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The Death Certificate in Rheumatoid Arthritis

Sir: In recent years more accurate informa-

tion has become available for an estimation of the prevalence and incidence of rheuma- toid arthritis. Developments in 2 areas have been mainly responsible for this more sophisticated evaluation: First, the estab- lishment of diagnostic criteria and the iden- tification of rheumatoid factor, and second, carefully designed and executed population studies, which have provided the best esti- mates available so far on the prevalence of rheumatoid arthritis.

This letter offers some objective evidence to confirm the suspected inadequacy of death certificates and autopsy protocols as sources of valid information regarding the incidence of RA.

The death certificates of 80 patients who were known to the Arthritis Unit at the University of Rochester Medical Center and who died in the city of Rochester were examined. These patients died in the 7-year period 1958-64. In each case the patients fulfilled at least 5 ARA criteria. In cases in which an autopsy was performed the re- port of it was also consulted.

Of these 80 patients with known definite rheumatoid arthritis 36 (45 per cent) had rheumatoid arthritis or some clue (for ex- ample “arthritis” or “probable periarteritis nodosa”) mentioned somewhere on the death certificate. In 55 per cent there was no clue to the presence of any rheuma- tological problem.

Among these 80 patients with known rheumatoid arthritis the diagnosis was more likely to be mentioned when the death cer-

tificate was signed by the patient’s personal physician (as it was in 5 of 7 such cases). Twenty-two of 48 (47 per cent) death cer- tificates signed by house officers, 8 of 16 (50 per cent) signed by medical officers of the County Hospital or tuberculosis Sanitarium, and 1 of 9 (11 per cent) signed by a coroner included the diagnosis of rheumatoid arthritis.

Of these 80 patients, 51 had autopsies ( 64 per cent). In 29 ( 57 per cent ) , rheuma- toid arthritis (or some clue such as “fusi- form swelling of proximal interphalangeal joints bilaterally” or “chronic synovitis” ) was mentioned in the final anatomical diag- nosis. In another 13 (26 per cent) rheu- matoid arthritis was mentioned only in the Clinical Summary accompanying the final anatomical diagnosis. In 9 instances (16 per cent) no mention was made of the rheu- matological problem. The fact that the criteria for the diagnosis of RA are largely clinical and that synovium and peripheral nodules are seldom examined postmortem in our institution may partially explain this discrepancy.

We support the widely held conclusion that both the death certificate and final anatomical diagnosis are inaccurate sources of information regarding the incidence of rheumatoid arthritis.

Edward C. Atwater, M.D. Ralph F. Jacox, M.D. Arthritis Unit, University of Rochester Medical Center Rochester, New York

Pernicious Anemia and Rheumatoid Arthritis

Sir: and/or serological manifestations of auto- The coexistence of differing clinical immunity in humans and their blood rela-

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Fig. 1.-A composite map showing Payne’s (Brit. Med. J., 1:1807, 1961) “comparative mortality figures (percent) for pernicious ane- mia in ten standard regions of England and Wales (both sexes)” and, in parentheses, Kell- gren’s (Arthritis Rheum. 9:658, 1966) “age- standardized inception rates of arthritis and rheumatism in men . . . by countries and re- gions, expressed as percentage of mean.” The regional figures appear similar with an incre- ment from Southeast to Northwest, represented by four zones. Kellgren’s “male” and “female” maps were comparable but the latter excluded married women. A separate study showed con- siderably more rheumatoid arthritis in Leigh (L) than in Watford (W).

tives can be used as a diagnostic marker (Mackay and Burnet: Autoimmune Dis- eases. Springfield, Thomas, 1963). Kunkel and Tan (Advances Immunol. 4:351, 1964) suggested that clinical and serological link- ages between human autoimmune diseases probably have a genetic basis. Hashimoto’s thyroiditis is cited to illustrate coexistences of human autoimmune diseases, and al- though Masi et al. (Lancet, 1:123, 1965) could not establish significant coexistences in a comparison of 74 cases with controls, Mulhern, Masi and Shulman (Lancet, 2: 508, 1966) subsequently found, in a com- parison of 170 cases with controls, a possi- bly significant coexistence with rheumatoid

arthritis. We are completing a family study on patients with pernicious anemia and simple atrophic gastritis as controls which shows more classical rheumatoid arthritis in the pernicious anemia sibs (4/67) than the atrophic gastritis sibs (OJ60); also there appears to be more thyroid disease, diabetes mellitus and vitiligo in the per- nicious anemia families. However, clearly significant data are not easy to obtain in studies such as ours, and that of Mulhern, Masi and Shulman (Lancet, 2:508, 1966), because of the relatively small number of cases and the infrequent occurrence of the relevant diseases: surveys of larger popula- tions are needed.

Kellgren (Arthritis Rheum. 9:658, 1966) presented a map of England and Wales showing age-standardized inception rates of “arthritis and rheumatism” by regions, expressed as a percentage of mean. “Ar- thritis and rheumatism” was more preva- lent in North England and Wales than Southeast England, with intermediate zones between. Kellgren discussed these differences in terms of environmental fac- tors-cold, wet weather and atmospheric pollution. The likelihood that the regional differences shown in Kellgren’s map were valid is strengthened by regional popula- tion surveys cited by Kellgren (Arthritis Rheum. 9:658, 1966) showing a greater prevalence of rheumatoid arthritis in Leigh and Wensleydale ( Northwest ) than in Watford ( Southeast ) , whether assessed by clinical criteria, radiological bony erosions in hands and feet, or rheumatoid factor in the serum. An alternative explanation (Am. J. Med. 38:793, 1965) might be differences in the proportion of a “subpopulation char- acterized by a specific genotype” suscepti- ble to rheumatoid arthritis.

It is of interest that Kellgren’s map com- pares with the map of Payne (Brit. Med. J., 1:1807, 1961) showing the comparative mortality for pernicious anemia (and can- cer of the stomach, which is a late com- plication of pernicious anemia) in the 10

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standard regions of England and Wales. This mortality was twice as great across North England and Wales as in Southeast England, with intermediate zones between. Pernicious anemia has a strong genetic component and is related to autoimmuniza- tion to gastric parietal cells (Quart. J. Exp. Physiol. 48:427, 1963), and environmental factors are probably irrelevant. A com- posite map (Fig. 1) combining KelIgren’s regions for “arthritis and rheumatism” with Payne’s regions for pernicious anemia shows four geographical areas in which there ap- pears to be a corresponding amount of “arthritis and rheumatism” and pernicious anemia; these are Southeast and South- central (low), Southwest (moderately low), Central (intermediate) and North and Wales (high).

Any genetic basis for the above associa-

tion would be complex, since our findings (in preparation) suggest that the 2 dis- eases may not necessarily coexist in the one individual but rather within families. Pre- sumed autoimmune diseases (which may include rheumatoid arthritis and pernicious anemia) may be initiated not by any spe- cific agent or process but by any one of many, possibly trivial, forms of injury, e.g. trauma or infection, and perpetuated by an autoimmune process which would thus represent a genetically determined anomaly in the response of the body to injury.

SENCA F. WHITTNGHAM, M.B. IAN R. MACKAY, MD.

Clinical Research Unit of The Walter and Eliza Hall Institute of Medical Research and The Royal Melbourne Hospital, Victoria, Australia.