Vol. 27, no. I, 1-4 (2014)



CUTANEOUS MANIFESTATIONS IN PATIENTS WITH CHRONIC RENAL FAILURE ON HEMODIALYSIS F. SPECCHIOl, I. CARBONI', S. CHIMENTI', F. TAMBURP and S. NISTIC03 JDepartment ofSystems' Medicine; University ofRome, "Tor Vergata", Rome, Italy; 2 Unit of Dermatology, Complesso Integrato Columbus, Rome, Italy; 'Department ofHealth Sciences; University ofCatanzaro "Magna Gracia", Catanzaro, Italy

Received November 17, 2013 - Accepted January 9, 2014 Patients with chronic renal failure (CRF) may exhibit various cutaneous abnormalities, including changes in skin colour, pruritus, xerosis, hair, nail and oral changes, metastatic calcinosis, and buUous dermatosis. These changes have a considerable negative effect on the patient's quality oflife. Early recognition of cutaneous signs and prompt initiation of treatment can dramaticaUy alter their course and decrease morbidity. A vast number of diseases may involve skin and kidney: these may be divided into three main groups: I) primitive kidney disease with secondary skin involvement; 2) genetic syndromes with dermatological and renal manifestations; 3) systemic diseases with dermatological manifestation with constant renal involvement.

Primitive kidney disease with secondary skin involvement The first group includes chronic renal failure, especially in advanced stages, which may be associated with many skin manifestations including uremic pruritus, onychopathy (half-and-half nail), bullous dermatoses, pigmentary changes, benign nodular calcification, calciphylaxis, and furthermore, with various dermatological diseases such as the acquired perforating dermatosis and nephrogenic sclerosing dermopathy. The skin may also be the site, albeit rarely, of metastases from renal neoplasms (I). Genetic syndromes with dermatological and renal manifestations In another category of pathologies it is possible

to place those genetic syndromes the clinical picture of which is characterized by the onset of both cutaneous and renal alterations, such as tuberous sclerosis of Pringle-Bourneville, Fabry-Anderson syndrome, Birt-Hogg-Dube syndrome, Hereditary leiomyomatosis and renal cell cancer (HLRCC), reactive perforating collagenosis (hereditary form) and nail-patella syndrome (2).

Systemic diseases with dermatological manifestation with constant renal involvement Lastly, a group consists ofthose systemic diseases (autoimmune, metabolic, infectious) with important cutaneous involvement and with possible renal implication, such as systemic lupus erythematosus, systemic sclerosis, Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, diabetes mellitus, mixed cryoglobulinemia, acquired immunodeficiency syndrome and cholesterol emboli. Clinical manifestations Patients with Chronic renal failure (CRF) may exhibit various cutaneous abnormalities, including hyperpigmentation, pruritus, xerosis, hair, nail

Key words: chronic renal failure. hemodialysis. dermatology. skin symptoms Mailing address: Prof. Steven Nistico, Dermatologist Associate Professor of Dermatology, University Magna Graecia, Catanzaro Viale Europa, Germaneto (CZ) 88100 Catanzaro, Italy Tel.lFax: +39 09613694001 email: [email protected]

0394-6320 (2014) Copyright © by BIOLIFE. s.a.s. This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties DISCLOSURE: ALL AUTHORS REPORT NO CONFLICTS OF INTEREST RELEVANT TO THIS ARTICLE.



and oral changes, metastatic calcinosis, elastosis, ecchymoses, uremic frost, half and half nails, gynecomastia, perforating disorders and bullous diseases. Pigmentation changes observed in uremic patients are among the common skin symptoms. Development of hyperpigmentation, particularly at the sites exposed to sun, is a characteristic symptom and is attributed to elevated levels of melatonin-stimulating hormone in the tissues (3). Changes related to color include: pallor, attributed to the anemia of chronic disease and erythropoietin deficiency; yellowing of the skin, due to retention of fat-soluble pigments in the dermis and subcutaneous tissue, such as carotenoids and urobilinogen; grayishbrown skin, due to the deposit of hemosiderin; hyperpigmentation associated with sun exposure, as well as elastosis; hyperchromia after initiation of dialysis. One of the common presentations is ecchymosis, secondary to platelet dysfunction (4). Pruritus may be localized or disseminated and is the most common symptom of CRF: it occurs in about 53% of these patients, causing great harm to their quality oflife. It is not associated with other primary or systemic skin diseases, psychological disorders or acute renal failure. Pathogenesis is not fully known, but there is a relationship with hyperparathyroidism, xerosis, hypervitaminosis A, iron deficiency anemia, and elevated serum levels of magnesium, calcium, phosphate, aluminum and histamine, though the latter may be associated with allergic sensitization to components in dialysis membranes (5,6). Uremic xerosis is suggested as the main factor in the onset of pruritus. Xerosis is a complication frequently observed in CRF patients in 50-85% of the cases, mainly in patients who have not started dialysis (7). It is known that in most cases it disappears after renal transplantation, it is classically absent in acute renal failure and is not correlated with the level of plasma urea. It is believed that xerosis should be considered a syndrome, according to topography and presence of clinical signs, such as itching and skin turgor. The pathophysiological mechanism of xerosis is unknown, but there is probably a relationship between the dysfunction of eccrine glands and depletion of volume attributed to the use of diuretics (8). Uremic frost, one of the rarer skin changes that can occur in the acute setting of severe uremia, consists of a white

