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Mucocutaneous manifestations and nail changes in patients with end stage renal disease: A cross-sectional study.

Byline: M Pushpa, SC Murthy and MI Anvar

Key words

Mucocutaneous, nail changes, chronic kidney disease, skin, systemic diseases.

Introduction

Chronic kidney disease (CKD) is characterised by slow and progressive loss of renal function resulting in various metabolic disturbances.1End stage renal disease (ESRD) or stage five CKD refers to the stage, when the glomerular filtration rate falls less than 15ml/min.2

Characteristic dermatological manifestations are commonly seen in patients with chronic kidney disease. Most of the patients with ESRD will have at least one associated cutaneous change.3

Most of the cutaneous manifestations are not life-threatening. However, conditions like uremic pruritus will be distressing and adversely affect quality of life. Certain conditions like calciphylaxis can result in sepsis and subsequent mortality. Cutaneous manifestations occur with renal disease, sometimes after the initiation of dialysis. Occasionally, these may be the presenting signs of renal failure.4

Further, the mucocutaneous manifestations may also vary with race, climate, nutritional status and other factors. Only a few studies are available in literature, particularly on end stage renal disease. Hence, we conducted this study, to find the prevalence and pattern of mucocutaneous manifestations and nail changes in end stage renal disease. We also tried to correlate these manifestations, in relation to the duration of renal disease, hemodialysis and serum creatinine levels. Since the staging of chronic renal failure is based on glomerular filtration rate which depends on serum creatinine levels, we tried to correlate mucocutaneous changes with serum creatinine levels.

Methods

This was a descriptive, cross-sectional study. After obtaining the institutional ethical committee clearance, 170 consecutive ESRD patients (based on Kidney Dialysis Outcome Quality Initiative guidelines), attending dermatology, nephrology, medicine OPD and those admitted in medicine and dialysis wards, in between January 2015 to December 2015 were included. All patients with ESRD on hemodialysis and those not on hemodialysis, willing to participate in study were included. Those with renal transplant or on peritoneal dialysis were excluded.

After taking informed consent, a detailed history about the duration of renal failure, type of treatment undertaken, duration of hemodialysis, were taken. Regarding dermatological complaints, detailed history about pruritus, onset and evolution of skin lesions were asked for. All the patients were subjected to a detailed general physical, mucocutaneous, hair, nails and systemic examination. Routine hematological, biochemical investigations and urine analysis were done. Gram's stain, potassium hydroxide mount, skin biopsy, etc., were done wherever necessary. Both groups received oral iron, folic acid, calcium and vitamin D supplements. Injection erythropoietin (6000 units per week), was also given for those patients with haemoglobin less than 10gm percent, in both the groups.

Data collected was entered in a specially-designed proforma and analysed using SPSS version twenty. Statistical tests for descriptive analysis, like mean, frequency, percentage, standard deviation were used. For inferential statistics, Chi-square test was applied, wherever necessary.

Results

Among 170 patients, 130 were males and 40 were females, with a M:F ratio 3.25:1.Their ages ranged from 14 to 85 years (mean 46.5years). Majority, 48 (28.2%) patients, belonged to 41-50 year age group. Hypertension was the most common [63 patients; 37.1%], cause of ESRD, followed by undetermined etiology [46; 27.1%]. Co-existent diabetes and hypertension [36; 21.2%] constituted important cause of ESRD in our study.

Majority of the patients i.e. 147 (86.5%) were undergoing hemodialysis and others (23; 13.5%) were not on hemodialysis. The duration of ESRD varied from less than six months to more than 10 years with most, 92 (54.1%) having duration less than six months. The duration of hemodialysis ranged from less than a month to five years. Most, 59 (40.1%) were on dialysis for less than a month.

Table 1 Specific mucocutaneous manifestations and nail changes in patients with ESRD.

