What Is Acrodermatitis Enteropathica

The appearance of any rash on our skin can be worrying but usually, not a cause for concern. Nowadays rashes can be simply and effectively treated.1 One such rash is acrodermatitis enteropathica, which is caused by zinc deficiency. Zinc is a micronutrient that plays a very important role in the proper functioning of different metabolic pathways that occur at all times in the human body. It also plays a vital role in brain function, strengthening the immune system and proper wound healing, and it has antioxidant and anti-inflammatory properties. It is important to note that the body stores zinc, so the body's need for this micronutrient must be met through the diet. However, although this skin condition has a simple treatment if left untreated, it can lead to further complications. 

Causes and risk factors 

This disorder is broadly categorised into two main forms: congenital and acquired. Congenital means that this disorder was inborn and was present from birth. It is an autosomal recessive condition, which means that this gene is not a dominant gene, and its effects will not appear in an individual unless they inherit this defect separately from each affected parent. If a person only inherits this gene from one affected parent, they will carry the gene as carriers but will not be affected by it or show any symptoms. The actual defect occurs in the zinc transporter,  which is situated in the intestines. Since it is defective, it hinders zinc absorption from the gut, resulting in the zinc deficiency.²

On the other hand, the acquired form of this disorder occurs when there is insufficient zinc in the diet, an increased demand for zinc, or any condition that can impair the absorption of this nutrient from the intestines. Insufficient zinc in the diet may occur from a significant reduction in the intake of required nutrients, as seen in conditions such as anorexia nervosa, malnutrition and an unbalanced vegetarian diet. It is also particularly prevalent in premature newborns due to their increased need for zinc at the time zinc is also present in maternal milk, and thus deficiency of this nutrient can be seen particularly in weaning breastfed infants. There are also diseases that impair the absorption of zinc from the intestines, such as inflammatory bowel disease, cystic fibrosis or a disease in the pancreas.^{2, 3}

Symptoms

The symptoms of congenital acrodermatitis enteropathica usually become first apparent a few days to weeks after birth and soon after weaning for breastfed babies; meanwhile, the symptoms can begin at any time for the acquired form of the disorder. The most dominant and early symptom is the associated rash, which usually occurs around the mouth (periorificial) without involving the lips, around the peri-anal and buttocks region, and on the elbows and knees (acral). Typically, the rash is very well defined and distinguishable from normal skin, and it appears as dry red (erythematous) plaques, which may progress to blisters and eventually dry out.⁴ There is a potential for these rashes to obtain secondary fungal or bacterial infections caused by Candida Albicans or Staphylococcus Aureus, respectively. It is also common to see some changes in the nails, which become brittle and soft with ridging or dystrophy, as well as some alopecia, which is defined as hair loss from the scalp. 

Other systemic symptoms apart from the rash may be any of the following: 

• Mild or severe diarrhoea  
• Lethargy and irritability
• Loss of appetite and growth failure 
• Problems associated with the eye such as sensitivity to light (photophobia), inflamed conjunctiva (conjunctivitis) and inflamed eyelids (blepharitis)
• Hypogonadism in males

Although this list of symptoms is not exhaustive, and it is not necessary to exhibit one or all of the symptoms, the classic triad for this disorder is considered to be the periorificial and acral rash, diarrhoea and alopecia.⁴ The differential diagnosis for this disorder can be celiac sprue (gluten enteropathy), eczema, psoriasis, seborrhoeic dermatitis or pellagra, which also exhibit symptoms which are similar.⁵

Diagnosis

In order to diagnose this condition, your doctor may order a number of different tests. The first and simplest of these tests might include a blood test to determine the level of zinc present in the blood plasma. This blood test can be done whilst fasting or non-fasting.  Acrodermatitis enteropathica is suspected if zinc levels in the blood plasma are below 70 microgram/L whilst fasting and below 65 microgram/dL whilst non-fasting.4 Although measuring the levels of zinc in the plasma is helpful for diagnosis, special precautions must be taken to avoid contamination of the results; the equipment used to draw blood generally should be acid-washed, as contaminated equipment can overestimate the levels of zinc in the blood. Stress levels can affect the test and vary according to the time of day so it is recommended to conduct this test first thing in the morning. 

