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GASTROINTESTINAL & NEUROMUSCULAR

Gastrointestinal System: Inflammatory Disorders ¹

Ulcerative Colitis

• General
  • Inflammation of variable regions of bowel
  • Clinical features: Bloody diarrhea
  • Course: Chronic
• Neuromuscular syndromes
  • Epidemiology
    • Frequency: Rare
    • Onset age: Mean 6th decade
    • Males > Females
    • May be associated with malabsorption
  • No typical associated syndromes
  • Occasional associations
    • CIDP
    • Axonal neuropathy
      • Pan-sensory: Older patients
      • Small fiber
    • Inflammatory myopathy
  • Metabolic disorders: Electrolyte disorders (K⁺, Mg⁺, Ca⁺⁺) cause weakness or tetany
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Crohn's Disease

• General
  • Pathology: Inflammation throughout GI tract
  • Chronic course
  • Genetic susceptibility: NOD2/CARD15
• Clinical features
  • Abdominal pain
  • Diarrhea (Non-bloody)
  • Intestinal obstruction
• Neuromuscular associations
  • General
    • Onset age: 6th decade
    • Males > Females
  • Peripheral neuropathy
    • B₁₂ malabsorption: Common
    • Sensory-Motor axonal neuropathy
      • Severity related to disease activity
      • Frequency: Occasional
      • Onset: Subacute
      • May improve with treatment of Crohn's disease
    • Subclinical: Sensory or Autonomic neuropathy
    • Demyelinating neuropathies
      • CIDP
      • MMN
    • Treatment related
      • Metronidazole
      • Thalidomide
  • Dermatomyositis: Rare
  • Myasthenia gravis: Rare
  • Electrolyte disorders (K⁺, Mg⁺, Ca⁺⁺)

Celiac Disease (Gluten-sensitive enteropathy) ²

• General: Allergic reaction to gluten in cereals
  • T-cell-mediated immune response against ingested gluten in genetically predisposed people
  • Antigenic target: Transglutaminase
  • Causes injury to mucosa in small bowel
  • Genetic factors
    • 10 percent prevalence of celiac disease among first-degree relatives
    • HLA types
      • HLA-DQ2: 90% to 95% express ((α)1501,(β)102) heterodimer
      • HLA-DQ8: Found in most other celiac disease patients
    • Concordance rates
      • Monozygotic twins: 70%
      • HLA-identical sibs: 30%
    • Predisposition in Finnish families: Linked to chromosome 15q11-q13
• Epidemiology
  • Female > Male
  • Frequency
    • Most common in Western Europe: Up to 1 in 120
    • Rare: African-Caribbean, Chinese, Japanese
• Onset: Childhood to 7th decade
• Clinical features: General
  • Adults
    • Hematologic
      • Anemia: Iron or Folate deficiency
      • Hemorrhage: Vitamin K deficiency
    • GI
      • Clinical: Diarrhea (50%); Flatulence; Weight loss
      • Pathology: Enteropathy of the proximal small bowel
    • Skin: Dermatitis herpetiformis, often with no GI symptoms
    • Osteopenia
    • Renal: IgA mesangial nephropathy
    • Other: Hyposplenism; Lymphoma
    • Associated disorders: Diabetes, Type 1; Thyroiditis; GI neoplasm
  • Children
    • Diarrhea
    • Failure to thrive
    • Abdominal distension
    • Short stature
    • Behavioral disturbances
• Clinical features: Neurological
  • Peripheral neuropathy: Varied patterns; Uncommon
    • Axonal
      • Most common pattern
      • Predominantly sensory: Panmodal sensory loss; Pain
      • Distribution: Distal; Symmetric; Hands & Feet
      • Progression: Slow
    • Motor-Sensory or Motor
    • Mononeuritis multiplex
  • Myopathies
    • Frequency: 5%
    • Inflammatory in some patients
    • Tetany: Hypocalcemia
  • Ataxia
    • May be familial
    • Onset: Adult or Childhood
    • Pattern: Gait disorder; Legs
    • Myoclonus: Occasional association
    • Progression: Slow or Rapid over 1 year
    • Pathology: Purkinje cell loss; Perivascular inflammation
  • Other CNS
    • Seizures: Complex partial
    • Headaches with CNS white matter changes
    • Cerebral calcification: Most commonly reported in Italians
  • Eye: Night blindness
• Laboratory
  • Antibody testing
    • Anti-endomysial antibodies: Serum IgA
      • Antigen is tissue transglutaminase
      • Less common in patients with neurological disease without bowel involvement
    • Anti-Gliadin antibodies: Serum IgA & IgG
      • Less specific for celiac disease than anti-endomysial antibodies
      • Bind to epitopes on Purkinje cells
      • IgG type: May be found in normals (10%); May not be reliable screening procedure
    • Transglutaminase antibodies
      • Celiac disease: Transglutaminase 2 (TG2)
      • Dermatitis herpetiformis: Transglutaminase 3 (TG3)
    • May be negative: Children; IgA deficiency
    • May disappear after gluten free diet treatment
  • Serum transaminases: High alkaline phosphatase
  • Tissue diagnosis: Intestinal biopsy is gold standard
    • Pathology: Absent villi; Hyperplastic crypts; Inflammation, Lymphocytes & Plasma cells
    • Recovery after gluten free diet
  • Gluten ataxia
    • Serum Ig binds to Purkinje cells
    • Transglutaminase 6 antibodies (70%) ³
      • IgG or IgA
      • Reduced with gluten free diet
      • Occur in some sporadic ataxias without enteropathy (30%)
• Treatment
  • Gluten free diet
  • Dietary correction of deficiencies
• External link: Celiac disease