Less Well-Recognized Manifestations of Systemic
Sclerosis (Scleroderma)
By Sergio Jimenez, M.D., Director of The Scleroderma Center and Dorrance
H. Hamilton Professor of Medicine at Thomas Jefferson University, Philadelphia,
Pa. (originally published in Scleroderma Foundation Newsline, Vol.
2, No. 3 [Summer–Fall 1999])
Skin induration and fibrosis affecting numerous internal organs such
as the lungs, heart, kidneys, and the gastrointestinal tract are well-known
clinical manifestations of systemic sclerosis (scleroderma).
Well-recognized also are the manifestations of the CREST syndrome which
include calcinosis (calcium deposits in the skin and surrounding joints),
Raynaud's phenomenon, esophageal dysfunction causing reflux and difficulty
swallowing, skin induration, and telangiectasis (dilated vessels in the
skin and occasionally in the lining of the mouth and gastrointestinal
tract).
However, there are several other clinical manifestations of the disease
that are not as well recognized and often are not ascribed to be caused
by systemic sclerosis.
lthough some of these manifestations are much less frequent than those
mentioned above, they often cause substantial symptoms and, occasionally,
anxiety in affected patients.
The following list shows the most frequent of these less well-recognized
manifestations of systemic sclerosis:
- Thyroid involvement
- Impotence
- Testicular fibrosis
- Bladder involvement
- Carpal tunnel syndrome
- Trigeminal nerve palsy
- Periodontal ligament resorption
- Vocal cord infiltration
Endocrine Manifestations
Hypothyroidism
Involvement of the endocrine system by systemic sclerosis is frequently
not recognized although it occurs with considerable frequency.
The most common endocrine manifestations are related to alterations in
the thyroid gland which often result in decreased or lost function (hypothyroidism).
The frequency of thyroid gland involvement has not been accurately determined
although prospective studies estimated that it was present in 30% to 35%
of patients with systemic sclerosis.
In our own experience, we have found that hypothyroidism related to systemic
sclerosis may be present in approximately 25% of patients.
The mechanisms responsible for thyroid gland dysfunction appear to be
the replacement of the functional components of the thyroid gland by fibrous
tissue and the infiltration of the gland by numerous inflammatory cells,
particularly lymphocytes.
Clinically, hypothyroidism manifests as progressive weight gain, decreased
tolerance to cold temperatures, sluggishness, slowing of mental functions,
and in advanced stages, the development of cutaneous lesions in the lower
extremities.
The inflammatory process affecting the thyroid gland may manifest in
the earlier stages as hyperthyroidism or excessive function of the gland
because the inflammation causes destruction of the colloid follicles which
are specialized structures in the thyroid gland responsible for storage
of the thyroid hormone.
The destruction of large numbers of colloid follicles results in exaggerated
release of thyroid hormone which can produce symptoms of excessive thyroid
function.
Subsequently, however, the extensive fibrotic replacement and progressive
inflammatory damage to the tissue results in loss of function and decreased
production of the thyroid hormone.
The presence of thyroid dysfunction can be easily tested by performing
blood analysis of circulating thyroid hormone and of a hormone that stimulates
the thyroid gland called thyroid stimulated hormone (TSH).
Elevated levels of TSH are correlated directly with the loss of function
of the thyroid gland since they represent an attempt of the body to stimulate
the gland and correct the low levels of circulating thyroid hormone.
On a few occasions, the attempts to restore the function of the thyroid
gland can lead to the formation of nodules within the thyroid gland which
can be diagnosed by clinical examination by a physician or by more specialized
tests such as ultrasound examination of the gland.
Thyroid hormone replacement often produces dramatic and substantial improvement
in these manifestations. However, it is essential to demonstrate conclusively
that there is indeed a deficient production of thyroid hormone and a decreased
circulating level of the hormone before initiation of treatment with thyroid
replacement.
Genitourinary Tract
Although not frequently recognized, Systemic Sclerosis can also affect
the genitourinary tract. Among the most common alterations of this system
caused by the disease are impotence, bladder fibrosis, and testicular
fibrosis.
Impotence
The occurrence of severe impotence, without a decrease in libido, in
male patients with systemic sclerosis was first recognized by our group.
This symptom has been subsequently described in numerous other patients
affected by the disease.
In many instances, impotence may be the result of the generalized fatigue
or the general effect that the disease produces on the body, or may be
related to psychological factors such as depression, loss of self-esteem
or anxiety.In other instances, it is an organic problem directly caused
by the pathologic alterations of the disease.
