Original Article

Cutaneous Manifestations in Egyptian Patients with Chronic

Renal Failure on Regular Hemodialysis
Maha M. Sultan, M.D.*, Hayam H. Mansour, M.D.†, Iman M. Wahby, M.D.‡ and
Ali S. Houdery, M.D.§
*Department of Dermatology and Venereology, †Department of Internal Medicine (Nephrology Unit),
‡Department of Community Medicine, Faculty of Medicine for Girls and §Department of Pathology,
Faculty of Medicine, Al-Azhar University, Egypt.

Background. Hemodialysis patients experience frequent and various cutaneous manifestations of often hypothetical
pathogenesis. Chronic renal failure (CRF) presents with an array of cutaneous manifestations. Objective. To evaluate
the prevalence and nature of cutaneous lesions, associated with CRF patients on hemodialysis in Egyptian patients.
Patients and methods. One hundred patients with CRF on regular hemodialysis from nephrology units were examined
for cutaneous changes. Specific investigations like skin biopsy, culture and sensitivity for bacterial infections, potassium
hydroxide mount and fungal culture were done when indicated. Results. All patients included in this study had at
least one cutaneous manifestation attributable to CRF. The most prevalent findings was pruritus (55%), followed by
xerosis (54%), hyperpigmentation (54%) and pallor (45%). Other cutaneous manifestations were wrinkles (40%),
fungal infections (33%), ecchymosis (27%), dermatitis (23%), yellow face (22%), Petichae (19%), delayed wound
healing (11%), follicular hyperkeratosis (10%), bacterial infections (5%), viral infections (2%) and uremic frost (1%).
Nail changes were koilonychia (39%), half and half nail (28%), splinter hemorrhages (16%), Muehrcke’s lines (12%),
subungual hyperkeratosis (10%), Mees’ lines (8%), brown nail (6%), onycholysis (3%) and Beau’s lines (2%). Hair
changes were brittle and lusterless hair (47%), sparse scalp hair (46%) and sparse body hair (27%). Oral changes
were macroglossia (42%), xerostomia (35%), coated tongue (27%), angular cheilitis (15%), ulcerative stomatitis (9%),
acquired perforating dermatosis (3%). Some rare manifestations of CRF like calciphylaxis (2%) were seen. There
was no association between any particular etiology of CRF and certain mucocutaneous, nail or hair abnormalities.
Conclusion. At least one cutaneous manifestation is found in all CRF patients. The most prevalent findings were
pruritus followed by xerosis and hyper-pigmentation then pallor. With the advent of hemodialysis, the life expectancy of
these patients has increased giving time for more and newer cutaneous changes to manifest. The aetiology of CRF does
not affect the development of cutaneous, nail or hair abnormalities. (J Egypt Women Dermatol Soc 2010; 7: 49 - 55)

Keywords. Chronic renal failure, hemodialysis, cutaneous manifestations, calciphylaxis

T he skin is a mirror for many systemic

diseases including renal diseases1. Chronic
renal failure (CRF) often produces specific
skin changes, which can develop long before failure
manifests clinically2. These symptoms tend to alter and
are aggravated relatively quickly when chronic renal
insufficiency leads to compulsory dialysis treatment3.
There are many reports of cutaneous changes in CRF
from different parts of the world4. The aim of this
study was to elucidate the prevalence and nature of
cutaneous manifestations in Egyptian patients with
CRF on regular hemodialysis.
PATIENTS AND METHODS
One hundred patients of CRF on regular
hemodialysis were selected from Nephrology Units
in Al-Zahraa University Hospital, Al-Aziz Bellah
and Al-Ber wa El-Takwa Hospitals in Cairo. All
patients were subjected to full history and clinical
examination. Complete dermatological examination
including skin, hair, nails and oral mucosa was done.
Complete blood picture, kidney function tests, liver
function tests and fasting and postprandial blood
glucose levels were done. Patients with elevated
liver enzymes were excluded. Specific investigations
like skin biopsy, culture and sensitivity for bacterial
infections, Gram’s stain, potassium hydroxide mount
and fungal culture were done when indicated, after
taking patients’ informed consent.
Statistical Analysis.
Data was analyzed by Statistical Package for
Social Science (SPSS) version 12. Parametric data

Corresponding Author. Maha M. Sultan, M.D., Lecturer of Conflict of interest. None declared.
Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar Copyright © 2009 Egyptian Women Dermatologic Society. All rights
University, Cairo, Egypt. E-mail. dr.maha_derm@yahoo.com reserved.

