Mixed Connective Tissue Disease Complicated by Retinal Microvasculopathy and Its Relationship with Fragile-X Syndrome

doi:10.4236/ojoph.2013.33017

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Open Journal of Ophthalmology, 2013, 3, 70-72

http://dx.doi.org/10.4236/ojoph.2013.33017 Published Online August 2013 (http://www.scirp.org/journal/ojoph)

Mixed Connective Tissue Disease Complicated by Retinal

Microvasculopathy and Its Relationship with Fragile -X

Syndrome

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: *[email protected]

Received April 28th, 2013; revised May 29th, 2013; accepted June 15th, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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.

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-

graphs.

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Mixed Connective Tissue Disease Complicated by Retinal Microvasculopathy and the Relationship with

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