Nutritional disorder, Nutritional disorders of skin

1. Nutritional Dermatoses : A Review
Dr. Sanjay Singh
Nutrition is complex series of events by which living organisms consume and assimilate foods and other nutrients to
live, grow, and maintain homeostasis. Proper nutrition involves the consumption of key macronutrients in balanced
tandem with essential micronutrients. Macronutrients consisting of carbohydrates, proteins,and lipids, needed in large
quantities by an organism to both fuel metabolic processes and provide the substrate for building and maintaining
cellular structure. By contrast, micronutrients signify vitamins and minerals, which, though required in relatively minute
quantities, are essential to good health. Clinical disease results when disturbances occur in that equilibrium—most
commonly from nutrient deficiencies, but also from an unbalanced ratio of consumed nutrients, or, less commonly, from
nutrient excesses.
Risk factors for nutritional deficiency:
Individuals at risk include those with derangements in their normal diets such as might be encountered with inadequate
dietary intake, eating disorders, unusual dietary habits, or with parenteral nutrition. Hypercatabolic states, exemplified
by cancer, acquired immunodeficiency syndrome, hepatic or renal disease, and certain disease states such as carcinoid
syndrome, may develop nutrient deficiencies even in the face of normal intake due to increased metabolic requirements.
Excessive nutrient losses may occur from decreased absorption arising from gastrointestinal diseases such as cystic
fibrosis, inflammatory bowel disease, celiac disease, or after gastrointestinal surgery. Those receiving chronic
medications, such as anticonvulsants or antibiotics, may experience impaired utilization of their nutrients when their
medications interfere with gastrointestinal absorption and normal metabolism. Underlying genetic metabolic defects,
enzyme deficiencies, hepatic disease, or drug-nutrient interactions may also impair utilization of nutrients. By contrast,
syndromes of nutrient excess generally stem from dietary surplus or iatrogenic therapeutic intake.
Prevalence of malnutrition is still very high in India; especially in rural area. In one study, conducted in rural areas
prevalence of malnutrition among the under five children was 50.46%. There is no significant reduction in prevalence
of malnutrition during last 12-13 years in spite of various programmes. There is high under five morbidity and mortality
in india. Protein energy malnutrition is major contributory factor in majority of these childhood morbidities and
mortalities. According to the 2005-06 National Family Health Survey 3 (NFHS-3), 20 % of Indian children under five
years old were wasted and 48% were stunted. Globally , more than 2 billion persons have micronutrient deficiencies,
most of them from developing countries. Data from the National Nutrition Monitoring Bureau (NNMB) over the
last three decades have consistently shown that more than 70% of pre-school children consume less than 50% of
the RDAs for vitamin A, iron, folic acid and riboflavin. Iron deficiency appears to be the most severe of all
the micronutrient deficiencies with barely one-third of any age group (except adult men) having normal
haemoglobin levels (≥12g/dl).
Macronutrients : Macronutrients are nutrients required in large amounts that provide the energy needed to maintain
body functions and carry out the activities of daily life. Macronutrients provide the bulk energy for an organism's
metabolic system to function. There are 3 macronutrients – carbohydrates, proteins and fats.
Disorders due to Macronutrient Deficiency :
i. Protein - Energy Malnutrition : refers to a spectrum of disorders describing varying degrees of protein and calorie
deficiency. Several types of PEM have been defined on the basis of relative deficiencies in protein and total calorie
intake.
1. Marasmus : The term marasmus derives from the Greek marasmus meaning “wasting.” Children with marasmus
suffer from severe wasting and stunting and are at less than 60 percent expected body weight for age. These changes are
the result of chronic and global nutrient deficiencies, often because of a lack of available food.
Pathophysiology : In marasmus there is decreased intake of all macronutrients, particularly carbohydrates. Decreased
glucose in blood suppresses insulin production. Catabolic hormones thereby act unopposed to stimulate the conversion
of glycogen into glucose. In the early stages, muscle breakdown occurs during the first 24 hours, permitting
gluconeogenesis to release glucose into the systemic circulation. Fat breakdown creates ketone bodies that can also be

2. utilized by the brain and central nervous system. This reduces the need for further muscle breakdown so that lean body
mass and some protein synthesis can be spared. In prolonged states of adapted starvation, wasting occurs and lean body
mass is eventually utilized.
Clinical findings : Marasmus typically affects infants younger than 1 year of age. The cutaneous findings of marasmus
include :
 Dry, thin, loose, wrinkled skin resulting from loss of subcutaneous fat with an emaciated appearance.
 Hair growth slows and examination may reveal easy hair loss, leading to thin, fine, brittle, hair and alopecia.
Increased lanugo hair may also be present.
 Nails may show signs of fissuring, with impaired growth.
 The loss of buccal fat pads creates the aged appearance that has been referred to “monkey facies”.
Systemic findings : Perianal fat loss can lead to rectal prolapse, and abdominal muscle hypotonia may result in
abdominal distention. Constipation may alternate with periods of diarrhea, which may or may not be associated with
concomitant gastrointestinal infection. Angular cheilitis and mucous membrane changes have also been observed in
patients with marasmus. Patients often show both decreased resting body temperature and bradycardia.
2. Kwashiorkor : Children with kwashiorkor have body weights less than 60 percent to 80 percent expected for age,
generally arising from a diet of grain-derived foods without adequate accompanying protein. The term kwashiorkor
derives from the Ghanese term for “the one who is deposed,” referring to the child who is weaned off of breast milk
onto a carbohydrate-rich but often protein-poor diet when the next sibling is born.
Pathophysiology : Disease occurs due to increased intake of carbohydrate and decreased intake of protein and fat.
Without concomitant fat and protein intake, insulin continues unabated, which suppresses protein production.
Hypoproteinemia and edema (due to decreased oncotic pressure) develops and affected individuals are unable to
Protein-energy malnutrition
Protein-energy deficient nutrition Protein energy excess nutrition
Exogenous or Primary Endogenous or Secondary
Insufficient and/or
inadequate food ingestion
Inadequate food absorbtion
and/or metabolism.
Increased nutritional
requirements
 Poverty
 Old age
 Alcoholism
 Psychiatric
disorders, e.g.
anorexia
nervosa,bulimia
 Diets
 Child Neglect

Obesity
Exogenous or primary Endogenous or
Secondary
Excessive and/or
high calorie food
ingestion
 Depression
 Anxiety
 Iatrogenic
Metabolic
alterations
 Genetic
factors