49
 Cutaneous Manifestations in Egyptian Patients with Chronic 50
Renal Failure on Regular Hemodialysis

was expressed as mean ± SD and non parametric Table 2. Etiology of chronic renal failure.
data was expressed as number and percentage of the
Causes n%
total.
HTN 60 (60%)
RESULTS
DM 14 (14%)
They were 66 males and 34 females. Their age Obstruction 7 (7%)
ranged from 15 - 73 years with mean age of 49.53
+ 18.54 years. The total duration of hemodialysis Analgesic 5 (5%)
ranged from 0.08 - 20 years with a mean of 4.95 + Unknown 4 (4%)
4.03 years (Table 1). The various causes leading to SLE 3 (3%)
renal failure are shown in table (2).
Polycystic kidney 2 (2%)

Table 1. Data of patients. RUTI 2 (2%)

Variables
Reflux 1 (1%)
Sex
- Male 66 (66%) FMF 1 (1%)
- Female 34 (34%) Wegener 1 (1%)
Age HTN: hypertension, DM: diabetes mellitus, FMF: familial
- Range 15 - 73 years mediterranean fever, RUTI: recurrent urinary tract infection, SLE:
- Mean ± SD 49.53 ± 18.54 years systemic lupus erythematosus.
Duration of hemodialysis All patients examined in the study showed at least
- Range 0.08 - 20 years one cutaneous manifestation. The most prevalent
- Mean ± SD 4.95 ± 4.03 years
finding was pruritus (55%) (Figure 1), followed by
Hemoglobin level xerosis (54%), hyper-pigmentation (54%) (Figure
- Range 5.3 - 14 gm % 2) and pallor (45%). Other cutaneous manifestations
- Mean ± SD 10.45 ± 1.64 gm % were wrinkles (40%) (Figure 3), fungal infections
Blood urea before hemodialysis (33%), ecchymosis (27%), dermatitis (23%), yellow
- Range 160 - 350 mg/dL face (22%), petichae (19%), delayed wound healing
- Mean ± SD 253.74 ± 58.38 mg/dL (11%), follicular hyperkeratosis (10%), bacterial
Blood urea during hemodialysis infections (5%), viral infections (2%) and uremic
- Range 60 - 160 mg/dL frost (1%).
- Mean ± SD 109.75 ± 28.88 mg/dL Nail changes were koilonychia (39%) (Figure
Serum creatinine before hemodialysis 4), half and half nail (28%) (Figure 5), splinter
- Range 6 - 22 mg/dL hemorrhages (16%), Muehrcke’s lines (narrow
- Mean ± SD 13.20 ± 5.41 mg/dL white transverse bands occurring in pairs) (12%),
Serum creatinine during hemodialysis Mees’ lines (white transverse bands, single or
- Range 6 - 11 mg/dL multiple) (8%) (Figure 6), subungual hyperkeratosis
- Mean ± SD 18.6 ± 1.63 mg/dL (10%), brown nail (6%), onycholysis (3%) and
Beau’s lines (transverse furrows that begin in the
Table 3. Percentage of cutaneous manifestations in relation to etiology.
Skin HTN DM Obstructive Analgesic FMF Polycystic R UTI Reflux SLE Wegener
Yellow face 16.67 14.29 14.29 40.00 - 100.00 100.00 100.00 33.33 -
Pallor 38.33 28.57 57.14 20.00 - 100.00 50.00 - 33.33 100.00
Hyperpigmentation 61.67 64.29 42.86 40.00 100.00 - 50.00 - 33.33 -
Pruritus 51.67 42.86 28.57 60.00 - - 100.00 - 33.33 -
Xerosis 58.33 71.43 42.86 60.00 100.00 - 50.00 - - 100.00
Dermatitis 25.00 21.43 28.57 - - - - - - -
Wound healing 8.33 7.14 14.29 20.00 100.00 - 50.00 - - -
Uremic frost 1.67 7.14 - - - - - - - -
Follicular hyperkeratosis 10.00 14.29 14.29 40.00 - - - - - -
Echymosis 33.33 50.00 57.14 40.00 - - - - - -
Petichae 18.33 28.57 28.57 40.00 - - - - - 100.00
Jaundice 23.33 28.57 14.29 20.00 - - - - - -
Wrinkles 33.33 35.71 57.14 60.00 100.00 - 50.00 - - -
Bacterial infection 5.00 14.29 - - - - - - - -
TC 6.67 7.14 - - - - - - - -
TP 11.67 7.14 28.57 - - - 50.00 - - 100.00
TV 16.67 21.43 14.29 20.00 - - - - 33.33 100.00
HZ - - 14.29 - - - - - - -
Wart 1.67 - - - - - - - - -
Sparse body hair 21.67 35.71 14.29 20.00 - 50.00 - - - -
Sparse scalp hair 40.00 64.29 14.29 80.00 100.00 50.00 50.00 - 33.33 100.00
Brittle and lusterless hair 43.33 57.14 14.29 80.00 100.00 50.00 50.00 - 33.33 100.00
HTN: hypertension, DM: diabetes mellitus, FMF: familial mediterranean fever, RUTI: recurrent urinary tract infection, SLE: systemic lupus
erythematosus, TC: tinea circinata, TP: tinea pedis, TV: tinea versicolor, HZ: herpes zoster.

