Protein-Energy Malnutrition

The World Health Organization (WHO) defines malnutrition as "the cellular imbalance between the supply of nutrients and energy and the body's demand for them to ensure growth, maintenance, and specific functions."[1]  The term protein-energy malnutrition (PEM) applies to a group of related disorders that include marasmus, kwashiorkor (see the images below), and intermediate states of marasmus-kwashiorkor.

Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting.[2]  Studies suggest that marasmus represents an adaptive response to starvation, whereas kwashiorkor represents a maladaptive response to starvation. Children may also present with a mixed picture of marasmus and kwashiorkor or with milder forms of malnutrition. 

Protein-energry malnutition is a global issue, seen primarily in resource-limited countries. Overall, malnutrition has decreased worldwide, but the rates vary by region. For example, Asia has seen declines in this condition, whereas there has been a continued increase in African nations.[3]

Malnutrition can be classified as acute versus chronic. Features of chronic malnutrition include stunted growth, mental apathy, developmental delay, and poor weight gain.[4, 5]  Acute malnutition manifests itself in two major forms: marasums (the most common form) and kwashiorkor, although some patients' condition may manifest as a combination of both forms (marasmic kwashiorkor).

Children with marasmus are often low weight-for-height and have a reduced mid-upper arm circumference, as well as a head that appears large relative to the rest of their body. Other findings include dry skin, thin hair, and irritability. Kwashiorkor is characterized by peripheral pitting edema, as well as "moon facies," hepatomegaly, and a pursed mouth.

In general, marasmus occurs when there is an insufficient energy intake to match the body's requirements. As a result, the body draws on its own stores, resulting in emaciation. In kwashiorkor, adequate carbohydrate consumption and decreased protein intake lead to decreased synthesis of visceral proteins. The resulting hypoalbuminemia contributes to extravascular fluid accumulation. Impaired synthesis of B-lipoprotein produces a fatty liver.

Protein-energy malnutrition also involves an inadequate intake of many essential nutrients. Low serum levels of zinc have been implicated as the cause of skin ulceration in many patients. In a 1979 study of 42 children with marasmus, Golden and Golden found that only those with low serum levels of zinc developed skin ulceration.[6] Serum zinc levels correlated closely with the presence of edema, stunted growth, and severe wasting. The classic "mosaic skin" and "flaky paint" dermatosis of kwashiorkor bears considerable resemblance to the skin changes of acrodermatitis enteropathica, the dermatosis of zinc deficiency.

In 2007, Lin et al stated that "a prospective assessment of food and nutrient intake in a population of Malawian children at risk for kwashiorkor" found "no association between the development of kwashiorkor and the consumption of any food or nutrient."[7]

Marasmus and kwashiorkor can both be associated with impaired glucose clearance that relates to dysfunction of pancreatic beta-cells.[8] In utero, plastic mechanisms appear to operate, adjusting metabolic physiology and adapting postnatal undernutrition and malnutrition to define whether marasmus and kwashiorkor will develop.[9]

A 2013 report from Texas noted an 18-month-old infant with type 1 glutaric acidemia who had extensive desquamative plaques, generalized nonpitting edema, and red-tinged sparse hair, with low levels of zinc, alkaline phosphatase, albumin, and iron.[10] This patient had a variation of kwashiorkor, and the authors suggested that it be termed acrodermatitis dysmetabolica.[10]

For complex reasons, sickle cell anemia can predispose sufferers to protein malnutrition.[11]

Protein-energy malnutrition ramps up arginase activity in macrophages and monocytes.[12]

Derangements to the gut microbiome in undernourished hosts also appear to play a role in the pathophysiology that results in persistent growth impairment in children.[13]

Worldwide, the most common cause of malnutrition is inadequate food intake. Preschool-aged children in developing countries are often at risk for malnutrition because of their dependence on others for food, increased protein and energy requirements, immature immune systems causing a greater susceptibility to infection, and exposure to nonhygienic conditions.

Another significant factor is ineffective weaning secondary to ignorance, poor hygiene, economic factors, and cultural factors. The prognosis is worse when protein-energy malnutrition occurs with human immunodeficiency virus (HIV) infection. Gastrointestinal infections can and often do precipitate clinical protein-energy malnutrition because of associated diarrhea, anorexia, vomiting, increased metabolic needs, and decreased intestinal absorption. In addition, parasitic infections play a major role in many parts of the world.

