ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY

BY PROF. SYED IMTIAZ ALI SHAH PROFESSOR & HEAD DEPARTMENT OF OPHTHALMOLOGY CHANDKA MEDICAL COLLEGE LARKANA PAKISTAN

INTRODUCTION Vitamin A, the first discovered fat soluble vitamin and chemically a retinol, is the Immediate precursor of two very important metabolites 1. Retinal and 2. Retinoic acid Retinal is a very important component of rhodopsin which is mandatory for functioning of photoreceptors. Retinoic acid has a vital role to play as messenger during transcription of a number of genes.

NATURAL AVAILABILITY Vitamin A is present in animal source particularly in the liver, beef, chicken, eggs and whole milk. Plants are devoid of vitamin A as such but do contain provitamin A like beta-carotene which is converted into retinol in intestinal mucosa during digestion. Plant source include carrots, mango, orange fruits, sweet potato and spinach.

FUNCTIONS OF VITAMIN A As it is important part of visual purple of both rods and cones, it serves both night and day vision. As the rods are affected first, night blindness has become a famous feature of vitamin A deficiency It Maintains epithelia of skin and mucous membranes all over the body Its immune strengthening function has led to the popularity of this vitamin as anti-infective.

FUNCTIONS OF VITAMIN A Reproductive function includes its need in spermatogenesis and female reproductive cycle. Skeletal development and maintenance is achieved by its need in the functioning of osteoblasts and osteoclasts.

DEFICIENCY STATES Blindness occurs as a result of photoreceptor dysfunction, xerophthalmia and keratomalacia. Increased fatigue. Increased risk of respiratory infections Increased risk of gastrointestinal infections

DEFICIENCY STATES Increased risk of infertility Increased mortality rate particularly in children due to infectious diseases like measles Abnormality in bone growth particularly in skull leading to compressive neuropathy including blindness due to optic nerve compression Elevated intracranial pressure due to inadequate absorption of CSF through meninges

BIOAVAILABILITY Retinol esterifies into retinyl esters and the retinyl esters of animal and plant origin are carried through micelles in the lymph to the blood and finally liver where 50 to 80% of vitamin A is stored by binding with the cellular RBP (retinol binding protein). In the blood, vitamin A is transported in bound form with retinol binding protein (RBP) which is in turn bound to transthyretin.

BIOAVAILABILITY Retinol binding protein, with normal serum levels of 40-50 mcg/dl, is synthesized in the liver in presence of amino acids and zinc. Therefore decreased levels of zinc, iron and RBP are strong reflection of vitamin A deficiency.

BIOAVAILABILITY Vitamin A supplementation alone is not effective in the treatment of vitamin A deficiency states when associated iron deficiency is present. This reflects the importance of associated iron and zinc deficiency.

5000 IU of Vitamin A are required by an adult per day VITAMIN A REQUIREMENT 5000 IU of Vitamin A are required by an adult per day Requirement is increased in sick children particularly suffering from measles

CAUSES OF DEFICIENCY Decreased ingestion and absorption, increased requirement and altered metabolism are actual mechanisms operative in vitamin A deficiency. Malnourishment particularly lack of animal protein as only 40-60% of beta-carotene from plant sources is absorbed by human body, whereas 90% of retinol and retinol esters from animal protein are absorbed by human body.

CAUSES OF DEFICIENCY Patients with sprue, pancreatic insufficiency, inflammatory bowel disease, small intestinal bypass surgery and cystic fibrosis are among the causes of deficiency due to defective absorption.

CAUSES OF DEFICIENCY Alcoholism causes deficiency by altering vitamin A metabolism. Normally enzyme alcohol dehydrogenase converts retinol to retinaldehyde. Oxidation of retinaldehyde produces retinoic acid. In alcoholism, ethanol metabolism is given priority by alcohol dehydrogenase resulting in hampered vitamin A metabolism.

SIGNS OF VITAMIN A DEFICIENCY REPORTED ALREADY IN LITERATURE Bitot spots, xerophthalmia, keratomalacia, dry skin, dry hair, broken fingernails, hypertrophy of periosteal bone, mucous membrane keratinization, zinc deficiency and iron deficiency anemia are reported in literature as reflection of vitamin A deficiency.

