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chain synthesis, improper triple-helix formation and
proteolysis by pepsin.
20
Moreover, disrupted processing
of the N-terminal propeptides can lead to production of
abnormal collagen fibrils.21
21
In a study examining the structure of collagen in OI,
investigators found collagen in patients with advanced
bone disease was more prone to depolymerization but
similar in amount to that of age-matched controls. In
contrast, patients with less bone fragility possessed col-
lagen with similar stability but decreased quantity com-
pared to that of controls. The results of this study suggest
more severe OI results from defects in the crosslinking of
collagen, whereas milder OI stems from a reduction in
the total collagen.
22
Both deficits in structure and quan-
tity of type I collagen may influence the cutaneous mani-
festations of OI.
HIS
TOPATHOLOGY OF SKIN I
N OI
Histopathologic studies in patients with OI show
decreased collagen content and dermal thickness, which
is similar to findings in aged skin (
Figure 30.3
).
23
While
collagen fibers extracted from mild OI cases are thinner
in diameter, collagen from severe OI cases tends to have
a normal diameter but a more frayed appearance with
visible microfibrils.24
24
The histopathologic heterogeneity
corresponds to the clinical variation of OI.
Histologic findings of EPS are also linked with OI
(
Figure 30.2
).
25
Fully developed lesions involve focal
areas of hyperplastic epidermis with perforating chan-
nels containing brightly eosinophilic fragmented elastic
tissue and basophilic nuclear debris. A keratinous plug
may occlude channels and bulge into the dermal layer.
The papillary dermis frequently exhibits increased elas-
tic fibers that appear irregular in outline and clumped by
the epidermis. Older lesions show focal scarring in the
dermis with a dearth of elastic fibers.26
26
The epidermal
and dermal histopathologic features of EPS are associ-
ated with OI.
FIGURE 30.3
Hematoxylin and eosin sections of normal skin
(A, B) compared to photoaged skin (C, D).
23
OI and photoaged skin
share similar histologic features of decreased dermal thickness.
Reproduced with permission from Dr. J. Varani.
decrease collagen synthesis.
28
Likewise, not only easy
bruisability, but also photodamage, platelet disorders,
child abuse and several other disorders are seen in OI.
Finally, one-third of individuals with EPS have an asso-
ciated connective tissue disorder: Down syndrome,
29-31
OI,
32
Ehlers-Danlos syndrome,
31
Marfan's syndrome,
33
cutis laxa
31
or scleroderma.
34,35
Clinically, cutaneous
manifestations of OI should be considered in the larger
context of a patient's history and symptoms. By studying
similarities in skin features between OI and other condi-
tions, we may further our understanding of the patho-
physiology and begin to develop novel treatments for OI.
TREATMENT OF CUTANEOUS
SYMPTOMS IN OI
DIFFERENTIAL DIAGNOSIS OF SKIN
FINDINGS IN OI
Current dermatologic management of OI relies more
on clinical experience than rigorous trials. Commonly
used supportive approaches include gentle skin care, sun
protection and targeted treatment of hyperhidrosis and
EPS as appropriate. Although no studies to date have
investigated the efficacy of topical prescription medica-
tions in OI, therapies used for aged and photoaged skin
may benefit OI dermal deficits. Overall, management of
OI skin conditions should be tailored to each patient's
symptoms, preferences and degree of skin involvement.
Preventive skin care measures are imperative for indi-
viduals with OI. Patients should eliminate use of harsh
The skin findings in OI can be fairly nonspecific, and
a broad differential must be considered in patients with
thin skin, easy bruisability and EPS. Thin skin has been
observed in a variety of collagen-associated patholo-
gies in addition to OI, including chronologic aging,
photoaging, steroid-induced atrophy, striae and atro-
phic scarring. Photodamaged skin results from loss of
dermal extracellular matrix and damage to collagen I
and III from chronic UV exposure.
27
Prolonged use of
topical steroids can inhibit fibroblast mitotic activity and
