Clinical and Laboratory Investigations

Dermatology 2007;215:284294
DOI: 10.1159/000107621

Received: March 8, 2007

Accepted: April 20, 2007

Dermatoporosis: A Chronic Cutaneous

Insufficiency/Fragility Syndrome
Clinicopathological Features, Mechanisms, Prevention and Potential Treatments

Grkan Kaya Jean-Hilaire Saurat

Department of Dermatology, University of Geneva, Geneva, Switzerland

Abstract
Background: Skin aging has long been considered only as a
cosmetic problem. With the increase in lifespan, we are now
more often experiencing a further dimension of skin aging,
which is no longer only cosmetic, but also functional, in the
sense that the skin has lost its protective mechanical function. Dermatoporosis is the name proposed to capture, in a
holistic approach, all the aspects of this chronic cutaneous
insufficiency/fragility syndrome. Observations: In this paper, we review the clinical aspects of dermatoporosis, its histological features and the current understanding of its etiological factors. The clinical manifestations of dermatoporosis comprise (i) morphological markers of fragility rather
trivial such as senile purpura, stellate pseudoscars and skin
atrophy, and (ii) functional expression of skin fragility resulting
from minor traumas such as frequent skin laceration, delayed wound healing, nonhealing atrophic ulcers and subcutaneous bleeding with the formation of dissecting hematomas leading to large zones of necrosis. Dissecting hematomas bear significant morbidity needing hospitalization and
urgent surgical procedures. Molecular mechanisms implying hyaluronate-CD44 pathways in the control and maintenance of epithelial growth and the viscoelastic properties of
the extracellular matrix offer new opportunities for preventive intervention. Conclusion: We propose to group the different manifestations and implications of this syndrome un-

2007 S. Karger AG, Basel

10188665/07/21540284$23.50/0
Fax +41 61 306 12 34
E-Mail karger@karger.ch
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der the umbrella term of dermatoporosis, because we think

it will help to capture the understanding of health professionals that, as osteoporosis, dermatoporosis should be
prevented and treated to avoid complications. Dermatologists should be aware of this emerging syndrome and function as key players in prevention and therapy. Randomized
clinical trials should demonstrate which intervention may
best prevent and/or reverse dermatoporosis.
Copyright 2007 S. Karger AG, Basel

Introduction

Skin aging should not be considered as only a cosmetic issue. With extreme aging, the loss of extracellular matrix (ECM) and its major component hyaluronate (HA),
which stabilizes the intercellular structures by forming a
viscoelastic network in which collagen and elastin fibers
are embedded, induces a loss of the skins mechanical
functions. In fact, HA, just as in the joints, provides a
cushion effect to the skin structures including the epidermis. The solidity of the skin is provided by the ECM, and
the loss of HA and consequently of this viscoelastic buffering system would contribute to easy tearing resulting
in skin lacerations.
With the increase in the number of elderly individuals,
this functional rather than cosmetic dimension of skin
aging has been realized. The loss of the protective mechanical function of the skin results in extreme fragility
leading to complications such as lacerations, nonhealing
Grkan Kaya, MD, PhD
Department of Dermatology, University of Geneva
24, rue Micheli-du-Crest
CH1211 Geneva 4 (Switzerland)
Tel. +41 22 372 75 14, Fax +41 22 372 94 77, E-Mail gkaya@hcuge.ch

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Key Words
Skin aging  Dermatoporosis  Hyaluronate  CD44