J Egypt Women Dermatol Soc. Vol. 7, No. 1, 2010

51 Maha M. Sultan et al.

Table 4. Percentage of nail changes in relation to etiology.

Nail HTN DM Obstructive Analgesic FMF Polycystic R UTI Reflux SLE Wegener

Koilonychia 40.00 35.71 57.14 40.00 100.00 50.00 50.00 - 33.33 -

Half & half 33.33 35.71 28.57 20.00 - - 50.00 - 66.67 -
Splinter hemorrhage 16.67 7.14 14.29 - - - - - - -

Subungual hyperkeratosis 13.33 - 14.29 - - 50.00 - - - -

Muehrcke’s line 10.00 14.29 14.29 - - 50.00 - - - -

Mees’ line 8.33 - - - - - - - - -
Brown nail 6.67 - - 40.00 - - - - - -
Beau’s line 3.33 - - - - - - - - -
Oncholysis 1.67 7.14 14.29 - - - - - - -
HTN: hypertension, DM: diabetes mellitus, FMF: familial mediterranean fever, RUTI: recurrent urinary tract infection, SLE:systemic lupus
erythematosus.

Table 5. Percentage of oral changes in relation to etiology.

Oral HTN DM Obstructive Analgesic FMF Polycystic R UTI Reflux SLE Wegener

Macroglossia 36.67 42.86 28.57 60.00 100.00 50.00 100.00 - - 100.00

Xerostomia 36.67 35.71 57.14 40.00 100.00 50.00 100.00 - 33.33 100.00
Coated tongue 23.33 50.00 28.57 80.00 100.00 - - - - 100.00
Angular cheilitis 18.33 7.14 - 20.00 - - - - - 100.00
Ulcerative stomatitis 11.67 7.14 - - - 50.00 - - - 100.00
HTN: hypertension, DM: diabetes mellitus, FMF: familial mediterranean fever, RUTI: recurrent urinary tract infection, SLE: systemic lupus
erythematosus.

matrix and progress distally as the nail grows)

(2%). Hair changes included brittle and
lusterless hair (47%), sparse scalp hair (46%)
and sparse body hair (27%). Oral changes
included macroglossia (42%), xerostomia
(35%), coated tongue (27%), angular cheilitis
(15%) and ulcerative stomatitis (9%). Some
rare manifestations of CRF like calciphylaxis
was found in 2% (Figures 7,8) and acquired
perforating dermatosis secondary to CRF was
found in 3% of patients (Figure 9).
Biopsies from lesional skin in patients with
CRF with acquired perforating dermatosis
showed broad crater in epidermis with
degenerated collagen in dermis with starting
transepidermal elimination (Figure 10).
Skin, nail and oral manifestations in relation
to causes of CRF are shown in tables 3, 4 and
Figure 2. Diffuse hyperpigmentation of the face.
5 respectively.

