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| ARTICLE |
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| Year : 1960 | Volume
: 8
| Issue : 2 | Page : 33-41 |
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Angular conjunctivitis and riboflavine deficiency
G Venkataswamy
Madurai Medical College and Erskine Hospital, Madurai, India
| Date of Web Publication | 6-May-2008 |
Correspondence Address:
G Venkataswamy
Madurai Medical College and Erskine Hospital, Madurai
India
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
Venkataswamy G. Angular conjunctivitis and riboflavine deficiency. Indian J Ophthalmol 1960;8:33-41 |
Long before the discovery of Riboflavine, Stannus (1911, 1912, 1913) described a group of symptoms including soreness of tongue and lips, with a sodden excoriated condition at the angles of the mouth, and palpebral fissures and a characteristic lesion at the free border of the prepuce, vulva and anus. Scott (1918) described a condition among the Jamaican coolies that shared some of the symptoms described by Stannus and in addition central neuritis, photophobia, indistinctness of vision, ulceration, discharge and burning sensation in the eyes. After the discovery of Riboflavine by Warburg (1932) and isolation of its crystals by Khun (1933) Sebrell and Butler (1938) in experimentally produced ariboflavinosis in men noted a "Scaly slightly greasy, desquamative lesion on a mildly crythematous base in the nasolabial folds, on the alae nasi, in the vestibule of the nose and occasionally at the ears and around the eyelids especially at the inner and outer canthi." Spies Vilter and Asche (1939) observed in patients suffering from malnutrition an ocular lesion characterised by bulbar conjunctivitis, lacrimation, burning of the eyes and failing vision that was cured by administering riboflavine. In the same year Sydenstrickcr and his colleagues (1939) in a study on riboflavine deficiency noted that conjunctivitis and photophobia were prominent symptoms. Bessey and Wolbach and Eckhardt and Johnson (1939) showed that the earliest sign of riboflavine deficiency in the rat is corneal vascularization. Kruse, Sydenstricker and their colleagues (1942) found corneal vascularization as a constant finding in man due to riboflavine deficiency.
Hou of China (1941) found ocular lesions more commonly than facial and oral lesions in ariboflavinosis. In his cases there was dermatitis of both eye-lids extending from the margin of the lids 3 to 6 mm outwards with a dark red discoloration, and papular lesions, and crusts of exuadates scattered over the lesions.
In the same year (1942) Metivier reported about the tropical nutritional amblvopia and corneal epithelial dystrophy due to riboflavine deficiency.
In India Aykroyd and Verma (1942) described superficial keratitis occurring in ariboflavinosis. Later Verma (1944) described angular conjunctivitis of Morax-Axenfeld type occurring in patients suffering from stomatitis and other signs of ariboflavinosis. In 1945-46, reports from Singapore captivity prisoners by Smith and Woodruff (1951) mention about the occurrence of keratitis, retro-bulbar neuritis and scrotal dermatitis occurring due to riboflavine deficiency.
From all these reports, although eyes seem to be implicated in riboflavine deficiencies, it will be seen that there is no consensus of opinion about the ocular lesions occurring in such deficiency. Standard text books in Ophthalmology and Physiology give conflicting reports about the ocular signs in ariboflavinosis. A summary of it is given in [Table - 1].
| Scope of Work | |  |
For this paper, work was limited to angular conjunctivitis and its relation to riboflavine deficiency.
In the Government Erskine Hospital attached to the Madurai Medical College in South India we get 4 or 5 new cases of angular conjunctivitis daily and they are usually associated with signs and symptoms of ariboflavinosis especially angular stomatitis. Even to a casual observer this association of angular conjunctivitis with angular stomatitis is striking. A study of bacterial flora of the conjunctival sac was made in these cases and also a bio-chemical estimation of riboflavine in blood and urine.
