Nephrol Dial Transplant (2004) 19: 2709–2712

doi:10.1093/ndt/gfh480
Advance Access publication 24 August 2004

Hypothesis

Uraemic xerosis

Jacek C. Szepietowski1, Adam Reich1 and Robert A. Schwartz2

1
Department of Dermatology, Venereology and Allergology, University of Medicine, Wroclaw, Poland and
2
Department of Dermatology, New Jersey Medical School, New Jersey, USA

Keywords: emollients; haemodialysis;
uraemic pruritus; uraemic xerosis
Introduction
Xerosis (rough and scaly skin) is a common chronic
dermatological complication among patients under-
going maintenance renal dialysis (MRD) [1–3].
Although uraemic xerosis can also be observed in
subjects with chronic renal failure before dialysis is
needed, a significant increase in frequency of xerosis
is observed when patients initiate dialysis. Further-
more, in the majority of cases, it typically disappears
after renal transplantation. Interestingly, it is classically
absent in acute renal failure, and is not correlated with
the plasma urea level.
Uraemic xerosis was suggested to be an important
factor influencing uraemic pruritus [1,3,4]. Based on
large published series, xerosis of moderate to severe
intensity leads to a 50–100% increase in uraemic
pruritus [3,5,6]. Moreover, some investigators postu-
lated that the uraemic pruritus level is directly related
to xerosis severity; the more intense the xerosis, the
greater the amount of pruritus [3,6,7]. However, other
studies did not find such a relationship when using
objective measures of skin dryness [8,9]. Therefore, it
seems that even if uraemic xerosis is not the primary
cause of pruritus, it might be that in the presence of
pruritus, uraemic xerosis will have a worsening effect
by reducing the threshold for itch [4].
xerosis among MRD patients ranged between 50 and
85% of the evaluated patients [3,5,7], whereas 30–40%
of patients reported this symptom before starting
dialysis [5,10]. In a number of large series, including
our own [3], the intensity of xerosis has been described
as mild in 30–40%, moderate in 35–50% and severe
in 15–30% of the MRD patients [3,5]. Uraemic xerosis
was found in a higher proportion in patients under-
going peritoneal dialysis than in those undergoing
haemodialysis [5].
For the calculation of the prevalence of uraemic
xerosis in the European Community, the most reliable
sources have been used, resulting in an MRD prev-
alence of 5.21:10 000. The proportion of uraemic
xerosis in the dialysis population has been evaluated
in eight published clinical series, comprising a total of
565 MRD patients (Table 1) [3,5,7–12]. Among this
population, 424 patients suffered from mild to severe
xerosis, representing an overall proportion of 75%
[95% confidence interval (CI) 71.4–78.6%] of MRD
patients. By applying this proportion of patients with
uraemic xerosis to the overall prevalence of MRD
patients, an estimated prevalence of 3.91:10 000 (95%
CI 3.72–4.10) can be deduced, resulting in an estima-
tion of 148 000 patients (95% CI 140 500–155 000)
with uraemic xerosis in the European Community by
the end of 2000. The progression rate of MRD in
Europe was 4.0% per year between 1995 and 2000,
Table 1. Frequency of patients with uremic xerosis in the clinical
series reported in the medical literature

Reference Total no. No of patients

of patients with uraemic
Frequency of uraemic xerosis xerosis (%)

Up until now, uraemic xerosis has been poorly Young et al., 1973 [7] 36 29 (80.5%)
documented in the medical literature, although clearly Gilchrest et al., 1980 [11] 27 16 (59.3%)
recognized by practitioners. The reported frequency of Nielsen et al., 1980 [10] 74 45 (60.8%)
Southi and Commens, 1987 [12] 40 30 (75.0%)
Stahle-Bäckdahl, 1989 [8] 29 27 (93.1%)
Balaskas et al., 1992 [5] 189 136 (72.0%)
Correspondence and offprint requests to: Professor Jacek C. Yosipovitch et al., 1995 [9] 40 31 (77.5%)
Szepietowski, MD, PhD, Department of Dermatology, Venereology Szepietowski et al., 2002 [3] 130 110 (84.5%)
and Allergology, University of Medicine, Ul. Chalubinskiego 1, Total 565 424 (75.0%)
50-368 Wroclaw, Poland. Email. jszepiet@derm.am.wroc.pl