In developed nations, inadequate food intake is a less common cause of malnutrition than that caused by decreased absorption or abnormal metabolism. Thus, diseases, such as cystic fibrosis, chronic renal failure, childhood malignancies, congenital heart disease, and neuromuscular diseases contribute to malnutrition in developed countries. Fad diets, inappropriate management of food allergies, and psychiatric diseases (eg, anorexia nervosa) can also lead to severe protein-energy malnutrition.

Populations in both acute- and long-term facilities are at risk for clinically significant involuntary weight loss (IWL) that can result in protein-energy malnutrition. IWL is defined as a loss of 4.5 kg or greater than 5% of the usual body weight over a period of 6-12 months. Protein-energy malnutrition occurs when weight loss of greater than 10% of normal body weight occurs.

Elderly patients are often at risk for protein-energy malnutrition because of inadequate nutrition, which has been determined to be a common comorbid factor for increased morbidity and mortality in elderly burn victims.[14]

Anorexia of aging, defined as the loss of appetite and/or decreased food intake in late life, is used to describe multifaceted clinical conditions that are common among frail older persons but not easily grouped into specific diseases or syndrome categories. Common causes of resulting malnutrition include decreased appetite, dependency on help for eating, impaired cognition and/or communication, poor positioning, frequent acute illnesses with gastrointestinal losses, medications that decrease appetite or increase nutrient losses, polypharmacy, decreased thirst response, decreased ability to concentrate urine, intentional fluid restriction due to fear of incontinence or choking if dysphagic, psychosocial factors such as isolation and depression, monotony of diet, higher nutrient density requirements, and other demands of age, illness, and disease on the body.[15]

Protein-energy malnutrition is one of the most common complications in liver cirrhosis patients, with reported rates of 25.1% to 65.5%.

Patients on long-term hemodialysis also may develop protein-energy malnutrition; this is associated with increased morbidity and mortality.

Patients with squamous cell carcinoma of the esophagus are at risk for protein-energy malnutrition.

Bariatric surgery can be associated with iatrogenic kwashiorkor.[16, 17]

United States data

Protein-energy malnutrition is the most common form of nutritional deficiency among patients who are hospitalized in the United States. Up to half of all patients admitted to the hospital have malnutrition to some degree. In a survey of a large children's hospital, the prevalence of acute and chronic protein-energy malnutrition was more than 50%.

Protein-energy malnutrition is very much a disease that occurs in 21st century, even in the United States and other developed nations.[18, 19]  The case of an 8-month-old child with kwashiorkor in suburban Detroit, Michigan, was reported in 2010,[20]  and additional US cases of kwashiorkor have been noted, such as that of a baby in 2013 with a clinical picture imitating Stevens-Johnson syndrome but who in fact had kwashiorkor.[21] Babies solely fed on rice milk can also develop kwashiorkor.

In a survey focusing on low-income areas of the United States, 22-35% of children aged 2-6 years were below the 15th percentile for weight. Another survey showed that 11% of children in low-income areas had height-for-age measurements below the 5th percentile. Poor growth is seen in 10% of children in rural populations.

In hospitalized elderly persons, up to 55% are undernourished. Up to 85% of institutionalized elderly persons are undernourished. Studies have shown that as many as 50% have vitamin and mineral intake that is less than the recommended dietary allowance, and up to 30% of elderly persons have below-normal levels of vitamins and minerals.

International data

In 2000, the World Health Organization (WHO) estimated that malnourished children numbered 181.9 million (32%) in developing countries.[22]  In addition, approximately 149.6 million children younger than 5 years were malnourished when measured in terms of weight for age. In south central Asia and eastern Africa, about half the children had growth retardation due to protein-energy malnutrition. This figure was five times the prevalence in the western world.

More recent data (2016) indicate that severe acute malnutrition including kwashiorkor and marasmus affects more than 18 million children each year, most living in low-income settings.[2]  According to 2018 WHO data, 52 million children younger than 5 years are wasted (low weight-for-height), 17 million are severely wasted, and 155 million are stunted (low height-for-age).[23]

A 2018 systematic review and meta-analysis of 1989-2017 data regarding the prevalence of underweight and wasting in Iranian children younger than 5 years found regional differences, which the investigators believed could be attributed to the varying level of development in these areas.[24] The prevalence of underweight among children at the national level was 6%, with the lowest at 5% in western Iran and the highest in central Iran. The prevalence of pediatric wasting was 4% at the national level, with the lowest at 4% in western Iran and the highest in southen Iran.[24]

A cross-sectional study of Palestinian adolescents found inadequate energy intake in 55.66% of boys and 64.81% of girls, and inadequate protein intake in 15.07% of boys and 43.08% of girls.[25]  The recommended daily allowance for micronutrients was met by less than 80% of the study subjects.

