Open Journal of Ophthalmology, 2013, 3, 70-72 Published Online August 2013 (
Mixed Connective Tissue Disease Complicated by Retinal
Microvasculopathy and Its Relationship with Fragile -X
David Woo1*, Kenneth Ooi2, Jennifer Sandbach2, Fredrick Joshua2
1Department of Ophthalmology, The Canberra Hospital, Canberra, Australia; 2Department of Ophthalmology, Prince of Wales Hos-
pital, Sydney, Australia.
Email: *
Received April 28th, 2013; revised May 29th, 2013; accepted June 15th, 2013
Copyright © 2013 David Woo et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose: To report an unusual case of retinal microvasculop athy secondary to mixed connectiv e tissue disease (MCTD)
on a background history of fragile-X syndrome (FXS). Methods: Case report and literature review. Results: A cotton
wool spot was discovered in a 29- year-old female who presented with an ischaemic digit secondar y to Raynaud’s phe-
nomenon. She also has a background history of MCTD and FXS. Fundus examination and automated perimetry find-
ings were normal. Magnet resonance imaging and computed tomography aortogram did not demonstrate any evidence
of vasculitis in the head and neck . She wa s tested positiv ely for U1-ribonu clear p eptide. In teresting ly, the re-distribution
of Fragile-X related gene 1 has been suggested to trigger autoimmune responses in experiments. This finding makes the
case peculiar as it suggests an alternate explanation for this patient’s clinical findings. Conclusion: Retinal vasculopa-
thy is a rare complication of MCTD. The background history of FXS potentially highlights an alternate autoimmune
pathogenetic mechanism.
Keywords: Retinal Microvasculopathy; Mixed Connective Tissue Disease; Fragile-X-Syndrome
1. Introduction
Mixed connective tissue disease (MTCD) is a systemic
condition immuno logically characterised by the presence
of T cells and autoantibodies against U1-ribonuclear
peptide (U1RNP). It commonly displays overlapping
clinical features of scleroderma (SD), systemic lupus
erythematosus (SLE), rheumatoid arthritis and inflam-
matory myopathy; but the main manifestations include
Raynaud’s phenomenon, arthralgia, finger or hand oe-
dema, sclerodactyly, myositis and pulmonary involve-
ment [1].
Retinal vasculopathy is rarely reported with MCTD
and its pathogenesis remains elusive. It is possible that
there may be alternate underlying autoimmune mecha-
nisms at play in the presence of Fragile-X syndrome
(FXS). The clinical relation between FXS and MCTD is
examined in this article.
2. Methods
Case report and literature review.
3. Results
A 29-year-old anxious female with FXS and MCTD pre-
sented with an acutely painful ischaemic left 3rd digit
(Figure 1(a)) related to Raynaud’s phenomenon, and
assorted digit splinter haemorrhages. She was referred to
our service for screening prior to hydroxychloroquine
commencement; and left thorascopic sympathectomy pre-
operative work up.
There were no visual complaints at presentation, and
her vision was 6/9 bilaterally unaided. No ptosis was
evident and her pupils were equal and reactive with no
relative afferent pupillary defect. Right fundus examina-
tion revealed a single cotton-wool spot (CWS), which
raised the concern of retinal microvasculopathy. There
were no other significant ocular findings.
Automated perimetry was within normal limits. Pho-
tographs were taken (Figure 1(b)) but no fluorescein
angiography (FA) was performed due to her anxiety
about the risks.
Consequently, magnetic resonant imaging of the brain
and arteries were performed, and showed no signs of
*Corresponding a uthor.
Copyright © 2013 SciRes. OJOph
Current Distortion Evaluation in Traction 4Q Constant Switching Frequency Converters 71
Figure 1. (a) Left ischaemic digit at presentation; (b) Right
fundus photograph demonstrating single cotton wool spot.
cerebral vasculitis. No further evidence of stenosis or
vasculitis was demonstrated on CT aortogram and duplex
ultrasound of the upper limbs and carotids.
Our patient tested positive for U1RNP antibodies,
Sjögren’s syndrome A antibodies, Smith antibodies and
cyclic anti-citrullinated protein. Anti-nuclear antibody
titre was > 1:1520.
A left thorascopic sympathectomy was performed be-
cause the ischaemic digit showed minimal response to
epoprostenol treatment. The procedure was uncompli-
cated and allowed further conservative management
without amputation. With still the possibility of a more
prevalent systemic small vessel vasculitis she also re-
ceived three doses of pulsed intravenous methylpredni-
sone 1 gm, followed by oral prednisone instead of hy-
droxychloroquine. She subsequently developed another
CWS in the other eye soon thereafter, but to date has not
developed extensive pan-retinal vasculitis.
4. Discussion
This case is peculiar in two regards, namely, the presen ce
of a retinal microvasculopathy and the associated history
of FXS.
Retinal vasculopathy is rarely reported in patients with
MCTD. Kraus et al examined the FA findings in patients
with MCTD, SLE, and SD. A higher frequency of vas-
cular leakages was observed in the MCTD population
(30%) compared to the other groups [2]. Systemic low
dose corticosteroid therapy was found to be beneficial by
Mimura [3]; however delays with treatment have lead to
severe visual impairment [4].
Our patient’s vision was fortunately unaffected despite
the threat of overt retinal vasculopathy. Her vision re-
mains stable with ongoing corticosteroid therapy despite
development of a further juxtapapillary CWS on the left.
The multifactorial immunopathogenesis of MCTD in-
cludes: immune activation via Toll-like receptors, B-
lymphocytes, CD 4 and 8 T-lymphocytes, autoantibodies,
the modification of the RNP antigens and associated
RNAs [1]. The last factor is of particular interest in this
case. Bolivar et al demonstrated that the Fragile-X re-
lated gene 1 (FXR1) in SD is capable of generating an
autoimmune response in vitro. In apoptotic cells, FXR1
displaces from its original ribosome-associated cyto-
plasmic binding site to a more punctate foci, which re-
semble bleb-like membrane organelles. It was postulated
that this re-distribution of FXR1 auto-antigen in apop-
tosis might form the basis of an autoimmune response
with IgG gener a t i on to F XR 1 [5] .
In this case, the cluster of symptoms related to MCTD
occurred in an individual with FXS. While this may be a
fortuitous appearance of two rare diseases in the same
patient, the presence of FXR1 certainly raises the ques-
tion of an alternate autoimmune mechanism in this pa-
tient. Nevertheless from a clinical standpoint it should be
emphasized that prompt screening in MCTD may avert
sight-threatening vasculitis.
5. Conclusion
Retinal vasculopathy is a rare complication of MCTD.
The background history of FXS potentially highlights an
alternate autoimmune pathogenetic mechanism.
6. Acknowledgements
The authors would like to thank the Prince of Wales
Ophthalmology clinic for supplying the clinical photo-
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Copyright © 2013 SciRes. OJOph
Mixed Connective Tissue Disease Complicated by Retinal Microvasculopathy and the Relationship with
Fragile-X Syndrome
Copyright © 2013 SciRes. OJOph
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