An Indistinguishable Case of Zinc Deficiency: Acquired Zinc

Deficiency or Acrodermatitis Enteropathica?

Putri Reno Sori, Reiva Farah Dwiyana, Yuri Yogya, Inne Arline Diana, R. M. Rendy, Ariezal Effendi

Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin Hospital,

Bandung 40161 Indonesia

Keywords: acrodermatitis enteropathica, , acquired zinc deficiency, zinc

Abstract: Zinc (Zn) is an essential micronutrient in growth and development in children. In some condition, zinc

deficiency occurred due to genetic or non-genetic caused. Skin disorders due to Zn deficiency are

differentiated into acrodermatitis enteropathica (AE) and acquired zinc deficiency (AZD). These conditions

are often indistinguished, since they have same skin disorders. However, AE is caused by genetic disorder

that need long-life Zn supplementation, and the other hand, AZD occurred by imbalance intake of Zn,

especially from breast milk. Therefore, further examination for baby and mother are required. Here, we

describe a case report of a 3-month old boy with zinc deficiency. Skin disorders evolved since the patient

was 2-month old as symmetrical dermatitis in perioral, acral, and skin folds area, accompanied with

diarrhea. Patient was born prematurely at 34-week of gestation and was a breast-fed infant. The diagnosis of

AZD was established based on typical skin lesion, diarrhea, and low serum Zn level. This decreased of

serum Zn also found in his mother. Patient was treated with 10 mg Zn sulphate supplement once daily and

clinical improvement was obtained after five days supplementation. Zinc level in patient remained high after

one month discontinuation of Zn supplement. Clinically, AZD is difficult to distinguish with AE, thus zinc

level examination in baby and mother are required, as well as observation during and after discontinued of

zinc supplementation, to support the diagnosis, both for AE or AZD.

1 INTRODUCTION

Zinc (Zn) is an essential micronutrient in proteins

and nucleic acids. Zn also plays role in cell growth

and division, wound healing, and immune cell

activity (Plum et al., 2010). Zn deficiency in

children results in growth retardation, emotional

disturbance, irritability, depression, gastrointestinal

disorders, hypogonadism, anemia, skin disorders,

and immune system disorders (Ackland et al., 2008).

Skin disorders due to Zn deficiency can manifest as

erythematous macules, vesicles, pustules, crusts,

erosion, and scales in the periorifisium, extremities,

and diaper area with symmetrical distribution (Yang

et al., 2012). These lesions could resemble atopic

dermatitis, seborrheic dermatitis, diaper dermatitis,

candidiasis, and skin disorders from vitamin and

other micronutrient deficiency (Kury et al., 2012;

Kharfi et al., 2010). Theredore, this skin disease

often misdiagnosis.

Zinc deficiency is classified into primary and

secondary (Ackland et al., 2008).Primary deficiency

results from low Zn intake or low bioavailability of

Zn. Secondary deficiency is caused by genetic

disorder or disease that interfere Zn absorption as

well as increased Zn excretion in intestinal.

Acquired zinc deficiency (AZD) and acrodermatitis

enteropathica (AE) are disease that occurs due to Zn

deficiency with very similar clinical manifestation

(Ackland et al., 2008). AE is caused by a genetic

disorder resulting in impaired absorption of Zn in

the intestinal with classic triad of periorifisium

dermatitis, diarrhea and alopecia, while AZD is due

to imbalanced intake and Zn requirement without

intestinal disturbance (Yang et al., 2012; Ruiz-

Maldonado& Orozco, 2008).

Here is one case of AZD that initially

undisguisable to AE because of same skin rashes.

However, serum Zn level examination from patient

and mother showed lower level that indicated to

AZD due to imbalance intake, thus Zn

supplementation was given. The purpose of this case

report is to report a Zn deficiency case that clinically

indistinguishable, but after discontinued of Zn

supplementation, the serum Zn level examination

remained normal, that indicated to AZD.

