XEROPHTHALMIA CONTROL

28

RICE BODIES IN RHEUMATOID JOINTS INVESTIGATION of rheumatoid arthritis is hampered by the absence of an animal model. That most frequently used, adjuvant arthritis in the rat, is closer to Reiter’s disease than to rheumatoid arthritis. The slow-acting drugs which may possibly modify the course of the disease are not active against such experimental disease. The chronicity of the human lesions is a puzzling feature, and one that is not readily reproduced in the laboratory. Some work by Popert and his colleagues2 throws light on the subject, and may have therapeutic implications. They found "rice bodies" in 72% of fifty rheumatoid joints aspirated before and after ’saline lavage with a wide-bore needle-14% on initial aspiration and the remainder after lavage. None were found in thirty-one similar aspirations from 12 patients with seronegative

synovitis. Although in

fragments of synovial villi. 5,11 The earliest rice bodies, however, are predominantly fibrinous in nature and seem to arise independently of synovial fragments.2Another curious aspect of the persistence of rice bodies in the joint is that enzymes present in the joint would dissolve the bodies in vitro, yet in rheumatoid joints most of them remain intact. There may be protective factors; or, alternatively, the balance between the rate of production and maturation of these structures and the rate of their disposal by phagocytosis and/or fibrinolysis favours their persistence. These results illustrate the important clues that may emerge from careful clinical observations linked with pathological investigation. In this instance the study procedures seem to have been good for the patients too.

, .

"

series- rice bodies

seemed specific for rheumatoid arthritis, such bodies were first reported in tuberculous arthritis.3 Most of the rice bodies consisted of coarsely reticular material, reacting immunologically with anti-fibrinogen and anti-fibronectin, and containing mononuclear cells. Some showed a vacuolation suggestive of fibrinolysis, but many displayed organisation akin to that seen in established connective tissues, with formation of mature collagen, reticulin, and elastin. When collagen was seen in the rice bodies, it was sharply demarcated from the other tissue. Other bodies consisted mainly of fibrin. Albrecht et al. earlier described the composition of rice bodies, in their two cases, as "fibrin-like", whereas Berg et al.5 were satisfied that the bulk of the material in their seven cases was truly fibrin. The importance of these observations is that fibrin may serve as an irritant and a potent stimulus to fibrogenesis when implanted in serous cavities.6 When instilled into joints even autologous fibrin can persist and evoke a persistent arthritis in a small proportion of animals.7 Persistent fibrin deposits may provide a continuous stimulus to antibody formation to other altered body constituents, possibly including products of inflammation in rheumatoid joints.8 In support of this suggestion is the reduction of synovitis and clinical improvement of those patients from whom rice bodies are removed. Arthroscopists have noted this after irrigation of the joint,9 although a controlled trial of joint lavage showed no significant improvement in rheumatoid patients." Some workers, having seen blood-vessels in occasional specimens, suggest that rice bodies originate from detached this

CM, Waksman BM, Sharp JT. Studies of arthritis and other lesions induced in by injection of mycobacterial adjuvant. J Exp Med 1961; 113: 485-509. 2. Popert HA, Scott DL, Wainwright AC, Walton KW, Williamson N, Chapman JH. Frequency of occurrence, mode of development, and significance of rice bodies in rheumatoid joints. Ann Rheum Dis 1982; 41: 109-17. 3. Reise H Die reiskorpchen in tuberculos erkranken Synovalsacken Dt Z cir 1895; 1. Pearson rats

42: 1-99. 4. Albrecht M, Marienetti GV, Jacox RF, Vaughan JH. A biochemical and electron microscopy study of rice bodies from rheumatoid patients. Arthr Rheum 1965; 8: 1053-63. 5. Berg E, Wamwright R, Barton B, Puchtler H, McDonald T. On the nature of rheumatoid rice bodies. An immunologic, histochemical and electron microscope study. Arthr Rheum 1977; 20: 1343-49. 6. Curran RC. Mucopolysaccharides and collagen formation in atherosclerosis. In: Chalmers DG, Gresham GA, eds. Biological aspects of occlusive vascular disease. Cambridge: Cambridge University Press, 1964: 76-83. 7. Dumonde DC, Glynne CE. The production of arthritis in rabbits by an immunological reaction to fibrin. Br J Exp Pathol 1962; 43: 373-83. 8. Glynn LE. The chronicity of inflammation and its significance in rheumatoid arthritis. Ann Rheum Dis 1968; 27: 105-21. 9. Bird HA, Ring EFJ. Therapeutic value of arthroscopy. Ann Rheum Dis 1978; 37: 78-79. 10. Lindsey DJ, Ring EFJ, Coorey PFJ, et al. Synovial irrigation in rheumatoid arthritis Acta Rheum Scand 1971; 17: 169-74.

