European Journal of Cardiovascular Medicine

Chronic renal failure (CRF) is associated with a complex array of different cutaneous manifestations caused either by disease or treatment. CRF patients may exhibit various cutaneous abnormalities, including changes in skin colour, pruritus, xerosis, hair, nail and oral changes, metastatic calcinosis, and bullous dermatosis [1]. Dermatological manifestations of chronic renal failure divided broadly into cutaneous manifestations of diseases associated with the development of ESRD, cutaneous manifestations of chronic renal failure on dialysis, and dermatological disorders associated with renal transplantation.

Globally, between 8% and 16% of the population were affected by chronic kidney disease (CKD) [2]. Chronic Kidney Disease (CKD) is defined by the presence of kidney damage or decreased kidney function for 3 or more months, irrespective of the cause, CKD is more prevalent in low- and middle-income than in high income nations and contributes to significant mortality and morbidity [3].

About 50–100% of patients with end-stage renal disease have at least one associated cutaneous change [4]. Incidence is lowest in children and highest in elderly and slightly higher in males than females [5]. Nunley [6] reported 50 – 100% patients have at least one dermatological disorder. It has been proposed that many cutaneous disorders experienced by patients undergoing dialysis have little to do with uremic syndrome and are related to the underlying pathologic process that induced the renal disease. On the contrary others proposed that changes in skin histology were related to the severity and duration of the renal failure and less with underlying etiology [7,8].

Patients' quality of life may reduce due to these cutaneous manifestations and even they may go into financial and family pressures due to repeated hemodialysis and add on infections. Early diagnosis of cutaneous manifestations, its management will help to reduce the economic burden to patients, alleviate the symptoms and decrease the morbidity. On the basis of this we did a study by aiming to know about the dermatological manifestations of chronic renal failure patients undergoing hemodialysis.

Globally, between 8% and 16% of the population were affected by chronic kidney disease (CKD) [2]. Chronic Kidney Disease (CKD) is defined by the presence of kidney damage or decreased kidney function for 3 or more months, irrespective of the cause, CKD is more prevalent in low- and middle-income than in high income nations and contributes to significant mortality and morbidity [3].

About 50–100% of patients with end-stage renal disease have at least one associated cutaneous change [4]. Incidence is lowest in children and highest in elderly and slightly higher in males than females [5]. Nunley [6] reported 50 – 100% patients have at least one dermatological disorder. It has been proposed that many cutaneous disorders experienced by patients undergoing dialysis have little to do with uremic syndrome and are related to the underlying pathologic process that induced the renal disease. On the contrary others proposed that changes in skin histology were related to the severity and duration of the renal failure and less with underlying etiology [7,8].

Patients' quality of life may reduce due to these cutaneous manifestations and even they may go into financial and family pressures due to repeated hemodialysis and add on infections. Early diagnosis of cutaneous manifestations, its management will help to reduce the economic burden to patients, alleviate the symptoms and decrease the morbidity. On the basis of this we did a study by aiming to know about the dermatological manifestations of chronic renal failure patients undergoing hemodialysis.

A Descriptive cross sectional study was conducted on patients diagnosed to have chronic renal failure on haemodialysis at Siddhartha Medical College, Vijayawada, Andhra Pradesh. A total of 100 patients attended nephrology and dermatology OPD with cutaneous manifestations were included in this study during the period of 18 months (December 2011 to May 2013). Ethical committee approved this study. Informed consent was taken from all the patients included in this study.

Inclusion Criteria:

Patients of all ages and both sexes were included in the study.

Exclusion Criteria:

Patients with acute renal failure.

Patients with chronic renal failure who had undergone renal transplantation.

Patients with chronic renal failure not undergoing dialysis.

Procedure: Details pertaining to patients such as history, presenting manifestations, relevant past history and examination findings were recorded in a pre-structured proforma. Clinical photographs were taken at the same sitting.

