|Year : 2014 | Volume
| Issue : 1 | Page : 27-35
Prevalence of cutaneous manifestations in chronic renal failure patients on regular hemodialysis: a hospital-based study
Eman M Sanad1, Neveen E Sorour1, Wael M Saudi2, Afaf M Elmasry3
1 Dermatology and Venereology Department, Faculty of Medicine, Benha University, Benha, Ethiopia
2 Department of Dermatology and Venereology, Misr University for Science and Technology, 6th October city, Ethiopia
3 El Mahalla Elkobra town, Ethiopia
|Date of Submission||01-Mar-2014|
|Date of Acceptance||16-Mar-2014|
|Date of Web Publication||24-Jul-2014|
Neveen E Sorour
MD, Dermatology and Venereology Department, Faculty of Medicine, Benha University, Benha
Source of Support: None, Conflict of Interest: None
Chronic renal failure (CRF) presents with an array of cutaneous manifestations. Newer changes are being described since the advent of hemodialysis (HD), which prolongs life expectancy, providing time for these changes to manifest.
The aim of this study was to estimate the prevalence and pattern of cutaneous manifestations among patients with CRF on regular HD.
Patients and methods
This case-series study included 100 patients with CRF on regular HD. They were subjected to a full assessment of history, and general and dermatological examinations of the skin, hair, nails, and oral mucosa.
All patients included in this study had at least one cutaneous manifestation attributed to CRF. The most prevalent finding was xerosis (72%), followed by pruritus (52%) and hyperpigmentation (44%), whereas purpura (2%) and bullous dermatosis (1%) were the least detected. Oral changes included xerostomia (46%), macroglossia with teeth markings (43%), fissured tongue (17%), ulcerative stomatitis (11%), and angular cheilitis (6%). The most common nail changes were absent lunula (61%), half and half nail (41%), and koilonychia (29%). Hair changes included sparse scalp hair (48%), sparse body hair (41%), and brittle and lusterless hair (39%). Hypertension and diabetes mellitus were the most common causes of CRF (53 and 18%, respectively).
Every CRF patient on HD had at least one cutaneous manifestation, which may appear before or after HD. The most common cutaneous manifestations were xerosis, pruritus, hyperpigmentation, xerostomia, macroglossia, absent lunula, half and half nail, sparse scalp hair, and sparse body hair.
Keywords: Chronic renal failure, cutaneous manifestations, hemodialysis
|How to cite this article:|
Sanad EM, Sorour NE, Saudi WM, Elmasry AM. Prevalence of cutaneous manifestations in chronic renal failure patients on regular hemodialysis: a hospital-based study. Egypt J Dermatol Venerol 2014;34:27-35
|How to cite this URL:|
Sanad EM, Sorour NE, Saudi WM, Elmasry AM. Prevalence of cutaneous manifestations in chronic renal failure patients on regular hemodialysis: a hospital-based study. Egypt J Dermatol Venerol [serial online] 2014 [cited 2017 Aug 18];34:27-35. Available from: http://www.ejdv.eg.net/text.asp?2014/34/1/27/137278
| Introduction|| |
Symptoms and signs in the skin and mucous membranes can be supportive of the diagnosis of internal disease or may even be a part of the initial presentation. Chronic renal failure (CRF), irrespective of its cause, often produces specific skin changes that can develop long before failure manifests clinically . It has been found that 50-100% patients with end-stage renal disease have at least one associated cutaneous change . Hemodialysis (HD) is one of the therapeutic modalities that can improve the survival in these patients . Skin changes can precede or follow the initiation of HD treatment, and there are more chances of developing newer skin changes during the course of HD therapy . Some of these cutaneous disorders disappear following kidney transplantation, confirming that the metabolic milieu resulting from the malfunctioning kidney is responsible for some of these changes . Although the majority of dermatological disorders in chronic kidney disease (CKD) are relatively benign, a few rare skin diseases have the potential to cause serious morbidity and mortality. Early recognition of these severe skin disorders and prompt initiation of treatment can markedly alter their course and even save a patient's life . The present study was designed to analyze the prevalence and pattern of cutaneous manifestations among patients with CRF on regular HD and correlates their onset to HD.
