The phlycten, a come-back?

H.C. KOPPERT and G. VAN RIJ

Department of Ophthalmology, Erasmus University, Eye Hospital, Schiedamsevest 180
3011 BH Rotterdam, The Netherlands

Abstract. In February 1980 acute keratoconjunctivitis was seen in a girls' class in a

school in Rotterdam. Bacteriological and virological examination was performed on 20
gifts. The agent causing this epidemic could not be demonstrated. Three patients had
phlyctens at the limbus. In the year following this observation (March 1980 till March
1981) 42 cases of phlyctenular keratoconjunctivitis were examined prospectively.
The condition was most commonly seen in 13- to 18-year old girls. The phlycten can be
considered as an elementary form of inflammation in the conjunctiva and cornea, based
on an immune reaction of the delayed type (Cell and Coombs' type IV). The hypersensitivity to tuberculin, which was formerly an important feature of this inflammation
('scrofulous ophthalmia'), is of little importance in the Netherlands at the present day.
However, in every case of phlyctenular keratoconjunctivitis tuberculosis should stiU be
excluded by the medical history, and if necessary by a Mantoux reaction.

Introduction
Since ancient times doctors all over the world have been confronted with a
whitish lesion, the size o f a pin's head, which can appear in the course o f a
keratoconjunctivitis. This nodule, surrounded b y a red ring, is usually found
on the bulbar conjunctiva or at the limbus. Its name is phlycten, from the
Greek ~korraut~, meaning blister; a term which became popular after the
description o f the lesion given b y the Greek doctor Paulus o f Aegina, working
in Alexandria in the seventh century A.D. The name is really not very suitable.
In the beginning the lesion somewhat resembles a blister through which the
episcleral vessels can be seen (Fig. 1), but it is actually a solid nodule (Fig. 2).
After 4 days the glistening appearance is lost through necrosis and ulceration
of the centre. The nodule then dries up and becomes flatter. After 2 or 3
weeks the necrotic part disappears and the surrounding hyperaemia decreases
(Fig. 3). The lesion disappears without trace, unless it was partially situated
on the cornea, in which case it leaves a small scar.
Migration of the phlycten over the cornea, as was often seen in the first
half o f this century, is not seen in Europe any more, except perhaps in a
foreign visitor from a country where the situation regarding nutrition, hygiene
and tuberculosis is poor (Fig. 4).
The phlycten is the typical lesion o f phlyctenular keratoconjunctivitis (or
339
Documenta Ophthalmologica 52, 339-345 (1982) 0012-4486/82/0524-0339 $1.05.
9 Dr W. Junk Publishers, The Hague. Printed in The Netherlands.

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Figure 1. A beginning limbaI phlycten, in a Dutch girl aged 15. Episcleral vessels still
visible through the lesion

Figure 2. Limbal phlycten, nodule, in a Dutch girl aged 14

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Figure 3. Conjunctival phlycten, necrosing nodule, in a Dutch girl aged 15

Figure 4. Corneal phlycten, fascicular ulcer, in a Turkish boy aged 14

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phlyctenulosis). Formerly, when the condition was often associated with
tuberculosis, the name scrofulous ophthalmia was used. (Scrofa is the Latin
word for brood sow, which children with lympatic swellings in the neck were
thought to resemble).
Histologically, the phlycten consists of an exudate of leucocytes, mainly
lymphocytes, to which polynuclear cells may be added in the acute phase. The
necrotic area contains fibrin and cells with round nuclei, such as histiocytes,
plasma cells and epitheloid cells. Bacteria have never been found in the lesion
itself.

Epidemiology
After the discovery of the tuberculin reaction the long-suspected relation
between scrofulous ophthalmia and tuberculosis became obvious. Calmette
(1908) was so impressed by it that he suggested, in an attempt to simplify the
tuberculin reaction, that it should be performed by instilling a 1% tuberculin
solution into the eye. This method was rapidly abandoned because of the
severe corneal reactions.
There has, however, always been a category of patients in whom
phlyctenulosis occurred without a demonstrable tuberculin hypersensitivity.
This category became relatively larger as the incidence of tuberculosis in the
population decreased. In the first half of this century 90% of phlyctenulosis
patients in the Netherlands reacted positively to tuberculin (Rochat, 1932);
in the fifties this figure - in California (Thygeson, 1954) - had decreased to
75%. Scrofulous ophthalmia disappeared in the Netherlands as nutrition
and hygiene improved in the second and third decades of this century
(Fig. 5).
Although in large areas of the world the phlycten is still associated with a
tuberculin allergy, in advanced areas other allergic mechanisms are involved.
This was apparent in the observations made in 1980 and 1981 in the
Out-Patient Department of the Rotterdam Eye Hospital.

Observation
In February 1980 acute keratoconjunctivitis occurred in a school near
Rotterdam. A remarkable feature was that in three of the twenty patients
examined, girls between 13 and 17 years old, phlyctens were found.
Extensive examination did not reveal the agent responsible for this inflammation. There was no trace of intestinal parasites and no eosinophilia in
the blood or conjunctival secretion. A Chlamydia infection was also
excluded.
By reason of these patients we decided to examine patients with phlyctens
prospectively.

