Ann Rheum Dis 1998;57:331–338 331 MASTERCLASS Series editor: John Axford Ann Rheum Dis: first published as 10.1136/ard.57.6.331 on 1 June 1998. Downloaded from Postural changes, dysphagia, and systemic sclerosis Pilar Barrera, Alphons A den Broeder, FrankHJvandenHoogen, BazielGMvanEngelen, LeoBAvandePutte Case history Routine laboratory investigations showed an In 1993, a 61 year old, previously healthy man, increased erythrocyte sedimentation rate developed stiVness and skin thickening of the (ESR) (63 mm/1st h), creatinine (108 µM/l; hands and upper limbs, Raynaud’s phenom- normal 60–100 µM/l), aspartate aminotrans- enon, and exertional dyspnea. Examination ferase (ASAT 53 u/l; normal <25), and alanine showed a diVuse systemic sclerosis (SSc), aminotransferase (ALAT 38 u/l; normal <25) moderate hypertension (160/95 mm Hg), a and a slight proteinuria (0.44 g/day). reduced pulmonary diVusion capacity (TLC The diagnosis ankylosing spondylitis was 107% predicted, DLCO 68% predicted), and considered mainly because of his posture. HLA asymptomatic oesophageal dysmotility. Treat- B27 typing was positive, however radiological ment with D-penicillamine (D-Pen) 750 mg/ examination showed only cervical arthrosis and day and enalapril was started and, except for periarticular calcifications in hands and feet. extension of the skin involvement to the trunk Radiographs and computed tomography of the and lower limbs, the disease’s course was pelvic joints showed no evidence of sacroiliitis. uneventful for three years. The anteflexion of the head was considered to In August 1996 he was examined in another be the result of dermal sclerosis and the slightly centre because of complaints of progressive increased transaminases and proteinuria were fatigue, cervical anteflexion, proximal dys- attributed to D-Pen treatment and considered phagia, and weight loss. The patient denied acceptable. Treatment with omeprazole was having low back pain, and there were no symp- started and the dose of D-Pen increased to toms suggesting arthritis, psoriasis, Reiter’s 1000 mg/day. http://ard.bmj.com/ syndrome or inflammatory bowel diseases. In November 1996 he was referred to our centre for further investigation. He complained of a progressive “dropped head”, which prevented him from being able to look straight ahead (fig 1). He had myalgias at the neck and shoulders, proximal dysphagia for solids and fluids, and choked regularly. He had noticed fatigue, a change in his voice to an open nasal on September 24, 2021 by guest. Protected copyright. speech and had lost 15 kg in eight months. At admission the dermal sclerosis aVected his hands, forearms, feet, lower legs, face, neck, and trunk and there were no skin changes sug- gestive for dermatomyositis. The anteflexion of Departments of the cervical spine (70 degrees) could be Rheumatology P Barrera corrected passively but not actively and resulted A A den Broeder FHJvandenHoogen LBAvandePutte and Neurology BGMvanEngelen University Hospital, Nijmegen, the Netherlands Correspondence to: Dr P Barrera, Department of Rheumatology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, Figure 2 Histological section. Note the variation in fibre the Netherlands. size, an atrophic fibre with pyknotic nuclei (upper left arrow), an atrophic fibre containing some myophages Accepted for publication Figure 1 Posture of the patient at referral. Note the (bottom right arrow). (Haematoxylin and eosin; black bar: 2 April 1998 weakness of neck extensor muscles causing head drop. 50 µm) 332 Barrera, den Broeder, van den Hoogen, et al normal <330) and a mild proteinuria (0.45 g/day). There was no evidence of cholestasis, Ann Rheum Dis: first published as 10.1136/ard.57.6.331 on 1 June 1998. Downloaded from serum electrolytes disturbances or monoclonal gammopathy. Antinuclear antibodies were posi- tive (homogeneous and nucleolar pattern), and a non-specific band was observed on counterim- munoelectrophoresis but not on immunoblot- ting. No disease specific antibodies, including anti-dsDNA, anti-histone, anti-mitochondrial, anti-skeletal muscle, anti-acetyl choline recep- tor, and other myositis (anti-Jo1) or scleroderma specific (anti-topoisomerase I, anticentromere) antibodies, were observed. HLA typing showed A 30,31; B 13,27; Bw4; DR 3,7; DR52; DR53. Electromyography (EMG) showed evidence of severe proximal myopathy with polyphasic potentials, small units, fibrillations, and dener- vation. A percutaneous biopsy specimen was obtained from the left quadriceps, which was clinically aVected and showed contralateral myopathic changes on EMG. Myopathic changes consisting of fibre size variation, inter- nalisation of nuclei, atrophic fibres with pyknotic nuclei, focal necrosis, and necrotic fibres filled with myophages were seen (fig 2). Inflammatory infiltrates were scarce and local- ised to the fascicles and neither trichinella or toxoplasma cysts nor basophilic vacuoles (characteristic for inclusion body myositis) or Figure 3 Posture of the patient after some weeks of treatment with corticosteroids and methotrexate. amyloid deposits were observed. Electrocardiography and echocardiography in an occiput wall distance of 32 cm. The respi- disclosed no abnormality. Chest radiography ratory excursion of the chest was limited by the showed no signs of basilar fibrosis and pulmo- sclerotic skin but the lumbar flexion index was nary function tests revealed no abnormality normal and there was no pain on pressure on the with exception of the pre-existing reduced dif- sacroiliac joints. The “dropped head” and nasal fusion capacity. Besides a moderate distal speech were caused by a profound weakness of oesophageal hypomotility on recumbence, gas- neck extensor (Medical Research Council trointestinal series showed cricopharyngeus (MRC) scale 2/5) and palatum muscles and muscle spasm and contrast aspiration. http://ard.bmj.com/ there was also a symmetric weakness of proximal D-Pen was discontinued and treatment with limb muscles (MRC scale 3–4/5). Myasthenic oral prednisone (initial dose 60 mg/day) and symptoms, such as involvement of ocular or methotrexate im (15 mg/week) was started. facial muscles or worsening fatigue on repetitive Clinical improvement was rapid: the strength of contraction, were absent. Laboratory data neck extensors and proximal muscles recovered showed a raised ESR (63 mm/1st h), increased within 2–4 weeks (fig 3). The fatigue, myalgias, serum enzymes (creatine kinase (CK) 1600 u/l; and proximal dysphagia gradually subsided on September 24, 2021 by guest. Protected copyright. normal <90), ASAT (74 u/l; normal <25), while prednisone was tapered oV. Proteinuria ALAT (43 u/l; normal <25), and LDH (899 u/l; ceased and serum muscle enzymes returned to normal values within five months (fig 4). Proteinuria 120 Muscular symptoms 1800 Discussion ESR mm/1st h 1600 We present a patient with SSc developing new 100 constitutional, muscular, and gastrointestinal ASAT u/l 1400 ALAT u/l symptoms three years after initial diagnosis. 80 CK u/l 1200 The slow onset of complaints and the fact that 1000 60 they could be partially attributed to the 800 pre-existent connective tissue disease were 40 600 misleading. Nevertheless, correct interpreta- 400 tion of the clinical history and the abnormali- 20 200 ties on physical and laboratory examination 00could have lead to an earlier diagnosis. Some Sept 95 Dec 95 Mar 96 Jun 96 Sep 96 Dec 96 Mar 97 Jun 97 diagnostic problems arising from this case will be further discussed here. D-Pen 0–1 g/day PRD 0–60 mg/day Before referral, ankylosing spondylitis MTX 0–15 mg/week was considered. Was this likely to be present and which investigations should Figure 4 Clinical course, treatment, and enzyme abnormalities. On the left y axis have been performed to find this out? erythrocyte sedimentation rate (ESR), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT). On the right y axis creatine kinase (CK), D-penicillamine Though both entities are not mutually exclu- (D-Pen), prednisone (PRD), methotrexate (MTX). sive, there is no known association between SSc Postural changes, dysphagia, and systemic sclerosis 333 Table 1 Toxicity of D-Penicillamine treatment Ann Rheum Dis: first published as 10.1136/ard.57.6.331 on 1 June 1998. Downloaded from Relatively frequent Rare Very rare General Fever Dizziness Mucocutaneous Pruritus Pemphigus Elastosis perforans serpiginosa Rash/dermatitis Alopecia Increased risk penicillin allergy? Oral ulcers and stomatitis Gastrointestinal Altered taste Anorexia, diarrhoea Hepatotoxicity Nausea/vomiting Renal Proteinuria Haematuria Nephrotic syndrome Rapidly progressive glomerulonephritis Membranous or proliferative glomerulonephritis Haematological Thrombocytopenia Haemolytic anaemia Neutropenia Aplastic anaemia Lung Bronchiolitis obliterans, alveolitis Muscular See autoimmune phenomena Autoimmune Circulating Myasthenia gravis Drug induced SLE phenomena autoantibodies Pemphigus Goodpasture’s syndrome Polymyositis/dermatomyositis Hypoglycaemia related to anti-insulin antibodies Sjögren’s syndrome Forty to sixty per cent of the patients treated with D-Penicillamine develop adverse events, in 20–30% this results in treatment discontinuation.8–13 D-Pen toxicity pattern in patients with SSc is similar to that observed in RA.910 and ankylosing spondylitis (AS). In our case, (AMAs in more than 90% of the cases) and the a priori chance for the presence of AS was increased serum IgM concentrations.2–4 The very low. Despite the patient’s posture, his age, presence of AMAs is however not diagnostic