Kwashiorkor

Continuing Education Activity

Kwashiorkor is a disease marked by severe protein malnutrition and bilateral extremity swelling. It usually affects infants and children, most often around the age of weaning through age 5. The disease is seen in very severe cases of starvation and poverty-stricken regions worldwide. In the 1950s, it was recognized as a public health crisis by the World Health Organization. However, there was a delay in its recognition, because most cases of childhood death were reported as being from diseases of the digestive system or infectious etiology. Since then, various relief efforts were aimed at eradicating it. As scientists continued to investigate the natural history of the disease in children, they discovered something very striking. Children who were dying from "digestive system diseases" and presenting with diarrhea, cough, coryza, and shortness of breath also were having symptoms of kwashiorkor during this time (pitting edema, anorexia, skin changes, etc.). This finding led to the medical conundrum of whether kwashiorkor was the primary or the secondary cause of death. It was concluded to be the secondary cause of death because many cases of the disease would not have developed without the precipitating stress of diarrhea, dehydration, and other infectious diseases such as HIV and measles. While kwashiorkor is a disease of edematous malnutrition, marasmus is similar in appearance. Marasmus is known also known as a wasting syndrome (malnutrition without edema). Children typically have a depletion of body fat stores, low weight for height, and reduced mid-upper arm circumference. Other features of the disease can include thin, dry skin; a head that appears large relative to the body; an emaciated, weak appearance; bradycardia; hypotension; hypothermia; and thin, shrunken arms, thighs, and buttocks with redundant skin folds. This activity reviews the evaluation and treatment of patients with kwashiorkor and highlights the role of the interprofessional team in successfully managing this condition.

Objectives:

• Review the pathophysiology of kwashiorkor.
• Describe the epidemiology of kwashiorkor.
• Summarize the physical findings expected in kwashiorkor.
• Outline the management of patients with kwashiorkor so that the interprofessional team can successfully manage this condition.

Introduction

Kwashiorkor is a disease marked by severe protein malnutrition and bilateral extremity swelling. It usually affects infants and children, most often around the age of weaning through age 5. The disease is seen in very severe cases of starvation and poverty-stricken regions worldwide. In the 1950s, it was recognized as a public health crisis by the World Health Organization. However, there was a delay in its recognition, because most cases of childhood death were reported as being from diseases of the digestive system or infectious etiology. Since then, various relief efforts were aimed at eradicating it.[1][2][3][4]

As scientists continued to investigate the natural history of the disease in children, they discovered something very striking. Children who were dying from "digestive system diseases" and presenting with diarrhea, cough, coryza, and shortness of breath also were having symptoms of kwashiorkor during this time (pitting edema, anorexia, skin changes, etc.). This finding led to the medical conundrum of whether kwashiorkor was the primary or the secondary cause of death. It was concluded to be the secondary cause of death because many cases of the disease would not have developed without the precipitating stress of diarrhea, dehydration, and other infectious diseases such as HIV and measles.[5]

While kwashiorkor is a disease of edematous malnutrition, marasmus is similar in appearance. Marasmus is known as the wasting syndrome (malnutrition without edema). Children typically have a depletion of body fat stores, low weight for height, and reduced mid-upper arm circumference. Other features of the disease can include thin, dry skin, a head that appears large relative to the body; an emaciated, weak appearance; bradycardia; hypotension; hypothermia; and thin, shrunken arms, thighs, and buttocks with redundant skin folds. 

Etiology

The etiology of kwashiorkor is fairly unknown, but diets based mainly on maize, cassava, or rice are frequently associated with the disease. It was previously believed to be due to protein deficiency and low levels of antioxidants and aflatoxins. Evidence for these associations exists; however, efforts targeted to replete diets with high-protein and antioxidants have not been successful. Aflatoxin, previously thought to be the etiology of kwashiorkor, is not always associated with the disease in certain populations. Some factors that are consistently associated with the disease include recent weaning, recent infection (particularly measles), and disruptions in childhood (parental death, temporary home environment, poverty).[6][7]

Epidemiology

Kwashiorkor is rare in the United States. Worldwide, the most affected regions include Southeast Asia, Central America, Congo, Puerto Rico, Jamaica, South Africa, and Uganda. Prevalence can vary, but it is seen mostly during times of famine. Rural and farming communities are often affected the hardest.[8]

Pathophysiology

Kwashiorkor is characterized by peripheral edema in a person suffering from starvation. Edema results from a loss of fluid balance between hydrostatic and oncotic pressures across capillary blood vessel walls. Albumin concentration contributes to the oncotic pressure, allowing the body to keep fluids within the vasculature. Children with kwashiorkor were found to have profoundly low levels of albumin and, as a result, became intravascularly depleted. Subsequently, antidiuretic hormone (ADH) increases in response to hypovolemia, resulting in edema. Plasma renin also responds aggressively, causing sodium retention. These factors contribute to the edema.

Kwashiorkor is also marked by low glutathione (antioxidant) levels. This is thought to reflect high levels of oxidant stress in the malnourished child. High oxidant levels are commonly seen during starvation and are even seen in cases of chronic inflammation. One measure at reversal would be improved nutritional status and sulfur-containing antioxidants. There is also an experimental theory proposing that alterations in the microbiome/virone contribute to edematous malnutrition, however, further studies are required to understand the mechanism.

