A 15-month-old girl was admitted with the chief complaint of lethargy. During the several days before admission to the hospital, she had decreased activity and ate poorly. There was no history of vomiting, diarrhea, fever, or other symptoms. During a scheduled appointment in the dermatology clinic for follow-up treatment of eczema, she was admitted to the hospital because of her nutritional status.
Her medical history was remarkable for eczema, which had been treated with a variety of topical steroids since she was approximately 9 months old. During the previous 3 months, as part of diet therapy instituted by her family, she was placed on a diet of rice milk and table food. She generally drank approximately 40 ounces of rice milk each day, in addition to eating a small amount of table food.
Her medical history was also remarkable for one urinary tract infection that was associated with vesicoureteral reflux, for which she received trimethoprim-sulfamethoxazole prophylaxis. Her birth history was unremarkable. DevelopmentalIy, she crawled, fed herself, pulledto-stand, babbled, and had a pincer grasp. Her receptive vocabulary was normal for age. Her family history was unremarkable.
On physical examination, she was pale, irritable, and malnourished. Vital signs were unremarkable. Her weight and length were 6.8 kg and 66 cm, respectively, both markedly below the 5th percentile. Her growth chart showed she grew along the 25th percentile until 4 months, when she began to fall off in weight; she fell below the 5th percentile at 9 months. She was 1 kg below her 9-month weight at this evaluation. Her length had been growing normally until 12 months, when it began to fall off. Her head circumference began falling off ages 6 and 9 months.
She had multiple erythematous plaques on her lower back that had a cracked glass appearance. There were angular erythematous plaques in her popliteal fossae bilaterally, with some scaling and intense erythema in the diaper region extending onto her thighs. HEENT exam was unremarkable. The lungs were clear. Cardiac exam was normal. The abdomen was soft without masses or organomegaly. There was non-pitting edema of the feet and hands bilaterally. The remainder of her physical examination was unremarkable.
Her laboratory evaluation included hemoglobin 6.2 g/dL, MCV 86. The white blood cell and differential counts were normal; platelet count was 133,000/mmp 3. The electrolytes were unremarkable. The total protein was 3.6 g/dL, albumin was 1.4 g/dL, AST was 86 IU, ALT was 173 IU, and phosphorus was 3.5 mg/dL. The prothrombin time was prolonged at 19.7 seconds, while the partial thromboplastin time was normal.
Robert Listcrnick, MD, moderator: I know everyone is dying to know which nutrients are in rice milk. This formulation contains l g of protein, 2 g of fat, and 25 g of carbohydrate per 8 oz serving. It has 2% of the Recommended Daily Allowance of calcium and no other minerals. Although I believe that the source of this child's nutritional problems is clear, in general, how should one approach a child with failure to thrive?
Kim Dilley, MD, general academic pediatrician: More so than with most diagnoses, the history is of paramount importance in cases of failure to thrive. Perhaps the most important piece of information is whether the caloric intake is sufficient for the infant's needs. If the infant is taking in sufficient calories and not gaining weight, then he or she may have increased caloric needs - a patient who has cardiopulmonary disease or a malabsorptive disorder such as cystic fibrosis or celiac disease, for example. Alternately, the information given by the parents is wrong, she truly is ingesting enough calories, and the child has a diagnosis of psychosocial failure to thrive. If, by nistory, the child is not eating enough calories to gain weight, he or she may suffer from a variety of pathologic processes such as neurologic dysfunction, which precludes normal sucking and swallowing, or cardiopulmonary disease, which prevents her from breathing and eating at the same time. This child clearly has inadequate caloric intake.
Timothy Sentongo, MD, pediatric gastroenterologist: I cannot overemphasize the importance of examining the growth chart in assessing children with failure to thrive. The pattern of growth of this child - weight falling off first, followed by length and ultimately head circumference - is classic for inadequate caloric intake.
Dr. Listernick: I agree. However, I have seen many children with inadequate caloric intake as a reason for failure to thrive, and I rarely have come across such a growth curve as this child's.
Stanford Shulman, MD, pediatrie infectious disease specialist: In the underdeveloped world, one might see such a growth chart with an infant who had acquired tuberculosis, HIV, or another chronic infection in the first year of life. With that said, I've never seen such a phenomenon in the United States.
Dr. Listernick: Does this child have kwashiorkor?
Dr. Sentongo: First, we should get our definitions straight. Kwashiorkor refers to children who are edematous and are between 60% and 80% of expected weight for age. Children who are less than 60% of expected weight for age have marasmus; if these children have edema, they suffer from marasmic -kwashiorkor. These are all forms of protein-energy malnutrition. Kwashiorkor occurs as a result of protein malnutrition in excess of caloric deprivation, leading to the formation of edema.