###Patients on maintainance###Patients not on maintainance

Manifestations###hemodialysis###hemodialysis###P Value

###Frequency###Percent###Frequency Percent

Symptom

###Generalised itch###47###32.0###12###52.2###0.058

Skin

###Xerosis###57'###38.8###9###39.1###0.974

###Aquired icthyosis###60###40.8###6###26.1###0.177

###Diffuse Hyperpigmentation###47###32.0###4###17.4###0.156

###APD###4###2.7###0###0.0###0.951

###Purpura/ Ecchymosis###4###2.7###0###0.0###0.951

###Prurigo###7###4.8###3###13.0###0.116

###Cutaneous Infections###21###14.2###4###17.3###0.695

Mucosa

###Oral Pallor###132###89.8###17###73.9###0.031

###Angular Chelitis###5###3.4###0###0.0###0.957

###Fissured/bald tongue###12###8.2###1###4.3###0.901

Hair

###Diffuse Alopecia###2###1.4###0###0.0###>0.99

Nails

###Longitudnal melonychia###40###27.2###7###30.4###0.747

###Half and half nail###57###38.8###5###21.7###0.114

###Koilyonochia###2###1.4###0###0.0###>0.99

###Absent lunula###97###66.0###8###34.8###0.004

###Splinter Haemorrhage###12###8.2###1###4.3###0.901

###Subungual hyperkeratosis###23###15.6###3###13.0###>0.99

###Onycholysis###39###26.5###6###26.1###0.964

Infections

###Fungal###12###8.2###1###4.3###0.901*

###Viral###10###6.8###1###4.3###0.912*

###Bacterial###4###2.7###2###8.7###0.374*

Various mucocutaneous manifestations and nail changes are shown in Table1. Generalised itching (pruritus) was a common complaint seen in many patients. It was more frequently seen in those not on hemodialysis. Among skin changes, xerosis/acquired icthyosis (Figure 1), was the most common finding, followed by diffuse pigmentation. Both were frequently seen in patients on hemodialysis. Pigmentation was seen mainly over the face, distal extremities and over sun exposed areas.Other findings like prurigo, purpura/ecchymosis and acquired perforating dermatoses (APD) (Figure2), were seen in that order. Cutaneous infections were observed in (30; 27.5%) patients commonest being fungal infections (Figure3), and frequently found in patients on hemodialysis.

Most of the patients were having oral pallor (Figure 4), more so in patients on hemodialysis and it was statistically significant (p-0.0031). Bald tongue, fissured tongue and angular cheilitis were the other mucosal findings.

Various nail changes were seen in our study (Table 1). Absent lunula (Figure 5) was the commonest, frequently seen in patients on hemodialysis. This observation was statistically significant (p-0.004). Half and half nail (Figure 6) was the next common finding, followed by others.

Mucocutaneous manifestations and nail changes in relation to the duration of disease is shown in Table 2. Although, most of the findings were frequently observed with disease duration more than one year, certain conditions like purpura/echymoses, prurigo, mucosal changes, splinter haemorrhages and bacterial infections were commonly seen in those with disease duration less than a year.

Table 3 represents comparison of dermatological manifestations in relation to duration of hemodialysis. Xerosis/acquired icthyosis and diffuse pigmentation were observed more frequently in patients undergoing hemodialysis for more than a year and was statistically significant. Other findings were more frequent in patients undergoing hemodialysis for less than a year.

Table 2 Mucocutaneous manifestations and nail changes in patients with ESRD in relation to duration of disease.

###a$?1 year (n=118)###>1 year (n=52)

Manifestations###P value

###Frequency###Percent###Frequency###Percent

Symptoms

###Generalised itch###36###30.5###23###44.2###0.083

Skin

###Xerosis###44###37.3###22###42.3###0.536

###Acquired icthyosis###41###34.7###25###48.1###0.101

###Diffuse hyperpigmentation###32###27.1###19###36.9###0.217

###Acquierd Perforating###1###0.8###3###5.8###0.171

###Dermatoses###4###3.4###0###0.0###0.457

###Purpura/ecchymosis###7###5.9###3###5.8###0.966

###Prurigo###16###13.5###9###17.3###0.524

Cutaneous infections

Mucosa

###Oral pallor###107###90.7###42###80.8###0.07

###Angular chelities###4###3.4###1###1.9###0.603

###Fissured/bald tongue###11###9.3###2###3.8###0.358

Hairs

###Diffuse alopecia###1###0.8###1###1.9###>0.99

Nails

###Longitudnal melonychia###28###23.7###19###36.5###0.085

###Half and half nails###38###32.2###24###46.2###0.081

###Koilynochia###2###1.7###0###0.0###0.961

###Absent lunula###68###57.6###37###71.2###0.094

###Splinter hemmorhages###10###8.5###3###5.8###0.792

###Subungual hyperkeratosis###18###15.3###8###15.4###0.982

###Onycholysis###29###24.6###16###30.8###0.399

Infections

###Fungal###9###7.6###4###7.7###0.988

###Viral###4###3.4###7###13.5###0.041

###Bacterial###5###4.2###1###1.9###0.808

Dermatological manifestations in relation to serum creatinine levels are shown in Table 4. Among skin changes, APD, purpura/ecchymosis were seen more frequently in patients with serum creatinine levels more than ten. Oral pallor was significantly associated with serum creatinine levels >10 (p-0.00060). Nail changes were more common, with serum creatinine levels more than 10, except subungual hyperkeratosis.

Discussion

Cutaneous manifestations of renal disease are not uncommon in patients with end stage renal disease. Earlier studies have shown that 50-100% of them will have at least one dermatological manifestation.3 As very few studies are done on this subject, especially in ESRD or stage five CKD, we conducted this study, to find the dermatological manifestations in ESRD in our region. We found that almost all the patients had, at least one dermatological manifestation. This is possibly due to increased life expectancy and improvised health care facilities.