Nephrol Dial Transplant Vol. 19 No. 11 ß ERA–EDTA 2004; all rights reserved
2710
whereas the annual growth of the population was 1%.
Based on these progression rates (4% annual growth
for MRD, 1% annual growth for the European popula-
tion), a prevalence of 4.27:10 000 patients (95% CI
4.06–4.48) can be estimated, resulting in a number
of patients with uraemic xerosis of 166 000 by the
end of 2003.
Clinical manifestation
We do believe that uraemic xerosis may be regarded
as a syndrome, gathering several characteristics accord-
ing to topography and the presence of other related
signs (e.g. turgor of the skin, pruritus). It is a chronic
condition that does not tend to resolve spontaneously,
although some limited seasonal variations still exist.
Moreover, unlike common xeroses which prevail on
the exterior surface of the lower limbs and commonly
are of mild severity, it has a widespread distribu-
tion with marked involvement of the legs, back, chest
and hands (Figures 1 and 2). Age is an aggravating
factor. In some patients, uraemic xerosis is associated
with poor wound healing [13]. Dry sky in uraemic
xerosis is usually associated with signs (skin turgor,
elastosis) indicating deeper alterations of the cutaneous
structures underlying the epidermis (increased skin
extensibility, dermal elastin fragmentation, atrophy
of sweat glands and sebaceous glands), which could
signify full-thickness skin dehydration [14].
The negative influence of climate and environ-
mental factors (wind, cold, low humidity) is reported
frequently. Associated signs are premature skin ageing
(elastosis) and pruritus [1,15]. Uraemic xerosis seems
also to be linked with diminished sweating [9,16], and
atrophy of sebaceous glands and of the secretory
and ductal portion of sweat glands [17,18]. A decrease
in the number of sweat glands has also been noted.
Objective measurements of xerosis in MRD patients
have been attempted, using non-invasive instrumental
techniques in vivo. The instrumental findings of water
content (corneometry) and barrier function (transepi-
dermal water loss) of the stratum corneum have been
equivocal, and did not show a clear and consensual
Fig. 1. Uraemic xerosis of moderate severity: clearly visible
desquamation of the lower extremity skin; single erosions caused
by scratching due to uraemic pruritus.
J. C. Szepietowski, A. Reich and R. A. Schwartz
Fig. 2. Severe uraemic xerosis: intense scaling with some fissures.
correlation between the clinical severity of xerosis
and these measurements [5,10,11,19]. However, xerosis
associated with low hydration of the stratum corneum
was evidenced in a great majority of patients [20].
Histologically, microangiopathy is a significant finding
in the skin of haemodialysis patients, associated with
mast cell infiltration, fragmentation of elastin, hyper-
pigmentation, hyperkeratosis and epidermal atrophy
[11]. Conversely, biopsy specimens of xerotic skin in
patients undergoing peritoneal dialysis do not show
microangiopathy. Uraemic xerosis is thus a promi-
nent feature in MRD patients that can be distinguished
from the symptom that occurs in physiological condi-
tions (e.g. dry skin of mild severity in winter) or
pathological conditions (e.g. atopic xerosis, associated
with a specific skin inflammation).
Psychological impact of uraemic xerosis
Uraemic xerosis may lead to discomfort and negative
psychological implications. In a recent survey, the
effect of uraemic xerosis of moderate to severe inten-
sity on quality of life was investigated in a group of
99 MRD patients (P. Dupuy, personal communica-
tion). The mean DLQI score was significantly higher
compared with the scores previously obtained in the
normal population. The SF-12 scores were also signifi-
cantly enhanced in both physical and mental compo-
nents. Moreover, resolution of uraemic xerosis by
treatment with moisturizing emollient was associated
with a significant improvement in patient life quality.
These data clearly emphasize that uraemic xerosis
has a significant psychosocial impact that appears to
be largely underestimated in clinical practice.
Pathogenesis of uraemic xerosis
The cause of uraemic xerosis in MRD patients
remains unclear. Multiple factors could contribute
towards the rough and scaly skin appearance of
MRD patients, including skin dehydration and
reduced sebum and sweat excretion [21]. Uraemic xero-
sis appears to be the result of systemic and/or local
factors. Typically, it associates three main events,
varying with causal elements, such as cutaneous
Uraemic xerosis
dehydration, altered barrier function and marked
irritancy to external substances such as surfactants.
Water depletion in the dermis, caused by a fluid
shift during a single dialysis session, has been proposed
as an explanation for uraemic xerosis. Skin perfusion
has also been demonstrated to be impaired in MRD
patients, which may contribute to the skin dehydra-
tion process [21]. Atrophy of sebaceous glands as well
as the secretory and ductal portions of the eccrine
sweat glands, resulting in lower levels of surface lipids
of the skin and loss of integrity of the water content
in the stratum corneum by skin barrier dysfunction,
may also be important in the pathogenesis of uraemic
xerosis [18]. Observations made among patients
with atopic dermatitis could support the role of lipid
abnormalities as a causal factor for uraemic xerosis.
Sator et al. [22] clearly demonstrated that the dry
skin of patients with atopic dermatitis is due not only
to a decrease in skin moisture but also to a reduction
of skin lipids. Moreover, the effectiveness of emollients
in improving uraemic xerosis can also indirectly con-
firm the theory of lipid depletion in skin as a reason
for xerosis in MRD patients [23].