3. manufacture lipoproteins, so fats accumulate in the liver. More important, necessary immune proteins are also not
produced. Because of edema kwashiorkor also known as edematous or “wet” PEM.
Clinical Findings : The hallmark features of kwashiorkor include failure to thrive in association with edema and is
primarily noted in children between 6 months and 5 years of age. Children are often initially irritable, but may become
lethargic and apathetic. In contrast to marasmus, skin findings are common in kwashiorkor. Necessary immune proteins
are not produced, so patients become susceptible to opportunistic infection and septicemia, which represent the major
causes of mortality in these patients.
Cutaneous findings : Cutaneous findings is known as dermatosis of kwashiorkor (DoK). DoK is described as initially
small black patches on extensor surfaces of ankles, knees, above wrists and on elbows. They gradually spread to cover
legs and forearms, knees and elbows. The character of the thickened epidermis is described as a ‘crazy pavement’. Few
days after appearing, patches mature and strip off, leaving the skin as a combination of crumbled, black patches and a
raw surface where these have peeled off. Hair often changes from its natural color, typically developing a red tint before
further pigment dilution results in light, gray-white hair. If a child experiences intermittent periods of kwashiorkor and
improved nutrition, alternating bands of light and dark color within the hair shaft may be observed and has been referred
to as the “flag sign”. Increased lanugo hair can also be noted in kwashiorkor. The manifestations in adults may be less
prominent, manifesting as xerosis or acquired ichthyosis.
Amount of both collagen and non-collagen nitrogen in the skin of oedematous malnourished children is reduced, when
compared with healthy children. This reduction is more pronounced in children who had skin lesions and worsened
with the severity of skin manifestations. An impaired maturation of collagen and cross-linking of fibres is also suggested,
based on the heightened proportion of labile collagen among children with kwashiorkor.
3. Marasmic Kwashiorkor : It is a hybrid form of malnutrition in which stunting of growth is associated with edema.
Treatment of PEM : Patients with severe PEM often require hospitalization due to the concurrent risks of
hypoglycemia, hypothermia, dehydration, and sepsis. Individuals who are not awake and responsive may require
intravenous hyperalimentation during the initial stages of therapy; care must be taken to avoid excessively rapid
rehydration due to the risks of congestive heart failure. Oral refeeding using oral rehydration salts containing a mixture
of essential electrolytes is generally preferred at least until diarrhea subsides or using fortified formulas as soon as these
can be tolerated.Because severely malnourished children are relatively immunocompromised,empiric antibiotic therapy
may be considered on admission for suspected sepsis, and any identified infections should be appropriately addressed.
ii. Essential Fatty Acids Deficiency :
Essential fatty acids (EFAs), those that cannot be synthesized by humans, are important substrates for many physiologic
processes. Linoleic and linolenic acid are the major dietary EFAs and are found in dairy products, meat, and vegetable
oils. EFAs are components of cell membranes, mediators of inflammation via synthesis of prostaglandins and
leukotrienes, and are building blocks throughout the body. Fatty acids also contribute to the permeability barrier of
the stratum corneum and, therefore, are important mediators of skin barrier function.
Patients at risk for EFA deficiency include those with poor dietary intake, including alcoholics and patients with anorexia
nervosa, or those with malabsorptive conditions such as biliary disease, inflammatory bowel disease, and post-
gastrointestinal surgery (e.g., bariatric surgery). Premature, low-birthweight infants are born with inadequate EFA stores
and are at special risk. EFAs represent a group of 18-, 20-, or 22-carbon polyunsaturated fatty acids that cannot be
synthesized de novo by the human body.
Clinical findings :
Cutaneous findings : Skin manifestations of EFA deficiency include:
 Xerosis; scaly, diffuse erythema; and associated intertriginous erosions.
 Poor wound healing, traumatic purpura secondary to capillary fragility, brittle nails, and alopecia may be
observed.
 Affected individuals may also demonstrate hyperpigmentation or hypopigmentation of the hair.
Systemic findings : Fatty liver infiltration, increased susceptibility to infection, a blunted immune response, anemia,
thrombocytopenia, and growth retardation can also be observed.

4. Treatment : Oral or intravenous supplementation of EFA. Topical application of sunflower seed oil and safflower oils,
which contain linoleic acid, may improve the clinical cutaneous findings of EFA deficiency, but topical absorption is
unpredictable.
Causes
Cutaneous
findings
Systemic
findings
Laboratory
Marasmus
• Decreased energy intake over
months to years
• Other primary causes:alcoholism,
psychiatric disorders (anorexia
nervosa,bulimia), diets for treatment
of diseases or “allergic disorders”,
child neglect/abuse
• Secondary causes: intestinal
malabsorption, chronic diarrhea,
malignancies, chronic systemic
diseases (e.g. hepatic failure),AIDS,
metabolic disorders
• Dry, thin, pale, lax and wrinkled skin
• Occasionally, fine scaling and
Hyperpigmentation
• Follicular hyperkeratosis and
folliculitis in adults
• Ulcerations
• Excess of lanugo-like hair
• Thin hair that grows slowly
and falls out readily
• Impaired growth of nails and
fissured nails
• Purpura
• Starved appearance but alert
• Reasonably preserved
Responsiveness to short-term
stress
• Loss of subcutaneous fat and
muscle
• “Monkey facies” or an aged
appearance (due to loss of
buccal fat pads)
• Suppression of growth
• Triceps skin-fold <3 mm
Kwashiorkor
• Decreased protein intake during periods
of stress lasting a few weeks or more
• Can result from diets consisting primarily
of rice or rice-based beverages (e.g.
“rice milk”) for perceived milk intolerance
• Other causes: protein-losing
enteropathies, extensive gastrointestinal
surgeries, HIV disease
• Dyschromia is a common
finding
• Pallor due to distention of
the skin and loss of pigment
• Hypopigmentation following
abrasions, and ulcerations
and hyperpigmentation in
areas subject to trauma.
• Superficial desquamation in mild
cases (“enamel paint spots”), but
in severe case large areas of
erosion (“flaky paint”).
• Other cutaneous signs include
erythema, thinning, petechiae,
ecchymoses and purpura.
• Hair is sparse, dry, lusterless and
brittle with a reddish tinge; bands
of light and dark coloration (“flag
sign”) reflect intermittent periods
of malnutrition; positive gentle
hair pull test.
• Nails are soft and thin
• Mucosal lesions: cheilitis,
xerophthalmia and vulvovaginitis
• Relatively well-nourished appearance
• Edema or even anasarca
• Apathy, anorexia, irritability
• Failure to thrive (retardation of
growth and mentaldevelopment)
• Superimposed bacterial and
fungal (e.g. candidal) infections
• Bilateral parotitis, hepatomegaly,
diarrhea, loss of muscle mass.
• Poor wound healing, decubitus
Essential fatty acid deficiency
• Protein–energy malnutrition
• Gastrointestinal disorders/surgeries
Causing severe fat malabsorption
• Long-term parenteral nutrition
without lipid supplementation
• Diets extremely low in fat
• Nephrotic syndrome
• The skin is dry, scaly, and
leathery with underlying
erythema
• Intertriginous erosions
• Alopecia and more lightly
pigmented hair
• Increase in transepidermal
water loss
• Petechiae
• Growth failure
• Poor wound healing
• Impaired reproduction
• Abnormal liver and kidney
function tests
• Capillary fragility
• Increased susceptibility to
infections
• Neurologic damage
• Low plasma levels of linoleic,

