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Fixed drug eruption to papaverine
FIXED DRUG ERUPTION
TO PAPAVERINE
KENT A. KIRBY, M.D. ROBERT COHEN, M.D. CHARLENE V UPSON, C.U.R.N. From the Departments of Urology and Dermatology, Cleveland Clinic Florida, Ft. Lauderdale, Florida
ABSTRACT-Papaverine
has offered new options for therapy in erectile dysfunction. Various complications have been reported with papaverine, the prominent ones being priapism and liver function abnormalities. We present a previously unreported case of a fixed drug eruption caused by papaverine.
Since its introduction by Virag in 1982,’ papaverine has been utilized for vasoactive injections to provide penile erections. Papaverine has certainly offered new options for therapy in erectile dysfunction, but complications have been reported, the prominent ones being priapism and liver function abnormalities.2 Additional complications include fibrotic nodule formation,3,’ infections from injection sites, pyogenic granuloma, and other idiopathic reactions.3,’ We describe a previously unreported complication of papaverine injection therapy, a genital fixed drug eruption. CASE REPORT A sixty-two-year-old man presented to the urology clinic for evaluation of a red, raised lesion on the dorsal aspect of his penis and a reddened lesion on the glans that seemed to wax and wain and had recently recurred. These lesions had been diagnosed as a condylomata after a positive aceto-whitening test and treated with carbon dioxide laser therapy by the patient’s local urologist. The lesion recurred and it was recommended that the patient have repeat laser surgery He presented to us for a second opinion in that regard. Questioning in regard to history revealed that this patient had no sexual exposure to anyone with condylomata or history of obvious warts. It was also noted that the patient was being treated for impotence with papaverine and phentolamine by intracavernous injections. In further questioning, it Submitted: 10, 1994
886
October
13, 1993,
uccepted
(with
r~visions):Jununr_y
appeared that there may be some relationship between the injections and the lesion. On examination, there was a fixed, red, raised lesion on the dorsum of the penis. The glans also had a red lesion, which was to the right. These lesions were inconsistent with condylomata, although the dorsal lesion did demonstrate acetowhitening. Subsequently, the patient had punch biopsy of the dorsal lesion. The pathologic examination revealed spongiosis, dermal lymphocytic infiltrate, with occasional polymorphonuclear leukocytes and occasional plasma cells consistent with a fixed drug eruption (Fig, 1). The patient was given care directed by the dermatologic service, which consisted of a topical corticosteroid cream applied twice daily. In addition, he abstained from his vasoactive injections. This resulted in abatement of the lesion. Subsequently, the patient reintroduced papaverine alone with a corporeal injection and the lesions recurred in the previous locales. The introduction of phentolamine alone produced no such response. His impotence therapy was changed to prostaglandin E, and he has had no further lesions of the phallus. COMMENT Fixed drug eruptions are fairly common and have been described for a variety of drugs. Fixed drug eruptions are most commonly encountered by the urologist with tetracycline and sulfonamides, when treating sexually transmitted diseases and urinary tract infections.5 The fixed drug eruption is the only cutaneous reaction for which drugs or chemicals are
UROLOGY / Jl’,\f
1994
/
L’OI l’hlf
4.3, Nr’hlfif,R
6
FIGURE I. Punch biopsy of the dorsal lesion shows spongiosis, dermal lymphocytic infiltrate, with occasional polymorphonuclear leukocytes and plasma cells. These findings are characteristic of fixed drug eruption. (Original magnification, x SO.)
considered the sole cause.h As the name Implies, they occur at a fixed site, that is, after reintroduction of the offending drug, a lesion will show itself at the same site as it occurred previously, thus differentiating it from a rash or a drug eruption5,” Recurrence of the eruption usually takes place within thirty minutes to eight hours.” The fixed drug eruption is characterized by an erythematous. round, or oval lesion ranging from a few millimeters to 20 cm.i,7 With time, the color turns to a dusky red or a violaceous hue.” The lesion may be edematous with occasional blistering patches, and usually involves mucocutaneous surfaces, most commonly the lips and genitalia.“’ The patient most frequently complains of warmth or burning and occasionally itching in the affected area, without systemic symptoms.’ Healing usually occurs seven to ten da),s after discontinuation of the offending drug and often leaves a dark hyperpigmented patch.” Usually, a single drug is responsible for a fixed drug eruption, although some patients react to multiple agents when the compounds arc chemi-
tally related.” In this particular patient, to dilferentiate between papaverine and phentolamine. we had him inject papaverine alone for the provocation test. The introduction of phentolamine as a single agent did not produce an eruption. The pathogenesis of the fixed drug eruption is not well understood. In some cases, topical application of the drug to the affected area will reexacerbate the reaction.4 A biopsy will confirm the diagnosis.’ Definitive therapy for genital fixed Idrug reactlons obviously revolve around careful history taking and isolating the specific instigating or offending drug. Provocation tests that involve reintroducing the drug to prove that it is indeed the causative agent is necessary as we11.5,”Withdrawal of the offending drug and localized care of the lesion with anti-inflammatory ointments or creams is usually sufficient treatment. The use of anti histamines or systemic corticosteroids has no effect on the course of a fixed drug eruption.” In the case of this particular patient, utilization of prostaglandin E, to provide erecl.lon was sufficient to treat both his baseline prohlem of impotence and also prevent further drug eruptions. Wc conclude that a fixed drug eruption to papaverine can be added to the list of potential complications with papaverine injection therap)- for erectile dysfunction.