History and Physical

The clinical manifestations of kwashiorkor include the following:

• Peripheral pitting edema that begins in dependent regions and proceeds cranially
• Marked muscle atrophy
• Abdominal distension (with/without dilated bowel loops and hepatomegaly)
• Round face (prominence of the cheeks, or “moon facies”)
• Thin, dry, peeling skin with confluent areas of scaling and hyperpigmentation
• Dry, full, hypopigmented hair that falls out or is easily plucked
• Hepatomegaly (from fatty liver infiltrates)
• Growth retardation
• Psychic changes (anorexia, apathy)
• Skin lesions/dermatitis (perineum, groin, limbs, ears, armpits)
• Subcutaneous fat retention with loose inner inguinal skin folds

Evaluation

The World Health Organization has a classification system for evaluating malnutrition severity that determines wasting versus kwashiorkor. They use three clinical measures: the mid-upper arm circumference (MUAC), weight-for-height/length Z score, and presence of symmetrical pitting edema. It is generally accepted that MUAC less than 110 mm is highly associated with mortality in infants younger than 6 months old. Criteria for hospital admission are based on reaching defined cutoffs set by the WHO. Nutritional history, past medical history, vaccination history, and family history are also important to elicit from patients suspected of being malnourished.[9][10]

Treatment / Management

Many pathophysiological steps are involved in the development of protein malnutrition from starvation. In the past, it was argued that hypoalbuminemia was not the cause of edema in kwashiorkor disease. Scientists performing experiments at that time concluded this because the edema went away with dietary treatment, even before the albumin concentration rose when albumin was given. However, re-analysis of this work has revealed a big error in this conclusion, and indeed, profound hypoalbuminemia was proven to be linked to the development of co-existing edema in the hypovolemic child.[11][12][13]

The following are ten primary principles used universally for the treatment of patients who are admitted for kwashiorkor. These principles are done in different phases from the time the child arrives requiring emergency stabilization through eventual rehabilitation.

1. Treating/preventing hypocalcemia 
2. Treating/preventing hypothermia 
3. Treating/preventing dehydration 
4. Correcting electrolyte imbalance 
5. Treating/preventing infection 
6. Correcting micronutrient deficiencies 
7. Starting cautious feeding 
8. Achieving catch-up growth 
9. Providing sensory stimulation and emotional support and 
10. Preparing for follow-up after recovery. 

It is important to highlight how critical it is to address the fluid imbalance in kwashiorkor. In the past, there was concern about aggressive rehydration causing acute heart failure. However, this was proven to be exaggerated. At the same time, severe hypovolemia could cause hypovolemic shock and death. So, the medical staff had to proceed cautiously. The standard normal saline solution contains too much sodium and too little potassium.

Differential Diagnosis

Following are some important differentials of kwashiorkor:

• Acrodermatitis enteropathica

• Actinic prurigo

• Angio-neurotic edema

• Atopic dermatitis

• Chronic kidney disease

• Cirrhosis

• Depression

• Inflammatory bowel disease

• Malignancies

• Nephrotic syndrome

Prognosis

In kwashiorkor, mortality decreases as the age of onset of the disease increases. Children may not grow or develop abnormally and may remain stunted. There can be serious complications when treatment is not started earlier in the disease course, including shock, coma, and permanent physical and mental disabilities. Kwashiorkor can be life-threatening if left untreated.

Complications

Some complications of kwashiorkor include:

• Hepatomegaly (from the fatty liver)
• Cardiovascular system collapse/hypovolemic shock
• Urinary tract infections
• Abnormalities of the gastrointestinal tract including atrophy of the pancreas with subsequent glucose intolerance, atrophy of the mucosa of the small intestine, lactase deficiency, ileus, bacterial overgrowth, which can lead to bacterial septicemia and death.
• Loss of immune function, antioxidant function, subsequent infections, septic shock, and death.
• Endocrinopathies where insulin levels are decreased; growth hormone is increased, but insulin-like growth factor levels are reduced. This leads to insulin intolerance
• Metabolic disturbances and hypothermia
• Impaired cellular functions, including endothelial dysfunction
• Electrolyte abnormalities are commonplace

Deterrence and Patient Education

Education on nutrition starts with the mother prior to childbirth. It is important to educate mothers to be healthy during pregnancy in order to meet the nutritional demands of the child and herself. Educating them on how to adequately nourish their child is also crucial.

Enhancing Healthcare Team Outcomes

The diagnosis and management of kwashiorkor are with an interprofessional team that includes the primary care provider, nurse practitioner, dietitian, internist, gastroenterologist, rheumatologist, and cardiologist. It is important to know that this is a chronic and complex calorie deprivation disorder that affects almost every organ in the body. Fluid correction requires care as these children often have poor heart function. Electrolytes disturbances have to be corrected and calories slowly increased. The primary condition causing the calorie deprivation must be treated, otherwise, the child will not recover The outcomes for many children are guarded, especially if the CNS has been affected. Even those who survive may have a significant delay in growth and complete recovery may not be possible.[14][15][16]

Review Questions

• Access free multiple choice questions on this topic.
• Click here for a simplified version.
• Comment on this article.

