WHAT’S YOUR DIAGNOSIS?
ANSWER: DERMATOPATHOLOGY OF SEVERE MALNUTRITION
The sweat chloride test result (which showed moderate elevation of sodium and chloride levels) was consistent with cystic fibrosis (CF). CF commonly results in malnutrition; however, it rarely presents as a rash. Although GI malabsorption, diarrhea, and failure to thrive would commonly prompt an investigation for CF around the sixth month of life, the complex of nutritional deficiencies necessary for a rash to result are not always present in CF-associated malnutrition.
PATHOPHYSIOLOGY OF THE RASH
The findings from one case suggest that development of a malnutrition-associated rash in CF is multifactoral.1 The authors reported biochemical evidence of essential fatty acid deficiency in both a 4-month-old girl who had an erythematous, desquamating, periorificially accentuated rash associated with malnutrition and her 2-year-old sister, who had concurrently received the diagnosis of CF but had no rash or sign of malnutrition.1 Pathogenesis of the rash appears to involve a complex interaction among congenital deficiencies of essential fatty acids, zinc, protein, and possibly copper that leads to disordered prostaglandin metabolism or cytokine production, or free radical–induced damage to cellular membranes from a lack of nutrient-derived protective antioxidants.2
This patient had many of the features of kwashiorkor, including edema; lethargy; failure to thrive; hypoalbuminemia; elevations in liver enzyme levels such as are seen in fatty liver; anemia; and a generalized, desquamating, erythematous rash. The pallor and facial and pedal edema had signaled significant progression to anemia and hypoalbuminemia.
MANIFESTATIONS OF CF ASSOCIATED WITH PANCREATIC INSUFFICIENCY
Although CF has a complex pathophysiology that is unlike other forms of malabsorption, kwashiorkor secondary to poor nutrient intake results in a syndrome that can provide insight into CF associated with pancreatic insufficiency. This infant’s skin inflammation stems from severe malabsorption that is caused by the inability to excrete significant quantities of pancreatic lipase—a result of pancreatic duct obstruction from thickened secretions produced by dysfunctional CF transmembrane conductance regulator proteins.
Paradoxically, some patients with CF can present with delayed transit of GI contents with obstruction, whereas others—such as this infant—have increased GI motility. In this patient, an increase in undigested fatty acids in the small-bowel lumen caused a chyme transit acceleration with further malabsorption of fatty acids, carbohydrates, and other essential nutrients—particularly fat-soluble vitamins—and amino acids, iron, and zinc. This may explain why her rash resembled acrodermatitis enteropathica of zinc deficiency.3 Prostaglandin metabolism alteration may account for some of this variability.4 However, the exact mechanisms of this rare presentation remain elusive.
Other clinical and laboratory signs of severe malnutrition associated with CF and pancreatic insufficiency typically include sparse hair, lack of mucous membrane involvement, elevated liver enzyme and ferritin levels, and low levels of serum trace metals.5 This infant was noted to have all of these signs, although the trace metal results from previous visits could not be confirmed.
CF should be included in the differential diagnosis of an infant with a red, scaly rash, especially when failure to thrive, hypoproteinemia, and edema are also present. Recognition of the rash as a sign of CF complicated by protein-energy malnutrition will allow earlier diagnosis and treatment, and it may improve the outcome for patients with this condition.6
The following, more common, conditions may present similarly but can be differentiated by key elements in the history and physical findings:
•Dermatophytosis typically appears as annular, tinea plaque colonies with raised edges or perifollicular pustules. This rash spares moister skin creases and is unresponsive to antifungal topical cream.
•Impetigo begins as a fluid-filled papule, which ruptures and forms a honey crust, and spreads rapidly. This eventually disfiguring condition has a predilection for the face.
•Seborrheic dermatitis is very uncommon in infants and occurs mostly in oil-producing skin around the scalp and face. It also typically responds at least partially to topical antifungal agents.
•Contact dermatitis appears after contact with a chemical irritant or antigen and adheres to a specific distribution, consistent with possible contact exposure.
•Dermatitis herpetiformis, a deposition of IgA in the papillary dermis associated with gluten sensitivity, manifests as intensely pruritic lesions. These typically appear as papules or plaques with herpetic-like vesicles primarily on extensor surfaces. There was no evidence of gluten in this patient’s diet.
•Breast milk allergy, an IgE-mediated process, is generally limited to vomiting and diarrheal illness related to intake. In the event of anergic manifestations, patients may have atopic dermatitis, rhinitis, or even wheezing.
•Psoriasis appears as scaly erythematous plaques on extensor surfaces and is quite rare in infancy. Patients may have a family history of this presumed autoimmune disease.
•Acrodermatitis enteropathica of zinc deficiency typically appears during the first few months of life, often after cessation of breastfeeding—which did not occur in this case. This rash—which consists of erythematous, periorificial, acral plaques and patches—and the associated diarrhea are similar to the findings in this patient. In fact, zinc deficiency is suspected to have played a role in this case.
TREATMENT AND OUTCOME
Figure – The happy infant 5 months after rash first appeared has no signs of dermatopathology from severe malnutrition. Growth parameters have steadily improved, but she still lags behind her peers.