Are You Confident of the Diagnosis?
What you should be alert for in the history
Kwashiorkor and marasmus are two separate diseases, but the former is so often superimposed on the latter that most clinical cases of kwashiorkor are better characterized as “marasmic kwashiorkor.”
Kwashiorkor is a disease syndrome resulting from a severe deficiency of dietary protein relative to caloric intake. It is characterized typically by retardation of growth and development, edema, fatty enlarged liver, anorexia, and alterations in the color and texture of the hair and the skin. The child is severely apathetic, and at the same time, irritable. Pneumonia and diarrhea are almost always present.
Kwashiorkor occurs in young children because at this period of life, protein requirements per kilo of body weight are relatively high, diets are more likely to be deficient in protein, and complicating infections that increase the need for protein are most common.
The name kwashiorkor comes from the Ga language of Ghana and means literally “first-second,” i.e. the disease of the first child when it is displaced at the mother’s breast. It has had many other names in different parts of the world, but the name kwashiorkor, given in its original description, is now universally accepted.
In the early 20th century, a form of kwashiorkor given the name mehlnahrschaden (starch dystrophy) was described in Europe in infants fed excessive starch and little else. Cases have been reported in Jamaica in children with a history of excessive calories from cassava starch and very little dietary protein. Kwashiorkor has been observed in older children and adults, but only rarely.
Inadequate dietary intake of protein is always part of the history. A deficient intake of some micronutrients is common, and this contributes to clinical variations among individuals and geographic regions.
Caloric intake is also usually low, and accounts for the marasmus, on which kwashiorkor is commonly superimposed, as a result of the adverse metabolic effects of infection on protein nutrition. These effects include anorexia (which causes a further decrease in protein intake) and an increase in the catabolic loss of nitrogen in the urine. In addition, diarrhea may reduce nitrogen adsorption from the gastrointestinal tract.
Characteristic findings on physical examination
The skin lesions and edema are diagnostic. These symptoms may be limited to the extremities, or extended over the entire body. Characteristically, the skin becomes hyperkeratotic, hyperpigmented, dry, cracked, scaly and peels. In Africa, it is sometimes referred to as “crocodile skin,” “flaky paint,” or “crazy pavement dermatosis.”
Changes in the color and texture of hair are a constant finding, but differ with racial origin. In black Africans, the hair takes on a reddish color, but in Latinos and Asians, it becomes almost white. In both cases it is fine, and easily and painlessly pluckable.
On admission, lifting the hair will usually reveal darker roots and a lighter band corresponding to the development of the acute episode of kwashiorkor. This has been referred to as the “flag sign.” Upon discharge, the roots are seen to be again growing out darker.
Marasmus is the name applied to wasting in infants and young children as a result of severe food deprivation. It is a chronic disease that develops over many months or even years.
Marasmic children are usually stunted. Atrophy of cutaneous and subcutaneous tissue occurs, but this is true of any wasting disease and is not specific to marasmus. In the final stages when all adipose tissue as a source of energy has been exhausted, death is near.
In most developing countries in the past century and in some today, it was kwashiorkor superimposed on marasmus that was the problem. Unlike kwashiorkor, marasmus does not show the pathological changes characteristic of protein deficiency . A cytokine-mediated response mobilizes amino acids from muscle and other tissues for gluconeogenesis and essential new protein synthesis.
Under conditions of extreme poverty or disaster, during which food is not available, marasmus is still seen and is a common cause of death in young children in refugee populations, usually because of dehydration and complicating diarrhea or respiratory infections.
In the early and mid-20th century, marasmus coexisted with kwashiorkor in most developing countries and was the prevailing form of severe protein calorie deprivation in some of them. It can also occur in adults under conditions of extreme poverty or disaster, when sufficient food is not available.
The etiology of marasmus is a prolonged lack of adequate food, i.e. slow starvation. As a result, such individuals must draw on their own tissues for as long as possible. At first, this provides sufficient nutrients to meet internal metabolic needs, but once body fat as a major internal source of energy is exhausted, death soon follows. At any time before this point is reached, it is possible to reverse the process by appropriate feeding, unless the child becomes severely dehydrated or is overwhelmed by a superimposed infection.
Marasmus will not be discussed further because it is not a dermatological problem except in combination with kwashiorkor.
Expected results of diagnostic studies
The medical history and physical examination must be sufficiently thorough to determine the type and severity of the case and the degree of hydration, as well as the presence of any infection. The determination of urine volume, density, chloride, and pH is essential to evaluate the dehydration and electrolyte imbalance, and to guide clinical decisions. Microscopic examination of the urine sediment may reveal a urinary infection, which requires prompt treatment. The severity and type of anemia should be determined as a guide to prompt therapy.