Therapeutic tests with riboflavine administration and zinc applications were applied in a group of cases against control groups.
| Bacteriological Examination | | |
This was done by smear and culture at the Bacteriology Department of the Madurai Medical College. It will be seen that in no case Morax-Axenfeld bacillus was isolated. [Table - 2].
| Biochemical Examination | | |
I. Estimation of riboflavine in urine:-
Urine riboflavine was estimated by a test called LOAD TEST. The patients were made to empty their bladder and then given i milligram of Riboflavine subcutaneously. At the end of 4 hours they were asked to empty their bladder again, and the amount of riboflavine in this urine was estimated microbiologically using LACTOBACILLUS CASE I, accorling to procedure recommended by the Association of Official Agricultural Chemists (A.O.A.C.). According to Horwitt's School (1951) with an average riboflavine intake of 1.6 to 3.5 milligrams per day, the riboflavine excretion ranging from 200 to 400 micrograms was noticed by this test. If there is deficiency of riboflavine in the tissues most of the riboflavine injected subcutaneously is retained in the tissues and the excretion in urine after the Load Test is low. In the dietary range of 0.55 to i.i milligram per day the riboflavine excretion ranged from 23 to 75 micrograms. Based on these data our findings denote that most of our patients have dietatry intake of riboflavine ranging from 0.55 to i.i milligram per day. The normal requirement is about 1.4 to 2.5 milligram per day. [Table - 3].
In [Table - 3] we find 2 cases with high excretion of riboflavine in urine. They were found to be diabetics. In the diabetic people though the intake of riboflavine may be normal there is a high excretion of riboflavine (as this is a water soluble Vitamin) and also as there is a negative nitrogen balance. Angular conjunctivitis was seen commonly in these people. It may be noted that a similar excess excretion of Vitamin B 12 occurs in patients with diabetic retinopathy.
2. Estimation of blood riboflavine and serum Protein levels in Blood :-
We did estimation of riboflavine in blood and also serum protein by the Tyrosine method [Table - 4]. In the discussion it will be found that protein and riboflavine are interdependent for their action. In these cases the serum protein was found to be within normal limits and there was only deficiency of blood riboflavine.
| Therapeutic Tests | | |
60 cases were taken up for treatment. They were divided into three groups of twenty cases each. The first group had local instillation of an aqueous solution of Zinc sulphate drops 5 grains to 1 oz. The second group had application of aureomycin or terramycin eye ointment and the third group had intramuscular injection of io milligrams riboflavine daily for io days with only saline drops for the eyes as a placebo. The third group which got the injections of riboflavine improved rapidly while the first two groups (lid not show any improvement.
| Clinical Picture | | |
The cases observed at Madurai Hospital showed in the early stages, hypereinia of the intermarginal strip in the medial and lateral angles of the eye. This was followed by excoriation of the epithelium in the intermarginal area of the canthi, which extended over the skin of the angles and the lower eyelid. In bad cases there was black pigment excrescens in the skin of the eyelids and haziness or some superficial opacities in the cornea. In severe cases ulceration at the mucocutaneous junction of the nose was observed. The bulbar conjunctiva was normal. [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4],[Figure - 5],[Figure - 6].
From all these findings, that is bacterial, biochemical, clinical and therapeutic, it is evident that angular conunctivitis like angular stomatitis is a manifestation of riboflavine deficiency: This observation is not new. Though it has been made by previous workers it has not been properly stressed. Stannus in (1911) has described the excoriated condition of the palpebral fissures. Scott (1918) also has described the ulceration and discharge of eyelids. Sebrell and Butler have mentioned about desquamative lesions around the eve-lids of inner and outer canthi. Hou's description of cases of ariboflavinosis seen in China closely resembles the cases seen at Madurai Erskin Hospital. Verma (1944) stressed about angular conjunctivitis occurring with angular stomatitis commonly in India. All these findings have been made by nutrition workers and so the description of ocular signs were vague. Stephen Rothman in his book "Physiology and Biochemistry of Skin" says that in man the muco-cutaneous junctions are more vulnerable to riboflavine deficiency than is the case in laboratory animals. It appears therefore that the lesions at the angles of mouth and eyes are of the same nature.
| Pathology | | |
The disease, angular conjunctivitis, is commonly known to be caused by Morax-Axenfeld Diplobacillus. It is worth while to study the pathogenesis of angular conjunctivitis due to this diplobacillus. The Morax-Axenfeld diplobacillus is a saprophyte and it is not found in healthy and active cells. It secretes exogenously a proteolytic ferment which acts by macerating the epithelium. This action is confined to the angles and lid-borders, although the organisms are present in the conjunctival sac.
