History

Fact Explanation
Diarrhoea [6] Zinc is an essential micronutrient for bodily functions. It is an essential component of the catalytic site of many enzymes in the body. [7] At the same time zinc as an intracellular regulatory ion that regulates the of cellular growth, differentiation, and apoptosis. [4] Zinc deficiency causes functional impairment of the immune system and of intestinal mucosal cell transport mechanisms which can result in frequent diarrhoea.
Acrodermatitis enteropathica [6] This is an inherited disorder with an autosomal recessive inheritance, [5] associated with features like diarrhoea, dermatitis and other skin problems. [6] Onset is usually, after the introduction of cow's milk or low-zinc formulas at the time of weaning. [5] It can also occur due to the reduced amount of zinc in the breast milk. Diarrhea is a prominent feature of acrodermatitis enteropathica.
Poor dietary supply [3] Zinc is absorbed in the small intestine using carrier-mediated mechanism. Zinc absorption is concentration dependent and is increased up to a maximum rate with dietary supply. Zinc is released from food as free ions during digestionabsorbed via specific transport proteins into the portal circulation. Usual zinc intake is around 107 μmol/day to 231 μmol/day. [3]
Inhibitors of zinc absorption [3] Phytic acid (inositol hexa- and penta-phosphate) which is a compound in plant seeds, especially, cereals and legumes is known to cause reduction of zinc absorption. [3]
Frequent infections [7] Most serious complication of acrodermatits enteropathica is the frequent secondary infections. [7] The most common pathogens for secondary infections are Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa. [7] Pneumonia and malaria like infections more common in people with zinc deficiency. Thymopoeitin, is known to be a zinc dependent hormone needed for T-cell maturation and therefore zinc deficiency affects T-cell functions and immunity result in frequent infections.
Long term non healing wounds [7] Zinc is an important factor for the wound healing. [2]
Dry skin Zinc finger proteins, are important for in structural differentiation of many organs including the skin. [1] Absence of it can cause loss of skin integrity and moisture.
Problems in hair growth Zinc is an essential component for the growth of the hair. Deficiency causes excessively fragile hair, short hair [6] and sparse or no scalp and pubic hair, even alopecia. [2]
Obstetric and gynecological complications Maternal zinc status affects the both prenatal and postnatal development. Adequate zinc is necessary for normal pregnancy outcome and child growth, immune function and neurobehavioral development. Therefore deficiency in the pregnancy is associated with premature deliveries, poor growth of the fetus and low birth weight. [1] Amenorrhoea is also associated with zinc deficiency. [7]
Chronic debilitating disorders, chronic renal diseases, malignancie and pancreatic disorders [7] These are risk factors for zinc deficiency. [7]
Use of oral contraceptive agents Is known to lower the serum zinc levels. [4]
Weight loss ans loss of appetite Most frequent non specific manifestations of zinc deficiency. [5]
References
  1. WESSELLS KR, BROWN KH. Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting PLoS One [online] , 7(11):e50568 [viewed 28 July 2014] Available from: doi:10.1371/journal.pone.0050568
  2. BASAVARAJ KH, SEEMANTHINI C, RASHMI R. DIET IN DERMATOLOGY: PRESENT PERSPECTIVES Indian J Dermatol [online] 2010, 55(3):205-210 [viewed 28 July 2014] Available from: doi:10.4103/0019-5154.70662
  3. ROOHANI N, HURRELL R, KELISHADI R, SCHULIN R. Zinc and its importance for human health: An integrative review J Res Med Sci [online] 2013 Feb, 18(2):144-157 [viewed 29 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724376
  4. YASUDA H, YOSHIDA K, YASUDA Y, TSUTSUI T. Infantile zinc deficiency: Association with autism spectrum disorders Sci Rep [online] :129 [viewed 30 July 2014] Available from: doi:10.1038/srep00129
  5. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 30 July 2014] Available from: doi:10.4103/0019-5154.103073
  6. BARNES PM, MOYNAHAN EJ. Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet. Proc R Soc Med [online] 1973 Apr, 66(4):327-329 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1644868
  7. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 12 September 2014] Available from: doi:10.4103/0019-5154.103073