In the developing world, kwashiorkor is unfortunately quite common in areas of war or great social turmoil, where the food source has been interrupted and children are fed diets high in carbohydrates and low in protein. In these areas, chronic infections and diarrhea may lead to excessive protein losses, exacerbating the formation of edema. In industrialized nations where access to food is not as great a problem, we may see children present with kwashiorkor if they have protein-losing enteropathies, such as cystic fibrosis.
Dr. Listernick: What are the clinical manifestations of kwashiorkor?
Dr. Sentongo: Constitutional symptoms such as lethargy or irritability are common. Failure to thrive may be masked by the development of edema. A flaky dermatitis with thin, sparse hair is common. Hepatomegaly from fatty infiltration of the liver is a late manifestation. If the malnutrition is severe enough to affect brain growth, the long-term developmental outcome may be poor.
Dr. Listernick: How should we provide this child with nutritional rehabilitation?
Dr. Sentongo: In children with either marasmus or kwashiorkor, there is a real danger of refeeding syndrome. This is especially true in the child with kwashiorkor, in whom massive fluid shifts may precipitate the sudden onset of congestive heart failure. If this happens, it usually develops during the first week of refeeding.
Reintroduction of protein and electrolytes to a chronically malnourished child may lead to rapid expansion of the intracellular fluid volume and increased glycogen synthesis, which in turn leads to hypokalemia and hypophosphatemia. Mild vitamin deficiencies may prevent the desired anabolic response to refeeding. Ultimately, this may lead to congestive heart failure, arrhythmias, and sudden death.
Dr. Listernick: How can we safely refeed this child?
Dr. Sentongo: First, she should have continuous cardiorespiratory monitoring during the initial week of refeeding. Unexplained tachycardia may be a hint of impending cardiac failure. You would expect children with kwashiorkor to lose weight initially as their serum albumen returns to normal and they lose their edema. In kwashiorkor, even more than with marasmus, the refeeding should begin at a very slow rate, with 1 mg/kg daily at most of protein. Gradually, the protein concentration and calories can be increased. Careful attention should be paid to the serum electrolytes, particularly the serum potassium and phosphorus.
Dr. Listernick: Does the osmolarity of the refeeding formula matter?
Dr. Sentongo: Chronic malnutrition may lead to villous atrophy. High osmolarity formulas with complex carbohydrates and proteins may lead to malabsorption and diarrhea. I generally start with an elemental formula composed of amino acids, simple sugars, and easily absorbed, medium-chain triglycérides. This patient initially developed ascites, vomiting, and diarrhea before she began tolerating the feedings.
Dr. Listernick: Moving on, what do we know about her initial skin disease?
Anthony Mancini, MD, pediatrie dermatologist: I didn't see her, but I believe she had a predominantly periorificial erosive dermatitis. Some common skin disorders, such as psoriasis or seborrheic dermatitis, might present this way in an infant. However, from the descriptions that I have heard, I believe that her skin disease at the beginning of this whole illness was fairly minimal. At the time of her hospitalization, looking at the entire picture of kwashiorkor and skin disease, I believe that she has a nutritional deficiency dermatosis. This has a fairly characteristic presentation in children, with periorificial predominance involving the groin, buttocks, and mouth. It is very inflammatory and erosive; often it is crusted and appears infected.
In the setting of this dermatosis and profound malnutrition, several diagnoses should be considered. Zinc deficiency may be present as a primary autosomal recessive disorder (acrodermatitis enteropathica) or as a secondary process. Cystic fibrosis also may present with a deficiency dermatosis, even before there are clinical manifestations of the pulmonary or gastrointestinal systems. Other conditions in the differential diagnosis would include biotin or biotinidase deficiency, essential fatty acid deficiency, branch chain aminoacidurias such as methylmalonic aciduria, and a variety of immunodeficiency syndromes. Finally, this rash may be seen in kwashiorkor. Classically, it's described as a "flaky paint" dermatitis, and presents as an erosive dermatitis with patches of desquamation. Associated edema is common in this setting.
Dr. Listernick: Her entire skin disease may be totally due to her underlying poor nutritional status?
Dr. Mancini: We've described 12 such children, all of whom had this dermatosis as a result of inadequate diets due to "food faddism," restrictive diets related to assumed food allergies, or ignorance of proper nutrition. Six of the 12 patients had secondary zinc deficiency, as measured by serum zinc levels. This child's zinc level was at the lower end of normal, and I recommended zinc supplementation.
Dr. Listernick: What about her hematologie abnormalities?
