A therapeutic trial of the use of penicillin V or erythromycin with or without rifampin in the treatment of psoriasis F. Yincent,a J. B. Ross,a M. Dalton,b and A. J. Wort e Halifax, Nova Scotia, Canada Background: After the publication of an uncontrolled trial of nine patients with streptococ-
cus-associated psoriasis who appeared to benefit from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days, we wished to confirm or refute the validity of this observation. Objective: Our purpose was to confirm the effectiveness of antibiotics in the treatment of streptococcus-associated psoriasis. Methods: Twenty patients were placed randomly into two groups. One group was given penicillin or erythromycin for 14 days with a placebo added during the last 5 of the 14 days. The other group received the same medication with the addition of rifampin in the last 5 days. Results: Although all the patients studied met the criteria of the reported preliminary study, we were unable to detect any evidence of improvement in their psoriasis. Conclusion: There was no apparent benefit for patients with streptococcus-associated psoriasis from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days in a 14-day trial. (J AM ACAD DERMATOL 1992;26:458-61.) The association of psoriasis with streptococcal infection has been well established. 1-3 A preliminary studt" of the use of rifampin with penicillin or erythromycin in the treatment of streptococcusassociated psoriasis was prompted by reports that treatment with a combination of rifampin and penicillin was more effective than penicillin alone. 5, 6 Nine streptococcus-associated psoriasis patients given oral penicillin or erythromycin with the addition of rifampin during the last 5 days have been reported. Five patients had an excellent response (more than 95% improvement) and four had a good response (80% to 90% improvement). It was concluded that "the apparent efficacy of rifampin in eliminating the presence of streptococci suggests that it may become a useful therapeutic agent in
From the Division of Dermatology, Department of Medicine, Faculty of Medicine, Dalhousie University"; the Department of Microbiology, Victoria General Hospitalb; and the Department of Pathology, Isaac Walton Killam Children's Hospital.c Supported by Merrell Dow Co. Reprint requests: 1. Barrie Ross, Division of Dermatology, Dalhousie University, c/o Victoria General Hospital, Halifax, N.S. B3H 2Y9, Canada.
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458
psoriasis patients whose disease is being sustained by a continuing presence of streptococci."4 (p. 763) This study was uncontrolled; because only nine patients had been entered into the study, there was reasonable doubt of the effectiveness of the treatment. We designed a randomized therapeutic trial to assess the effects of the addition of rifampin to a standard course of penicillin or erythromycin in patients with streptococcus-associated psoriasis. We calculated that a minimum of 40 patients would be required to demonstrate a statistically significant difference.
MATERIAL AND METHODS Between November 1987 and June 1989 we treated 20 patients with guttate psoriasis, psoriasis in a patient with a recent history of upper respiratory tract infection, inverse psoriasis, or recalcitrant psoriasis. None had recently received antibiotics. Informed consent was obtained, a history and physical examination was completed, and a Psoriasis Area and Severity Index (PASI) was determined by one person (F. Y.). Dry sterile swabs were taken from the throat and skin lesions of each patient and inoculated within 4 hours on 5% sheep blood agar. Streptococcal grouping was deter-
Volume 26 Number 3 March 1992
Penicillin or erythromycin with or without rifampin in psoriasis 459
Table I. Clinical and bacteriologic characteristics and treatment disposition Bacteriology"t Pre-Tx Patient No.
1 2 3 4 5 6
7
8 9 10 11 12 13 14 15 16 17 18 19 20
Post-Tx
Psoriasis groop* Age (yr)
Sex
1
23 24 23 47 28 28 43 77 66 23 43 46 42 27 30 42 40 14 12 15
M M F F M M F F M F F F F F M M F F F F
X X X X X X X X X X X X X X X
I
2
I
3
3wk
I
4
X
X X X
X X X X
T
S
T
0 0 0 0 0 2 0 0 0 0 0 0 0
0 0 0 1 3 1 1 1 0 3 1 0 1 0 1 0 0 ND 0 0
3 0 3 3 0 0 0 2 ND 0 ND 0 0 0 0 0 2 0 0 0
0 0
0 2 3 0 0
I
Trial groupt
6wk
S
T
0 0 1 3 3 1 1 0 ND 1 ND 3 1 0 0 0 0 0 0 3
0 0 0 0 N 2 0 2 3 0 0 0
0 ND 0
ND ND 0 ND 0
I
S
0 1 1 1 D 1 3 1 1 3 3 1 1 ND 1 ND ND 0 ND 0
A
A A A A A A A A A A A
I
B
B B
B B B
B B B B
*Psoriasis group: 1, Guttate; 2, inverse; 3, upper respiratory tract infection; 4, recalcitrant. tBacteriology: T, Throat; S, skin; 0, negative; 1, Staphylococcus epidermidis; 2, Candida a/bicans; 3, Streptococcus group A; ND, not done. tTrial group: A, Treatment group; E, control group.
