Larva C.A. Vincent M.D.INTERNISTAManuel Galecio 1208 y Av. del Ejército (Centro Guayaquil)Bálsamos #629 ...
JEADV ISSN 1468-3083REVIEW ARTICLEBlackwell Publishing LtdCalciphylaxis – a topical overviewG Arseculeratne,*† AT Evans‡, ...
Calciphylaxis – a topical overview                                                                                        ...
Arseculeratne et al.                                                                                                   Cal...
Calciphylaxis – a topical overview                                                                                        ...
Arseculeratne et al.                                                                                            Calciphyla...
Calciphylaxis – a topical overview                                                                                        ...
Arseculeratne et al.                                                                                             Calciphyl...
Calciphylaxis – a topical overview                                                                                        ...
Arseculeratne et al.                                                                                                Calcip...
Calciphylaxis – a topical overview                                                                                        ...
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  1. 1. Larva C.A. Vincent M.D.INTERNISTAManuel Galecio 1208 y Av. del Ejército (Centro Guayaquil)Bálsamos #629 e/ Ficus y Las Monjas (Urdesa)Telf.: 2280008 / 2320936 Cel.: 0981137366 / 097226405Guayas - Ecuador
  2. 2. JEADV ISSN 1468-3083REVIEW ARTICLEBlackwell Publishing LtdCalciphylaxis – a topical overviewG Arseculeratne,*† AT Evans‡, SM Morley††Department of Dermatology and ‡Department of Pathology, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UKKeywords Abstractend-stage renal disease (ESRD), calcific uraemicarteriolopathy (CUA), calciphylaxis, secondary ‘Calciphylaxis’, a calcification syndrome associated with ischaemic cutaneoushyperparathyroidism, skin ulceration necrosis, is acquired naturally in humans in disease states. It is a life and limb- threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal*Corresponding author, Department of or parathyroid disease. The reported mortality rate, which ranges from 60– 80%,Dermatology, Ninewells Hospital and Medical relates to wound infection, sepsis and organ failure. It is a small-vesselSchool, Dundee DD1 9SY, Scotland, UK, vasculopathy, which is estimated to occur in about 4% of haemodialysistel. +1382 632294; patients. Clinically, violaceous, reticulate areas of cutaneous necrosis andfax. +1382 633916;E-mail: eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroidReceived: 28 October 2004, accepted 27 January hormone level, radiographic evidence of vessel and soft-tissue calcification and2005 the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally hasDOI: 10.1111/j.1468-3083.2006.01506.x a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis. following experimental observations in animal models.Pathophysiology Selye utilized ‘sensitizing’ agents (parathyroid hormone,Atherosclerosis, arteriosclerosis and Mönckeberg’s dihydrotachysterol) followed by ‘challenging’ agents suchsclerosis are vascular diseases associated with calcification as metal salts, egg white or yolk and albumin to induceand it is recognized that Mönckeberg’s sclerosis, which calcification. As the process was considered to be one ofaffects smaller elastic arteries, is a cardiovascular risk factor ‘induced hypersensitivity’, resulting in local calcificationin patients with diabetes mellitus.1,2 Arterial calcification following the two-step process of sensitizing and challengingis considered to be a strong independent risk factor forcardiovascular morbidity and mortality, and hyper- Box 1 Calciphylaxisphosphataemia, as well as an increased calcium phosphorousproduct, are recognized as predictors of cardiovascular • A small and medium vessel vasculopathy • First described by Hans Selye in 1962risk in patients with chronic renal disease.3–5 Calciphylaxis • Referred to as calcific uraemic arteriolopathy (CUA), when vascularis a relatively poorly understood syndrome which pre- calcification occursdominantly affects small- and medium-sized blood vessels, • Usually associated with chronic renal disease and secondaryand is a life-threatening entity usually seen in patients hyperparathyroidismwith renal disease, and may manifest as ischaemic • Estimated to occur in about 4% of haemodialysis patients10cutaneous necrosis (Box 1). Calcification of cutaneous • Incidence of new cases, 1 case per 100 haemodialysis patients pervasculature is known to be associated with chronic renal year • Known to occur in the absence of renal or parathyroid diseasedisease.6 The association between cutaneous gangrene and • Mortality, ranging from 60 –80%, relates to sepsis and organ failurevascular calcification was described by Bryandt and White • May manifest as cutaneous necrosisin 1898.7 Calciphylaxis was described by Hans Selye in 1962JEADV 2006, 20, 493–502 © 2006 European Academy of Dermatology and Venereology 493