References

1.

Marks RR, Burgy JR, Davis LS. Acute kwashiorkor in the setting of cerebral palsy and pancreatic insufficiency. Cutis. 2019 Jan;103(1):E10-E12. [PubMed: 30758347]

2.

Teshome G, Bosha T, Gebremedhin S. Time-to-recovery from severe acute malnutrition in children 6-59 months of age enrolled in the outpatient treatment program in Shebedino, Southern Ethiopia: a prospective cohort study. BMC Pediatr. 2019 Jan 28;19(1):33. [PMC free article: PMC6348627] [PubMed: 30691437]

3.

West-Eberhard MJ. Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):723-731. [PMC free article: PMC6338860] [PubMed: 30598443]

4.

Derseh B, Mruts K, Demie T, Gebremariam T. Co-morbidity, treatment outcomes and factors affecting the recovery rate of under -five children with severe acute malnutrition admitted in selected hospitals from Ethiopia: retrospective follow up study. Nutr J. 2018 Dec 18;17(1):116. [PMC free article: PMC6299567] [PubMed: 30563516]

5.

Fevang P, Havemann K, Fevang B, Høstmark AT. Malaria and Malnutrition: Kwashiorkor Associated with Low Levels of Parasitaemia. Malar Res Treat. 2018;2018:7153173. [PMC free article: PMC6247571] [PubMed: 30533212]

6.

Grellety E, Golden MH. Severely malnourished children with a low weight-for-height have a higher mortality than those with a low mid-upper-arm-circumference: I. Empirical data demonstrates Simpson's paradox. Nutr J. 2018 Sep 15;17(1):79. [PMC free article: PMC6138885] [PubMed: 30217205]

7.

Grellety E, Golden MH. Severely malnourished children with a low weight-for-height have similar mortality to those with a low mid-upper-arm-circumference: II. Systematic literature review and meta-analysis. Nutr J. 2018 Sep 15;17(1):80. [PMC free article: PMC6138903] [PubMed: 30217196]

8.

Fitzpatrick M, Ghosh S, Kurpad A, Duggan C, Maxwell D. Lost in Aggregation: The Geographic Distribution of Kwashiorkor in Eastern Democratic Republic of the Congo. Food Nutr Bull. 2018 Dec;39(4):512-520. [PubMed: 30136596]

9.

Ahmed S, Ejaz K, Mehnaz A, Adil F. Implementing WHO feeding guidelines for inpatient management of malnourished children. J Coll Physicians Surg Pak. 2014 Jul;24(7):493-7. [PubMed: 25052973]

10.

Moges T, Haidar J. Management and outcome of severely malnourished children admitted to Zewditu Memorial Hospital, Ethiopia. East Afr J Public Health. 2009 Aug;6(2):162-7. [PubMed: 20000023]

11.

Sadler K, Kerac M, Collins S, Khengere H, Nesbitt A. Improving the management of severe acute malnutrition in an area of high HIV prevalence. J Trop Pediatr. 2008 Dec;54(6):364-9. [PubMed: 18450820]

12.

Jilcott SB, Masso KL, Ickes SB, Myhre SD, Myhre JA. Surviving but not quite thriving: anthropometric survey of children aged 6 to 59 months in a rural Western Uganda district. J Am Diet Assoc. 2007 Nov;107(11):1983-8. [PubMed: 17964320]

13.

Linneman Z, Matilsky D, Ndekha M, Manary MJ, Maleta K, Manary MJ. A large-scale operational study of home-based therapy with ready-to-use therapeutic food in childhood malnutrition in Malawi. Matern Child Nutr. 2007 Jul;3(3):206-15. [PMC free article: PMC6860523] [PubMed: 17539889]

14.

Ndzo JA, Jackson A. Outcomes of children aged 6-59 months with severe acute malnutrition at the GADO Outpatient Therapeutic Center in Cameroon. BMC Res Notes. 2018 Jan 24;11(1):68. [PMC free article: PMC5782382] [PubMed: 29361980]

15.

Obonyo N, Brent B, Olupot-Olupot P, Boele van Hensbroek M, Kuipers I, Wong S, Shiino K, Chan J, Fraser J, van Woensel JBM, Maitland K. Myocardial and haemodynamic responses to two fluid regimens in African children with severe malnutrition and hypovolaemic shock (AFRIM study). Crit Care. 2017 May 03;21(1):103. [PMC free article: PMC5415747] [PubMed: 28468633]

16.

Kabalo MY, Seifu CN. Treatment outcomes of severe acute malnutrition in children treated within Outpatient Therapeutic Program (OTP) at Wolaita Zone, Southern Ethiopia: retrospective cross-sectional study. J Health Popul Nutr. 2017 Mar 09;36(1):7. [PMC free article: PMC5345228] [PubMed: 28279227]

Disclosure: Onecia Benjamin declares no relevant financial relationships with ineligible companies.

Disclosure: Sarah Lappin declares no relevant financial relationships with ineligible companies.