Section 10. Nutritional and Metabolic Disorders

This syndrome results from inadequate absorption or dietary intake of zinc. Figure 10-1 shows erythema, crusting, and fissuring of the perioral skin and cheeks. The eruption that is pictured here may be preceded by blisters. Other features of acrodermatitis enteropathica include stomatitis, paronychia, and alopecia.

The diaper area lesion that is seen in this figure is diffusely erythematous and has a sharply marginated border on the abdomen. Acrodermatitis enteropathica may be inherited in an autosomal recessive fashion. This form of the disease seems to be related to an inability to absorb zinc.

Figure 10-3 shows a highly characteristic picture of the cutaneous changes of acrodermatitis enteropathica around the anus, the buttocks, and on the perineum. Note how psoriasiform this lesion and those on the feet in Fig. 10-4 are. The full-blown picture of acrodermatitis enteropathica goes far beyond the typical changes of skin and hair. Affected children have severe diarrhea, growth retardation, and irritability. Without treatment, the disease follows a progressive course and may even be fatal. The crucial relationship between acrodermatitis enteropathica and zinc deficiency was discovered in 1973. The child with suspected acrodermatitis enteropathica should be evaluated for a low zinc level or a low alkaline phosphatase level when zinc levels are normal or low normal. (Blood must be drawn in plastic, nonrubber stoppered tubes to avoid the possibility of zinc contamination.) Treatment with dietary zinc supplementation leads to a dramatic resolution of all symptoms and must be maintained indefinitely.

Acquired acrodermatitis enteropathica is seen in infants who have received parenteral alimentation lacking sufficient zinc and, rarely, in breast-fed premature infants who have larger zinc requirements. Occasionally, acrodermatitis enteropathica in a full-term breast-fed infant may be the result of low levels of zinc in the breast milk.

The patient with acquired acrodermatitis enteropathica requires temporary zinc replacement. The differential diagnosis of this eruption includes psoriasis, biotin and multiple carboxylase deficiencies, essential fatty acid deficiencies, and cystic fibrosis.

Kwashiorkor is a type of protein energy malnutrition. It is seen most commonly in developing countries, and onset tends to occur after weaning. At that time, the balance of protein and carbohydrate in breast milk is replaced by a diet that contains almost exclusively carbohydrates. The initial signs are diarrhea, irritability, and edema of the hands and feet. Small dark patches appear at pressure points of the elbows, ankles, wrists, and knees, and then spread. The patches have a sharp border and tend to peel; the superficial desquamation in these areas is often likened to the appearance of flaking paint or enamel. As the condition progresses, there develops a generalized red-brown discoloration. Other findings include fissuring at the edges of the mouth (Fig. 10-7) and the development of coarse, hypopigmented hair. Photosensitivity and easy bruising may also be present. The child with severe kwashiorkor appears extremely apathetic and has generalized edema. Pictured in Fig. 10-8 is a child with areas of desquamation and anasarca. Kwashiorkor carries a high mortality rate. With timely dietary intervention, it can often be reversed.

Pellagra is a disease caused by inadequate dietary intake of niacin. It is now seen in parts of the world where dietary intake of tryptophan, an amino acid precursor of niacin, is inadequate. In particular, diets that consist largely or exclusively of maize or millet predispose to this disease. The signs and symptoms of pellagra are often remembered by the mnemonic four Ds: dermatitis, diarrhea, dementia, and death. The classic cutaneous changes are inflamation, hyperpigmentation, and scaling in symmetric distribution and in areas exposed to heat or sunlight. Typical areas of involvement are the hands and forearms, legs and feet, and face and neck. Figure 10-9 shows moderate changes on the feet and legs. Figure 10-10 shows the scaling dermatitis on the face and an angular cheilitis. Edema and inflammation of the tongue are also common features of pellagra. The addition of supplemental niacin to the diet brings a quick resolution to the disease.

This is a rare metabolic disorder that is inherited in autosomal recessive fashion. Children with the disease have a defect in the enzyme phenylalanine hydroxylase and are unable to convert phenylalanine to tyrosine. There are several associated cutaneous changes. Affected individuals have fairer skin and lighter-colored hair than their normal siblings; Caucasians with the disease typically have blond hair and blue eyes. Because the melanocytes of patients with phenylketonuria are less able to manufacture melanin, patients tend to sunburn easily. In addition, an eczematous dermatitis is a common component of phenylketonuria. The lesions may resemble atopic dermatitis in morphology and distribution, as in these figures. In other patients, the dermatitis is more widespread. Treatment of this disease consists of dietary restriction of phenylalanine. The early institution of this diet limits the possibility of severe intellectual impairment which is the most significant aspect of the disease.