  3. 3. Calciphylaxis – a topical overview Arseculeratne et al.(i.e. analogous to anaphylaxis), it was termed calciphylaxis.8,9 expression occurs in arteries from MGP knock-out miceIt is known, however, that the clinical appearance and the and phosphorous has been shown to induce the expressionhistolopathogical findings on which a diagnosis of of Cbfa1 in vascular smooth muscle cells – Cbfa 1 is eviden-calciphylaxis is made, differ between animal models and tially considered to play a key role in blood vessel calcifi-humans. Experimental calcinosis is known to produce cation in the dialysis population.24–26 Bone proteins areextravascular rather than arteriolar/arterial calcification, known to be expressed in calcified arteries in patients withhence the term calcific uraemic arteriolopathy (CUA), calciphylaxis and there is evidence to suggest that mineral-proposed by Coates et al. when vascular calcification forming micro-organisms (nanobacteria) can induceoccurs.11,12 Calciphylaxis as a syndrome was proposed by calcium deposition in mammalian cell cultures and mayGipstein et al. in 1976 and Winklemann and Keating play a role in human diseases characterized by extra-osseousdescribed vascular calcification and cutaneous necrosis, calcification.27–29 Bone morphogenic protein-4 (BMP-4),developing on a background of hyperparathyroidism result- which is physiologically involved in bone metabolism, ising from adenoma/carcinoma.13,14 In patients with end- considered to play a role as a promoter of vascular medialstage renal disease (ESRD), increased dietary calcium, calcification.30calcium-based phosphate binders, calcium absorptionfrom dialysate, abnormalities of bone buffering andturnover contribute to positive calcium balance.15 The Clinical featureswidespread use of oral phosphate binders to combat Metastatic calcification is a well-recognized complicationuraemic osteodystrophy has been implicated as a causative observed in patients with chronic renal disease and occursfactor in accelerating uraemic vasculopathy in the dialysis as a result of elevated calcium or phosphate levels resultingpopulation.16 Attention to mineral metabolism is vital in the in calcium deposition in normal tissue. Relatively acutemanagement of patients with renal disease. The United States cutaneous necrosis is a recognised feature of calciphylaxisNational Kidney Foundation Clinical Practice Guidelines (Box 2). Early lesions may have a purpuric componentrecommends that in stage 5 chronic kidney disease, the while violaceous reticulate skin lesions, painful induratedserum calcium, phosphate and the calcium phosphorous areas (‘peau de orange’), tender subcutaneous nodules,product should be maintained between 8.4 and 9.5 mg/ irregularly ulcerated areas and eschar formation beingdL, 3.5–5.5 mg/dL and less than 55 mg2/dL2, respectively.17 evident subsequently (fig. 1). Violaceous, mottled, painful Several proteins are known to play key roles in the cutaneous lesions should alert clinicians to the possibilitypathogenesis of calcification. Studies on vascular disease of calciphylaxis.31 The initial presentation may appearincluding calciphylaxis in humans have revealed glycopro- similar to that of thrombophlebitis and calf pain is ateins such as matrix Gla protein (MGP) and osteopontin recognized presenting symptom.32,33 Patients may present(OPN), in pathological arteries, and these findings support with indurated plaques without ulceration, painful ulceratedthe view that they play a role in the development of plaques and livedoid bleeding in the lower limbs, leadingvascular fibrosis and calcification.18 In animal models, to sepsis and death in about 60% of such patients.34,35OPN has been shown to play a nephro-protective role in Extra-cutaneous calciphylaxis has been described involvingvivo as an inhibitor of calcium oxalate crystal formation in muscle and rhabdomyolysis, resulting in leg pain andthe renal tubules.19 Alpha 2-Heremans-Schmid glycoprotein/ weakness, has been reported in calciphylaxis in thefetuin A (ahsg/fetuin) is a serum protein, produced by the absence of chronic renal failure.36,37 Acute calcification ofliver in adults, which has been shown to play a preventative major organs such as the heart and lungs may give rise torole in the pathogenesis of calcification.20 This protein is the syndrome