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Kutane Kalziphylaxie

Cutaneous calciphylaxis

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Zusammenfassung

Die Kalziphylaxie ist ein dermatologischer Notfall mit einer Mortalität von bis zu 80%. Charakteristisch ist die Trias der arteriolären Mediaverkalkung, thrombotisch kutaner Ischämie und nekrotischer Ulzerationen. Früherkennung hilft, Komplikationen wie die Sepsis zu vermeiden. Der Dermatologe kann aufgrund der Hautveränderungen und mithilfe der Histopathologie frühzeitig die Diagnose stellen. Patienten mit terminaler Niereninsuffizienz sind am häufigsten von der Kalziphylaxie betroffen. Die häufigsten nichturämischen Erkrankungen sind der primäre Hyperparathyreoidismus, Malignome, alkoholbedingte Leberkrankungen und autoimmune Bindegewebserkrankungen. Die medikamentöse Behandlung zielt auf eine Normalisierung der Mineralstörungen ab, um die Serumkonzentration von Kalziumphosphat zu vermindern und somit auch Präzipitation und Kalzifizierung vorzubeugen. Neuere Substanzen sind Bisphosphonate, Nonkalzium-/Nonaluminium-haltige Phosphatbinder, Cinacalcet, Paricalcitol und Natriumthiosulfat. Unter den chirurgischen Methoden zeigt die alleinige Parathyroidektomie in retrospektiven Studien keinen signifikanten Überlebensvorteil. Ein verbessertes Überleben fand sich hingegen für eine (aggressive) chirurgische Therapie der nekrotischen Ulzera. Frühzeitige Diagnosestellung und multidisziplinäre Behandlung einschließlich Revaskularisierung durch den Gefäßchirurgen, wiederholtes chirurgisches Débridement und Hauttransplantation können zur verbesserten Wundheilung und zum Extremitätenerhalt beitragen.

Abstract

Calciphylaxis represents a dermatological emergency with a mortality of up to 80%. The disease is characterized by a triad of arteriolar medial calcification, thrombotic cutaneous ischemia and necrotic ulcerations. Recently several mechanisms of vascular calcification have been identified. This may led to preventive measures in the future. Early diagnosis is important to avoid complications such as sepsis. The dermatologist plays an important role in early diagnosis based on the recognition of clinical presentation and histopathology. Patients with end-stage renal disease are most commonly affected by calciphylaxis. The most frequent non-uremic predisposing conditions are primary hyperparathyroidism, malignancies, alcohol-induced liver disease, and autoimmune connective tissue diseases. Medical treatment aims to normalize mineral metabolism to reduce the serum concentration of sodium phosphate and thus to prevent precipitation and calcification. Newer compounds are bisphosphonates, non-sodium/non-aluminium phosphate binders, cinacalcet, paricalcitrol, and sodium thiosulfate. Among the surgical procedures parathyroidectomy did not result in a significant survival benefit. An aggressive surgical debridement of necrotic ulcerations, on the other hand, improved survival. Early diagnosis and a multidisciplinary treatment approach including re-vascularization by the vascular surgeon, repeated surgical debridement and split skin transplantation support wound healing and insure limb conservation.

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Literatur

  1. Acher-Chenebaux A, Maillard H, Potier A et al (2006) Cutaneous calciphylaxis treated by autologous keratinocytes graft and subtotal parathyroidectomy. Ann Dermatol Venereol 133(3):260–263

    CAS  PubMed  Google Scholar 

  2. Amuluru L, High W, Hiatt KM et al (2009) Metal deposition in calcific uremic arteriolopathy. J Am Acad Dermatol 61(1):73–79

    Article  CAS  PubMed  Google Scholar 

  3. Angelis M, Wong LL, Myers SA, Wong LM (1997) Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery 122(6):1083–1089

    Article  CAS  PubMed  Google Scholar 

  4. Arenas MD, Gil MT, Gutiérrez MD et al (2008) Management of calcific uremic arteriolopathy (calciphylaxis) with a combination of treatments, including hyperbaric oxygen therapy. Clin Nephrol 70(3):261–264