As a result of the protein deficiency, many serum enzymes will be lowered. Examples are: serum amylase, esterase, choline esterase, lipase, and alkaline phosphatase. If convenient, one or two of these are worth obtaining for further confirmation, although serum albumin is sufficient for this purpose. Serum choline esterase or amylase can be profitably followed as further measure of recovery. The blood examination must include basic hematological data. A stool examination should be done to check for amoeba and other intestinal parasites.
While kwashiorkor can usually be easily diagnosed by physical appearance and history, it should not be forgotten that a wide variety of pathological and biochemical changes are occurring. These include an enlarged fatty liver, atrophied pancreas, and serum biochemistry changes characteristic of protein deficiency. Episodes of diarrhea, as well as respiratory and other infections precipitate kwashiorkor, but both diarrhea and pneumonia are almost always present in patients with kwashiorkor, although sometimes pneumonia may be identified only by x-ray.
The signs and symptoms of kwashiorkor are so consistent and characteristic that the diagnosis is an obvious one to anyone familiar with them. Nevertheless, kwashiorkor has been misdiagnosed as pellagra in some countries because it also sometimes causes darkly pigmented scaly skin. However, the distribution of the skin lesions is quite different in the two conditions, and edema is not present in pellagra.
The first manifestation of pellagra may look very much like a sunburn and then become more like a severe burn. This can become secondarily infected. The appearance soon changes as the skin turns a somewhat dirty brown and frequently acquires a parchment appearance. It then quickly becomes more pigmented, scaling or cracking wherever exposure to the sun occurs (i.e. on the backs of the hands and forearms, elbows, knees, and around the neck as “Casal’s necklace”).
With pellagra, there may be intriginous maceration of the sensitive skin induced by poor personal hygiene, heat, and chaffing, not characteristic of kwashiorkor. The skin lesions stop itching and respond quickly to niacin or tryptophan therapy.
Who is at Risk for Developing this Disease?
These conditions are characteristically found in impoverished areas, where there is not adequate nutrition. Other circumstances include fad dieting (by choice or by psychiatric illness) and extreme conditions such as massive weight loss following bariatric surgery.
This is rarely seen in the United States or Europe. It can still be seen in parts of South and Central America, Africa, and Asia.
What is the Cause of the Disease?
A history of an inadequate diet, low in both protein and energy, is common to marasmus and kwashiorkor, but the appearance of the signs and symptoms of kwashiorkor described above are usually precipitated by one or more recent episodes of infection, most commonly diarrhea, a lower respiratory infection, or one of the common communicable diseases of childhood. Measles, whooping cough, or repeated episodes of diarrhea are particularly likely to be followed by kwashiorkor in a child with marasmus.
Systemic Implications and Complications
The pathology of kwashiorkor is diverse because most body functions depend on a steady supply of essential amino acids in appropriate proportions, as found in protein from animals, legumes, and oil seeds, plus additional available nitrogen for the essential amino acids that the body can synthesize from any biologically available source of nitrogen.
In both human subjects and experimental animals, a diet that is deficient in either total nitrogen or one or more essential amino acids will lead to physiological and pathological changes in most body systems characteristic of kwashiorkor. These changes include:
Cardiovascular: The heart is relatively small, but its size increases rapidly with treatment. Electrocardiographic findings include low voltage and alterations in the T wave and rhythm.
Exocrine glands: The liver is consistently enlarged due to a diffuse fatty change, which starts at the center of the lobule and eventually affects nearly all of the parenchymal cells. As a result, the sinusoids are generally collapsed. Acute inflammatory foci, but not cirrhosis, may also be found at autopsy. Changes in the exocrine pancreas include shrinkage in the size and number of the acinar cells with no evidence of a central lumen. Their enzyme granules are decreased. Salivary and intestinal glands are similarly affected, and the intestinal wall is sometimes so atrophic as to be nearly transparent.
Endocrine: The urinary excretion of 17-ketosteroids and 17- hydroxysteroids is decreased. The thyroid gland contains follicles that are smaller than normal and have cuboidal epithelium. The testes show only minimal signs of maturation as compared to those of normal children of the same age. The adrenals tend to be small in size and weight. Histopathological changes in the adrenal cortex indicate hypofunction.
Renal: A reduction in the glomerular filtration rate is reduced, initially in proportion to the degree of dehydration. The glomerular filtration rate and inulin and endogenous creatinine clearances are also reduced.