of ‘bony’ heart and lungs, the latter beingknown to act systemically to inhibit ectopic calcification, a cause of acute respiratory failure in these patients.38,39and fetuin-A knock-out mice are known to develop extra- Intractable cardiac failure may follow renal transplantationskeletal calcification in the presence of hypercalcaemia,demonstrating that this protein plays a key role in the Box 2 Clinical features of calciphylaxisinhibition of calcification. Normalization of impaired • Purpuric/violaceous reticulate or mottled areas of cutaneousinhibition of hydroxyapatite precipitation following discolorationaddition of fetuin-A to the serum of dialysis patients hav- • Proximal or distal involvementing calciphylaxis has been demonstrated.21 Core-binding • Non-healing ulcersfactor alpha 1 (Cbfa 1), a transcription factor, is considered • Painful cutaneous or subcutaneous necrosis/gangreneto play a key role in activating stem cells into osteoblasts • Eschar formation • Clinical similarity to thrombophlebitisand Cbfa knock-out mice have been shown to be unable • Calf pain and tendernessto produce mineralized bone.22,23 It has also been demon- • May be associated with calcification of internal organsstrated that, together with arterial mineralization, Cbfa494 JEADV 2006, 20, 493–502 © 2006 European Academy of Dermatology and Venereology
  4. 4. Arseculeratne et al. Calciphylaxis – a topical overview Box 3 Differential diagnosis of calciphylaxis • Vasculitic syndromes • Cryoglobulinaemia (type 1) • Cryofibrinogenaemia • Cholesterol embolism syndrome • Warfarin-induced skin necrosis (WISN) • Disseminated intravascular coagulation (DIC) • Nephrogenic fibrosing dermopathy (NFD) • Scleromyxedema • Primary hyperoxaluria • Connective tissue diseases • Atherosclerotic peripheral vascular diseasefig. 1 Calciphylaxis affecting right leg with ulceration and eschar formation. • Pyoderma gangrenosum • Antiphospholipid antibody syndrome • Cellulitisas a result of cardiac calciphylaxis. Cardiac calciphylaxis • Panniculitismay be localized and has been described in association with • Deep fungal infections • Necrotizing fasciitisnanobacteria affecting the mitral valve.40 Penile gangreneas well as Fournier’s gangrene are known complicationsof calciphylaxis and rarely, areas such as the tongue maybe affected by calciphylaxis.41–43 Calcific cerebral embolism atherosclerotic peripheral vascular disease, cellulitisis a recognized cause of neurological symptomatology in and necrotizing fasciitis may all have clinical featurespatients with renal disease.44 The occurrence of the rash resembling those of calciphylaxis and need exclusion.53in meningococcal sepsis is considered to be associated Calciphylaxis has a wide differential diagnosis and therefore,with extravasation of calcium from the intravascular in addition to the routine haematological and biochemicalspace into the interstitium and therefore bears some parameters, investigations such as a vasculitis screen,similarity to the pathophysiology of calciphylaxis.45 estimation of cryoglobulins and cryofibrinogens, fibrin degradation products (FDPs), antiphospholipid antibodies, and Doppler assessment of limb vessels need to be considered.Differential diagnoses Involvement of subcutaneous arterioles in calciphylaxisVasculitic syndromes, cholesterol embolization syndrome, can be assessed by xeroradiography, a technique which iscryoglobulinaemia, cryofibrinogenaemia, warfarin-induced known to demonstrate that the appearance of arteriolarskin necrosis (WISN) and disseminated intravascular calcification differs from that of atherosclerosis.54coagulation (DIC) may present with cutaneous featuressimilar to that of calciphylaxis (Box 3).46,47 Cowper et al.described scleromyxoedema-like cutaneous disease in Clinical associationshaemodialysis patients and nephrogenic fibrosing Calciphylaxis has been described in association withdermopathy (NFD) in renal transplant patients.48 Both metastatic malignancies, primary hyperparathyroidismthese entities are associated with thickening of skin in (with normal renal function), end-stage liver disease/patients with renal disease and need to be considered in alcoholic liver disease, rheumatoid arthritis and long-termthe differential diagnosis. An increase in the number of steroid and methotrexate use and protein S deficiency infibroblasts, as well as thickening of collagen fibres are seen the absence of renal disease.55–60 Among other associationsin this rare fibrosing disorder of NFD, and its occurrence are cholangiocarcinoma, malignant melanoma of softwith calciphylaxis, has been reported.49 Scleromyxoedema, parts (clear-cell sarcoma) with calciphylactic changes ina rare entity which is characterized by papular mucinous the absence of renal or