered however that with palliative surgery for Crohn’s disease active disease segments remain. Recognition of cutaneous complications such as fistula and abscess formation should therefore be expedient and aggressive immunosuppressive therapy instituted as appropriate.
If fistula formation fails to respond to conventional maximal medical therapy the subsequent treatment may consist of Infliximab, a monoclonal antibody which targets the pro- inflammatory cytokine tumour necrosis factor. The use of infliximab infusions in children with Crohn’s disease has been reported to permit a reduction in steroid dose 4 and allowed a significant reduction in the Pediatric Crohn’s Disease Activity Index in the short term with better results in those with early disease,5 although children with fistulating disease were not included in this study.
Conclusion
This case highlights the rare association between Crohn’s disease and Niemann-Pick disease type C and highlights the need for combining maximal medical treatment with a surgical approach aimed at maximizing quality of life and minimizing surgical morbidity in a child with a chronic disease combined with an inevitably progressive terminal illness.
REFERENCES
1 Imrie J, Wraith JE. Isolated splenomegaly as the presenting feature of Neimann- Pick disease type C. Arch Dis Child 2001;84(5):427-429
2 Kelly DA, Portmann B, Mowat AP, Sherlock S, Lake BD. Neimann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease. J Pediatr 1993;123(2):242-247
3 Jolliffe DS, Sarkany I. Neimann-Pick type III and Crohn’s disease. J R Soc Medi 1983;76:307-308
4 Stephens MC, Shepanski MA, Mamula P, Markowitz JE, Brown KA, Baldassano RN. Safety and steroid- sparing experience using infliximab for Crohn’s disease at a pediatric inflammatory bowel disease center. Am J Gastroenterol 2003;98(1):104-111
5 Hyams JS, Markowitz J, Wyllie R. Use of infliximab in the treatment of Crohn’s disease in children and adolescents. J Pediatr 2000;137(2):192-196