Clinical Manifestations of Dermatoporosis

Dermatoporosis is an emerging clinical condition of

aged people; the first clinical manifestations start from
the age of 60 years but well-developed disease is seen between 70 and 90 years.
The clinical manifestations comprise:
(i) morphological markers of fragility rather trivial such as senile purpura, stellate pseudoscars and skin
atrophy, and
(ii) functional expression of skin fragility resulting
from minor traumas such as frequent skin laceration, delayed wound healing and subcutaneous bleeding with the
formation of dissecting hematomas leading to large zones
of necrosis.
Morphological Markers of Skin Fragility
They have been well described for more than a century and have been considered as trivial, although they
indicate the risk for the occurrence of a functional expression of skin fragility.
Skin Atrophy
Skin atrophy is seen mainly in sun-exposed areas,
namely the posterior side of the forearms and the pretibial zones. Clinically the skin is very thin, transparent
and shows numerous wrinkles as well as senile purpura
and pseudoscars (see below) when compared to a younger skin (fig. 1A, B). Special skin ultrasonography of atrophic skin shows a significant decrease in the thickness of
the epidermis and dermis (around 0.70.8 mm) when
compared to that of normal skin (around 1.41.5 mm;
fig. 1C, D). Histologically there is thinning of the epidermis and dermis. The epidermis displays linearization
with loss of rete ridges, and an important degree of elastosis is found in the dermis where the subcutaneous fat is
mostly situated (fig. 1E, F). The collagen, elastic fiber and
mucin (mostly HA; fig. 6) content of the dermis is decreased (fig. 2AF).
Dermatoporosis: Features, Mechanisms,
Prevention and Potential Treatments

Senile Purpura
Senile purpura is localized mainly to extremities and
results from repetitive spontaneous or minimal traumaassociated dermal bleedings without any coagulation disorders. Its frequency is around 10% in an elderly population between 70 and 90 years with a female predominance, and it is associated, in 90% of the cases, with
pseudoscars (see below) [3]. These purpuric plaques disappear by leaving a deep brownish pigmentation corresponding to hemosiderin pigment (fig. 3A). Vitamin C
deficiency may also lead to dermal hematomas which are
also frequent in these patients, and a substitution therapy
should be considered. Histologically the senile purpura is
characterized by extravasation of red blood cells into the
dermis which are often found in a perivascular location.
The skin usually shows thinning of the epidermis and
dermis, marked solar elastosis and atrophy of collagen
bundles (fig. 3B).
Stellate Pseudoscar
Stellate pseudoscar is a spontaneous dermal laceration
displaying a stellar aspect [4]. The stellate pseudoscar is
encountered in 2040% of the elderly population between 70 and 90 years, and it is more frequent in females
[3]. These lesions are mainly seen on the back of the hands
and forearms and are accompanied by a senile purpura
in 3050% of the patients [3]. Clinically the pseudoscars
appear as whitish lesions. Initially 5 forms have been proposed [4]. In fact, there are 3 main types of pseudoscars:
star-shaped (fig. 4A), linear (fig. 4B) or plaque-type
(fig. 4C). These lesions are seen essentially after 60 years
of age, and become particularly frequent after 70 years.
Histologically the pseudoscar corresponds to a compact
hypocellular band of collagen under an atrophic epidermis which contains decreased amounts of elastic fibers
and mucin (fig. 4D, E, F; data not shown).
Functional Expression of Skin Fragility
They represent an emerging syndrome in the growing
population of elderly persons.
Dissecting Hematoma of the Skin
This important complication is due to mechanical fragility of the aged skin, occurs predominantly in the lower
extremities of elderly patients suffering from dermatoporosis and results in long and costly hospital stays (fig. 5D).
Dissecting hematoma is seen in elderly populations (between 70 and 99 years) with severe dermatoporosis (in
96% of the patients), showing a female predisposition
(M/F ratio: 1/5) [Kaya et al., submitted].
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atrophic ulcers and dissecting hematomas. The latter

cause significant morbidity which requires long hospital
stays and immediate surgical interventions [Prins et al.,
manuscript in preparation].
We propose the term dermatoporosis to cover the
different manifestations and implications of this chronic
cutaneous insufficiency/fragility syndrome and to facilitate the understanding that, as osteoporosis, dermatoporosis should be treated to prevent complications [1, 2].

porosis. Forearm skin of a dermatoporosis patient shows important atrophy, senile purpura and numerous pseudoscars (A) when
compared with the skin of a younger individual (B). Echographic
analysis of the skin of a primary dermatoporosis patient performed using a skin ultrasound system (Episcan; Longport Inc.,
Glen Mills, Pa., USA) displays a significant skin atrophy (average
of 3 measurements between the top level of epidermis and dermal-

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subcutaneous fat junction: 0.73 mm; C) compared to normal skin

(average of cutaneous thickness: 1.44 mm; D). Histologically dermatoporotic skin is characterized by an epidermal and dermal
atrophy: decrease in epidermal thickness with loss of rete ridges,
loosening of dermal connective tissue with thinning of dermis,
important elastosis and high localization of sweat glands and subcutaneous fat (E) when compared to normal skin (F). Hematoxylin-eosin. Original magnification !10.