Sori, P., Dwiyana, R., Yogya, Y., Diana, I., Rendy, R. and Effendi, A.

An Indistinguishable Case of Zinc Deﬁciency: Acquired Zinc Deﬁciency or Acrodermatitis Enteropathica?.

DOI: 10.5220/0008160404890492

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 489-492

ISBN: 978-989-758-494-7

489

2 CASE

A 3-month-old baby boy presented with 1-month

history of skin eruption, arising initially on his

inguinal area. These lesions spread bilaterally over

his back, hands and feet, then onto his face. The skin

lesion accompanied with diarrhea up to 6 times a

day. He was treated with topical corticosteroids for

skin lesion and antibiotic with other physician and

improvement was not achieved. He was premature,

delivered at 34 weeks, and full breast-fed infant.

Physical examination revealed bright red, eroded

plaques in perioral and extremities, especially folded

ares, as well as vesiculobullous lesions on his hands

and feet (Figure 1). Bacteria was found on Gram

stain and pseudohyphae and blastospore from skin

scrapings with 10% potassium hydroxide (KOH)

solution. Patient had underweight and stunted, and

from laboratory examination, there was

hyponatremia.

From history taking and physical examination,

led to Zn deficiency, which could be AZD and AE.

Therefore, serum Zn examination was needed. The

result were Zn level at patiet was 9 μg/l (reference

range 26–141 μg /l) and Zn level of his mother at 49

μg /l (reference range 60–130 μg /l). This result

confirmed AZD since usually in AE, Zn level of

mother is in normal limit, however, there is

genetically malfunction of Zn absorption in baby,

that lead to Zn deficiency.

The patient was given oral zinc sulphate

supplementation in 10 mg/day dose, and dramatic

improvement of skin lesion had achieved within a

few days. The lesions resolved completely over

following 2 weeks. Zn supplementation still

continued for 3 months, and the normal level of Zn

was achieved as 101 μg /l. After a months of Zn

supementation was stopped, Zn level remain normal

(96 μg /l) and there was no new skin lesion at all

(Figure 1). Based on this condition, the diagnosis of

this patient was AZD, that could be differentiated

with AE from thorough examination and follow up.

3 DISCUSSION

Zinc is an essential micronutrient for growth and

development (Plum et al., 2010). It is required for

the activity of more than 300 enzymes and 1,000

transcription factors, as well as controlling genetic

expression, and plays an important role in protein

and amino acids synthesis, cell replication and

regeneration (Krebs, 2013). Zn sources in infants are

mainly obtained from breast milk. Zn in breast milk

is better absorbed than cow's milk or soy milk,

because it contains zinc-binding ligand (Jen & Yan,

2012). Zn from food will be absorbed in the form of

+ 2

ions that bind to ZIP4 transporters to be

absorbed in duodenum and jejunum (Deshpande et

al., 2013).

Zinc deficiency characterized by abnormalities in

the skin, gastrointestinal tract, and alopecia (Ruiz-

Maldonado& Orozco, 2008). Skin disorders initially

presented as erythematous macules with scale and

may turn into vesicles, bullae, pustules, and erosion

with symmetrical distribution in periorifisial, and

extremities (Kharfi et al., 2010). Skin lesions may be

accompanied by secondary infections caused by

Candida or bacteria (Kaur et al., 2016). This disorder

is accompanied by diarrhea three to six times per

day which can leads to dehydration and electrolyte

imbalance. In mild cases there is dry and coarse hair,

which become alopecia in severe cases. Other

abnormalities that can be found are anorexia, growth

retardation, irritability, eye abnormalities and

photophobia (Jensen et al., 2008).

Diagnosis of Zn deficiency in this patient

established based on typical clinical features and

laboratory tests (Kury et al., 2012). Zn serum

concentrations was less than 50 μg / l are the gold

standard for the diagnosis of Zn deficiency (Jen &

Yan, 2012).