mined by standard methods. Five milliliters of blood was drawn from each patient to determine antibody levels to streptolysin 0, DNAase B, and the streptococcal antigenscreening test. Significant levels for the anti-streptolysin titer were those established at the Isaac Walton Killam Children's Hospital, Halifax. Interpretation of antiDNAase B and streptococcal antigen titers were those of the kit manufacturers. Criteria for entry to the study were cultural or serologic evidence of .a-hemolytic streptococcal colonization. Laboratory results were available within 72 hours and patients were then randomly allocated to one of two treatment groups: (l) Group A received oral penicillin V or oral erythromycin 250 mg four times a day for 14 days and an appropriate placebo supplied by the manufacturer twice a day for the last 5 days of the 14 days. (2) Group B received oral penicillin V or oral erythromycin 250 mg four times a day for 14 days and oral rifampin 300 mg twice a day for the last 5 days of the 14 days. During the study all other treatment for psoriasis was stopped except for topical emollients. Patients were evaluated by the PASI method at 3 and 6 weeks after treatment and repeat culture and streptococcal serologic tests
°
were done. A two-sample t test was used to comparePASI scores and streptolysin titers. McNamara's test was used to compare baseline and 3-week titers and baseline and 6-week titers.
°
RESULTS Of the 20 patients, 13 were female and seven were male patients from 12 to 77 years of age. Table I outlines the clinical and bacteriologic characteristics of the group and their treatment dispositions. Table II shows the serologic characteristics. Nineteen patients had guttate psoriasis, of whom two had the recalcitrant form and one man (patient 16) had recalcitrant psoriasis of another pattern. Only one patient (No.5) entered the study on the basis of positive cultures for ,a-hemolytic Streptococcus alone; the rest of the patients entered on the basis of positive serology or culture. Eleven patients wereallocated to treatment group A and nine to group B. No clinical change in psoriasis was detectable in either treatment group throughout the study. Be-
Journal of the American Academy of Dermatology
460 Vincent et al. Table II. Serologic characteristics Serology* Post-Tx Patient No.
1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16 17 18 19 20
Pre-Tx t
166 166 150 50 12 166 50 150 150 230 430 460 420 270 100 50 12 125 323 50
I
2
+ + ND + + + +
+ + + + + + ND + ND
I
6wk
3wk 3
1
cus-associated psoriasis who appeared to benefit from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days, we wished to confirm or refute the validity of this observation. Objective: Our purpose was to confirm the effectiveness of antibiotics in the treatment of streptococcus-associated psoriasis. Methods: Twenty patients were placed randomly into two groups. One group was given penicillin or erythromycin for 14 days with a placebo added during the last 5 of the 14 days. The other group received the same medication with the addition of rifampin in the last 5 days. Results: Although all the patients studied met the criteria of the reported preliminary study, we were unable to detect any evidence of improvement in their psoriasis. Conclusion: There was no apparent benefit for patients with streptococcus-associated psoriasis from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days in a 14-day trial. (J AM ACAD DERMATOL 1992;26:458-61.) The association of psoriasis with streptococcal infection has been well established. 1-3 A preliminary studt" of the use of rifampin with penicillin or erythromycin in the treatment of streptococcusassociated psoriasis was prompted by reports that treatment with a combination of rifampin and penicillin was more effective than penicillin alone. 5, 6 Nine streptococcus-associated psoriasis patients given oral penicillin or erythromycin with the addition of rifampin during the last 5 days have been reported. Five patients had an excellent response (more than 95% improvement) and four had a good response (80% to 90% improvement). It was concluded that "the apparent efficacy of rifampin in eliminating the presence of streptococci suggests that it may become a useful therapeutic agent in
From the Division of Dermatology, Department of Medicine, Faculty of Medicine, Dalhousie University"; the Department of Microbiology, Victoria General Hospitalb; and the Department of Pathology, Isaac Walton Killam Children's Hospital.c Supported by Merrell Dow Co. Reprint requests: 1. Barrie Ross, Division of Dermatology, Dalhousie University, c/o Victoria General Hospital, Halifax, N.S. B3H 2Y9, Canada.
16/1/32965
458
psoriasis patients whose disease is being sustained by a continuing presence of streptococci."4 (p. 763) This study was uncontrolled; because only nine patients had been entered into the study, there was reasonable doubt of the effectiveness of the treatment. We designed a randomized therapeutic trial to assess the effects of the addition of rifampin to a standard course of penicillin or erythromycin in patients with streptococcus-associated psoriasis. We calculated that a minimum of 40 patients would be required to demonstrate a statistically significant difference.
