|
[Treatment of systemic scleroderma using plasma
exchange. A study of 19 cases]
Schmidt C; Schooneman F; Siebert P; Weber M; Dureux JB;
Streiff F; Schmitt J
Secteur d'Angeiologie, Medecine H, Hopital Central, CHRU
Nancy.
Ann Med Interne (Paris) (France) 1988, 139 Suppl 1
p20-2
Generalized scleroderma (GS) is associated with dysimmunity
anomalies suggesting possible benefits of plasma exchange (PE)
therapy. Nineteen patients with GS were treated by PE (volume
of plasma exchange equivalent to 5-6% body weight and
replacement by 4% human albumin), initially three times
weekly, then weekly, bi-monthly and monthly (total duration
12-18 months). Clinical and paraclinical follow up was for an
average of more than 2 years after the end of PE (mean number
17 per patient). Clinical results were assessed as positive
and lasting in 11 cases (57.9%), two cases remaining stable
and three cases worsening (one death from heart failure). The
remaining three cases were failures in application of
treatment (difficult venous approach). Improvement was noted
in cutaneous sclerosis (62% of cases), trophic disorders
(recovery in 6 of 7 cases) and articular manifestations.
Vasomotor disorders were improved in only 20% of cases and
visceral lesions unaltered. Results of capillaroscopy showed
improvement in 5 of 11 cases. Biological values could not be
correlated with either the course or the therapeutic efficacy.
General tolerance to PE was good but the venous approach must
be of good quality. These findings suggest the need for a
randomized trial to define the place of PE in the treatment of
GS.
Captopril in the treatment of scleroderma renal
crisis.
Thurm RH; Alexander JC
Arch Intern Med (United States) Apr 1984, 144 (4)
p733-5
Scleroderma is a disease of unknown cause characterized by
interstitial fibrosis and vascular lesions in many organ
systems. Renal failure, often associated with malignant
hypertension, may ensue as a life-threatening component of
this disorder. Activation of the renin-angiotensin-aldosterone
system has been hypothesized as a cause of this complication.
Captopril has been used in 23 patients with this condition. Of
this group, 20 (87%) responded favorably with a decrease of
the supine diastolic BP to less than 90 mm Hg and a reduction
in the serum creatinine level in 14 patients. During long-term
therapy (median, 29 months), 11 of the 23 patients continued
to have a good clinical response while receiving captopril.
Six patients died and six patients were alive after captopril
therapy was discontinued. These data suggest that captopril is
beneficial in the treatment of scleroderma renal crisis.
Renal scleroderma: comparison of different
modalities of treatment.
Javier R; Dumler F; Levin NW
South Med J (United States) May 1980, 73 (5)
p657-9
A patient with scleroderma and severe renal failure was
initially treated with hemodialysis and minoxidil (Loniten)
without any improvement in her skin involvement. At a later
date bilateral nephrectomy and a successful cadaveric renal
transplant were performed. Her cutaneous manifestations have
improved remarkably during the four years since
transplantation. Because these patients do not tolerate
hemodialysis very well, renal transplantation appears to be
the most effective form of treatment, with the possible added
benefit of cutaneous improvement.
Treatment of progressive systemic sclerosis
(scleroderma, PSS) with a new drug influencing connective
tissue.
Herbai G; Blom B; Bostrom H
Acta Med Scand (Sweden) 1977, 201 (3) p203-6
Cyclofenil is a new diphenyl ethylene derivative related to
stilboestrol without oestrogenicity but with marked effects on
connective tissue metabolism. The drug has been tested, in a
daily dose of 200mg X3, in six patients with progressive
systemic sclerosis (PSS) to analyze the expected beneficial
effects on the PSS symptoms. The typical skin hardness, joint
and muscle rigidity, and reduced breathing capacity were
improved to varying dgrees. The only side-effect was a slight
transient liver enzyme elevation in 1 out of 6 patients. A
slight increase was found in urinary calcium and
hydroxyproline excretion. In several cases serum calcium,
cholesterol, triglyceride and in some cases the serum uric
acid levels were decreased. The ANF titres diminished to
varying degrees in 4 out of 6 patients. These results indicate
that further detailed clinical and laboratory studies on the
therapeutic potential of cyclofenil in PSS and other diseases
affecting connective tissue seen to be justified.
Barium impaction as a complication of
gastrointestinal scleroderma.
Thompson MA; Summers R
JAMA (United States) Apr 19 1976, 235 (16)
p1715-7
Two patients with scleroderma of the bowel experienced
life-threatening barium impaction after upper intestinal x-ray
studies. Although the frequency of this complication is
unknown, the difficulty of managing it when it occurs makes
prevention imperative. X-ray studies should be performed only
after careful consideration of the risks and benefits . When
x-ray studies are performed, the patient should be vigorously
purged soon thereafter, and a follow-up roentgenogram should
be obtained to confirm adequate removal of barium.
Physiatrics for deforming linear scleroderma.
Rudolph RI; Leyden JJ
Arch Dermatol (United States) Jul 1976, 112 (7)
p995-7
When linear scleroderma traverses several joints, severe
and mutilating deformities and contractures, with loss of limb
function, can result. Drugs and surgical procedures are
usually of little benefit in ameliorating the deformities.
Physiatrics on the other hand, is a readily available modality
than can restore much useful function and reverse the
contractures and is probably the most effective means of
treating patients with deforming linear scleroderma. This type
of therapy should be instituted at the inception of the
disease process so that the development and progression of any
contraction can be minimized or prevented.
Cyclophosphamide therapy for scleroderma
Akesson A.
Dr. A. Akesson, Department of Rheumatology, Lund University
Hospital, S-221 85 Lund Sweden
Current Opinion in Rheumatology (United States) 1998, 10/6
(579-583)
Pulmonary manifestations are the most common cause of death
in patients with scleroderma. Consequently, the importance of
treatment of both interstital lung disease and pulmonary
hypertension has become increasingly evident. Until a
placebo-controlled study of any drug has shown its beneficial
effect on pulmonary dysfunction, cyclophosphamide may be
useful for the treatment of scleroderma lung disease.
