Chapter 38 Cutaneous manifestations of renal disease
1. What types of skin changes are associated with renal disease?
There are three main categories of skin disease associated with renal diseases:
• Systemic diseases with prominent renal and cutaneous manifestations (e.g., Henoch-Schönlein purpura)
3. Do cutaneous signs of chronic renal failure resolve when the patient is treated with hemodialysis?
4. What cutaneous findings are present in patients being treated with dialysis?
Many of the skin changes described in patients with chronic renal failure are also found in patients with renal failure undergoing treatment with either peritoneal dialysis or hemodialysis. A high percentage of patients receiving dialysis complain of pruritus that may be severe. In some instances, the pruritus worsens with dialysis. Patients on renal dialysis may develop a bullous eruption similar to porphyria cutanea tarda (Fig. 38-1A). Acne has been described in association with dialysis and therapy with testosterone. Several perforating diseases are associated with chronic renal failure, with or without renal dialysis, including Kyrle’s disease, reactive perforating collagenosis, and perforating folliculitis. Some authors group all of the perforating diseases seen in these patients under one term—acquired perforating dermatosis of chronic renal failure. The pathogenesis of these conditions is not understood. Dialysis patients may also develop cutaneous complications from this treatment, such as infections or contact dermatitis in the area of the peritoneal cannula or arteriovenous fistula.
Fuchs E, Lynfield Y: Dialysis acne, J Am Acad Dermatol 23:125, 1990.
5. Describe the nail changes in chronic renal failure.
Both half-and-half nails and Muehrcke’s nails are associated with chronic renal failure. In half-and-half nails, the proximal half of the nail is white, and the distal portion retains the normal pink color (Fig. 38-1B). This is believed to be due to edema of the nail bed. Muehrcke’s nails are associated with hypoalbuminemia and have two transverse parallel white bands, separated from each other and from the lunula by areas of normal pink nail.
6. What is uremic frost?
Although a rare finding today, this discoloration of the face was originally described as a classic manifestation of chronic renal failure. Whitish deposits were noted about the face and neck, believed to be due to deposition of crystallized urea from sweat. Table 38-2 summarizes the abnormalities of skin color associated with renal failure.
Walsh SR, Parada NA: Images in clinical medicine. Uremic frost, N Engl J Med 352:e13, 2005.
8. What causes the pigmentary changes of the skin seen in chronic renal failure?
It is the result of increased amounts of melanin present in the basal layer of the epidermis and superficial dermis. It has been proposed that such patients have decreased metabolism of β-melanocyte–stimulating hormone (β-MSH) by diseased kidneys, leading to elevated plasma levels of β-MSH, a hormone that stimulates melanocytes to produce more melanin.
9. Is pruritus a common finding in all renal failure?
No. Patients with acute renal failure do not develop pruritus. However, it is common in patients with chronic renal failure. Also, some patients with chronic renal failure treated with dialysis have exacerbation of their pruritus. The precise cause of uremic pruritus is unknown. One study suggests that uremic patients have a histamine-releasing factor in their sera that is depleted or diminished by ultraviolet B (UVB) light. Nitric oxide or pruritogenic cytokines may play a role in the pruritus of chronic renal failure. Another study found a reduction in the total number of skin nerve terminals in uremic patients and proposed that skin innervation is altered in chronic renal failure patients, possibly as a consequence of neuropathy. Secondary hyperparathyroidism, which sometimes develops in chronic renal failure, may also induce pruritus.
Urbonas A, Schwartz RA, Szepietowski JC: Uremic pruritus: an update, Am J Nephrol 21:343–350, 2001.
10. How is the pruritus of renal failure treated?
First of all, a specific diagnosis should be sought. Patients with renal failure may develop other skin conditions associated with pruritus, such as scabies or allergic contact dermatitis. Also, reactions to medications may be associated with pruritus. Xerosis is often present and can be treated with avoidance of irritants, use of mild or no soap for cleansing the skin, and the frequent use of emollients. When pruritus is believed to be due to secondary hyperparathyroidism, surgical therapy may be indicated. When no specific cause for pruritus is found, treatment with ultraviolet B light may be beneficial.