    CAS  PubMed  Google Scholar 

  5. Arseculeratne G, Evans AT, Morley SM (2006) Calciphylaxis – a topical overview. J Eur Acad Dermatol Venereol 20(5):493–502

    Article  CAS  PubMed  Google Scholar 

  6. Basile C, Montanaro A, Masi M et al (2002) Hyperbaric oxygen therapy for calcific uremic arteriolopathy: a case series. J Nephrol 5(6):676–680

    Google Scholar 

  7. Bechara FG, Altmeyer P, Kreuter A (2009) Should we perform surgical debridement in calciphylaxis? Dermatol Surg 35(3):554–555

    Article  CAS  PubMed  Google Scholar 

  8. Beitz JM (2004) Calciphylaxis: an uncommon but potentially deadly form of skin necrosis. Am J Nurs 104:36–37

    PubMed  Google Scholar 

  9. Boccara O, Prost-Squarcioni C, Battistella M et al (2010) Calcinosis cutis: a rare reaction to subcutaneous injections of calcium-containing heparin in patients with renal failure. Am J Dermatopathol 32(1):52–55

    Article  PubMed  Google Scholar 

  10. Bonnecarrère L, Templier I, Carron PL et al (2009) Two cases of iatrogenic cutis and subcutis calcinosis after calcium-containing heparin injection. J Mal Vasc 34(5):366–371

    Article  PubMed  Google Scholar 

  11. Bronson N, Menon R, Butler J, Gordon I (2007) Parathyroidectomy, excision and skin grafting with topical negative pressure for calciphylactic ulcers. J Wound Care 16(7):295–297

    CAS  PubMed  Google Scholar 

  12. Carlson JA, Chen KR (2007) Cutaneous pseudovasculitis. Am J Dermatopathol 29(1):44–55

    Article  PubMed  Google Scholar 

  13. Cianciolo G, Donati G, La Manna G et al (2010) The cardiovascular burden of end-stage renal disease patients. Minerva Urol Nefrol 62(1):51–66

    CAS  PubMed  Google Scholar 

  14. Emohare O, Kowohl-Vern A, Latenser BA (2004) Vacuum-assisted closure use in calciphylaxis. J Burn Care Rehabil 25(2):161–164

    Article  PubMed  Google Scholar 

  15. Essary LR, Wick MR (2000) Cutaneous calciphylaxis. An underrecognized clinicopathologic entity. Am J Clin Pathol 113(2):280–287

    Article  CAS  PubMed  Google Scholar 

  16. Giachelli CM (2004) Vascular calcification mechanisms. J Am Soc Nephrol 15(12):2959–2964

    Article  PubMed  Google Scholar 

  17. Goenka AH, Das CJ, Sharma R (2009) Nephrogenic systemic fibrosis: a review of the new conundrum. Natl Med J India 22(6):302–306

    PubMed  Google Scholar 

  18. Hanafusa T, Yamaguchi Y, Tani M et al (2007) Intractable wounds caused by calcific uremic arteriolopathy treated with bisphosphonates. J Am Acad Dermatol 57(6):1021–1025

    Article  PubMed  Google Scholar 

  19. Hayden MR, Goldsmith D, Sowers JR, Khanna R (2008) Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate. Int Urol Nephrol 40(2):443–451

    Article  CAS  PubMed  Google Scholar 

  20. Hitti WA, Papadimitriou JC, Bartlett S, Wali RK (2007) Spontaneous cutaneous ulcers in a patient with a moderate degree of chronic kidney disease: a different spectrum of calciphylaxis. Scand J Urol Nephrol 42(3):181–183

    Article  Google Scholar 

  21. Hussein MR, Ali HO, Abdulwahed SR et al (2009) Calciphylaxis cutis: a case report and review of literature. Exp Mol Pathol 86(2):134–135