Treatment of systemic scleroderma patients with
calcitonin: Report on ten years experience
Hornstein O.P.; Steffan C.; Diepgen T.L.; Hiller D.; Albrecht
H.-P.; Gruschwitz M.S.
Dermatologische Universitatsklinik, Hartmannstrasse 14,91052
Erlangen Germany
H+G Zeitschrift fur Hautkrankheiten (Germany) 1993, 68/7
(437-442)
Patients with progressive systemic scleroderma (PSS) are
usually treated with antifibrotic, antiinflammatory and/or
vasoactive drugs. As good therapeutic experience by Staehelin
using calcitonin in PSS was reported 15 years ago, we treated
during the last 10 years 40/44 patients in different stages of
PSS with 284 turns of intravenous calcitonin application (100
I.U. salmon calcitonin/day for 10 days, two or three times a
year). This regimen was well-tolerated and resulted mostly in
reduced finger-swellings and decreased frequencies of
Raynaud's attacks. Concomitant side effects like nausea,
headache or lowered blood pressure were rare, allergic
reactions of other long-term side effects were not observed so
far. Disease progress (intermittent inflammatory reactivity)
occured in only 4/40 patients, whereas 36/40 remained within
their former stage of PSS. The vasoactive profile of
calcitonin was evaluated by determination of cutaneous
microcirculation using noninvasive methods as well as by
investigation of prostaglandin F(1a) serum levels during
calcitonin application. Our results strongly suggest that
intravenous calcitonin treatment is of therapeutical benefit
in the majority of patients suffering from PSS.
Laser-Doppler-flowmetry in prostaglandin Einf
1-therapy of scleroderma
Elsmann H.-J.; Rabe E.; Schuler-Pyrtek P.; Bauer R.
Universitats-Hautklinik und Poliklinik, Rheinische
Friedrich-Wilhelms-Universitat, Sigmund-Freud-Str. 25, 5300
Bonn 1 Germany
H+G Zeitschrift fur Hautkrankheiten (Germany) 1991, 66/6
(533-535)
Prostaglandin Einf 1 was administered intravenously to 17
patients with progressive systemic sclerosis and secondary
Raynaud's phenomenon. Microcirculation was measured by
Laser-Doppler immediately before and the day after therapy 3
weeks later. Skin blood flow in resting state and during
postocclusive reactive hyperemia was taken at the dorsum of
the middlefinger. Assessment of the pre- and post-ischemic
flux- and time parametes indicated a statistically significant
improvement after PGEinf 1 therapy. In 14 out of 17 patients
(82%) the number and severity of Raynaud attacks were reduced.
The results show the benefit of intravenous PGEinf 1 therapy
for patients with Raynaud's phenomenon in scleroderma and the
usefulness of Laser-Doppler-flowmetry in evaluating the
efficacy of vasoactive drugs in clinical practice.
Treatment of generalized scleroderma with
connective tissue inhibitors (Danish)
Asboe Hansen G.
Afd. Hudsygdomme, Rigshosp., Kobenhavn
Ugeskr.Laeg. 1976, 138/22 (1325-1329)
One hundred and three patients with generalized scleroderma
were followed up regularly for a period of 15 yr. Of these, 93
were treated with D penicillamine, benzyl penicillin diethyl
amino ethylester hydroiodide, corticosteroids, d-thyroxine,
hydralazine or 'mixed drug therapy' (one or more of the drugs
administered after one another or simultaneously). The effect
of d-thyroxine could not be assessed in this investigation. No
lasting benefit was observed after treatment with
corticosteroids. Hydralazine appears to have a favourable
effect. D-penicillamine resulted in improvement occurred in 12
out of 16 improvement in 25 out of 34 patients treated, while
improvement treated with Leocillin. In 6 patients, the dermal
sclerosis yielded completely. In 16 patients, complete
regression was observed with the exception of sclerosis of the
fingers. In 32 patients, partial regression occurred. In 20
patients, progression of the disease occurred, but no evidence
of regression was observed and 19 patients did not experience
any benefit from the treatment. The prognosis was better in
young than in older patients. The age at diagnosis was lowest
in the good groups. Better results were observed with higher
total doses. The duration of the treatment is probably of
significance. Short term cases had better prognosis than long
term cases. Twenty one untreated patients showed continued
progression. Side effects leading to withdrawal of therapy
occurred quite frequently, particularly after d penicillamine.
Twelve deaths which occurred during the period of observation
did not appear to be causally related to the treatment
administered. The results have not been obtained in controlled
clinical trials. Such trials, probably comprising several
departments, would be desirable.
Extracorporeal photochemotherapy in progressive
systemic sclerosis: a follow-up study.
Schwartz J; Gonzalez J; Palangio M; Klainer AS; Bisaccia
E
Department of Internal Medicine and Dermatology, Morristown
Memorial Hospital, NJ 07962-1956, USA.
Int J Dermatol (United States) May 1997, 36 (5)
p380-5
BACKGROUND: Extracorporeal photochemotherapy
(photopheresis), an immune-modulating therapy, has been
demonstrated to elicit a therapeutic response in the treatment
of several autoimmune disorders. We evaluated the use of
photopheresis in the treatment of patients with progressive
systemic sclerosis (PSS; scleroderma).
METHODS: Five patients with early-onset, diffuse PSS were
treated with photopheresis on 2 successive days monthly for an
average of 59 months (range 54-89 months). We initially
reported the response this group of patients had to
photopheresis treatment at an average of 11 months (range 6-21
months).
