Calciphylaxis

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Classification according to ICD-10
E83.50 Calciphylaxis
ICD-10 online (WHO version 2019)

The calciphylaxis or calciphylaxis (syn .: uremic-calcifying arteriolopathy , abbreviated UCA ; metastatic calcification ) is a particularly severe and painful onset form of bone loss due to kidney disease ( renal osteodystrophy ). It is characterized by pathological deposits of calcium and phosphate salts in the blood vessel walls and in the subcutaneous fatty tissue. These deposits lead to severe damage and inflammation of the affected blood vessels ( vasculitis ) and the subcutaneous fat tissue ( panniculitis ) and can lead to death ( necrosis ) of the affected tissues and vessels.

History

The term calciphylaxis was coined in the 1950s and 1960s by Hans Selye , who used it to describe the reaction process of a pathological calcium deposit based on anaphylaxis . After applying a “sensitizer” ( parathyroid hormone or dihydrotachysterin administered to Selye ) he was able to induce a hypercalcemic metabolic state in rats. The subsequent administration of a “challenger” (mechanical or chemical) can trigger calcification. Depending on the challenger, the affected tissues of calcification can be predicted.

causes

In most cases, calciphylaxis is based on a severe kidney disease ( nephropathy ) with functional impairment ( renal insufficiency ). The nephropathy leads to a disruption of the calcium and phosphate excretion of the kidneys. The calcitriol produced by healthy kidneys is no longer produced in sufficient quantities. This reduces the inhibiting influence of calcitriol on the production of parathyroid hormone (PTH) in the parathyroid gland, so that an increased production of parathyroid hormone takes place (secondary hyperparathyroidism ). Hyperphosphataemia (increased phosphate level in the serum) develops with simultaneous hypocalcaemia (reduced calcium in the serum). The increased phosphate levels as a result of the parathyroid hormone can lead to a combination of phosphate with calcium in the tissue, which in turn leads to calcium deposits. In addition to the calcifications in abnormal places, the result is a thinning of the bone substance ( renal osteodystrophy ), comparable to osteoporosis .

If these processes continue unchanged (for example in the event of inadequate therapy), there is a further increase in phosphate in the serum. Additional influences such as acidification of the blood ( acidosis ) favor the formation of calcium phosphate salts in non-natural areas such as the vessel walls of the small arteries ( arterioles ) or the subcutaneous fatty tissue. The salts formed there have a damaging effect on the tissue and cells, and if the amount increases, they are also fatal, so that the affected tissue dies (necrosis). Alternatively, the storage of salts, especially in the small arteries, in conjunction with the storage of fat, can lead to critical vascular bottlenecks or occlusions with subsequent circulatory disorders.

In rare cases, calciphylaxis can occur even in the absence of kidney disease. The underlying diseases are given as: primary hyperparathyroidism , cancer , alcoholic liver cirrhosis , collagenosis , therapy with glucocorticoids , warfarin , protein C deficiency and protein S deficiency .

classification

Clinically, two forms of the course can be distinguished according to the location of the occurrence of the calciphylaxis:

  • Leg-stomach type: This affects the soft tissues, especially the legs and the abdomen ( abdomen )
  • Limb type: The toes and fingers are mainly affected. The penis can also be affected.

The distinction between the leg and stomach type and the extremity type is of secondary importance. Only the local operative therapy of necrosis can differ according to the localization; there are no differences in terms of general treatment principles.

Symptoms

The first symptom is usually itching (pruritus), which can indicate a storage of calcium salts in the connective tissue. The itching symptom is not particularly specific to calciphylaxis and can have other causes even in the context of severe kidney disease ( uremia ). Subsequently, there is sometimes painful bluish discoloration of the skin over the affected areas with a reticular or speckled appearance ( livedo reticularis ). As the disease progresses, this discoloration changes to a typical necrosis (death) with dark blue to black discolored tissue and sometimes massive pain. In the fingers and toes in particular, necrosis can lead to mummification of the affected tissues. The dead tissue can also fall off.

