Clinical Presentation and Diagnosis of Childhood Langerhans Cell Histiocytosis

1
Clinical Presentation and Diagnosis of Childhood
Langerhans Cell Histiocytosis

• Jeffrey D. Hord, M.D.
• Director, Pediatric Hematology/Oncology
• Akron Childrens Hospital,
• Akron, Ohio

2
LCH Facts

• LCH prevalence in children is 1/50,000
• Annual incidence of LCH is 5-9/1,000,000 children
  lt15 years old
• Median age at diagnosis is 30 months old
• multisystem disease usually found in children lt 2
  yr old
• multifocal single site disease usually in
  children 2-5 yr old
• Males affected a little more often than females
• Affects all ethnic groups equally
• 70 of children have only 1 site of disease (bone
  most common)

3
Risk Factors for LCH

• Frequent infections and antibiotic use in first 6
  months of life
• Family history of thyroid disease
• Family history of relative of LCH (1 of children
  with LCH have an affected relative)
• Genetic basis for disease suggested by twin
  studies- 92.3 of time when one identical twin is
  affected so is the other this is only true 10
  of time in non-identical twins

4
Old LCH Classification

• Eosinophilic Granuloma
• isolated bone lesion
• Hand-Schuller-Christian Syndrome
• skull lesions, exophthalmos (protruding eyes),
  diabetes insipidus
• Letterer-Siwe
• organomegaly (enlarged liver and/or spleen),
  enlarged lymph nodes, localized bone lesions,
  bleeding tendencies, anemia

5
New LCH Classification

• Multisytem Risk patients
• involvement of 1 or more of following bone
  marrow, spleen, liver, lung
• Multisystem low risk patients
• Special sites
• multifocal bone disease (90 regression/resolution
  rate)
• central nervous system w/ higher risk of DI
  (facial bones, vertebral body with soft tissue
  mass compressing spinal cord)
• Single system/localized disease (skin, lymph node)

6
Clinical Presentation of LCH in Children

• Presenting signs and symptoms varies depending
  upon areas involved
• Disease can be isolated to one area or involve
  multiple organ systems
• Areas of potential involvement include bone,
  skin, ears, hypothalamic-pituitary axis, bone
  marrow, lung, liver, intestines

7
LCH- Bone Involvement

• Presents as pain and swelling rarely, fracture
• Loose teeth if jaw involved
• Involved in 80 of patients
• 1/2 with 1 lesion 1/2 with multiple lesions
• 1/2 of all bone lesions found in skull and facial
  bones
• Eye may be pushed outward (proptosis) if orbits
  involved
• Lesions in bones may last for years

Image from Histiocytic Disorders of Children and
Adults, Weitzman and Egeler (eds), 2005
8
LCH- Bone Involvement

• 10 of those with bone involvement have vertebral
  body involvement (collapsed vertebral body
  vertebra plana)
• May present with weakness or paralysis if there
  is a soft tissue mass pushing on the spinal cord

Image from Histiocytic Disorders of Children and
Adults, Weitzman and Egeler (eds), 2005
9
LCH- Bone Involvement

• Often times bone lesions are found on x-ray by
  coincidence
• Of those with bone lesions, 20 have lesions in
  proximal limbs and 5 in distal limbs

Image from Histiocytic Disorders of Children and
Adults, Weitzman and Egeler (eds), 2005
10
LCH- Skin Involvement

• Skin involved in over 50 of cases (2nd most
  commonly involved organ)
• Crusty, petechial papules in scalp often mistaken
  for seborrheic dermatitis
• Ear discharge may result from extension of scalp
  rash and secondary infection (but middle and
  inner ear can also be involved)

Image from Histiocytic Disorders of Children and
Adults, Weitzman and Egeler (eds), 2005
11
LCH- Skin Involvement

• Skin folds and diaper area frequently involved
• Distal limbs usually spared

Image from Histiocytic Disorders of Children and
Adults, Weitzman and Egeler (eds), 2005
12
LCH- Central Nervous System Involvement

• Involvement of hypothalamic-pituitary axis (HPA)
  seen in about 25 of LCH cases
• May present with excessive thirst and large urine
  output. This is diabetes insipidus and is
  usually permanent.
• Median age of onset of HPA dysfunction is 4 years
• This is seen more often in those with facial bone
  lesions.
• Seen on CT or MRI of brain
• Reactivation rate of disease is 2-3 times higher
  in those with HPA involvement
• In up to 10 of those with multisystem disease,
  other CNS problems are found (mass lesion at
  diagnosis or degenerative CNS changes 5-15 years
  after diagnosis)

13
LCH- Lung Involvement

• 15 of children with LCH have lung involvement
  (usually small nodules on high-resolution CT scan
  )
• Almost never seen as the only site of involvement
• May not have any symptoms or may be breathing
  faster than usual or feel short of breath
• May be confirmed by lung biopsy or
  bronchoalveolar lavage

14
LCH- Liver/GI Involvement

• Soft, enlarged liver often accompanied by
  enlarged spleen
• May see jaundice
• Decrease in proteins produced by liver (albumin,
  clotting factors)
• GI tract involvement is rarely reported but may
  present as diarrhea with blood and mucous

15
LCH- Bone Marrow Involvement

• Hematologic problems are most often seen in those
  lt 2 years old
• Found in patients with more severe disease
• May present with bruising, bleeding, pale
  appearance
• The reason that the blood cell counts are low is
  that histiocytes are engulfing the blood cell
  precursors

16
Basic Evaluation of a Child with Suspected LCH

• HISTORY - fever, pain, growth, diarrhea, urine
  output, thirst, ear infections, rashes, behavior,
  lumps
• PHYSICAL EXAM- height, weight, pubertal status,
  temperature, lumps/bumps, rashes, bruising,
  jaundice, ear discharge, orbits, gums, palate,
  teeth, lymph nodes, size of liver and spleen,
  neuro exam, eyes, breathing/lungs, swelling/edema
• LABS- CBC, iron studies, ESR, renal function
  tests, liver function tests, albumin, clotting
  studies, urine concentration, bone marrow
  aspiration, HLA-typing
• X-RAYS- chest x-ray, skeletal survey /- bone
  scan, chest CT scan

17
Diagnostic Findings of LCH

• CD1a antigen on the surface of lesional cells
• Birbeck granules in lesional cells by electron
  microscopy
• Provisional diagnosis made with characteristic
  morphology, S100 expression, and expression of at
  least 1 of these 3 markers ATPase,
  alpha-D-mannosidase, peanut lectin

Image from Histiocytic Disorders of Children and
Adults, Weitzman and Egeler (eds), 2005