11. Are there skin changes associated with renal transplants?
Skin signs of chronic renal failure may resolve following successful renal transplantation (in contrast to hemodialysis). Cutaneous infections (viral, bacterial, atypical mycobacterial, and fungal) may develop, secondary to immunosuppressive therapy given following transplantation. After years of immunosuppression, benign (verrucae, premalignant keratoses, porokeratosis) and malignant cutaneous tumors (squamous cell carcinoma, malignant melanoma, Kaposi’s sarcoma) may develop. Sometimes numerous tumors may arise simultaneously or at increasingly alarming rates, often demonstrating aggressive histology and a propensity to metastasize. Lowering immunosuppressive therapy, aggressive treatment of skin tumors, and potentially adding a systemic retinoid such as acitretin may help control this serious problem.
12. What is transepidermal elimination? What is its relationship to kidney disease?
These are a group of diseases in which altered components of skin are eliminated via the epidermis, a process termed transepidermal elimination. Several different perforating diseases have been associated with chronic renal failure, including Kyrle’s disease, reactive perforating collagenosis, and perforating folliculitis. Because features of more than one type of perforating disorder have been noted in skin biopsies from patients with chronic renal failure, it has been suggested that this condition be referred to as the acquired perforating dermatosis of chronic renal failure. This eruption occurs in up to 10% of patients on dialysis but has also developed in patients with renal failure even without dialysis treatment. The lesions consist of keratotic papules and nodules on the trunk and extremities (Fig. 38-2). They occur more commonly in black patients. Skin biopsy confirms the diagnosis. Recently, treatment with narrow band ultraviolet B radiation has been reported to be effective in the treatment of this condition. This eruption may resolve spontaneously over a period of months.
Patterson JW: The perforating disorders, J Am Acad Dermatol 10:561–581, 1984.
13. What are the differences between Kyrle’s disease, reactive perforating collagenosis, and perforating folliculitis?
All three disorders are classified as perforating diseases; however, as originally defined, Kyrle’s disease is due to an abnormal clone of keratinocytes that perforates through the epidermis down into the dermis. In contrast, reactive perforating collagenosis is a disease in which presumably abnormal collagen is being extruded from the dermis through the epidermis. Perforating folliculitis is a disease characterized by follicular plugs and curled-up hairs that perforate through the follicle into the dermis. Kyrle’s disease is a controversial entity, with some authorities doubting its existence.
14. Describe the porphyria-like eruption of dialysis.
Patients with chronic renal failure on dialysis sometimes develop skin fragility, blisters, hyperpigmentation, and hypertrichosis that is indistinguishable from the cutaneous lesions seen in porphyria cutanea tard (PCT). Although most of these patients do not have elevated levels of porphyrins (pseudoporphyria), some do. When these patients are anuric, plasma and fecal specimens are submitted for porphyrin studies. Elevated porphyrin levels are due to decreased elimination, poor erythropoiesis, decreased activity of uroporphyrinogen decarboxylase (enzyme responsible for PCT), and failure of hemodialysis to remove porphyrins. Hepatitis C infection, iron overload, and medications are exacerbating factors.
Green JJ, Manders SM: Pseudoporphyria, J Am Acad Dermatol 44:100–108, 2001.
Key Points: Cutaneous Manifestations of Renal Disease
1. Uremic frost is the presence of white deposits in the head and neck area seen in patients with severe renal failure.
15. What is Fabry’s disease?
Fabry’s disease (angiokeratoma corporis diffusum universale) is the result of defective activity of a lysosomal enzyme, α-galactosidase A, which leads to deposition of neutral glycosphingo-lipids, particularly trihexosyl ceramides, in many cells and tissues of the body. It is inherited in an X-linked recessive pattern, with nearly all patients being male. Heterozygous females are generally asymptomatic, although they often have characteristic corneal opacities.