Examination

Fact Explanation
Stunting (inadequate height for age) Poor growth [7] is the that is most studied clinical feature of zinc deficiency. Zinc is needed for protein, DNA synthesis and cell division. Therefore reduced protein synthesis causing stunting is more prevalent in zinc deficiency. [1] Stunting is considered as a public health problem when the prevalence of stunting among children less than 5 years of age is >20%. [1]
Dermatitis, infections of the skin and nail defects [6] These are cutaneous manifestations of zinc deficiency. Cutaneous lesions have a characteristic distribution primarily around the body orifices[6] and at the extremities. The lesions would be dry, scaly, sharply demarcated, red, eczematous patches or moist, erythematous erosions [6] with irregular margins over bilateral dorsa of hands and feet, perioral area, cubital fossae, perigenital, perineal area, gluteal region and even thigh. [5] In severe form there can be bullous-pustular dermatitis. Skin is more prone to secondary infections, specially with Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa. Nail defects are also associated with zinc deficiency. [2] If the zinc deficiency is associated with other nutritional deficiencies such as deficiency of essential fatty acids, albumin and amino acids, that may result in acrodermatitis enteropathica.
Poor wound healing [2] Zinc is important for the cell division and thus production of new cells. [7]
Poor hair growth [6] Zinc is an essential component for the growth of the hair. Deficiency causes excessively fragile hair and sparse or no scalp and pubic hair, even leading to alopecia. [2]
Erythematous oral mucosa [6] Due to the glossitis. [5]
Features of hypogonadism [7] : Underdevelopment of the testes Zinc is an important factor for the cell division. Testicular size and its functions may be diminished [7] in zinc deficiency. Zinc is required for the functions of several enzymes and deficiency may also affects the steroidogenesis (production of steroid hormones).
Irritability, nervousness, restlessness and decreased cognitive behaviour and intellectual development. [3] Associated neuropsychiatric manifestations [7] which improves with the treatment.
Hyperactivity Autism spectrum disorders are a group disorders characterized by impairments in reciprocal social interaction and communication and with speech and language problems. [4] Studies have found that children especially in the age group of 0-3 years who suffer from the autism spectrum disorder are known to be associated with zinc deficiency.
References
  1. WESSELLS KR, BROWN KH. Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting PLoS One [online] , 7(11):e50568 [viewed 28 July 2014] Available from: doi:10.1371/journal.pone.0050568
  2. BASAVARAJ KH, SEEMANTHINI C, RASHMI R. DIET IN DERMATOLOGY: PRESENT PERSPECTIVES Indian J Dermatol [online] 2010, 55(3):205-210 [viewed 28 July 2014] Available from: doi:10.4103/0019-5154.70662
  3. GEISER J, DE LISLE RC, FINKELSTEIN D, ADLARD PA, BUSH AI, ANDREWS GK. Clioquinol Synergistically Augments Rescue by Zinc Supplementation in a Mouse Model of Acrodermatitis Enteropathica PLoS One [online] , 8(8):e72543 [viewed 28 July 2014] Available from: doi:10.1371/journal.pone.0072543
  4. YASUDA H, YOSHIDA K, YASUDA Y, TSUTSUI T. Infantile zinc deficiency: Association with autism spectrum disorders Sci Rep [online] :129 [viewed 30 July 2014] Available from: doi:10.1038/srep00129
  5. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 30 July 2014] Available from: doi:10.4103/0019-5154.103073
  6. BARNES PM, MOYNAHAN EJ. Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet. Proc R Soc Med [online] 1973 Apr, 66(4):327-329 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1644868
  7. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 12 September 2014] Available from: doi:10.4103/0019-5154.103073

Differential Diagnoses

Fact Explanation
Pemphigus vulgaris and bullous pemphigoid [4] Pemphigus vulgaris (PV) is an autoimmune disease due to the autoantibodies causing blisters with loss of epidermal cell adhesion. [3] Bullous pemphigoid is a disease is a chronic inflammatory disease which presents with blisters, nodules and bullae. Direct and indirect immunofluorescence studies demonstrate the IgG and C3 deposits in these patients.
Anaemia These patients can present with the clinical features which are same as the features of anaemia.[4] Eg:- fatigability, lethargy. [1] Therefore evaluation is necessary to exclude the anaemia at-least with a full blood count.
Inflammatory bowel disease Diarrhoea is one of the prominent features of zinc deficiency especially in acrodermatitis enteropathica. [4] Inflammatory bowel disease including crohn's disease and ulcerative colitis is also presenting with the chronic diarrhoea on most occasions. There is a dysregulated mucosal immune response to the normal commensal flora in a genetically susceptible host. [2]They will present with systemic features such as fever, weight loss, malaise etc associated per rectal bleeding. They usually have a long term history of diarrhoea.
References
  1. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 30 July 2014] Available from: doi:10.4103/0019-5154.103073
  2. BLUMBERG RS. Inflammation in the Intestinal Tract: Pathogenesis and Treatment Dig Dis [online] 2009 Nov, 27(4):455-464 [viewed 08 July 2014] Available from: doi:10.1159/000235851
  3. Pemphigus vulgaris antigen, a desmoglein type of cadherin, is localized within keratinocyte desmosomes J Cell Biol [online] 1993 Jul 2, 122(2):409-415 [viewed 30 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119642
  4. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 12 September 2014] Available from: doi:10.4103/0019-5154.103073