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Fig. 1. Clinical, echographic and histological features of dermato-

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Prevention and Potential Treatments

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Fig. 2. Dermal collagen, elastic fiber and mucin content in dermatoporosis. Dermatoporotic skin shows a decrease in red-stained collagen (A), black/brown-stained elastic fiber (C) and blue-stained mucin (E) content
compared to normal skin (B, D, F). Note the presence of elastic fibers in normal skin (D, arrows) which are replaced by a heavy elastotic material in dermatoporosis (C , arrows). A , B Sirius red. C , D van Gieson elastin.
E , F Colloidal iron. Original magnification !10.

Fig. 3. Clinical and histological characteristics of senile purpura. The forearm skin of a patient with dermatoporosis shows multiple noninflammatory purpuric lesions of red-black color of different sizes (A) which are

histologically characterized by extravasation of erythrocytes forming large areas of hemorrhage in an atrophic

and elastotic dermis. Note also the presence of an epidermal atrophy (B). Hematoxylin-eosin. Original magnification !10.

Fig. 4. Clinical and histological characteristics of pseudoscar. Pseudoscars correspond clinically to whitish linear (A), star-shaped (B) or plaque-type (C) papular lesions. Histologically the center of the lesion is formed by a
hypocellular band of collagen under an atrophic epidermis (D, E). This collagen band shows decreased amounts
of elastic fibers (F). D Hematoxylin-eosin. Original magnification !2.5. E Sirius red. Original magnification
!10. F van Gieson elastin. Original magnification !10.

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skin and cause necrosis. In this case immediate surgical

evacuation of the hematoma and the necrotic tissue
should be performed to avoid extensive skin damage.
Large and deep excisions descending down to the muscular tissue resulting in important skin surface loss may
be necessary. The re-epithelization of these large defective skin surfaces may then be achieved by vacuum-assisted closure or autologous thin skin grafts [5].
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Minimal traumas may cause massive bleedings into a

virtual space between the dermis and subcutaneous fat or
the subcutaneous fat and muscle fascia. In the initial stages, the leg is erythematous, swollen and hot, and although
the patient does not show symptoms of infection, approximately half of the patients receive a diagnosis of erysipelas of the leg and are treated with antibiotics. Later, resulting large hematomas destroy the blood supply to the

Fig. 5. Clinical staging of dermatoporosis. Stage I is characterized by extreme skin atrophy, senile purpura and
pseudoscars (A); stage II shows localized skin lacerations (B); in stage III these lacerations are more numerous
and larger (C), and in stage IV dissecting hematomas are formed (D).

Dissecting hematomas of the skin may occur in patients with anticoagulation or topical or systemic corticosteroid therapy. Corticosteroids are known to cause
skin atrophy [6], and protective measures for the lower
extremities should be taken in these patients.
Delayed Wound Healing
Chronic posttraumatic wounds are a very important
problem in the elderly, and the exact mechanism for the
delay in wound healing is not completely understood
despite the molecular analysis of some genes thought to
play a role in chronic wounds [7]. A decrease in the proliferative capacity of keratinocytes and fibroblasts,
abundant production of matrix metalloproteinases
(MMPs) and secretion of cytokines which inhibit the
dedifferentiation of keratinocytes lead to tissue destruction.

Etiological Classification of Dermatoporosis

Primary Dermatoporosis
This is the most commonly seen type of dermatoporosis and results from chronological aging and long-term
and unprotected sun exposure (see below). In osteoporosis, heritability studies have shown evidence of significant genetic effects on key determinants of osteoporotic
fracture risk, including peak bone mass, muscle strength,
bone turnover markers and body mass index [8]. We currently do not know the genes implicated in primary dermatoporosis. However, we think that, as in osteoporosis,
genetic factors play a significant role in the regulation
and loss of ECM components, in the viscoelastic properties of the skin (see below) and therefore in susceptibility
to dermatoporosis.