| Patients and methods|| |
This case-series study included 100 patients with CRF on regular HD. They were recruited from the HD center of Benha University Hospital in the period from March 2011 to January 2012. Informed consent was obtained from each patient after approval from research ethics committee of the Faculty of Medicine in Benha University before the study. Inclusion criteria included patients with CRF on regular HD (three times weekly) with dialysis duration of 5 months or more and age ranging from 15 to 65 years. Exclusion criteria included patients who had undergone HD following renal transplant, patients who had undergone peritoneal dialysis, and patients with other systemic or cutaneous diseases. All patients were subjected to a complete assessment of history, with a special focus on the onset of cutaneous manifestations and their relation to HD and the etiology of CRF. Thorough general and dermatological examinations were performed including skin, hair, nail, and oral mucosa. Photos of lesions were taken using a Sony Cybershot 14.1 mega pixels camera (Sony Corp. Japan). Blood samples were obtained to investigate the complete blood count, fasting and postprandial blood glucose levels, liver function tests [serum glutamic pyruvic transaminase (SGPT) serum glutamic oxaloacetic transaminase (SGOT)], and for kidney function tests (serum urea and creatinine). Serum urea and creatinine levels were compared with their before dialysis levels (obtained from the patient's files).
The data collected were analyzed using the statistical package for social sciences (version 16; SPSS Inc., Chicago, Illinois, USA). Quantitative data were analyzed using mean and SD, whereas frequency and percentage were used to describe qualitative data. The Z-test and χ2 -test were used to compare frequencies. A P value of less than 0.05 was considered statistically significant and values less than 0.001 were considered highly statistically significant.
| Results|| |
Among the patients, there were 66 male and 34 female. Their age ranged from 15 to 65 years (mean ± SD 50.27 ± 11.23 years). The total duration of HD ranged from 0.5 to 16 years (mean ± SD 5.64 ± 3.45 years). The blood urea level before HD ranged from 120 to 250 mg/dl (mean ± SD 165.59 ± 30.22 mg/dl), which decreased to 40-120 mg/dl (mean ± SD 70.79 ± 21.97 mg/dl) during HD. The blood creatinine level before HD ranged from 6 to 16 mg/dl (mean ± SD 9.91 ± 2.11 mg/dl), which decreased to 4-9 mg/dl (mean ± SD 5.45 ± 1.33 mg/dl).
All the patients showed at least one cutaneous manifestation. The most common skin manifestation was xerosis (72%), which was predominantly observed over the extensor surfaces of the forearms, legs, and thighs [Figure 1], followed by pruritus (52%), hyperpigmentation (44%), and pallor (34%). Other skin manifestations were fungal infections (18%) [pityriasis versicolor (PV) in 11.1%, tinea pedis in 88.8%], Kyrle's disease (7%) [Figure 2], gynecomastia (7%), bacterial infections in 6% of patients in the form of folliculitis, viral infections in 4% of patients (disseminated plane warts in 50% of patients, common warts in 50%), and purpura in 2% of patients. Rare skin manifestations of CRF such as bullous dermatosis (1%) [Figure 3] were also observed. Xerostomia (46%) was the most common oral mucosal manifestation, followed by macroglossia with teeth markings (43%) [Figure 4], fissured tongue (17%), uremic breath (17%), ulcerative stomatitis (11%), and angular cheilitis (6%). The relation between the onset of skin and oral mucosal manifestations with HD showed that xerosis (65.3%), pruritus (69.2), and pallor (91.2%) statistically significantly manifested before HD (P = 0.006, 0.002, and <0.001, respectively), whereas hyperpigmentation (86.4%), wrinkles (93.9%), ecchymosis (90.6%), macroglossia (83.4%), fissured tongue (94.1%), and ulcerative stomatitis (81.8%) statistically significantly manifested after HD (P < 0.001 for all except ulcerative stomatitis, P = 0.006) [Table 1]. Nail changes were absent lunula (AL) (61%), half and half nail (41%) [Figure 5], koilonychia (29%), splinter hemorrhages (15%), subungual hyperkeratosis (12%), onycholysis (10%), onychomycosis (7%), Muehrcke's lines (7%) [Figure 6], Mees' lines (6%), and Beau's lines (1%) [Figure 7]. Hair manifestations included sparse scalp hair (48%), sparse body hair (41%), and brittle and lusterless hair (39%). The relation between the onset of nail and hair manifestations with HD showed that AL (96.7%) was the only manifestation that statistically significantly manifested before HD (P < 0.001), whereas half and half nail (95.1%), onycholysis (90%), and Muehrcke's lines (85.7%) statistically significantly manifested after HD (P < 0.001, <0.001, and 0.007, respectively) [Table 2].
|Table 1: Skin and oral mucosal manifestations and the relation between their onset and hemodialysis|
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|Table 2: Nail and hair manifestations and the relation between their onset and hemodialysis|
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The current study showed that hypertension and diabetes mellitus were the most common causes of CRF (53 and 18%, respectively), followed by urinary tract obstruction (9%), postanalgesic renal failure (6%), unknown (5%), systemic lupus erythematosus (4%), urinary tract infection (3%), and polycystic kidney (2%). Skin and oral mucosal manifestations in relation to the etiology of CRF are shown in [Table 3], whereas nail and hair manifestations are shown in [Table 4].
