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.