University of the Witwatersrand Department of Paediatrics Division of Community Paediatrics Assignment A: Is Conjunctival Pallor Useful in Detecting Anaemia? Yahya Atiya Anaemia Title Is conjunctival pallor a reliable sign for the detection of anaemia? Scenario Olivia is an 11 year old African girl who presented to paediatric casualty in mid-January 2004 complaining of fever, lethargy and general weakness. A diagnosis of acute Plasmodium falciparum malaria was made on the basis of a positive travel history to Malawi and general examination which revealed palmar and mild conjunctival pallor. It was confirmed by urinalysis, which revealed frank haematuria, and a peripheral blood smear, which showed parasites in the erythrocytes. Her full blood count revealed a haemoglobin level of 7.8 g/dl, and a mean cell volume of 75fl. Clearly she is anaemic, but the question is how reliable is conjunctival pallor in detecting this? Clinical Question In children assessed as being anaemic, how reliable is conjunctival pallor in detecting the anaemia? Search Cochrane Database of Systematic Reviews and Pubmed: Search criteria: anaemia +pallor +conjunctiva Limits: All child 0-18yrs Search outcome: Cochrane – None relevant Pubmed – 14 hits 7 relevant 6 in English 1 in Portuguese translated to English. 7 irrelevant 4 related to adults 1 assessed usefulness of haemoglobin colour scales 1 assessed maternal anaemia in obstetrics patients 1 referred to ocular findings in G6PD deficiency Summary of Relevant Papers Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study weaknesses Thaver IH, Baig L 1994 951 children Aged 6-60mo Validation Conjunctival, palmar, nail bed & tongue pallor Combinations yielded better results than any one site alone Possible selection bias d/t rural setting resulting in more patients with anaemia Luby SP et al 1995 1104 children Aged <5yrs Validation Conjunctival, palmar, nail bed & tongue pallor Severe anaemia is easier to detect than moderate anaemia Clinical findings can be used to detect anaemia Possible selection bias d/t rural setting resulting in more patients with anaemia Validation Conjunctival, nail bed, palmar & tongue pallor Nail bed pallor was best for assessing severe anaemia No significant difference noted for mod anaemia Possible selection bias d/t hospital setting Was confirmation of anaemia done? Validation Std history & exam incl pallor Conjunctival pallor is more useful than palmar pallor Anaemia is easier to detect in children with malaria Possible selection bias d/t hospital setting 1048 inpatient children Zucker JR et 1666 outpatient al 1997 children Aged 2mo-5yrs 1226 children in Bangladesh Kalter HD 668 children in et al 1997 Uganda Aged 2mo-5yrs Weber MW 368 children et al 1997 Validation Getaneh T et al 2000 574 children Aged 2-60mo Validation Spinelli MG et al 2003 135 children Aged 3mo-6yrs Validation Conjunctiva, nail bed and palmar pallor Conjunctiva, tongue & buccal mucosa, nail bed and palm; Hb results Palmar and conjunctival appearance, Hb results Conjunctival pallor alone is useful Palmar pallor had highest sensitivity Low levels of agreement. Conjunctival pallor more sensitive than palmar. Ages not provided Exam not done by physician The cut-off for det. of anaemia is not given Exam done by nurses Comparatively few subjects. Actual figures are not given Commentary Most studies assessed conjunctival pallor in association with other sites of pallor i.e. palm, nail bed, tongue and buccal mucosa. While this is clinically useful, it does not answer the question of whether conjunctival pallor alone is sufficient to diagnose anaemia. This is important because most clinicians rely on it almost exclusively, ignoring the other sites. As medical students, we find ourselves in a similar situation; we are never faulted, even in exams, for not checking elsewhere. Weber et al addressed this situation, and found that conjunctival pallor alone was useful. The only problem is that the ages of the children are not provided. Hence, is conjunctival pallor useful in older, younger, or all children? On the other hand, Kalter et al did not even specify where they checked for pallor, merely stating that a “standard history & exam incl pallor” was conducted. This raises the question of how reliable their data really is. It was quite a large study by comparison, but this subtle mistake brings the validity (or rather reliability) of the validation study under scrutiny! Further, this and several other studies may have had a selection bias due to the fact that they were conducted in a hospital setting. This is more than a technical issue because staff at tertiary institutions tend to be better trained and more skilled than staff at lower-level institutions. Spinelli et al found that conjunctival pallor was more sensitive than palmar pallor. Getaneh et al dispute this, but has no support from any other studies. However, they, along with Spinelli and others, did assess the inter-observer variation in assessment of pallor, using kappa values. They found that agreement was best for conjunctival pallor and lowest for palmar pallor. This suggests, to me, that conjunctival pallor probably is a better indicator of anaemia. One thing that all the studies seem to agree upon is that assessment at several sites is definitely better than assessment at any single site. This again goes back to what was first stated at the beginning of this review. Another is that severe anaemia, as can be expected, was easier to detect than mild or moderate anaemia. Weber, Kalter and Zucker et al assessed pallor in a malaria setting. This is probably not as important for us as it is for those working in malaria endemic areas, but it is significant that they felt that in a malarial setting, conjunctival pallor alone is a useful estimate of anaemia. Zucker et al go so far as to recommend malaria treatment for any child less than 36 months presenting with pallor. As a practical issue, most studies, including Kalter, Weber, Zucker and Luby et al, found that clinical examination can be a useful indicator of the status of the child, especially in resource-poor settings such as much of the rural areas of Southern Africa. Clinical Bottom Line In children presenting with pallor, conjunctival pallor, alone or in combination with pallor at other sites, is a useful indicator of anaemia. References 1. Thaver IH, Baig L. Anaemia in children: Part I. Can simple observations by primary care provider help in diagnosis? J Pak Med Assoc. 1994;44:282-4. 2. Luby SP, Kazembe PN, Redd SC et al. Using clinical signs to diagnose anaemia in African children. Bull World Health Organ. 1995;73(4):477-82. 3. Zucker JR, Perkins BA, Jafari H et al. Clinical signs for the recognition of children with moderate or severe anaemia in western Kenya. Bull World Health Organ. 1997;75 Suppl 1:97-102. 4. Kalter HD, Burnham G, Kolstad PR et al. Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in areas with and without malaria. Bull World Health Organ. 1997;75 Suppl 1:103-11. 5. Weber MW, Kellingray SD, Palmer A et al. Pallor as a clinical sign of severe anaemia in children: an investigation in the Gambia. Bull World Health Organ. 1997;75 Suppl 1:113-8. 6. Getaneh T, Girma T, Belachew T et al. The utility of pallor detecting anemia in under five years old children. Ethiop Med J. 2000 Apr;38(2):77-84. 7. Spinelli MG, Souza JM, Souza SB et al. Reliability and validity of palmar and conjunctival pallor for anemia detection purposes. Rev Saude Publica. 2003;37:404-8.