ARTICLE
Although a large number of treatments have been proposed for scleroderma,
there is still no drug available to cure this disorder. Octreotide (Sandostatine®)
has proven to be effective for the treatment of intestinal dysmotility
in patients with scleroderma [1]. For short-term administration, the somatostatin
analogue octreotide reduces bacterial overgrowth, stimulates intestinal
motility and improves abdominal symptoms [1, 2]. To date no data have
reported a possible global improvement of scleroderma manifestations with
long-term administration of octreotide.
Case report
A 53-year-old black woman was admitted in 1993 to our hospital for recurrent
acute intestinal pseudo-obstruction. She was diagnosed with a four-year
history of progressive and severe systemic scleroderma. The condition
started in 1989 with a Raynaud phenomenon rapidly followed by cutaneous
changes. On admission, physical examination showed a diffuse skin sclerosis
with the unpigmented area predominant on the arms, the face and the chest.
The skin was thickened preventing any venous blood puncture. The fingers
held in semiflexion. Myositic involvement was noted with proximal muscle
weakness and elevation of serum creatine phosphokinase. Lung functions
were abnormal with an impaired carbon monoxide transfer factor (57% of
the predicted normal value). Digestive involvement was severe with complaints
of dysphagia, vomiting and recurrent intestinal pseudo-obstruction. The
total weight loss was 18 kg. She had manometric evidence of abnormal esophageal
motility, with aperistalsis and decreased gastroesophageal-sphincter pressure.
Antinucleolar antibodies were present (1/1,000) whereas anticentromere,
anti-Scl 70, anti-Jo-I, and anti-DNA were not found. Prednisone was started
in November 1993 (1 mg/kg) and only provided relief of muscle symptoms.
Volvulus of the small intestine occurred in May 1994 for which the patient
underwent emergency surgery. Thereafter intestinal manifestations persisted
unchanged. Breath tests revealed bacterial overgrowth into the intestinal
lumen. The patient was placed under parenteral renutrition.
Octreotide (Sandostatine®, 75
µg/d) was initiated in November 1994. Prednisone was initially dosed
at 20 mg per day and progressively tapered. After one month of treatment,
oral feeding was restarted and weight gain of 6.5 kg was achieved. After
8 months of treatment, normal weight was obtained. On examination skin
induration was spectacularly reduced and pigmentation returned to a normal
state (Figs. 1
and 2). Venous blood puncture was possible and the ability
to straighten the fingers was restored. Dyspnea disappeared and physical
activity was quite normal. Octreotide was stopped in November 1996. In
October 1997, one year after the discontinuation of octreotide, carbon
monoxide transfer factor increased to 70% of that predicted for age and
sex. In February 1999, the skin involvement remained very limited.
Discussion
Effects of octreotide on intestinal motility in scleroderma are well
known and were rapidly observed in our case [1, 2]. Because of severe
intestinal manifestations, long-term administration of octreotide was
undertaken and induced an unexpected skin, muscle and respiratory improvement.
No side-effect was observed despite long-term administration. Octreotide
is a long-acting somatostatin analogue, principally used in the treatment
of endocrine tumors. Somatostatin elicits a wide range of biological effects
which may modulate inflammation. It inhibits the activity of immunocompetent
cells, including T lymphocyte proliferation and immunoglobulin production
by B lymphocytes [3, 4]. It modifies the secretory activity of neurons
and neuroendocrine cells [3, 4]. Octreotide effects on intestinal transit
are unclear and may be secondary to immunomodulation or neurotransmission
effects [5].
To our knowledge, extradigestive effects of
octreotide in scleroderma have not been studied. It is unlikely that the
relief of symtoms in this patient are strictly due to the increase of
the diet, and such improvement has not been described after parenteral
renutrition. Regression of sclerodermatous skin manifestations were reported
in acromegaly and in a patient with carcinoid syndrome treated by octreotide
[6, 7]. It is speculated that somatostatin has a direct action on dermal
fibroblasts and may act as a negative autocrine/paracrine factor [8].
This report suggests that long-term administration of octreotide may
be beneficial in the treatment of patients with systemic scleroderma.
Long-term trials are required to confirm these preliminary results.
REFERENCES
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