Letters to the Editor 9 Hemminki K, Fo¨rsti A, Lorenzo Bermejo J. Etiologic impact of known cancer susceptibility genes. Mut Res Rev 2008;658:42–54. 10 Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 2005;4:130–6. Rheumatology 2008;47:551–552 doi:10.1093/rheumatology/ken016 Advance Access publication 12 February 2008 Pseudoneuropathic CPPD arthropathy: magnesium matters A B clinic visit by the isolation of characteristic calcium pyrophosphate dihydrate crystals from left knee synovial fluid. His thiazide diuretic was stopped and he was reviewed by a nephrologist who prescribed magnesium replacement therapy. His serum magnesium level has remained between 0.63 and 0.68 g/l since. He has undergone a successful left ankle arthrodesis that has improved his pain and functional status with a plan for a rightsided arthrodesis in the future. There are few reports in the literature of pseudoneuropathic arthropathy caused by calcium pyrophosphate crystal deposition. It was first reported by McCarty and Haskin in 1963 [1]. There is no distinctive pattern of pseudoneuropathic arthropathy, but it does have a distribution that is atypical for OA. It affects both weight-bearing joints and non-weight-bearing joints as there have been a number of cases of destructive arthropathy of the temporomandibular joint reported [2, 3]. The natural history of this form of CPPD arthropathy has not been well documented; however, it does lead to pronounced joint destruction over a relatively short period of time. It is unclear whether pseudoneuropathic arthropathy has a distinct pathological process or whether it represents end-stage pseudogout-like CPPD. Hypomagnesaemia has been strongly associated with CPPD crystal deposition [4]. Low-serum magnesium can be due to a variety of disorders including Gitelman’s syndrome [5], short bowel syndrome [6] and familial forms of renal magnesium wasting [7] all of which have been reported as causes of chondrocalcinosis and CPPD arthropathy. The use of thiazide diuretics can also predispose to the development of chondrocalcinosis [4]. The impairment of the activity of pyrophosphatases that occurs in the relative absence of magnesium is the proposed pathological mechanism by which magnesium deficiency produces calcium pyrophosphate crystal production [8]. The clinical presentation of CPPD associated with hypomagnesaemia is generally severe and of early onset as was the case here [8]. There is an opinion that magnesium levels need not be checked in patients presenting after the age of 50 as any disorder of magnesium homeostasis is likely to have become clinically obvious before this [9]. This case illustrates the need to determine magnesium levels in patients with CPPD at all ages, particularly in the presence of thiazide diuretic use. The distinction between a true neuropathic joint and pseudoneuropathic joint is an important one. The presence of denervation obviously has a large bearing on the likelihood of successful surgery. Surgeons are naturally slow to operate on joints that have been denervated due to the risks of poor healing and infection [10] that exist in such cases. There is also evidence that the longterm outcome from arthrodesis procedures in patients with persistent neuropathy is poor. Those with even severe destructive arthropathy who have preserved neurological function do well post-operatively [10]. As this case illustrates, the absence of neuropathy should be established as it opens up the possibility of operative interventions in patients with severe destructive arthropathy. Rheumatology key message Hypomagnesaemia as a cause of CPPD should be considered in the context of thiazide diuretic use. Disclosure statement: The authors have declared no conflicts of interest. B. R. WHELAN, F. O’SHEA, G. MCCARTHY FIG. 1. (A) Posterior clinical image of the ankle joints (right ankle post-arthrodesis). Note the gross deformity of the left ankle. (B) The radiograph is an anteroposterior view of left ankle showing severe joint destruction and subluxation. Department of Rheumatology, Mater Hospital, Dublin, Ireland Accepted 8 January 2008 The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected] Downloaded from http://rheumatology.oxfordjournals.org/ by guest on September 9, 2014 SIR, Pseudoneuropathic calcium pyrophosphate deposition (CPPD) arthropathy is a rare form of arthropathy caused by deposition of calcium