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Contact Dermatitis from Topical Tyrothricin and Associated with Polyvalent Hypersensitivity to Various Antibiotics1
CONTACT DERMATITIS FROM TOPICAL TYROTHRICIN AND ASSOCIATED WITH POLYVALENT HYPERSENSITIVITY TO VARIOUS ANTIBIOTICS* REPORT OF A CASE LEON GOLDMAN, M.D., MILTON D. FELDMAN, M.D.j- AND WILLIAM A. ALTEMEIER, M.D. Cincinnati, Ohio
In contrast to penicfflin and other antibiotics, tyrothricin has to our know! edge not previously been reported as a sensitizing agent. We therefore wish to report the detailed study of a case of contact dermatitis following the topical application of a solution of tyrothricin. A 43 year old white woman developed an ulcer on the medial aspect of the left ankle tw°
years previously. Various types of treatment for a period of 6 months were of no avai' until application of tyrothricin solution compresses healed the lesion. The ulcer recurred two and one half months prior to admission to the hospital. Tyrothricin solution was again used and the ulcer began to heal. After about 6 weeks of this treatment an acute eczematoid dermatitis of the lower leg developed. Penicillin ointment was then used without relief and with perhaps further aggravation of the dermatitis. The past history was essentially negative except for a bilateral thrombophlebitis of the legs which followed a pregnancy 20 years before. There were no previous episodes of eczematoid dermatitis, no known fungous disease of the feet and, prior to the application of tyrothricin, no use of any antibiotic. The only physical findings were those relating to the acute dermatitis involving the lower one third of the left leg and the middle portion of the plantar surface and entire dorsum of the left foot. The skin of these areas was edematous, erythematous and eczema-
toid in character. There was also a moderately severe erythematous papulo-vesicular eruption of the upper extremities. There was no clinical evidence of fungous disease of the feet. Re-examination after 6 weeks likewise revealed no evidence of this type of infection. At the present time, the patient remains free from her dermatitis. The following patch tests were done: Material
Tyrothricin solution Tyrothriein ointment Penicillin ointment Penicillin G solution Streptomycin ointment Streptomycin solution Gliotoxin cream Gliotoxin ointment Trichophytin solution Coccidioidin ilistoplasmin Oidiomycin
Concentration
25 mg./cc.
0.5 mg/gm. 1000 units/gm. 500 Units 5000 units/gm. 25 mg. 1:1000 1:1000 1:30 1:1000
Resuli
++++ ++++ +++ ++ +++
1:10 Undiluted
* From the Department of Dermatology and Syphiology and the Department of Surgery of the College of Medicine of the University of Cincinnati. Received for publication May 17, 1948. f Bristol Fellow in Antibiotics.
243
244
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY Material
Bacitracin Ammoniated mercury ointment
ConcntraSon.
lIezuU
1200 units/cc. 3%
There was no reaction to repeated applications of adhesive. The following intradermal tests were done: Ma/erial
Penicillin G. solution Histoplasmin
Trichophytin Oidiomycin Streptomycin solution
Ca,,centra(ien
500 units 1:100 1:30 1:100 25 mg.
Residis
++++ ++++ + ++f
120 units Bacitracin 1:100 Cocci dioidin * Later ecematoid reaction also. f Two spontaneous flare-up reactions (++) two weeks, and three weeks afterwards. DISCUSSION
Because of the enthusiasm with which penicillin was accepted and used, tyrothricin, until recent periods, has not been used as extensively as a topical agent. Its hemolytic properties and low water solubility have further limited the use of tyrothricin to topical medication. Some workers feel that this remedy possesses
some advantages and has not received the full consideration it deserves. It is our opinion that topical tyrothricin is less effective than topical penicillin or even topical streptomycin or topical bacitracin. In the case presented, we believe that we are dealing with a polyvalent hypersensitivity associated with therapy with (and initiated by?) topical tyrothricin. There is no reason to suspect that this patient, prior to the demonstration of her
sesitivities, was sensitive to the agents to which she later reacted. A prior sensitization to a common fungus or yeast-like antigen could not explain all the sensitivities, for hypersensitivity to tyrothricin and bacitracin was demonstrated. There is no ready explanation, also, for the flare-up reactions to bacitracin. In the past history, it will be recalled that the patient gave a history of thrombophlebitis of both legs 20 years previously. It is interesting to note the relative ease with which the skin of the lower extremity uith underlying circulatory disturbances becomes sensitized in contrast to the normal skin (1). The reaction of
sensitization is to be differentiated from the "grease reaction" on the lower extremities. This problem is under study at the present time. CONCLUSIONS
Contact dermatitis following the use of tyrothricin solution in a case of stasis syndrome is described. There was a wide range of eczematoid and tuberculin type sensitivities to various antibiotics including bacitracin demonstrated by skin test. REFERENCE 1. Naide, M.: Allergic lesions following thrombophiebitis. Arch. mt. Med. 80: 388 (Sept.) 1947.