Dermatoporosis: Features, Mechanisms,

Prevention and Potential Treatments

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Secondary Iatrogenic Dermatoporosis

This type is due to the chronic use of topical and systemic corticosteroids. Corticosteroids are known to reg-

Clinical Staging of Dermatoporosis

Since dermatoporosis is very frequent in the elderly

population, it is important for clinical purposes to distinguish several stages based on its severity. In our practice,
we have been using 4 stages as follows (table 1).
Stage I. This stage is characterized by the presence of
extreme skin thinning, senile purpura and pseudoscars
(fig. 5A). It is clear that several levels in this stage may exist, and that further quantitative definition of each component may be necessary. Clinical evaluation of viscoelasticity (see below) might be a key item.
Stage II. In addition to the lesions found in stage I,
some localized skin lacerations are found (fig. 5B). These
lesions result from the cleavage between epidermis and
dermis.
Stage III. Skin lacerations are more numerous and
larger, and may involve the whole surface of the extremity (fig. 5C); delayed healing is prominent.
Stage IV. Advanced lesions result in dissecting hematomas (fig. 5D).
We currently consider these stages as a working proposal that should be further defined and accepted by the
current methodology of evidence-based dermatology.

Potential Mechanisms of Skin Fragility in

Dermatoporosis

ECM Modifications
The clinical manifestations of skin aging have been
associated with modifications in the ECM. These modifications can be the consequence of direct damage as provoked by aging-related genomic instability, by ultraviolet
irradiation, by nonenzymatic glycation of structural proteins and also by the inflammatory response to environmental factors or by endogenous stressors [9, 10].
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Table 1. Proposed clinical staging of dermatoporosis: a basis for

further evidence-based quantitative definitions

Skin
Senile
Pseudo- Skin
Dissecting
atrophy purpura scar
laceration hematoma
Stage I
Stage II
Stage III
Stage IV

+
+
+
+

+
+
+
+

+
+
+
+

+
++
++

Stage I: + = presence of any senile purpura or pseudoscars;

stage IA: <10 pseudoscars, <10 senile purpura lesions; stage IB:
<10 pseudoscars, >10 senile purpura lesions; stage IC: >10 pseudoscars, <10 senile purpura lesions; stage ID: >10 pseudoscars,
>10 senile purpura lesions. Stage II: + = <10 lacerations. Stage III:
++ = >10 lacerations. Stage IV: + = presence of any dissecting hematoma.

It has been shown that during chronological skin aging MMPs 1, 2 and 3 were upregulated and tissue inhibitor of MMPs 1 was downregulated [11]. This imbalance
results in the degradation of dermal collagen, elastic fibers and other components of the ECM.
Alterations in Skin Viscoelasticity
Viscoelasticity, also known as anelasticity, describes
materials that exhibit both viscous and elastic characteristics. Viscous materials, like honey, resist shear flow and
strain linearly with time when a stress is applied. Elastic
materials strain instantaneously when stretched and just
as quickly return to their original state once the stress is
removed. Whereas elasticity is usually the result of bond
stretching along crystallographic planes in an ordered
solid, viscoelasticity is the result of the diffusion of atoms
or molecules inside an amorphous material [12].
The dermis is composed of a 3-dimensional network
of collagen and elastic fibers. The ECM of the skin contains two major glycosaminoglycans, dermatan sulfate
and HA (see below) [13]. Dermatan sulfate is tightly
bound to the collagen fiber network, and HA occupies
the space between the fibers. Collagen and elastic fibers
constitute the elastic, the HA forms the viscous compartment of the skin. It has been demonstrated that HA reduces the frictional wear between the collagen fibers [14,
15].
The mechanical response of skin to applied loads involves both a viscous component associated with energy
dissipation and an elastic component associated with energy storage [16, 17]. Dissipation of loads applied to the
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ulate the expression of genes encoding collagens I, III,

IV, V, decorin, elastin, MMPs 1, 2, 3, tenascin and tissue
inhibitors of MMPs 1 and 2 [6]. However, the exact molecular mechanisms of skin atrophy induced by corticosteroids are not yet known. Clinically there are no significant differences between primary and secondary iatrogenic dermatoporosis; however, skin ultrasonography
shows a more significant skin atrophy with a skin thickness between 0.5 and 0.7 mm. Secondary iatrogenic dermatoporosis may occur earlier, and be severer, in patients
susceptible to primary dermatoporosis.