RESULTS: An improvement or stabilization was noted in most
patients in skin thickening, joint mobility, pulmonary
function studies, oral aperture, functional index, as well as
symptoms including Raynaud's phenomenon, dyspnea, fatigue,
dysphagia, arthralgias, and cutaneous ulcers. Renal function
tests remained within normal range. A total of 296 monthly
treatments were administered without significant toxicity.
CONCLUSIONS: This study suggests that extended use of
extracorporeal photochemotherapy in the management of
early-onset, diffuse PSS is well tolerated and may provide an
increasingly beneficial clinical outcome.
Extracorporeal photochemotherapy in progressive
systemic sclerosis.
Di Spaltro FX; Cottrill C; Cahill C; Degnan E; Mulford GJ;
Scarborough D; Franks AJ Jr; Klainer AS; Bisaccia E
Department of Medicine, Columbia University College of
Physicians and Surgeons, New York, New York.
Int J Dermatol (United States) Jun 1993, 32 (6)
p417-21
BACKGROUND. Extracorporeal photochemotherapy, an
immune-modulating form of therapy, has been shown to be
effective in the treatment of autoimmune diseases. We
evaluated the effects of extracorporeal photochemotherapy in
the treatment of patients with progressive systemic sclerosis
(PSS).
METHODS. Nine patients with active progressive systemic
sclerosis were treated with extracorporeal photochemotherapy
on 2 successive days monthly. The duration of therapy ranged
from 6 to 21 months.
RESULTS. A significant improvement was noted in the skin,
musculoskeletal system, functional index, and symptoms
including Raynaud's phenomenon, dyspnea, fatigue, dysphagia,
and arthralgias, as well as improvement of cutaneous ulcers.
Stabilization of the pulmonary function studies was also noted
in the majority of patients over the course of therapy. No
serious side effects were noted throughout the course of
therapy in the 9 patients.
CONCLUSIONS. The results suggest that photopheresis may be
beneficial in selected early cases of progressive systemic
sclerosis.
Visceral improvement following combined
plasmapheresis and immunosuppressive drug therapy in
progressive systemic sclerosis.
Akesson A; Wollheim FA; Thysell H; Gustafson T; Forsberg L;
Pahlm O; Wollmer P; Akesson B
Department of Rheumatology, University Hospital, Lund,
Sweden.
Scand J Rheumatol (Sweden) 1988, 17 (5) p313-23
In a two-year prospective therapeutic trial, 15 patients
with progressive systemic sclerosis (PSS) were treated with
immunosuppressive drug therapy with or without long-term
plasmapheresis. Before the trial all patients had severe
involvement of either the esophagus, lungs or kidneys. One
patient died of renal failure and another 2 patients withdrew
unimproved. In the remaining 12 patients, objective
improvement occurred in all but one. The degree and extent of
skin involvement decreased significantly (p less than 0.01).
Cineradiography revealed increased esophageal motility in 4
patients. Pulmonary function measured as total lung capacity
and static lung compliance improved (p less than 0.01). In 4
patients the number of premature atrial or ventricular
contractions at 24 h ECG monitoring decreased, as did the
concentrations of immunoglobulins and ANA titres in serum.
Although it could not be ascertained whether the clinical
improvement was associated with combined therapy or
immunosuppressive drug treatment alone, our results suggest
that immunosuppressive therapy is beneficial in advanced
PSS.
Effects of prostaglandin E1 on microvascular
haemodynamics in progressive systemic sclerosis.
Martin MF; Tooke JE
Br Med J (Clin Res Ed) (England) Dec 11 1982, 285 (6356)
p1688-90
The effects of prostaglandin E1 infusion on nailfold
capillary haemodynamics were studied in eight patients with
Raynaud's phenomenon secondary to progressive systemic
sclerosis. Using a modified Landis microinjection technique
the mean (+/- SEM) transcapillary pressure gradient was
increased during and six weeks after infusion by 13.9 +/- 3.2
cm H2O (p less than 0.05) and 5.5 +/- 2.5 cm H2O (p less than
0.05) respectively. Capillary red cell velocity measured in
two patients by video television microscopy also increased
during and after infusion with prostaglandin E1. Six patients
claimed subjective benefit and in three their ulcers healed.
These findings support the observed beneficial effect of
prostaglandin E1 and suggest that it improves the nutritive
capillary circulation by lowering precapillary resistance.
Progressive systemic sclerosis: Management. Part
II: D-Penicillamine
Nassonova V.A.; Ivanova M.M.
Inst. Rheum., Acad. Med. Sci. USSR, Moscow Russia
Clinics in Rheumatic Diseases (United States) 1979, 5/1
(277-288)
Objective assessment of the efficacy of D-penicillamine
(DPA) in the treatment of PSS is complicated by the absence of
control trials. Our analysis of the available data suggests
the following:
1. Application of DPA is indicated in rapidly progressive
cases of PSS.
2. DPA exerts a pronounced effect on skin induration and,
to a lesser extent, on visceral disturbances.
3. The beneficial effects of DPA are manifested no earlier
than two months after initiation of therapy and are correlated
with duration of treatment (2.5 years on average).
4. A maintenance dose of 300 to 600 mg DPA a day is
recommended.
5. Clinical experience has demonstrated the expediency of
combining DPA and corticosteroids for increasing the efficacy
of treatment and reducing the frequency of side effects,
especially of allergic reactions, and especially during the
first few weeks of treatment.
6. The efficacy of therapy with DPA increases with early
use of the drug, and falls in cases of more advanced PSS.
7. Side effects, both early (allergic) and late (toxic as a
rule), are common during the course of treatment with DPA,
necessitating that the physician exert the greatest possible
care in choosing this form of treatment and in maintaining
close surveillance of the patient during the entire course of
such therapy.
Thymus -dependent (T) lymphocyte deficiency in
progressive systemic sclerosis.
