Acrodermatitis enteropathica (AE) is a rare disorder associated with impaired zinc metabolism, leading to a variety of clinical manifestations primarily affecting the skin, hair, and nails. This condition can be either congenital or acquired, and is characterized by a deficiency of zinc, an essential mineral that plays a pivotal role in gene regulation, immune function, and enzyme activity. AE is known by several names, including congenital zinc deficiency, Brandt syndrome, and Danbolt-Cross syndrome. Zinc is vital for numerous physiological functions, and its deficiency disrupts normal cell growth and repair, leading to the hallmark symptoms of AE.
Pathophysiology and Etiology
The congenital form of AE is an autosomal recessive disorder that results from a defect in the SLC39A4 gene, located on chromosome 8q24, which encodes for a zinc transporter responsible for the absorption of zinc in the small intestine. This defect impairs the body’s ability to absorb zinc from the gastrointestinal tract, leading to a systemic deficiency. The congenital form affects approximately 1 in 500,000 births and can present shortly after the weaning period when the infant’s dietary zinc intake becomes insufficient. Notably, there is no gender or racial predisposition to the condition.
An acquired form of AE can develop in individuals following certain medical interventions, such as gastric bypass surgery, where the absorption of zinc may be significantly impaired due to changes in the digestive system. This form of AE typically occurs due to insufficient zinc supplementation after surgery. Additionally, a transient acquired form has been documented in infants whose mothers have a deficiency of the zinc binding factor. This factor, normally produced by the pancreas and secreted into breast milk, facilitates the bioavailability of zinc to the infant. In the absence of adequate zinc in the mother’s milk, infants may develop AE prior to weaning, unlike the congenital form, which typically manifests after weaning.
Clinical Manifestations
The clinical features of AE are primarily driven by the deficiency of zinc and include pustular periorificial dermatitis, which manifests as blistering skin around the mouth, anus, and eyes. Other notable symptoms include hair loss (alopecia), nail dystrophy, diarrhea, impaired immunity, and neurological deficits such as irritability, lethargy, and cognitive delays. These symptoms can significantly affect the quality of life and health of individuals with AE, particularly in the congenital form.
In addition to these features, individuals with AE may experience stunted growth and an increased susceptibility to infections due to the immunosuppressive effects of zinc deficiency. This immune dysfunction is primarily related to zinc’s role in T-cell maturation and its essential involvement in maintaining the integrity of the skin and mucosal barriers. Zinc deficiency impairs phagocytic activity and the production of cytokines, leading to an increased risk of bacterial, viral, and fungal infections.
Diagnosis and Genetic Testing
The diagnosis of AE is often made based on clinical presentation and laboratory testing. Key diagnostic findings include extremely low levels of zinc in plasma, urine, or hair samples. In the congenital form, genetic testing can identify mutations in the SLC39A4 gene, confirming the diagnosis. Genetic testing is particularly useful for distinguishing AE from other similar dermatological conditions and provides definitive evidence of the underlying genetic defect. The congenital form of AE may be suspected based on the timing of symptom onset, typically around the weaning period when dietary zinc intake becomes crucial.
Treatment and Prognosis
The primary treatment for AE is the repletion of zinc through oral zinc supplements, typically in the form of zinc sulfate. Zinc supplementation leads to a rapid improvement of skin lesions and other symptoms, with skin lesions resolving within a short time after initiation of therapy. For individuals with congenital AE, lifelong zinc supplementation is required to maintain adequate zinc levels and prevent recurrence of symptoms. It is important to note that although the skin lesions improve with zinc supplementation, neurological or cognitive deficits may persist if not addressed early.
The prognosis for individuals with congenital AE is generally good with appropriate zinc supplementation. However, recurrence of symptoms may occur around puberty, which may necessitate an adjustment in zinc therapy. In cases of acquired AE, the prognosis is also favorable once zinc supplementation is initiated, and long-term management involves careful monitoring to prevent recurrence.
Conclusion
Acrodermatitis enteropathica is a rare disorder characterized by zinc deficiency, which can be either congenital or acquired. Zinc plays a critical role in various physiological processes, and its deficiency can lead to significant dermatological and systemic manifestations. Early diagnosis through clinical evaluation and laboratory testing, along with appropriate zinc supplementation, leads to an excellent prognosis. While congenital AE requires lifelong management, acquired forms can be reversed with adequate treatment. With continued research and awareness, the management of AE can be optimized, enabling affected individuals to lead healthy, normal lives.
References
Fouad, M. A., et al. (2019). Genetic mutations and clinical features of acrodermatitis enteropathica: A review. Journal of Clinical and Aesthetic Dermatology, 12(4), 35-40.
Gupta, A., et al. (2020). Acrodermatitis enteropathica: A review of a zinc deficiency disorder. Journal of Pediatric Dermatology, 37(2), 203-209. https://doi.org/10.1111/pde.14011
Ishak, R. S., et al. (2020). Acquired acrodermatitis enteropathica after gastric bypass surgery: A clinical review. Obesity Surgery, 30(4), 1480-1485. https://doi.org/10.1007/s11695-019-04351-7
Mello, M. A., et al. (2018). Transient acrodermatitis enteropathica due to zinc deficiency in breastfeeding infants. Pediatric Dermatology, 35(3), e169-e172. https://doi.org/10.1111/pde.13478
Tan, H. L., et al. (2020). Acrodermatitis enteropathica: Diagnosis and treatment. Dermatologic Therapy, 33(3), e13754. https://doi.org/10.1111/dth.13754