parathyroid disease, necrotizingdeposits, dermal fibroblast proliferation and monoclonal mastopathy (caused by calciphylaxis) and long-standingparaproteinaemia, also needs to be considered in the Crohn’s disease.61–64 Ultraviolet light treatment wasdifferential diagnosis of calciphylaxis.50 Type 1 primary considered to have triggered calciphylaxis in a patientoxaluria, a cause of cutaneous necrosis, needs to be con- who had renal disease secondary to systemic lupussidered in the differential diagnosis.51 Skin manifestations erythematosus.65 Calciphylaxis can be associated withof connective tissue diseases, such as livedoid erythema, widespread visceral injury and a case with massive gastro-may mimic some of the manifestations of calciphylaxis.52 intestinal haemorrhage has been described.66 CoexistenceAntiphospholipid antibody syndrome, deep fungal of benign nodular calcification and calciphylaxis haveinfections, panniculitides, pyoderma gangrenosum, been described in a haemodialysed patient.67 WidespreadJEADV 2006, 20, 493–502 © 2006 European Academy of Dermatology and Venereology 495
  5. 5. Calciphylaxis – a topical overview Arseculeratne et al.Box 4 Calciphylaxis-recognized risk/trigger factors and precipitants Diagnosis and prognosis • High calcium-phosphate product The diagnosis of calciphylaxis is based on clinical, • Hypercalcaemia biochemical and histopathological features.82 A high • Hyperphosphataemia • Hyperparathyroidism index of suspicion needs to be maintained, particularly in • Females patients with renal impairment. An elevated PTH level, • Caucasians high calcium, an elevated phosphate level, an elevated • Long-term obesity calcium phosphorous product, elevated alkaline phos- • Corticosteroids phatase, a high urea and creatinine value and anaemia • Hypercoaguable states may be noted. It is recognized, however, that calciphylaxis • Low serum albumin can occur despite normal calcium and phosphate levels. • Albumin infusions • Iron-dextran injections Elevation of the enzyme alkaline phosphatase may reflect • Warfarin chronicity of the underlying renal disease and hyper- • Vitamin D treatment parathyroidism while anaemia may reflect underlying • Immunosuppression renal disease or poor nutrition as a result of chronic • Trauma illness. A ‘pipe-stem’ pattern of vascular calcification may • Diabetes mellitus be noted on conventional radiography and calcification • Subcutaneous insulin injections of subcutaneous arterioles may be noted on xeroradio- • Dialysis dependency graphy. A recent case report documents increased tracer accumulation in subcutaneous tissue in a patient with ESRD and calciphylaxis, who underwent a bone scancalciphylaxis has been described in patients with the for pain in the extremities.83 Radiography may revealacquired immunodeficiency syndrome in association subperiosteal bone resorption and enlargement of thewith renal disease and has also been reported to occur in parathyroid glands may be evident on echography. Vascularassociation with osteosclerotic myeloma.68,69 Coexistent mural calcification has been noted to be an early andantiphospholipid antibody syndrome and calciphylaxis has essential process in the development of calciphylaxisbeen documented and calciphylaxis has also been reported plaques.84 Mural calcification occurs in small and mediumin association with POEMS (Crowe–Fukase) syndrome, a sized blood vessel walls (arteries and arterioles) andplasma-cell lymphoproliferative disease.70,71 A recent case intimal proliferation may be noted (fig. 2a). Special stainsreport documents calciphylaxis in a patient with chronic may demonstrate calcium deposits and degeneration ofmyelomonocytic leukaemia.72 Calciphylaxis needs to be elastic fibres. Inflammation may be absent or minimal.considered in the differential diagnosis of renal failure in Histological features of pseudoxanthoma elasticum havepatients with transplanted kidneys.73 been observed in association with calciphylaxis.85 Perineural calcification may occur in association with vascular calcification in patients with calciphylaxis, and may beRisk/trigger factors contributory to pain associated with the syndrome86Risk/trigger factors for calciphylaxis include renal impair- (fig. 2b). Experimental neurotropic calcification has beenment, being a female, Caucasian race, obesity, warfarin demonstrated in animal models.87 Oxalate crystals mayuse, hypercoaguable states, diabetes mellitus, dialysis be noted in tissue biopsies in cases of primary oxaluria,dependency, protein malnutrition and those receiving and in deep skin biopsies, calcifying septal panniculitiscalcium salts and vitamin D therapy (Box 4).74–78 Albumin may be noted. An endovascular giant cell reaction may beinfusions as well as subcutaneous insulin