Nephrogenic systemic fibrosis

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Classification according to ICD-10
M35.8 Other specified diseases with systemic involvement of the connective tissue
ICD-10 online (WHO version 2019)

The nephrogenic systemic fibrosis (NSF) , formerly known as fibrosing dermopathy Nephrogenic or as dialysis -associated systemic fibrosis refers to is a pathological increase of the connective tissue of the skin, muscle and internal organs such as liver, heart, lungs and diaphragm. The disease is very rare and only occurs in patients with severely impaired kidney function , dialysis patients, or liver transplant recipients ; it is progressive and can lead to severe disability and death. The diagnosis is made by examining a tissue sample.

history

The clinical picture was first described in 2000. There are no known cases prior to 1997. In 2006 a possible connection with the administration of contrast media containing gadolinium was reported for the first time . Also in 2006, the US Food and Drug Administration announced that it had reports of 90 patients with NSF who had previously received gadolinium as a contrast agent as part of an MRI scan. So far 315 NSF cases have been described worldwide.

Clinical picture

Nephrogenic systemic fibrosis affects women and men equally. Early signs are symmetrical red or dark spots, nodules (papules) or plates (plaques) on the hands and feet, which over the course of days to weeks progress to thickening and hardening of the skin (indurations) that are reminiscent of an orange peel. The trunk of the body can be affected, the head and neck are often spared. The skin thickening is similar to scleroderma , impairs joint mobility and eventually leads to contractures . This can result in affected patients being unable to use their hands or walk. Infestation of the lungs , heart muscle , skeletal muscles and diaphragm has also been described.

root cause

The disease occurs within a period of two days to 18 months after the administration of gadolinium-containing contrast media. These are used for examinations on the magnetic resonance tomograph or magnetic resonance tomography . Often times higher doses than those specified by the manufacturer were given. Gadolinium deposits could be detected in skin samples from patients. An NSF has so far been described in connection with the gadolinium-containing contrast agents Omniscan , OptiMARK (only approved in the USA), Magnevist and MultiHance . The majority of the cases that have been confirmed and published in the scientific literature occurred after the use of Omniscan , but some also occurred after the use of Magnevist. The Federal Institute for Drugs and Medical Devices (BfArM) therefore ordered a license change for Omniscan and Magnevist in May 2007 , so that Omniscan and Magnevist can no longer be used in patients with severe kidney impairment or in patients who have had or are planning to have liver transplants.

Today it is assumed that the release of highly toxic free gadolinium ions causes or contributes to the development of NSF. Although it cannot be ruled out that all preparations containing gadolinium can cause NSF, the Pharmacovigilance Working Group (PhVWP) of the European Committee for Medicinal Products for Human Use (CHMP) assumes that the chemical properties of the contrast media allow a certain risk classification:

  • low risk: contrast media with a cyclical structure (release of gadolinium ions rather unlikely): Dotarem , Gadovist and ProHance
  • medium risk: contrast medium with linear-ionic structure: Magnevist. MultiHance. Primovist and Vasovist
  • high risk: contrast media with linear nonionic structure (release of gadolinium ions likely): Omniscan and OptiMARK

In line with this assessment, the PhVWP recommended further, graded changes to the approval for all contrast media containing gadolinium. These approval changes have now been implemented in Germany.

diagnosis

Specific changes in laboratory values ​​are not known. C-reactive protein and blood sedimentation are often elevated. In contrast to scleromyxedema , no paraproteins are detectable. In the fine-tissue examination of tissue samples of the skin, a considerable thickening of the dermis is found with an accumulation of thick bundles of collagen fibers in the stratum papillare and subcutaneous tissue , which are separated from one another by large fissures. In addition, thick strands of connective tissue run through the subcutaneous fatty tissue to the fascia . The mucins can be slightly increased, but there are no inflammatory changes. CD34 + dendrocytes are abundant, factor XIIIa + and CD68 + monocytes as well as multinucleated cells are increased.

