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Recurrent attacks in Reiter's disease.

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Recurrent attacks in Reiter’s Disease
By G. W CSONKA
Recurrent attacks play a n important part
in the course of Reiter’s disease, but little
is known of their incidence. The average
risk of a recurrence is estimated in this
long-term prospective study. Recurrences
occurred in over half of the patients.
The risk of a first recurrence remained
fairly uniform and substantial throughout the observation period. The incidence
of urethral infections during the period
following the initial attack and especially its relationship to recurrent attacks
of Reiter’s disease have also been
investigated.
Attaccos recurrente ha un rolo importante in le curso de morbo de Reiter,
sed pauco es cognoscite de lor incidentia.
I n le presente studio prospective a longe
vista, le risco medie de un recurrentia
es estimate. Recurrentias occurreva in
plus que un medietate del patientes.
Le risco de u n prime recurrentia remaneva satis uniforme e considerabile
in omne phases del periodo de observation. Le incidentia de infectiones urethral durante le periodo post le attacco
initial e specialmente su relation con
recurrente attaccos de morbo de Reiter
ha etiam essite investigate.
I
T IS GENERALLY RECOGNIZED that recurrent attacks play an im-
portant part in the course of Reiter’s disease. The average risk of a recurrence has never been defined nor has its relationship to fresh urethral infections been analysed. To obtain a measure of the expected risk of recurrence, and
to study the role of urethral infection occurring especially during the period
following the initial attack, the records of patients with Reiter’s Disease who
attended the venereal disease clinic, of St. Mary’s Hospital, London, for at
least two years between 1944-58, were studisd. The majority of these patients
were seen personally.
MATERIAL
The diagnostic criteria were: ( 1) an association of urethritis, arthritis, conjunctivitis or
iritis; ( 2 ) an association of urethritis and arthritis, without eye involvement. The two
groups were compared in a preliminary study. Where there was no important difference in
relation to the problems investigated here, they were analyzed together; where such
differences were found, the two groups are shown separately, as in table 3. In all, 216
patients (212 inales and 4 females) satisfied the diagnostic criteria; of these, 144 patients
( 141 males and 3 females) were observed for two or more years and are included in this
study. The series is, therefore, selected by excluding the early defaulter, and the resnlts are
not necessarily representative of completely unselected patients with venereal Reiter’s disease.
There is some evidence that the group of early defaulters contains a higher proportion of
mild and short illness than the group observed for a longer period (Csonka, 1959). The
present figures may, therefore, tend to emphasize the more seriously affected case.
A ‘recurrent attack‘ is defined as one or more major manifestations of Reiter’s disease such
as arthritis, conjunctivitis or iritis with or without urethritis, occurring after a period of not
less than six months following the end of the previous episode of tho disease. Solitary iritis
This work was carried out under the negis of the Medicel Research Council Working Pa&j
on Nnnapecific Urethritis, with the uid of a grant front the CJ. S. Prchlic Health Swcice.
From the S t . Martt’s Hmpital, London, England.
164
165
RECURRENT ATTACKS IN REITER’S DISEASE
was not infrequently encountered 3s n recurrent episode; conjunctivitis was not observed
alone. Urethritis without other signs was not taken to constitute a recurrence.
Recurrence rate (attacks) is based on the number of episodes occurring; the denominator
is the number of person-years observations.
RESULTS
Frequency of recurrent attacks.-Table 1 shows the distribution of cases
according to the number of recurrent attacks; 56 (38.2 per cent) patients had
no recurrences, 88 (61.8 per cent) had more than one attack. A total of 156
recurrences was recorded. The observation period was shortest in the group
without recurrent attacks and increased with the number of recurrences.