    Article  CAS  PubMed  Google Scholar 

  22. Joukhadar R, Bright T (2009) Calciphylaxis in primary hyperparathyroidism: a case report and brief review. South Med J 102(3):318–321

    PubMed  Google Scholar 

  23. Kalajian AH, Malhotra PS, Callen JP, Parker LP (2009) Calciphylaxis with normal renal and parathyroid function: not as rare as previously believed. Arch Dermatol 145(4):451–458

    Article  PubMed  Google Scholar 

  24. Kalisiak M, Courtney M, Lin A, Brassard A (2009) Calcific uremic arteriolopathy (calciphylaxis): successful treatment with sodium thiosulfate in spite of elevated serum phosphate. J Cutan Med Surg 13(Suppl 1):S29–S34

    PubMed  Google Scholar 

  25. Lal G, Nowell AG, Liao J et al (2009) Determinants of survival in patients with calciphylaxis: a multivariate analysis. Surgery 146(6):1028–1034

    Article  PubMed  Google Scholar 

  26. Lee JL, Naguwa SM, Cheema G, Gershwin ME (2008) Recognizing calcific uremic arteriolopathy in autoimmune disease: an emerging mimicker of vasculitis. Autoimmun Rev 7(8):638–643

    Article  CAS  PubMed  Google Scholar 

  27. Lee JS, Basalyga DM, Simionescu A et al (2006) Elastin calcification in the rat subdermal model is accompanied by up-regulation of degradative and osteogenic cellular responses. Am J Pathol 168(2):490–498

    Article  CAS  PubMed  Google Scholar 

  28. Li X, Yang HY, Giachelli CM (2008) BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis 199(2):271–277

    Article  CAS  PubMed  Google Scholar 

  29. Martin R (2004) Mysterious calciphylaxis: wounds with eschar – to debride or not to debride? Ostomy Wound Manage 50(4):64–66, 68–70

    PubMed  Google Scholar 

  30. Mazhar AR, Johnson RJ, Gillen D et al (2001) Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int 60(1):324–332

    Article  CAS  PubMed  Google Scholar 

  31. McMurtry MS (2009) Is this an ischemic ulcer? An approach to peripheral arterial disease for dermatologists. J Cutan Med Surg 13(Suppl 1):S12–S16

    PubMed  Google Scholar 

  32. Milas M, Bush RL, Lin P et al (2003) Calciphylaxis and nonhealing wounds: the role of the vascular surgeon in a multidisciplinary treatment. J Vasc Surg 37(3):501–507

    Article  PubMed  Google Scholar 

  33. Miyazaki-Anzai S, Levi M, Kratzer A (2010) Farnesoid X receptor activation prevents the development of vascular calcification in ApoE–/–mice with chronic kidney disease. Circ Res (im Druck)

  34. Mohammed IA, Sekar V, Bubtana AJ et al (2008) Proximal calciphylaxis treated with calcimimetic „Cinacalcet“. Nephrol Dial Transplant 23(1):387–389

    Article  CAS  PubMed  Google Scholar 

  35. Musso CG, Enz P, Vidal F et al (2009) Use of sodium thiosulfate in the treatment of calciphylaxis. Saudi J Kidney Dis Transpl 20(6):1065–1068

    PubMed  Google Scholar 

  36. Nazarian RM, Van Cott EM, Zembowicz A, Duncan LM (2009) Warfarin-induced skin necrosis. J Am Acad Dermatol 61(2):325–332

    Article  PubMed  Google Scholar 

  37. Negri AL (2005) Vascular calcifications in chronic kidney disease: are there new treatments? Curr Vasc Pharmacol 3(2):181–184

    Article  CAS  PubMed  Google Scholar 

  38. Nigwekar SU, Wolf M, Sterns RH, Hix JK (2008) Calciphylaxis from nonuremic causes: a systematic review. Clin J Am Soc Nephrol 3(4):1139–1143

