Oral steroids for the treatment of inflammatory Complex Regional Pain Syndrome type-1

The treatment of Complex Regional Pain Syndrome type 1 (CRPS-1) still remains
difficult, there is no clear proven medical or interventional therapy that
improves clinical outcome of this syndrome. A lack of understanding the
underlying pathophysiology of CRPS contributes to the difficulty in developing
definitive treatments. (Cossins, 2013)
It is obvious that CRPS-1 needs to be treated as early as possible to avoid the
syndrome from becoming chronic. (v Eijs, 2012) About 30% of CRPS-1 patients may
become chronic despite treatment. (Duman, 2006, Schwartzmann 2009, de Mos 2009)
Chronic CRPS-1 is debilitating and may lead to a completely non functional and
extremely painful limb which eventually may even result in amputation. (Bodde,
2011) Pathophysiological studies have shown that inflammation is a key factor
in the etiology of CRPS-1 (Parkitney, 2013) Several studies on
anti-inflammatory mediators have shown different success rates. (Dirckx, 2012)
It is suggested that anti-inflammatory agents such as prednisolon,
biphosphonates and topical application of dimethyl sulfoxide may be beneficial
in the acute stage of CRPS-1. (Birklein, 2015) The possible favourite response
to prednisone 30 mg thrice daily was first demonstrated in an non blinded
randomized trial in 23 patients. (Christensen, 1982) Other studies with oral
steroids suggest the possible benefits of its use in post stroke CRPS-1.
(Braus, 1994, Kalita, 2006) A recent retrospective evaluation of prednisolone
30 mg / day, tapered by 5 mg/day until discontinuation after 3 weeks in 45
patients with CRPS-1 showed significant improvement in clinical symptoms.
(Atalay, 2014) So oral steroids may be useful in Crps-1 but good quality
evidence is still lacking. Oral steroids may improve functional outcome of
early CRPS-1 by diminishing swelling and pain and facilitating physical
therapy. It may prevent patients with an affected extremity from becoming
permanently disabled. Although almost all studies have been performed with pain
reduction as the primary outcome parameter, we feel that early improvement in
functional outcome is more important for the long term outcome when treating
this syndrome. Therefore we aim for functional restoration as the primary
outcome measurement and pain as the secondary outcome measurement

Primary Objective:

Assessment of a group difference in clinically important improvement in
functional outcome of at least 10 points as measured by the DASH questionnaire

Secondary Objective(s):

1. To determine if there is a group difference in improvement in global
perceive effect of therapy as measured on a 7 point scale
2. To determine if there is a group difference in improvement in pain intensity
scores as measured by pain diary three times daily during the week
before each study visit.
3. To determine if there is a group difference in improvement in edema as
measured by a measurement tape
4. To determine if there is a group difference in improvement in discoloration
as measured on a 3 point scale
5. To determine if there is a group difference in improvement in
skin temperature difference as measured on a 5 point scale
6. To determine if there is a group difference in cortisol levels of responders
to treatment versus non responders.

double blinded randomized controlled trial in 2 x 26 subjects. Expected
inclusion period will last two years. Follow up at 1, 3, 6, 9 and 12 months
after randomization. The total duration is estimated at 3 years. Primary
endpoint is at 3 months after randomization, secondary endpoint at 12 months
follow up.

prednisolon tablets
first week: 3 x 10 mg dd
sec week: 3 x 5 mg dd
third week 1 x 5 mg dd

the filling in of a questionnair of 3-5 minutes duration (DASH)
Pain diary 3x/day during 1 week before a study visit: 6 visits in total time 0,
1, 3, 6, 9 en 12 maanden.
Physical examination of the involved limb, edema measurement