Dermatologic findings appear more significant and occur more frequently among darker-skinned peoples. This finding is likely explained by the greater prevalence and the increased severity of protein-energy malnutrition in developing countries and not to a difference in racial susceptibility.

Marasmus most commonly occurs in children younger than 5 years. This period is characterized by increased energy requirements and increased susceptibility to viral and bacterial infections. Weaning (the deprivation of breast milk and the commencement of nourishment with other food) occurs during this high-risk period. Weaning is often complicated by geography, economy, hygiene, public health, culture, and dietetics. It can be ineffective when the foods introduced provide inadequate nutrients, when the food and water are contaminated, when the access to health care is inadequate, and/or when the patient cannot access or purchase proper nourishment.

In some studies, the protein-energy malnutrition prevalence among elderly persons is estimated to be as high as 4% for those living in the community, 50% for those hospitalized in acute care units or geriatric rehabilitation units, and 30-40% for those in long-term care facilities. A 2019 systematic review, meta-analysis, and meta-regression of the prevalence of protein-energy malnutrition among the elderly found that rural communities were affected twice as much as urban communities and women were affected more than males.[26] Other recent studies of geriatric patients hospitalized for orthopedic conditions[27] or heart failure[28] also note protein-energy malnutrition is prevalent in this population.

The extent of growth failure and the severity of hypoproteinemia, hypoalbuminemia, and electrolyte imbalances are predictors of a poorer prognosis. Additionally, underlying human immunodeficiency virus (HIV) infection is associated with a poor prognosis. 

Approximately 45% deaths each year in developing countries occur because of malnutrition in children younger than 5 years.[2, 13, 23] In kwashiorkor, mortality tends to decrease as the age of onset increases.

Protein-energy malnutrition has also been found to be a primary factor of poor prognosis in elderly persons. In a study designed to assess the quality of care in nursing home residents, there was a direct association between mortality and anorexia in elderly residents of both genders with an almost two-fold higher risk of death for all causes in patients with anorexia.[29] In a separate propensity-matched study of 32,771 elderly patients hospitalized for heart failure, protein-match malnutrition was associated with higher mortality, cardiogenic shock, cardiac arrest, acute kidney failure, acute respiratory failure, and mechanical ventilation.[28]

Patients with liver cirrhosis are also at risk for protein-energy malnutrition,[30] which portends a poor prognosis for survival.[31] Protein-energy malnutrition is associated with an increased risk of liver cirrhosis complications, including ascites, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome.[30, 32]

Complications

Complications of protein-energy malnutrition can be many, including the following[33] :

• Hypothermia
• Hypoglycemia
• Encephalopathy
• Diarrhea
• Heart failure
• Infection

Another important complication of malnutrition is micronutrient defiencies. Vitamin deficiencies can be seen, with deficiencies in the fat-soluble vitamins (A, D, E, and K) being more common. Vitamin A deficiency can have ocular effects, causing night blindness among other problems; vitamin D deficiency can have bony effects; vitamin E deficiency can cause neuropathy and ataxia; and vitamin K deficiency can cause bleeding.

Deficiencies in the water-soluble vitamins has a multitude of effects. Folic acid (vitamin B9) and cobalamin (vitamin B12) deficiency can both cause megaloblastic anemia. Deficiency in thiamine (vitamin B1) can cause beriberi and high-output heart failure, whereas deficiency riboflavin (vitamin B2) can cause glossitis and seborrheic dermatitis. Niacin (vitamin B3) deficiency can result in pellagra, leading to dermatitis, dementia, diarrhea, and weakness. Pyridoxine (vitamin B6) deficiency can lead to neuropathy, irritability, and weight loss. 

Minerals or trace elements such as phosphorus, iron, and zinc can also be deficient in protein-energy malnutrition. Phosphate deficiency, if severe, can cause rhabdomyolysis, bone pain, or osteomalacia. Iron deficiency can lead to microcytic anemia and, if severe, can result in cardiomegaly, lethargy, and impaired psychomotor and mental development. Zinc deficiency can lead to growth failure, increased infections, and cognitive dysfunction.

Education regarding adequate nutrition starts with the mother, often prior to childbirth. It is important to educate the mother to be healthy during pregnancy to meet the nutritional demands not only of her child, but also herself. Educating these women regarding the importance of breastfeeding and how to adequately nourish a child is also essential.

Obtain a detailed dietary history, growth measurements, body mass index (BMI), as well as perform a complete physical examination.

