Kwashiorkor

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](B2)

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