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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2007  |  Volume : 18  |  Issue : 3  |  Page : 443-447
Chronic Kidney Disease and Stiff Hands

Nephrology Department, Armed Forces Hospital, Riyadh, Saudi Arabia

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How to cite this article:
Bukhari R, Mousa D. Chronic Kidney Disease and Stiff Hands. Saudi J Kidney Dis Transpl 2007;18:443-7

How to cite this URL:
Bukhari R, Mousa D. Chronic Kidney Disease and Stiff Hands. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2022 Aug 11];18:443-7. Available from: https://www.sjkdt.org/text.asp?2007/18/3/443/33768

   Introduction Top

Nephrogenic fibrosing dermopathy (NFD), which is probably a subset of a condition termed nephrogenic systemic fibrosis (NSF) has recently been described. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] This entity is a progressive form of fibrosis that develops in many organ systems and can result in severe contractures of joints secondary to fibrosis in the overlying skin in patients with end­stage renal disease. We report here a case of NFD developing after repeated gadolinium­menhanced MRI procedures.

   Case Report Top

A 35-year-old man who had living non­related renal transplant (LNRRT) in 1992 was admitted in July 2001 with generalized tonic clonic seizures and a period of loss of consciousness. There was no neurological deficit and other systems examinations were unremarkable. Lab investigations revealed: Na 132 mmol/L, K 3.8 mmol/L, urea 30 mmol/L, creatinine 495 µmol/L, and hemo­globin (HB) 104 g/L. Computerized tomo­graphy (CT) scan and magnetic resonance imaging (MRI) of the brain were within normal limits. Internal jugular catheter was inserted and dialysis initiated due to failing allograft secondary to chronic allograft nephropathy confirmed by allograf biopsy.

Later, an arterio-venous graft was created and the patient continued on regular hemodialysis.

Six months later, the patient was readmitted to the hospital with fever, fatigue, confusion, and agitation. On examination, the patient had a temperature of 38 o c, BP130/78, looked sick, pale and confused, but without any detectable neurological deficits. The laboratory investigations revealed WBC 7,300 µL, Hb 91 g/L, Platelets 283,000 µL, Ca 2.9 mmol/L, Urea 10 mmol/L, creatinine 750 µmole/L. Blood Culture was positive for coagulase negative staphylococci. MRI of the brain revealed high signal intensity on the right parietal region post gadolinium enhancement. The cerebrospinal fluid examination was normal. Immunoglobulin electrophoresis was normal. The bone marrow biopsy was normal. The patient improved with the administration of antibiotics and intense hemodialysis.

A month later, the patient started to complain of poor grip secondary to hand stiffness. He had tender hands and feet with restriction of movement, and with thick hard skin [Figure - 1]. No joint effusion was detected [Figure - 2]. The patient was evaluated by the rheumatologist for mixed connective tissue disease (CTD) and /or scleroderma. Auto-antibodies were negative, complements levels were within normal limits, CK 30 U/L, and LDH 800 U/L. MRI of the upper limbs to role out mixed CTD revealed probable myositis. The patient was started on steroids for a probable diagnosis of overlap syndrome.

The patient was readmitted again after two months with joints' pain in the hands, feet, knees with inability to walk. The patient became chair bound. The laboratory investigations revealed ESR 63, rheumatoid factor 44 Units (normal 0-15), negative ANA, AMA, ANCA, and Anti-RNP. Echocardiogram disclosed mild dilated left ventricle with ejection fraction (EF) of 55-­60% and normal valves. The skin biopsy showed prominent fibroblasts [Figure - 3],[Figure - 4] with positive CD34 staining [Figure - 5]. Accordingly, the diagnosis of NSF was`made in view of this clinical picture with the history of repeated MRI and the skin biopsy findings. The patient was advised to have regular physiotherapy and to maintain adequate dialysis. He had a living non-related renal transplant (LNRRT) three years after the onset of the NSF. The patient's general condition improved and the skin changes Ameliorated. He eventually was able to walk with the help of a walking aide.

   Discussion Top

NSF/NFD was first identified in 1997 with the use of high dose erythropoietin [1] Until December 2006 the US Food and Drug administration (FDA) received 90 reports of CKD patients who developed NSF/NFD within two days to 18 months after recei­ving high dose of gadolinium (Omniscan, OptiMark or Magnevist) for MRI or MRA, usually in high dose [2],[9],[10] A European report described NFD in a similar group of 13 patients who also received Omniscan.

In our patient, the first exposure to MRI was during the evaluation for his convulsion in July 2001, and the second exposure was six month later, when the MRI was performed twice. The patient started to complain of hand stiffness one week later, and his symptoms worsened gradually until the diagnosis was confirmed mainly by skin biopsy.

