1967, the 31-paged August issue of Indian Pediatrics had four
original articles besides case reports and the editorial. Amongst these,
we decided to review the original article on "Kwashiorkor in Kabul and
Hyderabad – A comparison on certain salient features." Nearly seventy
years post-independence, malnutrition still continues to be a major
scourge responsible for mortality and morbidity in Indian children.
Through this communication, we present the changes in understanding of
the etiopatho-genesis and the management of children with edematous
malnutrition over last 50 years.
The study published by Samadi  in August 1967
issue of Indian Pediatrics was a cross-sectional study on 45
cases of Kwashiorkor <6 years of age admitted in the Department of
Paediatrics at Mirmano Rooghtoon, Kabul (Afghanistan). The objective of
the study was to evaluate the role of diet, environment and
socioeconomic factors on the phenotypic features of kwashiorkor, and to
compare the clinical profile of their cases with that reported from
Hyderabad (India) . After a comprehensive history with special
attention to nutrition and examination of the children, serum protein,
albumin and globulin were determined. The peak incidence of kwashiorkor
in the Kabul series was reported in 1-3 years (42.3%) compared to 2-4
years (55.1%) in the Hyderabad series. Nearly all cases belong to low
socioeconomic strata; nutritional inadequacy and chronic diarrhea was
associated in 60% of the enrolled children. The higher proportion of
infants (4.4%) with kwashiorkor reported in the index study than in
Hyderabad series (2.8%) were attributed to probable maternal
malnutrition with suboptimal breast milk output.
The author reported behavioral (irritability, apathy
and peevishness), skin and hair changes in 89%, 6.7% and 80% of the
children, respectively. The frequency of vitamin A deficiency in the
Kabul series (11.2%) was much lower than in the Hyderabad series
(32.6%). The authors attributed this to prolonged breastfeeding, which
would have helped meet the children’s vitamin A requirements. Prevalence
of vitamin B complex deficiency was also lower in the Kabul series
(22.2%) as compared to the Hyderabad series (32%); a likely explanation
for the higher incidence of skin lesions (55%) in the latter. In
concordance with the Hyderabad series, the Kabul series found low mean
serum protein (4.54 g/dL) and albumin (1.86 g/dL) levels while serum
globulin (2.68 g/dL) levels were relatively high. Thus, the study
highlighted the spectrum of clinical and biochemical profile in
kwashiorkor and the associated regional variations, though the precise
etiopathogenesis remained to be unravelled.
Historical background and past knowledge: The
term kwashiorkor, introduced by Cicely D Williams in 1935, was taken
from the Ga language of Ghana to indicate ‘disease of the deposed baby
when the second one is born’ . She described this clinical syndrome
amongst children living on the Western coast of Africa, who were weaned
onto low-protein and starchy diet (cooked plantain, sweet potato and
cassava), after being displaced from the breast by a younger sibling.
The phenotype comprised of edema in the hands and feet, darkening and
thickening of the skin followed by peeling, and a reddish tinge to the
hair in the worst affected cases. The disease was largely confined to
the tropical and subtropical parts of Africa, Asia and America, and the
poor townships of the southern European countries. Post Second World
War, it was widely accepted that kwashiorkor was due to primary protein
deficiency (Classical theory) , while marasmus was considered an
outcome of combined energy and protein deficit. Infections (particularly
measles and gastroenteritis) were observed to complicate and precipitate
this clinical syndrome.
The latest WHO classification of children (under 5
years of age) with severe malnutrition divides them into edematous and
non-edematous category based on the presence of bilateral pitting edema
(of nutritional origin) regardless of other features of kwashiorkor .
The presence of edema is used as an independent tool to screen cases of
malnutrition as it has a strong association with mortality .
Kwashiorkor represents the most severe phenotype of edematous
malnutrition, when other striking clinical features such as the skin
(flaky paint dermatosis/crazy pavement sign) and hair changes are
Since the publication of the reported article, there
has been a lot of research on the etiology and pathogenesis of
kwashiorkor. The mechanism of edema still remains elusive and several
hypothesis have been put forth to explain it. The classical theory was
refuted by Golden, et al.  as he failed to establish the
causal relationship of serum albumin with edema. In 1968, Gopalan
proposed the theory of dysadaptation to elucidate the clinical phenotype
in kwashiorkor . He explained the genesis of edema to be due to the
impaired hormonal response to stress; mediated via insulin, cortisol and
growth hormone. Srikantia  postulated that malnutrition results in
structural and functional changes in liver, which leads to defective
inactivation of ADH. Golden, et al.  proposed the landmark
hypothesis of oxidative stress to account for the pathological changes
in kwashiorkor. This was later supported by other researchers who
observed high blood concentration of biomarkers of inflammation while
the antioxidants levels were low in children with kwashiorkor .
However, the free radical/anti-oxidant theory was challenged by
Ciliberto, et al. , who failed to establish protective effect
of antioxidant cocktail in such children. A recent research has put
forth the association of the Gut Microbiota (GM) dysbiosis with
edematous malnutrition. This study reported a greater diversity in the
gut microbiota in children with edematous malnutrition than in cases
without edema .
Children with edematous malnutrition are recommended
to be managed in a health facility as inpatients with therapeutic diets
. These children are in a state of reductive adaptation and hence
overzealous introduction of a diet rich in calories and proteins can
precipitate refeeding syndrome .
To conclude, kwashiorkor represents the worst form of
edematous malnutrition and its genesis is multifactorial. There is a
need to strengthen the reporting of cases with edematous malnutrition,
and to determine the factors that complicate its clinical course and
outcome. Genome wide linkage studies can go a long way to explore the
host factors that can explain the variability in clinical phenotype.
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