Department of Pathophysiology and
1 Department of Neurology, School of Medicine, University of Athens, Greece
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Abstract |
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Patients and methods. Three out of 518 (0.6%) pSS patients followed in our department over a period of 15 yr (19852000) also presented IBM. The diagnosis was based on histological criteria. Previous reports described four more patients with IBM associated with pSS. Five out of six were females; the mean age of IBM onset was 53.3±14.0 yr and the disease duration 8.0+5.8 yr.
Results. Four out of six patients presented IBM several years after the onset of pSS. Four out of six patients presented extraglandular manifestations, such as arthralgias, vitamin B12 deficiency, interstitial kidney disease and biliary cirrhosis. The serological picture did not differ significantly from that observed in pSS alone.
Conclusion. Although rare, IBM may be seen in patients with pSS and it affects predominantly women. The clinical and pathological pictures do not differ from those observed in idiopathic IBM. A common autoimmune pathway in these two diseases, but no definite conclusions can be drawn.
KEY WORDS: Sjögren's syndrome, Inclusion body myositis, Anti-ro/SSA, Anti-La/SSB.
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Introduction |
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The inflammatory myopathies comprise three major and discrete groups: those of polymyositis, dermatomyositis and inclusion body myositis (IBM) [4]. The last of these is the most common acquired myopathy in patients older than 50 yr. IBM has been reported previously in three patients with pSS [57]. Here we report the clinical, immunological and pathological picture of three new cases with IBM and pSS, analyse the data from all six reported cases and discuss the possible association between pSS and IBM.
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Patients and methods |
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Results |
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During the preceding 4 months she had complained of increased muscle weakness, especially during exercise. Physical examination revealed hepatomegaly and splenomegaly (2 cm each beneath the costal arc) and slight impairment of muscle function in the adduction and abduction of the left thigh, left calf (4/5) and left arm (4+/5). No weakness was detected on examination of other muscle groups. The rest of the clinical examination was normal. The patient was receiving hydroxychloroquine 200 mg/day, ursodesoxycholic acid 750 mg/day, allopurinol 100 mg/day, amiloride hydrochloride 5 mg/day, hydrochlorothiazide 40 mg/day, alfacalcidol 1 µg/day and vitamin E 200 mg/day. She received no steroids.
Laboratory data revealed mild anaemia (haemoglobin 12.9 mg/dl) and normal white blood cell and platelet counts (7x109/l and 260x109/l respectively). The creatine kinase (CK) concentration was high, at 432 U/l. Serum levels of thyroid hormones (triiodothyronine, thyroxine and thyroid-stimulating hormone) were within normal ranges.
A biopsy of the left quadriceps muscle disclosed IBM The patient received intravenous immunoglobulin (1 g/kg body weight on two consecutive days per month) with a slight improvement in muscle strength, but this treatment was stopped after 4 months due to an episode of acute renal failure. She then received azathioprine at a dose of 100 mg/day for 4 months; she developed leucopenia and this treatment was also stopped. She continued on physiotherapy and after a follow-up of 2 yr her clinical picture is stable.
Case 2.
A 74-yr-old man presented with progressive muscle weakness that lasted 8 yr. At the same time the patient reported dry mouth and dry eyes. He presented with dry, thin skin and dry mouth and eyes. Schirmer's test was negative but the Rose Bengal test was positive (4/9 bilaterally). He was positive for ANA, with a titre of 1:160 (fine speckled pattern), and for anti-Ro/SSA antibodies. A labial minor salivary gland biopsy had a focus score of 1.0/mm2 according to Chisholm's classification [9]. The muscle stretch reflexes were symmetrically diminished. The scapular, thoracic and forearm muscles were mildly atrophic and muscle strength was reduced.
A skinmuscle biopsy was performed but the findings were non-specific. The patient was diagnosed as having pSS associated with myositis and was treated with methylprednisolone 32 mg/day and methotrexate 20 mg/week. This treatment continued for 6 months with no beneficial outcome. The patient was still complaining of increased muscle weakness that extended to the proximal muscles of the legs, especially the gluteus and quadriceps muscles on both sides.
The clinical picture of the patient worsened progressively. He presented clinically apparent atrophy of the proximal muscles of the upper and lower limbs, with normal distal muscle strength. He was no longer able to climb stairs or to stand from a sitting position. Laboratory data were normal except for the CK, which was elevated at 302 U/l (normally <180 U/l). Cryoglobulins were not detectable. A new biopsy from the left quadriceps muscle disclosed a histological picture compatible with IBM.
Case 3.
A 55-yr-old woman presented with muscle weakness. She was suffering from Sjögren's syndrome that had been diagnosed 2 yr earlier. The diagnosis of pSS was based on subjective xerostomia and dry eyes, a positive Schirmer's test and Rose Bengal staining. She complained of arthralgia in her hands and knees and progressive muscle weakness, especially in the lower extremities, for approximately 8 yr. She was treated with hydroxychloroquine.