The skin lesions in this patient are erythematous

macule with scale in symmetrically distributed

between the thighs, buttocks, back and hands and

around the mouth and nose, accompanied by

vesicles and bullae in the legs. Complaints also

accompanied with diarrhea and hair loss. We found

bacteria on Gram stain and pseudohyphae and

blastospore from skin scrapings with 10% KOH

solution. On physical examination, the nutritional

status was underweight and stunted, alopecia, and

from laboratory examination, the patient was

hyponatremia.

Zinc deficiency can be differentiated into congenital

and acquired (Yanagisawa, 2004). AE is a

congenital Zn deficiency arising from a gene

mutation encoding the Zip4 protein, which is a Zn

transporter in the pancreas, so there is no Zn

transport from the duodenum and jejunal lumen to

the epithelium (Azevedo et al., 2008). Protein Zip4

is also produced by the mother's milk glands

secreted into breast milk. Therefore, in AE there is

no Zn deficiency in exclusively breast-fed infants

(Jen & Yan, 2012). In infants with AZD there is an

imbalance between the Zn requirement and the Zn

intake, one of which is due to the low Zn levels in

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

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the mother.

AZD occured due to low levels of Zn in

breast milk. Low levels of Zn in breast milk can be

caused by uptake Zn uptake in serum by mammary

glands, due to mutations of Zn SLC30A2 (ZnT-2)

transporter (Krebs, 2013). Other studies suggest that

low levels of Zn in breast milk may be due to low

maternal serum Zn levels (Scheplyagina, 2005).

Symptoms of Zn deficiency in AZD usually occur in

first six months of life. At that time there was a rapid

growth in infants so the requirement for Zn also

increased. AZD occurs mostly in premature infants

given breast milk. This is because early in life of

premature infants, Zn absorption in the intestine is

inadequate (Mashhood, 2007), and Zn transfer from

mother to fetus via the placenta occurs mostly in the

last ten weeks of pregnancy (Ackland &

Michalczyk, 2006). In breast-fed infants with AE,

the symptoms of Zn deficiency occur after weaning,

while infants fed formula, symptoms arise more

quickly (Jen & Yan, 2012).

Figure 1: Skin lesion

An Indistinguishable Case of Zinc Deﬁciency: Acquired Zinc Deﬁciency or Acrodermatitis Enteropathica?

491

This patient was born prematurely at eight

months of gestation. From birth, the patient received

exclusive breastfeeding from her mother. Clinical

manifestations of typical skin disorders and diarrhea

begin to develop since the patient two months old.

On laboratory examination, patient had low Zn

levels, as well as in her mother. Patient was given by

oral Zn supplementation and the Zn level remain

normal limit after discontinued Zn supplement.

Therefore, diagnose of AZD was established based

on low level of Zn in patient and mother, as well as

the remain of Zn level of patient after discontinued

therapy.

The main therapy for Zn deficiency is

supplementation of Zn sulphate 10-20 mg per day

for up to three to four months. Skin disorders and

diarrhea usually start improving after two to three

days, and skin infections show improvement after

one week (Mashhood, 2007). In AZD, after

discontinuation of Zn supplementation, skin

disorders do not reoccured. However, in AE,

discontinuation of Zn supplementation results in a

decrease in serum Zn levels, and skin disorders will

reappear (Kharfi et al., 2010).

In this case, patient was given by 10 mg/day Zn

sulphate supplements and after one week there were

clinical improvement as skin lesions healed and no

diarrhea. After three months of Zn supplementation,

serum Zn level was 101 μg/l, and after one month

discontinuation of supplement, obtained Zn level

was normal, as 96 μg/l.

4 CONCLUSIONS

It may be concluded from this case report that Zn

deficiency can cause acrodermatitis, perioral

dermatitis, alopecia, and diarrhea, that both found in

AE and AZD. Clinically, AZD is difficult to

distinguish with AE, thus in order to differentiated

them, zinc level examination in mother and baby are

required.

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