Transcript dr.chandrika rao

COLLAGEN DISEASES IN
ADOLESCENTS
DR.CHANDRIKA RAO
PROFESSOR AND HOD.
M.S.RAMAIAH MEDICAL
COLLEGE AND HOSPITAL
BANGALORE
Definition
• Collagen-Greek-`Glue producer`
• Collagen diseases-A small group of disorders
due to structural or metabolic defects in
collagen.
CASE
6'4",
Armspan of 6'7“.
He has hypermobile joints
in his knees, shoulders
and ankles.
CASE
CASE
Collagen-Structure
• Generic term for proteins forming
a triple helix of three polypeptide
chains .
• All members of the collagen family
form these in the extracellular
matrix .
• Size, function and tissue
distribution vary considerably.
• N=28
Type
Collagen Distribution
Disorders
Osteogenesis imperfecta,
Fibril-I,II,III,V,XI
I
II
III
IV
Most abundant .Scar
tissue,tendons, skin, artery walls,
cornea, bones and teeth.
Hyaline cartilage,. Vitreous
humour .
Ehlers–Danlos syndrome
especially type IV,
Infantile cortical hyperostosis aka
Caffey's disease
Collagenopathy, types II and XI
Granulation tissue, Reticular fiber. Ehlers–Danlos
artery walls, skin, intestines and
syndrome, Dupuytren's
the uterus
contracture
Basal lamina; eye lens, glomeruli
Alport syndrome, Goodpasture's
syndrome
VI
Most interstitial tissue, assoc. with
type I
Ulrich myopathy, Bethlem
myopathy, Atopic dermatitis
VII
Forms anchoring
fibrils in dermoepidermal junctions
Epidermolysis bullosa dystrophica
VIII Some endothelial cells
IX
FACIT collagen-(IX,XII,XIV,XV),
cartilage, assoc. with type II and XI
fibrils
Posterior polymorphous corneal
dystrophy
EDM2 and EDM3
Hypertrophic and mineralizing
X
Schmid metaphyseal dysplasia
cartilage
Collagen vascular disorders
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Discoid lupus erythematosus
Systemic lupus erythematosus
Neonatal lupus erythematosus
Juvenile dermatomyositis
Childhood scleroderma
Approach
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Detailed history
Progressive
Multiple areas involved
Skin,Musculo-skeletal involvement
Family history
Remmision and relapse
GENETICS
Different Types of Mutations in Collagen I Chain Genes
Cause Different Disease Severities
Gene
location mutation
Syndrome
COL1A1
17q22
Null alleles
OI type I
Partial deletions; C-terminal
substitutions
OI type II
N-terminal substitutions
OI types I, III or IV
Deletion of exon 6
EDS type VII
Splice mutations; exon deletions
OI type I
C-terminal mutations
OI type II, IV
N-terminal substitutions
OI type III
Deletion of exon 6
EDS type VII
COL1A2
7q22.1
Family Tree
45
AAA
?
69
28 aortic
aneurysm,
aneurysm of
kidney
28
AA
31 AA, cerebral
hemorrhage
44
45 ?valve
replacement
13 aortic
aneurysm
28
AA
Ehlers-Danlos syndrome
The signs and symptoms of Ehlers-Danlos syndrome vary
from mildly loose joints to life-threatening complications
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Diseases of Elastic
Fiber
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Cutis laxa
Williams syndrome
Buschke-Ollendorff syndrome
Menkes disease
Pseudoxanthoma elasticum,
Marfan's syndrome
SLE
Revised Diagnostic Criteria
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Renal disorder
8. Haematologic disorder
9. Neurologic disoder
10. Immunologic disoder
11. ANA
4/11 are present serially or simultaneously.
Preliminary Classification Criteria for Undifferentiated
Connective-Tissue Disease
Inclusion Criteria
Exclusion Criteriaa
Laboratory Criteriaa
Signs and symptoms
suggestive of a CTD but
not fulfilling the
diagnostic or
classification criteria for
any of the defined
CTDs b for at least 3
years c
Malar rash
Discoid Lupus
Cutaneous sclerosis
Heliotrope rash
Gottron papules
Erosive arthritis
Anti-dsDNA
Anti-Smith
Anti-U1-RNP
Anti-Scl70
Anticentromere
Anti-La/SSB
Anti-Jo1
Anti-Mi2
Presence of antinuclear
antibodies determined
on two different
occasions
Investigation
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CBC,ESR,CRP
Urinalysis
Serum creatinine
Rheumatoid factor (RF)
ANA-IFA
X-ray
CT Scan
Early renal biopsy
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Other:
CK,C3, ,TSH,Anti-Ro/SSA,Anti-La/SSB
Anti-Smith,Anti-cardiolipins,
Lupus anticoagulant
Vitamin D - 25(OH)D3
Treatment
• Early diagnosis.HEADDSS
• May still utilize tried & tested agents initially
• Phenytoin, Cyclosporine,Ca Channel blocker-
Nifedipine-stimulatory drugs.
• Newer immunosuppressive & immunomodulatoryNASAIDS,Cox-2inhibitor, Cyclosporine, Azathioprine,
Ca channel blocker.
CONCLUSION
• A multidisciplinary approach.
• The aim should be to reduce disease activity to a minimum
level and to allow treatment free intervals, so that the
growth, development, and fertility of these children are
ensured.
•Thank you
•Q:Acquired collagen disorder?