Along with zinc plasma levels, the levels of zinc present in urine, maternal milk or hair may also be determined. A full blood count may also be done, which might exhibit low levels of red blood cells (anaemia ) and low levels of white blood cells (leukopenia). Serum alkaline phosphatase levels may also be obtained to support the diagnosis of acrodermatitis enteropathica, which would be lower than normal in this disorder. It should be noted that zinc levels may also be lower than normal in other pathological conditions, such as low serum albumin and various inflammatory conditions, which should be ruled out before reaching a conclusive diagnosis. More complicated and invasive procedures like a skin biopsy are not usually conducted because the histopathology of a skin biopsy from acrodermatitis enteropathica will appear very similar to the histopathology of other skin conditions such as eczema or psoriasis. A skin biopsy is usually only conducted in cases where diagnosis is uncertain, and even then, the results would be more helpful than confirmatory.

Treatments

Following diagnosis, the treatment of this disorder is quite simple. It often entails zinc supplementation, which is prescribed for both the congenital and acquired form, as well as a treatment of the underlying condition for the acquired form of the disorder. Zinc supplements can be taken via the mouth or injections and the usual dose is roughly 3mg/kg/day⁴ which may have to be taken throughout life, depending on the cause. Zinc sulphate is usually the preferred oral supplement, and zinc chloride is preferred for injections.

After the commencement of treatment, signs of improvement can occur mere days after. The first noticeable symptoms usually include an improvement in lethargy and irritability, followed by improvements in skin rashes. Throughout the course of treatment, regular monitoring (roughly every 3-6 months) of zinc levels in the blood plasma, full blood count, serum alkaline phosphatase and serum copper levels are required. Serum copper levels may fall in proportion to increased zinc levels, and conversely, serum alkaline phosphatase levels may rise. 

During the course of treatment, care should be taken not to overdose on zinc as it may cause toxicity when present in high doses. Acute signs of zinc toxicity include light-headedness, abnormal gait, nausea, vomiting and stomach cramps. Long-term side effects of zinc overdose can be recognised by anaemia, leukopenia and copper deficiency, as well as failure to grow.²

Prognosis 

Generally, individuals diagnosed with acrodermatitis enteropathica have a good prognosis with a full response rate. With prompt treatment, an affected individual can lead a normal life. However, it is imperative to treat this nutrient deficiency swiftly, especially in infants because the untreated condition can possibly lead to adverse events including death in the first couple years of life. If the congenital form of this disorder is known in a family, it is important to make genetic counselling available to the family in order to discuss the need for zinc supplements, which have to be taken throughout their life. Though it may appear daunting to commit to lifelong supplementation, the individual affected will be able to lead normal lives with the help of these zinc supplements.⁴

In order to prevent zinc deficiency, it is important to have a good and varied diet with extra attention to food rich in zinc. This includes but is not limited to beef, fish, nuts, beans, whole grains, eggs and dairy products.⁶

Summary  

Zinc is an important micronutrient that helps the body develop and function in a variety of different ways, and it is especially important for proper infant growth. Deficiency of this nutrient can lead to a disorder called acrodermatitis enteropathica, which is relatively easily treatable and is not usually cause for concern. This disorder has two main forms, and both forms can be promptly and effectively treated by zinc supplements, which are also available to purchase over the counter. If this condition is present in families, all members of this family should be offered genetic counselling. 

In order to prevent acrodermatitis enteropathica it is important to maintain a healthy and varied diet and it is also important to keep a close eye on any changes noted in the body, whether those changes appear as rashes in the skin or if there are any changes to a person's energy levels or growth. This holds particularly true for infants because this condition can be potentially fatal if not treated promptly with immediate zinc supplementations. It should be noted that any worrying rashes should be seen by a doctor to obtain the best medical advice.