XEROPHTHALMIA CONTROL XEROPHTHALMIA is the most widespread and serious nutritional disorder leading to blindness. It afflicts infants and young children, and yet the aim of the World Health Organisation to control blindness resulting from xerophthalmia is not unrealistic. A report of a meeting held in Jakarta in October, 1980, on the control of vitamin A deficiency and xerophthalmia has lately been published by the World Health Organisation.12 The report summarises existing knowledge of xerophthalmia and makes recommendations for future research and for control programmes. The term xerophthalmia is used to cover all the ocular manifestations of vitamin A deficiency from night blindness to corneal ulceration and scarring. A new classification of xerophthalmia, illustrated by colour photographs, is proposed with grades for night blindness, conjunctival xerosis, Bitot’s spots, corneal xerosis, corneal ulceration/ keratomalacia, corneal scars, and xerophthalmic fundus. Perhaps the most important change from the previous classification is that the division between primary and secondary signsl3 has been abolished so that night blindness becomes a valid sign of xerophthalmia. 12 Identification of night blindness has proved useful in screening surveys, especially where there is a local name for it. In those countries where xerophthalmia is frequent, most vitamin A comes from the provitamin A carotenoids of vegetables, especially dark green leafy ones, and from some fruit. (The introduction of reverse-phase high-pressure liquid chromatography for estimation of provitamin A has shown that previous methods were inaccurate, but this technique has yet to be applied to dark green leafy vegetables.) After absorption most vitamin A is taken up by the liver and stored as retinyl ester. The esters are hydrolysed to retinol which binds to a carrier, retinol binding protein (RBP), before release from the liver. In the blood the retinol-binding protein forms a complex with thyroxine-binding prealbumin. Protein deficiency hampers the release of RBP, which may partly explain why xerophthalmia is often associated with protein-energy malnutrition. It is important that affected children should receive both protein and vitamin A (or its precursors). Outside the target cell the retinol leaves plasma 11. Fassbender HG. Pathology of the rheumatoid diseases (translated byG.Loewi).Berlin: Springer Verlag, 1975: 114-15. 12. Control of vitamin A deficiency and xerophthalmia. WHO Tech Rep Ser No. 672, Geneva: W H.O., 1982 13. Vitamin A deficiency and xerophthalmia. WHO Tech Rep Ser No. 590, Geneva: W.H.O, 1976.

29

RBP, but once inside it is picked up by a cellular RBP which the site of action. Vitamin A has a role in and is necessary for the maintenance of glycosylation epithelial tissues. The recommended treatment schedule has changed since the previous report and now consists of oral administration of

transports it

to

retinyl palmitate (110 mg) or retinyl acetate (60 mg) on two successive days: A third dose is given before discharge, or 2-4 weeks after the first dose, or if there is clinical deterioration. Intra-muscular injection is preferred only when there is repeated vomiting or severe diarrhoea. Another change from the earlier recommendations is that the prevalence criteria for determining the public health significance of xerophthalmia and vitamin A deficiency have been lowered and that night blindness in more than 1% of the pre-school population has been added as a new criterion. Vitamin A deficiency is associated not only with proteinenergy malnutrition but also with infections-notably, diarrhoeal syndromes and measles. And because malnutrition, susceptibility to infection, and inadequate water and sanitation are all so closely interrelated there sometimes seems no hope for infants in the third world; yet the report, after a depressing section on the global occurrence of vitamin A deficiency and xerophthalmia, is optimistic about the control of these conditions. Strategies for control range from the short-term distribution of vitamin A capsules to populations with low vitamin A status, to education on local sources of vitamin A or carotenoids and fortification of staple foods. The basis of the periodic dosing of pre-school children with capsules is that, with reasonable absorption, enough vitamin A can be stored in the liver to protect a child for 180 days. This method has been applied in South-East Asia and in Central and South America. Evaluation of programmes in India showed a reduced prevalence of conjunctival signs of vitamin A deficiency. Education has to be an important part of any programme to control xerophthalmia and all possible agencies have been brought into the campaign. The ultimate answer to xerophthalmia will be the increased consumption of vitamin A from local sources, so educational programmes encourage breast-feeding and the consumption of dark green leafy vegetables. In Madurai, India, the child with its mother is passed from the ophthalmic outpatient department to a nutrition rehabilitation centre where the mother participates in the purchase and cooking of food, which is based on rice but includes carotene-rich vegetables. Fortification of staple foods with vitamin A should play a part in any strategy to control xerophthalmia. Dried skim milk sent for supplementary feeding projects is now fortified with vitamin A by the major source organisations. Several Central American countries have instituted sugar fortification, with improvements in