Elaine Morgan, MD, pediatrie hematologist: It's difficult to explain. While the bone marrow may be affected by malnutrition, I would have expected all of the cell lines to be depressed; the white blood cell count and differential were normal. The patient did have a bizarre smear with burr cells, schistocytes, and target cells. These abnormalities may have been the result of a specific vitamin or mineral deficiency, such as copper or vitamin E, which we didn't identify.
Dr. Listernick: What about vitamin C deficiency?
Dr. Mancini: The skin disease of the vitamin deficiencies looks very different. For instance, vitamin C deficiency classically presents with 4pericapiUary leak and hemorrhage (classic scurvy).
Dr. Listernick: This child's malnutrition was the result of a proteinand calorie-deficient diet due to the perceived relationship of food allergies to eczema. What are the data about this relationship?
Jacqueline Pongracic, MD, pediatrie allergist: There's obviously a bit of controversy. In evaluating the possibility of such a relationship, a thorough history is very important. One would need to establish a careful dietary history, including the presence of breastfeeding, the timing of introduction of all foods, and the relationship of the foods and worsening of the skin condition. In addition, the type and quality of the dermatosis is important. Even the diet of mothers who are breastfeeding may influence a child's skin disease, because food antigens are transmitted through the breast milk.
The published data show approximately 15% to 30% of children who have eczema have an immunemediated, food-related component to their skin diseases. As an allergist, I don't feel that it's appropriate to look for this food-related component in every child with mild eczema. Rather, I take into account a number of factors including dietary history, a family history of atopy, and level of involvement. If I decide to pursue the diagnosis, I will perform skin-prick testing on areas of uninvolved skin with the possible offending foods.
A skin-prick test has a very high negative predictive value; if the test is negative, the likelihood of the food causing an allergic response is extremely low. However, the specificity of the test is only approximately 50%. In other words, a positive skin-prick test has about as great a likelihood of being a false positive as it does being a true positive.
Dr. Listernick: Which foods are commonly involved?
Dr. Pongracic: The two most common foods are milk and egg. If the skin-prick test is positive, I recommend a 2- to 4-week trial of dietary avoidance of the antigen. At the end of the trial, if there's no demonstrable improvement, we'll put the antigen back into the diet and move on.
Dr. Listernick: How do the dermatologists approach this subject?
Dr. Mancini: Generally in the same way. Our literature agrees that 20% to 30% of children with atopic skin disease have food allergy as a trigger. We consider allergy evaluation primarily in children with severe, recalcitrant disease. Parents of these children often are desperately looking for the one or two triggers to the skin disease. However, food elimination rarely makes a big impact, even in those children who have positive skin-prick tests. Too often, I see children with eczema who are inappropriately placed on severe elimination diets without any substantive proof of their efficacy.
Dr. Listernick: I've seen several children who had vitamin D-deficient rickets as a result of an inappropriate milk elimination diet.
Robert Tanz, MD, general academic pediatrician: There also have been reports of children placed on gluten-free diets for a wheat allergy or celiac disease without appropriate testing. At a minimum, normal children are being placed on severely restrictive diets that are difficult to maintain. At worst, children who really have celiac disease are being inappropriately managed.
Dr. Listernick: This child was nutritionally replenished during several weeks in the hospital. In reviewing the growth chart, she clearly began falling off in weight before the introduction of the rice milk. She had been seeing her family practitioner during this period of poor weight gain and then actual weight loss, who, as far as we know, had done nothing about it I can't relate more of the private social details concerning this family. Given what we know about malnutrition, early brain growth, and development, is it safe to send this child home?
Dan Leonhardt, MD, child abuse specialist: There isn't an easy answer. On the surface, this child was loved, fed, cared for, and seen regularly by a physician. The family and the physician are both still somewhat resistant to the idea that this child's nutritional status is solely the result of the rice milk and inadequate caloric diet. For the moment, the wisest course would be to send her home with close supervision and weight monitoring performed by us, as well as their health practitioner.
Dr. Listernick: We don't want to make any assumptions until we have all the facts. However, assuming it's true that the physician ignored the warning signs and is unaccepting of the new dietary therapy, what options as consultants do we have?
Elaine Morgan, MD, pediatrie oncologist: We certainly don't police ourselves as much as we should. However, our ability to report gross physician incompetence to the appropriate authorities has become increasingly hampered. I recently had the experience of trying to report to the state gross incompetence by a health care deliverer that led to the death of one child and placed a second child at risk. The families of these children were completely devoted to this provider and would not give me permission to release their information to the reporting agency. As the confidentiality statutes prevented me from releasing the children's names on my own, the authorities said that their hands were tied, and the allegations went uninvestigated.
Dr. Listernick: Hopefully we can enlist this physician's support and it won't come to that with this family. Thank you, everybody.