REFERENC lib I, Virag R: lntracavernous injcctlon 01 papa\,erine for erectile failure. Lance1 2: 938. 1982. 2. Levine 58, .4lthof SE, Turner I-,4, Risen C B. Bodncr DR. Kursh ED, and Resnick Ml: Sldc effects CIIwlf-administration of intracavcrnous papavennr and phrntolamine for the treatment of Impotence. J Ural 141: 5-t-57. I YHY 3. Larsen EH, Gasser TC, and E3ruskewil.z KC- l’lbrcrsis of corpus cavcrnosum after intracavernous tnjectu~il of phentolamtne/papavertne. J Urol 137: 292-21) 3. 1k37 4. Lewis RM’: The pharmacologic t‘wctlon Pt-ohl 1 rol 5: 541-558.1991. 5. Varghesc M. and Klndcl S: F’igmentary dlwrders and inflammatory lessons of the cxtcrnal genitalia Uroi Clin I\orth Am 19: I 11-l 21, 1992. 6. DiPiro JT. Talbert RL, Hayes PE, Yet Cz<.,and Poscy LM: Phuwnacothcrupv: A Pathophvsiologir Appn>lccII. NW York. Elscvtc‘r. 1989, p 972. 7. Bruinsma W- A Guide to FIwd I)ru>; Et upt~on,. Oosthulzcn, The Net herlands, DC Zwaluw. I WC! 8. ColdIron BM. and Jacobson C:: Comnwn pc,nile Itsions I rol Clm North Am 15: 671-685. 1988. 9. Kiorki.j U: and Soltani K: Fixed drug Lwptlon. .\ hr-ief rc’vlcw. Arch Dcrmatol 120: 520-524. I Ott-1
TO PAPAVERINE
KENT A. KIRBY, M.D. ROBERT COHEN, M.D. CHARLENE V UPSON, C.U.R.N. From the Departments of Urology and Dermatology, Cleveland Clinic Florida, Ft. Lauderdale, Florida
ABSTRACT-Papaverine
has offered new options for therapy in erectile dysfunction. Various complications have been reported with papaverine, the prominent ones being priapism and liver function abnormalities. We present a previously unreported case of a fixed drug eruption caused by papaverine.
Since its introduction by Virag in 1982,’ papaverine has been utilized for vasoactive injections to provide penile erections. Papaverine has certainly offered new options for therapy in erectile dysfunction, but complications have been reported, the prominent ones being priapism and liver function abnormalities.2 Additional complications include fibrotic nodule formation,3,’ infections from injection sites, pyogenic granuloma, and other idiopathic reactions.3,’ We describe a previously unreported complication of papaverine injection therapy, a genital fixed drug eruption. CASE REPORT A sixty-two-year-old man presented to the urology clinic for evaluation of a red, raised lesion on the dorsal aspect of his penis and a reddened lesion on the glans that seemed to wax and wain and had recently recurred. These lesions had been diagnosed as a condylomata after a positive aceto-whitening test and treated with carbon dioxide laser therapy by the patient’s local urologist. The lesion recurred and it was recommended that the patient have repeat laser surgery He presented to us for a second opinion in that regard. Questioning in regard to history revealed that this patient had no sexual exposure to anyone with condylomata or history of obvious warts. It was also noted that the patient was being treated for impotence with papaverine and phentolamine by intracavernous injections. In further questioning, it Submitted: 10, 1994
886
October
13, 1993,
uccepted
(with
r~visions):Jununr_y
appeared that there may be some relationship between the injections and the lesion. On examination, there was a fixed, red, raised lesion on the dorsum of the penis. The glans also had a red lesion, which was to the right. These lesions were inconsistent with condylomata, although the dorsal lesion did demonstrate acetowhitening. Subsequently, the patient had punch biopsy of the dorsal lesion. The pathologic examination revealed spongiosis, dermal lymphocytic infiltrate, with occasional polymorphonuclear leukocytes and occasional plasma cells consistent with a fixed drug eruption (Fig, 1). The patient was given care directed by the dermatologic service, which consisted of a topical corticosteroid cream applied twice daily. In addition, he abstained from his vasoactive injections. This resulted in abatement of the lesion. Subsequently, the patient reintroduced papaverine alone with a corporeal injection and the lesions recurred in the previous locales. The introduction of phentolamine alone produced no such response. His impotence therapy was changed to prostaglandin E, and he has had no further lesions of the phallus. COMMENT Fixed drug eruptions are fairly common and have been described for a variety of drugs. Fixed drug eruptions are most commonly encountered by the urologist with tetracycline and sulfonamides, when treating sexually transmitted diseases and urinary tract infections.5 The fixed drug eruption is the only cutaneous reaction for which drugs or chemicals are
UROLOGY / Jl’,\f
1994
/
L’OI l’hlf
4.3, Nr’hlfif,R
6
FIGURE I. Punch biopsy of the dorsal lesion shows spongiosis, dermal lymphocytic infiltrate, with occasional polymorphonuclear leukocytes and plasma cells. These findings are characteristic of fixed drug eruption. (Original magnification, x SO.)
