Rheumatology 2001; 40: 357-358
© 2001 British Society for Rheumatology
Letters to the Editor |
EMO syndrome as a late explanation for pretibial swelling
Medizinische Klinik VI,
1 Division of Radiology and
2 Division of Neuropathology, Universitätsklinik der Albert-Ludwigs-Universität Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany
SIR, A 53-yr-old man presented in April 1999 with a 10-yr history of left pretibial swelling and reddening. After a minor trauma in spring 1998 he also started to feel a continuous intense pain in that area. His physical examination was normal except for a painful, left-sided pretibial inflammation, exophthalmos and hypertension of 170/100 mmHg. The laboratory values included a moderate elevation of C-reactive protein (2.4 mg/dl) and C3d (12.7 mg/l, normal <10 mg/l). Furthermore, his thyroid hormone levels were increased, and as anti-TSH receptor autoantibodies were also significantly elevated (70.4 U/ml), the diagnosis of Graves disease was established and therapy with thiamazole was instituted. A biopsy of the anterior part of the left tibia was performed but showed only non-specific inflammatory changes. For symptomatic relief the patient was then started on systemic corticoid therapy. After addition of methotrexate, his pain decreased. MRI was performed and showed the presence of increased water signal intensity consistent with muscle oedema and myositic changes in the dorsal parts of both calves. Furthermore, signs of periostitis were present around the anterior part of the left tibia (Fig. 1
). A biopsy of the left gastrocnemius was performed, which showed single-fibre atrophy and marked fibrosis. There was no marked inflammatory reaction as only a few activated macrophages or T-cells were detectable by immunofluorescent staining for CD68 and CD3. Interestingly, fatty vacuoles were shown to be present by electron microscopy, a finding which is often seen in thyrotoxic myopathy. We re-examined the second biopsy from September 1998 and the first biopsy, which was taken 10 yr ago, when the symptoms first appeared. Both of these biopsies showed signs of periostitis ossificans such as focal and perivascular lymphocytic infiltration and ossification (Fig. 2).
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Periostitis ossificans is the pathological correlate of osteoarthropathy as part of the EMO syndrome (exophthalmos, pretibial myxoedema and osteoarthropathy), a rare condition seen in patients suffering from Graves disease [1]. It is related to acropachy, which is a limited form confined to the metacarpals and phalanges of the first three fingers. In some cases, bones of the feet are also affected and there may be painful swelling of the surrounding tissues. Isolated involvement of one tibial bone combined with endocrine myopathy, as present in our patient, is an unusual finding. Since hypertrophic osteoarthropathy of the long tubular bones may also be caused by chronic respiratory or metabolic illness (which is then called Marie–Bamberger syndrome), it is important to exclude an underlying systemic disease. Little is known about the pathogenesis of the EMO syndrome. Autoantibodies against thyroid antigens and autoreactive T-lymphocytes are suspected to cross-react with muscle and connective tissue antigens [2]. There is a higher prevalence of the A2 allele of the interleukin-1 receptor antagonist gene in those patients with Graves disease who also have extrathyroid manifestations such as pretibial dermopathy and acropachy, compared with patients who have only limited disease [3]. It was suggested that localized activation of endothelial cells by an abnormal platelet population results in release of fibroblast growth factors. Activated fibroblasts seem to play a decisive role in the pathogenesis of connective tissue manifestations of Graves disease [4]. The differential diagnosis of pretibial swelling includes erythema nodosum and morphea. Proper treatment of thyrogenic myopathy and osteopathy consists of establishing a euthyroid state. It is important to avoid both hyper- and hypothyroidism. If this does not result in control of the symptoms, a more definite approach is indicated, including radioiodine therapy and surgery. As topical therapy, fluorinated steroids under an occlusive dressing have shown some benefit [5]. Our patient improved under treatment with thiamazole, methotrexate and prednisolone.
In conclusion, osteoarthropathy is correlated with Graves disease. Sometimes the typical symptoms manifest long after proper treatment of the endocrinopathy has been instituted. Our patient exhibited symptoms of osteoarthropathy long before clinical or laboratory signs of Graves disease were present. This order of events may cause difficulty in establishing the proper diagnosis in similar clinical settings.
Notes
Correspondence to: M. Imgrund. 
References
- Becker KL. Principles and practice of endocrinology and metabolism. 2nd edn. Philadelphia: J.B. Lippincott, 1995.
- Kiljanski J, Nebes V, Wall JR. Significance of tissue specific and tissue non specific autoimmune reactions of Graves' disease. Clin Exp Rheumatol1996;15(Suppl.):S69–76.
- Cuddihy RM, Bahn RS. Lack of an association between alleles of interleukin-1 alpha and interleukin-1 receptor antagonist genes and Graves disease in a North American Caucasian population. J Clin Endocrinol Metab1996;81:4476–8.[Abstract]
- Bahn RS. The fibroblast is the target cell in the connective tissue manifestations of Graves disease. Int Arch Allergy Immunol1995;106:213–8.[Web of Science][Medline]
- Parker LN, Wu SY, Lai MK, Ramadan MB, Rajan RK, Yusi AM. The early diagnosis of atypical thyroid acropachy. Arch Intern Med1982;142:1749–51.
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