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Pachydermoperiostosis

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Pachydermoperiostosis 416 Annals ofthe Rheumatic Diseases 1992; 51: 416-419 Bone abnormalities and severe arthritis in pachydermoperiostosis R G Cooper, A J Freemont, M Riley, P J L Holt, D C Anderson, M I V Jayson Abstract (normal value <10 MU/1) suppressing to 2 2 Two patients with pachydermoperiostosis MU/l during a standard glucose tolerance test; were studied in whom the predominant chest and skull radiographs were normal. In features at presentation were severe and view of the normal endocrine results, the disabling knee and ankle joint pain in asso- patient was referred to a rheumatologist. ciation with distal long bone pain. Analysis Subsequent investigations showed that IgM of synovial fluid from the knee joints showed rheumatoid factor, antinuclear factor, and lupus non-inflammatory changes. In one patient a erythematosus cells were negative and that bicortical iliac crest bone biopsy specimen, plasma calcium, inorganic phosphate and taken after labelling with demeclocycline, alkaline phosphatase, and serum iron, iron showed appositional rates which were in- binding capacity, immunoglobulin levels and creased in cortical bone but reduced in liver function tests (serum aspartate amino- trabecular bone. This mismatching resulted in transferase and serum alanine aminotransferase, trabecular osteoporosis, which occurred in and bilirubin) were normal. Twenty four hour association with increased numbers of osteo- urinary calcium excretion was also normal clasts, fidings which suggest differential (4- 1-5 2 mmol), but that of hydroxyproline was functional changes affecting the two bony increased to 35-45 mg/M2 (normal 20 mg/M2). University of envelopes. A radiological examination showed a periosteal Manchester, reaction along the distal ulnae, tibiae, and Rheumatic Diseases Centre, Hope Hospital, fibulae and a bone scan using labelling with Salford, United Kingdom Pachydermoperiostosis, or primaryhypertrophic strontium 87 confirmed increased isotope R G Cooper osteoarthropathy, was first described in 1935.' uptake at these sites. A synovial biopsy sample M I V Jayson It is an inherited disease which is autosomal from the right knee showed venous dilatation University of and it is without inflammation whereas a biopsy sample Manchester, dominant with variable penetration Department of phenotypically more severe in men. The disease of skin from the ankle showed gross dermal Medicine is characterised clinically by digital clubbing, thickening with hypertrophy of the sweat (Endocrinology), periostitis, and hypertrophic skin changes glands. A biopsy sample ofthe tibial metaphysis, Hope Hospital, Salford, United Kingdom (pachydermia), which may cause marked after labelling with demeclocycline, showed D C Anderson furrowing of the brow, seborrhoea with hyper- normal osteoid seams with minimal separation University of hidrosis, and arthralgia or arthritis.2A The of the labelled lines, indicating that the hyper- Manchester, onset of symptoms, which is often preceded by ostosis was relatively inactive. Department of the Pachydermoperiostosis was diagnosed, the Radiology, symptomless clubbing, is usually during Manchester Royal second decade of life.4 Although up to 40% of increased hydroxyproline excretion reflecting Infirmary, Oxford Road, patients may develop synovial effusions these the increased metabolic rates of collagen and Manchester, are if bone. In view of the severity of the patient's United Kingdom usually symptomless and, painful, usually M Riley respond to non-steroidal anti-inflammatory joint pain, which had responded poorly to University of drugs (NSAIDs).4 We report two patients with treatment with NSAIDs, a trial with high doses Manchester, primary hypertrophic osteoarthropathy in whom of corticosteroids was thought to be justified Department of bone changes were investigated histologically (enteric coated prednisolone, 50 mg/day) and Rheumatology, Manchester Royal and in whom severe joint pain was the initial the effects were monitored biochemically using Infirmary, Oxford Road, reason for presentation and which was refractory the excretion levels of urinary hydroxyproline. Manchester, to treatment. These decreased towards normal values rapidly United Kingdom but the symptoms continued intermittently and P J L Holt improved only gradually. By 1979 the patient University of Manchester, Case reports still had disabling joint pain and his 24 hour Bone Disease PATIENT 1 urinary hydroxyproline excretion was still Research Centre, In 1971 a healthy 16 year old white boy raised, at 32 mg/M2, but he was now working Manchester, United Kingdom presented to an endocrinologist with severe full time and the prednisolone, which had been A J Freemont joint pain in association with excessive