Neurological: Electroencephalographic studies have shown diminished voltage and excessively slow rhythmic activity. Some authors have reported abnormal focal activity and other alterations. These abnormalities disappear as recovery progresses.
THE THERAPEUTIC LADDER
(for children 1-5 years old* with kwashiorkor)
• Correct dehydration and electrolyte imbalance
• Start penicillin
• Keep patient warm
• Introduce gastric feeding tube and begin feeding formula of acidified half-skim milk, half strength (protein 1-2 g/kg/day, calories 30-60g/kg/day)
Second to Fourth Day:
• Continue electrolyte solution
• Continue penicillin
• Diet: half-strength acidified skim milk (protein 2-5g/kg/day, calories 60-100/day) 5% sugar may be added.
As soon as appetite returns, withdraw tube and begin oral feeding.
First to Second Week:
• Add electrolytes or potassium to the formula
• Continue penicillin
• Diet: whole milk (protein 5-7g/kg/day, calories 100-130/kg/day) plus banana, orange juice, vegetables
Second to Fourth Week:
• Diet: Same (protein 5-7g/kg/day, calories 130-150/kg/day) plus meat, eggs, cereals, and vegetables
• Diet: balanced high-protein high-calorie diet (protein 5-6g/kg, calories 140-150/kg/day)
• Physical and mental stimulation
*This age range will cover the great majority of all cases of kwashiorkor. Obvious modifications will have to be made for infants and the very rare older child or adult with kwashiorkor .
MANAGEMENT OF ELECTROLYTE IMBALANCES
Mild (kwashiorkor with no clinical signs of dehydration)
In very mild cases, adding sufficient potassium chloride to provide a total of 4 to 6mEq of potassium per kg of body weight daily is sufficient. One gram of potassium chloride provides 13mEq, and whole milk contains about 40mEq per liter. In mild cases, treatment for the first 2-3 days is sufficient.
Moderate and Severe (kwashiorkor with marked clinical signs of dehydration)
The basic problems in these cases are severe dehydration, hyperosmolarity, metabolic acidosis, and multiple anion and cation loss, especially of potassium. As soon as possible after admission, the child should be given a buffered hypotonic solution intravenously to counteract the acidosis and hyperosmolarity, and should begin the correction of the dehydration and oliguria. If laboratory facilities for determining CO2 combining power and serum electrolytes are not available, this therapy must depend on clinical observation.
A so-called 1-2-3 solution of one part 1/6 molar sodium lactate, two parts Ringer’s solution, and three parts 5% glucose is recommended. The lactate in this solution combats the acidosis, the glucose diminishes the ketosis, and the Ringer’s solution, which contains 6mEq of calcium and 4mEq of potassium per liter helps to correct the hyperkalemia and potassium depletion. The dosage varies from 40ml per kg to 50ml per kg, administered intravenously at a rate of 40-50 drops per minute.
If facilities are not available for preparing this solution, the Ringer-lactate solution of Hartman can be used, which, however, contains less lactate. Ringer’s Solution contains per 1,000ml: NaCl 8.5g, KCl 0.3g, CaCl2 0.2g, and Na lactate 3.1g.
In most cases, diuresis begins after the preceding treatment has been administered. If not, the solution can be continued some hours longer at a slower rate. It is advisable to continue with Darrow’s solution more slowly, approximately 20-25 drops per minute at a dosage of 90-110ml per kg per day, and to give an additional 5% glucose, in either normal saline or Ringer’s solution, to help replace the total water loss. It is usually necessary to give between 160ml and 200ml of fluid per kg in the first 24 hours.
Close and frequent examination is required to guide this therapy, since clinical signs of diuresis are the best indices of the amount of fluids required. Oral feeding should begin as soon as the patient’s condition permits, even within a few hours after admission.
Ringer’s Solution contains per 1000ml: NaCl 8.5g, KCl 0.3g, CaCl2 0.2g
Ringer’s Lactate Solution (Hartmann’s solution) contains per 1000ml: NaCl 6.0g, KCl 0.3g, CaCl2 0.2g, and Na lactate 3.1g
Darrow’s Solution contains per 1000ml: NaCl 3.0g, KCl 2.7g, and NaHCO2 4.4g
Moderate (kwashiorkor with moderate to severe vomiting as well as diarrhea)
These cases are rare and present a slightly different problem due to the loss of HCl from the stomach and the superimposition of metabolic alkalosis on the fluid and electrolyte disturbances described. If vomiting has been sufficiently acute to produce alkalosis, the sodium lactate should be omitted from the solution given. The remainder of the treatment is essentially the same.
