Zinc Deficiency (Acrodermatitis Enteropathica)
Overview
Plain-Language Overview
Zinc deficiency, also known as Acrodermatitis Enteropathica, is a rare condition that affects the body's ability to absorb zinc, an essential mineral. This deficiency can cause a variety of symptoms including skin rashes, hair loss, and problems with the immune system. People with this condition may also experience diarrhea and delayed growth. It often appears in infancy or early childhood but can occur at any age. The condition is caused by a genetic mutation that affects zinc absorption in the intestines.
Clinical Definition
Acrodermatitis Enteropathica is a rare autosomal recessive disorder characterized by impaired intestinal absorption of zinc due to mutations in the SLC39A4 gene, which encodes a zinc transporter protein. This leads to systemic zinc deficiency, manifesting clinically with a triad of periorificial and acral dermatitis, alopecia, and diarrhea. The skin lesions are typically erythematous, scaly, and vesiculobullous, often involving the face, hands, feet, and genital areas. Patients may also present with growth retardation, immune dysfunction, and neuropsychiatric symptoms. Laboratory findings include low serum zinc and alkaline phosphatase levels. Diagnosis is confirmed by clinical presentation, biochemical tests, and genetic analysis. Untreated zinc deficiency can result in severe complications including increased susceptibility to infections and delayed wound healing. Lifelong zinc supplementation is required to manage the condition effectively.
Inciting Event
- Weaning from breast milk to zinc-deficient formula or diet in infants.
- Onset of malabsorption due to gastrointestinal disease.
- Genetic mutation leading to defective intestinal zinc absorption.
Latency Period
- Symptoms typically develop within weeks after weaning from breast milk.
Diagnostic Delay
- Misdiagnosis as eczema or other common dermatologic conditions.
- Lack of awareness of zinc deficiency in non-nutritional contexts.
- Variable presentation leading to delayed recognition of systemic symptoms.
Clinical Presentation
Signs & Symptoms
- Characteristic periorificial and acral dermatitis.
- Diarrhea due to gastrointestinal mucosal involvement.
- Alopecia with hair thinning or loss.
- Irritability and impaired immune function leading to recurrent infections.
History of Present Illness
- Periorificial and acral dermatitis with erythematous, scaly, and sometimes vesiculobullous lesions.
- Chronic diarrhea and failure to thrive in infants.
- Recurrent infections due to impaired immune function.
- Alopecia and delayed wound healing.
Past Medical History
- History of prematurity or low birth weight.
- Previous episodes of malnutrition or gastrointestinal disease.
- Known genetic disorders affecting zinc metabolism.
Family History
- Positive family history of acrodermatitis enteropathica or similar dermatologic conditions.
- Consanguinity increasing risk of autosomal recessive inheritance.
- Relatives with unexplained immune deficiencies or growth delays.
Physical Exam Findings
- Periorificial and acral dermatitis with erythematous, scaly, and sometimes vesiculobullous lesions.
- Alopecia characterized by patchy hair loss.
- Stomatitis with painful oral mucosal erosions.
- Nail dystrophy including brittle or ridged nails.
Diagnostic Workup
Diagnostic Criteria
Diagnosis of Acrodermatitis Enteropathica is based on clinical features of characteristic dermatitis, alopecia, and diarrhea combined with laboratory evidence of low serum zinc levels. Confirmation involves identifying mutations in the SLC39A4 gene through genetic testing. Additional supportive findings include low alkaline phosphatase and rapid clinical improvement following zinc supplementation.
Pathophysiology
Key Mechanisms
- Zinc deficiency impairs zinc-dependent enzymes and transcription factors, disrupting DNA synthesis and cell division.
- Deficient zinc leads to impaired immune function and defective skin barrier repair.