Figure 1. Chronic scratching resulting from uremic pruritus. Figure 3. Extensive wrinkling as a sign of actinic elastosis in 42 aged female.

J Egypt Women Dermatol Soc. Vol. 7, No. 1, 2010

 Cutaneous Manifestations in Egyptian Patients with Chronic 52
Renal Failure on Regular Hemodialysis

Figure 4. Koilonychia secondary to chronic renal failure.

Figure (4): Koilonychia secondary to

Figure 7. Calciphylaxis secondary to chronic renal failure.
chronic renal failure.

Figure 5. Half and half nail secondary to chronic renal failure.

Figure (5): Half and half nail secondary to
Figure 8. Calciphylaxis secondary to chronic renal failure, causing loss
of little toe and distal phalanx of the 2 toe. nd

chronic renal failure.

Figure 6. Mees’ line (white transverse band) secondary to chronic Figure 9. Acquired perforating dermatosis (Kyrle’s) secondary to
renal failure. chronic renal failure.

J Egypt Women Dermatol Soc. Vol. 7, No. 1, 2010

53 Maha M. Sultan et al.
Figure 10. Acquired perforating dermatosis. Epidermis shows broad
crater and the dermis shows degenerated collagen with starting
transepidermal elimination (H&E x200).
DISCUSSION
Pruritus was the most common cutaneous
abnormality (55%) in Egyptian CRF patients on
hemodialysis. Its prevalence among hemodialysis
patients ranges from 19 to 90% in the other previous
studies5,7. Udayakumar et al.17 reported pruritus in
53% of indian patients while Avermaete et al.3 reported
pruritus in 48% of patients with CRF. It is one of the
most characteristic and annoying cutaneous symptoms
of CRF6. It is not present in acute renal failure and
does not necessarily subside with dialysis although it
improves with kidney transplantation7. The etiology
of pruritus in CRF is unknown. However, it has been
associated with the degree of renal insufficiency (urine
output of < 500 mL)8. Hypervitaminosis A may be
a cause as CRF patients exhibit increased epidermal
levels of retinol (pre-formed vitamin A). The regular
ingestion of fat-soluble vitamins (i.e. vitamin A) as
replacement for what is lost with dialysis, places
the patient at increased risk for accumulation and
toxicity secondary to impaired excretion9. Another
proposed origin for pruritus in CRF patients is dry
skin. In a study by Kato et al.10 the skin water content
was quantified by using hygrometer, final analysis
concluded that dialysis patients have less water
content in the stratum corneum of their skin. Retention
of middle molecules (molecular weight range 300 -
12.000 daltons) is thought to cause pruritic symptoms
J Egypt Women Dermatol Soc. Vol. 7, No. 1, 2010
in CRF patients. Beta2 microglobulin, advanced
glycosylation end products and parathyroid hormone
are middle molecules that have been evaluated but
their role is still uncertain11. A study by Chou et al.12
examined the effect of parathyroidectomy on uremic
pruritus and found that the best indicator was the
level of calcium and phosphate product (Ca x P). A
higher Ca x P was associated with a greater degree of
pruritus after parathyroidectomy. Neuronal theory is
also considered a probable cause for CRF pruritus.
There is an abnormal pattern of cutaneous innervation
in end stage renal failure and this led to the neurogenic
hypothesis of uremic pruritus. Neuron-specific,
enolase-positive fibres may sprout throughout the
epidermis in uremic patients in contrast to healthy
controls, in whom these nerve endings reached
only the stratum basale. Many patients on dialysis
suffer from peripheral neuropathy and are prone to
nerve damage. Itching may be a manifestation of the
uremic neuropathy13. Another suggested cause of
uremic prutitus is increased serum histamine levels
which may be due to allergic sensitization to various
dialyzer membrane components and due to impaired
renal excretion of histamine. So, UVB radiation
is effective in uremic pruritus by suppressing
histamine-releasing factors in the sera of uremic
patients. Also, it reduces vitamin A levels in the
epidermis. Lastly, other possible causes for pruritus