MATERIAL AND METHODS Between November 1987 and June 1989 we treated 20 patients with guttate psoriasis, psoriasis in a patient with a recent history of upper respiratory tract infection, inverse psoriasis, or recalcitrant psoriasis. None had recently received antibiotics. Informed consent was obtained, a history and physical examination was completed, and a Psoriasis Area and Severity Index (PASI) was determined by one person (F. Y.). Dry sterile swabs were taken from the throat and skin lesions of each patient and inoculated within 4 hours on 5% sheep blood agar. Streptococcal grouping was deter-
Volume 26 Number 3 March 1992
Penicillin or erythromycin with or without rifampin in psoriasis 459
Table I. Clinical and bacteriologic characteristics and treatment disposition Bacteriology"t Pre-Tx Patient No.
1 2 3 4 5 6
7
8 9 10 11 12 13 14 15 16 17 18 19 20
Post-Tx
Psoriasis groop* Age (yr)
Sex
1
23 24 23 47 28 28 43 77 66 23 43 46 42 27 30 42 40 14 12 15
M M F F M M F F M F F F F F M M F F F F
X X X X X X X X X X X X X X X
I
2
I
3
3wk
I
4
X
X X X
X X X X
T
S
T
0 0 0 0 0 2 0 0 0 0 0 0 0
0 0 0 1 3 1 1 1 0 3 1 0 1 0 1 0 0 ND 0 0
3 0 3 3 0 0 0 2 ND 0 ND 0 0 0 0 0 2 0 0 0
0 0
0 2 3 0 0
I
Trial groupt
6wk
S
T
0 0 1 3 3 1 1 0 ND 1 ND 3 1 0 0 0 0 0 0 3
0 0 0 0 N 2 0 2 3 0 0 0
0 ND 0
ND ND 0 ND 0
I
S
0 1 1 1 D 1 3 1 1 3 3 1 1 ND 1 ND ND 0 ND 0
A
A A A A A A A A A A A
I
B
B B
B B B
B B B B
*Psoriasis group: 1, Guttate; 2, inverse; 3, upper respiratory tract infection; 4, recalcitrant. tBacteriology: T, Throat; S, skin; 0, negative; 1, Staphylococcus epidermidis; 2, Candida a/bicans; 3, Streptococcus group A; ND, not done. tTrial group: A, Treatment group; E, control group.
mined by standard methods. Five milliliters of blood was drawn from each patient to determine antibody levels to streptolysin 0, DNAase B, and the streptococcal antigenscreening test. Significant levels for the anti-streptolysin titer were those established at the Isaac Walton Killam Children's Hospital, Halifax. Interpretation of antiDNAase B and streptococcal antigen titers were those of the kit manufacturers. Criteria for entry to the study were cultural or serologic evidence of .a-hemolytic streptococcal colonization. Laboratory results were available within 72 hours and patients were then randomly allocated to one of two treatment groups: (l) Group A received oral penicillin V or oral erythromycin 250 mg four times a day for 14 days and an appropriate placebo supplied by the manufacturer twice a day for the last 5 days of the 14 days. (2) Group B received oral penicillin V or oral erythromycin 250 mg four times a day for 14 days and oral rifampin 300 mg twice a day for the last 5 days of the 14 days. During the study all other treatment for psoriasis was stopped except for topical emollients. Patients were evaluated by the PASI method at 3 and 6 weeks after treatment and repeat culture and streptococcal serologic tests
°
were done. A two-sample t test was used to comparePASI scores and streptolysin titers. McNamara's test was used to compare baseline and 3-week titers and baseline and 6-week titers.
°
RESULTS Of the 20 patients, 13 were female and seven were male patients from 12 to 77 years of age. Table I outlines the clinical and bacteriologic characteristics of the group and their treatment dispositions. Table II shows the serologic characteristics. Nineteen patients had guttate psoriasis, of whom two had the recalcitrant form and one man (patient 16) had recalcitrant psoriasis of another pattern. Only one patient (No.5) entered the study on the basis of positive cultures for ,a-hemolytic Streptococcus alone; the rest of the patients entered on the basis of positive serology or culture. Eleven patients wereallocated to treatment group A and nine to group B. No clinical change in psoriasis was detectable in either treatment group throughout the study. Be-
Journal of the American Academy of Dermatology
460 Vincent et al. Table II. Serologic characteristics Serology* Post-Tx Patient No.
1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16 17 18 19 20
Pre-Tx t
166 166 150 50 12 166 50 150 150 230 430 460 420 270 100 50 12 125 323 50
I
2
+ + ND + + + +
+ + + + + + ND + ND
I
6wk
3wk 3
1
