Scleredema is a rare disease that is characterized by symmetrical and nonpitting induration of the skin due to thickened dermis with abundant mucin deposition among large collagen bundles (1). Although many methods have been tried, there is currently no standard treatment.
We report three cases of scleredema diabeticorum treated with tranilast. It is well established that histopathology of pathogenic skin in patients with scleredema diabeticorum shows collagen fiber thickening and type I collagen metabolism abnormalities. In our inspection, a higher level of TGF-β can be seen by immunohistochemistry in patients with scleredema diabeticorum compared with healthy patients. It has been reported that tranilast was able to suppress the TGF-β–induced upregulation of type I collagen mRNA expression and the basal level of type I collagen mRNA in human dermal fibroblasts (2).
A 45-year-old man with type 2 diabetes visited our hospital and told us that his posterior neck and upper back had progressive thickening and wooden induration for 5 years. A skin biopsy showed an expanded reticular dermis and thickened collagen bundles. Epidermal thickness was 8.7 mm. Because there is no standard therapy, the patient did not take other medicine except hypoglycemic drugs. We gave him tranilast 0.3 g/day (we used the recommended dose for the treatment of keloids and asthma to ensure its safety) without any other drugs. The patient’s skin was softened after 3 months’ treatment and ultrasound images showed that his skin thickness was reduced to 6.7 mm.
The second patient was a 49-year-old man with type 2 diabetes complaining of a progressive thickening of his posterior neck, deterioration in his everyday routines, and discomfort. The biopsy also showed an expanded reticular dermis with abundant mucin deposition among thickened collagen bundles. Epidermal thickness was 7.0 mm. After treatment with tranilast (0.3 g/day) for 3 months, however, the condition of the skin started improving, showing a progressive normalization of cutaneous softness, and ultrasound images showed skin thickness was reduced to only 6.0 mm.
We treated the third patient in the same way. She was a 62-year-old woman with a history of chronic and poorly controlled diabetes who complained of a progressive thickening of her skin, worsening daily life activities. Through our treatment, the patient felt that the symptoms of restricted movement were reduced, and her skin thickness got 0.6 mm thinner than before.
In the three cases, all patients had a progressive normalization of cutaneous softness and we could objectively monitor changes in skin thickness by ultrasound imaging. The mechanism of tranilast remains to be clarified; it may be related to the inhibition and regulation of collagen as reported (3,4), thus resulting in a reduction in the thickness of the skin. This is the first report showing that tranilast treatment can benefit patients with scleredema diabeticorum, and it provides a new idea for the therapy of this disease. There is also a need to expand the number of clinical cases to demonstrate the precise efficacy.
Funding. This work was supported by National Natural Science Fund (31371383), Jiangsu provincial Six Talent Peaks (2013-WSN-031), and Jiangsu Education Science 12th Five-Year program (D/2013/01/015).
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. M.S. managed the patients, collected relevant information, and wrote the manuscript. F.Y. analyzed the data and wrote the manuscript. M.H. designed the experiment and the diagnosis and treatment of this disease, reviewed the data and manuscript, and approved the final version. M.H. is the guarantor of this work and takes responsibility for the integrity of the data and the final version of the manuscript.
M.S. and F.Y. are co-first authors.