Differential diagnosis

The clinical picture of calciphylaxis shows diseases which, for other reasons, lead to circulatory disorders. These diseases are

Some of the above conditions can co-occur with or contribute to calciphylaxis. Calciphylaxis can be aggravated or accelerated by vasculitis caused by an autoimmune disease, especially if the kidney is also damaged by the autoimmune disease (often). Many patients with diabetic angiopathy also have severe to extremely severe damage to the kidneys (diabetic nephropathy). The damage to the kidneys and the resulting calciphylaxis aggravate the mostly already existing diabetes-related vascular damage (diabetic angiopathy).

Complications

The most serious complication of calciphylaxis is the superinfection of the skin ulcers and necrosis, mostly with bacteria .

therapy

The therapy is primarily directed against the underlying hypercalcemia and includes the elimination of risk factors. The lowering of the calcium and phosphate level in the serum should be aimed either through dietary measures, the administration of calcium-free phosphate binders or through dialysis to a low-normal level. Existing vitamin D or iron therapy should also be discontinued.

As a cumulative effect of these measures, the overproduction of parathyroid hormone should be stopped. If the hyperparathyroidism cannot be eliminated with medication alone - especially in the case of massive enlargement of the parathyroid glands - their partial surgical removal is indicated. If calciphylaxis has occurred, partial removal of the parathyroid glands is usually indicated.

Fighting bacterial superinfections is difficult because the tissue (mostly also the surrounding area) is severely damaged and wound healing is therefore restricted. Systemic antibiotics are often indicated because of the dangerous nature of bacterial superinfection , but their effectiveness is limited by the poor blood supply to the affected tissue.

Local measures for improved wound healing such as vacuum drainage or special wound dressings are used to treat the affected tissue. If a superinfection cannot be brought under control or if the corresponding tissue has already died, nothing usually remains except for the amputation or removal of the affected area.

forecast

The prognosis for calciphylaxis is serious and the mortality rate is high (up to 80%). In particular, the bacterial superinfections of the affected areas often elude effective control.

swell

  • L. Goldman, D. Ausiello (Eds.): Cecil Textbook of Medicine. 22nd edition. WB Saunders Company, 2003.
  • H. Selye, G. Gabbiani, B. Tuchweber: About a calcifying form of anaphylactoid inflammation. In: Allerg. Asthma. 1962; 8, pp. 177-181.
  • H. Selye: The dermatologic implications of stress and calciphylaxis. In: Journal of Investigative Dermatology . 1962; Volume 39, pp. 259-175.
  • H. Selye, G. Gentile, JM Dieudonne: Effect of adjuvants upon cutaneous calciphylaxis induced by topical or systemic challenge. In: Int. Arch. Allergy. 1962; 20, pp. 80-92.
  • MN Budisavljevic et al: Calciphylaxis in chronic renal failure . In: J Am Soc Nephrol . No. 7 , 1996, pp. 978-982 ( article abstract ).

Individual evidence

  1. ↑ Wesley Yung-Hsu Yu, Tina Bhutani, Rachel Kornik, Laura B. Pincus, Theodora Mauro: Warfarin-Associated Nonuremic Calciphylaxis . In: JAMA Dermatology . doi : 10.1001 / jamadermatol.2016.4821 ( jamanetwork.com [accessed January 15, 2017]).
  2. ↑ Sagar Nigwekar et al: Calciphylaxis from Nonuremic Causes: A Systematic Review . In: Clin J Am Soc Nephrol . No. 3 , 2008, p. 1139-1143 ( abstract ).
  3. ↑ D. Lipsker, O. Chosidow, F. Martinez, E. Challier, C. Francès: low-calcium dialysis in Calciphylaxis. In: Arch Dermatol. 1997; 133, pp. 798-799.
  4. ↑ SM Moe, M. Reslerova, M. Ketteler et al: Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). In: Kidney Int . 2005; 67, pp. 2295-2304.
  5. ^ HY Wang, CC Yu, CC Huang: Successful treatment of severe calciphylaxis in a hemodialysis patient using low-calcium dialysate and medical parathyroidectomy: case report and literature review. In: Ren Fail. 2004; 26, pp. 77-82.
  6. ↑ Gerd Herold: Herold internal medicine. 1st edition. 2013, ISBN 978-3-9814660-2-7 , pp. 648 ff.

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