5. and
Diagnostic
Findings
Treatment
Prognosis
• Mid-arm muscle circumference
<15 cm
• Creatinine-height index <60%
of standard
• Low zinc levels
• Epidermal acanthosis or atrophy
(depending upon the stage),
hyperkeratosis
• Most hair bulbs are in the
telogen phase
• Abundant broken hairs
• Slowly replacing proteins and
calories, allowing readaptation
of metabolic and intestinal
functions
• Supplementation with linoleic
acid and zinc
• Monitor for hypophosphatemia
and cardiorespiratory failure
(associated with overly aggressive
nutritional replacement)
• Treatment of underlying diseases
if possible
• 10% mortality, often secondary
to diarrhea or pneumonia
• Mortality rate related to
underlying disease(s)
ulcers or skin breakdown
• Anergy
• Hypoalbuminemia (<2.5 g/dl)
• Total iron-binding capacity
<200 microg/dl
• Peripheral lymphocyte count
<1500/microl
• Steatohepatitis
• In “enamel paint spots”, thickened,
pigmented stratum corneum with
an underlying stratum lucidum
• Decreased number of anagen hair
follicles and increased number of
telogen follicles
• Structural abnormalities in anagen
follicles – severe atrophy, shaft
constriction, depletion of pigment
• Exclude nephrotic syndrome
• Aggressive nutritional support is
indicated to rapidly restore metabolic
balance; correction of any
electrolyte disturbances or
hypoglycemia
• Institute diet with adequate protein
and caloric intake; supplementation
with minerals and vitamins is
required as patients often have
multiple nutritional deficiencies
• Identify and attempt to treat
underlying cause(s),including bacterial
and parasitic diseases
• Prognosis in adult patients is poor, even
with aggressive nutritional support
• In children, a lesser degree of stress is
required to precipitate the disorder,
so it is less foreboding
• Severe, relapsing cases and those
with coexistent HIV disease have
a high mortality rate
linolenic and arachidonic acids
• Accumulation of 5,8,11
eicosatrienoic acid
• Elevated levels of palmitoleic
and oleic acids
• Anemia, thrombocytopenia
• Orthokeratotic hyperkeratosis,
acanthosis with hypergranulosis,
atrophic sebaceous glands,
and papillary dermal vasodilation
with a mixed cell infiltrate
(in rat models)
• Steatohepatitis
• Essential fatty acid replacement,
depending upon severity:
– topical
– oral
– intravenous
• Correction of coexisting
nutritional deficiencies
• Prognosis depends on the
severity and coexistence of
other nutritional deficiencies
Micronutrients Deficiency Disorder
Micronutrients consist of vitamins and minerals.
Vitamins are divided in two group: (i)Fat soluble (ii)Water soluble. Fat soluble vitamins are vit. A, D, E, K. All others
are water soluble.
● Vitamin A (Retinol) : Vitamin A is a fat-soluble vitamin important in keratinization, epithelial proliferation, and
photoreceptor production. The two most clinically important metabolites of vitamin A are retinal, which is a key
component of rhodopsin generation, and retinoic acid, which regulates cell differentiation.
Dietery sources : Vitamin A is present in plant as well as animal sources. Plant sources include dark, green, leafy
vegetables; red palm oil; and brightly colored fruits such as papaya, mango, carrots, tomatoes, apricots, and cantaloupe.
Animal sources of vitamin A include egg yolk, liver, fish, fortified milk, and other dairy products. In plants vitamin A

6. exists as ß – carotene, it is converted in retinol in intestinal villous cells. In animal sources, vitamin A exists as retinyl
esters, which are then hydrolyzed to retinol in the intestinal lumen and then absorbed into intestinal mucosal cells.
Deficiency : Deficiency develops with chronic decreased intake or increased utilization, as the liver can store a several
months’ supply.Vitamin A deficiency (VAD) can result in cutaneous as well as ocular complications. It is, in fact, the
most common cause of preventable blindness in children, according to the WHO. The primary causes of vitamin A
deficiency continue to be inadequate intake, fat malabsorption states, and liver disease.
Clinical findings : The earliest manifestations of Vitamin A deficiency are ocular changes. Patient develops impaired
dark adaptation (nyctalopia) followed by xerophthalmia. Due to abnormal keratin desquamation of sclera patient
develops white patches known as Bitot spots. Severe deficiency may lead to corneal xerosis, ulceration, and
keratomalacia, which may result in corneal perforation, prolapse of the iris, and blindness.
Cutaneous findings : Result of abnormal keratinization.
 Mild deficiency may manifest as xerosis and scaling.
 Severe deficiency may result in deep skin fissuring referred to as dermomalacia.
 Squamous metaplasia of the salivary glands as well as the nasal and oral mucosa may occur, leading to
xerostomia, hyposmia, and hypogeusia. Laryngeal, bronchial, and vaginal mucosa can also become involved.
 Phrynoderma, meaning “toad skin,” is typically associated with vitamin A deficiency. These keratotic follicular
papules often first develop on the anterolateral thighs and posterolateral upper arms, which then spread to
extensor surfaces of the extremities, shoulders, abdomen, back, buttocks, face, and posterior neck.
 Phrynoderma, is highly characteristic of vitamin A deficiency but is not specific and is associated with
other nutrient deficiencies.
Treatment : The recommended daily allowance (RDA) of vitamin A is between 1000 and 5000 IU, with younger
individuals requiring a lower intake of vitamin A. Recommended treatment for vitamin deficiency disorder is 100,000
to 300,000 IU of oral vitamin A daily until symptoms resolve and serum levels normalize.
● Vitamin A Toxicity : Vitamin A toxicity is the result of excess intake of vitamin A and can occur on an acute or
chronic basis. Acute toxicity occurs when excessive amounts of vitamin A are ingested over a period of several hours
or days. Toxicity typically results when intake exceeds 20 times the RDA in a child or 100 times the RDA in an adult.
Chronic toxicity results from daily ingestion of greater than 25,000 IU for more than 6 years or greater than 100,000 IU
for more than 6 months of pre-formed vitamin A. Individuals most at risk for toxicity include patients taking systemic
vitamin A derivatives for the treatment of dermatologic conditions such as acne, psoriasis, and ichthyosis.
Clinical findings of toxicity :
Acute toxicity : Cutaneous findings - Individuals with acute vitamin A toxicity have dry, scaly skin, with large areas
of desquamation and fissuring of the lips and angles of the mouth.
Systemic findings : Include headache, fatigue, anorexia, nausea, vomiting, blurred vision, pseudotumor cerebri,
myalgias, and arthralgias.
Chronic toxicity : Cutaneous findings –
 Early cutaneous sign of toxicity in adults is dryness of the lips, which may progress to diffuse, dry, pruritic,
scaly skin with peeling of palms and soles, alopecia, follicular hyperkeratosis, and hyperpigmentation of the
face and neck.
 Coarse hair with diffuse alopecia, coarse skin with generalized exfoliation, hyperpigmentation, and exfoliative
cheilitis.
Systemic findings : Pseudotumor cerebri may cause headaches and papilledema. Skeletal changes are common with
vitamin A toxicity. Deposition of excess vitamin A in adipose tissue and perisinusoidal fibrosis of the liver leading to
cirrhosis are the most significant effects of long-term vitamin A toxicity. Anorexia, fatigue, and weight loss may also
occur.