Hughes P; Holt S; Rowell NR; Dodd J
Br J Dermatol (England) Nov 1976, 95 (5) p469-73
Circulating thymus -dependent (T) lymphocytes were
estimated in twenty-seven patients with progressive systemic
sclerosis (PSS) and in forty-five normal controls using the
property of T lymphocytes to form rosettes with sheep red
blood cells. The patients with PSS were found to have a
reduction of T lymphocytes which correlated with the extent of
visceral involvement by the disease, those with the lowest
counts having the most extensive disease. These findings
support the suggestion that immunological factors may be
involved in the pathogenesis of PSS.
Monocytes of patients wiht systemic sclerosis
(scleroderma spontaneously release in vitro increased amounts
of superoxide anion.
Sambo P; Jannino L; Candela M; Salvi A; Donini M; Dusi S;
Luchetti MM; Gabrielli A
Institute of Internal Medicine, Hematology and Clinical
Immunology, University of Ancona, Italy.
J Invest Dermatol (United States) Jan 1998, 112 (1)
p78-84
It has been suggested that toxic oxygen free radicals can
be involved in the pathogenesis of systemic sclerosis
(scleroderma) (SSc). Because the cells that contribute to the
generation of free radicals are not known, our aim was (i) to
evaluate the ability of unmanipulated and phorbol 12-myristate
13-acetate-stimulated monocytes and polymorphonucleate
neutrophils of SSc patients to generate superoxide anion
(O2*-); and (ii) to investigate whether the O2*- produced by
these cells involved the activation of nicotinamide-adenine
dinucleotide diphosphate oxidase biochemical pathway.
Employing the superoxide dismutase-inhibitable reduction of
cytochrome c to evaluate the generation of O2*-, unmanipulated
monocytes of SSc patients generated more O2*- than primary
Raynaud's phenomenon patients and normal control monocytes (p
= 0.0001), and the release was higher in patients with diffuse
cutaneous involvement and 5 y or less disease duration (p =
0.02). The involvement of nicotinamide-adenine dinucleotide
diphosphate oxidase in the enhanced 02*- production was
demonstrated by the finding that the cytosolic components of
the enzyme, p47phox and p67phox, were both translocated to the
plasma membrane of enriched but otherwise unmanipulated
monocytes of SSc patients. The involvement of mitochondrial
oxidases was excluded by the lack of inhibition of O2*-
production when monocytes were incubated in the presence of
rotenone, a mitochondrial oxidase inhibitor. Upon stimulation
with phorbol 12-myristate 13-acetate, monocytes of SSc
patients produced more O2*- than controls. In SSc patients
untreated polymorphonucleate neutrophils generated
significantly less O2*- than monocytes (p = 0.0001) and only
slightly more than polymorphonucleate neutrophils of primary
Raynaud's phenomenon patients and normal controls (p = 0.03).
In conclusion, we demonstrate that in patients with
scleroderma, unmanipulated and phorbol 12-myristate
13-acetate-stimulated monocytes release in vitro increased
amounts of superoxide anion through the activation of
nicotinamide-adenine dinucleotide diphosphate oxidase and,
thus, contribute to the oxidative stress found in this
disease.
The value of the Health Assessment Questionnaire
and special patient-generated scales to demonstrate change in
systemic sclerosis patients over time.
Steen VD; Medsger TA Jr
Georgetown University School of Medicine, Washington, DC
20007-2197, USA.
Arthritis Rheum (United States) Nov 1997, 40 (11)
p1984-91
OBJECTIVE: To determine the validity and usefulness of a
modified Health Assessment Questionnaire (HAQ) for measurement
of disease status and changes in disease status over time in
patients with systemic sclerosis (SSc).
METHODS: Since 1985, 1,250 patients attending the
University of Pittsburgh Scleroderma Clinic have completed a
modified HAQ annually. In addition to the standard HAQ
questions about disability, the questionnaire includes visual
analog scales (VAS) to evaluate SSc organ system symptoms,
Raynaud's phenomenon, gastrointestinal (GI) tract and lung
involvement, pain, and overall disease severity. In this
study, the disability index (DI) (from the HAQ) and the VAS
scores (on a 0-3 scale) were compared with various clinical
and laboratory features recorded within 3 months of
administration of the HAQ and VAS, using t-tests and
Spearman's correlation tests.
RESULTS: The HAQ DI correlated directly with skin
involvement, scleroderma heart or kidney disease, tendon
friction rubs, hand contractures, and proximal muscle
strength. Over time, the DI correlated with changes in skin
score and was a good predictor of survival. There was a
significant improvement in the DI during a 2-year time period
in patients treated with D-penicillamine. The VAS for digital
ulcers, GI symptoms, and lung symptoms correlated very closely
with subjective and objective findings for these organ
systems. The presence of new digital ulcers or improvement in
digital ulcers showed significant associations with the
Vascular scale, new GI symptoms or improvement in GI symptoms
and institution of H2-blockers showed appropriate strong
correlations with the GI scale, and changes in the forced
vital capacity had an excellent correlation with the Lung
scale (r = 0.58, P < 0.001). By Cox regression analysis,
the HAQ DI was one of the best predictors of survival.
CONCLUSION: These data provide convincing evidence that a
self-administered questionnaire is an accurate and inexpensive
tool to measure disease status changes in SSc. Prospective
studies with the HAQ administered at regular intervals, as in
controlled trials, should be performed to further assess the
benefits and limitations of this instrument.
Hematopoietic stem cell transplantation in
rheumatic diseases other than systemic sclerosis and systemic
lupus erythematosus.
Tyndall A
Department of Rheumatology, Basle University,
Switzerland.
J Rheumatol Suppl (Canada) May 1997, 48 p94-7
Hematopoietic stem cells (HSC) are increasingly available
as an alternative to whole marrow aspirate for bone marrow
transplantation (BMT). They may be derived from an HLA matched
individual (allogeneic) or from the patient (autologous).
