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Knight and Symmons report a very interesting case of a man with Whipple’s disease and provide us with a timely update on this rare condition.1 They describe how six months after initial presentation the diagnosis of adult onset Still’s disease (AOSD) was made and despite regular review at several centres, this diagnosis was upheld for a further five years. Multiple investigations were performed adding little to the original diagnosis. It is not mentioned whether a serum ferritin was taken. This may have been useful given the initial diagnosis of AOSD as it might have resulted in questioning this diagnosis, permitting an earlier diagnosis of Whipple’s disease.
It is widely reported in the literature, as far back as 1975,2 that increased serum ferritin may be of use in both diagnosis3-5 and monitoring of AOSD.6 ,7Hyperferritinaemia is not however exclusive to AOSD, as various malignancies, hepatic necrosis and haemachromatosis can all cause it. However, values up to 25 000 μg/l have been recorded in AOSD and reportedly, values rarely exceed 3–5000 μg/l in the above conditions. The pathogenesis is not clearly understood, but it has been hypothesised that in AOSD, cytokine upregulation of ferritin mRNA translation may occur.8 This compares with the iron regulated pathway of ferritin synthesis in haemachromatosis and iron overload syndromes.
A comparative study of diagnostic criteria in AOSD by Masonet al 9 suggest the Yamaguchi criteria are superior to the others tested, including Cushet al quoted by Knight and Symmons. However, none of the criteria to aid diagnosis make use of serum ferritin measurement despite the claims for its use in the literature and acceptance in clinical practice. Although undoubtedly useful if very high, it is not clear what the relevance of a normal value in AOSD is, in a case satisfying clinical diagnostic criteria (although we have never seen such a case). In rare diseases such as AOSD, it is difficult to assess and evaluate diagnostic criteria and calculate sensitivity and specificity of possible disease markers. If serum were stored on this patient it would be interesting to know the serum ferritin measurement and how, if at all, it would have affected this patient’s management.
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Authors’ reply
We thank Drs Quinn and Gough for their interest in our paper. Our patient did have his serum ferritin measured in 1992. It was 197 μg/l (normal range 15–200). This was therefore a situation in which the patient satisfied clinical diagnostic criteria for adult onset Still’s disease (AOSD) but had a normal ferritin concentration. As the authors point out, had the ferritin concentration been high, this would have helped to confirm the diagnosis but given that it was in the normal range, it could not actually be used to refute the diagnosis. It was always felt that this patient’s disease was not typical of AOSD and the various physicians who looked after the patient were always willing to consider alternatives. However, it is difficult, even with the benefit of hindsight, to conclude that Whipple’s disease could have been diagnosed earlier. Although the normal serum ferritin was not in keeping with the diagnosis of AOSD it did not point towards any other diagnosis in particular.