Desnick RJ, Brady RO: Fabry disease in childhood, J Pediatrics 144:S20–S26, 2004.
16. Describe the skin lesions in Fabry’s disease.
Angiokeratomas are the skin lesions seen in Fabry’s disease. They begin as pinpoint erythematous to purplish macules or flat papules with slight scaling and often start in early childhood with progressive increase in size and number. They are typically distributed in the “bathing suit area,” the area between the waist and the knees. These lesions may be quite subtle. A skin biopsy may aid in establishing the diagnosis because special stains such as Sudan black B, scarlet red, or periodic acid–Schiff may demonstrate glycolipid deposition in the skin. Electron microscopy is frequently used to help establish the diagnosis because it demonstrates characteristic cytoplasmic glycolipid deposits (typically, within endothelial cells). Other findings in patients with Fabry’s disease include acroparesthesias and acute attacks of severe pain, particularly in the palms and soles, often beginning in childhood. In adult life, cardiac ischemia and infarcts, transient ischemic attacks, stroke, and progressive kidney failure may develop. Recently, treatment with enzyme replacement therapy has become available in Europe (α Gal A) and the United States (agalsidase β [Fabrazyme]).
17. What are the five vasculitic diseases that frequently involve both the kidneys and skin?
• Wegener’s granulomatosis
When skin lesions suggestive of vasculitis occur, a skin biopsy should be done to confirm the diagnosis and determine the type of vessel and inflammation involved (see also Chapter 15). Vessel involvement may vary from small postcapillary venules (leukocytoclastic vasculitis) to medium-sized arteries (polyarteritis nodosa). If vasculitis is confirmed, testing should be done to determine if the kidneys are also involved.
18. How should skin biopsy be used for the diagnosis of systemic amyloidosis?
In primary systemic amyloidosis, immunoglobulin light-chain proteins and serum amyloid P (SAP) are deposited in skin, tongue, heart, spleen, joints, peripheral nerves, and carpal ligaments due to an underlying plasma cell dyscrasia or multiple myeloma. Cutaneous changes may be present, including purpura of the upper trunk, face, and neck and eyelid purpura, which is very characteristic of primary systemic amyloidosis (Fig. 38-3). Waxy papules, particularly on the palms and fingertips, have also been reported. Secondary systemic amyloidosis is due to chronic inflammatory diseases such as tuberculosis and other infections, connective tissue diseases, hidradenitis suppurativa, and familial periodic fever syndromes, and is due to deposition of a distinctive nonimmunoglobulin protein designated AA (amyloid A protein), of which the precursor is an acute-phase reactant produced by the liver. Cutaneous lesions due to amyloid deposits are rarely seen in this type of amyloidosis. Even when there are no cutaneous changes present, skin biopsy may help make a diagnosis of primary or secondary systemic amyloidosis. Clinically, normal skin, abdominal fat, tongue, rectal, and minor salivary gland biopsies have been used to confirm the diagnosis, thus avoiding the need for more invasive biopsies of internal organs.
Wong CK, Wang WJ: Systemic amyloidosis. A report of 19 cases, Dermatology 189:47–51, 1994.
19. What is nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy)?
Nephrogenic systemic fibrosis is a recently described systemic disorder with prominent cutaneous findings seen in patients with impaired renal function who have received gadolinium-based contrast media. Many, but not all, of the patients have been on hemodialysis. It presents as thickened or edematous skin that primarily affects the extremities and trunk. Some patients may also demonstrate discrete papules or plaques. In severe cases, there may be restriction of movement or disabling contracture of the joints. Fibrosis may also involve extracutaneous sites including the sclera (yellow scleral plaques), the heart, lungs, and the skeletal muscle. Histologically, biopsies demonstrate increased numbers of CD34-positive and procollagen-positive fibroblasts and increased mucin in early lesions with marked fibrosis in later lesions, often involving the subcutaneous fatty septae. By energy dispersive spectroscopy, particles of gadolinium can be detected within involved tissues. Treatment has been disappointing as the condition is often refractory to all treatments.
