-4 C’ompnrative Study of 150 C‘asrs.

By

OLE MORTENSEN1

(Snhmittetl for publication October 9, 1950.)

Once the diagnosis of a bacterial disease has been established, a number of different drugs, which all have a pronounced effect on that disease, will often available for the treatment.

The drug of choice must be that which results in the quickest cure of the disease, prevents complications and recurrences, and offers least discomfort to the patient: pecuniary considerations are here left out of account.

The study presented here is an attempt a t finding the more suitable of two active substances - penicillin and ~-sulfa1~ilamido-S-niethyl-l,3,4,thiodia~ol~ (“Lucosil”) - in the treatment of erysipelas.

The effect of the sulfonamides on this disease has long been known; inter alia, reports from the Blegdam Hospital by Ole Bang ( l) , 1936, and B. Chr. C‘hristensen (3), 1939, have contributed to this.

So far reports on the efficacy of penicillin in the treatment of erysipelas have apparently not been published. Dowling (4) states that “sufficient data are not yet available”. He states that penicillin is a t least just as effective as the sulfon- amides, and tha t “in view of the results obtained in other streptococcic infec- tions i t is probably more effective”. He expresses the view that “penicillin is the drug of choice because of the low incidence of toxic reactions”.

I n the following report a brief survey of the selection and composition of the patient material is given, certain clinical features are summarized, and finally the dosage and results of treatment are reviewed. _ . ~

1 Prevent address: Anrhus I<ommunchospitnl, Denmiirk.

4titi OLE NORTENSEN.

P : k t i en t Mil terid . ‘Flit$ series of cases coinpriscd patients with erysipelas adiiiitted to the Blegdaiii

Hospital during the period from February 1948 t o January 1950. Patients admitted 011 ~ v e n dates were treated with Lucosil, those admitted on uneven dates with penicillin.

Ihiring this period erysipelas wms diagnosed in 204 cases; 14 of these were treated with othcr drugs or received no treatment a t all.

Of the remaining 190 patients 124 were treated with penicillin, 66 with Lucosil. Somc of these patients, i . c. 21 per cent of both groups, were treated in their own honie3 with various preparations in varying and partially unknown dosage. In order to arrive a t the hest possible evaluation of the results of the treatment these patients were excluded.

Thus, the series studied comprised 98 patients treated with penicillin and 82 patients treated with Lucosil.

The distribution according to the time of year showed maxima during the spring and autumn, as has previously heen reported by other investigators, c . q. Plensborg (6) .

The sex distribution showed a preponderance of women, the ratio being about 1 to 2..?, which is in conformity with Bartels & Riskm’s ( 2 ) and Plenshorg’s stntenients, b u t as stated by the latter author, is a t variance with the majority of previous reports.

The age distribution was almost identical with that reported in previous Danish studies, 44 per cent of the patients being between 40 and 60 years of age and only 2 per cent under the age of I0 years.

In i G cases (50 per cent) the disease was localized to the lower extremities, in 70 cases (47 per cent) to the face and scalp, and in 4 cases (3 per cent) t o the upper extremities. This series thus differed from previous reports, in which the largest numher of cases were localized to the head. Thus, Dowling reported that 85 per cent of his patients had facial erysipelas, and the corresponding figures given by I3. Chr. Christensen, Bartels & Riskw, and Flensborg were 60 ( 7 3 ) , 60, and 57 pcr cent respectively.

The preponderance of erysipelas affecting the extremities was very conspicuous in the women, not less than 80 per cent of the cases with this localization being found in females. The corresponding figure for facial erysipelas was 60 per cent.

Pronounced epidermophytosis was observed in 13 patients (9 women) and chronic crural ulcer in 15 patients (14 women), i . F . in 17 and 20 per cent of the patients with extreniital erysipelas.

The increasing incidence of epidermophytosis and the high incidence of crural ulcer in women may possibly, a t Ieast in part, account for the frequency of extrem- ital erysipelas in the present series.

The more effective therapy, by which the development of chronic strepto- coccal foci (e. q. otitis media chronica) is prevented, may be a contributory cause of the decreasing frequency of facial erysipelas.

A primary focus of infection was demonstrated in 101 cases (67 per cent),

THE TREATMENT OF ERTSII’ELAS. 4ii

equally frequent in the two groups of treatment and of exactly the sailit’ fre- quency in facial and extremital erysipelas.

Bacteriological examination was carried out in 89 cases, and in 28 instances streptococci were found, the types Ax, A1, and A, being most frequent.

Chills occurred in 46 per cent of the patients, i . P . twice as frequently a- 01)- served in Flensborg’s series.

On admission, the average sedimentation rate of the patients in the Lucwsll group was 56 nim and in the penicillin group 48 mm.

Pig 1. A. The tli>tribiition of the patienti ae~oidiiig to t h r time tlnpwd from the Imcct 0 1 t h L diwa\c to ailmiwon to hospital.