vitamin A status. The costs were originally met by the sugar manufacturers, but the programme is now being reduced on grounds of expense-only 7 cents per inhabitant in 1976. Fortification of wheat flour and monosodium glutamate is being considered in Indonesia. The studies of xerophthalmia in Indonesia have lately been summarised by Sommer.14 He estimates that the world incidence of active corneal xerophthalmia may approach one milion14 and these are essentially all children of pre-school age. An Indonesian investigation revealed that the major reason for low consumption of green leafy vegetables was that children dislike them. It seems that children everywhere need 14. Sommer A. Nutritional blindness,

University Press,

1982.

xerophthalmia and keratomalacia.

Oxford: Oxford

nutritional re-education until instant child appeal.

someone

develops greens with

GOODBYE NEUROSIS? A TASK force has been in action, under the command of Dr Robert Spitzer of the New York State Psychiatric Institute. Its terrain has been the murky caverns and treacherous quagmires of psychiatric diagnosis; its battles have been with the inconsistent and long-cherished diagnostic habits of American psychiatrists; and its most illustrious casualty has been the word "neurosis". Its Orders for the Day have been published in a large manual known as DSM-IlI, complete with an extensive glossary. By a stroke of the pen, neurosis, as a condition to be diagnosed, has ceased to exist. Henceforth, millions of American citizens will suffer instead from anxiety and other "disorders". The term neurosis, as signifying some sort of mental disturbance, was introduced by William Cullen at the end of the 18th century. During the next hundred years it was applied to a wide variety of conditions. Clouston, for instance, referred to what would now be called mental handicap as a form of developmental neurosis. In the development of psychoanalytic theory, neurosis underwent a process of reification-some would say deification. It became a collective noun not for a particular pattern of symptoms but for a particular process, involving unconscious mechanisms, which caused the symptoms. These could not be relieved until the neurosis had been treated by a process of metaphorical psychosurgery, with the neurosis laid out on the transference table for skilled dissection and treatment. It is scarcely surprising that in the U.S.A., where psychoanalytic theories have held sway for two generations, the disappearance of "neurosis" has caused not merely irritation but alarm. The obscure object of therapeutic desire and of professional remuneration has been removed. In Archives of General Psychiatry1 a correspondent cries, "Must we really part, dear word?", and goes on to point out that "the diagnosis of tuberculosis is not merely descriptive, it identifies the organism. We all still need you... to help us unite in a battle against our common foe: neurosis". What is the solution to this dilemma? Mass emigration from the U.S.A. might be an answer. The rest of the psychiatric world uses the International Classification of Diseases, published by the World Health Organisation. But even outside the U.S.A. things are changing. What were "neuroses" in ICD8 have become "neurotic disorders" in ICD9. No wonder then that General Spitzer, confident behind his well-fortified G.H.Q. and with sanctions operated by his allies in Geneva, can answer the correspondent’s plea with a piece of arrogant doggerel: Had your neurosis Bacillus been found In D.S.M. III the term would abound... Use D.S.M. III for a diagnostic description And neurosis to help you with your prescription.2

In other words, classify by DSM-III and treat by anyway you like. Neurosis is still assured a long life, since the term has become part of folklore. Long after the scientific captains and kings have departed, and when DSM gathers dust on the shelves, we shall still hear the words "I’m not mental. It’s my nerves". Neurosis is not dead. It has merely retreated in Disorder. 1. 2.

Janulis PT. Tribute to a word: neurosis. Arch Gen Psychlalry 1982; 39: 623. Spitzer RL, Skodol AE, Gibbon M. Reply. Arch Gen Psychiatry 1982; 39: 623-24.