According to Duke-Elder this proteolytic enzyme (PE) destroys the cellular protein (CPr). Tears which have an anti-tryptic substance (antiPE) protect the cellular proteins (CPr) and so the action is confined to unwetted parts of the lids, namely the angles and the lid-borders. Thus
PE +Anti PE (Tears) -Normal CPr.
PE-Anti PE-CPr destroyed.
This argument of Duke-Elder does not satisfactorily explain the preponderance of clinical lesions occurring in the angles of the eye and along the lower lid border in diplobacillarv conjunctivitis as well as in ariboflavinosis, where you find that there is actually more collection of tears. [Figure - 5] and 6 prove the presence of a greater collection of tears at the inner angles and along the lower lid border. The plausible explanation must therefore be different.
We must know the biochemistry of riboflavine and its functions. The riboflavine compunds (RF) join together with protein (Pr) compounds to form flavo-protein enzymes (FPr), which are necessary for cellular respiration [Table - 5]. Thus in synthesis of flavoproteins, proteins as well as riboflavine take part.
Proteins, whether the intake is large or small, are not metabolised in severe deficiency of riboflavine and vice versa a disturbance of protein metabolism reduces the utilisation of riboflavine.
So when the proteolytic ferment from the Morax-Axenfeld diplobacillus destroys the available proteins a local relative fiavo-protein enzyme deficiency occurs.
Thus :-RF - Pr - - FPr.
This results in disturbance of cellular metaboliam of the epithelial cells. Similarly in riboflavine deficiency a similar effect is arrived at by diminished RF.
Thus :-RF - Pr - - FPr.
Therefore in both, Morax-Axenfeld infection and ariboflavinosis the excoriation is produced because of deficiency of riboflavine enzymes, in which deficiency the lesions are more confined to muco-cutaneous junctions. The deficiency is more of a localised type in Morax-Axenfeld infection and so confined to the eyes, whereas it is more generalised in ariboflavinosis, being manifestable in the angles of the eyes as well as the mouth.
The tears with their supposed antitryptic action cannot be exercising a protective action in these cases because photographic evidence shows greater collection of tears opposite the most affected parts. The slightly greater watering may act in one or more of the following ways to precipitate and accentuate the lesions and confine them to the angles and the lower lid borders :
1. Diminished anti-tryptic action in these cases.
2. Dilution of tlavo protein enzymes.
3. Mechanical soddening of the wetted epithelium in which there has been a disturbance of the cellular metabolism.
4. Greater mechanical maceration produced in the process of wiping of accumulated tears or rubbing by the patient's fingers because of itching.
| Conclusion | | |
1. Angular conjunctivitis better termed "Angular Blcpharitis" is a definite ocular sign of riboflavine deficiency.
2. Conjunctivitis due to MoraxAxenfeld diplobacillus can be called "Diplobacillary conjunctivitis". Here also the lesion is brought about by deficient riboflavine utilization due to destruction of local tissue proteins by the proteolytic enzyme of the Morax-Axenfeld bacillus.
| Summary | | |
Large number of cases of ariboflavinosis were observed and angular conjunctivitis was seen as a common ocular manifestation in them. Bacteriological, and therapeutic tests with proper controls are presented by way of confirmation.
A review of literature on this subject is given.
For the similarity of clinical manifestations in "Angular blepharitis" due to aribofiavinosis and "Diplobacillarv conjunctivitis" due to MoraxAxenfeld infection, an explanation is offered both having a similar pathology, namely deficient formation of flavo-protein enzymes, arrived by different routes, aggravated by watering of the eyes.[31]
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]
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