include increased serum levels of magnesium and
albumin (due to inadequate excretion by the failing
kidneys), iron deficiency anemia which are present
in CRF patients14.
Xerosis was found in 54% of patients in the
present study as observed in previous reports (46-
90%)9,15,16. Xerosis was predominantly seen over
the extensor surfaces of the forearms, legs and
thighs. The abdomen and chest showed fine scaling.
The etiology of xerosis in CRF may be due to
complication of diabetes; a reduction in the size of
eccrine sweat glands may be contributory although
high dose diuretic regimens are also implicated16.
Two types of pigmentary changes were observed
in the present study: hyperpigmentation seen in
54% and a yellowish tinge to the skin (22%). In
the present study, the result of hyperpigmentation
is higher than other studies (20 - 43%)5,6,9,17.
Diffuse hyperpigmentation on sun-exposed areas is
attributed to an increase in melanin in the basal layer
and superficial dermis due to failure of the kidneys
to excrete beta-melanocyte stimulating hormone
(β-MSH)18. A yellowish tinge to the skin has been
reported in 22% in the current study; whereas other
studies reported it in 10 %17 and 40% 5. Yellow tinge
may be due to accumulation of carotenoids and
nitrogenous pigments (urochromes) in the dermis19
or the presence of lipochromes and carotenoids in the
epidermis and subcutaneous tissues20.
Pallor was seen in 45% of patients, which is less
than the result of Udayakumar et al.17 which was
 Cutaneous Manifestations in Egyptian Patients with Chronic
Renal Failure on Regular Hemodialysis
60% in the indian patients. Pallor is due to anemia
which was reported as the hallmark of CRF. Anemia
is primarily the result of inadequate erythropoietin
production by the failing kidneys. Other contributory
factors of anemia in CRF patients include iron
deficiency, folic acid or vitamin B12 deficiency and
decreased erythrocyte survival11.
Skin infections were seen in 40% of patients in this
study, fungal (33%), bacterial (5%) and viral (2%).
Udayakumar et al.17 reported skin infections in 67%
of patients while Bencini et al.8 reported the fungal
infection only in 67% of CRF patients. Skin infections
in CRF patients may be due to associated diabetes
mellitus, low albumin, elevated intracellular calcium,
acidosis21, iron overload17, inhibition of chemotactic
factors and repetitive vascular procedures21. Also,
CRF patient´s host defence response is disrupted by
depressed neutrophil function, leucopenia related
to complement activation, impaired phagocytosis,
diminished T and B lymphocytes function and a
reduction in natural killer cell activity. In addition
to these, the presence of inflammation has been
suggested as a cause for reduced immunity.
Inflammation in hemodialysis patients may be due
to the use of non sterile dialysate, non biocompatible
membranes and evidenced by accumulation of pro-
inflammatory agents5.
Ecchymosis was seen in 27% of hemodialysis
patients and petichae in 19% in the current study. The
causes may be due to defects in primary hemostasis
like increased vascular fragility, abnormal platelet
function and the use of heparin during dialysis22.
Early wrinkles which occurred at the age of 38
- 45 years were seen in 40% of CRF patients of the
present study. It occurs due to early occurrence of
actinic elastoses in patients undergoing long-term
haemodialysis3.
Koilonychia was the most common nail
abnormality (39%) followed by half and half nail
(28%). The results of the present study disagreed
with Amatya et al.1 who found white nail the most
common followed by brown and half and half nail;
while Udayakumar et al.17 and Salem et al.23 found
half and half nail the most common in 21% and 20%
respectively. The highest prevalence of koilonychia
in patients of the present study may be due to the
long duration of the disease as 55% of patients of
the present study were on hemodialysis more than
5 years. In half and half nail, the white appearance
of proximal half of the nail is due to nail bed edema