Patients were advised to undergo investigations required such as CBC, CUE, renal function tests, glucose, viral screenings, electrolytes and other relevant tests. If required special investigations including tzanck smear, wet mount preparations from scraping and microscopy, nail clippings and skin scrapings for 10% KOH, fungal culture, skin biopsy for histopathology, pus for culture and sensitivity whenever required were done.

Data Collection: The data required for this study was entered into a spread excel sheet. Data was analysed and tabulated. All descriptive quantitative variables were expressed as numbers and percentages.

Out of 100 cases studied 63 (63%) were males and 37 (37%) were females.  The age group of patients studied ranged from 14 to 70 years. Maximum the number of patients in the study belonged to the age group of 41-60 years and the least number of patients belonged to an age less than 20 years (Table 1).

Table: 1 Age group and sex distribution of study patients

Dermatological Manifestations:

The most common manifestation in our study was xerosis in 55 patients followed by nail changes in 52 patients, pruritus in 43 patients, hyperpigmentation in 40 patients,  pallor in 32 patients,  cutaneous infections in 23 patients, mucosal changes in 15 patients, diffuse alopecia in 15 patients, perforating dermatosis in 3 patients, calcinosis cutis in 2 patients and miscellaneous 21 patients (Table 2).

Table: 2 Distribution of dermatological manifestations in relation to sex of patients

Xerosis was the most common findings in our study observed in 55 patients, out of which 40 patients had generalized xerosis. It was confined to upper limbs in 6 patients, lower limbs in 6 patients and face in 3 patients. Pruritus was documented in 43 patients, generalized in 28 patients and localized in 15 patients. Diffuse hyperpigmentation was observed in 40 patients in our study. Pigmented macules seen in palms and soles in 3 patients. Three patients were diagnosed clinically as perforating dermatosis. On histopathology features of kyrle’s disease were seen in 3 patients.

Nail Changes: Nail changes were observed in 52 patients in our study, which include dystrophy of nails in 18 patients, leuconychia in 10 patients, onychomycosis in 12 patients, discoloration of nails in 9 patients and half and half nails in 3 patients. The changes are presented in Fig1.

Fig 1. Types of nail changes observed in the study

Mucosal Changes: Mucosal changes were observed in 15 patients, which include tooth decay 5 patients, bald tongue in 4 patients, oral candidiasis in 4 patients, geographic tongue in 1 patient, black hairy tongue in 1 patient. The results are presented in Fig 2..

Fig 2. Types of mucosal changes observed in the study

Cutaneous Infections: Cutaneous infections in CRF were observed in 23 patients. The fungal infections seen in 10 patients include dermatophytosis in 8 patients and intertrigo in 2 patients. The bacterial infections seen in 11 patients include folliculitis in 9 patients, furunculosis in 2 patients and the viral infections include verruca vulgaris in 1 patient, herpes zoster in 1 patient. The results are presented in Fig-3.

Fig 3 Types of cutaneous infections in CRF patients on haemodialysis

 Miscellaneous Cutaneous Manifestations: Other associated cutaneous findings include dermatosis papulosa nigra,  vitiligo, acne vulgaris, acrochordons, lichen simplex chronicus,, keratolysis exfoliativa, leucoderma, nonpalpable purpura, arteriovenous fistula dermatitis (Table 3).

Table-3. Miscellaneous cutaneous manifestations in CRF patients on haemodialysis

Chronic renal failure is defined as the irreversible, substantial and usually long standing loss of renal function, glomerular filtration rate < 60 ml/m². Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and progressive decline in glomerular filtration rate greater than three months. End stage renal disease ( ESRD) represents a clinical state in which there has been irreversible loss of endogenous renal function of a degree sufficient to render a patient permanently dependent on renal replacement therapy either dialysis or renal transplantation in order to avoid life threatening uremia.

