Elsevier

The Journal of Pediatrics

Volume 159, Issue 6, December 2011, Pages 1004-1011
The Journal of Pediatrics

Original Article
Cysteamine Toxicity in Patients with Cystinosis

https://doi.org/10.1016/j.jpeds.2011.05.057Get rights and content

Objective

To report new adverse effects of cysteamine.

Study design

Detailed clinical information was obtained from the patients’ physicians.

Results

New adverse events were reported in 8 of 550 patients with cystinosis treated with cysteamine in Europe during the last 5 years. Detailed clinical information was not available for 2 of these patients, 1 of whom died from cerebral ischemia. The 6 evaluable patients developed vascular elbow lesions (6/6), neurologic symptoms (1/6), bone and muscle pain (2/6), and/or skin striae (2/6). Analysis of biopsy specimens from the elbow lesions demonstrated angioendotheliomatosis with irregular collagen fibers. In 3 of the 6 patients, the daily cysteamine dose exceeded the recommended maximum of 1.95 g/m2/day. Dose reduction led to improvement of signs and symptoms in all 6 patients, suggesting a causal relationship with cysteamine administration.

Conclusion

Cysteamine administration can be complicated by the development of skin, vascular, neurologic, muscular, and bone lesions. These lesions improve after cysteamine dose reduction. Doses >1.95 g/m2/day should be prescribed with great caution, but underdosing is not advocated.

Section snippets

Methods

Detailed information, including age at diagnosis of cystinosis, CTNS gene mutations, cysteamine dosage, white blood cell (WBC) cystine levels (measured in blood samples obtained 5-6 hours after the last cysteamine administration), adverse events and date of occurrence, further investigations, and follow-up, was collected from the patients’ medical records by their physicians. (All cysteamine doses mentioned hereinafter refer to the amount of cysteamine free-base that was administered,

Results

The Table presents clinical characteristics of the patients who experienced adverse events, along with detailed information on these adverse events, including neurologic symptoms, musculoskeletal weakness, skin striae primarily on the stretchable surfaces of the extremities, and bruise-like lesions of the elbows.

Discussion

We have reported some newly recognized side effects of cysteamine. In all of our patients, the skin lesions and neurologic symptoms diminished or disappeared after the cysteamine dosage was reduced. In 1 of the 2 patients with bone and muscular pain, these symptoms decreased in response to a cysteamine dose reduction. In patient 6, skin lesions relapsed after the cysteamine dose was increased. Based on these findings, we suggest that cysteamine plays a causative role in these symptoms, although

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  • Cited by (0)

    Supported by the Cystinosis Research Foundation. E.L. is supported by the Foundation for Scientific Research Flanders (grant 1801110N). The sponsors had no role in the study design; the collection, analysis and interpretation of data; the writing of the report; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest.

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