Last month, we discussed the non-specific dermatologic manifestations of end-stage renal disease, which included pruritis and xerosis. We now address the specific disorders. You’ll find that appropriate evaluation and workup will lead to successful diagnosis and intervention.

Metastatic calcification

Metastatic calcification refers to the precipitation of calcium salts in normal tissue because of defects in calcium or phosphate metabolism. Calcification can affect the kidneys, lungs, blood vessels, gastric mucosa, and subcutaneous and cutaneous tissues.

Benign nodular calcification (calcinosis cutis)/metastatic calcinosis cutis

Calcinosis cutis is relatively rare. Calcifications are found in the skin and lab investigations reveal an elevated serum calcium (CA) and sometimes hyperphosphatemia. It’s the most common metabolic condition associated with renal failure.

Examination reveals firm papules, plaques and nodules, and there may be a chalky discharge. The most common sites include periarticular areas and fingertips. Periarticular involvement is mostly asymptomatic unless joint mobility is compromised but fingertip lesion can be quite painful. The degree of involvement correlates with calcium and phosphate levels, so lesions can disappear with normalization of levels.

The main principle of treatment is to help normalize the calcium and phosphate levels. Decreasing dietary phosporus (i.e. milk, milk products; vegetables: broccoli, brusssel sprouts, artichokes; protein: oyster, liver, salmon; beverages: beer, colas, cocoa, ale) is key. Phosporus-binding antacids and parathyroidectomy are other options.

Calciphylaxis

Calciphylaxis refers to a progressive cutaneous necrosis caused by small and medium vessel calcification. It can be life threatening as it’s usually complicated by infection and sepsis (i.e. staphylococcal sepsis after infection of chronic ulcerations). Mortality rates range from 60-80% with a 5-year mortality rate of more than 50%. Its incidence ranges from 1% in patients with chronic renal failure to 4% of patients receiving hemodialysis (HD). Risk factors for its development include female sex, dietary factors, obesity, and diabetes.

Clinically, lesions are bilateral, symmetric, firm, painful, non-ulcerating purpuric plaques or nodules. There may be a mottling or violaceous discoloration on the limbs, often with a reticulated pattern. It progresses to ecchymosis, with cordlike nodules. Flaccid or hemorrhagic bullae may form over ischemic tissue. Local necrosis results in superficial or deep angulate or stellate ulcers with gangrene. Peripheral pulses tend to be preserved distal to areas of necrosis.

The distribution of the lesions has prognostic value. Patients with acral lesions (fingers, toes) and distal lesions (calves, forearms) tend to have a better prognosis (23%) than those with proximal lesions (thighs, buttocks and trunk) (63%).

Cutaneous calciphylaxis can be associated with systemic calciphylaxis with a range of manifestations including myopathy, hypotension, fever, dementia and infarction of the CNS, bowel or myocardium. The most useful technique for diagnosis is incisional biopsy. The diagnosis tends to be clinical as biopsy and radiographic findings are usually nonspecific. Lab investigations can help rule out vasculitides, cryoglobulinemias, connective tissue diseases and pancreatic paniculitis.

Treatment is challenging, as the course tends to be progressive despite therapy. Known triggers should be minimized such as blood products, immunosuppressants, obesity and injections into proximal adipose tissue.

Goals of therapy involve normalizing calcium and phosphate products and controlling secondary hyperparathyroidism with a low phosphate diet, low calcium dialysate and the use of dietary phosphate binders without calcium carbonate. IV pamidronate therapy is used in severe cases, as well as calcium chelators. A subtotal parathyroidectomy, or total with autotransplantation of one gland into the forearm, if there is hyperparathyroidism, is also an option.

Bullous dermatosis

Porphyria cutanea tarda

Porphyria cutanea tarda (PCT) is a disorder of the hepatic heme biosynthesis pathway associated with uroporphyrinogen decarboxylase deficiency. It’s a vesiculobullous skin disorder with a prevalence of 1.2-18% in patients receiving HD. PCT associated with ESRD is similar to sporadic PCT induced by other agents. The blistering photosensitive rash is composed of tense vesicles and bullae distributed on the dorsa of the hands, face and sometimes feet. The skin is fragile. Secondary features include erosions and crusts. Blisters heal with scarring and milia formation.

Diagnosis relies on measuring porphyrins in the urine, stool and blood and treatment involves avoiding triggers such as alcohol and estrogens. Sun avoidance is very important as visible light can induce skin lesions.

Standard HD doesn’t effectively remove uroporphyrins. Small volume phlebotomies should be done weekly.

Pseudoporphyria

Pseudoporphyria refers to patients with clinical and histologic features similar to PCT without abnormal porphyrin levels. Similar clinical features to PCT are seen; however, most do not show hypertrichosis or sclerodermoid plaques.

Acquired perforating dermatosis

Acquired perforating dermatosis (APD) is the result of altered connective tissue within the dermis being eliminated through the epidermis with little damage to surrounding structures. Patients will often complain of severe pruritus. Up to 10% of patients receiving HD should expect to develop APD.

Clinically, there are keratotic, dome-shaped, grouped papules, and nodules, 1-10 mm in diameter. Papules may be umbilicated with a central keratotic plug. In lighter skin they appear pink, while in darker-skinned patients they appear brown or hyperpigmented. Lesions are typically distributed on hair bearing, friction areas. The trunk and extremities are most commonly affected, followed by the face and scalp. The course is often chronic with new lesions appearing as old lesions fade.

Hydrating the skin (i.e. use of emollients), and treating the pruritus of ESRD (i.e. phototherapy) can improve the perforating disorder. Topical retinoids, doxycline and systemic isotretinoin have all been effective in flattening lesions. APD may resolve after renal transplantation.

Fibrosing dermopathy of uremia

Fibrosing dermopathy of uremia is a newly recognized fibrosing skin condition found in dialysis patients and those post-renal-transplantation.

Characteristic lesions involve diffuse thickening of the skin with hyperpigmentation, with occasional discrete papules and nodules most prominent on extremities and less commonly on the torso. Soft tissue calcification is rare.

Treatment is challenging. Immunosuppressive therapy is of little benefit and topical retinoids, steroids, and vitamin D are not effective.