Blog
About

16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Calciphylaxis in a 33-year-old man with end-stage renal disease

      Annals of Saudi Medicine

      King Faisal Specialist Hospital and Research Centre

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Calciphylaxis is an uncommon and poorly understood cutaneous phenomenon associated with chronic renal failure (CRF). The cardinal features are cutaneous purpura and necrosis as well as histopathologic findings of calcifications of cutaneous vessel walls. There is significant morbidity from this disease, which is mainly caused by overwhelming sepsis.1 Case Report A 33-year-old man known to have end-stage renal disease (ESRD) of unknown cause who had kidney transplantation twice was referred to the dermatology clinic in November 2002 with a one-week history of rash over both thighs associated with a severe burning sensation. The patient was diagnosed with ESRD requiring haemodialysis in 1988. He underwent a first renal transplantation (living, unrelated) in India in 1991 and had a rejection after 3 years, which required a return to haemodialysis. Four months prior to presentation he had a second renal transplantation in Iran (living, unrelated), which also rejected after 6 weeks. As a consequence he was put on hemodialysis again. This patient had severe hyperparathyroidism as well. Current medications were oral prednisolone 17.5 mg once daily, oral tacrolimus 2 mg twice daily, oral ferrous sulphate 325 mg thrice daily, gancyclovir 500 mg orally thrice weekly, amlodipine 5 mg orally once daily, omeprazole 20 mg orally once daily, prazocin hydrochloride 2 g orally thrice daily and aluminum hydroxide 2 tablets thrice daily. Physical examination revealed multiple purpuric macules and papules over the medial aspect of both upper thighs down to the knees. The legs and buttocks were not involved. Systemic examination was unremarkable. Blood work showed a low haemoglobin and haematocrit (Table 1). Mean corpuscular volume, mean corpuscular haemoglobin, white blood cell count, platelets count, bilirubin level, prothrombin time, and partial thromboplastin time were normal. Parathyroid hormone was very high. Serum urea and serum creatinine were elevated. Serum sodium, chloride, protein C, protein S and fasting glucose were within normal limits. Total calcium was normal, but due to low albumin, the corrected calcium was high. Serum phosphate was elevated, and accordingly, the calcium phosphorus product was high. Urinalysis is shown in Table 1. HIV serology was negative. X-ray of lower limbs showed a significant calcification of blood vessels. Initial skin histopathological examination showed intradermal hemorrhage but no evidence of vasculitis. Two weeks later, the patient showed up in clinic with more progressive lesions, which were very painful. There were multiple large subcutaneous indurated plaques covered with multiple small hemorrhagic vesicles and black eschar over both thighs (Figure 1). A second skin biopsy revealed that the epidermis, dermis and subcutaneous tissue were necrotic and there was a significant amount of microthrombi. Several subcutaneous vessels contained calcium deposits in their walls (Figure 2). This picture is consistent with calciphylaxis. Bacterial, fungal and mycobacterial cultures were all negative. The patient was admitted to hospital and had a parathyroidectomy. Histopathological examination revealed hyperplasia of all parathyroid glands. Despite parathyroidectomy, the patient showed progressive skin necrosis and blistering over thighs, legs, feet, abdomen, buttocks and distal fingers (Figure 3). Wound dressing was carried out daily, without significant improvement. Discussion Calciphylaxis occurs mostly in patients with chronic renal failure and recent renal transplantation, although patients with normal renal function have been reported.2 Pre-dialysis patients and those undergoing both haemodialysis and peritoneal dialysis have presented with calciphylaxis.3 Kidney transplant recipients account for 32% to 38% of calciphylaxis cases, including patients with normally functioning grafts.4,5 Our patient had ESRD and was on haemodialysis after rejection of two kidney transplants. He received glucocorticoids and immunosuppressive medications, mycophenolate mofetil, tacrolimus, and ferrous sulphate. All are known precipitating factors for calciphylaxis.6,7 Because of lowered vitamin D in ESRD patients (the active metabolite of vitamin D is transformed in the kidney), there is decreased calcium absorption from the intestine. Low serum vitamin D, low serum calcium, and high serum phosphate lead to secondary hyperparathyroidism. Most patients with calciphylaxis have abnormalities of calcium-phosphate homeostasis with elevated levels of parathyroid hormone, but these changes