Most common age group in our study belonged to 41-50 years, which is consistent with the study by Udaykumar et al.5 The mean age of patients in our study was 46.5 years similar to earlier studies.

As observed in previous studies, men were more commonly affected. Hypertension was the most common cause of ESRD, in accordance with earlier studies.3,8,10 However, Udaykumar et al.5 found diabetes to be the most common cause.

Table 3 Mucocutaneous manifestations and nail changes in relation to duration of dialysis.

###0.99

###Purpura/ ecchymosis###4###3.4###0###0.0###0.767

###Prurigo###4###3.4###3###9.7###0.325

###Cutaneous infections###18###15.5###3###9.7###0.614

Mucosa

###Oral pallor###107###92.2###25###80.6###0.058

###Angular chelities###4###3.4###1###3.2###>0.99

###Fissured tongue###11###9.5###1###3.2###0.466

Hairs

###Diffuse alopecia###1###0.9###1###3.2###0.756

Nails

###Longitudnal melonychia###29###25.0###11###35.5###0.244

###Half and half nails###44###37.9###13###1.9###0.684

###Koilynochia###1###0.9###1###3.2###0.756

###Absent lunula###77###66.4###20###64.5###0.845

###Splinter hemmorhages###12###10.3###0###0.0###0.102

###Subungual hyperkeraosis###18###15.5###5###16.1###0.933

###Onycholysis###30###25.9###9###29.0###0.722

Infections

###Fungal###10###8.6###2###6.5###>0.99

###Viral###9###7.8###1###3.2###0.669

###Bacterial###4###3.4###0###0.0###0.767

Pruritus is the characteristic and distressing cutaneous symptom, which adds to the morbidity of the renal disease. In our study, 34.7% patients had generalized pruritus, similar to Hajyehdari et al.10 and Khanna et al.11 Among hemodialysis patients, pruritus was present in 32% of our patients, which is consistent with an earlier report of its prevalence of 19-90 percent.12 Patients not on hemodialysis, had pruritus, more frequently than those undergoing hemodialysis. Further, we observed that pruritus was more in patients with longer duration of renal disease and hemodialysis, similar to other studies.10,13 Also, more patients started experiencing itching after the onset of hemodialysis.

Uremic pruritus has been attributed to hypercalcemia, hyperphosphatemia, hyper-magnesemia and elevated concentrations of parathyroid hormone, with high calcium phosphate product. Also, the cytokines produced by the contact of blood with dialyser membrane, especially cuprophane and regenerated cellulose, will initiate an inflammation, inducing pruritus. The pruritogenic substances thus accumulated, which cannot be removed by dialysis, might exert effects on itch centers or receptors.14 This indicates that dialysis has no role in alleviating pruritus. More prevalence of itching in our study may also be due to higher prevalence of patients with xerosis/acquired icthyosis and associated malnutrition.

Pruritus was commonly seen in our patients with serum creatinine levels less than 10mg/dl than with more than 10mg/dl, suggesting that, levels of serum creatinine has no role in itching in these patients, in contrast to Hu, et al. who found the levels of creatinine to be significantly higher in patients with itching, than without.15

Table 4 Mucocutaneous manifestations and nail changes in patients with ESRD in relation to serum creatinine levels.

###Sr. creatinine10mg/dl) and also with longer duration of hemodialysis, and was statistically significant. This suggests that, dialysis has no beneficial effect in controlling xerosis. Chronicity of the disease, regional, racial differences and associated malnutrition may be the causative factors.

Renal failure leads to retention of chromogens and poorly dialyzable beta-melanocyte stimulating hormone, causing deposition of melanin in basal layer and superficial dermis.17,18

Diffuse pigmentation was observed in about one third of patients in our study which is in accordance with other studies.1,19 Kolla et al.20 have reported higher prevalence of pigmentation. Majority of our patients had shorter duration of disease and this might account for the lower prevalence of pigmentation in our study. Prevalence of pigmentation was high with longer duration of renal disease and was significantly associated with longer duration of hemodialysis, in our study. It has been shown in earlier studies that prevalence of hyperpigmentation increases with duration of dialysis.21

Acquired perforating dermatoses, are seen most commonly, in the context of patients with ESRD or Diabetes mellitus.The reported incidence is 4.5 to 17% of patients on hemodialysis.5,22 In our study, APD were found to be quite low, consistent with Sultan et al.8 Higher prevalence was found in a study by Sheikh et al.1 The association between Diabetes Mellitus and APD has been established earlier. Lesser number of patients with diabetes in our series, may be the reason for low prevalence of acquired perforating dermatoses. Also there was no correlation with duration of disease and hemodialysis.