|Table 3: Skin and oral mucosal manifestations and their relations to the etiology of chronic renal failure|
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|Table 4: Nail and hair manifestations and their relations to the etiology of chronic renal failure|
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| Discussion|| |
The results of the present study showed that all patients with CRF had one or more cutaneous manifestations, which was in agreement with the results of Pico et al.  and Sultan et al. , whereas Bencini et al.  observed cutaneous changes in 79% of patients of CRF on regular HD.
In this study, xerosis was the most common cutaneous abnormality detected. Its prevalence was found in 72% of the patients studied, which was in agreement with Udayakumar et al.  and Falodun et al. , who reported xerosis in 79 and 60% of CRF patients, respectively. However, Hajheydari et al.  reported xerosis only in 23% of Iranian patients and they attributed this to geographic distribution. The onset of xerosis statistically significantly manifested before HD (65.3%).
The possible etiological factors for xerosis include 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. Loss of integrity of the water content in the stratum corneum by skin barrier dysfunction may also be important in the pathogenesis of xerosis .
Pruritus is one of the most characteristic and annoying cutaneous symptoms of CRF. Its prevalence among HD patients ranges from 19 to 90% . In this study, pruritus was the second most common skin manifestation, found in 52% of the patients studied. Pruritus statistically significantly manifested before HD (69.2%).
The etiology of pruritus in CRF is unknown; however, several hypotheses have been suggested. Immunohypothesis considers uremic pruritus (UP) as an inflammatory systemic disease rather than a local skin disorder. This idea is supported by the beneficial effects of ultraviolet B radiation exposure on UP, and the amelioration of UP with thalidomide treatment or calcineurin inhibitors such as tacrolimus . The neurophysiological hypothesis is considered to play an important role in CRF-associated pruritus .
The prevalence of hyperpigmentation in this study was 44% and presented as localized or diffuse brownish-black pigmentations on sun-exposed areas. Abdelbaqi-Salhab et al.  reported that pigmentary alteration occurs in 25-70% of the dialysis population and increases over the duration of renal disease. Our results were different from those obtained by Falodun et al. , who detected hyperpigmentations in 7.5% of the Nigerian CRF patients studied. This could be attributed their dark skin color as hyperpigmentation in black skin may be masked unless it is extensive. The onset of hyperpigmentation in our study statistically significantly manifested after HD in 86.4%. Hyperpigmentation can be attributed to the retention of chromogens and deposition of melanin in the basal layer and superficial dermis because of failure of the kidneys to excrete b-melanocyte-stimulating hormone .
Pallor was observed in 34% of patients in this study. This is in agreement with Attia et al. , who observed pallor in 42.2%, but not in agreement with Udayakumar et al. , who observed pallor in 60% of Indian patients, which may be attributed to nutritional factors. The onset of pallor in our study statistically significantly manifested before HD (91.2%). Patients with CKD are at risk of blood loss because of platelet dysfunction. Erythropoietin deficiency is considered the most important cause of anemia in CKD . Other contributory factors included absolute iron deficiency as HD patients may lose 3-5 g of iron per year ; the survival of red blood cells is reduced by approximately one-third in HD patients and vitamin B12 deficiency .
The prevalence of early wrinkling and exaggerated skin markings was observed in 33% of the patients in this study. These results are in agreement with those of Sultan et al. , who observed early wrinkles in 40% of patients. The onset was because of the early occurrence of actinic elastosis in patients undergoing long-term HD . The onset of appearance of wrinkles in our study statistically significantly manifested after HD (93.9%).
Ecchymosis was detected in 32% of the studied patients. It was observed around the arteriovenous fistula, which is in agreement with Hajheydari et al.  and Sultan et al. , who observed ecchymosis in 30 and 27% of their patients, respectively. In contrast, Attia et al.  observed ecchymosis in 1.8% of their dialysis patients. Defects in primary hemostasis such as increased vascular fragility, abnormal platelet function, and the use of heparin during dialysis are the main causes of ecchymosis in CKD patients on HD . In this study, ecchymosis appeared in 90.6% of patients after HD, and this was statistically significant. This may be because of the repeated venopuncture necessary for HD in addition to the lack of connective tissue-supporting blood vessels that occur with aging and debilitating conditions.