7. Treatment : Almost all of the symptoms of vitamin A toxicity subside after the excess vitamin intake is discontinued,
with the exception of liver cirrhosis and consequences of pseudotumor cerebri.
● Carotenemia and Carotenoderma : Occurs due to excessive intake of carotene, characterized by yellow-orange skin
pigmentation. Carotenes are converted to vitamin A in the gastrointestinal tract, but approximately one-third of carotene
is directly absorbed. Several factors can affect carotene absorption, including thyroid hormone, pancreatic lipase and
bile acid concentrations, processing of foods, and dietary fat and fiber content besides excessive intake.
Clinical findings : Excessive ingestion of carotenes does not result in hypervitaminosis A. Excess carotene deposits in
the stratum corneum due to its high lipid content. The yellow discoloration of skin secondary to carotenemia is called
carotenoderma. The carotene is excreted by sebaceous glands and in sweat, so the yellow pigmentation appears first on
the face, predominantly in the nasolabial folds and forehead, and then becomes diffusely distributed, with accentuation
on the palms and soles. The pigmentation is particularly noticeable in artificial light. Carotenoderma, in contrast to
jaundice, spares mucous membranes, including the sclera.
Treatment : Improves after discontinuation of excess intake.
● Vitamin D (Calcitriol) : No specific cutaneous changes develop due to deficiency.
● Vitamin E (Tochopherol) :
Vitamin E is rarely associated with deficiency or excess states of disease. Vitamin E is found in oils, various fortified
grains, dark green leafy vegetables, legumes, nuts, avocado, and fishes. The main physiological activity of tocopherol
is antioxidation. Whether the vitamin is essential to humans is still a matter of debate. Fat soluble vitamin E is
located in the stratum corneum and seems to play a role in protecting this layer from damage. An inhibitory effect on
hyaluronidase and a protective effect on cellular membranes and on vitamin A oxidation have been suggested
Clinical findings : Deficiency states are rare. Haemolysis and purpura can occur. Neurological disorder can develop.
● Vitamin K (Phytonadione) :
Vitamin K is a necessary co-factor in the carboxylation of glutamate residues on coagulation factors II, VII, IX, X, and
proteins C and S.
Dietery sources : Dietary vitamin K, phylloquinone, is found in green, leafy vegetables, certain legumes, soybeans,
cereals, and beef liver. Approximately one half of the body’s vitamin K is obtained though these dietary sources, and
the other half is synthesized by gastrointestinal flora as menaquinones, which are passively absorbed in the distal small
bowel and colon.
Vitamin K deficiency beyond the newborn period is rare, but may result from malabsorption, liver disease, inadequate
dietary intake, or medications. Antibiotic use can result in vitamin K deficiency by altering the populations of normal
bowel flora. Coumarin interferes with vitamin K epoxide reductase, an enzyme important in the recycling of inactive
vitamin K into its active form. Other medications that can interfere with vitamin K metabolism include anticonvulsants
(phenytoin), rifampin, isoniazid, high-dose salicylates, cholestyramine, and cephalosporins.
Clinical findings : Vitamin K deficiency leads to impaired coagulation and hemorrhage and can present in the neonatal
period, when it is referred to as hemorrhagic disease of the newborn(HDN). Neonates are particularly prone to vitamin
K deficiency because of poor transplacental transfer, low dietary intake, and a sterile bowel. HDN is divided into early
presentation and late presentation.
Early HDN causes unexpected bleeding in the first week of life in an otherwise healthy neonate. It can present as
ecchymoses, cephalohematomas, or nasal, subgaleal, umbilical, intestinal, or intracranial hemorrhages.
Late HDN presents in 2- to 12-week-old infants who are primarily breast-fed and who received no or inadequate neonatal
vitamin K prophylaxis. Vitamin K deficiency in older children and adults can present as purpura, ecchymoses, gingival
bleeding, and gastrointestinal, genitourinary, and retroperitoneal hemorrhage.

8. Treatment : Neonatal prophylaxis is traditionally administered as a single intramuscular dose of 0.5 to 1.0 mg of vitamin
K. Acute treatment of vitamin K deficiency with hemorrhage is with fresh frozen plasma to replace deficient coagulation
factors. Vitamin deficiency can also be treated with parenteral or intramuscular 5 to 10 mg vitamin K per day to correct
severe deficiency.
Water-Soluble Vitamins:
1. Vitamin B1 (Thiamine) :
Thiamine is an essential coenzyme for several enzymes involved in nicotinamide adenine dinucleotide phosphate
(NADPH) synthesis, carbohydrate metabolism, and deoxyribose and ribose synthesis.
Dietery sources : Obtained from whole grains, enriched bread products, dried peas and beans, potatoes, and fish.
Polished rice eliminates the thiamine containing husk and predisposes to thiamine deficiency.
Clinical Findings : Deficiency causes beri-beri disease which means “extreme weakness”. Early signs include
irritability, apathy, restlessness, and vomiting. Other symptoms include congestive heart failure, tachycardia, dyspnea,
and cyanosis. As the disease progresses, neurologic signs of wernicke encephalopathy may develop.
Adult beriberi has been categorized into dry and wet forms. Dry beriberi describes a symmetric distal peripheral
neuropathy involving both sensory and motor systems. Wet beriberi includes neuropathy and signs of cardiac
involvement, peripheral edema, and tachycardia. A red, burning tongue and peripheral edema have also been
observed with wet beriberi.
Management : Usually, treatment for beriberi is initiated with intravenous or intramuscular thiamine of 50 to 100 mg
per day for 7 to 14 days, then oral supplementation is provided until full recovery is documented.
2. Vitamin B2 ( Riboflavin ) :
Riboflavin is fluorescent yellow-green substance found in milk. Riboflavin is used in two coenzymes, flavin
mononucleotide (FMN) and flavin-adenine dinucleotide (FAD), both of which are involved in oxidation-reduction
reactions in cellular respiration and oxidative phosphorylation. These two enzymes are also involved in pyridoxine
(vitamin B6) metabolism.
Dietery sources : Riboflavin is typically obtained through dairy products, nuts, meat, eggs, whole grain and enriched
bread products, fatty fish, and green leafy vegetables. Deficiency states can be caused by decreased intake, inadequate
absorption, and phototherapy. Alcoholics, the elderly, and adolescents are groups at risk for riboflavin deficiency
secondary to poor nutritional intake.
Visible light phototherapy for jaundiced neonates causes photodecomposition of riboflavin. Chlorpromazine and other
tricyclic drugs inhibit transport of riboflavin in the gastrointestinal tract, predisposing to deficiency states.
Clinical Findings : Acute deficiency - Deep red erythema, epidermal necrolysis, and mucositis. The severity of
symptoms depends on the severity of deficiency.
Chronic deficiency : Clinical signs begin 3 to 5 months after initiation of an inadequate diet.
 Skin and mucous membrane findings predominate. Initially, angular stomatitis manifests as small papules at the
corners of the mouth that enlarge and ulcerate before developing into macerated fissures that extend laterally
and often bleed. Pronounced cheilosis with erythema, xerosis, and vertical fissuring of lips can occur.
 Early glossitis appears as prominent lingual papillae, but after these papillae are lost, the tongue becomes
smooth, swollen, and magenta in color.
 The dermatitis of riboflavin deficiency resembles seborrheic dermatitis in that it involves the nasolabial folds,
nostrils, nasal bridge, forehead, cheeks, and posterior auricular regions. Flexural areas of the limbs may also be
affected. Plugging of the sebaceous glands (dyssebacia) may be observed around the nose.
 The dermatitis can affect the genitalia, more often to a greater extent in males than in females.
 A red, confluent, crusty, or lichenified dermatitis of the scrotum often spreads to involve the inner thighs. In
general, the dermatitis is worse in areas of chafing or trauma. Infants frequently manifest the dermatitis in the

