Transcript CONNECTIVE TISSUE DISORDERS ex

CONNECTIVE TISSUE
DISORDERS
Presenter: Dr. Gituri Philip
Moderator: Dr. Kingori
Outline
1. Introduction
2. Classification & Types of connective tissue diseases
3. Presentations of CTDs
4. Specific Issues
5. Conclusions
Introduction to CTDs
 May affect predominantly bone, bone and soft tissues, systemic,
 May complicate orthopedic procedures
 musculoskeletal operations differ in preoperative preparations &
outcomes
 May be classified into:
1. Congenital
2. Acquired
3. Inflammatory
4. Immune-mediated
Collagen
1. 40% of the dry weight of bone is Organic components
 Collagen (90% of organic component)
 Collagen is primarily type I: provides tensile strength
2. Type II collagen
 95% of collagen content in articular cartilage
 Provides cartilaginous framework and tensile strength
 Very stable, with a half-life of approximately 25years
Cont…
 Collagen type X
 Produced by hypertrophic chondrocytes during enchondral ossification:
i.
Growth plate
ii.
Fracture callus
iii. Heterotopic ossification formation
iv. Calcifying cartilaginous tumors
 Is associated with calcification of cartilage
 A genetic defect in type X collagen responsible for
 Schmid’s metaphyseal chondrodysplasia (affects the hypertrophic
physeal zone).
Cont…
 Collagen type XI
 an adhesive that holds the collagen lattice together
Introduction
 Inherited disorders of connective tissue: clinically and
genetically diverse group of conditions affecting
primarily the skin, joints, and, often, the cardiovascular
system.
 severity of the musculoskeletal phenotype depends on
i. the type of mutation
ii. the role & function of the affected protein on
musculoskeletal structure
Types of collagen
Type Tissues
 I Skin, tendon, bone, meniscus, annulus fibrosus
 II Articular cartilage, vitreous humor, nucleus pulposus
 III Skin, muscle, blood vessels
 IV basement membrane (basal lamina)
 V,VI,IX,X articular cartilage
 X Articular cartilage, mineralization of cartilage in hypertrophic zone
of physis
 XI Articular cartilage
 XII Tendon
 XIII endothelial cells
Marfan syndrome
 Incidence is 1 in 10,000
 Autosomal dominant; 25% new mutations
 Mutation in fibrillin-1 gene on chromosome 15q21; multiple
mutations identified
 Affected individuals:
 Dolichostenomelia
 Arachnodactyly
 Positive wrist sign (Walker sign)
 Positive thumb sign (Steinberg sign)
 Arm span-to-height ratio >1.05
 Cardiac defects, especially aortic root dilatation
 Scoliosis is seen in 60% to 70% of patients
 dural ectasia is common (>60%)
 Pectus excavatum and spontaneous pneumothoraces
 Pectus carinatum or asymmetric deformity of anterior chest
 Superior lens dislocation (ectopia lentis) and myopia
 Protrusio acetabuli and severe pes planovalgus
Diagnosis
 Clinical assessment
 mutational or linkage analysis in familial phenotypes
Classification of Marfans syndrome
1. Ghent system: 1 major criterion in each of two different
organ systems and involvement in a third system
2. MASS (mitral valve prolapse, aortic root diameter at
upper limits of normal, stretch marks, skeletal
manifestations of Marfan) phenotype
Treatment
i.
Multi-disciplinary
ii. Nonsurgical
a) Beta blockers for mitral valve prolapse, aortic dilatation
b) ii. Bracing for early scoliosis, pes planovalgus
iii. Surgical
a) For progressive scoliosis- long scoliosis fusion
b) progressive protrusio acetabuli, closure of the triradiate cartilage
c) progressive pes planovalgus, corrective surgery
Ehlers-Danlos syndrome (EDS)
 hypermobile joints, hyperextensible skin, fragile tissues extremely
susceptible to trauma
 40% to 50% of patients: mutation in COL5A1 or COL5A2 (type V
collagen gene)
 7 types
 classic form: AD
 Type VI, AR (mutation in lysyl hydroxylase. Severe kyphoscoliosis characteristic)
 Type IV, AD(mutation in COL3A1 thus abnormal collagen III; arterial,
intestinal, and uterine rupture seen
Clinical Presentation
 Skin: velvety and fragile. Severe scarring with minor trauma
common
 Joints: hypermobile, esp the shoulders, patellae, and ankles
 Pes planus
 “double-jointed” fingers
 frequent sprains or subluxation of larger joints spontaneously or after
slight trauma
 1/3 of patients: aortic root dilatation
 vascular subtype: spontaneous visceral or arterial ruptures
 c/o chronic joint and limb pain despite normal skeletal
radiographs
 joint hypermobility leads to the onset of OA (3rd or 4th
decade)
 Muscle hypotonia & delayed gross motor development
Importance to surgery
 skin splits from trauma,
 is relatively painless
 does not bleed excessively,
 wounds tend to gape
 wound margins tend to retract
 heal slowly& often become infected
 Dehiscence common, &
 complete wound breakdown may require repeated suturing or
healing by secondary intention
Beighton Criteria for Joint Hypermobility
1. Passive dorsiflexion of the fifth finger > 90 degrees
2. Passive apposition of the thumbs to the flexor aspect of the forearm
(Beighton sign)
3. Hyperextension of the elbow > 10 degrees
4. Hyperextension of the knees > 10 degrees