BITOT SPOTS

XEROPHTHALMIA

KERATOMALACIA

DRY SKIN

DRY HAIR

BROKEN FINGERNAILS

HYPERTROPHY OF PERIOSTEAL BONE

SIGNS OF VITAMIN A DEFICIENCY REPORTED ALREADY IN LITERATURE These signs develop when vitamin A levels fall in the blood as low as 0.70 umol/L. (WHO/UNICEF. Indicators for assessing vitamin A deficiency and their application in monitoring and evaluating intervention programmes. Geneva: WHO/NUT/94.1,1994.

NORMAL VITAMIN A LEVELS IN BLOOD Normal range of vitamin A in adults is 25-75 ug/100ml. Normal range of vitamin A in infants is 15-60 ug/100ml. The normal range for carotene is 50-250 ug/100ml. (Clinical Laboratory Methods: John D. Bauer, Philip G. Ackermann, Gelson Toro. Mosby, Eighth Ed. 1974, 457-458)

METHODS OF LABORATORY ASSESSMENT OF VITAMIN A Serum retinol level (vitamin A level) is very costly and not available in many countries including PAKISTAN. Serum RBP level is relatively less costly but not available in many countries including PAKISTAN.

METHODS OF LABORATORY ASSESSMENT OF VITAMIN A Serum iron level Serum zinc level (not available in many countries including PAKISTAN) Serum albumin level Dark adaptation threshold LFT X-ray of long bones to determine excessive deposition of periosteal bone.

METHODS OF LABORATORY ASSESSMENT OF VITAMIN A These studies are costly, time consuming but were performed on selected patients with positive IMTIAZ SIGN. All the patients with positive IMTIAZ SIGN had subnormal parameters for vitamin A levels in the body.

MATERIAL & METHODS THE STUDY WAS CONDUCTED FROM SEPTEMBER 1999 TO SEPTEMBER 2006 AT OPHTHALMOLOGY DEPARTMENT CHANDKA MEDICAL COLLEGE AND SYED EYE CLINIC LARKANA PAKISTAN. 300 PATIENTS, 70 MALES AND 230 FEMALES WERE IDENTIFIED CLINICALLY AS CASES OF HYPOVITAMINOSIS A ON THE BASIS OF PRESENCE OF “IMTIAZ SIGN” DURING THIS PERIOD.

MATERIAL & METHODS ASSOCIATED SYMPTOMS AND SIGNS OF VITAMIN A DEFICIENCY WERE NOTED. PATIENTS WERE GIVEN THERAPEUTIC DOSES OF VITAMIN A ORALLY AND IMPROVEMENT OBSERVED. PATIENTS WITH LIVER DISEASE AND MALABSORPTION SYNDROME WERE NOT INCLUDED IN THE STUDY.

ASSOCIATED EVIDENCE OF VITAMIN A DEFICIENCY AGE IN YEARS EVIDENCE MALE FEMALE 5-10 11-20 IRON DEFICIENCY LOW ALBUMIN 4 9 5 8 21-30 31-40 DISTURBED LFT 2 1 3

ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY IMTIAZ SIGN IS THE STAINING OF A DOT OR FEW DOTS OF CONJUNCTIVA WITH SURMA OR KAJAL. THESE DOTS APPEAR BLACK AND ARE A CAUSE OF CONCERN FOR THE PATIENT. THESE STAINED AREAS OF CONJUNCTIVA ARE THE EARLIEST SIGN OF VITAMIN A DEFICIENCY.

ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY

ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY The rough areas of conjunctiva produced as a result of sub clinical deficiency of vitamin A get this natural stain of kajal or surma used for cosmetic or religious purpose. These patients often confirm the difficulty in vision in dim light reacting to a leading question which indicates forthcoming nyctalopia.

ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY Administration of dietary or therapeutic supplements of vitamin A quickly resolves these stained areas and also resolves associated symptoms of vitamin A deficiency like problem in working in dim light, fatigue, recurrent respiratory infections and GIT upsets in addition to skin and hair effects.

TREATMENT Treatment includes promotion of vitamin A rich diet and 2000 IU to 8000 IU daily in children and 10000 IU daily in adults Resolution of signs and symptoms of vitamin A deficiency is also taken as a therapeutic test.

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