9. inguinal areas. In older individuals, the dermatitis is often more pronounced in facial creases and wrinkles, and,
if incontinent, can involve the perianal and buttock areas.
Management : Measurement of erythrocyte glutathione reductase activity can be used as a screening test. Treatment
for deficient infants and children is 1 to 3 mg per day, and for adults, 10 to 20 mg.
3. Vitamin B3 ( Niacin ) :
Niacin (vitamin B3) is a vitamin co-factor that can be obtained in the diet or synthesized endogenously from the essential
amino acid tryptophan. It is an essential water-soluble vitamin that is used to produce nicotinamide adenine
dineucleotide (NAD and NADP). These two agents act as hydrogen donors and acceptors in oxidation-reduction
reactions involved in the synthesis and metabolism of carbohydrates, fatty acids, and proteins.
Dietery Sources : Niacin is found in whole grains and enriched bread products, nuts, dairy products, liver, animal meat,
mushrooms, and dried beans.
Corn and maize contain bound niacin, so without alkaline hydrolysis to release the niacin, it is unavailable for absorption.
Jowar, a type of millet found in parts of India, contains adequate levels of niacin, but large quantities of leucine interfere
with the conversion of tryptophan to niacin. Alcoholics develop pellagra from a combination of poor diet and
malabsorption.
Patients with carcinoid syndrome are at risk for pellagra. Normally, about 1% of tryptophan is metabolized to serotonin,
but in carcinoid syndrome, an excessive amount, about 60%, is converted to serotonin. Because of this diversion of
tryptophan to serotonin production, less tryptophan is available to make niacin.
Medication like isoniazid, 5-fluorouracil, 6-mercaptopurine, phenytoin, chloramphenicol, azathioprine, sulfonamides,
and antidepressants can also induce symptoms of pellagra.
Clinical Findings : Derived from the Italian terms ‘‘pelle’’meaning skin and ‘‘agra’’ meaning rough, pellagra dermatitis
presents as a photodistributed erythema. Involved skin is often sharply demarcated from surrounding healthy areas.
Pellagra is classically described with the four “ Ds” of dermatitis, diarrhea, dementia, and death.
The characteristic photosensitive dermatitis begins as erythematous, painful, or pruritic patches. The skin becomes
progressively more edematous, and several days later may develop vesicles and bullae that can rupture, leaving crusted
erosions, or develop into brown scales. Over time, the skin thickens into sharply demarcated, keratotic, hyperpigmented
plaques. Painful fissures can develop in the palms and soles, resembling goose skin. The dorsum of the hands is the
most commonly affected site, and when the rash extends proximally, more on the radial than ulnar side, it forms the
“gauntlet” of pellagra. A butterfly distribution may be apparent on the face when it extends from the nose to the cheeks,
chin, and lips. When the dermatitis affects the upper central portion of the chest and neck, it is referred to as “Casal’s
necklace.”
Mucous membrane involvement may manifest as cheilitis, angular stomatitis, glossitis, and ulceration of the buccal
mucosa and vulva.
Systemic findings : Gastrointestinal symptoms may represent the earliest signs of pellagra. Diarrhea, nausea, vomiting,
abdominal pain, and anorexia have been reported. Neurologic symptoms, such as insomnia, fatigue, nervousness,
apathy, impaired memory, and depression, can progress to psychosis and dementia in later stages. Without treatment,
pellagra leads to death from multiorgan failure.
Management : Treatment with 500 mg per day of nicotinamide or nicotinic acid is given over several weeks.
Nicotinamide is preferred over nicotinic acid because nicotinic acid is frequently associated with headache and flushing.
Neuropsychiatric symptoms may remit after 24 to 48 hours of treatment, but skin lesions often take 3 to 4 weeks to
clear.
4. Vitamin B6 (Pyridoxine) :
Pyridoxine is present in meats, whole grains, vegetables, and nuts. Processing of these foods can decrease the amount
of available vitamin B6. The most common form of vitamin B6 is pyridoxal-5-phosphate. Vitamin B6 is employed in
multiple pathways, including the decarboxylation and transamination of amino acids, gluconeogenesis, conversion of
tryptophan to niacin, sphingolipid synthesis, prostaglandin synthesis, and neurotransmitter synthesis.

10. Medications implicated in causing deficiency include isoniazid, hydralazine, penicillamine, and oral contraceptives.
Isoniazid, hydralazine, and penicillamine bind to pyridoxal-5-phosphate and increase excretion and/or decrease activity
of the coenzyme.
Clinical Findings : Vitamin B6 deficiency presents as a seborrheic-like dermatitis of the face, scalp, neck, shoulders,
buttocks, and perineum. Clinical features resemble niacin deficiency, including photodermatitis, glossitis, and cheilitis.
Glossitis appears as redness, burning, and ulceration of the tongue, leading to flattening of the filiform papillae. Other
manifestations include angular stomatitis, cheilosis, and conjunctivitis. Vitamin B6 deficiency often resembles pellagra
because vitamin B6 is needed for the conversion of tryptophan to niacin.
Somnolence, peripheral neuropathy, paresthesias, weakness, and confusion can occur. Other signs and symptoms are
nonspecific, and include nausea, vomiting, depression, anorexia, and anemia.
Management : Treatment involves discontinuation of inciting medication where relevant and initiating replacement
therapy with 100 mg of pyridoxine per day. Oral lesions resolve in days, skin and hematologic changes resolve in weeks,
and neurologic symptoms over several months.
5. Vitamin B9 ( Folic acid ) :
Folate can be found in almost all foods, particularly in liver, wheat bran and other grains, leafy green vegetables, and
dried beans. Tetrahydrofolate, the coenzyme form of folate, is used for single-carbon transfers in amino acid, purine,
and pyrimidine metabolism. Malabsorptive states and antifolate medications (such as methotrexate, trimethoprim, oral
contraceptives, and pyrimethamine, phenytoin, phenobarbital ) have been implicated in producing folate deficiency. In
children, folate deficiency can be also associated with excessive boiling of milk or a goat’s milk diet because of its low
bioavailability of folate when compared with human or cow’s milk.
Clinical findings : The primary manifestation is hematologic: hypersegmented neutrophils, macrocytosis, and
megaloblastic anemia. Neutropenia, thrombocytopenia, diarrhea, and irritability may also be observed.
Cutaneous findings : Mucocutaneous findings include glossitis with atrophy of the filiform papillae, angular cheilitis,
mucosal ulceration, perirectal ulcerations, perineal seborrheic dermatitis, and diffuse brown hyperpigmentation
concentrated in the palmar creases and flexures.
Management : Folic acid supplementation is typically curative. Discontinuation of antifolate agents if implicated is
recommended if involved. Treatment involves 1 to 5 mg of folic acid per day.
6. Vitamin B12 ( Cobalamin ) :
Vitamin B12 is an important coenzyme for two biochemical pathways in humans. Methylcobalamin is a coenzyme for
methyltransferase that converts methylate homocysteine to methionine, which is used in DNA, protein, and lipid
metabolism. 5′-Adenosylcobalamin is required to catalyze the reaction by methylmalonyl coenzyme A (CoA) mutase
to convert methylmalonic acid to succinyl-CoA, which is used in fat and carbohydrate metabolism.
Vitamin B12 is found primarily in animal products, with liver, eggs, milk, beef, and organ meats being excellent sources.
The body is able to store large amounts of vitamin B12, so symptoms of deficiency often take 3 to 6 years to develop.
Causes of deficiency include inadequate intake, decreased gastric acid states (chronic proton pump inhibitors and
histamine H2 receptor blockers), decreased intrinsic factor (pernicious anemia, atrophic gastritis, postgastrectomy),
microbial competition in the gut (bacterial overgrowth, Diphyllobothrium latum infection), and impaired absorption
(Crohn disease, Whipple disease, Zollinger-Ellison syndrome, celiac disease).
Clinicals findings :
 Mucocutaneous manifestations of vitamin B12 deficiency include glossitis, angular cheilitis, hair
depigmentation, and cutaneous hyperpigmentation.
 Glossitis is characterized by an atrophic, red, and painful tongue with atrophy of the filiform papillae, which is
referred to as Hunter glossitis. Hunter’s glossitis (or Moeller-Hunter) is the most classic form. Hunter’s glossitis,
which presents in up to 25% of cases.