Annual risk of a first recurrence.-Table 2 is constructed according to the
conventional life-table method (Frost, 1941), and gives the annual risk of
a first recurrence according to the length of history from the onset. The number
of patients at risk in any one year is compiled from those initial attacks termTable 1.-Distribution of Cases According to Number
Attacks of Reiter’s Disease
Recurrent
episodes
No. of
cases
None
56
52
18
1
2
3
4
5
6
7
Table 2.-Risk
No. of years
after onset
11
3
2
1
1
144
No. of recurrent
episodes
52
36
33
12
10
6
7
156
of
Recurrent
Person-years
observation
248.5
383.5
207.0
191.5
42.5
40.0
12.0
15.0
1239.0
of a First Recurrence of Reiter’s Disease b y Duration after Onset
Percentage risk
of firat
recurrent attack
No. persons
at risk
First recurrent
attack
111
94
78
60
49
17
14
14
5
42
30
25
19
17
7
5
10
11
12
13
14
16
3
2
7
7
1
14.3
15+
11
4
36.4
0-
123456-
789-
12
9
6
6
2
1
8.3
12.2
10.5
6.0
1
166
G. W. CSONKA
inated at least six months previously and who were still attending for surveillance. It appears that the risk of a first recurrence remains fairly uniform
over a great many years and is substantial throughout the observation period.
The longest period of remission in this series was 36 years. The practical
implication of this finding is that prophylactic measures such as avoidance
of promiscuous intercourse should operate for a prolonged period, possibly for
life.
No detailed analysis of second and subsequent recurrent attacks was made,
because the number of cases was small.
Clinical features of first and subsequent attacks.-There is a tendency for
certain clinical features of the first attack to be present in recurrences (table
3 ) . Thus, when the eye was initially involved there was a greater likelihood
that it would also be a feature of a recurrence than when there were no eye
lesions during the first attack. Of the 88 patients with recurrences, 13 had
eye lesions on all occasions, 39 had none at any time, and 36 had eye lesions
during some, but not all attacks.
Recurrence rate according t o age of patient at onset.-There was no consistent relationship between age at onset and recurrence rate (table 4).The
experience at the age of 50 and over was too small for a reliable estimate of
recurrence rate.
Relationship of urethritis io recurrent uttacks.-Table 5 indicates the types
of urethritis found at the first and subsequent attacks. The recurrence rate
ranged narrowly from 57.7 per cent to 63.0 per cent, according to the type of
urethritis at onset: Clearly, urethritis is not a factor determining recurrence
(table 6).
Table 3.-Distribution of First Attacks and Recurrence Rates According to Presence
or Absence of Eye Lesions at Onset
~
_
_
Cases with recurrent attacks
~
~~
Eye lesion
a t onset
No. of
eases
No.
With eye
lesions
Without eye
lesions
Both types
of attacks
Person-years
observation
Present
Absent
62
82
35
53
13
7
17
39
"
5
563.0
676.0
144
88
20
56
12
1239.0
Table 4.-Distribution
of
of Single Attacks and Recurrences According to Age
Patient at Onset of Reiter's Disease
Age
at onset
(Yrs.)
Total
no. of
patients
Patients
with single
attacks
1520 25 30 35 40 45 50 55+
8
31
29
24
13
13
13
2
1
1
8
16
9
144
56
5
6
9
1
1
Person-years
observation
Patients
with recurrent
attacks
2.0
70.5
101.5
61.0
38.0
22.5
35.5
4.0
3.0
7
23
23
15
338.0
88
8
7
4
1
_____
Recurrenee
rate
(attacks)
Person-years
observation
111.5
263.5
298.0
99.0
57.5
47.5
16.0
80
-
901.0
6.1
7.0
5.7
10.7
8.4
10.1
7.7
8.3
-
-
_
167
RECURRENT ATTACKS IN REITER’S DISEASE
Table 5
Urethritis
Gonorrhoea
Nonspecific urethritis
Gonorrhoea and nonspecific urethritis
Undiagnosed urethritis
No urethritis
Associated with
initial attack of
Reiter’s disease
Associated with
recurrent attacks of
Reiter’s disease
Urethritis occurring
after initial attack
and not associated
with Reiter’s disease
24
62
10
53
38
54
52
6
-
22
5
66
8
-
144
156
100
Table 6
Type of
urethritis associated
with initial attack
of Reiter’s disease
Gonorrhoea
Nonspecific urethritis
Gonorrhoea and nonspecific urethritis
Undiagnosed urethritis
No. of
cases
No. of
cases with observed
recurrences
Person-years
observation
24
82
16 ( 6 1 . 5 % )
39 ( 8 3 . 0 % )
189.5
384.5
53
6
30 ( 5 7 . 7 % )
3
492.0
73.0
144
88
1239.0
The relationship of urethral infection to recurrent attacks of Reiter’s disease
is rather complex. Unlike in first attacks, the close association of urethritis
and arthritis, or urethritis and iritis, is less frequent. In the present series, no