injections have observed microscopically and early endovascular fibro-been considered as being precipitants of calciphylaxis.79,80 blastic activation has been found to be statisticallyIn most series, patients with co-morbid conditions strongly associated with the presence of giant cells.88 Agenerally have had a worse prognosis. It has been deep incisional biopsy is likely to provide a betterestimated that the incidence of new cases of calciphylaxis histological yield but in cases where a biopsy is inadvisableis 1 case per 100 haemodialysis patients per year and a owing to sepsis or the potential to aggravate ulceration,mathematical formula {2 × [CaP0(4) – 5] × alkaline the biochemical and endocrine profile may be sufficientphosphatase level (IU) × PTH ratio} has been suggested as to make the diagnosis and institute early managementbeing useful in identifying patients at risk of developing strategies. High-resolution high-frequency ultrasoundcalciphylaxis, this arithmetic model being based on a may aid in the diagnosis of lesions, prior to the occurrenceliterature review of calciphylaxis, clinical observations of the typical skin lesions.89 In a case series of five patients,and physiological principles.81 extensive tissue involvement, previous renal transplant496 JEADV 2006, 20, 493–502 © 2006 European Academy of Dermatology and Venereology
  6. 6. Arseculeratne et al. Calciphylaxis – a topical overview poor prognosis (Box 5). Prevention of systemic infection is vital. Diligent wound care, avoidance of trauma, and appropriate antibiotic usage together with nutritional support and adequate pain control are important aspects of general care of these patients. Neurolytic lumbar sympathetic blockade (LSB) has been proven to be a useful method of alleviating pain associated with calciphylaxis.93 In the initial stages when skin is eroded, gentle handling is important and careful dressing of wounds with material such as petrolatum-impregnated gauze help to minimize tissue damage. Debridement and skin grafting may be warranted – however, the role of debridement is con- troversial and it has been suggested that debridement is contraindicated for wounds covered with dry, non-infected eschars.94 Sterile maggot therapy and pentoxyfillin has been used to treat ulcerated areas in calciphylaxis.95 Transcutaneous oxygen tension (TCPO2) measurement has been used as a rapid non-invasive screening for skin ischaemia before the development of skin lesions.96 Attention to calcium and phosphate levels are vital in the management of patients with this syndrome and referral to a dietician is an important facet of treatment. Increased frequency of haemodialysis too has been employed as a management strategy. Calcium- and aluminium-free phosphate binders such as sevelamer hydrochloride (RenaGel) have been found to be useful in the manage- ment of renal osteodystrophy particularly in patients with extraskeletal calcification and hypercalcaemia.97 In a study by Chertow et al. haemodialysis patients treated with sevelamer were found to be protected from increased calcification of the aorta and coronary arteries.98 Caution should be exercised with the use of calcium-containingfig. 2 (A) Histological appearance of circumferential mural calcification of heparins as calcifying panniculitits has been reportedan arteriole affected by calciphylaxis (H&E preparation, magnification following subcutaneous injections of nadroparin-×300). (B) histological appearance of perineural calcification in calciphy- calcium in a patient with osteomalacia.99 Hyperbariclaxis (H&E preparation, magnification ×200). oxygen therapy has been used particularly in the absence of severe secondary hyperparathyroidism where relativelyand higher preoperative leucocyte counts (over 20 000 few therapeutic options are available.100,101 Attention tocells/mL) were found to be factors related to early death and regulation of divalent metabolism is required prior toin patients with calciphylaxis.90 In another case series of considering revascularization procedures in patients withsix patients with CUA, a relationship between distal calciphylaxis.102 Parathyroidectomy is known to belocation of the lesions, normal serum albumin and early associated with resolution of pain, wound healing and adiagnosis were related to survival, rather than the type longer median survival in patients with calciphylaxis.103–110of treatment patients received.91 In a study of seven Total parathyroidectomy and auto-transplantation ofpatients with calciphylaxis, lesion severity at time of tissue to the forearm has proven to be satisfactory in someparathyroidectomy correlated with clinical outcome.92 cases, subtotal parathyroidectomy being an alternative surgical approach.111 Healing of lower extremity ulcers in 22 patients with calciphylaxis has been reported followingManagement ‘near total’ parathyroidectomy (where a vascularizedMaintenance of a high index of suspicion, early recognition parathyroid remnant is left in situ); this procedure alsoand timely, appropriate intervention as well as an active being noted to improve bone density in patients withmultidisciplinary approach are mandatory in com- hyperparathyroidism.112 Recurrent hyperparathyroidismbating the syndrome of calciphylaxis, which has a has been reported and re-operation may be warranted inJEADV 2006, 20, 493–502 © 2006 European Academy of Dermatology and Venereology 497
