*Zurita G, **Geffner L, ***Maldonado B, ****Uraga E, ****Armijos
L.
Background:
Psoriasis is a common inflammatory disease of the skin marked by
excessive scaling associated with inflammation, affecting about
2 % of the word population
(1).
The severity of psoriasis runs from relatively minor disease
consisting of 1 or 2 small plaques to erythrodermic psoriasis
covering the entire cutaneous surface. Many treatments have been
developed for psoriasis, none of them satisfying the whole
therapeutic needs in terms of disease control, relapses and
collateral effects, which in many cases turn their repeated use
unadvisable.
Clinical trials have reported early remission of refractory
autoimmune disorders, including diabetes mellitus, multiple
sclerosis, rheumatoid arthritis, systemic lupus erythematosus,
after autologous hematopoietic stem cells transplantation
(2, 3).
In reference with psoriasis we have found several reports about
a patient with leukemia and severe psoriasis who, after
allogeneic bone marrow transplantation, experienced remission of
psoriasis
(4, 5, 6, 7, 8).
Having this possibility in mind we have designed a study to
investigate the use of autologous stem cells implants as a new
therapy of psoriasis.
Objective:
Determine if intravenous implanting of authologous SC have any
therapeutic effect in psoriasis, and if it is comparable with an
established treatments for psoriasis like Systemic-PUVA-therapy.
Patients and Method:
Patient selection:
Patients suffering from psoriasis attending the Dermatology
Department of the Luis Vernaza Hospital were included in the
study if, the baseline Psoriasis Area Severity Index (PASI) was
equal or higher than 10, older than 18 years, any types of
psoriasis were considered. Patients were not receiving or had
received phototherapy UVB, Psoralen plus UVA radiation (PUVA),
oral retinoids, immunosuppressive or biologic agents within the
last month; but could receive a topic treatment (corticoid,
salycilic acidic, moisturizer).
Patients were willing and motivated to participate in this
study; they were allocated in two groups according their
preference after being orally informed: patients who received
autologous SC, and patients who received systemic PUVA-therapy.
An informed consent was signed.
Group 1 (Autologous stem cells group):
Cardiologic evaluations including chest X-ray and EKG, haematic
biometry, HIV determination and coagulation profile were
performed prior to the implants. Evidence of alcohol or drug
abuse, morbid obesity, mild to severe coagulopathy (clothing
time higher than twice the normal range) and patients who take
anti clothing drugs were excluded. Bone marrow was harvested
from both iliac crests under epidural anaesthesia with
bupivacaine 0.5%. It was processed by repeated centrifugation
and the CD34 + fraction was separated by difference in density
by submerging it into a ficol solution (density 1072). The final
volume was about 110+/- ml. Once the cell suspension was
obtained it was infused intravenously once diluted in 100 ml of
saline solution in 15 minutes.
Group 2 (Systemic- PUVA therapy group):
Irradiation was performed using Houva II (National Biologic)
cabinet with 24 UVA (F72T12 BL/HO) lamps. Treatment was given
tree times a week. Liver and renal function test were performed
before initiation of therapy. Patients were instructed to ingest
8-methoxypsoralen (0.3 mg/kg, 2 hours before exposure). Standard
initial dose of 1 J/cm2 was started on all patients.
The irradiation dose was increased by 1J/cm2 for each
subsequent visit until 15 J/cm2 or 100% clear was achieved.
Clinical assessment:
In both groups, disease severity assessments comprising
Psoriasis Area Severity Index (PASI) were performed by a
dermatologist at baseline and at weeks 1, 2, 3, 4, 12 and 24.
Reduction mean PASI values were assessed. A 75% of PASI
reduction was established as goal (PASI 75); it was evaluated at
1, 4 and 12 weeks.
In all cases digital pictures were taken.
Statistical analysis:
In accordance with descriptive statistics, mean ± standard
deviation values were used. ANOVA test and Student’s Newman
Keuls test were used to compare reduction mean PASI in
autologous SC patients vs. those receiving PUVA therapy. P<0.05
was considered as statistically significant. To determine
the PASI 75 we used the Proportion Hypothesis test.
Results:
A total of 30 patients (13 women and 17 men; 50±11
years old age average and 24±10 baseline PASI average) were
treated with
autologous SC implant. Meanwhile, 19 patients (3 women and 16
men;
45±12 years old; baseline PASI: 23±12) were treated with
systemic PUVA-therapy. From the first group, 8 patients quitted
and remained 22 at week 24. From the second group, 6 quitted
and remained 13 at week 24.
PASI reductions mean values
for those who received
autologous SC implant was:
20.2±47.2%
(CI 95%:0.378/0.026); 21.6±50.8%
(CI 95%0.406/0.026)
29.2±51.6%
(CI 95% 0.485/0.1),
31.5±55.8%
(CI 95%:0.523/0.107); 55±40%
(CI 95%:0.720/0.380); 63±30.9%
(CI 95%:0.766/0494), at 1, 2, 3, 4,
12 and 24 weeks respectively.
For those who received systemic PUVA-therapy PASI reduction mean
values were: 14±17%
(CI 95%:0.228/0.052); 21±47.3%
(CI 95%:0309/0.052);
35±28.8% (CI 95%:0.499/0.202);
43.4±38%
(CI 95%:0.629/0.238); 66.4±35.9%
(CI 95%:0.871/0.456); 61±31%
(CI 95%:0.79/0.44) at 1, 2, 3, 4, 12 and 24 weeks
respectively. There was not a significant difference between
both treatments (week 1: p-value= 0.60; week 4: p-value=0.44;
week 12: p-value=0.39).
PASI 75 in SC group was reached by 40% (p=0.11), 47% (p=0.51)
and 55% (p=0.92) at 4, 12 and 24 weeks. In PUVA group: 40%
(p=0.5); 65% (p=0.068) and 65% ( p=0.080) at 4, 12 and 24 weeks
respectively.
Conclusions:
In our study we have found that autologous SC
implant in psoriasis patients presents no
statistically significant differences when compared with PUVA-systemic.
At 4 weeks 40% of the SC group and PUVA group got success (PASI
75), at 12 weeks it was 47% and 65% respectively, whiles at 24
weeks it was 55% and 65% respectively.
Nevertheless, results of this study encourage longer follow up,
and more cases need to be studied.
This has been a pilot study through which we have determined the
correct size of the universe for an appropriate evaluation of
this prospective therapy. Using the formula to calculate the
size of the sample for proportions (
)
(9)
with 95% confidence, with 5% error range, and
considering that the incidence of psoriasis in Latin America
population is 1%,
with a population of 13´000,000.00 (Ecuador), and that we have
obtained a 55% of PASI 75 at
24 weeks, the proper statistical universe size for an adequate
study must be 380 patients.
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9.-Ríus F, Barón FF J,, Sanchez E, Parra L. nombre del capitulo.
En: Editores. Bioestadística: métodos. y aplicaciones.
Universidad de Málaga. Año del libro.
P. 187-88
*Dermatologist, Luis Vernaza Hospital’s Phototherapy Department.
**Director, Program of Investigation on Stem Cells, Luis Vernaza
Hospital.
*** Hematologist, Sociedad Lucha contra el Cancer Hospital
(SOLCA).
****Chief Dermatologist, Luis Vernaza Hospital’s Dermatology
Department
*****Science Master, Luis Vernaza Hospital’s Stadistic
Department