Sensitive measures of nutritional deficiency in children include height-for-age or weight-for-height measurements that are less than 95% and 90% of expected, respectively, or greater than two standard deviations below the mean for age. In children older than 2 years, growth of less than 5 cm per year may also be an indication of deficiency.

Low intake of calories or an inability to absorb calories is the key factor in the development of kwashiorkor. A variety of syndromes can be associated with this condition.[34]   For example, there have been cases of kwashiokor resulting from a diet that included multivitamins, health supplements, and organic milk and cereals to treat eczema[35] ; a rice milk diet used to treat atopic dermatitis[36] ; as well as a diet consisting only of potatoes, gelatin, and juice.[37]

In children, the findings of poor weight gain or weight loss; slowing of linear growth; and behavioral changes, such as irritability, apathy, decreased social responsiveness, anxiety, and attention deficit may indicate protein-energy malnutrition. In particular, the child is apathetic when undisturbed but irritable when picked up. Kwashiorkor characteristically affects children who are being weaned. Signs include diarrhea and psychomotor changes.

Adults generally with protein-energy malnutrition lose weight, although, in some cases, edema can mask weight loss. Patients may describe listlessness, easy fatigue, and a sensation of cold. Global impairment of system function is present.

Patients with protein-energy malnutrition can also present with nonhealing wounds. This may signify a catabolic process that requires nutritional intervention. Lewandowski et al reported kwashiorkor and an acrodermatitis enteropathica–like eruption after a distal gastric bypass surgical procedure[38] . Kwashiorkor was reported in an infant presenting with diarrhea and dermatitis, due to infantile Crohn disease.[39] The infant's diarrhea and dermatitis improved in 2 weeks with treatment.

Sander et al reported the case of a 3-year-old child with coexisting celiac and Hartnup disease that resulted in kwashiorkor, anemia, hepatitis, hypoalbuminia, angular cheilitis, glossitis, conjunctivitis and diffuse alopecia, erythematous skin, desquamation, erosions, and diffuse hyperpigmentation was reported by in 2009.[40]  These findings resolved with the proper nutritional supplementation.

Note that "cupping" (the placement of heated suction cups on the body to cure disease) on the abdomen of patients with diseases that result in abdominal swelling (eg, kwashiorkor) can cause interesting clinical presentations.[41]

Maintenance hemodialysis can result in protein-energy-malnutrition and it relates strongly with mortality, with serum albumin being the only predictor of death.[42]  In another study of 134 adult Croatian outpatients on dialysis, malnourishment (particularly hypoproteinemia) and age were associated with higher overall mortality.[43]

 

In marasmus, the child appears emaciated with marked loss of subcutaneous fat and muscle wasting. The skin is xerotic, wrinkled, and loose. Monkey facies secondary to a loss of buccal fat pads is characteristic of this disorder. Marasmus may have no clinical dermatosis; however, inconsistent cutaneous findings include fine, brittle hair; alopecia; impaired growth; and fissuring of the nails.

In protein-energy malnutrition, more hairs are in the telogen (resting) phase than in the anagen (active) phase, a reverse of normal. Occasionally, as in anorexia nervosa, marked growth of lanugo hair is noted.

Kwashiorkor typically presents with a failure to thrive, edema, moon facies, a swollen abdomen (potbelly), and a fatty liver. When present, skin changes are characteristic and progress over a few days. The skin becomes dark, dry, and then splits open when stretched, revealing pale areas between the cracks (ie, "crazy pavement" dermatosis, "enamel paint" skin). This feature is seen especially over pressure areas. In contrast to pellagra, these changes seldom occur on sun-exposed skin.

Depigmentation of hair causes it to be reddish yellow to white. Curly hair becomes straightened. If periods of poor nutrition are interspersed with good nutrition, alternating bands of pale and dark hair, respectively, called" the flag sign," may occur. Also, hairs become dry, lusterless, sparse, and brittle; they can be pulled out easily. Temporal recession and hair loss from the back of the head occur, likely secondary to pressure when the child lies down. In some cases, hair loss can be extreme. Hair can also become softer and finer and appear unruly. The eyelashes can undergo the same change, having a so-called broomstick appearance.

Nail plates are thin and soft and may be fissured or ridged. Atrophy of the tongue papillae, angular stomatitis, xerophthalmia, and cheilosis can occur.

Inflammatory bowel diseases, such as Crohn disease and ulcerative colitis, may also produce skin manifestations secondary to malnutrition.[44]

In elderly persons, an indicative sign of malnutrition is delayed healing and an increased presence of decubitus ulcers of stage III or higher.