treatment

The avoidance of gadolinium-containing contrast media in high-risk patients or preventive measures when administration of such contrast media is absolutely necessary, including dialysis after the administration of contrast media, should reduce the incidence of NSF. Intensive physical therapy is recommended to prevent contractures caused by hardening of the skin . The intravenous administration of sodium thiosulfate can possibly have a beneficial effect on the disease. Sodium thiosulfate, by forming chelates, may increase the solubility of gadolinium, which can lead to better removal from tissues. Sodium thiosulfate also has antioxidant properties.

literature

  • HJ Michaely, HS Thomsen, MF Reiser , SO Schoenberg: Nephrogenic systemic fibrosis (NSF) - implications for radiology. In: Radiologe , 2007, 47, pp. 785-793. PMID 17624507

Web links

Individual evidence

  1. ↑ Alphabetical index for the ICD-10-WHO version 2019, volume 3. German Institute for Medical Documentation and Information (DIMDI), Cologne, 2019, p. 273
  2. ^ SE Cowper, HS Robin, SM Steinberg, LD Su, S. Gupta, PE LeBoit: Scleromyxoedema-like cutaneous disease in renal-dialysis patients. In: The Lancet . 2000; 356, pp. 1000-1001. PMID 11041404 .
  3. ^ T. Grobner: Gadolinium-a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? In: Nephrol Dial Transplant . 2006, 21, pp. 1104-1108. doi: 10.1093 / ndt / gfk062 PMID 16431890 .
  4. ↑ Development of Serious, Sometimes Fatal Nephrogenic Systemic Fibrosis / Nephrogenic Fibrosing Dermopathy following exposure to Gadolinium-based Contrast Agents. FDA Information for Healthcare Professionals; Retrieved November 30, 2012.
  5. ^ SE Cowper: Nephrogenic Fibrosing Dermopathy . NFD / NSF website, 2001–2009; Retrieved August 9, 2009.
  6. ^ WW Ting, MS Stone, KC Madison, K. Kurtz: Nephrogenic fibrosing dermopathy with systemic involvement . In: Arch Dermatol. , 2003, 139, pp. 903-909. PMID 12873886
  7. ↑ JA Schroeder, C. Weingart, B. Coras et al .: Ultrastructural evidence of dermal gadolinium deposits in a patient with nephrogenic systemic fibrosis and end-stage renal disease. In: Clin J Am Soc Nephrol . , 2008, 3, pp. 968-975. doi: 10.2215 / CJN.00100108 PMID 18385397
  8. ↑ Omniscan (gadodiamide) and other gadolinium-containing MRI contrast media: restrictions on use for patients with impaired renal function and other warnings . Federal Institute for Drugs and Medical Devices, 2007; accessed on March 7, 2019.
  9. ↑ Rote-Hand-Brief on Magnevist ® . (PDF; 144 kB) AkdÄ - Drugs Commission of the German Medical Association; Retrieved November 30, 2012.
  10. ↑ Increased risk of nephrogenic fibrosing dermopathy / nephrogenic systemic fibrosis and gadolinium-containing MRI contrast agents. (PDF) EU PhVWP; accessed on March 7, 2019.
  11. ↑ F. Jan, H. Mahboob, AB Schwartz: Quiz page February 2008: A hemodialysis patient with thickened skin. Nephrogenic fibrosing dermopathy . In: Am J Kidney Dis . , 2008, 51, pp. A33-A34. PMID 18215691
  12. ↑ M. Heinrich, M. Uder: Nephrogenic systemic fibrosis after the use of gadolinium-containing contrast media - a status paper on the current state of knowledge. In: Fortschr Röntgenstr. , 2007, 179, pp. 613-617. PMID 17497597
  13. ↑ P. Yerram, G. Saab, PR Karuparthi, MR Hayden, R. Khanna: Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure - role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. In: Clin J Am Soc Nephrol. , 2007, 2, pp. 258-263. doi: 10.2215 / CJN.03250906 PMID 17699422