In contrast to penicfflin and other antibiotics, tyrothricin has to our know! edge not previously been reported as a sensitizing agent. We therefore wish to report the detailed study of a case of contact dermatitis following the topical application of a solution of tyrothricin. A 43 year old white woman developed an ulcer on the medial aspect of the left ankle tw°
years previously. Various types of treatment for a period of 6 months were of no avai' until application of tyrothricin solution compresses healed the lesion. The ulcer recurred two and one half months prior to admission to the hospital. Tyrothricin solution was again used and the ulcer began to heal. After about 6 weeks of this treatment an acute eczematoid dermatitis of the lower leg developed. Penicillin ointment was then used without relief and with perhaps further aggravation of the dermatitis. The past history was essentially negative except for a bilateral thrombophlebitis of the legs which followed a pregnancy 20 years before. There were no previous episodes of eczematoid dermatitis, no known fungous disease of the feet and, prior to the application of tyrothricin, no use of any antibiotic. The only physical findings were those relating to the acute dermatitis involving the lower one third of the left leg and the middle portion of the plantar surface and entire dorsum of the left foot. The skin of these areas was edematous, erythematous and eczema-
toid in character. There was also a moderately severe erythematous papulo-vesicular eruption of the upper extremities. There was no clinical evidence of fungous disease of the feet. Re-examination after 6 weeks likewise revealed no evidence of this type of infection. At the present time, the patient remains free from her dermatitis. The following patch tests were done: Material
Tyrothricin solution Tyrothriein ointment Penicillin ointment Penicillin G solution Streptomycin ointment Streptomycin solution Gliotoxin cream Gliotoxin ointment Trichophytin solution Coccidioidin ilistoplasmin Oidiomycin
Concentration
25 mg./cc.
0.5 mg/gm. 1000 units/gm. 500 Units 5000 units/gm. 25 mg. 1:1000 1:1000 1:30 1:1000
Resuli
++++ ++++ +++ ++ +++
1:10 Undiluted
* From the Department of Dermatology and Syphiology and the Department of Surgery of the College of Medicine of the University of Cincinnati. Received for publication May 17, 1948. f Bristol Fellow in Antibiotics.
243
244
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY Material
Bacitracin Ammoniated mercury ointment
ConcntraSon.
lIezuU
1200 units/cc. 3%
There was no reaction to repeated applications of adhesive. The following intradermal tests were done: Ma/erial
Penicillin G. solution Histoplasmin
Trichophytin Oidiomycin Streptomycin solution
Ca,,centra(ien
500 units 1:100 1:30 1:100 25 mg.
Residis
++++ ++++ + ++f
120 units Bacitracin 1:100 Cocci dioidin * Later ecematoid reaction also. f Two spontaneous flare-up reactions (++) two weeks, and three weeks afterwards. DISCUSSION
Because of the enthusiasm with which penicillin was accepted and used, tyrothricin, until recent periods, has not been used as extensively as a topical agent. Its hemolytic properties and low water solubility have further limited the use of tyrothricin to topical medication. Some workers feel that this remedy possesses
some advantages and has not received the full consideration it deserves. It is our opinion that topical tyrothricin is less effective than topical penicillin or even topical streptomycin or topical bacitracin. In the case presented, we believe that we are dealing with a polyvalent hypersensitivity associated with therapy with (and initiated by?) topical tyrothricin. There is no reason to suspect that this patient, prior to the demonstration of her
sesitivities, was sensitive to the agents to which she later reacted. A prior sensitization to a common fungus or yeast-like antigen could not explain all the sensitivities, for hypersensitivity to tyrothricin and bacitracin was demonstrated. There is no ready explanation, also, for the flare-up reactions to bacitracin. In the past history, it will be recalled that the patient gave a history of thrombophlebitis of both legs 20 years previously. It is interesting to note the relative ease with which the skin of the lower extremity uith underlying circulatory disturbances becomes sensitized in contrast to the normal skin (1). The reaction of
sensitization is to be differentiated from the "grease reaction" on the lower extremities. This problem is under study at the present time. CONCLUSIONS
Contact dermatitis following the use of tyrothricin solution in a case of stasis syndrome is described. There was a wide range of eczematoid and tuberculin type sensitivities to various antibiotics including bacitracin demonstrated by skin test. REFERENCE 1. Naide, M.: Allergic lesions following thrombophiebitis. Arch. mt. Med. 80: 388 (Sept.) 1947.