Investigations - for Diagnosis

Fact Explanation
Plasma Zinc concantration [1] Plasoma levels of zinc may be reduced. (normal range 70-170 micgrams/100ml) [3] Is used to identify children who are more likely to have a growth response to zinc supplements. This hypozincemia can also occur during the acute phase of infection which is not clinically significant.
Hair zinc concentrations Determination of zinc concentration in scalp hair samples are used to evaluate the zinc deficiency. [2] Though this test is possible to use, it is not routinely used in the practice.
References
  1. WESSELLS KR, BROWN KH. Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting PLoS One [online] , 7(11):e50568 [viewed 28 July 2014] Available from: doi:10.1371/journal.pone.0050568
  2. YASUDA H, YOSHIDA K, YASUDA Y, TSUTSUI T. Infantile zinc deficiency: Association with autism spectrum disorders Sci Rep [online] :129 [viewed 30 July 2014] Available from: doi:10.1038/srep00129
  3. BARNES PM, MOYNAHAN EJ. Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet. Proc R Soc Med [online] 1973 Apr, 66(4):327-329 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1644868

Investigations - Fitness for Management

Fact Explanation
Full blood count Zinc deficiency favors the recurrent infections in the individual. [3]
Stool full report The present with frequent diarrhoea. [2]
Hemoglobin [1] Anaemia is one of the systemic features of the zinc deficiency. [3] Person may presents with nonspecific symptoms like lethargy, loss of weight and loss of appetite. Therefore it is necessary for evaluate the level of hemoglobin as it can reduced in anaemia or malignancies.
References
  1. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 30 July 2014] Available from: doi:10.4103/0019-5154.103073
  2. BARNES PM, MOYNAHAN EJ. Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet. Proc R Soc Med [online] 1973 Apr, 66(4):327-329 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1644868
  3. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 12 September 2014] Available from: doi:10.4103/0019-5154.103073

Investigations - Followup

Fact Explanation
Serum zinc levels [2] When patient is on zinc therapy, monitoring should be done by regular assessment of serum zinc levels. [1]
Occult blood in stool Is done during the treatment with zinc as it causes gastric irritation as a side effect. [1]
References
  1. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 30 July 2014] Available from: doi:10.4103/0019-5154.103073
  2. BARNES PM, MOYNAHAN EJ. Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet. Proc R Soc Med [online] 1973 Apr, 66(4):327-329 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1644868

Investigations - Screening/Staging

Fact Explanation
Serum albumin level Hypoalbuminemia is known to cause reduction in the serum zinc level. [1]
References
  1. YASUDA H, YOSHIDA K, YASUDA Y, TSUTSUI T. Infantile zinc deficiency: Association with autism spectrum disorders Sci Rep [online] :129 [viewed 30 July 2014] Available from: doi:10.1038/srep00129

Management - General Measures

Fact Explanation
Prevention of zinc deficiency in pregnant mothers Dietary zinc requirement is increased during the pregnancy. [2] If the mother is at risk of zinc deficiency, preventive zinc supplementation is effective in reducing the incidence of premature delivery, decreases morbidity from childhood diarrhea and acute lower respiratory infections. [1]
References
  1. WESSELLS KR, BROWN KH. Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting PLoS One [online] , 7(11):e50568 [viewed 28 July 2014] Available from: doi:10.1371/journal.pone.0050568
  2. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 12 September 2014] Available from: doi:10.4103/0019-5154.103073

Management - Specific Treatments

Fact Explanation
Improving dietary intake Dark meet, beef, pork, yoghurt, beans are rich sources of zinc. Calcium and phytate in the diet reduces dietary zinc absorption. [2]
Zinc supplementation for diarrhoea Therapeutic zinc supplementation is shown to be effective during diarrheal episodes as it reduces the duration and severity of the illness. [1]
Treatment with zinc Severe complication of zinc deficiency, acrodermatitis enteropathica was considered as fatal condition before the treatment with zinc. Zinc is supplemented as elemental zinc at a dose of 2 mg/kg/ day, at least two or three times. [2] Side effects are gastric irritation, gastric hemorrhage and hypocupremia.
References
  1. WESSELLS KR, BROWN KH. Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting PLoS One [online] , 7(11):e50568 [viewed 28 July 2014] Available from: doi:10.1371/journal.pone.0050568
  2. SARITHA M, GUPTA D, CHANDRASHEKAR L, THAPPA DM, RAJESH NG. Acquired Zinc Deficiency in an Adult Female Indian J Dermatol [online] 2012, 57(6):492-494 [viewed 30 July 2014] Available from: doi:10.4103/0019-5154.103073