Vitamin C deficiency commonly manifests in elderly persons as perifollicular hemorrhages, petechiae, gingival bleeding, and splinter hemorrhages, in addition to hemarthroses and subperiosteal hemorrhages. Anemia may result, and wound healing may be impaired. Niacin deficiency clinically manifests as pellagra (ie, dermatitis, dementia, diarrhea) in advanced cases. The dermatitis manifests in sun-exposed areas, including the back, neck (Casal necklace), face, and dorsum of the hands (gauntlet of pellagra), initially as painful erythema and itching. Subsequently, vesicles and bullae may develop and erupt, creating crusted, scaly lesions. Finally, the skin becomes rough and covered by dark scales and crusts. Striking demarcation of the affected areas from the normal skin is noted.

Protein-energy malnutrition is also associated with an increased likelihood of calciphylaxis, a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis, and thrombosis. As a result, ischemia and necrosis of skin occurs. Other tissues affected include subcutaneous fat, visceral organs, and skeletal muscle.

Harima et al reported on the effects of an evening snack in patients receiving chemotherapy for hepatocellular carcinoma (HCC), in which there was a lower nonprotein respiratory quotient in patients with advanced HCC compared with cirrhotic patients without HCC and patients with early-stage HCC.[45] Patients with cirrhosis and advanced HCC who were receiving chemotherapy and who received the late-evening snack had an improved nonprotein respiratory quotient, branched-chain amino acid/tyrosine ratio, alanine aminotransferase level, and prealbumin level compared with controls.[45]

In suspected cases of protein-energy malnutrition, it is imperative to perform a thorough and comprehensive metabolic and nutritional assessment. It begins with a detailed history, including dietary, medical, and pharmacologic (medications). It is essential to perform a thorough physical examination, including height, weight, and other growth measurements to be detailed below. In addition, it is important to perform necessary laboratory and radiologic testing. Combined, these steps should help clinicians to diagnose and assess the severity of protein-energy malnutrition.

In a study that compared 21 hospitalized children with kwashiorkor, 19 hospitalized children with marasmus, 78 children with stunted growth, and 79 children with nonstunted growth, the metabolic profiles differed between children with kwashiorkor and those with marasmus at admission, and both phenotypes were metabolically distinct from either community control group.[2] Most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Differences in several phosphatidylcholines and some acylcarnitines were also present. Levels of amino acids and biogenic amines generally improved with nutritional rehabilitation, but measurements of most sphingomyelins and phosphatidylcholines did not.[2]

The following laboratory studies are recommended in the workup of protein-energy malnutrition:

• Complete blood cell (CBC) count
• Electrolyte levels (potassium, calcium, phosphate, magnesium)
• Blood urea nitrogen
• Serum albumin and prealbumin (transthyretin) levels
• Micronutrient levels: Zinc, iron, vitamin D

Significant findings in kwashiorkor include hypoalbuminemia (10-25 g/L), hypoproteinemia (transferrin, essential amino acids, lipoprotein), and hypoglycemia. Plasma cortisol and growth hormone levels are high, but insulin secretion and insulinlike growth factor levels are decreased. The percentage of body water and extracellular water is increased. Electrolytes, especially potassium and magnesium, are depleted. Levels of some enzymes (including lactase) are decreased, and circulating lipid levels (especially cholesterol) are low. Ketonuria occurs, and protein-energy malnutrition may cause a decrease in the urinary excretion of urea because of decreased protein intake. In both kwashiorkor and marasmus, iron deficiency anemia and metabolic acidosis are present. Urinary excretion of hydroxyproline is diminished, reflecting impaired growth and wound healing. Increased urinary 3-methylhistidine is a reflection of muscle breakdown and can be seen in marasmus.

Malnutrition also causes immunosuppression, which may result in false-negative tuberculin skin test results—and the subsequent failure to accurately assess for tuberculosis.

One way to further evaluate patients for protein-energy malnutrition is to look at his or her measurements, or anthropometrics. A clinical tool, known as a Z-score, can be used to describe a person's weight-for-height and height-for-age relative to the rest of the population. The calculator takes into account the individual's age in months, length in centimeters, and weight in kilograms. As discussed later, any score greater than -2 indicates no stunting or wasting, whereas any up to -3 indicates severe stunting or wasting; any score in between these indicates moderate stunting or wasting.

Another way to screen for malnutrition is the mid-upper arm circumference. It is an accurate and efficient screen method, especially when resources are limited. The measurement is taken using the circumference of the left upper arm at the halfway point between the tips of the shoulder and elbow.[46]

Procedures

Skin biopsy and hair-pull analysis may be performed (see Histologic Findings).