This is among the more common porphyrias; onset is usually during early childhood. The typical presentation of this disease features the development of pruritus and burning of the skin in areas of recent sun exposure. These sensations may be accompanied by erythema, edema, and vesiculation. Over time, superficial scarring and a waxy thickening of the involved areas develop. These changes, as seen on the hands and feet, are illustrated here. The bridge of the nose is another common area of involvement. Children with erythropoietic protoporphyria have inherited a deficiency of the enzyme ferrochelatase, which normally converts protoporphyrin to heme. The disease can be readily diagnosed from the combination of the clinical findings outlined above and an elevated free erythrocyte protoporphyrin level. The most serious complication is the development of hepatic involvement. Treatment of the skin disease consists of avoidance of the sun and oral therapy with beta-carotene.

This is a rare autosomal recessive disease that is caused by the deposition of hyaline material in the skin and mucous membranes. Laryngeal involvement may be present from birth and eventually produces a characteristic hoarseness in every affected individual. Cutaneous disease begins during the first 2 years of life and consists of papules, nodules, and areas of thickening and hyperkeratosis. The cutaneous lesions on the alae nasi and in the choanae are shown in Fig. 10-15. In Fig. 10-16, the mucosal surface of the lower lip is extensively involved with the characteristic papules. Not shown here are the numerous small papules that dot the free margins of the eyelids. The disorder is due to a defect in the extracellular matrix protein 1 gene mapped to chromosome 1q21.

Pictured here are a plaque and lesions of smaller sizes on and around the elbow. Most children with lipoid proteinosis continue to develop additional lesions during adult life. Lesions in the mouth and oropharynx cause the most serious sequelae. The tongue may become thick and bound down, and dysphagia and respiratory obstruction may result from lesions in the pharynx and larynx. Finally, intracranial calcifications are a common feature of lipoid proteinosis. For most patients, these are asymptomatic but seizure disorders may occur.

This inherited condition results in the accumulation of chondroitin sulfate B in the skin and other organ systems. Dwarfism and an unusual facial appearance are also aspects of the disease. This figure is an excellent representation of shagreen skin, an appearance that is also seen in tuberous sclerosis. Shagreen refers to a type of leather that is embossed with knobs by processing and then variably stained.

Xanthomas are papules or nodules of the skin or mucous membranes that contain lipids. The appearance of xanthomas during childhood should prompt a thorough search for underlying systemic disease. The yellowish papules seen in Fig. 10-19 are a form of planar xanthoma. These may occur on any part of the body and may be an indicator of a hereditary lipoproteinemia, diabetes mellitus, or liver disease. Multiple myeloma and histiocytosis X are less common etiologies. The patient pictured here has biliary cirrhosis.

The lesions illustrated here are typical of xanthoma striatum palmare, a form of planar xanthoma. This patient also has biliary cirrhosis. Note how the yellowish papules and plaques follow the creases of the fingers and the palmar folds. The familial hyperlipidemias, particularly types II, III, and V, may present with an identical clinical picture. Patients with these disorders are at high risk for ischemic heart disease.

These small papules on the dorsa of the feet are also xanthomas. The patient is a 4-year-old child with type II hyperlipoproteinemia. This is an autosomal dominant condition in which there may be massive elevations in serum cholesterol. Individuals with this disease often develop ischemic heart disease during young adulthood. The recognition of the cutaneous lesions is important in identifying children who may require dietary or medical management of their hypercholesterolemia.

These yellow-red nodules, which often occur on the elbows and knees, are termed tuberous xanthomas. They may also be found in other areas where ordinary trauma is common, e.g., buttocks, knuckles, and heels. Similar lesions that overlie extensor tendons are sometimes called tendon xanthomas. Lesions of this sort are almost always caused by a hyperlipoproteinemia and should prompt investigation of serum cholesterol and triglycerides. Types II, IV, and V are those most commonly associated with tuberous and tendon xanthomas.

Not all xanthomatoses are rooted in abnormalities of cholesterol metabolism or other systemic disease. In this illustration, xanthomatous papules that developed in a lymphedematous leg are shown. Since serum lipids are normal, local causes stemming from the lymphatic obstruction must account for the lesions. The condition does not have the serious import of those xanthomatoses associated with abnormalities of serum lipids.

When calcification occurs in the skin, it may represent an isolated local event, or it may be a sign of an underlying systemic disease. The lesion pictured here is a solitary nodular calcification. These sometimes result from local trauma, such as an insect bite, or from the rupture of an epidermal cyst (dystrophic calcinosis cutis). When such nodules occur on the face of an infant, they are usually idiopathic and of no medical significance.

The nodular calcifications pictured here also turned out to be idiopathic. However, grouped calcifications like these may also be seen in children with CRST syndrome (calcinosis cutis, Raynaud's phenomenon, sclerodactyly, telangiectasia) or dermatomyositis. Pseudoxanthoma elasticum and Ehlers-Danlos syndrome are other causes. The so-called metastatic calcinosis cutis, with widespread precipitation of calcium salts, is a sign of abnormal calcium metabolism and may result from parathyroid tumors, chronic renal failure, or vitamin D intoxication.