Rheumatology Advance Access originally published online on February 12, 2008
Rheumatology 2008 47(4):551-552; doi:10.1093/rheumatology/ken016
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Pseudoneuropathic CPPD arthropathy: magnesium matters
Department of Rheumatology, Mater Hospital, Dublin, Ireland.
Correspondence to: B. Whelan, Department of Rheumatology, Mater Hospital, Eccles St, Dublin 7, Ireland. E-mail: bryanwhelan{at}ireland.com
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 15° 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).
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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 µg/l, but transferrin levels were normal. Genetic screening for haemochromatosis revealed no characteristic polymorphisms. He was found to be hypomagnesaemic at 0.48 µg/l (normal range 0.64–0.87 µg/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 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 µg/l since.
He has undergone a successful left ankle arthrodesis that has improved his pain and functional status with a plan for a right-sided 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 pseudo-neuropathic 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 long-term 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.
Disclosure statement: The authors have declared no conflicts of interest.
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[Abstract/Free Full Text]
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