as well as an elevation of the calcium-phosporus product are not always present in this disease.5 This suggests that other important elements must contribute to calciphylaxis. Skin biopsy of the lesions showed numerous organized thrombi, which means a coagulation defect might be the missing link.8 Our patient had severe hyperparathyroidism. A pre-existing hypercoagulable status has also been hypothesized to predispose affected patients to calciphylaxis.8,9 In support of this mechanism, functional abnormalities in either protein C or protein S have been reported in several patients with calciphylaxis. However, these proteins have also been normal in other patients, including our case.4,5,10 Early lesions of calciphylaxis manifest either as non-specific violaceous mottling, livedo reticularis, purpuric patches and plaques or as erythematous papules, plaques or nodules. More developed lesions have a stellate purpuric configuration with central cutaneous necrosis. Later lesions are exquisitely tender, extremely firm to touch, evolving into irregular ulcers covered by thick dark eschars. Lesions can be distributed proximally (on the thighs, buttocks and abdomen) or distally (below the knee). Our patient had proximal lesions initially, which later extended distally. Ninety percent of lesions are found on the lower extremities.1,11,12 Necrosis of the penis secondary to calciphylaxis has also been described.7,13 Despite the dramatic cutaneous necrosis, no internal organ failure is reported in patients with calciphylaxis. Our patient’s cutaneous manifestations started as a very mild purpura over the thighs, which did not suggest calciphylaxis. Two weeks later they progressed to full-blown typical calciphylaxis lesions with bullae (which is a rare manifestation). Typical histologic findings are calcification within the media of small and medium-sized arterioles with extensive intimal hyperplasia and fibrosis. Subcutaneous calcium deposits with panniculitis and fat necrosis may sometimes be found. Frequently, vascular microthrombi are seen. Necrosis of overlying epidermis, and often surrounding dermis and subcutis is frequently seen.1,14 In our patient, typical histological findings were obvious. Treatment of calciphylaxis is largely supportive. Aggravating conditions should be addressed and trigger factors eliminated. Normalization of abnormal calcium and phosphorus levels by diet, phosphate binding agents, low-calcium hemodialysis and parathyroidectomy might help.1,15 Aggressive wound care and careful debridement of necrotic tissue are necessary to avoid wound infection and sepsis. Treatment of infections with appropriate antibiotics can be helpful.9 Treatment with hyperbaric oxygen16 and prednisone17 have been anecdotally reported. Patients with hypercoagulability may benefit from judicious anticoagulation. However, the role of anticoagulation in other cases of calciphylaxis is controversial. Prophylactic use of warfarin or heparin is probably not indicated since precipitation of calciphylaxis has occurred with indiscriminate use. In addition, most patients with ESRD have a prolonged bleeding time due to the uremic condition so anticoagulation may be contraindicated.8,18 Total or subtotal parathyroidectomy with auto-transplantation is of therapeutic benefit to many but not all patients.1,19 Only few studies have been able to demonstrate a decrease in mortality rate in those patients who underwent parathyroidectomy.20,21 Normalization of calcium and phosphorus, continuous wound dressing, and total parathyroidectomy did not help our patient. Because of a normal coagulation profile and protein C and S levels, he was not a candidate for anticoagulation. The prognosis in patients with calciphylaxis is poor and the mortality rate is as high as 80%.4 In a review of 104 cases, Hotner et al found that 75% of patient with distal localization of lesions survived compared to 25% with proximal lesions.22 Unfortunately, most patients with calciphylaxis die of overwhelming infection and sepsis resulting from a compromised skin barrier in an immunosuppressed patient with chronic renal failure or after kidney transplantation. 14 No data exist regarding long-term survival, if one survives an episode of calciphylaxis. Two important and unique points about our case are the initial presentation with trivial purpuric lesions and the appearance of blisters, which is a rare manifestation of calciphylaxis. Fortunately, calciphylaxis is a rare disease. Its prevalence has not been established in our area, but is probably lower than estimations in other reports. Because of its generally aggressive behavior, and lack of effective treatment in most cases, early recognition of this disease is crucial. Our poor knowledge of the exact pathophysiology is still the limiting factor for intervention.