UV-Mediated Effects
Skin aging due to UV irradiation is called photoaging.
In recent years, the exposure of human skin to environmental and artificial UV irradiation has increased dramatically. UVB directly interacts with the DNA of skin
cells. The deleterious effects of UVA are principally due
to the formation of oxygen free radicals, which results in
alterations in nuclear and mitochondrial DNA, but also
in the activation of MMPs [25].
The clinical presentation corresponds to elastosis localized predominantly in the superficial dermis resulting
from the degradation of collagen and elastic fibers by
MMPs. However, a defective synthesis of collagen and
elastic fibers by fibroblasts also contributes to this process [26, 27].
We have recently shown that UVA or UVB irradiation
significantly decreased the content of HA and the expression of its receptor CD44 (see below) in the epidermis of
hairless mice [28].
Dermatoporosis: Features, Mechanisms,
Prevention and Potential Treatments

HA- and CD44-Dependent Growth Factor

Signalization Defect
An important mechanistic feature is the linear, agerelated decrease in HA in human aged skin [29, 30]. HA
is the major component of the ECM [31, 32] and is found
in high quantities in the skin. HA is a nonsulfated linear glycosaminoglycan composed of repeating units of
D -glucuronic acid and N-acetyl-D -glucosamine. In normal skin, HA is synthesized essentially by dermal fibroblasts and epidermal keratinocytes. Because of its negatively charged residues, HA can accommodate many water molecules which help to maintain the normal
hydration and viscoelasticity of the skin (see above) [32].
Several lines of evidence have suggested that many of
the functions of HA are mediated by its cell surface receptor, CD44. CD44 is a polymorphic transmembrane glycoprotein which has multiple isoforms generated by alternative splicing and posttranslational modifications
[33, 34]. In a recent study we have shown that two major
functions of CD44 in the mouse skin are the regulation
of keratinocyte proliferation in response to extracellular
stimuli and the maintenance of local HA homeostasis
[35].
Furthermore, we have shown that CD44 and HA levels
were decreased in the dermatoporotic skin when compared to the skin of young individuals [30] (fig. 6) as well
as those of erbB1 [30].
We thus studied the mechanisms by which epidermal
CD44 deficiency may lead to skin atrophy, and how this
atrophogenic CD44 deficiency could be corrected. Selective suppression of CD44 in mouse keratinocytes leads to
epidermal atrophy [35]. In fact, keratinocytes with CD44
expression loss show a defect in their ability to proliferate
in response to various stimuli in vivo and in vitro [30, 35].
Epidermal CD44 deficiency may result in the absence of
a proliferative response of keratinocytes to heparin-binding epidermal growth factor (HB-EGF) since HB-EGF
interaction with its receptors requires presentation by
heparan sulfate side chains of a specific isoform of CD44,
CD44v3.
Based on the observations indicating the potential role
of HA in epidermal and dermal reconstitution, we topically applied hyaluronate fragments (HAF) of intermediate size (HAFi; 50400 kDa) to mouse skin and observed
an epidermal hyperplasia and an increase in epidermal
and dermal HA content, by stimulating CD44v3 and the
proteins associated with this variant, HB-EGF and its receptor, erbB1, in the keratinocytes [30, 36]. Topical application of HAFi twice a day for 1 month resulted in a significant improvement in the atrophic skin of dermatopoDermatology 2007;215:284294