11.  Other oral manifestations of vitamin B12 deficiency: glossodynia, recurrent ulcers, lingual paresthesia, burning,
pruritus, dysgeusia, intolerance to dental prosthesis, intermittent xerostomia, stomatitis, and cheilitis.
 Recently, glossitis with linear lesion has been described as early feature for detection of the disease, even in
absence of anaemia.
 Hair depigmentation may be localized or diffuse.
 Hyperpigmentation can be diffuse and symmetric or involve a few scattered macules. The greatest concentration
is usually observed on the hands, nails, and face, with the most commonly affected areas being the palmar
creases, flexural regions, and pressure points.
 Hyperpigmentation often resembles Addison disease, but patients show no evidence of adrenal insufficiency.
Cobalamin deficiency can cause the neurologic manifestations of subacute combined degeneration of the dorsal and
lateral spinal column. Generalized weakness with paresthesias, paraplegia can develop.
Management : Peripheral blood smear shows hypersegmented neutrophils and macrocytic RBCs. Bone marrow biopsy
reveals a hypercellular marrow secondary to disordered maturation. Deficiency is diagnosed by measuring serum
cobalamin levels, with levels less than 200 pg/mL indicating definite B12 deficiency and 200 to 300 pg/mL being
borderline low.
For vitamin B12 deficiency in adults, supplementation with 30 μg administered via the intramuscular or subcutaneous
route for 5 to 10 days, followed by 100 to 200 μg per month is recommended. In children, a dose of 100 μg/day for 10
to 15 days followed by 100 μg per week for several months may be required.
7. Vitamin C ( Ascorbic Acid ) :
Vitamin C is an antioxidant and essential co-factor in several biologic reactions, including collagen biosynthesis,
prostaglandin metabolism, fatty acid transport, and norepinephrine synthesis. Humans are unable to synthesize ascorbic
acid because they lack gulonolactone oxidase, an enzyme involved in synthesis of ascorbic acid. Ascorbic acid is
required for the hydroxylation of proline residues on procollagen, allowing the formation of hydrogen–hydrogen
bonding in the triple helix of mature collagen.
As it stimulates collagen synthesis, it appears crucial for the healing/regeneration process and wound repair. Oral
administration of 0.5 to 1.0 g/day of vitamin C are recommended to accelerate healing. Adequate supplies of vitamin C
are needed, especially for postoperative patients, in whom a rapid utilization of the vitamin occurs at the site of wounds.
Because vitamin C is the major water-soluble antioxidant found in extracellular and intracellular compartments, it
appears to be a crucial factor in skin. Topical application of vitamin C demonstrates photoprotective properties and
modifications of skin relief and ultrastructure, suggesting a positive role in the prevention and treatment of skin aging.
Finally, vitamin C can rescue keratinocytes from UV-mediated cytotoxicity and UV-induced skin cancer.
Dietery sources : Obtained from fruits and vegetables, like potatoes, tomatoes, berries, citrus fruits, and green
vegetables.
Depletion of body stores occurs after 1 to 3 months of a deficient diet. Inadequate intake is the most common cause of
deficiency.Increased vitamin C requirements are encountered with certain drugs, including aspirin, indomethacin,
tetracycline, oral contraceptives, corticosteroids, and tobacco smoking. Peritoneal dialysis and hemodialysis can induce
scurvy because the water-soluble vitamin is removed during the dialyzing process. Cooking reduces vitamin C content
by 20–40%,with further decomposition after long-term storage.
Clinical findings :
Cutaneous findings : The earliest cutaneous sign of scurvy is phrynoderma—enlargement and keratosis of hair follicles,
especially on the posterolateral aspect of the arms, resembling keratosis pilaris. The keratotic plugging generalizes,
extending to the back, buttocks, posterior thighs, calves, and shins. The hairs within these plugged follicles become
curled, resulting in corkscrew hairs. As the disease progresses, the perifollicular area become red from congestion and
proliferation of surrounding blood vessels, then turn purple, and finally red and hemorrhagic. This palpable perifollicular
purpura is characteristically found on the legs. “Woody edema” of the lower extremities is associated with pain and
ecchymosis.
Poor wound healing and even dehiscence of old wounds in skin and bone can occur. Splinter hemorrhages in the nail
bed can also occur.

12. Oral manifestations are common. Gingival disease manifests as swelling, ecchymoses, bleeding, and loosening of teeth.
Interdental and marginal gingivae become red, smooth, swollen, and shiny before becoming purple, black, and necrotic.
Hemorrhage can occur in areas other than the skin, mouth, and nails.
Systemic findings : Hemorrhage can be intra-articular, intramuscular, and subperiosteal. This can lead to pain and
disruption of the growth plates. Epistaxis, hematuria, intracerebral hemorrhage, subconjunctival hemorrhage, and
gastrointestinal hemorrhage can occur. Bowing of the long bones and a depressed sternum with an outward projection
of the end of the ribs are noted on musculoskeletal examination.
Management : Diagnosis is largely made on clinical grounds, and a high index of suspicion must be maintained in
children presenting with the constellation of cutaneous and musculoskeletal complaints. With vitamin C (100 to 300
mg/day )supplementation, clinical symptoms rapidly improve.
8. Biotin :
Biotin is an essential co-factor for several carboxylating enzymes: acetyl-CoA carboxylase in fatty acid synthesis and
lipogenesis; pyruvate carboxylase in gluconeogenesis; and propionyl-CoA and 3-methylcrotonyl-CoA carboxylases,
both involved in amino acid catabolism. Eggs, liver, milk, peanuts, mushrooms, and hazelnuts are common sources of
biotin.
Individuals following fad diets high in raw egg whites can be at risk for deficiency. Avidin presents in raw eggs binds
biotin and makes it poorly absorbable.
Individuals on unsupplemented parenteral nutrition and on long-term antibiotics are particularly at risk because the
antibiotics eradicate biotin-producing enteric flora. Symptoms can develop 3 to 6 months after initiation of
unsupplemented parenteral nutrition or a raw egg white–rich diet, but appear earlier in infants because of the greater biotin
requirement for growth.
Clinical findings :
 An erythematous, scaling, and crusting dermatitis usually begins around the eyes, nose, and mouth and continues
to involve multiple periorificial areas, including the perianal region.
 Alopecia, conjunctivitis, and glossitis have also been associated.
Neurologic findings include irritability, lethargy, paresthesias, hypotonia, developmental delay, and myalgias.
Management : Dietery history should be taken. If dietary history does not adequately explain findings suggestive of
biotin deficiency, evaluation for inborn errors of metabolism is recommended. Acquired deficiency is treated with 150
μg of biotin per day until resolution of symptoms.
Vitamin Recommended daily doses Replacement therapy
A
D
K
C
5,000 I.U.
•Infants & children: 100,000–200,000 IU every 4–6
months from age 6 months to 5 years
• In measles : 200,000 IU once daily × 2 days
• Postpartum women: 200,000 IU within 6 weeks
of delivery
5 to 10 μg/day
Neonatal prophylaxis is traditionally administered as a
single intramuscular dose of 0.5 to 1.0 mg of vitamin K.
40 – 60 mg/day
• Based on severity of ophthalmologic impairment
• 10,000–50,000 IU/day PO or IM in infants on
days 1, 2 & 14
• 2,00,000 IU/day PO or IM in children and adults
on days 1, 2 & 14
• Higher doses given if keratomalacia is present
• 200 to 400 μg vitamin D per day until resolution
of symptoms, about 2 to 3 months
• Newborns: 0.5–1 mg sc or IM
• Children: 2 mg
• Adults: 5–10 mg
• Intravenously in emergencies
• Fresh frozen plasma
• Adults: 800 mg/day orally
• Children: 150 mg/day orally

