Less Well-Recognized
Manifestations of Systemic Sclerosis (Scleroderma)
 |
| Sergio
Jimenez, M.D. |
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])
Editor's note: You can skip directly to the subheads
that interest you, by clicking on these links:
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. |