pyrophosphate crystals within the joint space. We wish to present a case of severe destructive pseudoneuropathic CPPD of the ankles due to hypomagnesaemia, treated successfully with ankle arthrodesis. A 56-yr-old man with a 2-yr history of bilateral ankle joint pain and swelling of sudden onset was referred to rheumatology services from orthopaedics because of the suspicion of an underlying inflammatory arthropathy. He had previously had a right total knee replacement aged 48 for what was diagnosed as early degenerative OA. His only other significant medical history was of hypertension for which he had received a thiazide diuretic (bendroflumethiazide 5 mg once daily) for the previous 4 yrs and quinapril 10 mg o.d. for the previous 2 yrs. He had no family history of early onset OA or other inflammatory arthropathy. Initial assessment by rheumatology revealed him to have a markedly antalgic gait. He had a 158 fixed flexion deformity of his left knee with a genu varus but with no clinically appreciable joint effusion. His right knee, which had previously been replaced, was of normal alignment and moved well. He had marked deformity of his ankles with his feet held in eversion and in prominence of his medial malleoli (Fig. 1A). Investigations revealed normal full blood count, renal profile, serum calcium, free T4 and TSH, fasting glucose and glycosylated haemoglobin. Alkaline phosphatase was normal at 101 mmol/l. A glucose tolerance test was also normal. Initial ESR was 4, ferritin was on the upper limit of normal at 336 g/l, but transferrin levels were normal. Genetic screening for haemochromatosis revealed no characteristic polymorphisms. He was found to be hypomagnesaemic at 0.48 g/l (normal range 0.64–0.87 g/l). Plain radiographs (Fig. 1B) showed a severe destructive arthropathy of both ankles. Radiographs of the left knee revealed evidence of articular chondrocalcinosis. Formal sensory nerve conduction studies and EMG of the lower limbs were within normal limits. He was diagnosed with pseudoneuropathic calcium pyrophosphate deposition arthropathy that was confirmed at a subsequent 551 552 Letters to the Editor Correspondence to: B. R. Whelan, Department of Rheumatology, Mater Hospital, Eccles St, Dublin 7, Ireland. E-mail: [email protected] Rheumatology 2008;47:552–553 doi:10.1093/rheumatology/kem357 Advance Access publication 15 February 2008 Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab SIR, We report the case of a 57-yr-old patient who presented with an 18-month history of scleroderma. This had been diagnosed previously in another institution where she was treated with i.v. infusion therapy of methylprednisolone at 10 mg/kg and cyclophosphamide 15 mg/kg. She failed to respond to the initial six courses of therapy, and had a further five infusions. Unrelated to her medical condition, she moved to our region where she presented to the respiratory service in February 2004 with worsening dyspnoea. She reported hand pain, stiffness and swelling and restriction of shoulder movements, with worsening Raynaud’s phenomenon, and was also referred to rheumatology. When she attended the rheumatology clinic in August 2004, she was wheelchair bound due to dyspnoea and had an intermittent cough, but not productive of sputum. There was no chest pain or haemoptysis. The patient was in respiratory distress and had difficulty talking, with a resting respiratory rate of 40/min and oxygen saturation of 92% on room air. She was not centrally cyanosed and had bibasal coarse crackles, but her jugular venous FIG. 1. HRCT showing (A) pre-retreatment with rituximab and (B) post-treatment with the second course of rituximab, demonstrating a reduction of the ground glass appearance and resolution of the air bronchograms in midzones (arrows). At this stage, the lung bases demonstrated irreversible fibrotic changes with honeycombing. The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected] Downloaded from http://rheumatology.oxfordjournals.org/ by guest on September 9, 2014 1 McCarty D, Haskin M. The roentgenologic aspects of pseudogout (articular chondrocalcinosis). An analysis of 20 cases. Am J Roentgenol 1963;90:1248–57. 2 Osano H, Matsumoto K, Kusama M. Calcium pyrophosphate dihydrate arthropathy with condylar destruction of the temporomandibular joint. J Oral Sci 2003;45:223–6. 