          Related collections

          Most cited references 21

          • Record: found
          • Abstract: found
          • Article: not found

          Panniculitis. Part II. Mostly lobular panniculitis.

           L. Requena,  E Yus (2001)
          The second part of our review of panniculitis summarizes the clinicopathologic features of the mostly lobular panniculitides. Erythema induratum of Bazin (nodular vasculitis) represents the most common variant of lobular panniculitis with vasculitis, although controversy persists about the nature of the involved vessels. Mostly lobular panniculitides without vasculitis comprise a series of disparate disorders. These include sclerosing panniculitis that results from chronic venous insufficiency of the lower extremities; panniculitis with calcification of the vessel walls such as calciphylaxis and oxalosis; and inflammatory diseases with crystals within the adipocytes such as sclerema neonatorum, subcutaneous fat necrosis of the newborn, and poststeroid panniculitis. Connective tissue diseases, such as systemic lupus erythematosus and dermatomyositis, pancreatic diseases, and alpha(1)-antitrypsin deficiency may also show a mostly lobular panniculitis with characteristic histopathologic features. Lobular panniculitis may also be an expression of infections, trauma, or factitial causes involving the subcutaneous fat. Lipoatrophy refers to a loss of subcutaneous fat due to a previous inflammatory process involving the subcutis, and it may be the late-stage lesion of several types of panniculitis. In contrast, lipodystrophy means an absence of subcutaneous fat with no evidence of inflammation and often the process is associated with endocrinologic, metabolic, or autoimmune diseases. Finally, cytophagic histiocytic panniculitis is the term that has been used to describe two different processes: one is inflammatory, a lobular panniculitis, and the other one is neoplastic, a subcutaneous T-cell lymphoma. The only common feature of these two different processes is the presence of cytophagocytosis in the lesions. (J Am Acad Dermatol 2001;45:325-61.) At the completion of this learning activity, participants should be familiar with the pathogenesis, clinical manifestations, histopathologic findings, and treatment options for the most frequent variants of the lobular panniculitides.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Calcifying disorders of the skin.

            Calcium is vital to many biologic processes. In skin, it has a profound effect on keratinocyte proliferation, differentiation, and cell-cell adhesion. Serum calcium is tightly regulated by parathyroid hormone and 1,25(OH)2D3. Despite this careful regulation, calcification and ossification of cutaneous and subcutaneous tissues may occur. Cutaneous calcification may be divided into four major categories: dystrophic, metastatic, idiopathic, and iatrogenic. Dystrophic calcification occurs as a result of local tissue injury or abnormalities. Metastatic calcification results from abnormal calcium and/or phosphate metabolism. Virtually any process that calcifies may secondarily ossify. Primary ossification may rarely occur.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy.

              Uremic small-artery disease with medial calcification and intimal hyperplasia can lead to life-threatening skin necrosis or acral gangrene. It is a distinct complication of chronic renal failure that must be differentiated from soft-tissue calcification. An increased calcium-phosphate product and secondary hyperparathyroidism are the main underlying conditions. The benefit of parathyroidectomy is controversial. This article is based on a literature search to determine prognostic factors and, in particular, the benefit of parathyroidectomy. The literature on uremic small-artery disease (so-called calciphylaxis) was reviewed (full data set: 104 cases, including five of our own). The therapeutic benefit of parathyroidectomy and the relation between prognostic predictors (localization, dialysis, and transplant) and outcome were analyzed. The relation between diabetes and acral gangrene was also examined. Further epidemiologic data on the reviewed group of patients were established. Thirty-eight of 58 patients who underwent parathyroidectomy survived compared with 13 of 37 patients who did not undergo parathyroidectomy (p = 0.007, n = 95). Forty of 53 patients with distal localization of necrosis survived compared with 11 of 42 patients with proximal pattern (p < 0.00001; n = 95). Dialysis and kidney transplantation followed by immunosuppression showed no relation to disease outcome. No association was found between diabetes and acral gangrene (p = 0.50). Uremic small-artery disease is a distinct complication of chronic renal failure. Its recognition and early diagnosis should allow more effective treatment. In our retrospective study parathyroidectomy was significantly related to survival. Only a randomized, controlled, prospective trial (parathyroidectomy vs conservative treatment of secondary hyperparathyroidism) can establish the value of parathyroidectomy in uremic small-artery disease.
                Bookmark

                Author and article information

                Journal
                Ann Saudi Med
                Ann Saudi Med
                Annals of Saudi Medicine
                King Faisal Specialist Hospital and Research Centre
                0256-4947
                0975-4466
                Sep-Oct 2005
                : 25
                : 5
                : 415-418
                Affiliations
                From the King Saud University, College of Medicine, Dermatology Department, Riyadh, Saudi Arabia
                Author notes
                Correspondence: Khalid M. Al Ghamdi, MD, King Saud University, College of Medicine, Dermatology Department, P.O. Box 240997, Riyadh 11322, Saudi Arabia, Tel: 966-1-467-1938, Fax:966-1-467-9444, kmgderm@ 123456yahoo.com
                Article
                asm-5-415
                10.5144/0256-4947.2005.415
                6089724
                16270767
                Copyright © 2005, Annals of Saudi Medicine
                Categories
                Case Report

                Medicine

                Comments

                Comment on this article