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Early Spondyloarthritis in an HLA-B27-positive Monozygotic Twin Pair: A Highly Concordant Onset, Sites of Involvement, and Disease Course To the Editor: Susceptibility to ankylosing spondylitis (AS) and the related spondyloarthropathies (SpA) is determined by a strong polygenetic predisposition interacting with as-yet unknown environmental factors. HLA-B27 is one of the major disease susceptibility genes, and studies of HLA-B27-positive twins have shown a concordance rate of 63% among monozygotic versus 24% in dizygotic twin pairs1-5. Making an early diagnosis of AS and related SpA is often challenging, and there are no validated diagnostic criteria6-10. Magnetic resonance imaging (MRI) is the imaging method of choice for early detection and assessment of inflammatory lesions in the axial skeleton prior to the development of structural damage seen on standard radiographs11. We describe HLA-B27-positive monozygotic Caucasian twin brothers who had experienced the onset of undifferentiated spondyloarthritis at 23 years of age only 10 months apart, and with almost identical clinical manifestations: stiffness of the neck and dactylitis of a toe in the left foot, followed by right-side sacroiliitis. The twins were living far apart in 2 different cities. Twin A developed neck stiffness (that resolved within a few weeks) and dactylitis of the fourth toe of his left foot (that lasted about 6 months), followed 4 weeks later by recurrent right buttock pain with frequent flares. His buttock pain and subsequent plantar fasciitis in his left foot showed symptomatic response to treatment with indomethacin. An MRI [short-tau inversion recovery (STIR) sequence] performed 9 months after the onset of right-side buttock pain showed inflammatory lesions of the distal (cartilaginous) part of the right sacroiliac joint and the adjacent sacral and iliac bones (Figure 1, top). He was found to have HLA-B27. A standard pelvic radiograph at 12 months after the onset of buttock pain displayed right-side grade 3 sacroiliitis (Figure 1, bottom). A whole-body MRI was performed during a period of low disease activity a month later because of the patient's academic interest. It confirmed the presence of chronic inflammatory changes in the right sacroiliac joint (Figure 2A). There was no active inflammatory lesion in the entire spine, the anterior chest wall, and the shoulder and pelvic girdles (Figure 3A).
Ten months after the onset of symptoms in Twin A, his monozygotic twin brother (Twin B) also developed neck stiffness and associated dactylitis that affected the second toe of his left foot, and MRI showed flexor tenosynovitis with synovitis of metatarsophalangeal joint of that toe. As in Twin A, there was no history of psoriasis or inflammatory bowel disease and no gastrointestinal or genitourinary symptoms. He was also found to possess HLA-B27. Dactylitis persisted despite treatment with naproxen, and 4 months later, even though he did not complain of clinically relevant buttock or low back pain, a standard pelvic radiograph was performed because of his twin brother's diagnosis of spondyloarthritis. The radiograph showed bilateral grade 1 sacroiliitis (equivocal structural changes). Four months later, when he had just begun to notice morning stiffness of his lumbar spine without back pain, a whole-body MRI (performed on the same day as in Twin A, and on the same MRI machine) showed acute inflammatory lesions of both the iliac and the sacral sides in the distal part of the right sacroiliac joint (Figure 2B). As in Twin A, there were no active inflammatory lesions in the spine, the anterior chest wall, and the shoulder girdle, but it is of interest that both twins showed remarkably identical early lumbar degenerative disc lesions at L3/L4 and L4/L5, with annulus fibrosus tear (Figure 3).
The MR signal alterations observed in the distal part of the asymptomatic right sacroiliac joint in Twin B may represent a very early sign of as-yet subclinical but evolving sacroiliitis. Previous studies have shown that early sacroiliitis starts in the distal portion of the sacroiliac joints12,13. Twin A showed a right-side grade 3 sacroiliitis only 12 months after onset of back pain. Possible explanations may be a rapidly progressive inflammation or a prior subclinical sacroiliitis long before back pain becomes relevant for the patients. In a study of 68 patients with inflammatory back pain of less than 2 years' duration, only 14 had radiographic sacroiliitis that fulfilled the modified New York classification criteria for AS14. Recent progress in MR technology (new coil designs, multichannel technology, and parallel image acquisition) has led to a new technique of whole-body MRI that provides T1-weighted spin-echo and STIR images in the coronal and sagittal planes in just 30 minutes, including patient positioning, and its spatial resolution equals that of the standard MRI15. It is a promising new tool to help diagnose SpA early (within 4 months after symptom onset in the case of Twin B), and for comprehensive assessment of inflammatory lesions in the entire axial skeleton, including the chest wall and hip and shoulder girdles. There is a need to develop standards in reporting the observed inflammatory signal alterations, including their sensitivity and specificity, and to demonstrate whether they predict future radiographic structural damage16. These issues must be addressed before the radiographic evidence of sacroiliitis in the modified New York classification criteria for AS17 may be replaced by an assessment by MRI. Our case report illustrates the high clinical relevance of dactylitis in making a diagnosis of spondyloarthritis. A recent literature review focusing on various clinical features, laboratory findings, and skeletal imaging techniques that clinicians rely on to diagnose AS showed that dactylitis has a specificity of 96%18. In both twins, long-lasting dactylitis accompanied by relatively transitory neck pain was the first manifestation of undifferentiated spondyloarthritis. A high degree of concordance of disease onset, sites and patterns of involvement, and the disease course in identical twins is a dramatic example of genetic influences in not only the predisposition to spondyloarthritis but also its clinical onset, clinical presentation, and phenotypic expression. Our report also highlights the potential role of the whole-body MRI in very early diagnosis of spondyloarthritis and in assessing inflammation in the entire axial skeleton. ULRICH WEBER, MD, Department of Rheumatology; CHRISTIAN W.A. PFIRRMANN, MD, Department of Radiology; RUDOLF O. KISSLING, MD, Department of Rheumatology, Balgrist University Hospital, Zurich, Switzerland; C. RONALD MACKENZIE, MD, Department of Rheumatology, Hospital for Special Surgery, New York, New York; MUHAMMAD A. KHAN, MD, Department of Medicine, Division of Rheumatology, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA. Address reprint requests to Dr. U. Weber, Department of Rheumatology, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland. E-mail: ulrich.weber@balgrist.ch
The Whole Body Magnetic Resonance Imaging in Ankylosing Spondylitis project is supported by the Walter L. and Johanna Wolf Foundation, Zurich, and the Foundation for Scientific Research at the University of Zurich, Switzerland. ACKNOWLEDGMENT We thank both the patients, who have read and approved the manuscript, and Eva Kirchwey (Balgrist University Hospital) for her secretarial assistance.
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