Skim milk has been found most readily available for the dietary treatment of kwashiorkor and marasmus, but some workers have obtained good therapeutic results with vegetable protein mixtures. In Guatemala, a mixture of cottonseed flour and lime-treated maize with added nutrients has given results equivalent to those with skim milk powder. Properly processed soybean, peanut meal, or cotton seed meal can also be used in this manner if skim milk is not available.
General Treatment Measures
Because the skin of the child with kwashiorkor is likely to be excoriated, good nursing care is required to control secondary infection of the involved areas.
Because of their initial apathy and anorexia, these children will not ordinarily eat well enough of their own accord for satisfactory recovery and may stay in one position without moving. This must be taken into consideration by the nursing staff, particularly in the feeding of children during early treatment.
It is important from the beginning to try to get these children’s attention and treat them sympathetically and with understanding. In general, they are backward in psychosocial and psychomotor development because of neglect and a longstanding lack of good nutrition. A friendly attitude on part of the staff and a play area with toys will result in a better outcome.
Advantage should be taken of the visits by the parents, as this is a good time to explain to them the purely dietary nature of the treatment and the fact that a poor diet was responsible for the development of the disease in their child.
MANAGEMENT OF OTHER COMORBIDITIES
It is important to recognize that children with kwashiorkor are very susceptible to infections and almost always have pneumonia on admission. Even when the child is not febrile and pneumonia cannot be detected by auscultation, pneumonia will be evident on an x-ray of the lungs. It is for this reason that penicillin or another antibiotic should be started on admission and continued throughout the initial recovery.
Even when infections are not initially present, the susceptibility of the child with kwashiorkor to infections is so great that routine antibiotic therapy is recommended. In advanced kwashiorkor, neither fever nor elevated leucocyte count may develop, even when the infection is severe. Best results are obtained when penicillin or a broad-spectrum antibiotic is given as soon as possible after admission for 6 to 8 more days.
During treatment, the child with kwashiorkor should be isolated from cross infections as much as possible. In early studies, children with kwashiorkor treated on an open pediatric ward frequently showed little or no growth for weeks after initial recovery. When it was possible to study kwashiorkor children in individual cubicles, such a stationary growth period was never again observed.
There is no doubt that episodes of infectious diarrhea are frequently precipitating factors for kwashiorkor in an already malnourished child, but diarrhea is such a constant accompaniment of kwashiorkor that it may or may not be due entirely to infection. This cannot be said, however, of the diarrhea that persists after initial recovery. This must be considered and treated as infectious.
Children with human immunodefficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and tuberculosis are frequently severely malnourished and may develop either marasmus or marasmic kwashiorkor. In addition to the treatment described for severe malnutrition, specific treatment for these infectious diseases should be provided promptly.
Children living under circumstances responsible for their severe malnutrition are almost certain to have one or more common intestinal parasites such as Ascaris, Tricuris, Giardia, and others. These are not likely to be a major factor in the development of either marasmus or kwashiorkor, but after initial recovery, should be eliminated by specific treatment.
Children with kwashiorkor usually have anemia, but its cause may be complex. When potential etiological factors are explored sequentially, there is a mild reticulocyte response to the protein therapy that soon ends. The administration of iron usually results in a more marked and prolonged reticulocyte response and recovery from the anemia. However, there often remains some anemia that responds only to B vitamins. It is best to give iron and B vitamins routinely early in therapy.
Optimal Therapeutic Approach for this Disease
The principles of therapy do not differ with severity, but the rapidity of moving from one stage of treatment to the next may vary. The need for this is usually evident from the response of the child, guided by both clinical response and the rate of improvement in the laboratory findings.
Since nearly all kwashiorkor patients will be young children, it is important to spend time explaining to the mother the cause of her child’s life-threatening illness and helping her find ways that she can prevent its reoccurrence.
Any permanent cognitive damage is due to dietary and other factors affecting the child’s earlier development. The child’s performance on cognitive tests will be reduced during acute kwashiorkor, but usually will recover to the level achieved before the acute disease.
Opportunities for exercise, games, and other stimulation appear to hasten complete recovery. These principles also apply to the rare older child or adult that may be seen with this disease.
Weeks 2-9 can be considered the rehabilitation period, during which close attention must be given to continuing the initial treatments, as required. The World Health Organization manual suggests a follow-up period of 7-26 weeks, depending upon the individual case. This is consistent with the experience of the author in Central America.