13 lhitrihiition arrortling to t h r tcmpc.rature on admiwon. - pc*nic~illin group; x - - - ~ - - ~ x J , i i ( ~ i \ i I group. ._ ~~~~

Thirty-eight patients (25 per cent) had had one or more previous attack\ of erysipelas. Fifteen patients (10 per cent) gave a history of rheumatic fever and 2 i (18 per cent) of scarlatina. These two diseases, in the etiology of which streptococci are generally considered to play a part, are thus far more frequent in these patients than in a non-selected material.

The proneness of the patients t o contract these diseases and the high incidriice of recurrence of erysipelas are here stressed without any attempt lieinp niatle to explain these facts.

(‘oaip:ir:ibility of the T w o Groups.

In spite of the nianner of selectim the two groups differed in size, and thrreforr it was necessary to subject them to an analysis to make certain that their com- position was so uniform that a comparison of the results of treatment was perinis- sihle.

In this analysis the time elapsed from the onset of the disease to admission to hospital was considered (fig. 1 A) and the temperature on admission was taken as a rough measure of the condition of the patients a t that] time (fig. 1 B). The age and sex distribution as well as the localization of the disease were practically identical i n the two groups.

Accordingly, it appears that the composition of the two groups was so uniform that the results of the treatment may be coinpared.

I ) O S ~ L ~ P iLat l I’rcpnriitiorls.

The treatment was initiated shortly after admission, i . e. in most cases in the afternoon of the day of admission.

2-sulfanilamido-5-methyl-l,3,4,thiodiazole (*‘Lucosil” from H. Liindbeck R- Co.) was given by mouth every fourth hour in doses of 1 g; the two first doses, however, were of 2 g. The average total dose was 34.6 g; 32 patients received doses ranging between 30 and 40 g.

Penicillin (“Leo”) was given intramuscularly a t 12 hour intervals; adults were given 180,000 Oxford units per dose. The average total dose was 1,830,000 units; 70 patients received doses ranging between 1-2 million units.

The improvement of the general condition followiiig penicillin therapy was a t least as good as that observed after sulfonamide treatment, but obviously i t is impossible to give any numerical expression thereof.

To obtain a more exact expression of the course of the disease the following features were studied:

1. The course of the temperature. 2. The subsidence of cutaneous symptoms. 3. The duration of the hospitalization. 4. Complications. .?. Side effects of the treatment.

Temperature.

The average temperature for each 24 hour period was calculated for all the patients. Fig. 2 A shows the percentile distribution of the patients becoming afebrile (< 37”) within the first 8 days of treatment. It appears that on the third day 36 per cent of the patients treated with penicillin were afebrile as compared with 25 per cent of those treated with Lucosil. On the fourth day the corresponding figures were 54 and 40 per cent.

Fig. 3 shows the average temperature for each 24 hour period calculated for all the patients.

Cutaneous Symptoms.

Secondly, it was determined when the local process began to subside. The first day on which the process showed definite regression, either fading or a decrease in extent, without subsequent progression was noted for 47 patients treated with

T l l E TREATMENT OB ERYGIl’EI,AS. 4G9

1,ucosil and 91 treated with penicillin. The result appears from fig. 2 U, indicating thv percentile distribution. It will be seen that on the second day of treatment 37 per cent of the latter group but only 17 per cent of the former showed regression. On the third day the corresponding figures were 76 and 64 per cent.

PC+ 00

9 0

8 0

70

6 0

5o t 4 0

30 t 2 0 - I

1 0 .

I-. 1 2 3 4 5 6 7 8 I 2 3 4 5 6 ?&ys

Fig. 2 . S~iinin~ition curves showing the percentile distribution (A) of patients becoming afebrile (<3i’) within the first 8 days in hospital and (B) of patients, in whom the rrysiprlatons blush faded

o r was reduced in size during the first 7 days. The abscissa indicates the time in clays. .~~ ~- ~_____ . penicillin group; x - - - - - - - - x Lncosil gronp.

Durat im of Hospitalization.

The time spent in hospital averaged 12.9 days for patients treated with penicillin and 14.4 days for those treated with Lucosil. If 4 per cent of both groups, i. e. those who for other reasons required longer treatment, arc? excluded, the figures become 11.5 and 13.5 days respectively.

Complications.

The frequency and types of complications are shown in table 1. Among the abscesses one case of a phlegmonous nature was included in either group. I n the penicillin group one abscess was found on the eyelid and in the Lucosil group one WRS localized to the nose, while the remaining abscesses occurred in extremital erysipelas. Only one case of slight phlebitis occurred among the patients treated with penicillin. I n two other instances phlebitis was present on admission, i. e . , it had developed before the institution of treatment. The four instances of phlebitis in the Lucosil group were diagnosed 4, 9, 13, and 14 days after the institution of t r t~i tment .