13. B1
B2
B3
B6
B9
B12
0.5 mg per 1000 kcal energy
0.6 mg per 1000 kcal energy
15 – 20 mg/day
Adult males require at least 2 mg per day; adult females
require at least 1.6 mg per day; and infants require
about 0.3 mg per day
100-150 μg/day
2 to 3 µg per day
• 100 mg TID IV × several days, followed by 100
mg/day orally until complete recovery
• Riboflavin 3–10 mg/day orally
• In refractory cases, 2 mg IM TID
• Mild cases – nicotinic acid 50 mg TID orally
• If symptomatic, nicotinic acid 25 mg TID IV
• Advanced stages – nicotinic acid 50–100 mg
IM TID × 3–4 days, followed by similar
quantities PO
• Pyridoxine 50–100 mg/day prevent neuropathy
• 100 mg/day IV in those with seizures
• Folate 1 mg TID PO, followed by 1 mg/day
• 30 μg administered via the intramuscular or
subcutaneous route for 5 to 10 days, followed
by 100 to 200 μg per month
Minerals :
(i) Iron :
Iron is used in several biologic pathways, including heme synthesis, oxidation-reduction reactions, collagen synthesis,
and as a co-factor for enzymes such as succinic dehydrogenase, monoamine oxidase, and glycerophosphate oxidase.
Dietery Sources : Red meats, egg yolks, dried beans, nuts, dried fruits, green leafy vegetables, and enriched grain
products. Deficiency states result from inadequate intake or chronic blood loss. Groups at high risk include infants,
menstruating females, and individuals with chronic gastrointestinal bleeds. Infants on an iron fortified formula are at
risk for deficiency 3 to 6 months after transitioning to cow’s formula because of the lower iron content of cow’s milk.
Clinical findings – Iron deficiency causes microcytic hypochromic anaemia.
Nails : Fragile, longitudinally ridged, lamellated, or brittle nails. As deficiency progresses, the nail plate shows thinning,
flattening, and a spoon-shaped convexity known as koilonychia. Even after iron replacement therapy begins,
koilonychias resolves slowly.
Hairs : Lusterless, brittle, dry, and focally narrow or split hair shafts, likely caused by impaired keratin production.
Heterochromia of black scalp hair with alternating segments of dark brown, white, and silver bands has been described.
Several studies have examined the relationship between iron deficiency and hair loss. Almost all have addressed women
exclusively and have focused on noncicatricial hair loss. Some suggest that iron deficiency may be related to alopecia
areata, androgenetic alopecia, telogen effluvium, and diffuse hair loss, whereas others do not. Currently, there is
insufficient evidence to recommend universal screening for iron deficiency in patients with hair loss. In addition, there
is insufficient evidence to recommend giving iron supplementation therapy to patients with alopecia and iron deficiency
in the absence of IDA. The decision to do either should be based on clinical judgment.
Mucous membrane manifestations include aphthous stomatitis, angular stomatitis, glossodynia, and absent or atrophied
tongue papillae.
Management : Diagnosed by peripheral blood smear, measurement of serum iron levels, ferritin, total iron binding
capacity, and transferrin saturation. Treatment involves appropriate iron supplementation.
Hemochromatosis : Due to chronic iron overload. Hyperpigmentation and ichthyosis-like changes of the skin are seen.
Associated findings are cirrhosis of the liver, diabetes mellitus, and cardiomyopathy.

14. (ii) Zinc :
Zinc, a critical component of the body’s metalloenzymes, is an essential trace element. Zinc-dependent enzymes have
important roles in gene regulation, protein synthesis, and immune cell function. Adequate zinc levels are also important
for wound healing and for T-cell, neutrophil, and natural killer cell function. Dietary sources of zinc include meat, fish,
shellfish, eggs, dairy products, and legumes, with the highest and most bioavailable forms of zinc found in meats, fish,
and shellfish. Phytates (found in cereal grains, legumes, and nuts) and fiber interfere with intestinal zinc absorption.
Human breast milk contains very high levels of zinc during the first 1 to 2 months of lactation, averaging 3 mg/L;
subsequently, zinc levels decrease. Human breast milk also contains a zinc-binding ligand that increases the
bioavailability of breast milk zinc. Once in the plasma, zinc is bound to albumin or macroglobulin, making those with
hypoalbuminemia, such as found in nephrotic syndrome, at risk for acquired zinc deficiency.
Although total body zinc is stored primarily in the bones, muscles, prostate, and skin, there is no free exchange of stored
zinc, and metabolic needs must be met by a continued supply of dietary zinc.
Zinc deficiency may be either inherited or acquired. The inherited form of zinc deficiency (acrodermatitis enteropathica),
classically presents during infancy on weaning from breast milk to formula or cereal, which have lower zinc
bioavailability than breast milk. There is defect in an intestinal zinc transporter, the human ZIP4 protein, which prevents
appropriate enteral zinc absorption.
Acquired zinc deficiency may result from states associated with inadequate intake, impaired absorption, or increased
excretion, including pregnancy, lactation, extensive cutaneous burns, generalized exfoliative dermatoses, food
faddism, parenteral nutrition, anorexia nervosa, and even excessive sweating. Intestinal malabsorption syndromes, such
as inflammatory bowel disease and cystic fibrosis, result in impaired intestinal absorption of zinc, whereas alcoholism
and nephrotic syndrome result in increased renal zinc loss.
Clinical findings : Acrodermatitis enteropathica (AE) presents soon after weaning in affected infants or during the
fourth to tenth week of life in infants who are not breast-fed.
 The classic features of AE include alopecia, diarrhea, lethargy, and an acute eczematous and erosive dermatitis
favoring acral areas—perioral, periocular, anogenital, hands, and feet.
 The cutaneous findings are highly characteristic and often present initially as a nonspecific, acrally distributed,
symmetric, eczematous dermatitis.
 Over time, bullae and erosions with a characteristic peripheral crusted border develop.
 Delayed wound healing, acute paronychia, conjunctivitis, blepharitis, and photophobia may also be observed.
Patients also appear to be predisposed to systemic infections as a result of impaired cell-mediated immunity, and
superinfection with Candida albicans and bacteria, usually Staphylococcus aureus, is common.
Diarrhea may be prominent but is not seen in all cases. If untreated, the disease is fatal. Acute zinc deficiency secondary
to impaired absorption of zinc, inadequate intake, or excessive renal or intestinal losses may result in a clinical picture
that resembles AE and occurs also in adults.
A chronic or subacute form of zinc deficiency is also recognized. These patients often have zinc levels in the mildly
deficient range (40 to 60 μg/dL). Clinical manifestations include growth retardation in children and adolescents,
hypogonadism in males, dysgeusia, poor appetite, poor wound healing, abnormal dark adaptation, and impaired
mentation. Cutaneous manifestations, when present, are usually less striking and present predominantly as a
psoriasiform dermatitis involving the hands and feet and, occasionally, the knees.
Histopathology : The histopathologic features of AE are generally regarded as indistinguishable from those of other
forms of so-called deficiency dermatitis, which typically also includes niacin/vitamin B3deficiency (pellagra). Nearly
pathognomonic in the histopathologic examination of deficiency dermatitis is the presence of fully developed
‘‘necrolysis,’’ a term describing cytoplasmic pallor, vacuolization, ballooning degeneration, and subsequent confluent
necrosis of keratinocytes within the superficial stratum spinosum and stratum granulosum of the epidermis. The affected
keratinocytes often have pyknotic nuclei. In many or most instances, however, necrolysis is not fully developed, and
only pallor may be present.

