Camurati-Engelmann disease is characterized by
hyperostosis of the long bones and the skull,
muscle atrophy, severe limb
pain, and progressive joint
contractures in some patients. It is caused by heterozygous mutations in the
transforming growth factor β1 (TGFβ1) believed to result in improper folding of the latency-associated peptide domain of TGFβ1 and thus in increased or deregulated bioactivity.
Losartan, an
angiotensin II type 1 receptor antagonist, has been found to downregulate the expression of TGFβ type 1 and 2 receptors. Clinical trials with
losartan have shown a benefit in
Marfan syndrome, while trials are underway for
Duchenne muscular dystrophy and other
myopathies associated with TGFβ1 signaling. We hypothesized that due to its anti-TGFβ1 activity,
losartan might be beneficial in
Camurati-Engelmann disease. This report concerns a boy who presented at age 13 years with severe limb
pain and difficulty in walking. Clinical and radiographic evaluation results were compatible with
Camurati-Engelmann disease and the diagnosis was confirmed by mutation analysis (c.652C > T [p.Arg218Cys]). The boy underwent an experimental treatment with
losartan at a dosage of 50 mg/day, orally. During the treatment period of 18 months, the intensity and frequency of limb
pain decreased significantly (as shown by a
pain diary), and muscle strength improved, allowing the boy to resume walking and climbing stairs. No obvious side effects were observed. We cautiously conclude that TGFβ1 inhibition with
losartan deserves further evaluation in the clinical management of
Camurati-Engelmann disease.