On clinical examination, she presented dry eyes and mouth. Muscle strength was 4/5 for the upper extremities, 23/5 for the upper segment of the lower extremities and 4/5 for the lower segment of the lower extremities.
Laboratory data revealed an increased erythrocyte sedimentation rate, while CK and aldolase levels were within normal ranges. She was positive for ANA, with a titre of 1:320 (speckled pattern), and for anti-Ro/SSA and anti-La/SSB antibodies, and negative for RF. Serum levels of thyroid hormones (triiodothyronine, thyroxine and thyroid-stimulating hormone) were within normal ranges.
A muscle needle biopsy showed an inflammatory response, several fibres containing red-rimmed vacuoles with two or three ragged red fibres in the cross-section; in addition, there were scattered necrotic fibres and atrophy of type II fibres were seen on staining for ATPase.
The patient was recommended a physiotherapy programme, and after 3 yr of follow-up her condition was stable.
Clinical and serological picture of patients with pSS and IBM (Table 1)
Five out of six patients with pSS and IBM were female. The mean age at the time of pSS diagnosis was 48.4 yr and at the time of IBM appearance 53.3 yr. In three out of five patients, pSS symptoms preceded IBM symptoms (by a mean of 1.8±7.7 yr); in one patient pSS and IBM symptoms appeared simultaneously, while in one patient IBM onset preceded pSS onset by 7 yr. The diagnosis of IBM was made 017 yr after the first symptom (mean 8.0±5.8 yr).
Four out of six patients had one or more extraglandular manifestations of pSS, including arthralgias/arthritis, peripheral neuropathy, interstitial kidney disease and primary biliary cirrhosis. Muscle involvement included the quadriceps in five out of six patients studied, proximal and distal limb muscles in four out of six patients, the brachial triceps in three out of six patients, and the brachial biceps and iliopsoas in two out of six patients. In all patients, muscle involvement appeared to be symmetrical.
All six patients had a high titre of ANA. Three out of six had RF. Four out of six patients had antibodies to Ro/SSA, while one of them also had antibodies to La/SSB. One patient had AMA.
CK was slightly elevated in two out of four patients studied (430 for patient 5 and 302 for patient 6; normally <180 IU/l).
The three patients diagnosed in our department were followed up for 2, 1 and 3 yr after the IBM diagnosis respectively. All three patients are in a stable clinical condition with respect to muscle involvement.
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Discussion |
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All forms of inflammatory myopathies are characterized by proximal and often symmetrical muscle weakness, which usually develops slowly. IBM, described first by Chou in 1967 [12], is characterized by the involvement of distal muscles, especially the foot extensors and finger flexors. The weakness and atrophy can be asymmetrical, with selective involvement of the quadriceps, iliopsoas, triceps and biceps. The clinical picture and outcome of muscle involvement in patients with pSS and IBM did not differ substantially from that in patients with IBM alone. The diagnosis of IBM in our cases was based on characteristic findings in muscle biopsies, which included endomysial inflammation, basophilic granular inclusions distributed around the edge of slit-like vacuoles (rimmed vacuoles), eosinophilic cytoplasmic inclusions and angulated fibres, often in small groups [4].
The cause of IBM is unclear but autoimmune mechanisms probably play a major role, for the following reasons. (i) The muscle fibres are invaded by CD8+ T cells and express MHC class I antigens, suggesting a T-cell-mediated cytotoxic process [13]. (ii) More than a third of patients have a variety of non-organ specific autoantibodies in their serum (including ANA, RF, anti-Ro/SSA and anti-cardiolipin) or present with an autoimmune disease [14]. (iii) IBM can be associated with primary immunodeficiency or infection with retroviruses [4].
In this paper, we describe three new cases and review all six patients with pSS and IBM who have been reported so far. In most cases, the onset of pSS preceded that of IBM, while the time elapsing between the appearance of muscle weakness and the confirmation of IBM diagnosis ranged from 4 months to 17 yr. One interesting finding of this study is that five out of six patients with pSS and IBM were female. pSS affects predominantly females (female/male ratio 9:1), while IBM has a male preponderance (male/female ratio 3:1). Therefore, IBM in pSS has the sex phenotype of pSS and it should be suspected in patients with pSS when they present with progressive muscle weakness.
In conclusion, IBM can be seen in patients with pSS and affects predominantly women. The clinical and pathological pictures do not differ from those observed in idiopathic IBM. A prospective study of muscle biopsy in patients with pSS presenting with progressive muscle weakness will address the question of whether IBM is another autoimmune disease associated with pSS.
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Acknowledgments |
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Notes |
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References |
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