Skin infections was observed in 28% of the patients studied: fungal infections in 18% (PV in 11.1% and tinea pedis in 88.8%), bacterial infections in 6% (in the form of folliculitis), and viral infections in 4% (disseminated plane warts in 50% of patients and common warts in 50%). Sultan et al.  reported skin infections in 40% of patients in their study (fungal infections, bacterial infections, and viral infections in 33, 5, and 2%, respectively). Udayakumar et al.  reported skin infections in 67% of their HD Indian patients (fungal infections, bacterial infections, and viral infections in 30, 13, and 12%, respectively). The lower percentage of skin infections in the present study may be because of the lower percentage of DM associated with CRF patients (18%), whereas it was 38% in the Indian patients; also, onychomycosis (19%) was also observed in addition to the skin infection, whereas onychomycosis was a nail manifestation in the present study. Excessive use of antibiotics in our community may be the reason for this lower incidence.
In terms of fungal infections, we believe that the lower percentage of PV infection in comparison with tinea pedis resulted from the reduction in the function of the pilo sebaceous and eccrine sweat glands in patients with CRF as the sebum is one of the important factors in the development of PV. There was no statistically significant difference between the onset of skin infection and HD.
Kyrle's disease was detected in 7% of the patients in the present study. This was in agreement with Sultan et al. , who reported Kyrle's disease in 3% of the CRF patients on HD. However, Deshmukh et al.  and Udayakumar et al.  reported Kyrle's disease in 17.14 and 21%, respectively, in their patients. This difference could be explained by the higher frequency of diabetic patients (51 and 38%, respectively) compared with 18% in our patients. The onset of Kyrle's disease manifestations in our study was not statistically significantly related to HD. The pathogenesis of the disease is not known, but it may occur as a result of dermal connective tissue dysplasia and decay. Suspected causes include an inflammatory skin reaction secondary to the presence of uremic toxins, uric acid deposits, or scratching-induced trauma . Microvascular deposition of calcium may interrupt blood flow to connective tissue in the dermal layer, causing death and necrosis .
Gynecomastia was observed in the present study in 7% of patients, whereas Udayakumar et al.  reported it in 1% of patients. This difference may be because of associated schistosomiasis in our patients.
In this study, bullous lesions in the form of pseudoporphyria (PP) were noted in 1% of patients, which matched with the reported percentage of bullous disease range of 1-18% in patients with CRF on HD . Usually, this PP is equivalent to porphyria cutanea tarda, showing blistering and mechanical fragility of skin subjected to sunlight and incidental trauma. It typically begins only after several months or years of dialysis therapy. Hypertrichosis is less common and plasma porphyrin levels are usually normal . The etiology of PP remains unclear; however, CRF patients with PP show abnormal porphyrin profiles because of impaired excretion, rather than a deficiency in the enzyme uroporphyrinogen decarboxylase, in contrast to true porphyria cutanea tarda .
AL was the most common nail change observed in the present study (61% of patients). This is in agreement with Martinez et al. , who reported AL in 62.9% of CRF patients on HD. However, Saray et al.  and Salem et al.  observed AL in 31.9 and 17% of patients, respectively. Visible lunula is a good sign in healthy cases of CRF on HD  and the lower percentage in their reports may be because of the better general health of their patients. The onset of AL was the only nail manifestation that statistically significantly appeared before HD.
In total, 41% of the patients in this study had nail manifestation in the form of half and half nail (HHN), which is in agreement with Lubach et al.  and Pico et al. , who reported HHN in 50.6 and 40% of their patients, respectively. In contrast, Deshmukh et al.  and Salem et al.  reported HHN in 19.04 and 20% of their patients, respectively. Malnutrition is an important cause for HHN  and its presence in some patients may be the reason for the higher percentage in this study. The pathophysiology of this phenomenon is related to the proximal half of the nail appearing white because of edema associated with a dilated capillary network and the other half of the nail bed appearing normal .
Koilonychia was observed in 29% of CRF patients in this study. Our results were in agreement with those of Sultan et al. , who reported koilonychia in 39% of their patients. However, Onelmis et al.  reported koilonychia in 19% of their CRF patients on HD. This difference may be because of the fact that the prevalence of koilonychia increased with increasing HD duration .
Splinter hemorrhage was present in 15% of the patients in this study, which is in agreement with Sultan et al. , who observed it in 16% of their patients. In contrast, Martinez et al.  and Udayakumar et al.  reported splinter hemorrhage in 7 and 5% of their patients, respectively. Splinter hemorrhage was widely considered to result from microtrauma  .
Subungual hyperkeratosis was found in 12% of patients in this study, which is in agreement with Udayakumar et al.  and Tercedor et al. , who reported subungual hyperkeratosis in 12% of their studied patients. In contrast, Salem et al.  observed subungual hyperkeratosis in 3% of their patients.