5. Ability of the palms to completely touch the floor during forward
flexion of the trunk with knees fully extended
Treatment
1. triad of
a) anticipatory guidance,
b) pain management
c) Physical therapy
2. Avoid surgery for lax joints; soft-tissue procedures unlikely to
work
3. Progressive scoliosis in type VI (necessary )
4. Orthopedic procedures: Bracing & longer fusions for
Progressive scoliosis in type VI
Osteogenesis imperfecta (OI)
 Types I through IV : mutation in the COL1A1 and COL1A2 genes
 bone that has decreased number of trabeculae and cortical
thickness (wormian bone)
 Types V through VII no collagen I mutation but
o similar phenotype and
o abnormal bone on microscopy
Clinical presentation of OI
 Child abuse should not be ruled out
 types II and III, basilar invagination and severe scoliosis
may occur
 Olecranon apophyseal avulsion fractures characteristic
 dentinogenesis imperfecta, hearing loss, blue sclerae,
joint hyperlaxity, and wormian skull bones
 frequency of fractures declines sharply after
adolescence
Type
Severity
Features
Sclerae
Inheritance
IA, IB
Mild
Most common, mild
to moderate bone
fragility, little or no
deformity
Blue
AD
II
Lethal, rarely survive Extremely fragile
infancy
bones, severe
deformity, perinatal
Blue
AR
III
Severe
Progressively
deforming,
moderate to severe
deformity,
progressive,
neonatal fractures
Normal
AR
IVA, IVB
Moderately severe
Mild to moderate
bone fragility, long
bone/spine
deformity, A with
dental involvement
Normal
AD
Treatment of OI
 multi-disciplinary approach.
 Manage fractures with light splints
 IV & PO Bisphosphonates and growth hormone
 severe bowing of the limbs or recurrent fracture:
intramedullary fixation is indicated with or without
osteotomy.
 Progressive scoliosis/basilar invagination is treated with
spinal fusion
 Transplantation of adult mesenchymal stem cells
Other collagen associated diseases
1. Scurvy
Acquired: vitamin C deficiency
decrease in chondroitin sulfate and collagen
synthesis
greatest deficiency seen in the metaphysis
P/E: microfractures, hemorrhages, and collapse of the
metaphysis
Characteristic radiographic findings :line of Frankel
and osteopenia of the metaphysis.
Scurvy
 Vitamin C (ascorbic acid)
deficiency
 Produces a decrease in
chondroitin sulfate synthesis
 defective collagen growth
and repair
 impaired intracellular
hydroxylation of collagen
peptides
 Clinical features:
i.
Fatigue
ii. Gum bleeding
iii. Ecchymosis
iv. Joint effusions
v. Iron deficiency
 Radiographic findings:
o thin cortices & trabeculae
and metaphyseal clefts
(corner sign)
features of scurvy on X-ray of long
bones
Scurvy cont…
o normal bone formation
reduced
o lacking in tensile strength
o defective in structural
arrangement
o Bow legs
o stunted bone growth
o swollen joints.
Multiple epiphyseal dysplasia
 gene mutation is in COMP
 AD
 Radiologic findings: irregular, delayed ossification at multiple
epiphyses
 P/E: Short, stunted metacarpals and metatarsals,
 irregular proximal femora,
 abnormal ossification (tibial “slant sign” & flattened femoral
condyles, patella with double layer)
 valgus knees (early osteotomy should be considered),
 waddling gait, and early hip arthritis
 14yr old
Treatment of MED
1. bone survey to differentiate between MED and single
epiphyseal dysplasia, as well as to identify all areas of
involvement.
2. Treat limb alignment and perform early joint
replacement.
Spondyloepiphyseal dysplasia
 Genetic defect: gene encoding type II collagen
 abnormal epiphyseal development in the upper and
lower extremities
 Scoliosis: sharply curved apex over a small number of
vertebrae
 Retinal detachment and respiratory problems common.
Kniest Syndrome
 Defect within type II collagen
 AD inheritance
 Presentation
• short-trunked, disproportionate dwarfism
• joint stiffness/contractures,
• Scoliosis, kyphosis,
• dumbbell-shaped femora, and hypoplastic pelvis and spine
• Otitis media and hearing loss frequent
 Xray: Osteopenia and dumbbell-shaped bones
 Rx: Early therapy for joint contractures.
 Reconstructive procedures for early hip degenerative arthritis.
Arthritides
Rheumatoid (seropositive) arthritis (RA)
 inflammatory autoimmune arthritis
 causes joint destruction at a younger age
 synovium thickens, fills with B-cells, T-cells, and
macrophages, that erode the cartilage
 multiple hot, swollen, morning stiffness. Subcutaneous
calcified nodules and iridis
 Radiographs: symmetric joint space narrowing,
periarticular erosions, and osteopenia
Treatment of RA
1. Nonsurgical: NSAIDs & DMARDs
2. Surgical
i. synovectomy
ii. joint realignment early
iii. joint arthroplasty later stages.
Conclusions
1. Mutation in the genes coding for various collagen a chains result in a
heterogeneous group of heritable conditions (collagenopathies)
2. Mutations in types II, IX, and XI collagens affects the musculoskeletal,
ocular, visual systems, or all three
3. Diagnosis : clinical findings, radiographic findings, & genetic test results
4. Follow-up and management: multidisciplinary
5. Rx is symptomatic and individualized