Allogeneic BMT is associated with a 15 to 35% mortality,
largely due to graft versus host disease. Autologous HSC are
used to rescue the patient after severe immunosuppression, and
the transplant related mortality is 3 to 5%. The opportunity
to ablate severe autoimmune disease with increased safety is
particularly attractive for necrotizing vasculitides,
polymyositis/dermatomyositis, primary Sjogren's syndrome,
systemic juvenile arthritis, relapsing polychondritis, and
Behcet's disease, where correct selection of cases would
ensure an acceptable benefit /risk ratio. Rheumatoid arthritis
(RA), psoriasis associated arthritis (PsA) and some
non-rheumatic diseases such as inflammatory bowel disease
(IBD), multiple sclerosis, and type 1 diabetes mellitus may
also be candidates, but careful selection of patients with a
poor prognosis is necessary. There are allogeneic BMT data
from patients with aplastic anemia or leukemia and concurrent
RA, PsA, and IBD and also autologous HSC BMT data from animal
models to support the concept of cure. Patient studies should
proceed using recently published protocol guidelines and
centralized data collection. (25 Refs.)
Treatment of systemic sclerosis.
van den Hoogen FH; van de Putte LB
Department of Rheumatology, University of Nijmegen, The
Netherlands.
Curr Opin Rheumatol (United States) Nov 1994, 6 (6)
p637-41
The treatment of systemic sclerosis remains therapeutically
challenging. Until just recently, no disease-modifying
intervention was proved to be effective. Over the past year,
much effort has gone into setting up proposals for outcome
measures and response criteria in clinical trials. Several
intervention studies were published. Aminobenzoate potassium
was found to be ineffective in a double-blind,
placebo-controlled trial. Possible efficacy for antithymocyte
globulin was suggested in two small open studies, and the
dispute about the use of extracorporeal photopheresis
continues. The results of another open trial of methotrexate
showed improvement of skin involvement in the majority of
patients, and attention was drawn to the nephrotoxic side
effects of cyclosporine. Combination therapy with
cyclophosphamide and low-dose corticosteroids seems promising
for improving pulmonary function in scleroderma patients with
progressive lung involvement. Iloprost was shown to be
superior to placebo in the treatment of Raynaud's phenomenon
secondary to scleroderma. Anecdotal data indicate a possible
beneficial effect of octreotide treatment in pseudoobstruction
intestinalis due to scleroderma. (49 Refs.)
Cardiopulmonary hemodynamics in systemic sclerosis
and response to nifedipine and captopril.
Sfikakis PP; Kyriakidis MK; Vergos CG; Vyssoulis GP; Psarros
TK; Kyriakidis CA; Mavrikakis ME; Sfikakis PP; Toutouzas
PK
Cardiac Department, Hippokration Hospital, Athens,
Greece.
Am J Med (United States) May 1991, 90 (5) p541-6
PURPOSE: This prospective study was performed to evaluate
the response of the cardiopulmonary vasculature to two
vasodilators in patients with systemic sclerosis and either
minimal or no central hemodynamic abnormalities.
PATIENTS AND METHODS: Twenty patients with systemic
sclerosis, Raynaud's phenomenon (19 of 20 patients), and
clinically normal cardiac function underwent right heart
catheterization. Rest and exercise hemodynamic measurements,
including cardiac output by thermodilution, were performed
before and after oral administration of nifedipine 20 mg and
captopril 25 mg.
RESULTS: Half of the patients had normal hemodynamics
(Group A); the other half (Group B) had abnormal baseline
elevations in pulmonary vascular resistance and four of them
showed "borderline" pulmonary arterial hypertension. Group A,
with significantly shorter disease duration compared with
Group B, responded poorly to nifedipine and captopril.
However, Group B had significant decreases in pulmonary
vascular resistance (from 148 +/- 20 to normal levels of 94
+/- 21 dynes.second.cm-5) and pulmonary mean pressure in
response to nifedipine treatment but not to captopril.
CONCLUSION: These observations show a short-term beneficial
effect of nifedipine in the cardiopulmonary vasculature of
patients with systemic sclerosis and suggest that a
potentially reversible vasoconstrictive element is included in
the vascular lesion of this disorder.
Effects of immunomodulating therapy in systemic
sclerosis.
van den Hoogen FH; Boerbooms AM; van de Putte LB
Department of Rheumatology, University Hospital Nijmegen, The
Netherlands.
Clin Rheumatol (Belgium) Sep 1990, 9 (3) p319-24
We reviewed studies concerning immunomodulating therapy in
systemic sclerosis. These comprise mostly uncontrolled trials
and case reports. Some of these studies hint at a possible
beneficial effect of antimetabolites (azathioprine,
5-fluoro-uracil and methotrexate), cyclosporine and
interferon-gamma. However, to give a clearcut answer on the
efficacy of these drugs in systemic sclerosis, controlled
studies are urgently needed. (32 Refs.)
The effect of captopril on thallium 201 myocardial
perfusion in systemic sclerosis.
Kahan A; Devaux JY; Amor B; Menkes CJ; Weber S; Venot A;
Strauch G
Department of Rheumatology, Rene Descartes University, School
of Medicine, Hopital Cochin, Paris, France.
Clin Pharmacol Ther (United States) Apr 1990, 47 (4)
p483-9
In systemic sclerosis, abnormalities of myocardial
perfusion are common and may be caused by a disturbance of the
coronary microcirculation. We evaluated the long-term effect
of captopril (75 to 150 mg per day) on thallium 201 myocardial
perfusion in 12 normotensive patients with systemic sclerosis.
Captopril significantly decreased the mean (+/- SD) number of
segments with thallium 201 myocardial perfusion defects (6.5
+/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment
with captopril; p less than 0.02) and increased the mean
global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/-
2.1 after captopril; p less than 0.05). In a control group of
eight normotensive patients with systemic sclerosis who did
not receive captopril, no significant modification in thallium
results occurred. Side effects with captopril included
hypotension (six patients), taste disturbances (one patient),
and skin rash (one patient). These side effects subsided when
the dosage was reduced. These findings demonstrate that
captopril improves thallium 201 myocardial perfusion in
patients with systemic sclerosis and may therefore have a
beneficial effect on scleroderma myocardial disease.