    Article  PubMed  Google Scholar 

  39. Picazo M, Bover J, La Fuente J de et al (2005) Sterile maggots as adjuvant procedure for local treatment in a patient with proximal calciphylaxis. Nefrologia 25(5):559–562

    CAS  PubMed  Google Scholar 

  40. Prey S, Sparsa A, Durox H et al (2009) Calciphylaxis treated by cinacalcet: a medical alternative to parathyroidectomy (in French). Rev Med Interne 30(2):186–189

    Article  CAS  PubMed  Google Scholar 

  41. Prinz Vavricka BM, Barry C, Victor T, Guitart J (2009) Diffuse dermal angiomatosis associated with calciphylaxis. Am J Dermatopathol 31(7):653–657

    Article  Google Scholar 

  42. Polizzotto MN, Bryan T, Ashby MA, Martin P (2006) Symptomatic management of calciphylaxis: a case series and review of the literature. J Pain Symptom Manage 32(2):186–190

    Article  PubMed  Google Scholar 

  43. Raffetto JD (2009) Dermal pathology, cellular biology, and inflammation in chronic venous disease. Thromb Res 123(Suppl 4):S66–S71

    Article  CAS  PubMed  Google Scholar 

  44. Reed KB, Davis MD (2007) The incidence of physician-diagnosed calciphylaxis: a population-based study. J Am Acad Dermatol 57(2):365–366

    Article  PubMed  Google Scholar 

  45. Requena L (2007) Normal subcutaneous fat, necrosis of adipocytes and classification of the panniculitides. Semin Cutan Med Surg 26(2):66–70

    Article  CAS  PubMed  Google Scholar 

  46. Rockx MA, Sood MM (2010) A necrotic skin lesion in a dialysis patient after the initiation of warfarin therapy: a difficult diagnosis. J Thromb Thrombolysis 29(1):130–133

    Article  PubMed  Google Scholar 

  47. Rogers NM, Coates PT (2008) Calcific uraemic arteriolopathy: an update. Curr Opin Nephrol Hypertens 17(6):629–634

    Article  PubMed  Google Scholar 

  48. Rusanescu G, Weissleder R, Aikawa E (2008) Notch signalling in cardiovascular disease and calcification. Curr Cardiol Rep 4(3):148–156

    Article  CAS  Google Scholar 

  49. Russell R, Brookshire MA, Zekonis M, Moe SM (2002) Distal calcific uremic arteriolopathy in a hemodialysis patient responds to lowering of Ca × P product and aggressive wound care. Clin Nephrol 58(3):238–243

    CAS  PubMed  Google Scholar 

  50. Schlieper G, Brandenburg V, Ketteler M (2009) Sodium thiosulfate in the treatment of calcific uremic arteriolopathy. Nat Rev Nephrol 5(9):539–543

    Article  CAS  PubMed  Google Scholar 

  51. Selye H, Gentile G, Pioreschi P (1961) Cutaneous molt induced by calciphylaxis in the rat. Science 134(3493):1876–1877

    Article  CAS  PubMed  Google Scholar 

  52. Simionescu A, Simionescu DT, Vyavahare NR (2007) Osteogenic response in fibroblasts activated by elastin degradation products and transforming growth factor-β1. Role of myofibroblasts in vascular calcification. Am J Pathol 171(1):116–123

    Article  CAS  PubMed  Google Scholar 

  53. Song J, Volkov S, Shea CR et al (2009) Nephrogenic systemic fibrosis associated with stromal and vascular calcification, report of two cases. J Cutan Pathol 36(Suppl 1):31–34

