COLLAGEN DISEASES IN ADOLESCENTS

DR.CHANDRIKA RAOPROFESSOR AND HOD.M.S.RAMAIAH MEDICAL COLLEGE AND HOSPITALBANGALORE

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

I

Fibril-I,II,III,V,XI

Most abundant .Scar tissue,tendons, skin, artery walls, cornea, bones and teeth.

Osteogenesis imperfecta, 

Ehlers–Danlos syndrome especially type IV, 

Infantile cortical hyperostosis aka Caffey's disease

II Hyaline cartilage,. Vitreous humour . Collagenopathy, types II and XI

IIIGranulation tissue, Reticular fiber. artery walls, skin, intestines and the uterus

Ehlers–Danlos syndrome, Dupuytren's contracture

IV Basal lamina; eye lens,  glomeruli Alport syndrome, Goodpasture's syndrome

VIMost interstitial tissue, assoc. with type I

Ulrich myopathy, Bethlem myopathy, Atopic dermatitis

VIIForms anchoring fibrils in dermoepidermal junctions

Epidermolysis bullosa dystrophica

VIII Some endothelial cells Posterior polymorphous corneal dystrophy

IXFACIT collagen-(IX,XII,XIV,XV), cartilage, assoc. with type II and XI fibrils

EDM2 and EDM3

XHypertrophic and mineralizing 

cartilageSchmid metaphyseal dysplasia

Collagen vascular disorders

•Discoid lupus erythematosus•Systemic lupus erythematosus•Neonatal lupus erythematosus•Juvenile dermatomyositis•Childhood scleroderma

Approach

•Detailed history•Progressive•Multiple areas involved•Skin,Musculo-skeletal involvement•Family history•Remmision and relapse

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

COL1A2 7q22.1 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

GENETICS

Different Types of Mutations in Collagen I Chain Genes Cause Different Disease Severities

Family Tree

?

13 aortic aneurysm

44

69

28 aortic aneurysm, aneurysm of kidney

28 AA

28 AA

31 AA, cerebral hemorrhage

45 AAA

45 ?valve replacement

Ehlers-Danlos syndrome

The signs and symptoms of Ehlers-Danlos syndrome vary from mildly loose joints to life-threatening complications•

Diseases of Elastic Fiber• Cutis laxa• Williams syndrome• Buschke-Ollendorff syndrome • Menkes disease • Pseudoxanthoma elasticum, • Marfan's syndrome 

SLERevised Diagnostic Criteria

1. Malar rash2. Discoid rash3. Photosensitivity4. Oral ulcers5. Arthritis6. Serositis7. Renal disorder8. Haematologic disorder9. Neurologic disoder10.Immunologic disoder11.ANA 4/11 are present serially or simultaneously.

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 rashDiscoid LupusCutaneous sclerosisHeliotrope rashGottron papulesErosive arthritis

Anti-dsDNAAnti-SmithAnti-U1-RNPAnti-Scl70AnticentromereAnti-La/SSBAnti-Jo1Anti-Mi2

Presence of antinuclear antibodies determined on two different occasions

Preliminary Classification Criteria for Undifferentiated Connective-Tissue Disease

Investigation •CBC,ESR,CRP X-ray•Urinalysis CT Scan•Serum creatinine Early renal

biopsy•Rheumatoid factor (RF)•ANA-IFA

•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 &

immunomodulatory-NASAIDS,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?