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11 t LL.I

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Figure 5. The disappearance of scrofulous ophthalmia in two hospitals in the Netherlands

(Rochat, 1932)
Patients and m e t h o d s

Patients who visited the Out-Patient Department of the Rotterdam Eye

Hospital during one year (March 1980 till March 1981) were included in
the study. A total of 42 patients was examined. Conjunctival smears were
cultivated virologically and bacteriologically. A dry swab was applied to the
inferior fornix and then placed in a transport medium. For the bacterial
culture the Stuart transport medium was used, and for virus isolation a
buffered saline solution with Gentamycine and Fungizone. The media were
then ,sent immediately to the Rotterdam Health Centre laboratory
(Dr. G.J.P. Schaap, Dr. J.R.J. B/inffer, Dr. J.K. Sch6nfeld). Mantoux's intracutaneous tuberculin reaction with purified protein derivative ITU in 0.1 ml
was also performed.

Results

Phlyctens were found mainly in females (38 x).

The infection was most frequent in 12- to 18-year-old girls (Fig. 6).
The youngest patient was a girl o f 4 years old.
The Mantoux test was only positive in 2 cases:
1. A 15-year-old Turkish girl who had been in the Netherlands for 3 months;
2. A 58-year-old Moroccan man who had been treated for lung tuberculosis
the year before.
- There was no seasonal variation.
- It was only possible in 2 cases to Cultivate a bacterium: 1 x Staphylococcus
aureus, 1 x Staphylococcus epidermidis. This small number is related to
the fact that some patients had already been treated with antibiotic drops
before they came to the Clinic.
- The virus cultures were negative.

344
number of
patients
8
6

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12

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~
16

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~
28

~ 312 J 3 L
6

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Figure 6. The occurrence of phlyctenular kerato-conjunctivitis in Rotterdam according

to age. Peak-period between the ages of 12 and 18

Therapy
Phlyctenulosis was formerly a frequent condition which was difficult to treat,
but this is not true at the present time, at least in prosperous parts of the
world. In the group under examination the phlyctens disappeared within a
fortnight, irrespective of the therapy applied. In a few cases a recurrence
occurred.
Comment

Immunologically the phlycten is classified under the delayed form of immunity associated with T-lymphocytes, i.e., Gell and Coombs's type IV
(Allansmith, 1980).
The reaction is not specific and can be activated by various antigens. Not
only bacteria, but also protozoa and worms may be involved in the sensitization of the cornea and conjunctiva. For instance, Busacca (Brazil, 1952) - who
refuses to use the term 'phlycten' because histologically there is no sign of a
blister - cured persistent phlyctenulosis with therapy for intestinal parasites
such as lambliae. Jeffery (India, 1955) showed epidemiologically that there is
a relationship between helminthiasis and phlyctens. Khalef Al-Hussaini
(Egypt, 1979) established a connection between phlyctenulosis and infection
with Hymenolepis nana.
Experimentally it has been demonstrated that certain chemicals can also
cause phlyctens (Funaishi, 1923, for cocaine, and others).
Pathogenic and commensal Staphylococci and Micrococci have some
common lipoproteins and polysaccharides in their cell walls (van Bijsterveld,
1981). These common molecules can give rise to common antigens (Galinski,
1974).
Which antigens gave rise to the observed phlyctenular keratoconjunctivitis
in Rotterdam last year cannot be said with certainty. We presume that both

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pathogenic and non-pathogenic Staphylococci played an important part, and
that crossed reactions between different strains may have been involved.

Conclusion
Although phlyctenular keratoconjunctivitis at the present time in the
Netherlands has no connection with tuberculin allergy, it is advisable, in view
of the number of people in the country coming from areas where tuberculosis
is endemic, to exclude a tuberculous cause by means of the medical history
and a Mantoux reaction.

References
Allansmith MR (1980) Phlyctenular keratoconjunctivitis. In: T.D. Duane (ed.) Clinical
Ophthalmology, vol. IV, chapter 8, p. 1. New York, Harper & Row
Busacca A (1952) Biomicroscopie et histopathologie de l'oeil, vol. I. Ztirich, Schweizer
Bijsterveld OP van ( 1981) Personal communication
Duke-Elder S (1965) Phlyctenular kerato-conjunctivitis. In: S. Duke-Elder (ed.) System
of Ophthalmology, vol. VIII, part I, p. 461. London, Kimpton
Funalshi S (1923) Experimentelle Untersuchungen tiber die Aetiologie der phlyktinulS.ren
Augenentztindungen. Klin Mbl Augenheilk 71:141
Galinski G (1976) Serological cross-reactions between Staph. aureus type 187. Zbl Bakt
Parasitenk Infektionskr Hyg Abt Orig A suppl 5:87
Jeffery MP (1955) Ocular diseases caused by nematodes in India. Amer J Ophthal 40:41
Khalef A1-Hussaini (1979) Phlyctenular keratitis in Egypt. Brit J Ophthal 63:627
Paul of Aegina (+ 680) Hypomnena, Book III
Rochat GF (1932) Over de sterke vermindering der scrofuleuse ophthalmic. Maandschr
Kindergeneesk 1: 298
Thygeson P (1954) Observations on non-tuberculosis phlyctenular kerato-conjunctivitis.
Trans Amer Acad Ophthal Otolaryng 58:128