manu r. sood - home | the ehlers danlos society sood.pdf“idiopathic” myositis and neuropathies...
TRANSCRIPT
Manu R. Sood
Children’s Hospital of Wisconsin
& Medical College of Wisconsin
Milwaukee, WI
Joint hypermobility syndrome (JHS) was first described by Kirk and colleagues in 1967
1980s – phenotypic overlap of JHS with heritable disorders of connective tissue recognized (EDS type III)
Gynecological problems
Chronic pain and dysautonomia
Last decade - association with GI disorders
Review the association of pediatric functional GI and motility disorders with joint hypermobility syndrome (JHS)
Explore possible mechanisms for GI symptoms in JHS
Discuss therapeutic approaches to functional GI and motility disorders
Spontaneous bowel perforation
GI haemorrhage
Hiatus hernia
Intestinal diverticula
Rectal prolapse
0%
10%
20%
30%
40%
50%
60%
70%
80%
IBS FunctionalConstipation
GERD
N=135
Prevalence of JHS 33% ◦ Heartburn
◦ Water brash
◦ Postprandial fullness
Upper and lower GI symptoms increased with increasing severity of JHS phenotype.
•Structural support
•Nourishment to the mucosa
•Rich in immune cells
•Contains cells which help
maintain homeostasis
1950 1960 1970 1980 1990 2000 2013
Abnormal Motor Function
Visceral Hyperalgesia
Brain Gut Interaction
Genetics, Microbial-mucosal, Neuro-immune
Purely Psychosocial Disorders
Pathophysiology of Pain Related
Functional GI Disorders
Fifteen year old with 2 year history of abdominal pain and nausea
Pain worse after eating
Intermittent vomiting
Episodes of dizziness but no fainting
No heartburn or feeling of food getting stuck in the chest
Intrinsic System: ◦ Myenteric plexus
◦ Submucosal plexus
Extrinsic Neural Interactions: ◦ Parasympathetic
Dorsal motor nucleus of vagus
Sacral spinal cord
◦ Sympathetic reflexes
Celiac, superior & inferior mesenteric ganglia
71% pediatric gastroenterologists (n=362) used Rome criteria
Only 45% of the surveyed pediatric gastroenterologists found the Rome criteria useful
The reported prevalence of POTS in joint hypermobility syndrome is 78%
Storage
Breakdown of ingested food
Controlled emptying of food into the small bowel
Volume
Pre
ssure
Satiety
Discomfort
Volume
Pre
ssure
Satiety
Discomfort
Gastric pain perception in children with RAP lower than controls p<0.005 and IBS patients (p<0.01)
Volume of water consumed ◦ Chronic abdominal pain 395 ± 198 ml
◦ Controls 528 ± 257 ml. (p < 0.01)
◦Using a cut off of 275 ml the sensitivity was 33% and specificity 100%
28 patients with dyspepsia and 15 obese subjects
As a group, children with
functional dyspepsia ingested
significantly smaller meal
volume and had slower gastric
emptying time.
Titurbation of Gastric Contents
◦ Solids mechanically disrupted
◦ Empty sizes of only 1-2 mm
◦ Larger non-digestable contents empty during fasting MMC
Gamma
Camera 99mTc in 300 kcal
egg meal
Four hour studies are more reliable
Always use a meal which has been cooked after adding the radioisotope
Also pay attention to the first 60 min (rapid emptying)
Stomach
Chitkara DK, Camilleri MC et al. Journal of Pediatrics 2005
15 adolescent patients
15 young adult controls
Life style changes ◦ Small frequent meals
◦ Low fiber and low fat diet
Prokinetic ?
Cyproheptadine
Visceral hypersensitivity ◦ TCA
◦ Neurontin
POTS and autonomic dysfunction: ◦ Fluid intake
◦ Salt supplements
◦ Fludrocortisone
Target the most bothersome symptom
Article Intervention Outcome
Robins et al, 2005
n=69; 6-16 y
CBT vs. SMC
FU: 1 y
CBT Improvement in pain
Benefit maintained at 1 y FU
Duarte et al, 2006
n=32; 5-13 y
CBT vs. SMC
4 monthly sessions
FU: 4 m
CBT: Improvement in pain scores (86.6% vs.
33.3%)
Hicks et al, 2006
n=47; 9-16 y
CBT: vs. SMC
FU: 3 m
CBT: Improvement in pain scores (72% vs.
14%)
Weydert et al,
2006
N=22; 5-18y
Guided imagery vs
breathing exercises
Four sessions , FU: 3m
Guided Imagery: Greater decrease in pain
and missed activities ( 82% vs. 45%) at 2 m
van Tilburg et al,
2009
n=34; 6-15y
Home based guided
imagery vs. SMC
2 months treatment and
FU: 6m
Guided imagery group: more treatment
responders (63.1% vs. 26.7%).