Onycholysis was observed in 10% of the included patients, which is in agreement with Salem et al.  and Onelmis et al. , who reported onycholysis in 10 and 9% of their patients, respectively, whereas both Sultan et al.  and Hajheydari et al.  reported onycholysis in 3% only of their patients. Certain medications that cause photosensitivity can induce photo onycholysis as reported in HD patients who receive large doses of cephalordine or cloxacillin .
Onychomycosis was observed in 7% of the patients in this study, is in agreement matched with Bencini et al. , who reported onychomycosis in 6.2% of their patients. However, Saray et al.  reported it in 19.2% of their patients. This may be because of the difference in the number of study patients; they included 182 patients in their study.
In this study, sparse scalp hair was the most common hair disorder. Its prevalence was 48%, followed by sparse body hair in 41% and brittle and lusterless hair in 39% of the patients studied. These results were in agreement with those of Sultan et al. , who found sparse scalp hair in 46%, sparse body hair in 27%, and lusterless hair in 47% of their patients. Our results were different from those observed by Udayakumar et al. , who reported sparse scalp hair in 11%, sparse body hair in 30%, and lusterless hair in 16% of their Indian patients. Also, Hajheydari et al.  reported sparse scalp hair in 10%, sparse body hair in 9%, and lusterless hair in 2% of their Iranian patients. The higher percentage of hair changes in the Egyptian patients detected in this study in comparison with Indian and Iranian patients may be because of the racial variation in hair density .
This study detected no statistically significant relation between the onset of hair manifestations in patients with CRF on regular HD.
The most common oral mucosal manifestation in this study was xerostomia, found in 46% of patients. This is in agreement with Malekmakan et al.  and Onelmis et al. , who reported it in 48.6 and 40% of their patients, respectively. However, Udayakumar et al.  found xerostomia in 31% of their patients and the lower percentage may be because of the inclusion of fewer hypertensive patients (18%) and administration of antihypertensive drugs. Dry mouth in HD patients is a multifactorial phenomenon that may be because of water restriction, excessive water intake may increase the risk of elevated blood pressure and heart failure, and low saliva flow, minor salivary glands parenchymal fibrosis and atrophy, medication use (fundamentally antihypertensive agents), and oral breathing secondary to lung perfusion problems .
Macroglossia and teeth markings were detected in 43% of the patients in this study. This result is in agreement with that of Sultan et al. , who found it in 42% of the patients studied, but it was different from the results detected by Udayakumar et al. , who reported it in 35% of their patients. In many patients, the abnormality of the tongue was found to disappear gradually and the tongue regained its normal color, size, and shape with the clinical and histopathological correlations soon after renal transplantation. This original observation in uremic patients should be designated as the 'tongue sign of uremia' .
Ulcerative stomatitis was detected in 11% of the patients in this study. This is in agreement with Sultan et al. , who found ulcerative stomatitis in 9%, but not in agreement with Udayakumar et al. , who reported ulcerative stomatitis in 29% of patients. This may be because of their patients' intake of alcohol, spices, hot food, and tobacco smoking, which are the precipitating factors of ulcerative stomatitis. It has been suggested that stomatitis appears when blood urea levels exceed 300 mg/ml, although there have been reports of mucosal changes at urea levels of less than 200 mg/ml .
In this study, angular cheilitis was found in 6% of the patients. This result was in agreement with that of King et al. , who found angular cheilitis in 4% of their HD patients. However, Udayakumar et al.  and Sultan et al.  reported angular cheilitis in 12 and 15% of their patients, respectively. Their higher percentage may be related to the larger numbers of diabetic patients (38%) in their study. Angular cheilitis appears with nutritional deficiencies, namely riboflavin (vitamin B 2 ), iron-deficiency anemia, or zinc deficiency. Angular cheilitis occurred most commonly with fungal infections and can be caused by bacteria.
In terms of the etiology of CRF patients on HD, this study estimated that hypertension (53%) and diabetes mellitus (18%) were the most common causes of CRF. This was in agreement with Sultan et al. , who confirmed that hypertension and DM were the most common causes for CRF (60 and 14%, respectively).
| Conclusion|| |
Every CRF patient on HD had at least one cutaneous manifestation, which may appear before or after HD. The most common cutaneous manifestations were xerosis, pruritus, hyperpigmentation, xerostomia, macroglossia, AL, half and half nail, sparse scalp hair, and sparse body hair. Hypertension and diabetes mellitus were the most common causes of CRF.
| Acknowledgements|| |
Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]