NSF/NFD occurs exclusively in patients with kidney disease be it acute or chronic and usually presents with hard skin and skin biopsy that reveals increased number of fibroblasts. [3],[4],[8],[11] It is a systemic disease with fibrosis that may involve skin, diaphragm, lung, heart and skeletal muscle. [3],[4],[5],[7]

NSF/NFD affects males and females equally and may be associated with hyper­coagulable status that may result in the clotting of AV fistulas and thrombotic loss of renal transplants. [3]

The skin lesions are usually symmetrical with swollen, tight, and thick skin in the upper and lower limbs, However the skin of the face is, spare. Thick skin inhibits the flexion and extension of the joints and results in contractures with inability to walk. Hyper­pigmentation of the skin, patches and plaques with itching may occur. Pain, Raynaud's phenomenon, or telangiectasia have not been reported with NFD. The skin biopsy with CD34 staining is diagnostic. Careful testing for coagulation factors levels is recommended. A recent article described three patients in Europe who responded with softening of plaques after several courses of extracorporeal photopheresis (ECP). 6 Pento­xifylline, in a dose of 1200 mg /day orally, has been tried because of its antifibrotic activity, but it proved to be of limited use. Renal transplantation is the definitive treatment for the NSF/NFD. MRI with gadolinium should be avoided in NSF/NFD. In January 2007, US FDA alerted healthcare professionals to reports of NSF/NFD in patients with renal failure exposed to gadolinium. [2] When a CKD patient requires an imaging study, the physician should select an imaging method other than MRI, or MRA without a gado­linium based contrast agent for the study whenever possible. If such patients need to receive a gadolinium-based contrast agent, prompt dialysis following the MRI or MRA should be considered. Excretion of gadolinium during three consecutive hemodialysis sessions are 78%, 96%, 99%.respectively. [2]

   Questions Top

Dr. Akram Asker (KKUH, chairman of RNTC): The case is open for discussion. Audience: are there any cases reported of NSF in children?

Dr. Bukhari: not that I know of.

Dr. Dujanah Mousa: I do not know if any of the audience could explain why there no cases of NSF reported before 1997?

Dr. Khurchid (Security Forces Hospital): I concur with you. There must be a missing factor. Gadolinium has been used in abun­dance long before 1997. Whether acidosis that can change the nature of gadolinium and lead to stimulation of fibroblasts is the mechanism, I am not sure. It is not clear at present. Further study is warranted.

Prof. Jamal Alwakeel (King Khaled University Hospital): There maybe drug interaction that should be sought for such as erythropoietin and gadolinium. The search for such interaction and all the possible factors should be exhausted.

Dr.Askar: Research is needed to elucidate the pathogenesis of NSF and the possible interactions of factors involved in this entity.

Audience (from King Faissal Specialist Hospital): I still have my doubt that NSF is merely a result of gadolinium. This association is merely observational in nature and may turn out to be not real Cause and effect relationship has not been proven beyond any doubt as we have only obser-vations and not a prospective controlled study. There are other examples in the literature about presumed cause and effect associations that were not substantiated with further study.

   Acknowledgment Top

We would like to thank Dr Hussah Al Husseini the histopathologist at Riyadh Military Hospital for her help in the skin biopsy.

   References Top

1.Swaminathan S, Ahmed I, McCarthy JT, et al. Nephrogenic fibrosing dermopathy and high-dose erythropoietin therapy. Ann Intern Med 2006;145:234-5.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.www.fda.gov FDA reports on NSF and Gadolinium (December 21.2006).  Back to cited text no. 2    
3.Daram SR, Cortese CM, Bastani B. Nephrologenic fibreosing dermopathy/­nephrogenie systemic fibrosis: report of a new case with literature review. Am J Kidney Dis 2005;46:754-9  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Ohtake T, Negishi K, Okamoto K, et al. Managanese-induced Parkinsonism in a patient undergoing maintenance hemo­dialysis Am J Kidney Dis 2005:46(4): 749-53.  Back to cited text no. 4    
5.Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004; 30:569-77.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Gilliet M, Cozzio A, Burg G, Nestle FO. Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis. Br J Dermatol 2005;152:531-6.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing dermo­pathy with systemic involvement. Arch Dermatol 2003; 139:903-6.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Mosehellah SL, Kay J, Mackool ST, Liu V, Case records of the Massachusetts General Hospital. Weekly Cliniocopatho­logical exercises case 35-2004. A 68 year old man with end stage renal disease and Thickening of the skin N Engl J Med 2004;351:2219-27.  Back to cited text no. 8    
9.Grobner, T. Gadolinium a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?. Nephrol Dial Transplant 2006; 21:1104-6.  Back to cited text no. 9    
10.Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17 (9):2359-62.  Back to cited text no. 10    
11.Swartz RD, Crofford LJ, Phan SH, et al. Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure. Am J Med 2003;114:563-5.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]

Correspondence Address:
Rafat Bukhari
Nephrology Department, Armed Forces Hospital, P.O. Box 7897, Riyadh 11159
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 17679762

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]


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