Purpura/ecchymosis were relatively infrequent in our study similar to prior studies.3,23 The reason could be that most of our patients were undergoing dialysis for a shorter duration. It may be possible that vascular fragility and other changes like defects in primary haemostasis develop late, during the course of dialysis.

Cutaneous infections were present in 27.5% of patients, which is consistent with earlier studies.1,17 Our study had higher prevalence of fungal infections rather than viral and bacterial infections seen in other two studies.1,17 This may be due to impaired cellular immunity and climatic variations like high temperature and sweating, prevalent most of the year, in our region.

Various mucosal changes were seen in our study. Most common change was oral pallor seen in 87.6% patients. It was seen frequently, in patients with hemodialysis and in those with serum creatinine levels more than 10, and both were statistically significant. Blood loss during hemodialysis, relative erythropoietin deficiency, iron deficiency, reduced erythrocyte survival, infection, inflammation, hyperparathyroidism, hemolysis and progression of renal disease affecting haemoglobin production, may be the possible explanations.24,25 Although we found a statistically significant p value for oral pallor in relation to hemodialysis, the results should be interpreted with caution as anemia in ESRD may be due to several causes and we had not planned for the removal of all confounding factors.

Other mucosal changes like angular cheilitis, fissured/bald tongue, nutritional cheilitis, candidal balanoposthitis and actinic cheilitis were also seen, similar to other studies.5,8 Among them mucosal changes attributable to nutritional deficiency, could have resulted due to restrictive dietary prescription, poor appetite and uremia related anorexia.

Characteristic nail changes are seen in renal disease. The etiology of nail pathologies remains unclear: some of them are apparently direct relation to the renal conditions, while others may be due to complications of the disease or therapy. Most common specific nail change in our study was absent lunula followed by half and half nails. Similar findings were reported by Sanad et al.3 However, Salem et al.26 found half and half nails to be the commonest change followed by absent lunula. Absent lunula is likely to be related to the metabolic disturbances and anemia occurring in renal failure patients.27

Appearance of half and half nail is caused by deposition of melanin in the nail plate due to stimulation of matrix melanocytes, increase of capillaries and thickening of their walls while proximal half of the nail appears white because of edema of the nail bed.28 A higher prevalence of absent lunula was seen in patients without hemodialysis and was statistically significant. Thomas et al.15 found half and half nail in 36.36% which is in accordance with our study, but it was the most common finding in their study. Udaykumar et al.5 reported half and half nail in only 21% of patients, while Khanna et al.11 found absent lunula in 22% of patients. Higher prevalence of these changes in our study may be due to high levels of urea, anemia and poor hygiene in our patients.

Prevalence of onycholysis, subungual hyperkeratosis and koilonychias were similar to study by Peres et al.9 Onychomycosis was seen in 6.5% of patients which are in agreement with Sanad et al.3 We found a higher prevalence of Muehrcke's lines in contrast to Udaykumar et al.5 who reported in 5% of patients. End stage renal disease and associated malnutrition may be responsible for this discordance. Splinter haemorrhages were similar to the reports by Udaykumar et al.5 Other nail findings such as Terry's nail, clubbing, apparent leukonychia and Beau's lines, were also observed in our study, which were infrequently reported in earlier studies.17,20

Dry, lustreless hair and diffuse alopecia were seen in 41.2% and 2.4% of our patients. This result is in concordance with Sultan et al.8 and Sanad et al.3 who reported a prevalence of dry lustreless hair of 47% and 39% respectively. Udaykumar et al.5 found a lower prevalence of 16%. This could be due to reduced sebum secretion. Other findings such as androgenic alopecia, scalp psoriasis, alopecia totalis and pressure alopecia were also seen in our patients.

Most common non-specific findings were seborrheic keratosis followed by acrochordons, cherry angiomas, senile comedones and other changes. These changes were similar to the findings reported by Udaykumar et al.5 Our study also had a few limitations. Patients without hemodialysis were less in number. We had not planned for overcoming the effects of confounding factors for anemia.

Conclusion

Mucocutaneous manifestations and nail changes are common in patients with end stage renal disease. The prevalence of mucocutaneous manifestations is almost 100% in these patients. Mucocutaneous manifestations may increase in frequency with duration and stage of the disease. Both patients on hemodialysis and those not on hemodialysis are equally affected. Pruritus is the commonest presenting symptom while xerosis/icthyosis followed by diffuse pigmentation are common signs. Xerosis, diffuse pigmentation and oral pallor may be more prevalent with longer duration of the disease. Hence, early diagnosis and treatment may reduce morbidity and improve the quality of life in these patients.

References

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Author:M Pushpa, SC Murthy and MI Anvar
Publication:Journal of Pakistan Association of Dermatologists
Date:Jun 30, 2021
Words:3307
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