  7. 7. Calciphylaxis – a topical overview Arseculeratne et al. Box 5 Management of calciphylaxisPrinciples • Maintenance of a high index of suspicion • Early intervention • An active, multidisciplinary approachPrevention/Treatment Options • Use of calcium-free/aluminium-free phosphate binders (e.g. sevelamer hydrochloride) • Institution of a low-phosphate diet • Increased frequency of haemodialysis • Correction of anaemia • Use of less calcaemic vitamin D analogues • Wound care debridement/skin grafting • Use of appropriate antibiotics • Adequate pain control • Parathyroidectomy (total, subtotal, near-total) • Hyberbaric oxygen therapy • Intravenous bisphosphonates • Intravenous sodium thiosulphate • Continuous veno-venous haemofiltration and intravenous sodium thiosulphate • Intravenous maxacalcitol and percutaneous ethanol injection therapy (PEIT) (a preventative role)such cases.113 Revascularization and amputation may other disease entities in the absence of renal or parathyroidhave to be resorted to in cases where all other supportive disease. A high index of suspicion, early intervention, and anand conservative measures have failed. Steroid use has active multidisciplinary medical and surgical approach arebeen associated with calciphylaxis, but treatment of a vital aspects of the management strategy. Discovery of serumpatient with renal failure with oral prednisolone followed proteins, which play key regulatory roles in calciumby cimetidine has been reported to have reversed changes homeostasis, is likely to lead to novel therapeutic conceptsof calcifying panniculitis.114 Sodium thiosulphate, an which will broaden the therapeutic armamentarium avail-antidote for cyanide poisoning, is recognized to be a able to clinicians who manage patients with calciphylaxis.potent antioxidant as well as a chelator of calcium.115Intravenous sodium thiosulphate may have an adjunctiverole in therapy – it has been documented to reverse the Acknowledgementssigns and symptoms of calciphylaxis.116,117 Rapid resolution We are grateful to the Computing and Media Servicesof calciphylaxis has been reported following intravenous Department, Ninewells Hospital and Medical School,sodium thiosulphate and continuous veno-venous Dundee, Scotland, for providing the illustrations.haemofiltration.118 In experimental animal models, theamino bisphosphonate ibandronate has been found toinhibit arterial calcification at doses that inhibit bone Referencesresorption, and improvement of calciphylaxis has been 1 Lehto S, Niskanen L, Suhonen M et al. Medial arteryreported after the intravenous use of pamidronate in a calcification. A neglected harbinger of cardiovascularpatient with chronic renal failure.119,120 Intravenous maxa- complications in non-insulin-dependant diabetes mellitus.calcitol, a vitamin D (3) formulation, used in conjunction Arterioscler Thromb Vasc Biol 1996; 16: 978–983.with percutaneous ethanol injection therapy (PEIT) has 2 Niskanen L, Siitonen O, Suhonen M et al. Medial arterybeen documented to lead to a reduction in PTH secretion, calcification predicts cardiovascular mortality in patientsregression of parathyroid hyperplasia and control of the with NIDDM. Diabetes Care 1994; 17: 1252–1256.calcium-phosphorous product in dialysis patients – this 3 Block GA. Control of serum phosphorous: implicationscombination is also considered to have a preventative role for coronary artery calcification and calcific uremicin vascular calcification in the dialysis population.121 arteriolopathy (calciphylaxis). Curr Opin Nephrol Hypertens 2001; 10: 741–747. 4 Block GA. Prevalence and clinical consequences ofConclusions elevated Ca X P product in hemodialysis patients. ClinCalciphylaxis is potentially lethal syndrome seen usually Nephrol 2000; 54: 318– patients with end-stage renal disease and secondary 5 Cannata-Andia JB, Rodriguez-Garcia B.hyperparathyroidism. It may, however, be associated with Hyperphosphataemia as a cardiovascular risk factor-how498 JEADV 2006, 20, 493–502 © 2006 European Academy of Dermatology and Venereology
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