Cutaneous  manifestations  in  patients  with  chronic  renal  failure  on  haemodialysis  were  studied   in  100   patients. This  is  comparable  to other  studies  including  the  study  conducted  by  Uday kumar  et  al [9]   and  Pico  et  al [11]  who  had  documented  cutaneous  disorders  in  all  the  patients  (100% )  in  the   study. Hajheydari  et  al [12]  had  94.1%  patients  suffering  from  cutaneous  manifestations  due  to CRF.

Eighty-two per cent patients complained of some skin problem. However, on examination, all patients had at least one skin lesion attributable to CRF. The most prevalent finding was xerosis (79%), followed by pallor (60%), pruritus (53%) and cutaneous pigmentation (43%). Other cutaneous manifestations included Kyrle's disease (21%); fungal (30%), bacterial (13%) and viral (12%) infections; uremic frost (3%); purpura (9%); gynecomastia (1%); and dermatitis (2%). The nail changes included half and half nail (21%), koilonychia (18%), onychomycosis (19%), subungual hyperkeratosis (12%), onycholysis (10%), splinter hemorrhages (5%), Mees' lines (7%), Muehrcke's lines (5%) and Beau's lines (2%). Hair changes included sparse body hair (30%), sparse scalp hair (11%) and brittle and lusterless hair (16%). Oral changes included macroglossia with teeth markings (35%), xerostomia (31%), ulcerative stomatitis (29%), angular cheilitis (12%) and uremic breath (8%). Some rare manifestations of CRF like uremic frost, gynecomastia and pseudo-Kaposi's sarcoma were also observed [9].

One hundred and forty-three patients were evaluated. Among them, there were 113 male and 30 females. The mean age of these patients was 43.8 ± 13.0 yrs (14–70). Among the skin changes, pruritus accounted for 56%, Xerosis was observed in 52%, Diffuse blackish hyper pigmentation was seen in 40%. Skin infections were seen in 53% of patients, of these fungal, bacterial and viral infections were 27.2%, 14.6%, and 11.2%, respectively. Kyrle’s disease was observed only in 6.9%. Other skin manifestations include eczema 4.8%, psoriasis 2.7%, and drug rash 2.1%. Nail changes were observed in 46 patients of whom 27 patients had onychomycosis. Other changes include discoloration, onycholysis, and splinter hemorrhages. Hair changes were observed in 21.7%. Mucosal changes were seen in 27.3% [10].

Xerosis  was  the  most  common  finding  in  the  present  study  documented  in  55%  of  patients. Tawade   et al [13]  reported an incidence of 46%  xerosis.  Gurucharan  et  al [14] reported  xerosis  in  90%  and  Hajheydari  et  al [12]  had  reported  in  22.8%  patients  to  have  xerosis  in their  study. Significant xerosis has been reported in 50 to 75% of the dialysis population [15].

Pruritus was documented in 43% of patients in the present study. Pico  et  al [11]  has  recorded  pruritus   in  42%,  and  Hajheydari  et  al [12] found  38.6%  to  have  pruritus.

Diffuse  hyperpigmentation  was  noted  in  40%  of  patients  in  the  present  study. Pico  et  al [11]  has  reported  diffuse  pigmentation  70%,  Uday kumar  et  al [9]  in 43%,  Dyachenko  et  al [16] in   75.7%,  Hajheydari  et  al [12]  in  66.3%  and   36 %   in  the  present study. Pigmentary alteration occurs in 20 to 70% of the dialysis population [17]. Pico et al [11] reported that 70% of dialysis patients manifested with cutaneous pigmentary changes.

Pallor  was  reported  in  32 %  of  patients  in  the  present  study. Dyachenko  et  al [16] has  reported  pallor  in  75.7 %   and  Udaykumar  et  al [9]  has  found  60%  incidence  of  pallor  which  is  significantly  higher  compared  to  present study. The  cause  of  anemia  may  be  decreased  erythropoietin  production  by  the  diseased  kidney  or  malnutrition  or  anemia  of  chronic   disease. Acquired  Perforating  Dermatosis  was   found  in  3%  of  patients  in  the  present  study. Hood  et  al [18]  has  reported  4.5 %  and  Morton CA  et  al [19]  has  reported  10%  incidence of  Acquired  Perforating  Dermatoses  in  CRF  patients  who  underwent  dialysis. Acquired perforating dermatoses has become a well recognized association of chronic renal failure, where the underlying cause is diabetic nephropathy and in patients undergoing hemodialysis [20]. An Indian study reported an incidence of 17% and all of them who are diabetics [16]. In North America the reported incidence of acquired perforating disorders varies from 4.5 to 10%. A similar incidence of 11% reported in Britain [19].