3 Onodera K, Ichinohasama R, Saito M, Ooya K. A case of the calcium pyrophosphate dihydrate (CPPD) deposition disease without condylar destruction of the temporomandibular joint. Pathol Int 1997;47:622–6. 4 Jones AC, Chuck AJ, Arie EA, Green DJ, Dohrerty M. Diseases associated with calcium pyrophosphate deposition disease. Semin Arthritis Rheum 1992;22:188–202. 5 Punzi L, Calo L, Schiavon F, Pianon M, Rosada M, Todesco S. Chondrocalcinosis is a feature of Gitelman’s variant of Bartter’s syndrome. A new look at the hypomagnesemia associated with calcium pyrophosphate dihydrate crystal deposition disease. Rev Rhum Engl Ed 1998;65:571–4. 6 Richette P, Ayoub G, Bardin T, Bouvet S, Orcel P, Badran AM. Hypomagnesemia and chondrocalcinosis in short bowel syndrome. J Rheumatol 2005;32:2434–6. 7 Milazzo SC, Ahern MJ, Cleland LG, Henderson DR. Calcium pyrophosphate dihydrate deposition disease and familial hypomagnesemia. J Rheumatol 1981;8:767–71. 8 Rosenthal A. Crystal induced arthropathies. In: Wortmann RL, Schumacher HR, Becker MA, Ryan LM, eds. New York: Taylor and Francis, 2006; 104 (chapter 3). 9 Becker MA. Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition disease. UptoDate, v. 15.3, 2007. (http://patients.uptodate.com/topic. asp?file¼crystald/3066, date last accessed 15 February 2007). 10 Wetmore RS, Drennan JC. Long-term results of triple arthrodesis in CharcotMarie-Tooth disease. J Bone Joint Surg Am 1989;71:417–22. pulse was not elevated, heart sounds were normal, no murmurs were detectable and she had no dependent oedema. She had puffy scleroderma of the hands with marked synovitis and bilateral shoulder capsulitis. There was extensive telangiectasia on her hands and face, and facial skin tightening with beaking of the nose. She also had symptoms of heartburn and was taking omeprazole 20 mg daily. The chest X-ray demonstrated signs of pulmonary fibrosis at both bases. Her blood count was normal, ESR and CRP were 30 mm/h and 28 mg/l (normal <10 mg/l), respectively; rheumatoid factor was negative but ANA was strongly positive at a titre of 1 : 2560 with a homogeneous pattern; extractable nuclear antigens including Scl-70 were negative. High-resolution CT (HRCT) performed before her rheumatology review showed basal honeycombing and a ground glass appearance compatible with scleroderma-related interstitial lung disease (ILD). Her pulmonary function test showed a forced vital capacity (FVC) of 1.84 l (100% predicted), forced expiratory volume in 1 s (FEV1) to FVC ratio was 88.01, and the diffusing capacity of the lung for carbon monoxide (DLCO) was 1.1 mmol/min/kPa (62.7% predicted). In September 2004, she was treated with rituximab 1000 mg 2 weeks apart with 100 mg of methylprednisolone premedication prior to the infusions. She improved within 3 weeks and managed to walk up to 500 m. Her FVC improved to 2.01 l (109.5%). Her arthropathy resolved completely. She started prednisolone 5 mg daily and cyclosporin 50 mg twice daily. In late 2005, there was deterioration in her symptoms, and in February 2006 a repeat HRCT showed ground glass changes compatible with midzone pneumonitis (Fig. 1A). Her FVC had reduced to 1.69 l (93.5% predicted) and her DLCO was 0.62 mmol/min/kPa (34.3% predicted). She was developing cor pulmonale; an echocardiogram performed confirmed an enlarged right ventricle with impaired function with right ventricular systolic pressure of 132 mmHg and raised pulmonary artery pressures. In view of the success of the original infusion she was retreated with the same rituximab regimen. Following therapy she resumed her walking distance of 500 m. Her repeat FVC and DLCO improved to 2.02 l (113% predicted) and 0.84 mmol/min/kPa (48% predicted), respectively, and the repeat HRCT (Fig. 1B) showed an improvement. Air bronchograms evident on HRCT in the upper and mid-zones were less conspicuous following therapy. Peripheral blood cytometric evaluation using a sensitive assay after the second treatment was determined. Following therapy the B-cells were 0.0001 109/l (normal levels 0.060.66 109/l) and pre-plasma cells 0.0002 109/1. The good clinical response noted in the face of peripheral blood B-cell lymphopenia likely reflects the presence of pathogenic B cells in the lymphoid and possibly pulmonary tissues. The monoclonal antibody rituximab is directed against the CD20 antigen that is expressed on B lymphocytes. Rituximab has been used to treat non-Hodgkin’s lymphoma where it has good