Benoxaprofen in treatment of systemic
sclerosis.
Halkier-Sorensen L; Ternowitz T; Bjerring P; Poulsen JH;
Alsbirk KE; Herlin T; Ravnsbaek J; Zachariae E; Zachariae
H
Acta Derm Venereol (Sweden) 1986, 66 (2) p177-9
Ten patients with systemic sclerosis were treated with
benoxaprofen, a potent lipoxygenase inhibitor, for a period of
6 months. In an attempt to evaluate the efficacy a number of
physical disease parameters were followed during the trial.
None of these parameters revealed any significant differences.
There was, however, a trend for a change towards normalisation
of a defect monocyte chemotaxis. In view of the slow and
progressive nature of systemic sclerosis the present study
leaves undetermined whether benoxaprofen exerts a beneficial
effect on systemic sclerosis.
Lack of clinical benefit after treatment of
systemic sclerosis with total lymphoid irradiation.
O'Dell JR; Steigerwald JC; Kennaugh RC; Hawkins R; Holers VM;
Kotzin BL
Department of Medicine, University of Colorado Health Science
Center, Denver.
J Rheumatol (Canada) Aug 1989, 16 (8) p1050-4
Six patients with systemic sclerosis and internal organ
involvement were randomized to receive total lymphoid
irradiation (TLI) or to serve as untreated controls. Despite
evidence of profound immunosuppression, we were unable to
detect any longlasting clinical benefit in the treated
patients, with follow-ups ranging from 1-4 years after TLI.
Moreover, the results suggest that this therapy may accelerate
pulmonary and gastrointestinal deterioration in
scleroderma.
Recombinant interferon-gamma in the treatment of
systemic sclerosis.
Kahan A; Amor B; Menkes CJ; Strauch G
Department of Rheumatology, Rene Descartes University, School
of Medicine, Paris, France.
Am J Med (United States) Sep 1989, 87 (3) p273-7
PURPOSE: Recombinant interferon-gamma (IFN-gamma) is a
potent and selective inhibitor of collagen production by
dermal fibroblasts in vitro and has numerous immunoregulatory
activities. We assessed the effects of recombinant IFN-gamma
in the treatment of patients with systemic sclerosis.
PATIENTS AND METHODS: Ten patients entered the study and
nine completed the six-month study period. Recombinant
IFN-gamma was administered once daily for seven days per week
by intramuscular injections: 10 micrograms/day for 10 days, 25
micrograms/day for 10 days, 50 micrograms/day for 10 days, and
100 micrograms/day for the next five months.
RESULTS: After the six-month treatment period, a
significant improvement, as compared with base-line values,
was observed in total skin score, maximal oral opening, range
of motion of wrists and elbows, grip strength, functional
index, dysphagia, and creatinine clearance. No serious side
effects were observed; however, a significant decrease in
white blood cell counts and in peripheral blood lymphocytes
was noted.
CONCLUSION: These results suggest that recombinant
IFN-gamma may be beneficial in the treatment of patients with
systemic sclerosis.
Isotretinoin in the treatment of systemic
sclerosis.
Maurice PD; Bunker CB; Dowd PM
Department of Dermatology, Middlesex Hospital, London,
U.K.
Br J Dermatol (England) Sep 1989, 121 (3)
p367-74
Thirteen patients with systemic sclerosis were treated with
isotretinoin. Nine patients completed between 6 and 14 months
of treatment and all showed an improvement in the cutaneous
manifestations of their disease. The drug did not appear to
benefit internal organs affected by the disease. Most patients
experienced the well-recognized side-effects of retinoids,
which in three cases necessitated withdrawal from the study
within 3 months. Serum levels of type III procollagen
aminopropeptide did not show a consistent decline during
treatment, despite a clinical improvement. The mode of action
of the reported therapeutic effect of isotretinoin in systemic
sclerosis is unclear. There may be a preferential suppression
of the synthesis of type I collagen, or the drug may be acting
by an unrelated mechanism.
Treatment of progressive systemic sclerosis with
plasma exchange. Seven cases.
Guillevin L; Leon A; Levy Y; Bletry O; Gayraud M; Andreu G;
Godeau P
Int J Artif Organs (Italy) Nov 1983, 6 (6)
p315-8
Seven patients, 4 women and 3 men afflicted with severe
progressive systemic sclerosis (PSS) were treated with Plasma
Exchange after failure of different other treatment. All
patients presented Raynaud phenomenon and arthritis, 6
patients presented extensive skin lesions, 5 of them digestive
manifestations, 3 pulmonary fibrosis. In one case PSS was
associated with polymyositis, one patient presented bilateral
recurrent cornea ulcerations, (Sjogren Syndrome++) and one
patient numerous skin ulcerations. In 5 patients adjuvant
corticosteroid therapy was given during the course of PE. In 3
patients PE must be stopped after one or two sessions because
of insufficient venous access. Among the 4 other patients 8 to
20 PE were performed: the patient with cornea ulcerations
became blind during the treatment, skin ulcerations and severe
Raynaud phenomenon did not improved in two other patients.
Benefit of PE was noted in only one patient with regressive
myositis, and improvement of articular and cutaneous symptoms.
Therefore, PE are not useful in most patients afflicted with
PSS, they are difficult to realize in numerous patients and
did not improve clinical symptoms in most cases.
Penicillamine therapy in systemic sclerosis.
Jayson MI; Lovell C; Black CM; Wilson RS
University of Bristol Department of Medicine.