- Malabsorption or genetic defects in the SLC39A4 gene reduce intestinal zinc uptake.
| Involvement | Details |
|---|---|
| Organs | Skin: Organ exhibiting dermatitis and alopecia due to zinc deficiency. |
| Small intestine: Organ responsible for zinc absorption, affected in acrodermatitis enteropathica. | |
| Immune system: Organ system compromised by zinc deficiency resulting in increased infection risk. | |
| Tissues | Epidermis: The outer skin layer showing characteristic lesions in zinc deficiency. |
| Intestinal mucosa: Tissue responsible for zinc absorption, dysfunctional in acrodermatitis enteropathica. | |
| Immune tissue: Lymphoid tissues affected by zinc deficiency leading to impaired immune responses. | |
| Cells | Keratinocytes: Primary skin cells affected by zinc deficiency leading to characteristic dermatitis. |
| Lymphocytes: Immune cells requiring zinc for proper function, contributing to immunodeficiency in deficiency. | |
| Enterocytes: Intestinal cells involved in zinc absorption, impaired in acrodermatitis enteropathica. | |
| Chemical Mediators | Metallothionein: A zinc-binding protein regulating zinc homeostasis and protecting against oxidative stress. |
| Alkaline phosphatase: A zinc-dependent enzyme important for cellular metabolism and skin integrity. | |
| Tumor necrosis factor-alpha (TNF-α): An inflammatory cytokine whose regulation is affected by zinc status. |
Treatment
Pharmacological Treatments
Zinc supplementation
- Mechanism: Replenishes systemic zinc levels essential for enzymatic functions and immune response
- Side effects: nausea, vomiting, metallic taste, abdominal pain
Non-pharmacological Treatments
- Ensure a nutrient-rich diet with adequate zinc-containing foods such as meat, shellfish, and legumes.
- Implement nutritional counseling to prevent recurrence of zinc deficiency.
- Maintain good skin hygiene to reduce secondary infections in affected areas.
Prevention
Pharmacological Prevention
- Lifelong oral zinc supplementation to maintain adequate serum levels.
Non-pharmacological Prevention
- Early diagnosis and nutritional counseling to ensure adequate dietary zinc intake.
- Avoidance of factors that impair zinc absorption, such as phytate-rich diets.
Outcome & Complications
Complications
- Severe immune deficiency increasing risk of life-threatening infections.
- Growth retardation and developmental delays in children.
| Short-term Sequelae | Long-term Sequelae |
|---|---|
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Differential Diagnoses
Zinc Deficiency (Acrodermatitis Enteropathica) versus Atopic Dermatitis
| Zinc Deficiency (Acrodermatitis Enteropathica) | Atopic Dermatitis |
|---|---|
| Presence of vesiculopustular periorificial dermatitis and acral erosions. | Chronic, pruritic eczema with lichenification mainly on flexural surfaces. |
| Low serum zinc levels confirm zinc deficiency. | Elevated serum IgE levels and personal or family history of atopy. |
| Onset in infancy with associated diarrhea and alopecia. | Absence of periorificial and acral vesiculopustular lesions. |
Zinc Deficiency (Acrodermatitis Enteropathica) versus Biotin Deficiency
| Zinc Deficiency (Acrodermatitis Enteropathica) | Biotin Deficiency |
|---|---|
| Characteristic periorificial and acral dermatitis with vesiculopustular lesions. | Presence of alopecia and seborrheic dermatitis primarily affecting the face and scalp. |
| Serum zinc levels are low, confirming zinc deficiency. | Neurologic symptoms such as depression, lethargy, and hallucinations are common. |
| Onset in infancy with diarrhea and failure to thrive. | Laboratory tests show low serum biotin levels and elevated 3-hydroxyisovaleric acid in urine. |
Zinc Deficiency (Acrodermatitis Enteropathica) versus Essential Fatty Acid Deficiency
| Zinc Deficiency (Acrodermatitis Enteropathica) | Essential Fatty Acid Deficiency |
|---|---|
| Typical vesiculopustular and erosive dermatitis around orifices and acral areas. | Presence of scaly dermatitis predominantly on the extensor surfaces and trunk. |
| Serum zinc deficiency is diagnostic. | Increased transepidermal water loss leading to dry, flaky skin without vesiculopustular lesions. |
| Associated with diarrhea and alopecia in infancy. | Serum fatty acid profile shows low levels of linoleic and alpha-linolenic acids. |