Another possible explanation is an alteration in
the metabolism of vitamin A, which is present in
increased concentration in uraemic patients [24].
Xerotic skin of the hypervitaminosis A syndrome
resembles the cutaneous lesions of xerotic patients
subjected to dialysis. Other potential factors include
thyroid underactivity and skin inflammation pro-
voked by an increased number of cutaneous mast
cells releasing histamine [25]. The possible explana-
tion for skin dryness in MRD patients can also be
disturbances of the pH in the stratum corneum. Elias
et al. [26] indicated the pH level as one of the pos-
sible factors which regulate the cohesion/desquamation
process in patients suffering from recessive X-linked
ichtyosis. The increase of skin surface pH may activate
different proteases, which mediate desquamation in
the outer layer of the stratum corneum. It was shown
that stratum corneum pH is elevated in MRD patients
[9], which could lead to disturbance in activation of
proteases and, as a consequence, to damage of the
skin barrier in MRD patients. Although some data
are currently available, further investigations on this
phenomenon are needed.
Uraemic xerosis and uraemic pruritus
In dialysis subjects, the higher frequency of pruritus
in severely xerotic areas leads one to consider the latter
as an important factor. In a series of 72 MRD patients,
pruritus of the legs was observed in only 16% of
the cases without xerosis, and in 29% of the cases
with moderate to severe xerosis. Thus, moderate to
severe xerosis of the legs was overrepresented among
the pruritic population, compared with the non pru-
ritic population [6]. Moreover, pruritic patients in
both the haemodialysis and peritoneal dialysis group
had significantly reduced stratum corneum hydration
2711
compared with non-pruritic patients [6]. Similarly, in
a large series of 189 MRD patients, pruritus was
present in 39% of the cases with no xerosis, and in 77%
of the cases with moderate to severe pruritus [5]. In
our series of 130 patients, pruritus was experienced in
significantly more patients with severe xerosis (34%)
than in those without xerosis (21%) [3]. These findings
suggest a direct clinical relationship between uraemic
xerosis and uraemic pruritus.
Treatment of uraemic xerosis
In MRD patients, the skin appears rough, stiff, frag-
ile and inelastic in large areas of the cutaneous
surface, which, together with pruritus, facilitates the
development of lichenification and in some prurigo
nodularis [7]. Severe involvement of certain areas, such
as the hands and feet, leads to greater discomfort
and possible functional impairment. Because the cuta-
neous barrier function is reduced, the skin is more
easily exposed to external insults by physical factors
such as wind, cold, sun and reduced air humidity.
As in some other severe xerotic conditions, a greater
susceptibility to irritation caused by chemical irri-
tants such as soaps and detergents may be observed.
Therefore, patients should be advised to avoid frequent
hand washing and bathing in order to limit cumula-
tive soap-induced irritation [27]. Clothing should be
of natural fabrics, such as cotton.
Because the pathogenesis of uraemic xerosis is
unknown, no specific therapy has been tailored for
it. Moisturizing emollients are used daily by many
people to improve subjective and objective symptoms
of common xeroses. When properly used, emollients
reduce scaling and overall patient discomfort and
improve quality of life. The beneficial effects of emol-
lients on xerosis in MRD patients have also been clearly
recognized by practitioners. Recently our group has
observed a significant reduction of uraemic xerosis
in haemodialysis patients after a 3 week applica-
tion of a cream containing structured lamellar lipids
and endocannabinoids: N-acetylethanolamine and
N-palmitoylethanolamine. This was also clearly asso-
ciated with a lowering of pruritus intensity (J. C.
Szepietowski et al., unpublished data). Although the
exact mechanism in which endocannabinoids could
modify pruritus is not known, there are several
possibilities. They have been demonstrated to down-
modulate mast cell degranulation induced either by
neurogenic (substance P) or immune-mediated stimuli,
both in vitro and in vivo [28]. They also exert a potent
inhibitory effect on cytokine (interleukins-4, -6 and -8)
release from macrophages and peripheral blood
mononuclear cells, and decrease the levels of tumour
necrosis factor-a (TNF-a) during inflammation [29].
Moreover, in the rat paw formalin-induced pain test,
endocannabinoids were able to activate an analgesic
response [30].
A reduction of uraemic pruritus was also documen-
ted after oil bath therapy [23]. It was postulated that
2712
emollient therapy acts on uraemic pruritus mainly by
a direct effect on uraemic xerosis.
Conclusions
Uraemic xerosis may produce significant discomfort
in some patients. In particular, it may provoke or
exacerbate the bothersome symptom of pruritus, and
be at least in part the cause of cutaneous complica-
tions including lichen simplex chronicus, prurigo
nodularis and the secondary complication of impetigo
[1]. Emollients should be used in MRD patients
affected by xerosis with or without pruritus, either
alone or in association with more specific anti-pruritic
treatments.
Acknowledgements. The authors are grateful to Professor Dr
Marian Klinger, the head of the Department of Nephrology and
Transplantation Medicine in Wroclaw, Poland for his help in
obtaining clinical pictures of the xerotic skin of patients on
maintenance haemodialysis.
Conflict of interest statement. None declared.
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Received for publication: 19.5.04
Accepted in revised form: 26.7.04