End stage renal disease and the skin
Part 1 — Non-specific manifestations
by John Kraft, MD and Charles Lynde, MD
Vol.17, No.08, October 2009

End-stage renal disease (ESRD) is a progressive and irreversible kidney dysfunction that lasts longer than 3 months. Nearly all patients with ESRD have at least one dermatological disorder. These skin and nail changes can occur before or even after initiation of dialysis or transplantation. Some propose that the skin manifestations are caused by renal failure while others maintain that a common underlying pathologic process lies behind both renal disease and skin changes.

Advances in treatment have not only improved the life expectancy and quality of life of ESRD patients, they’ve also changed the types and frequency of skin disorders. It’s now rare to find ESRD patients with uremic frost.

What are the skin manifestations of ESRD?

Non-specific

  • pruritus
  • xerosis
  • pigmentary disorders
  • uremic frost
  • ecchymoses
  • elastosis
  • half-and-half nails

Specific disorders

  • metastatic calcification
    • calcinosis cutis
    • calciphylaxis
  • bullous dermatoses
    • PCT (porphyria cutanea tarda)
    • pseudoporphyria
  • acquired perforating dermatosis
  • fibrosing dermopathy of uremia

Pruritus

Pruritus or itching is the most common symptom of ESRD — and ESRD is the commonest systemic cause of pruritus. Up to half of patients with chronic renal failure and up to 90% of patients undergoing dialysis experience pruritus, though this number is falling with better dialysis. It’s very uncommon in acute renal failure.

Its pathophysiology is unknown but several theories have been proposed, all without substanstial empiric support. These include uremic toxemia, xerosis, secondary hyperparathyroidism, hypervitaminosis A, retention of urochrome exciting cutaneous sensory nerve endings, increased mast cells, iron deficiency anemia, increased serum histamine levels, abnormal pattern of cutaneous innervation, and also allergy against compounds in dialysis (i.e. ethylene oxide).

The pruritus of ESRD is either localized or generalized. The commonest presentation is generalized and mild (66%), but it can be severe (8%) and unremitting. It’s not associated with any primary skin lesions. However, chronic itch results in secondary skin changes such as prurigo nodularis, excoriations, and lesions of lichen simplex chronicus. Pruritus may contribute to the Koebnerization of acquired perforating dermatosis.

Management

Renal transplantation is virtually curative.

A stepwise approach can be taken for treating pruritus of ESRD.

  • general measures such as emollients should be used to help reduce xerosis that contributes to pruritus
  • phototherapy
    • Narrow band UVB and broadband UVB have been shown to be effective
    • The mechanism is a subject of speculation, but it’s thought that it induces the formation of photoproducts with antipruritic effects, and the photoinactivation of pruritogenic substances
  • topical tacrolimus
  • opioid µ-receptor antagonists such as naltrexone
  • charcoal (6 g/day) is another option but side effects including nausea and diarrhea are limiting
  • cholestyramine 5g 2x/day
  • gabapentin 3x/week following each hemodialysis session

Xerosis

Xerosis refers simply to dry or roughened skin. It has a prevalence of 50-75% in dialysis patients. Extensor surfaces of extremities are particularly affected. Xerosis can be very uncomfortable with the development of fissures, ulcers, lichen simplex chronicus, and irritant or allergic contact dermatitis. Due to the dysfunction of the normal skin barrier, xerosis predisposes patients to infections (i.e. cellulitis) and this is further aggravated by delayed wound healing in ESRD patients.

Pigmentary disorders

These affect 25-70% of dialysis patients to some degree. Its incidence increases with the duration of renal disease. There is a spectrum of pigmentary changes ranging from hyperpigmentation, to yellowish discoloration, to pallor.

Uremic frost

Uremic frost is a late feature of severe ESRD. It’s rarely seen. It refers to superficial white deposits caused by crystallized urea excreted from sweat.

Ecchymoses

Ecchymoses are common and result from platelet dysfunction.

Elastosis

Elastosis — yellow, atrophic plaques, with wrinkling of the skin — is often seen in sun exposed areas as elastin is broken down. Its relationship to ESRD is unclear. A possible explanation may be that this acceleration of cutaneous aging is a function of the time on dialysis.

Half-and-half nails

Half-and-half nails are also referred to as Lindsay’s nails. They’re found in roughly 1/3 of patients with azotemia and up to 40% of patients on dialysis. The proximal half of the nail is white due to edema of the nail bed and capillary network. The distal portion appears normal or even brown due to increased melanocyte stimulating hormone in patients with ESRD. The nail plate is unaffected. These changes can become more likely the longer a patient is on dialysis; however, there may be no correlation with the severity of uremia. Half-and-half nails tend to disappear after successful transplantation.

Other non-specific skin findings

  • increased susceptibility to low temperatures and Raynaud’s phenomenon
  • hypertrichosis lanuginosa
  • thickening of eyebrows
  • increased malignant skin tumours.

Charles Lynde, MD, FRCP(C) is an assistant professor of dermatology at the University of Toronto.

John Kraft, MD, is in his third year of the Dermatology Residency Program at the University of Toronto.

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