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Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 84-86

Nephrogenic systemic fibrosis: A rare complication following exposure to gadolinium-based contrast media

Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan

Date of Web Publication27-Dec-2018

Correspondence Address:
Dr Seema Hashmi
Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Ranchore Lane, Karachi 74200
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AJPN.AJPN_28_18

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Nephrogenic systemic fibrosis (NSF) is a rare complication following exposure to gadolinium-based contrast media. Gadolinium-based contrast agents (GBCAs) are widely used for imaging throughout the world. NSF, formerly known as nephrogenic fibrosing dermopathy, is a rare progressive fibrosing disorder associated with administration of GBCA in patients with severely compromised renal functions. The condition is well reported in adults, but pediatric cases are rarely reported. Out of 1280 cases in the literature of NSF associated with GBCA, only 12 were found in the pediatric age group. We are reporting a pediatric case of a 7-year-old child with chronic kidney disease Stage VD, who developed NSF following magnetic resonance imaging.

Keywords: Chronic kidney disease, gadolinium, nephrogenic fibrosing dermopathy

How to cite this article:
Qaiser H, Tresa V, Khatri S, Ali IB, Lanewala A, Hashmi S. Nephrogenic systemic fibrosis: A rare complication following exposure to gadolinium-based contrast media. Asian J Pediatr Nephrol 2018;1:84-6

How to cite this URL:
Qaiser H, Tresa V, Khatri S, Ali IB, Lanewala A, Hashmi S. Nephrogenic systemic fibrosis: A rare complication following exposure to gadolinium-based contrast media. Asian J Pediatr Nephrol [serial online] 2018 [cited 2021 Sep 19];1:84-6. Available from: https://www.ajpn-online.org/text.asp?2018/1/2/84/248641

  Introduction Top

Nephrogenic systemic fibrosis (NSF) is an extremely rare phenomenon, characterized by progressive tissue fibrosis that diffusely affects the skin and other organs, including the heart, liver, lungs, and muscles. It occurs exclusively in patients with severely compromised renal function who have had exposure to gadolinium-based contrast agents (GBCA) during magnetic resonance imaging (MRI).[1]

  Case Report Top

A 7-year-old boy presented to us with generalized tonic–clonic seizures and altered level of consciousness in October 2014. In the past, he was diagnosed as a case of nephrotic syndrome at 18 months of age. He had a steroid-resistant clinical course and was shown to have mesangioproliferative glomerulonephritis on renal biopsy. He had progressive renal impairment since 2012 and eventually required initiation of hemodialysis 1 week before presentation to our hospital. On admission, he required endotracheal intubation and ventilatory support. MRI brain using contrast (gadodiamide) was performed due to repeated seizure activity. Findings revealed a left parieto-occipital infarct with generalized cerebral edema. Later on, he was extubated as he showed neurological improvement and a good respiratory effort. He was discharged on maintenance dialysis 5 days later but complained of generalized itching all over the body for which antihistamine was advised. He was readmitted 1 week later with seizures and developed extreme irritability accompanied by constant crying. It was also noticed that he had developed a small circular induration over the sacral area. He was discharged after the management of his symptoms. He was maintained on routine hemodialysis twice a week; when, during a hemodialysis session after 50 days of exposure to the contrast agent, skin tightening was noticed all over the body. On further inquiry, it was revealed that he had gradually developed skin thickening over the previous 2 weeks and was unable to sit or stand for last 1 week. Examination showed that he had partially flexed and fixed posture of both the upper and lower limbs. There was thickening, hardening, and dryness of skin texture involving the whole body and cheeks. These were more marked over the distal half of the extremities, and there was multiple hypopigmented irregular-shaped plaque-like lesions present over his back [Figure 1]. Further examination revealed multiple palpable nodules over the forehead and scalp which were nontender, fixed, and firm-to-hard in consistency, ranging in size from 0.5 to 2 cm. Ocular findings included telangiectatic lesions with scleral plaques. Locomotor system examination revealed restricted flexion and extension of all large and small joints with more pronounced restriction of small joints of the hands and feet [Figure 2]. There was also restricted movement of his spine. Laboratory investigations are shown in [Table 1]. Serologies, including for antinuclear antibodies, antineutrophil cytoplasmic antibodies, antiphospholipid antibodies and panel of autoantibodies against double stranded DNA, Smith antigen, histone, SS-B. scleroderma-70, Jo-1, ribonuclear protein and ribosomal-P antigen, were negative or non-reactive.
Figure 1: Hypopigmented plaque-like lesions on the back

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Figure 2: Restriction of movements in lower extremities

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Table 1: Laboratory investigation report