The mechanisms responsible for erectile failure in systemic sclerosis
have not been entirely clarified. However, it is very likely that this
problem is due to either fibrosis of the cavernous bodies, the organs
that become engorged with blood during penile erection, or to decreased
arterial blood flow secondary to narrowing and thickening of the vascular
wall of arteries supplying blood flow to the penis.
Impotence in systemic sclerosis, when present, can cause substantial
emotional distress, frustration, and anxiety; and requires expert evaluation.
Psychological evaluation and support are often helpful, in addition to
other therapeutic measures to successfully overcome the serious difficulties
caused by this manifestation of systemic sclerosis.
Bladder Fibrosis
The exact frequency of occurrence of urinary bladder dysfunction in patients
with systemic sclerosis has not been determined.
However, numerous patients develop symptoms of urgency and frequency
which do not appear to be related to other causes except for bladder involvement.
In these cases, the bladder wall is infiltrated by fibrotic tissue and
the contractile muscles responsible for normal function of the bladder
have become ineffective.
Some studies have demonstrated decreased dispensability of the bladder
and reduction of the bladder capacity to hold urine. Pathologic studies
at autopsy have shown that the bladder wall is thickened and is infiltrated
with abundant amounts of collagen and other components of the connective
tissue causing atrophy of the muscles responsible for normal contractile
activity of the organ.
Frequently, bladder involvement becomes apparent by the presence of microscopic
hematuria (red blood cells in the urine) which is usually detected in
routine urine analysis. A careful evaluation by a specialist is necessary
to determine the cause of hematuria and specialized tests may be required
to ascertain whether it is due to systemic sclerosis bladder involvement
or to other problems such as bladder cancer.
Testicular Fibrosis
A rare complication of systemic sclerosis also found in males is testicular
fibrosis. This alteration manifests by enlargement of the testicles which
occasionally may be tender or painful.
Although it does not appear that this process causes infertility (due
to alterations in production of normal semen), it is possible that affected
younger individuals may have difficulty in their ability to effectively
fertilize the ovum.
This is a rare complication and we have observed only very few patients
with this clinical situation.
Neurologic Involvement
Alterations of the central peripheral nervous system are rare in systemic
sclerosis. However, there are two manifestations which appear with more
frequency.
Carpal Tunnel Syndrome
Carpal tunnel syndrome is occasionally one of the earliest manifestations
of the disease and usually appears during the edematous phase (swelling
and puffiness). It appears to be related to swelling of the connective
tissues surrounding the carpal ligaments resulting in compression of the
nerves that traverse this tight channel on their way to the hands.
The symptoms usually improve spontaneously when the disease progresses
from the edematous stage to the sclerotic or fibrotic stage and surgery
is not necessary.
Trigeminal Nerve Palsy
A less common involvement of the nervous system affects the fifth cranial
nerve or trigeminal nerve which normally provides sensation to the lower
part of the face and to the tongue. In these cases, affected patients
may develop pain and loss of sensation in the lower part of the face or
just on one side and often they also develop lack of sensitivity in the
tip of the tongue.
The mechanisms responsible for trigeminal neuralgia are not known at
the present time. However, it is likely that compression of the trigeminal
ganglion against the bones of the skull inside the brain may cause this
problem. In most cases, the symptoms subside spontaneously and no therapy
other than analgesia is required.
Other Miscellaneous Manifestations
Vocal cord infiltration
Other less frequently recognized manifestations of systemic sclerosis
are vocal cord involvement in which the vocal cord tissues are replaced
by connective tissue and lose their proper function. In these cases, severe,
persistent, and progressive hoarseness develops.
Hoarseness related to vocal cord fibrosis should be distinguished from
that due to reflux of gastric acid contents causing irritation and inflammation
on the vocal cords. In these latter cases, the symptoms are intermittent
and usually respond well to acid suppressive therapy.
Periodontal Ligament Resorption
Another manifestation of systemic sclerosis which occasionally produces
clinical symptoms is due to the excessive accumulation of collagen in
the periodontal ligament, the membrane that holds the root of the teeth
attached to the mandibular or maxillar bones. In these cases there might
be pain at the root of the affected teeth and, occasionally, loosening
of the root with movement of the teeth can occur.
Conclusion
This brief review provides some information regarding less well-recognized
manifestations of systemic sclerosis which, although rare in frequency,
can nevertheless result in substantial symptoms for affected patients.
The knowledge that these manifestations are related to the disease can
often provide an explanation for a variety of symptoms which otherwise
would remain unexplained. Although there is no specific treatment for
the majority of these manifestations, in a few instances they can be improved
or ameliorated by medical or pharmacological treatment.
Furthermore, the understanding that some of these symptoms may be related
to the disease is often sufficient to assuage the anxiety that many patients
with scleroderma may feel when they develop unexplained symptoms.
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