Unusual Clinical Scenarios to Consider in Patient Management
The first week is the period of initial treatment. In the first 1-2 days, hypoglycemia, hypothermia, and dehydration should receive priority attention. Low body potassium is always present in individuals with severe malnutrition and can have fatal consequences. Therefore, the correction of electrolyte imbalances must be given a given high priority.
Correction of electrolyte imbalances must begin immediately and may need to be continued for at least 4 weeks. Correction of potassium deficiency within cells is rapid (about 1 week). Replenishing total body potassium takes much longer. On admission, treatment must be initiated for any infections present.
What is the Evidence?
Scrimshaw, NS, Viteri, FE. “INCAP studies of kwashiorkor and marasmus”. Food Nutr Bull. vol. 31. 2010 Mar. pp. 34-41. (This recent publication summarizes and integrates more than 25 years of experience of Institute of Central America and Panama [INCAP] scientists studying all aspects of marasmus and kwashiorkor, and describes their interrelations during the period when these diseases were still highly prevalent worldwide.)
Williams, CD. ” A nutritional disease of childhood associated with a maize diet”. Arch Dis Child. vol. 8. 1933. pp. 423-33. (This is the excellent original description of the epidemiology, etiology, treatment, prevention, and naming of kwashiorkor. Unfortunately, World War II soon followed. The author spent it in a Japanese prison camp in Malaysia and her work was overlooked until a WHO/FAO mission in 1952 found the widespread distribution of the condition in Africa and determined the nature of the disease. . .)
Béhar, M, FViteri, FE, Scrimshaw, NS. “Treatment of severe protein deficiency in children (kwashiorkor)”. Am J Clin Nutr. vol. 5. 1957. pp. 506-15. (This is the single most useful reference for treatment. In the 1950s, marasmic kwashiorkor was first recognized as an almost universal problem in developing countries . Intensive experience by INCAP clinicians in Guatemala, and their treatment of a large number of cases [many of them severe], resulted in the development of a treatment regimen that minimized case fatality and expedited recovery. It was widely adopted and served as the basis for later World Health Organization recommendations.)
Goldberger, J, Milton, T. “Pellagra: its nature and prevention”. Goldberger on pellagra. 1964. pp. 373-80. (This is the original description of the clinical signs of pellagra by the person whose studies in the southern United States during the Great Depression were the first to identify it as a dietary deficiency disease. His work led to the recognition that dietary niacin and tryptophan deficiency was the cause of this disease. It provides the best detailed descriptions of the skin lesions.)
Béhar, M, Viteri, FE, Bressani, B, Arroyave, G, Squibb, RL, Scrimshaw, NS. Principles of treatment and prevention of severe protein malnutrition in children (kwashiorkor). 1959. pp. 954-Guatemala City, Guatemala. (This paper recapitulates the advice on treatment of kwashiorkor and goes on to describe factors responsible for the development of clinical cases and principles of prevention. It also describes the full range of protein sources available for the prevention and recuperation of cases of kwashiorkor in developing countries.)
Scrimshaw, NS, Béhar, M. “Protein malnutrition in young children”. Science. vol. 3470. 1961. pp. 2039-46. (This paper recapitulates and details further experience with the various forms and combination of kwashiorkor and marasmus. It contains good pictures of edema and skin lesions, as well as hair changes, in kwashiorkor. It clarifies and illustrates the multiple combinations of kwashiorkor and marasmus and how this impacts treatment and recovery.)
Management of severe malnutrition: a manual for physicians and other senior health workers. 1999. (This manual was developed as a cooperative effort of experts in different parts of the world with first-hand experience in the treatment of kwashiorkor and other forms of severe protein energy malnutrition. The advice on treatment takes into account the necessity of adapting treatment procedures to regional variations in the signs, symptoms, and pathologies in different populations. The treatment and case management of kwashiorkor suggested in this chapter are consistent with its recommendation.)
Severe malnutrition: report of a consultation to review current literature. 2004. (This is the report of an informal consultation convened by WHO in Geneva in 2004. Temporary advisers for this meeting included representatives from Bangladesh, England , Germany, South Africa, and the United States , all of whom had in-depth experience with the management of severe protein malnutrition in one or more developing countries. The charge given to this group was to critically review new evidence relevant to the current WHO guidelines, consider if changes to the guidelines are required as a result of new evidence, and assess the guidelines in relation to care of the poorest severely malnourished children with HIV/AIDS.The consultation found only very limited new research data and no need to revise current WHO guidelines for the dietary management of kwashiorkor; however, experience with the treatment of kwashiorkor has programmatic implications for the management of patients with advanced HIV/AIDS.)
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