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Incisional skin biopsy was done from two sites, lower back and calf region of the right leg, which showed haphazardly arranged thick collagen bundles with intervening cleft-like spaces and proliferating spindle cells within myxoid stroma in the reticular dermis [Figure 3]. Increased amount of elastic fibers was also noted with focal mucin deposition. Immunohistochemical staining for CD34 showed diffuse positivity in dermal spindle cells [Figure 4].
Figure 3: (a and c) Low-power view showing normal epidermis, and reticular dermis containing irregularly distributed thick collagen bundles with interspersed spindle cells (H and E, ×100). (b) Medium and (d) High power views showing irregularly distributed thick collagen bundles with interspersed cleft-like spaces and spindle cells (H and E, ×200, and ×400, respectively)

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Figure 4: (a) Medium-power view showing acidic stromal mucin highlighted by alcian blue (Alcian blue, ×200). (b) High-power view showing numerous thin elastic fibers running parallel to thick collagen bundles in the dermis (Elastic, ×400). (c) Medium-power view showing CD34-positive spindle cells interspersed among the dermal collagen bundles (CD34 immunohistochemistry, ×200). (d) Medium-power view showing spindle cell proliferation and fibrosis extending to the subcutaneous fat (H and E, ×200)

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On the basis of clinical symptoms and skin biopsy report, a diagnosis of NSF was made. While on maintenance hemodialysis, there was a slight improvement in his condition with increased mobility at elbow and knee joints over 2 weeks. However, subsequently his condition worsened with progressive skin fibrosis and respiratory compromise, and he eventually died 6 weeks after the start of illness.

  Discussion Top

NSF, formerly known as nephrogenic fibrosing dermopathy, is a rare phenomenon, with approximately 23 cases reported between January 1997 and September 2012. Only 17 out of 23 cases were associated with documented exposure to gadolinium.[2] It usually presents as skin thickening, predominantly of the lower limbs. Facial involvement, as seen in our patient, is extremely rare. Contracture formation at joints with limited range of movement of the limbs is present in a significant number of cases. Scleral plaques may also be present.

Histological findings include proliferation of dermal fibroblasts, thickened collagen bundles with intervening clefts, and increased amount of elastic fibers. Most of the spindle dermal cells show positivity for CD34 on immunochemical stains. Mucin deposition along with calcification may also be observed.

Differential diagnosis of NSF includes generalized morphea, scleroderma, and eosinophilic fasciitis, which were excluded in our patient on the basis of clinical features and serological investigations.

Pathophysiology of the development of NSF is still unclear.[3] Majority of the reported cases show an association with exposure to GBCA compounds, but a number of cases have had no prior exposure. Renal failure is almost always present and a pro-inflammatory state contributes to increased predisposition. It is hypothesized that gadolinium, like other metals, is toxic, and that it causes an inflammatory response where it is deposited. Gadolinium is administered in a chelated state to encourage its removal from the body through kidneys. In patients who are in a pro-inflammatory state, the gadolinium ion is dechelated and deposited in tissues. Renal failure further prevents its clearance. The ion then elicits an inflammatory response which results in the recruitment of fibroblasts and deposition of collagen. The incidence of NSF is significantly more in patients undergoing peritoneal dialysis as compared to those undergoing hemodialysis due to slower clearance of contrast in the former.[4]

Many different treatment options have been considered, including steroids, extracorporeal photopheresis, plasmapheresis, cyclophosphamide, thalidomide, ultraviolet light therapy, pentoxifylline, high-dose intravenous immunoglobulin therapy, increased frequency of hemodialysis, and renal transplantation.[4]

As a preventive strategy in children, more emphasis should be given to estimate the glomerular filtration rate (GFR) and consult a nephrologist in case of borderline GFR, avoid double dosing of gadolinium, and consider keeping a record of cumulative contrast exposure for children undergoing multiple MRI.[2]

  Conclusion Top

GBCAs have become an invaluable aid in MRI diagnosis. However, since they carry risk of adverse effects, they should be used judiciously and only when the potential clinical benefits outweigh the theoretical risk.

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Conflicts of interest

There are no conflicts of interest.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

  References Top

Nardone B, Saddleton E, Laumann AE, Edwards BJ, Raisch DW, McKoy JM, et al. Pediatric nephrogenic systemic fibrosis is rarely reported: A RADAR report. Pediatr Radiol 2014;44:173-80.  Back to cited text no. 1
Soares BP, Lequin MH, Huisman TA. Safety of contrast material use in children. Magn Reson Imaging Clin N Am 2017;25:779-85.  Back to cited text no. 2
Thomsen HS. Nephrogenic systemic fibrosis: A serious adverse reaction to gadolinium – 1997-2006-2016. Part 1. Acta Radiol 2016;57:515-20.  Back to cited text no. 3
Morcos SK, Thomsen HS. Nephrogenic systemic fibrosis: More questions and some answers. Nephron Clin Pract 2008;110:c24-31.  Back to cited text no. 4


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

  [Table 1]


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