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skin occurs by molecular and viscous sliding of collagen

fibrils during alignment with the force direction [18],
whereas elastic energy is stored as a result of stretching of
flexible regions in the collagen triple helix. The tensile
strength (stress at break) of the skin depends on the size
and integrity of its collagen network [14]. When the skin
is subjected to stress, the stress load is directly transferred
to the collagen fiber network [19] which may result in the
breakage of the collagen bundles just as in bone fracture.
The extensive response of the skin shows individual
variation and depends on several factors such as the composition of the ECM, the elastin content and the fiber intensity of the collagen network [19]. The decrease in the
collagen fibril viscosity and length associated with an increase in the strain rate reflects a decrease in the viscosity of skin [20]. The fracture pattern of the collagen fibers
can be classified into three main patterns [21]: (1) fracture
occurring in a single plane perpendicular to the fiber
axis, or smooth fracture; (2) fracture starting as a smooth
fracture but resulting in the splitting of the fiber along
the axis, or step fracture; (3) fracture with a split open
end resembling the bristles of a brush, or fibrillation
fracture [22]. These patterns have been found to be extremely characteristic in both collagen [23] and elastoidin
fibers [24] tested at different strain rates.
Therefore we can assume that the decrease in HA with
age (see below) also decreases the viscoelastic properties
of the skin, and a minor trauma may cause a fracture of
the dermis leading to complications such as tearing and
dissecting hematoma.

Fig. 6. CD44 and HA content of dermatoporotic skin. Forearm biopsy specimens of dermatoporosis patients
show a decrease in CD44 (A) and HA (C) amounts in the epidermis and also in the dermis. Note the expression
of CD44 mainly by keratinocytes and the epidermal and superficial dermal presence of HA in normal skin (B,
D). A , B Mouse anti-human CD44 antibodies (Bender MedSystems; 2.5 g/ml). C , D Biotinylated HA binding

protein (Seikagaku Kogyo, Japan; 25 ng/ml).

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topical application of retinaldehyde upregulated the expression of CD44 and HA synthases in mouse skin [42].
Topical application of retinaldehyde and HAFi increased the levels of these molecules in the skin of dermatoporosis patients and corrected the skin atrophy by
showing a synergistic effect at both molecular and clinical levels [Kaya et al., manuscript in preparation].
These observations suggest that the defects in the interaction of CD44 and HA play an important role in dermatoporosis and should be considered as a new target for
the development of novel therapeutic strategies for cutaneous pathologies characterized by skin atrophy and
ECM modifications.

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rosis patients [30]. Small (150 kDa) or large (4001,000

kDa) HAF did not show any proliferative effect on keratinocytes in vitro or in vivo [30].
Topical retinoids have been shown to stimulate epidermal hyperplasia [37]. This effect was linked to the selective induction of HB-EGF in the epidermis [38]. It has
been shown that HA is selectively stimulated by retinoids
in hairless mouse skin [39] and human epidermis in skin
organ culture [40]. Topical treatment of the photodamaged skin with retinoic acid increases the thickness of the
epidermal HA meshwork and its concentration in suction
blister fluid, suggesting that HA is involved in the epidermal change induced by topical retinoic acid therapy in
photodamaged skin [41]. We have recently shown that

Treatment and Prevention

Prevention and therapy of dermatoporosis imply longterm measures because any significant benefit cannot be
obtained within less than several months of intervention,
and any reversal might be maintained only with continuous use of the program.
Due to the harmful and accelerating effects of UV irradiation in dermatoporosis mentioned above, sun exposure should be minimized and protective measures
should be taken.
Emollients can be used for the epidermal barrier disturbance secondary to prolonged topical corticosteroid
application.

Treatment of dermatoporosis requires interventions

that are easy to apply to allow daily use, skin friendly, well
tolerated, cheap and devoid of side effects.
Recent observations suggest that candidates for such
an intervention may include retinoids, as well as size-defined HAF [30]. The role of other compounds such as
antioxidants or hormones may deserve evaluation.
Well-designed randomized clinical trials should be
key in order to demonstrate that dermatoporosis is a syndrome worth recognizing because it may be prevented
and/or reversed. It is hoped that such trials are organized.

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Dermatoporosis: Features, Mechanisms,

Prevention and Potential Treatments

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