Ann Rheum Dis: first published as 10.1136/ard.28.6.607 on 1 November 1969. Downloaded from Ann. rheum. Dis. (1969), 28, 607 PENICILLIN ALLERGY IN RHEUMATOID ARTHRITIS WITH SPECIAL REFERENCE TO SJ0GREN'S SYNDROME BY B. 0. WILLIAMS,* R. A. ST. ONGE,** A. YOUNG,* G. NUKI, W. CARSON DICK, AND K. WHALEY From the Centre for Rheumatic Diseases and the University Department of Medicine, Glasgow Royal Infirmary An increased prevalence of penicillin allergy has by the method described by Williamson, Cant, Mason. been noted in certain connective tissue disorders, in Greig, and Boyle (1967). In each patient a Schirmer I particular polyarteritis nodosa (Rose and Spencer, tear test was carried out, using standardized sterile paper strips* in an atmosphere between 60 and 70°F. and a 1957) and systemic lupus erythematosus (Harvey, relative humidity greater than 40 (Williamson and Shulman, Tumulty, Conley, and Schonerich, 1954). Allison, 1967). Patients were considered normal if There is, to our knowledge, no reported study of the wetting of the paper exceeded 15 mm. after 5 minutes. prevalence of penicillin allergy in rheumatoid arth- In patients with a subnormal Schirmer I tear test a ritis, although an increased prevalence has been Schirmer II test was performed: this test is identical to observed in patients with Sj0gren's syndrome, in- the Schirmer I test, except that lacrimation is stimulated by copyright. cluding those individuals with co-existing rheuma- with a 10 per cent. solution of ammonia held 6 inches toid arthritis (Bloch, Buchanan, Wohl, and Bunim, from the nose. 1965). The Rose Bengal test was performed by instilling a 1 per cent. solution of the dye into the conjunctival sacs, In this paper we have studied the prevalence of followed by normal saline irrigation and examination penicillin allergy in patients with rheumatoid arth- with a Zeiss or Haag-Streit slit lamp for punctate or ritis, in particular to ascertain whether penicillin filamentary keratitis. was to Sj0gren's syndrome compli- Keratoconjunctivitis sicca was said to be definitely allergy related present when the Schirmer II tear test was subnormal cating rheumatoid arthritis or to rheumatoid arthritis and the Rose Bengal dye showed a punctate or filament- per se. ary keratitis on slit-lamp examination. In patients with http://ard.bmj.com/ a subnormal Schirmer II test but without evidence of keratitis, a diagnosis of "possible" keratoconjunctivitis Materials and Methods sicca was made. 298 patients with definite or classical rheumatoid arthritis (Ropes, Bennett, Cobb, Jacox, and Jessar, 1958), Oral Symptoms.-Each patient was carefully ques- who had had previous penicillin therapy, were questioned tioned regarding a history of xerostomia and related oral related allergic phenomena. 161 (53 per cent.) symptoms of Sjogren's syndrome (Bloch and others, regarding on September 30, 2021 by guest. Protected of these patients had a positive sheep cell agglutination 1965). "Symptomatic" xerostomia was diagnosed when test and all exhibited articular erosions on radiological the patient admitted to having a dry mouth, but had no examination of the joints. reduction in salivation or associated difficulty in mastica- tion requiring increased fluid intake. These patients' In addition to the age and sex of the patient, subcutan- mouths were normal on clinical examination, and parotid eous nodule formation and salivary gland enlargement salivary studies (using a modified Carlsson-Crittenden (Bloch and others, 1965) were recorded. cup with an inner chamber diameter of 10 mm., an outer chamber diameter of 20 mm., and a depth of 4 mm.) were All ofthe patients were carefully examined for evidence within the normal range. The inner chamber of this of Sj0gren's syndrome (Bloch and others, 1965). cup fits over the end of Stensen's duct, and suction is exerted on the outer chamber to hold the cup in position Keratoconjunctivitis sicca.-An ophthalmological ex- and prevent the leakage of saliva, which passes down a amination for keratoconjunctivitis sicca was performed tube into a collecting vessel. *Fourth year medical students, University of Glasgow, Scotland. **First year medical student, Yale University, School of Medicine, *Supplied by Contactisol Inc., Lindehurst, New York, U.S.A. New Haven, Connecticut, U.S.A. 607 Ann Rheum Dis: first published as 10.1136/ard.28.6.607 on 1 November 1969. Downloaded from 608 ANNALS OF THE RHEUMATIC DISEASES Sialography was performed by the hydrostatic tech- connective tissue disease, nor had any of these patients nique of Park and Mason (1966). The contrast medium been attending hospital as a direct result of penicillin is allowed to flow into the parotid duct from a