growth. gradually reduced, was discontinued. The D C Anderson There was no relevant family history. Physical patient subsequently continued to have joint Correspondence to: examination showed a tall (196 cm) adolescent symptoms, which were not progressive, and he Dr R G Cooper, Rheumatic Diseases Centre, with marked digital clubbing, gross periarticular remains otherwise well. University of soft tissue hypertrophy around the wrists, Manchester, Hope Hospital, knees, and ankles, and bilateral knee joint Eccles Old Road, effusions. Acromegaly was suspected clinically. PATIENT 2 Salford M6 8HD, United Kingdom. Initial investigations showed: haemoglobin 126 In 1989 a 17 year old healthy white boy Accepted for publication g/l, erythrocyte sedimentation rate 26 mm/hour, developed severe pain and swelling of his knees 18 June 1991 baseline plasma growth hormone 2-6 MU/I and ankles after playing football. There was no Bone abnormalities and arthritis in pachydermoperiostosis 417 relevant family history. The joints did not withdrawn and treatment with sulphasalazine settle with rest. Rheumatological examination was begun, but without success. In view of the revealed a healthy patient with marked digital severity of his continued problems, which had clubbing and an inflammatory arthritis affecting precluded his finishing A level and business his knees and ankles with bilateral knee joint degree studies, a second rheumatological opinion effusions. As a testicular swelling was also was sought. found, a paramalignant syndrome was suspected The patient now also described hyperhidrosis and a testicular exploration was performed with 60 minutes of morning stiffness and pain and a biopsy sample taken; the histology was affecting the small joints of his fingers and toes. normal. Other investigations with normal His general health remained good, his weight results included haemoglobin, erythrocyte was steady, and his bowel action normal. sedimentation rate, IgM rheumatoid factor, Physical examination now showed synovitis of antinuclear factor, a chest radiograph, and com- the proximal and distal interphalangeal joints of puted tomography examination of the abdomen. his fingers and toes, and tender bony swellings Treatment with an NSAID was begun, but gave of the distal radius, ulna, tibia, and fibula little symptomatic relief, and two months later bilaterally. Further investigations showed a the patient developed severe upper abdominal baseline growth hormone level of 2-8 MU/1, pain. A perforated duodenal ulcer was confirmed decreasing to 0 5 MU/I (normal <10) during a on admission to hospital and vagotomy and glucose tolerance test. A chest radiograph was pyloroplasty were performed. The NSAID was normal. Examination of the synovial fluid showed a very low white cell count (100/mm3) which was within the normal range. Unusually, however, the predominant cell was densely stained with non-specific esterase-that is, the cells were macrophages. This contrasts with normal subjects in whom synoviocytes pre- dominate. In all other aspects the fluid resembled that of a non-inflammatory arthropathy. Radio- graphs of his hands, feet, femora, and pelvis showed exuberant periosteal deposition of new bone (fig 1) and a bone scan using labelling with technetium confirmed increased uptake in the distal ends of his limb long bones (fig 2). A small bowel enema and duodenal biopsy sample were normal. A full thickness iliac crest bone biopsy sample, following labelling with deme- clocycline, showed hyperactive cortical bone deposition, but with marked trabecular osteo- porosis in association with increased numbers of osteoclasts (fig 3, table). A diagnosis of pachy- dermoperiostosis was made. As the patient's joint symptoms were severe and persistent a trial of high dose prednisolone Figure I Plain radiograph ofthe wrist ofpatient 1. lPeriosteal reaction is seen along the distal radius and ulnar extending across the arrested growth plate and onto the epiphvsis, afeature thought to be specificforprimary hypertrophic osteoarthropathv only.' Figure 3 Reverse prints offull thickness, bicortical bone biopsy specimensfrom the posterior iliac crests of (A) a normal subject and (B)patient 2. The outer cortices lie at the bottom ofthe print in both instances. A comparison Figure 2 Bone scan ofpatient 2 using bisphosphonate labelled with technetium, showing ofthe biopsy specimens showed markedly thickened cortices, markedly increased uptake in the distal radius and ulnar. This was not due to the epiphysial especially the inner cortex, in patient 2, but with trabecular growth plate, which wasfused on plain radiographs. thinning as a result ofrelative osteoporosis. 418 Cooper, Freemont, Riley, et al Histomorphometric results for trabecular and cortical bone out inflammation."b Radiological studies have from
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