Treatment trial with Losartan of a patient with stiff skin syndrome.

Stiff skin syndrome (SSS)is a rare disorder. Losartan (Cozaar) is a registered
drug with blood pressure lowering properties which is expected to have a
therapeutic effect in SSS. In our center only one patient is known with this
disorder. She is severely affected. Physiotherapy and ultraviolet radiation
therapy did not reduce the joint limitations or skin hardening. Losartan is a
widespread used medicine devoid of significant adverse effects. To relieve the
complaints of the patient use of Losartan could be tried without severe
objections. Recently specific mutations in the fibrillin-1 gene were found in
some families with SSS. Fibrillin can interact with TGFβ signaling. It is
hypothesized that in SSS TGFβ signaling is increased. Losartan is a TGFβ
anatagonist and is believed to suppress the TGFβ activation in SSS. To gain
insight in the pathogenesis of SSS and the effect of Losartan, histopathologic
and functional investigations of the TGFβ pathway will be performed. Before and
after 3 months of treatment the joint excursions and the hardening of the skin
will be measured.

1. The effect of Losartan on the joint excursions and the Hardening of the skin
in a patient with SSS.
2. Gain insight in the pathogenesis of SSS
3. Gain insight in the functional effect of Losartan in SSS.

Observational study in which the therapeutical effect of a registered drug
(Losartan) will be tested in a patient with SSS. The effect will be measured by
goniometric measurement of joint excursions, ultrasound of the skin,
histopathologic and functional analysis of the TGFβ-signaling in fibroblasts.

Treatment with the maximal tolerated dose till a maximum of 100 mg Losartan
during 3 months.

The patient will be asked to undergo physical examination, blood pressure, 2
skin biopsies, goniometric measurement of joint excursions and ultrasound of
the skin at different sites of the body. The initial dose of 50 mg Losartan per
day will be prescribed with a check of bloodpressure and electrolytes, renal
and liver function after 2 weeks. if Losartan is well tolerated the maximum
dose of 100 mg per day will be prescribed with a check-up after 2 weeks (blood
pressure and blood parameters). After 3 months of treatment the above described
examinations will be repeated. The risk (adverse side effects) of the treatment
is very low. The dose will be modified if side effects occur.