Side Effects.

These were few in the penicillin group. One case of abscess in the gluteal region, treated in the Surgical Department two months later, was included, as i t may

470 OLE MORTEXSEN

have been caused by the injections. In two cases slight exanthema occurred. They may have been of medicamental origin, but did not require any therapy.

Of four patients in the Lucosil group with medicamental exanthema two had to be transferred to the Dermatological Department for treatment. I n one instance

1 ' 2

3 9" 7

- 5 ~ .

I 370L- -L-

, , t -: ~. .--,

, ~ - ~ . . . ~ ~ ~ treatment had to he interrupted owing to drug fever, and in one patient henintitria i ----

3 i 4 7 I 8

I dzJa developed. . Mortali ty . i

. . ~

Only one of the 150 patients died; this was a 77-year-old woman with diahetes inellitus and incompensated cardiac diseasr. She had been treated with Lucosil.

Comments 011 ('rrtnin P;itient's. I In a 71-year-old woman the cutaneous s y m p I toms and the fever persisted for 11 days in

spite of treatment with Lucosil. I n one case the eruption abated, but did riot completely tlis- i appear, and the temperature did not return to normal.

- In one patient the teniperaturr reniaiiied Fig. 3. The average temperatiire during the

first days (taken t\vice in 24 hours), culated for !M patients treated Tvith penicillin Recurrences on previously involved areits

(. .) and 5 2 patients treated with were not observed in ariy of the patients during the hospitalization. In one patient of the Lucosil group a new process occurred on

the opposite side of the face four days after the treatment had been discontinuccl. One patient treated with penicillin was readmitted 12 days after the first discharge

with a recurrence and was then given Lucosil treatment. In June 1949 he entered hospital again - with his sixth attack of erysipelas.

unaffected by the penicillin treatment.

Lucosil ( x - - - - x ) .

Conclusions.

-4s might be expected in a streptococcal infection, penicillin possesses a pro- nounced curative effect on erysipelas.

A coniparison of the results of treatment with penicillin a d Lucosil shows that at the present time penicillin may be regarded as the drug of choiw. as it gives

TIM0 1.

Corriplications in 150 cases of tvysipelas.

1 ' Penicillin groiip, I T,iicosil group, 1 in per cent ~ in per rcnt

.it)scess . . . . . . . . . . . . . . ' 7.1 ~ 11.5 I

Phlehitis . . . . . . . . . . . . 1 (3.1) 7.7 .4 rute nephritis . . . . . . I 0

THE TREATMENT O F ERYSIPELAS. 47 I

the quickest cure, as assessed by the course of the temperature and the subsidence of the cutaneous symptoms. Penicillin therapy results in a shorter period of hospitalization and gives fewer complications and side effects during the treat- ment.

The easier peroral administration of the sulfonamides must lead us to suppose tha t this therapy will be preferred in a large numher of cases, particularly those treated b y a general practitioner. According to the study presented here the results obtained by the use of Lucosil are so good as to warrant the further use of sulfonamides in the treatment of erysipelas.

Summary.

During the period from February 1948 to January 1950 204 patients with ery- sipelas were admitted.

The present study comprised 150 of these patients, who had not received any treatment in their homes.

The sex distribution showed a preponderance of women, the ratio being 1 to 2 . :); 44 per cent of the patients were between the ages of 40 and 60 years.

This series differs from those previously reported in tha t i t showed a considerably higher frequency of the disease localized to the lower extremities (50 per cent). The preponderance of extremital erysipelas was most pronouiiced in women.

In 28 of 89 cases subjected to bacteriological examination streptococci were found to be present.

98 patients were treated with penicillin and 52 with %sulfanilamido-S-~nethyl- 1, 3,4,thiodiazole (“Lucosil”).

The distribution of the patients in the two groups was uniform with regard to sex, age, the localization of the disease, its duration hefore admission, and tempma- ture on admission.

The dosage of the preparations is reported. Following treatment with penicillin a niore rapid fall of temperature and sub-

sidence of cutaneous symptoms was obtained; further the hospitalization period was shorter and fewer complications were encountered than after Lucosil therapy.

Recurrences on previously involved areas did riot develop during the stay in hospital.

One patient from the Lucosil group died of cardiac disease. The difference between the results obtained by treatment with the two drugs

is sufficiently slight to justify the use of the sulfonaniides in the treatment of erysipelas in cases where practical considerations may make it desirable.

References.

1. Bang, O., TJgeskrift for Lager, 98: 1018, 1936. - 2. Bartcls, E. I)., and Riskm, N., . k t a med. Scant]., 118: 489, 1944. - 3. Christensen, H. C., Nord. Med., 2: 1379, 1939. - 1. Dowling, H. F., Tile Acute Bacterial Diseases (R. B. Sarinders Comp.), 1948. - 5 . Flensborg, E. W., Acta med. Scand., 112: 455, 1942.