Proc R Soc Med (England) 1977, 70 Suppl 3 p82-8
Twenty-two patients with progressive systemic sclerosis
were treated with D-penicillamine in doses ranging up to 1250
mg/day for periods varying between a few months and four
years. Side-effects occurred in 7 patients, necessitating drug
withdrawal in 2. Cutaneous benefit occurred in 15 patients,
but owing to side-effects from the drug, relapses, and
development, persistence or advancement of visceral
complications, an overall good result only occurred in 5.
Seven patients showed improvements in joint function, but only
3 were regarded as having an overall good result. Peripheral
vascular disease and visceral involvement seemed not to be
influenced by D-penicillamine and sometimes appeared or
advanced during treatment. Six patients died from visceral
manifestations of systemic sclerosis and one from another
cause. D-penicillamine is of limited value for the cutaneous
features of progressive systemic sclerosis, but probably of no
value for the vascular and visceral manifestations of the
disease.
Interferon-gamma in the treatment of systemic
sclerosis: A randomized controlled multicentre trial
Grassegger A.; Schuler G.; Hessenberger G.; Walder-Hantich
B.; Jabkowski J.; Macheiner W.; Salmhofer W.; Zahel B.; Pinter
G.; Herold M.; Klein G.; Fritsch P.O.
A. Grassegger, Department of Dermatology, University of
Erlangen, Erlangen Germany
alfred.grassegger@uibk.ac.at
British Journal of Dermatology (United Kingdom) 1998, 139/4
(639-648)
We report the results of a randomized controlled
multicentre study on interferon-gamma (IFN-gamma) treatment of
systemic sclerosis as determined by skin sclerosis, renal and
other organ involvement, global assessment, subjective
symptoms and quality of life. Forty-four patients were
enrolled into the trial, 27 in the treatment group and 17 in
the control group. All patients presented with type I or type
II scleroderma. Twenty-nine patients (64%) finished the study.
The mean duration of Raynaud's phenomenon and skin sclerosis
was 15.3 and 10.8 years, respectively. The skin scores tended
to improve in the treatment group (P > 0.05). Mouth
aperture increased significantly from 38.5 to 47.7 mm in the
treatment group (P < 0.001). Subanalysis of IFN-gamma
treated patients with normalized skin sclerosis scores <=1
showed significant improvement in both skin involvement and
subjective symptoms (P < 0.05). Organ involvement improved
in eight of 18 treatment patients and in three of 11 control
patients. It worsened in three of 18 treatment patients and in
four of 11 control patients. One control patient died due to
cardiorespiratory failure during the study. No deterioration
of renal function occurred during IFN-gamma treatment. There
was a significant improvement in quality of life parameters in
the control group but not in the treatment group. Plasma
levels of neopterin increased significantly during IFN-gamma
treatment but not in the control group, whereas N-terminal
procollagen III peptide levels did not change in either group.
There was a high frequency of mild to moderate influenza-like
adverse events during IFN-gamma treatment. Only four of nine
drop-out patients, however, experienced symptoms most probably
associated with IFN-gamma treatment. We conclude that
IFN-gamma therapy has mild beneficial effects on skin
sclerosis and disease-associated symptoms in type I and II
scleroderma. IFN-gamma treatment was associated with
acceptable tolerability and did not induce major renal
dysfunction in our patients.
Intravenous Lipo-PGE1 (Eglandin(R)) therapy in
peripheral vascular diseases secondary to systemic lupus
erythematosus and systemic sclerosis
Lee S.-H.; Park Y.-M.; Oh E.-S.; Min J.-K.; Park S.-H.; Cho
C.-S.; Kim H.-Y.
Department of Internal Medicine, Kangnam St. Mary's Hospital,
Catholic University Medical College,Seoul South Korea
Journal of Korean Society for Clinical Pharmacology and
Therapeutics (South Korea) 1996, 4/1 (29-34)
Background: Prostaglandin E1 (PGE1), a potent vasodilator
and an inhibitor of platelet aggregation, has been reported to
be useful in the treatment of peripheral vascular diseases and
severe Raynaud's phenomenon. Lipo-PGE1 which is a drug
preparation of PGE1 incorporated in lipid microspheres has
advantage for its longer action and smaller requirement dosage
because of less inactivation in the lung than original
PGE1.
Methods: We evaluated the efficacy and safety of Lipo-PGE1
in the treatment of peripheral vascular diseases including
ulcer, gangrene, and severe Raynaud's phenomenon in systemic
lupus erythematosus (SLE) and systemic sclerosis (SSc). The
study population included 25 patients (mean age: 36.7 +/-
12.8, F:M = 23:2; SLE (13), systemic sclerosis (12)).
Intravenous Lipo-PGE1 (10 mug) was infused every day for 4
weeks. The assessment of efficacy was monitored by patient's
subjective questionnaire, ulcer size and digital hemodynamics
using finger systolic pressure.
Results: The overall patient's assessment by subjective
symptoms including coldness, numbness or rest pain were
improved in 17 patients (68%), but not changed in 8 patients.
The decreases of ulcer or gangrene size were noted in 21
patients, but 4 patients remained unchanged. There was a
significant increase in the finger systolic pressure at 15
minutes following cold stimuli after the treatment (P <
0.01). Significant adverse reactions were not found except
pain on injected site (2), mild transaminase elevation (1) and
fever (1).
Conclusion: These data suggested that Lipo-PGE1 is
relatively safe and beneficial as well as convenient for
administration in the treatment of peripheral vascular disease
secodary to connective tissue diseases.
Influence of calcitonin on eicosanoid serum levels
in the treatment of patients with systemic sclerosis
Gruschwitz M.S.; Collenberg C.; Albrecht H.-P.