15. Management : A low plasma zinc level is the gold standard for diagnosing zinc deficiency. In cases in which the plasma
zinc level is equivocal and the diagnosis is uncertain, skin biopsy for routine histology may be helpful. The characteristic
features are variable psoriasiform hyperplasia with confluent parakeratosis, spongiosis and pallor of the upper epidermis,
focal dyskeratosis, and variable epidermal atrophy, These findings, however, are not specific; any may be seen in a
number of other nutritional deficiencies.
Zinc supplementation with either an enteral or parenteral formulation is appropriate. Clinical response is usually rapid,
with initial improvement noted within several days.
Although several zinc formulations are available, the most commonly used enteral formulation is zinc sulfate. Zinc
chloride is recommended for parenteral supplementation. In children, 0.5 to 1.0 mg/kg of elemental zinc given as one
to two daily doses is recommended for mild to moderate zinc deficiency. Higher doses may be required in cases of
acquired zinc deficiency due to intestinal malabsorption. In adults, 15 to 30 mg of elemental zinc per day is usually
sufficient in cases of acquired zinc deficiency.
(iii) Copper :
Copper is an essential component of several metalloenzymes, including tyrosinase and lysyl oxidase. Tyrosinase is
involved in melanin biosynthesis, and lysyl oxidase is involved in collagen cross linking. Other copper enzymes are
involved in catecholamine production, free radical detoxification, and oxidation reduction reactions. Copper is found in
fish, oysters, whole grains, beef and pork liver, chocolate, eggs, and raisins.
Copper deficiency can result from malnutrition, malabsorptive states, chronic unsupplemented parenteral nutrition,
infants with a strictly cow’s milk diet, and excessive intake of antacids, zinc, iron, or vitamin C, which can interfere
with absorption.
Clinical findings : Hypopigmentation of hair and skin and bony abnormalities (osteoporosis, fractures, periosteal
reaction, and flaring of anterior ribs). Microcytic anemia, neutropenia, hypocupremia, and hypoceruloplasminemia can
be observed. Neutropenia is the earliest and most common sign of copper deficiency and is a sensitive measure of
treatment adequacy.
Management : Treatment is with supplemental copper in the diet.
(iv) Selenium : Selenium is an essential component of glutathione peroxidase, an antioxidant. Selenium is found in
seafood, red meat, egg yolks, grain products, and chicken. Two disorders have been attributed to selenium deficiency:
Keshan disease and Kaschin-Beck disease.
Keshan disease : Keshan disease is a multifocal myocarditis leading to fatal cardiomyopathy. Muscle pain and weakness
with hepatic congestion, mesenteric lymphadenosis, erythrocyte macrocytosis without anemia, and pancreatic exocrine
dysfunction have also been seen.
Cutaneous findings in these patients have included white nail beds, similar to those of Terry’s nails in hepatic cirrhosis,
and hypopigmentation of skin and hair (pseudoalbinism).
Kaschin-Beck disease : an osteoarthropathy that affects the epiphyseal and articular cartilage and the epiphyseal growth
plates, resulting in enlarged joints and shortened fingers and toes.
Management : Diagnosis of selenium deficiency is through measurement of plasma selenium levels and glutathione
peroxidase activity. Selenium supplementation is used for both acute correction and long term maintenance.
(v) Mangnese : Mangnese deficiency can be associated with development of miliaria crystallina. Excess has been
associated with neurologic sequelae.

16. Clinical signs that may be due to nutrient deficiency.
Clinical Sign Nutrient Deficiency Clinical Sign Nutrient Deficiency
Hair
Transverse depigmentation
Easily pluckable
Sparse and thin
Skin
Dry, scaling
Flaky paint dermatitis
Follicular hyperkeratosis
Perifollicular petechiae
Petechiae, purpura
Pigmentation, desquamation
Nasolabial seborrhea
Pallor
Scrotal/vulvar dermatoses
Subcutaneous fat loss
Nails
Spooning
Transverse lines, ridging
Head
Temporal muscle wasting
Parotid enlargement
Eyes
Night blindness
Corneal vascularization
Xerosis, Bitot spots,
keratomalacia
Conjunctival inflammation
Protein, copper
Protein
Protein, zinc, biotin
Zinc,vitamin A,essential fatty
acids
Protein, niacin, riboflavin
Vitamins A, C, E and EFA
Vitamin C
Vitamins C and K
Niacin
Niacin,riboflavin, pyridoxine
Iron, folate, vitamin B12, copper
Riboflavin
Calories
Iron
Protein–calorie
Protein–calorie
Protein
Vitamin A, zinc
Riboflavin
Vitamin A
Riboflavin
Mouth
Glossitis (scarlet, raw)
Bleeding gums
Cheilosis, angular stomatitis
Atrophic lingual papillae
Hypogeusia
Tongue fissuring
Chest
Thoracic rosary
Extremities
Muscle tenderness, pain
Muscle wasting
Edema
Bone tenderness
Other
Delayed wound healing
Niacin, pyridoxine,riboflavin,
vitamin B12, folate
Vitamin C, riboflavin
Riboflavin
Niacin, iron, riboflavin, folate,
vitamin B12
Zinc, vitamin A
Niacin
Vitamin D
Thiamine, vitamin C
Protein–calorie
Protein, thiamine
Vitamin C, vitamin D, calcium,
phosphorus
Zinc,protein–calorie, vitamin C