The  incidence  of  nail  changes  in  the  present  study  was  52%.  The most common nail change was nail dystrophy (18%), followed by Onychomycosis (12%). Leuconychia  (10%), Half & Half nails characteristic  of  CRF  patients  on  haemodialysis  was  found  in  3%  of   patients  only. Altmeyer  et  al [21] has  reported  nail  disorders  in  71.4%  uremic  patients.  The  reported  incidence  of  nail  disorders  in  published literature  ranges  from  52%  to  71%  and is comparable to present study.  Dyanchenko  et  al [16] has  reported  half  &  half  nails  in  18.6%  patients. Nail disorders have been reported to occur in approximately 71.4% of uremic patients [21] The most common disorder being half and half nails, absent lunula and splinter hemorrhages [22]. In half and half nails the proximal half is white and the distal half is brown.

Mucosal  changes  were  found  to be present  in  15%  of  patients  in  the  present  study  and it  included   bald  tongue,  geographic  tongue,  oral candidiasis  etc.  Hajheydari et al [12]  has reported 23.8%  incidence  of   mucosal  changes. Oral mucosal changes have been reported in 90% of patients with chronic renal failure [23].

Cutaneous  infections  occurred  in  23%   of   patients  in  the  present  study,  with  10%  fungal,  11%  bacterial  and   2%  viral  infections. . Bencini et al have reported the incidence of fungal infection in patients undergoing hemodialysis to be 67% [24]. Tinea pedis, tinea corporis and pityriasis versicolor are also reported to be common. CRF patients have impaired cellular immunity due to decreased T lymphocyte count this could explain incidence of fungal infections. The most common viral infections include warts, herpes simplex and herpes zoster.

 Miscellaneous  cutaneous  findings  found  in  21%  of  patients  included  Dermatoses  Papulosa  Nigra,  Acrochordons,  Acne,  Keratolysis  Exfoliativa, Vitiligo,  Arteriovenous (AV)  Fistula  Dermatitis,  Non  Palpable  Purpura,  And  secondary Leucoderma. A.V  fistula  dermatitis  was  an  iatrogenic  skin  manifestation  found  at  the  site  of  A.V fistula  which  was  created  for  haemodialysis.   None  of  our  patients  had  other  rare  manifestations  of  CRF  like  Uremic  Frost,  Bullous Dermatoses,  Nephrogenic  Systemic  Fibrosis  and  Gynecomastia [Table 4].

Table 4. Comparison of Cutaneous Findings between Present Study and Other Published Studies.

A comparison of cutaneous findings between the present study and other published studies is presented in the tabular form. The incidence of various cutaneous findings is widely variable from one study to another. The incidence of xerosis ranged from 52% to 79% and it was 55% in the present study. The incidence of pruritis ranged from 43% to 53% and it is 43% in the present study. The incidence of diffuse hyperpigmentation varied from 32% to 43% and it was 40% in the present study. The incidence of nail changes and mucosal changes in the present study are comparable to other studies, whereas incidence of pallor, perforating dermatosis and infections are less in the present study when compared to others.

Dermatological manifestations most commonly observed in CRF patients on hemodialysis were xerosis, nail changes, pruritus, pallor, diffuse hyperpigmentation, infections, mucosal changes, and perforating dermatosis. Early and accurate recognition and management of dermatological manifestations under the supervision of a nephrologist and dermatologist can help to reduce morbidity and mortality.

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