Levy et al, 2010
n=200; 7-17 y
CBT vs. Educational support
3 session each group
FU: 6m post treatment
CBT: Improvement in pain and GI symptoms and less parental solicitous responses
Almost 80% of children with
pain associated FGIDs improve
with CBT
Digestion and
Absorption of Nutrients
Cleansing when asleep
• Normal
• Extrinsic (autonomic) neuropathy
• Intrinsic (enteric) neuropathy
• Antral postprandial hypomotility
• Intestinal myopathy
• Rumination
• Mechanical obstruction
• Nonspecific conditions
Water perfused AD manometry High resolution AD manometry
UK (n=35)
43%
47%
10% 56%
38%
6%
S. Heneyke, et al. Arch Dis Child 1999;81:21-27
Mousa H, et al. Dig Dis Sci 2002;47:2298
USA (n=85)
“Idiopathic” myositis and neuropathies
Eosinophilic enterocolitis and neuropathy
Systemic lupus erythematosus/ Crohn’s
Autoimmune (ANNA-1)
Mitochondrial diseases (MNGIE)
Deficient Interstitial Cells of Cajal
New drug effects- Perinatal Zidovudine
Viral infections (CMV, EBV, HSV, rotavirus)
Yamazaki-Nakashimada MA, et al. JPGN 2009;48:482
Smith VV, et al. Gastroenterol 1998;114:421 Ruuska TH, et al. Gastroenterol2002;122:1133 Smith VV, Milla PJ. Histopathology 1997;31:112
Eosinophilic myenteric ganglionitis
Mega-mitochondria in ganglion cells
Autoimmune enteric leiomyositis
Malrotation: almost 25% to 28% of CIP patients
After Ladd’s procedure: persistent feeding
intolerance, vomiting & abdominal distension
investigate for CIP
Megacystis and hydronephrosis are present in
41% to 44% of patients with CIP
Developmental delay 40%
Autonomic dysfunction 22%
S. Heneyke, et al. Arch Dis Child 1999;81:21-27
Mousa H, et al Dig Dis Sci 2002;47:2298
200 patients and 100 controls
JHS - 32% patients and 14% controls
JHS group ◦ Constipation score, abdominal pain, use of
laxatives and need for manual assistance were significantly higher
JHS group more likely to have incomplete rectal clearance and anorectal anatomical problems
Dr. Nichopoulos own words “I realized during the autopsy how much more severe Elvis’s discomfort must have been than I had realized”.
Thick muscle
Better propulsive force
Less stool load
Thin muscle
Poor propulsive force
More stool load
Stool expulsion
Slow transit
Gutierrez, et al J Pediatr Gastroenterol Nutr;2002
Cook BJ, et al. J Pediatr Surg;2005
Benninga MA, et al. Arch Dis Child;2004
Chitkara DK, et al. Am J Gastroenterol 2004
n=69 n=22 n=19
Children with functional constipation
have increased rectal compliance
compared to children who had
recovered from functional constipation W.P. Voskuijl WP, et al. J Pediatr 2006
Baseline (n=101) rectal compliance ◦ Normal in 36% ◦ Moderately increased in 40% ◦ Severely increased in 24%
After 1 year, treatment success was similar between groups ◦ 42% normal ◦ 41% moderately increased ◦ 40% with severely increased compliance
Van den Berg MM, et al. Gastroenterology 2009
Ascending
Colon
Trans. Colon
Trans. Colon
Descending
Colon
Sig. colon
Rectum
Anal canal
HAPC
Rectal propagating
contractions
Anal canal
High Resolution Colon Manometry
Almost 70% of patients report successful outcome
Absence of HAPCs in the entire colon associated with poor outcome
Almost 40% able to discontinue antegrade enemas within 2 yrs.
Youssef N, et al. J Pediatr Gastroenterol Nutr. 2002
van den Berg MM, et al. J Pediatr Surg. 2006
13 females ◦ Median age at onset of symptoms
15.2 yrs. (range 10-18yrs.) ◦ Median duration of laxative therapy
7 yrs. (range, 1–17 yrs.)
Slow colon transit in 7 patients Follow up after sacral
neuromodulation ◦ 6 months (n=13) ◦ 1 year (n=5)
Complications: ◦ Pain at the site of implant ◦ Lead problem requiring revision
Functional GI and motility problems are common in patients with JHS and EDS
Altered biomechanics and sensory bowel abnormalities contribute to symptom generation
Good diagnostic test are not available
Referral to a specialist center with a multidisciplinary team approach should be considered
Gisela Chelimsky, MD
Thomas Chelimsky, MD
Julie Banda, PNP
B U K Li, MD
Adrian Miranda, MD
Katja Kovacic, MD