Pseudoxanthoma elasticum-like changes in longstanding gadolinium-naïve nephrogenic systemic fibrosis in a patient with chronic kidney disease

Sir,

Nephrogenic systemic fibrosis is a rare systemic fibrosing disorder which has been recently described in settings of renal insufficiency, especially with gadolinium exposure.¹ The exact etiopathogenesis is still to be elucidated. Almost no treatment described for the disease has been completely successful. Histopathological features are similar to the sclerodermoid spectrum of disorders. A pseudoxanthoma elasticum like pattern has been rarely reported as an incidental finding in the setting of calciphylaxis. We present such a case in an adolescent with chronic kidney disease.

A 16-year-old boy presented with a history of pruritic skin thickening of one year duration, initially presenting over thighs and later involving the abdomen and legs. It was also associated with multiple, soft swellings which developed from the thickened skin. He was diagnosed with nephrotic syndrome at the age of five years and was on long-term systemic steroids, at a starting dose of 60 mg prednisolone. This dose was tapered gradually to 5 mg till the age of 12 years. He was not on medication at present and was recently detected with stage 5 chronic kidney disease, for which he was on multiple sessions of haemodialysis and erythropoietin injections. Patient also had a history of hypothyroidism and hypogonadotropic hypogonadism, but no exposure to gadolinium. Patient was on 50 μg thyroxine and currently on no drug for hypogonadotropic hypogonadism.

General examination revealed a short stature (height –134 cm), gross ascites, hydrocoele and micropenis. Dermatological examination revealed multiple irregular discrete and confluent sclerotic indurated plaques with amoeboid borders and uneven surface, with soft nodules distributed over the abdomen [Figure 1], anterior chest, thighs and legs. In addition, there were multiple linear atrophic fissured plaques over the upper limbs, axillae and sides of abdomen. Plaques over thighs had a cobblestone texture [Figure 2]. No restriction of range of motion was noticed in any joint.

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Figure 1:

Sclerotic indurated plaques with amoeboid borders (white arrow) and uneven surface with soft nodules distributed over abdomen and anterior chest

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Figure 2:

Cobblestoning of plaques over the thighs

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Relevant investigations demonstrated features of chronic kidney disease: anaemia (haemoglobin - 9 g/dL), hypoalbuminemia (albumin - 1.6 g/dL) and glomerular filtration rate of 28 ml/min/1.73 m². Serum calcium was 8.2 mg, serum phosphorus 3.2 mg and calcium/ phosphorus product was 26.24. Antinuclear antibody and antiphospholipid antibody tests were negative. Ultrasound abdomen with kidney, ureters and bladder showed gross ascites and chronic nephropathy. High resolution computed tomography of chest showed a right-sided pleural effusion without any parenchymal fibrosis. Echocardiogram was normal. Skin biopsy taken from the sclerotic plaque over abdomen and thighs showed dermal fibrosis with haphazardly arranged collagen bundles in a background of a few spindle shaped fibroblasts [Figure 3]. Immunohistochemistry highlighted the CD34 positive fibroblasts in the dermis [Figure 4].

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Figure 3:

Skin biopsy showing dermal sclerosis with spindle shaped fibroblasts, Haematoxylin & Eosin ×400

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Figure 4:

Spindle-shaped fibroblasts with positive CD34 staining, CD34 stain ×400

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Von Kossa staining demonstrated the presence of calcium deposits over fragmented and altered elastic fibres [Figure 5]. The clinical and histological findings were diagnostic of nephrogenic systemic fibrosis with pseudoxanthoma elasticum like changes. The patient was started on NB-UVB phototherapy along with levocetirizine and white soft paraffin application.

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Figure 5:

Dermis showing altered calcified elastic fibres as black irregular strands, Von Kossa ×400

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Our patient was a known case of chronic kidney disease with a history of hypothyroidism and multiple treatment sessions of haemodialysis and erythropoietin therapy, all risk factors for nephrogenic systemic fibrosis, even though he was gadolinium naïve.² Clinical presentation with sclerotic indurated plaques with amoeboid border, cobble-stoning and linear indurated fissured plaques was suggestive of nephrogenic systemic fibrosis and histopathology demonstrating dermal fibrosis with spindle shaped fibroblasts positive for CD34 was diagnostic of nephrogenic systemic fibrosis according to latest European guidelines, while fragmented altered elastic fibres with calcium deposits by Von Kossa stain was diagnostic of pseudoxanthoma elasticum.^3,4 Therefore, we made a final diagnosis of nephrogenic systemic fibrosis with pseudoxanthoma elasticum like changes. This condition is a recently described entity, the pathogenesis being aberrantly directed circulating fibroblasts to the dermis and the subcutis. It resembles other fibrosing dermopathies such as scleromyxedema, scleredema and eosinophilic fasciitis. The systemic features such as joint contractures, cardiomyopathy and interstitial lung disease were absent in our patient. The hallmark of the present case report is the histopathological feature of pseudoxanthoma elasticum-like changes with calcium deposits on the altered elastic fibres, which is extremely rare and hitherto reported in only one case report.⁵ Previously, pseudoxanthoma elasticum-like histopathology has been reported in the context of calciphylaxis.^4-6 However, in our case, there was no clinical evidence of calciphylaxis at the time of presentation. The patient was not toxic and there were no necrotic painful ulcers on the limbs discharging chalky material, which is a classical feature of calciphylaxis. Calcium deposits in a case of nephrogenic systemic fibrosis could be explained in the context of chronic kidney disease, but the pathogenesis of elastic fibre damage in the dermis is still to be elucidated. Pseudoxanthoma elasticum like changes, perforating osteoma cutis and cutaneous mucinosis are rare associations of nephrogenic systemic fibrosis reported in the literature.^5,7,8

This case is reported due to the uniqueness of its presentation, in an adolescent without prior gadolinium exposure and the extremely rare histopathology of pseudoxanthoma elasticum changes in the setting of nephrogenic systemic fibrosis. Calcification of elastic fibres in the setting of nephrogenic systemic fibrosis could be a forerunner of calciphylaxis and systemic involvement, which warrants further investigations and monitoring.