In an examination of skin biopsy samples taken from 20 children with protein-energy malnutrition (using hematoxylin and eosin staining, as well as staining for collagen, elastic fibers, mucopolysaccharides, and melanin), Thvaraj and Sesikeran found variable degrees of hypertrophy of the stratum corneum with atrophy of both the stratum granulosum and the prickle cell layers.[47]  A large amount of melanin was also found in the basal layer in all samples. Moreover, there was a reduced amount of collagen and associated crowding of elastic fibers.

In kwashiorkor, microscopic studies of hair have revealed a decrease in the proportion of anagen follicles. The anagen hairs were usually abnormal, exhibiting severe atrophy and shaft constriction. Most of the hairs examined were in the telogen phase, and the loss of pigment was consistent with the lack of melanin production during the telogen cycle.

In patients with marasmus, essentially no hairs were in the anagen phase, with a shift to the telogen phase. Many more broken hairs were found in patients with marasmus when compared to patients with kwashiorkor. Hair analysis has been advocated as a useful diagnostic procedure for both conditions.

McKenzie et al found that childhood malnutrition correlates with a reduction in the total melanin content of scalp hair.[48]

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain in patients with protein-energy malnutrition can show cerebral atrophy and ventricular dilatation. One study showed that 75% of children with protein-energy malnutrition had abnormal MRI findings, including all with cerebral atrophy and 75% with concurrent ventricular dilatation.[49]

X-rays of the hand and wrists can also be obtained to assess bone formation and determine if differences exist between chronologic age and comparisons to children of similar age and gender. Bone density scans can also be considered if it is believed that the patient is at risk for osteopenia; however, this imaging modality is generally not recommended in children.[50]

The World Health Organization (WHO) classification for children with protein-energy malnutrition is outlined below.[46]

Infants younger than 6 months 

No gold standard exists for infants younger than 6 months. It is recommended that clinicians follow the same criteria used for older children.[51]

Children aged 6-59 months

Z-score: Weight-for-height and height-for-age, relative to the rest of the population

Severe acute malnutrition (Any of the following three findings)

• Mid-upper arm circumference of less than 115 mm 
• Z-score less than -3
• Bilateral pitting edema

Moderate acute malnutrition

• Mid-upper arm circumference of 115-124 mm
• Z-score -2 to -3

Stunting (chronic malnutrition)

• Severe: Z-score less than -3
• Moderate: Z-score of -2 to -3

Severe acute malnutrition is managed in health facilities and therapeutic feeding centers in developing countries. However, limited coverage and impact, cost, cross infections, and high mortality rate have been observed.

In Ethiopia, mixed results were reported from implementation of a community-based outpatient management program of children with severe acute malnutrition and without medical complications.[52] Although the recovery rate was 64.9%, the likelihood of recovery was 2.6 times higher for children with kwashiorkor than for those with marasmus. Children residing in areas with less than 25 minutes of travel from the program site had a 1.53 times higher odds of recovery than those residing in regions with travel of 25 minutes or longer.[52]

Surgical care

In general, malnutrition is managed medically. However, some infections, particularly of the skin, may require surgical intervention for debridement and infection stabilization.

Children who are unable to obtain their nutritional requirements via oral intake may be candidates for enteral nutrition, which may require surgical placement of a feeding tube or other method of nutrition.

In both children and adults, the first step in the treatment of protein-energy malnutrition (PEM) is to correct fluid and electrolyte abnormalities and to treat any infections. The most common electrolyte abnormalities are hypokalemia, hypocalcemia, hypophosphatemia, and hypomagnesemia. Macronutrient repletion should be commenced within 48 hours under the supervision of nutrition specialists.

A 1980 double-blind study of eight children with kwashiorkor and skin ulceration found that topical zinc paste was more effective than placebo in healing areas of skin breakdown. Oral zinc supplements were also found to be effective.

The second step in the treatment of protein-energy malnutrition (which may be delayed 24-48 h in children) is to supply macronutrients by dietary therapy. Milk-based formulas are the treatment of choice. At the beginning of dietary treatment, patients should be fed ad libitum. After 1 week, intake rates should approach 175 kcal/kg and 4 g/kg of protein for children and 60 kcal/kg and 2 g/kg of protein for adults. A daily multivitamin should also be added.

For most of the cutaneous manifestations of inflammatory bowel disease, the primary therapy remains treatment of the bowel.