Div. of Connective Tissue Research, Dept. of Dermatology,
Medical School, University of Erlangen-Nuremberg,
Hartmannstrasse 14,91052 Erlangen Germany
Journal of the European Academy of Dermatology and
Venereology (Netherlands) 1996, 7/2 (139-148)
Background: Treatment of scleroderma (systemic sclerosis,
SSc) patients (stages I-III) with intravenous (i.v.)
calcitonin for 10 days (100 IU/day, Karil(R), Sandoz AG,
Germany) 3 times/year leads to subjective and objective
improvement of microcirculatory parameters determined by
Laser-Doppler fluxmetry and cutaneous pOinf 2 (pcuOinf 2)
measurement.
Aim: As previously suggested some rheologic effects of
calcitonin might be mediated by vasoactive metabolites of the
arachidonic acid metabolism. Alterations of eicosanoid plasma
levels were determined in 15 SSc patients during i.v.
calcitonin therapy.
Methods: Peripheral blood was obtained on the 1st and 9th
days of therapy during a 2 h intravenous calcitonin
administration. Samples were taken after 45, 90, 135 and 160
min as well as 1, 5 and 19 days after therapy was stopped.
Serum levels of 6-keto-prostaglandin F(1alpha) (6-keto-PGF), a
stable end product of prostacyclin synthesis, prostaglandin
Einf 2 (PGEinf 2), leukotriene Binf 4 (LTBinf 4), and
thromboxane Binf 2 (TXBinf 2) were determined by enzyme- or
radio-linked assays.
Results: In contrast to healthy controls we measured
elevated 6-keto-PGF, LTBinf 4 and PGEinf 2 serum levels in SSc
patients before i.v. treatment, whereas TXBinf 2 levels showed
no significant differences. Calcitonin administration led to
an increase of plasma 6-keto-PGF after 45 min falling back to
the starting level during further treatment as well as to a
longer-lasting increase of PGEinf 2 on both the 1st and 9th
days of therapy. Calcitonin treatment decreased LTBinf 4, but
did not influence TXBinf 2 levels significantly during
intravenous administration.
Conclusion: Our data suggest a compensatory mechanism of
the damaged vascular system with respect to the PGIinf 2
(prostacyclin) and PGEinf 2 formation in SSc patients measured
by a constant elevation of these vasodilatory metabolites.
LTBinf 4 may be involved in the microvascular damage in SSc.
Calcitonin administration leads to a short-lasting elevation
of 6-keto-PGF(1alpha) and an increase of PGEinf 2 combined
with a reduction of LTBinf 4 resulting in longer-lasting
beneficial effects on microcirculatory functions in diseased
skin. Since non-steroidal anti-inflammatory agents had no
influence on long-term vasoactive effects, improvement of
microcirculatory properties by calcitonin may be additionally
mediated by smooth muscle relaxation of arterioles.
Cyclosporin in the treatment of systemic
sclerosis
Rubisz-Brzezinska J.; Lis A.; Kucharz E.; Brzeziinska-Wcislo
L.; Kulawik I.
I Klinika Dermatologiczna, Slaska Akademia Medyczna, ul.
Francuska 20/24,40-027 Katowice Poland
Przeglad Dermatologiczny (Poland) 1995, 82/5
(459-464)
Nine patients with progressive systemic sclerosis lasting
for 1 to 10 years were treated with cyclosporin A at dosages
2.0-3.5 mg/kg/day, for 4-7 months. Patients were classified
according to Holzmann: as type III - 5 patients and as type IV
- 4 patients. In 6 patients there was observed marked
improvement. Beneficial therapeutic effects included softening
of the involved skin (6/9, 67%, improvement of muscle and
joint pains (3/6, 60%), and healing of persistent digital
ulcers (3/5, 60%). In 3 patients no improvement was noted. The
progression of the disease did not occur in any of the
patients. In no case serious side effects requiring
discontinuation of the therapy were noted.
Interferon-gamma therapy for systemic
sclerosis
Fierlbeck G.; Schreiner T.; Rassner G.
Liebermeisterstrasse 25,D-72076 Tubingen Germany
Allergologie (Germany) 1994, 17/8 (389-392)
The results of Interferon-gamma therapy for systemic
sclerosis (SSc) are reported in this paper. 25 patients were
evaluated after a median follow up of three and a half years
and a significant improvement of the skin score could be
demonstrated in early forms of SSc. Visceral manifestations of
SSc did not improve in general, whereas individual patients
also benefited from therapy. Interferon-gamma therapy was
generally well tolerated, only flue-like symptoms occured.
Soluble and cellular markers of immune activation
in patients with systemic sclerosis.
Degiannis D, Seibold JR, Czarnecki M, Raskova J, Raska K
Jr
Department of Pathology, UMDNJ--Robert Wood Johnson Medical
School, Piscataway 08854.
Clin Immunol Immunopathol 1990 Aug;56(2):259-70
The peripheral blood lymphocyte pattern, the lymphocyte
responses in vitro, as well as the soluble markers of immune
activation were studied in 24 patients with systemic sclerosis
(SSc patients). The proportions of total T cells (CD3), their
CD4 subset, as well as B lymphocytes were within the normal
range. The relative proportion of CD8 lymphocytes, however,
was significantly reduced. Patients with SSc had a slightly
lower percentage of CD4/4B4+ cells, whereas their proportion
of CD4/2H4+ cells was elevated as compared to healthy
controls. The proportion of lymphocytes expressing the
interleukin-2 receptor (IL-2R) was significantly higher in SSc
patients. The proliferative responses of peripheral blood
mononuclear cells to PHA stimulation were reduced in the
patient group, while expression of IL-2R on lymphocytes after
such in vitro stimulation was comparable to that of controls.
Expression of IL-2R on patient but not control lymphocytes was
increased after in vitro exposure to laminin. Such exposure
failed to induce IL-2 production or cell proliferative
responses. Soluble plasma IL-2R level (sIL-2R) and soluble CD8
(sCD8) molecule levels in SSc patients were significantly
elevated. These results indicate the presence of an ongoing
lymphocyte activation in this disease process.
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