associated with a dilated capillary while the other
half of the nail bed appears normal21. Salem et al.23,
in an Egyptian study, concluded that the cause of nail
changes in uremic patients undergoing hemodialysis
remained obscure and could not be traced to a
particular abnormality in the renal condition,
medication or the procedure itself.
In the present study, brittle and lusterless hair was
found in 47% of patients, sparse scalp hair was found
54
in 46% and sparse body hair was found in 27% of
CRF patients while, Udayakumar et al.17 found sparse
body hair in 30%, sparse scalp hair in 11% and dry
hair in 16% of CRF patients. This higher incidence
of sparse scalp hair in the Egyptian patients of the
present study in comparison with the Indian patients
of Udayakumar et al.17 study may be due to racial
variation.
Oral mucosal changes have been reported in up
to 90% of patients with CRF24. Teeth marking with
macroglossia (tongue sign of uremia) was seen in
42% of patients compared with Udayakumar et al.17
result which was 35%. This finding was first described
by Mattew et al. in 92% of patients with CRF25.
Xerostomia was found in 35% compared with 31% in
Udayakumar et al.17 study. It was attributed to mouth
breathing and dehydration. Ulcerative stomatitis
was found in 9% which is less than that reported by
Udayakumar et al.17 (29%). The high percentage of
ulcerative stomatitis was attributed to elevated blood
urea levels which were more than 150 mg/100 ml in
their patients and due to bad oral hygiene24. Angular
cheilitis was found in 15% while Udayakumar et al.17
study reported angular cheilitis in 12%. Coated tongue
was found in 27% which is much higher than that
reported by Udayakumar et al.17 (11%). This difference
may be due to associated candidal infection which
may be due to cigarette smoking26 and associated
xerostomia27 which showed high percentage in the
present study.
Perforating disorders such as perforating
folliculitis, Kyrle’s disease and reactive perforating
collagenosis have been described in CRF3. Perforating
disorder of renal disease or acquired perforating
disorders has been used to describe the hyperkeratotic
follicular papules present in these patients. Acquired
perforating disorders was seen in 3% of the present
study patients while other studies showed acquired
perforating disorders in 4.5 – 17% 5,15,17 of patients
on hemodialysis. The exact pathophysiological
mechanism of acquired perforating disorders in CRF
patients is unknown, but it may occur as a result
of dermal connective tissue dysplasia and decay.
Microvascular deposition of calcium may interrupt
blood flow to connective tissue in the dermal layer
causing death and necrosis. Trauma to the skin in
patients with pruritus secondary to CRF could be
the inciting agent in producing these lesions28.
Calciphylaxis was seen in 2% of the patients
in the current study. This result is in concordance
with the international prevalence of calciphylaxis
in end stage renal disease patients which is
1- 4 % 29. It is primarily described in patients
with CRF associated with hemodialysis. It is
characterized by local calcinosis, inflammation and
necrosis. Calciphylaxis results from secondary or
tertiary hyperparathyroidism. Abnormal elevated
level of parathyroid hormone triggers deposition
of crystalline calcium pyrophosphate in the dermis,
J Egypt Women Dermatol Soc. Vol. 7, No. 1, 2010
55 Maha M. Sultan et al.
subcutaneous fat or arterial wall. Calcified vessels
may thrombose acutely, resulting in calciphylaxis30.
Conclusion
At least one cutaneous manifestation is found in
all CRF patients. The most prevalent findings were
pruritus followed by xerosis and hyper-pigmentation
then pallor. With the advent of hemodialysis, the life
expectancy of these patients has increased giving time
for more and newer cutaneous changes to manifest.
The aetiology of CRF does not affect the development
of cutaneous, nail or hair abnormalities.
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