reservoir allergy. held 70 cm. above the patient's head. Filling was stopped when the patient experienced pain due to dis- Age of Patients and Controls tension of the gland. This technique overcomes the major hazards of injection sialography. For instance, The mean age and age range of the male and female underfilling rarely occurs as the film is taken while the patients with rheumatoid arthritis and the control sub- contrast medium is still flowing and the pressure, there- jects are shown in Table 1, together with their age distri- fore, maintained. Overfilling also is extremely unusual bution in decades. The age distribution in decades is because an almost constant pressure is employed in all identical in both groups, and the mean ages and age cases. Degrees of abnormality were based on the ranges are very similar. criteria of Bloch and others (1965). Serological Methods Penicillin Allergy Antinuclear factor (ANF) was detected by the indirect This was recorded when the patient experienced a immunofluorescence techniques of Beck (1961), using definite skin eruption, angioneurotic oedema, asthma, or rat liver as substrate. Sera were initially tested at a a clinical picture resembling serum sickness with fever, dilution of 1 in 16 and positive sera were then titrated in painful swollen joints, myalgia, and lymphadenopathy quadrupling dilutions till an end-point of nuclear staining following exhibition of penicillin or a penicillin drug was obtained. analogue (Goodman and Gilman, 1955). Postadminis- Rheumatoid factor was determined by the sheep cell tration phenomena, for example, nausea, vomiting and agglutination test (Ziff, Brown, Lospalluto, Baden, and diarrhoea, or generalized malaise, were not included. McEwen, 1956); screening was carried out at a dilution of 1 in 32, positive sera being titrated at doubling dilutions. Control Subjects These were in-patients or out-patients of the general Results medical and surgical departments of various hospitals in Glasgow. 298 such subjects, matched for age and sex, The prevalence of penicillin allergy, as definedby copyright. were included in this study. None had clinical evidence overleaf, is shown in Table II. It can be seen that of Sj0gren's syndrome, rheumatoid arthritis, or other 63 of the 298 patients with rheumatoid arthritis TABLE I AGE AND SEX DISTRIBUTION OF PATIENTS WITH RHEUMATOID ARTHRITIS AND CONTROL SUBJECTS Age (yrs) Age Distribution in Decades Group Sex No. of Cases Mean Range 0-19 20-29 30-39 40-49 50-59 60-69 70-79 http://ard.bmj.com/ Rheumatoid Male 108 47 8 15-78 3 14 18 19 31 19 4 Arthritis Female 190 48 * 6 16-71 11 20 23 31 50 43 12 (298) Controls Male 108 46-9 14-75 3 14 18 19 31 19 4 (298) Female 190 49*1 17-79 11 20 23 31 50 43 12 TABLE II on September 30, 2021 by guest. Protected PENICILLIN ALLERGY IN PATIENTS WITH RHEUMATOID ARTHRITIS AND CONTROLS, BY AGE AND SEX Total with Penicillin Penicillin Allergy Group Allergy Sex No. of Age Distribution in Decades No. Per Cases No. Per cent. cent. 0-19 20-29 30-39 40-49 50-59 60-69 70-79 63 21-1 Male 108 21 19-4 0/3 0/14 6/18 1/19 8/31 4/19 2/4 Rheumatoid (0%) (0%) (33 *3%) (5*3%) (25.8%) (21 1%) (50%) Arthritis (298) Female 190 42 22-1 1/11 5/20 1/23 7/31 14/50 11/43 3/12 (9*1%) (25%) (4 3%) (22-6%) (28 0%) (25 3%) (25 0%) Controls 38 12*8 Male 108 15 13*9 1/3 2/14 2/18 3/19 4/31 3/19 0/4 (298) (33 3%) (14-3%) (11-1 %) (15-8%) (12-9%) (15-8%) (O%) Female 190 23 22*1 0/11 2/20 5/23 4/31 5/50 5/43 2/12 (0%) (10%) (21-7%) (12-9%) (10%) (11-6%) (16 7%) Ann Rheum Dis: first published as 10.1136/ard.28.6.607 on 1 November 1969. Downloaded from PENICILLIN ALLERGY IN RHEUMATOID ARTHRITIS 609 (21 -1 per cent.) were allergic to penicillin, compared P < 0X001). The prevalence of penicillin allergy with only 38 of the 298 control subjects (12-8 per in patients with Sj0gren's syndrome and rheumatoid cent.). This difference is statistically significant (x2= arthritis is significantly higher (X2 = 19 59; P < 7 45; P < 0 01). Table II also shows that there is a 0 00025) than that in the control subjects. How- higher prevalence of penicillin allergy in both male ever, the prevalence of penicillin allergy in those with (19 4 per cent.) and female (22* 1 per cent.) rheuma- rheumatoid arthritis alone is not significantly higher toid patients than in male (13 * 9 per cent.) and female than the prevalence in the control subjects (x2 = (12-1 per cent.) control subjects. However, only 1 769). It would thus appear that the increased in the female patients with rheumatoid arthritis is this prevalence ofpenicillin allergy in rheumatoid patients difference statistically significant (x2 = 6-69; is related to the presence of co-existing Sj0gren's P < 0 01).