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 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 kwashiokor so that the interprofessional team can successfully manage this condition.

Objectives:

• Review the pathophysiology of kwashiokor.
• Describe the epidemiology of kwashiokor.
• Summarize the physical findings expected in kwashiokor.
• Outline the evaluation and treatment of patients with kwashiokor 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, 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 the 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 for 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 is 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 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, medical staff had to proceed cautiously. The standard normal saline solution contains too much sodium and too little potassium. However, ReSoMal (Rehydration Solution of Malnutrition) is a customized solution that can be given orally or via nasogastric tubes that contains the exact amount of mineral/electrolytes, sugar, and water that the WHO recommends.

Differential Diagnosis

• Acrodermatitis enteropathica

• Actinic prurigo

• Angio-neurotic oedema

• Atopic dermatitis

• Chronic kidney disease

• Cirrhosis

• Depression

• Inflammatory bowel disease

• Malignancies

• Nephrotic syndrome

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

Enhancing Healthcare Team Outcomes

The diagnosis and management of kwashiorkor is with an interprofessional team that includes the primary care provider, nurse practitioner, dietitian, internist, gastroenterologist, a rheumatologist, and a 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]