What is the most likely cause of an eczematoid rash at intertriginous areas in a patient receiving prolonged Total Parenteral Nutrition (TPN)?

Zinc Deficiency Causes Eczematoid Rash in Intertriginous Areas with Prolonged TPN

The eczematoid rash at intertriginous areas in a patient receiving prolonged total parenteral nutrition is caused by zinc deficiency.

Evidence for Zinc Deficiency

Zinc deficiency is a well-documented complication of prolonged total parenteral nutrition (TPN) when zinc supplementation is inadequate. According to ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition, zinc deficiency is commonly reported in patients on long-term PN and is specifically associated with a "typical skin rash" 1.

The characteristic dermatologic manifestation of zinc deficiency includes:

• Moist eczematoid dermatitis, particularly in intertriginous areas
• Typically affects skin folds and periorificial regions
• May be accompanied by alopecia in more severe cases

Pathophysiology and Clinical Presentation

Zinc is an essential trace element involved in:

• Metabolism of energy, proteins, carbohydrates, lipids, and nucleic acids
• Essential for tissue accretion and wound healing
• Component of over 70 different enzymes, including alkaline phosphatase and RNA/DNA polymerase 2

When zinc deficiency develops during TPN:

1. Initial manifestation is often the characteristic eczematoid rash
2. The rash typically appears in intertriginous areas (skin folds)
3. The condition resembles acrodermatitis enteropathica, a genetic disorder of zinc malabsorption 3
4. The skin lesions are often painful, erythematous, and moist 4

Supporting Clinical Evidence

Multiple case reports and studies have documented this association:

• Patients receiving prolonged TPN without adequate zinc supplementation develop characteristic skin lesions 5
• These skin manifestations respond dramatically to zinc supplementation 4
• In one documented case, a patient developed characteristic skin lesions after zinc was removed from their TPN solution, with prompt resolution after zinc was reintroduced 3

Differential Diagnosis

Other potential causes of rash during TPN that should be ruled out:

• Fatty acid deficiency - typically presents with more generalized dry, scaly dermatitis rather than moist eczematoid lesions in intertriginous areas
• Hypersensitivity reactions - usually more urticarial in nature and related to components like polysorbate 6
• Copper deficiency - primarily presents with hematologic abnormalities (anemia, neutropenia) rather than skin manifestations 7
• Niacin deficiency - causes pellagra with a photosensitive dermatitis rather than an intertriginous rash

Management

When an eczematoid rash develops in intertriginous areas during prolonged TPN:

1. Check serum zinc levels (though normal levels don't exclude deficiency)
2. Ensure adequate zinc supplementation in TPN
3. According to guidelines, zinc requirements in TPN are:
   • 400-500 μg/kg/day in preterm infants
   • 250 μg/kg/day in term infants to 3 months
   • 100 μg/kg/day for infants 3-12 months
   • 50 μg/kg/day in children >12 months (maximum 5 mg/day) 1
   • For adults with TPN, 3-4 mg/day is typically required 7

Clinical Pearls and Pitfalls

• Patients with high gastrointestinal fluid losses (ileostomy, diarrhea) have significantly higher zinc requirements 1
• Serum zinc levels should be monitored regularly in patients on long-term TPN
• The response to zinc supplementation is typically rapid and dramatic, with skin lesions improving within days
• Zinc deficiency can occur even when standard trace element solutions are used if requirements are increased

In conclusion, when evaluating an eczematoid rash in intertriginous areas in a patient on prolonged TPN, zinc deficiency should be the primary diagnostic consideration, and appropriate supplementation should be promptly initiated.