In a study of patients undergoing chemotherapy for advanced hepatic cancer, those who received a late-evening snack enhanced with branched-chain amino acids had improvements in energy metabolism parameters compared with control subjects.[45]

In discussing that protein-energy malnutrition is highly prevalent among peritoneal dialysis patients, Chung et al noted that although nutritional status assessments had improved over the decade from 1997 to 2007, no definitive single test was available to assess nutritional status.[53] Instead, they proposed that several different markers of nutrition must be used to understand nutritional status. For example, the treatment for peritoneal dialysis patients with malnutrition must be multifaceted, and they suggested using nontraditional strategies such as appetite stimulants, anti-inflammatory diets, and anti-inflammatory pharmacologic agents combined with more traditional forms of nutritional support to abate the protein-energy malnutrition.[53]

An intervention that brought "buddies" to the homes of the elderly who were at risk for protein-energy malnutrition was successful at decreasing such malnutrition.[54]

Long-term care

Patients should receive follow-up care with nutrition professionals and social services, and their growth and development should be monitored.

Diet

Nutritional support guidelines are available in the National Institute for Health and Clinical Excellence Nutrition Support in Adults quick reference guide.

Dietary Guidelines for Americans, 2015-2020, 8th edition, are available from the US Department of Health and Human Services and US Department of Agriculture.[55]

Activity

It is recommended that children who suffer from malnutrition be started early with exercises and physical therapy, as well as resources to encourage stimulation. Also, parents should be educated on the importance of activity. [56]

 

Any patient at risk for nutritional deficiency should be referred to a registered dietitian or other nutrition professional for a complete nutritional assessment and dietary counseling.

Other subspecialty referrals should be considered if findings from the initial evaluation indicate that the underlying cause is not poor nutritional intake. If signs indicate malabsorption, a gastroenterologist should be consulted. Further, in pediatric cases, a pediatrician, preferably one with experience in the management of protein-energy malnutrition, should oversee care of the patient. Any patient with significant laboratory abnormalities, as discussed previously, may benefit from consultation with the appropriate subspecialty (eg, endocrinology, hematology).

Children with poor nutrition secondary to inadequate intake and/or neglect should be referred to the appropriate social agencies to assist the family in obtaining resources and providing ongoing care for the child.

In the setting of malnutrition, the risk of refeeding syndrome represents an additional clinical challenge. Prolonged starvation followed by rapid feeding leads to this condition,[57]  in which there is resultant biochemical disturbance and physical symptoms/signs. Insulin release leads to the anabolic activity that underlies the pathophysiology of refeeing syndrome, and feeding overwhelms the dearth of electrolytes and micronutrients, which disrupts cellular function. Tissue edema, hypophosphatemia, and pathologic fluid shifts define refeeding syndrome.

Refeeding syndrome remains underrecognized, and patients on parenteral nutrition are considered to be at high risk. In a United Kingdom study, although refeeding syndrome was identified in 4% of cases of patients on parenteral nutrition, ​physicians only recognized it in half the cases.[57]  Using protocols with slower and lower rates of refeeding reduces deaths attributable to this syndrome.[57]

Death can be avoided if refeeding syndrome is recognized and patients are treated with dietary adjustment and clinical guidelines are followed.  A 13-month-old Kuwaiti male with marasmic kwashiorkor presented initially with normal levels of blood sugar and serum electrolytes.[58] However, by admission day 3, refeeding syndrome occurred with severe hypomagnesemia, hypokalemia, hypophosphatemia, and hypocalcemia, and the child then was given a lower calorie intake. The child survived following a gradual increase of caloric intake with vitamins, thiamine, and electrolyte supplementation.[58]

Refeeding syndrome guidelines are available in the National Institute for Health and Clinical Excellence Nutrition Support in Adults quick reference guide.

Refeeding syndrome can also occur in patients with anorexia nervosa who are replenished with food, vitamins, and electrolytes,[59]  although some investigators have argued that hypophosphatemia is not a problem in refeeding this patient population.[60]

Protein in 1 gram of food provides approximately 15 mg of phosphorus.[61]  Marasmic kwashiorkor is marked by phosphorus deficiency. Chronic phosphorus deficiency in humans causes proximal myopathy, and acute hypophosphatemia can precipitate rhabdomyolysis. Low blood phosphorus impedes the concentration of red blood cell synthesis as well as depletes stored levels of 2,3-diphosphoglycerate, which in turn affects hemoglobin's affinity for oxygen. Moreover, nervous system dysfunction (eg, apathy, weakness, intention tremors, a bedridden state) may occur in severe cases of phosphorus deficiency.[61]

Other groups at risk for refeeding syndrome include alcoholic individuals undergoing detoxification, extremely-low-birth-weight neonates who were intrauterine growth-restricted, cancer patients who have suffered from cachexia, and adults with kwashiorkor who receive enteral rather than parenteral feeding.