urethral infection could be detected in 66 (42.3 per cent) of all recurrent episodes. I believe that a high proportion of recurrences without preceding
urethritis are relapses rather than new attacks. This accords with the claim
of many patients that these episodes, in contrast to the first one, occurred
during periods of sexual abstinence. In 90, or 57.7 per cent, of all recurrences,
urethritis of various types was found. Some of these recurrences were apparently provoked by sexual intercourse and were indistinguishable from
the original attack; in others, recent sexual contact was firmly denied, and it is
possible that a number of such attacks, even in the presence of nonspecific
urethritis, were flare-ups. The picture is made more complex by the fact that
not every freshly acquired urethral infection following an attack of Reiter’s
disease precipitated a further episode of the disease. There were 100 instances of
urethritis of various types which remained uncomplicated, and there was
nothing to distinguish the uncomplicated urethritis clinically from urethritis
which was associated with an attack of Reiter’s disease. It is, of course, possible
that the development or nondevelopment of Reiter’s disease and its recurrences depend on the way in which the preceding urethritis is managed. Such
factors as to how soon after onset of urethritis treatment is given, the type
and amount of drugs used and the clinical response must all be considered.
These problems are being studied at present, but so far no significant lead
has emerged.
Mention should be made that 47.7 per cent of our patients had had gonorrhea,
nonspecific urethritis or a combination of both on one or more occasions at
168
C. W. CSONKA
various and often long intervals before the onset of Reiter’s disease. Some of
these points are illustrated from representative case records (fig. 1 ) .
COMMENT
The pattern of recurrent attacks of Reiter’s disease in this series shows interesting similarities to that in rheumatic fever (Wilson and Lubschez, 1944;
Bland and Jones, 1951; Hitchens, 1958). Rheumatic fever carries a substantial
risk of first recurrences for a number of years after onset of the same order as
we found in Reiter’s disease. There is also a tendency for certain manifestations,
such as chorea, to appear in recurrent attacks if it was initially present. The
similarities might well be due to the fact thdt both the arthritic conditions are
in some way precipitated by infection.
It has been shown that various types of urethritis are apparently equally
capable of initiating Reiter’s disease; on the other hand, urethritis occurs at
other times in these patients, without an associated Reiter’s disease.
SUMMARY
The experience of recurrent attacks of Reiter’s disease in a group of patients
who attended St. Mary’s Hospital from 1944-58 is as follows.
1. Recurrences occurred in 61.8 per cent of the 144 cases who were observed
for two or more years.
2. The risk of a first recurrence of Reiter’s disease remained fairly uniform
and substantial throughout the observation period.
3. When eye lesions were present initially, there wits an increased likelihood
Elm
t
N
A.L.~
Ago
20
t t
t
N G / N G / N
t
N
r n t
N
NN
N
Recent sexuaI contact
dona
Fig. 1.-Three representative cases with Reiter’s disease, showing recurrences
and the incidence of urethral infections.
RECURRENT ATTACKS IN REITER’S DISEASE
169
that they would feature in recurrent attacks. The recurrence rate, however,
did not differ materially whether eye lesions were present during the first
attack or not.
4. The age at onset did not appear to influence the recurrence rate, nor did
the type of urethritis which was associated with the first attack.
5. In 42.7 per cent of the recurrent attacks, no urethral infection was found
and it is thought that they may represent relapses, rather than new attacks.
6. Only half of venereally-acquired urethritis led to recurrences in the
patients with past Reiter’s disease. If one also takes into account the number
of urethral infections preceding the onset of Reiter’s disease, about 20.0
per cent of all urethral infections recorded precipitated an attack. Clinically
the urethritis which was associated with Reiter’s disease and the urethritis
which was not, appeared to be indistinguishable from each other.
G. W. Csonka, M.D., S t . Mary‘s Hospital, London, England.
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