or yellowish coating of urea crystals on the beard area and other parts of the face, neck and on the trunk. It is due to eccrine deposition of urea crystals on the skin surface of patients with CRF (9). Nails may show a number of changes and the most typical alteration of CRF is called half-andhalf nail and is frequently found in 21% of the patients. It is characterized by a marked brownish or pinkish discoloration in the nail extremity and such manifestation is more prevalent in dialysis patients. There may be remission after renal transplantation. The pathogenesis is attributed to an increase of the melanocyte-stimulating hormone (MSH) (7). Gynecomastia may be observed in patients with chronic renal failure, which is attributed to the accumulation of prolactin and its high serum levels (above 30 micrograms / L) are directly related to worsening of the renal function. In such cases, hyperprolactinemia inhibits the release of the follicle-stimulating hormone (FSH) and luteinizing hormone, resulting in lower production of estrogen and progesterone. The dermatologic implications are gynecomastia in men, hirsutism and acne in women. Acanthosis nigricans may develop due to insulin resistance promoted by excess prolactin (10). Among the calcifying disorders ofthe skin in chronic renal patients, metastatic calcification, cutaneous calcinosis and calciphylaxis have been reported. The first occurs by the precipitation of high levels of serum calcium and phosphorus and chronic kidney disease is the major metabolic condition associated. Calcification can affect the gastric mucosa, vascular walls, lung, kidneys and subcutaneous tissue. Cutaneous calcinosis or benign nodular calcification consists in the deposition of insoluble calcium salts in the skin and subcutaneous tissue. It is characterized by stony papules, nodules and plaques of varied size, and there may be elimination of material through the epidermis. Sites most commonly affected are the periarticular regions and fingertips, the latter being extremely painful. The degree of involvement is correlated with high blood levels of calcium and phosphate, the normalization of which can lead to the regression oflesions (4, 11). Calciphylaxis, also known as necrotizing cutaneous calcification syndrome and, more recently, calcific uremic arteriopathy, is a rare but significant cause of morbidity and mortality in patients with

Int. J. Immunopathol. Pharmacol.

chronic kidney disease. It is most commonly seen in patients with severe renal failure as well as in patients with secondary or tertiary hyperparathyroidism and those transplanted, but it may occur in other diseases. A clinical symptom consists offirm purpuric plaques or nodules, symmetrical, bilateral, with a reticulated pattern, resembling livedo reticularis (12, 13). The perforating disorders observed in CRF patients share similar characteristics with primary perforating dermatoses, such as Kyrles disease, perforating folliculitis and reactive perforating collagenosis. They may present as keratotic, umbilicated lesions, nodules and occasionally verrucous plaques with marked pruritus. They are distributed in exposed areas: face, upper and lower limbs, with minor involvement of the trunk (14). Within the group of bullous diseases observed in advanced kidney disease, we highlight Porphyria Cutanea Tarda (PCT) and Pseudoporphyria. PCT is the result of congenital or acquired deficiency of the enzyme uroporphyrinogen III decarboxylase and it is characterized by multiple and painful bullae on the hands and extensor surfaces of the forearms that are exacerbated when exposed to sun. As opposed to porphyria cutanea tarda, hypertrichotic and sclerodermoid changes are not usually observed in pseudoporphyria cutanea tarda (3). Nephrogenic fibrosing dermopathy (NFD), a recently described etiology, resembles disorder of unknown scleromyxedema in some aspects. Most affected patients have been on hemodialysis and many have restarted dialysis after failure of a renal transplant. It is clinically characterized by the progressive development of erythematous, sclerotic dermal plaques, usually pruritic on the arms and legs, with sparing of the head and neck (9). Recently, NSF has been described in patients with end-stage renal failure with metabolic acidosis who underwent magnetic resonance angiography, probably with an injection of a large amount of gadolinium-based paramagnetic contrast agents. This substance is toxic, so there is greater concern in patients with renal failure due to decreased clearance. Skin manifestations occur sixteen days after the injection of contrast and this prolonged duration may explain why this relationship has not been previously described. The safety of administration of these contrast agents in patients with renal failure is not well established (15, 16).


With the advent of increasingly effective renal replacement therapies and others related to different skin diseases (17, 22), some skin changes, previously seen with frequency in end-stage renal disease patients - for instance, uremic frost syndrome - have become increasingly rare, but others, such as uremic pruritus and calciphylaxis, which do not respond to dialysis, often constitute therapeutic challenges. Early recognition and treatment reduce morbidity and improve these patients' quality of life. REFERENCES 1.




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Cutaneous manifestations in patients with chronic renal failure on hemodialysis.

Patients with chronic renal failure (CRF) may exhibit various cutaneous abnormalities, including changes in skin colour, pruritus, xerosis, hair, nail...
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