Prevention of protein-energy malnutrition begins with addressing the underlying cause. Economic and social factors are a major contributor to malnutrition. Extreme poverty leads to poor living conditions and often inadequate hygiene, as well as limited access to food and water. Children often do not receive the care they need. All of these can also lead to an increased risk of infections. In addition, diarrhea and vomiting can exacerbate the malnutrition due to water losses.

Prevention of malnutrition also must involve education. Educate mothers on the importance of breastfeeding and on how to adequately nourish their child. These women should also receive education regarding access to immunizations and the importance of fortification of food with necessary nutrients and vitamins.

World Health Organization management guidelines for severe acute malnutrition

Antibiotic Treatment[62]

• Outpatient (uncomplicated malnutrition): Oral (PO) amoxicillin 
• Inpatient (complicated malnutrition): intravenous (IV) benzyl penicillin or ampicillin, and then PO amoxicillin plus IV/intramuscular (IM) gentamicin 

Vitamin A treatment[51]

• Children with severe acute malnutrition should also receive 5000 IU vitamin A daily (not needed if receiving F-75 formula [75 kcal + 0.9 g protein per 100 mL], F-100 formula [100 kcal + 2.9 g protein per 100 mL], or ready-to-use therapeutic food)

Rehydration guidelines[51]

• Those with severe dehydration, but not in shock, should be rehydrated slowly (PO or via nasogastric [NG] tube) at around 5-10 mL/kg/hour for up to 12 hours.
• Children with dehydration and signs of shock should receive IV fluids if they are unable to be rehydrated via other means.

Feeding guidelines[51]

• Children with diarrhea should be treated in the same way as those without diarrhea.
• Inpatients: Provide F-75 in the stabilization phase and then administer ready-to-use therapeutic food over 2-3 days in the rehabilitation phase once they have an appetite. The recommended energy intake is 100-135 kcal/kg/day

Treating malnourished children with concomitant HIV[51]

Children infected with human immunodeficiency virus (HIV) should be started on antiretroviral therapy once they are stable.

• Use the same feeding approach as children without HIV infection.
• Administer zinc in addition to vitamin A.

US Health and Human Services, US Department of Agriculture dietary guidelines

Guidelines and key recommendations from Dietary Guidelines for Americans, 2015-2020, 8th edition, are outlined below.[55, 63]

Guidelines

1. Follow a health eating pattern across the lifespan.
2. Focus on variety, nutrient density, and amount.
3. Limit calories from added sugars and saturated fats, and reduce sodium intake.
4. Shift to healthier food and beverage choices.
5. Support healthy eating patterns for all.

Key recommendations

Consume a healthy eating pattern that accounts for all foods and beverages within an appropriate calorie level, such as the following:

• Vegetables from all subgroups
• Fruits
• Grains
• Fat-free or low-fat dairy
• A variety of protein foods
• Oils 

Limit the intake saturated fats, trans fats, added sugars, and sodium, as follows:

• Sugars and saturated fats: Consume less than 10% of calories per day of each.
• Sodium: Consume less than 2,300 mg per day.
• Alcohol: If consumed, consume in moderation (women: ≤1 drink per day; men: ≤2 drinks per day), and only by adults of legal drinking age.

Americans of all ages should meet the 2018 Physical Activity Guidelines for Americans, which can help in balancing calories and managing body weight.[64, 65]

There is no single medication to treat malnutrition. Management of patients with malnutrition starts with treating any metabolic derangements (eg, hypoglycemia, hypokalemia). If the patient is hypothermic, he or she should be warmed appropriately. If any signs of infection are present, select the appropriate antibiotic regimen.

It is recommend that children requiring inpatient treatment be started on broad spectrum antibiotics. The following is regimens are recommended:

• Ampicillin 50 mg/kg intramuscularly or intravenously (IM/IV) q6h and gentamicin 7.5mg/kg IM/IV q daily x 7-10 days (Clinicians can consider ceftriaxone 50 mg/kg IM/IV q daily for ill children or those in areas of high rates of antibiotic resistance.)

• Metronidazole 10-12 mg/kg orally (PO) q8h for those with a long course of diarrhea

• For oral antibiotics, amoxicillin, amoxicillin clavulanate, or a third-generation cephalosporin