considered the sole cause.h As the name Implies, they occur at a fixed site, that is, after reintroduction of the offending drug, a lesion will show itself at the same site as it occurred previously, thus differentiating it from a rash or a drug eruption5,” Recurrence of the eruption usually takes place within thirty minutes to eight hours.” The fixed drug eruption is characterized by an erythematous. round, or oval lesion ranging from a few millimeters to 20 cm.i,7 With time, the color turns to a dusky red or a violaceous hue.” The lesion may be edematous with occasional blistering patches, and usually involves mucocutaneous surfaces, most commonly the lips and genitalia.“’ The patient most frequently complains of warmth or burning and occasionally itching in the affected area, without systemic symptoms.’ Healing usually occurs seven to ten da),s after discontinuation of the offending drug and often leaves a dark hyperpigmented patch.” Usually, a single drug is responsible for a fixed drug eruption, although some patients react to multiple agents when the compounds arc chemi-
tally related.” In this particular patient, to dilferentiate between papaverine and phentolamine. we had him inject papaverine alone for the provocation test. The introduction of phentolamine as a single agent did not produce an eruption. The pathogenesis of the fixed drug eruption is not well understood. In some cases, topical application of the drug to the affected area will reexacerbate the reaction.4 A biopsy will confirm the diagnosis.’ Definitive therapy for genital fixed Idrug reactlons obviously revolve around careful history taking and isolating the specific instigating or offending drug. Provocation tests that involve reintroducing the drug to prove that it is indeed the causative agent is necessary as we11.5,”Withdrawal of the offending drug and localized care of the lesion with anti-inflammatory ointments or creams is usually sufficient treatment. The use of anti histamines or systemic corticosteroids has no effect on the course of a fixed drug eruption.” In the case of this particular patient, utilization of prostaglandin E, to provide erecl.lon was sufficient to treat both his baseline prohlem of impotence and also prevent further drug eruptions. Wc conclude that a fixed drug eruption to papaverine can be added to the list of potential complications with papaverine injection therap)- for erectile dysfunction.
REFERENC lib I, Virag R: lntracavernous injcctlon 01 papa\,erine for erectile failure. Lance1 2: 938. 1982. 2. Levine 58, .4lthof SE, Turner I-,4, Risen C B. Bodncr DR. Kursh ED, and Resnick Ml: Sldc effects CIIwlf-administration of intracavcrnous papavennr and phrntolamine for the treatment of Impotence. J Ural 141: 5-t-57. I YHY 3. Larsen EH, Gasser TC, and E3ruskewil.z KC- l’lbrcrsis of corpus cavcrnosum after intracavernous tnjectu~il of phentolamtne/papavertne. J Urol 137: 292-21) 3. 1k37 4. Lewis RM’: The pharmacologic t‘wctlon Pt-ohl 1 rol 5: 541-558.1991. 5. Varghesc M. and Klndcl S: F’igmentary dlwrders and inflammatory lessons of the cxtcrnal genitalia Uroi Clin I\orth Am 19: I 11-l 21, 1992. 6. DiPiro JT. Talbert RL, Hayes PE, Yet Cz<.,and Poscy LM: Phuwnacothcrupv: A Pathophvsiologir Appn>lccII. NW York. Elscvtc‘r. 1989, p 972. 7. Bruinsma W- A Guide to FIwd I)ru>; Et upt~on,. Oosthulzcn, The Net herlands, DC Zwaluw. I WC! 8. ColdIron BM. and Jacobson C:: Comnwn pc,nile Itsions I rol Clm North Am 15: 671-685. 1988. 9. Kiorki.j U: and Soltani K: Fixed drug Lwptlon. .\ hr-ief rc’vlcw. Arch Dcrmatol 120: 520-524. I Ott-1