    Article  PubMed  Google Scholar 

  54. Strippoli D, Simonetti V, Russo G, Motolese A (2008) Calciphylaxis: a case report. Dermatol Ther 21(Suppl 3):S26–S28

    Article  PubMed  Google Scholar 

  55. Thornton JJ, Dolph J (2008) Breast necrosis: calciphylaxis a rare cause. Can J Plast Surg 16(3):165–167

    PubMed  Google Scholar 

  56. Tittelbach J, Graefe T, Wollina U (2001) Painful ulcers in calciphylaxis – combined treatment with maggot therapy and oral pentoxyfillin. J Dermatolog Treat 12(4):211–214

    Article  CAS  PubMed  Google Scholar 

  57. Vargemezis V, Liakopoulos V, Kriki P et al (2010) Pivotal role of paricalcitol in the treatment of calcific uremic arteriolopathy in the presence of a parathyroid adenoma. Am J Kidney Dis 55(1):144–147

    Article  PubMed  Google Scholar 

  58. Vassa N, Twardowski ZJ, Campbell J (1994) Hyperbaric oxygen therapy in calciphylaxis-induced skin necrosis in a peritoneal dialysis patient. Am J Kidney Dis 23(6):878–881

    CAS  PubMed  Google Scholar 

  59. Vattikuti R, Towler DA (2004) Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol Endocrinol Metab 286(5):E686–E696

    Article  CAS  PubMed  Google Scholar 

  60. Weenig RH, Gibson LE, El-Azhary R (2007) The role of the hospital dermatologist in the diagnosis and treatment of calciphylaxis and nephrogenic systemic fibrosis. Semin Cutan Med Surg 26(3):163–167

    Article  CAS  PubMed  Google Scholar 

  61. Weenig RH, Sewell LD, Davis MD et al (2007) Calciphylaxis: natural history, risk factor analysis, and outcome. J Am Acad Dermatol 56(4):569–579

    Article  PubMed  Google Scholar 

  62. Wollina U (2007) Pyoderma gangraenosum – a review. Orphanet J Rare Dis 2:19

    Article  PubMed  Google Scholar 

  63. Wollina U, Hein G (2005) Lupus erythematosus – clinical spectrum of common and uncommon presentations. Clin Dermatol 23:470–479

    Article  PubMed  Google Scholar 

  64. Wollina U, Abdel-Naser MB, Hansel G et al (2005) Leg ulcers are a diagnostic and therapeutic challenge. Int J Low Extrem Wounds 4(2):97–104

    Article  PubMed  Google Scholar 

  65. Wollina U, Hansel G, Gruner M et al (2007) Painful ANA-positive scleroedema-like disease with acral ulcerations – a case of chronic gangraenous ergotism. Int J Low Extrem Wounds 6:148–152

    Article  PubMed  Google Scholar 

  66. Wollina U, Helm C, Hansel G et al (2008) Deep ulcer shaving combined with split-skin transplantation in distal calciphylaxis. Int J Low Extrem Wounds 7(2):102–107

    Article  PubMed  Google Scholar 

  67. Yamanaka Y, Yokota K, Furuya K et al (2006) Successful treatment of calcific uraemic arteriolopathy with wide local excision. Clin Exp Dermatol 31(3):474–475

    Article  CAS  PubMed  Google Scholar 

  68. Yonova D (2009) Vascular calcification and metabolic acidosis in end stage renal disease. Hippokratia 13(3):139–140

    CAS  PubMed  Google Scholar 

  69. Zechlinski JJ, Angel JR (2009) Calciphylaxis in the absence of renal disease: secondary hyperparathyroidism and systemic lupus erythematosus. J Rheumatol 36(10):2370–2371

    Article  PubMed  Google Scholar 

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  1. Klinik für Dermatologie und Allergologie, Krankenhaus Dresden-Friedrichstadt, Städtisches Klinikum, Akademisches Lehrkrankenhaus der Technischen Universität Dresden, Friedrichstr. 41, 01067, Dresden, Deutschland

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Wollina, U. Kutane Kalziphylaxie. Hautarzt 61, 1063–1072 (2010). https://doi.org/10.1007/s00105-010-2026-4

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