Acute cutaneous vasculitis associated with prolonged intravenous ritodrine hydrochloride therapy Stacie Bosnyak, MD: Joseph M. Baron, MD: and James Schreiber, MD" Chicago, Illinois A patient with twin gestation was hospitalized because of preterm labor and treated with intravenous ritodrine hydrochloride (Yutopar, Astra Pharmaceutical Products, Westborough, Mass.). After >4 weeks of therapy, the patient had a petechial rash and prolonged bleeding time, which were diagnosed and confirmed by skin biopsy at cesarean section as vasculitis. This is the first documented case of vasculitis associated with ritodrine use. (AM J OBSTET GYNECOL 1991 ;165:427-8.)
Key words: Preterm labor, cutaneous vasculitis, ritodrine Preterm delivery, before 37 weeks' gestation, occurs in 5% to 10% of all pregnancies in developed countries and accounts for 60% to 90% of perinatal mortality in infants without anomalies. I3-Sympathomimetic amines are a well-accepted and frequently used treatment for preterm contractions since Food and Drug Administration approval in 19S0. Ritodrine hydrochloride (Yuto par, Astra Pharmaceutical Products, Westborough, Mass.) is a 132-adrenergic agonist that relaxes uterine muscle by a hypothesized cyclic adenosine 5'-monophosphate-mediated mechanism. Common side effects include tachycardia, nausea, hypokalemia, and flushing, which necessitate discontinuation of therapy in 3% to 10% of patients. More serious side effects include hypotension, cardiac arrhythmias, myocardial ischemia, and pulmonary edema, which have been observed in 1 % to 5% of cases. In our institution we encountered a case of vasculitis, previously unreported, after prolonged l3-sympathomimetic tocolysis. Case report A 30-year-old woman, gravida 1, para 0, was diagnosed by ultrasonography to have twins at 10 weeks' gestation. She had no significant medical or surgical history, including no history of arthritis, autoimmune disease, petechial rash, or thrombocytopenia. Platelet counts of 2S0,000/mm' and 209.000/mm' were measured at IS and 14 months, respectively, before delivery. At 29 weeks' gestation, the patient noted mild contractions, and she was placed on bed rest and started on a regimen of oral ritodrine hydrochloride, 10 mg every 6 hours. One week later she felt increasing conFrom the Departments of Obstetrics and Gynecologya and Medicine/ The University of Chicago. Received for publication September 25,1990; revised February 13, 1991; accepted March 1, 1991. Reprint requests: James R. Schreiber, MD, Box 446, Department of Obstetrics and Gynecology, The University of Chicago, 5841 S. Maryland Ave., Chicago, 1L 60637.
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tractions and was admitted to the hospital in pre term labor. At that time she had a sonogram consistent with her dates, a cervical examination showing 2 cm dilatation and 50% effacement, and monitored contractions occurring every 4 to 6 minutes. Admission laboratory studies included white blood cell count, 6400/mm 3 ; hematocrit, 35.6%; platelet count, 149,000/mm 3 (150,000 to 450,000/mm 3 is normal); fibrinogen, 3S0 mg/dl (200 to 400 mg/dl is normal); and antithrombin III, 91% (S4% to 116% is normal). She was begun on a regimen of intravenous ritodrine hydrochloride at 100 /-Lg/min and contractions abated. Any attempt to change to a regimen of oral ritodrine or to decrease the amount of intravenous ritodrine resulted in return of contractions. On this medication regimen fibrinogen, hematocrit, and serum potassium level remained stable. She was continued on the regimen of intravenous ritodrine at 100 /-Lg/min for 5 weeks. At 34 weeks' gestation (5 weeks after admission) a nonpalpable, nonpruritic petechial rash appeared initially on the forearms and later extended to all extremities. She had no mucosal bleeding, hematuria, hematochezia, or palpable hepatosplenomegaly. Hematologic studies included white blood cell count, 5000/mm'; hematocrit, 34%; platelets, 125,000/mm 3 ; prothrombin time, 11.1 seconds (normal); partial thromboplastin time, 25.2 seconds (normal); fibrin degradation products, > 10
Key words: Preterm labor, cutaneous vasculitis, ritodrine Preterm delivery, before 37 weeks' gestation, occurs in 5% to 10% of all pregnancies in developed countries and accounts for 60% to 90% of perinatal mortality in infants without anomalies. I3-Sympathomimetic amines are a well-accepted and frequently used treatment for preterm contractions since Food and Drug Administration approval in 19S0. Ritodrine hydrochloride (Yuto par, Astra Pharmaceutical Products, Westborough, Mass.) is a 132-adrenergic agonist that relaxes uterine muscle by a hypothesized cyclic adenosine 5'-monophosphate-mediated mechanism. Common side effects include tachycardia, nausea, hypokalemia, and flushing, which necessitate discontinuation of therapy in 3% to 10% of patients. More serious side effects include hypotension, cardiac arrhythmias, myocardial ischemia, and pulmonary edema, which have been observed in 1 % to 5% of cases. In our institution we encountered a case of vasculitis, previously unreported, after prolonged l3-sympathomimetic tocolysis. Case report A 30-year-old woman, gravida 1, para 0, was diagnosed by ultrasonography to have twins at 10 weeks' gestation. She had no significant medical or surgical history, including no history of arthritis, autoimmune disease, petechial rash, or thrombocytopenia. Platelet counts of 2S0,000/mm' and 209.000/mm' were measured at IS and 14 months, respectively, before delivery. At 29 weeks' gestation, the patient noted mild contractions, and she was placed on bed rest and started on a regimen of oral ritodrine hydrochloride, 10 mg every 6 hours. One week later she felt increasing conFrom the Departments of Obstetrics and Gynecologya and Medicine/ The University of Chicago. Received for publication September 25,1990; revised February 13, 1991; accepted March 1, 1991. Reprint requests: James R. Schreiber, MD, Box 446, Department of Obstetrics and Gynecology, The University of Chicago, 5841 S. Maryland Ave., Chicago, 1L 60637.
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tractions and was admitted to the hospital in pre term labor. At that time she had a sonogram consistent with her dates, a cervical examination showing 2 cm dilatation and 50% effacement, and monitored contractions occurring every 4 to 6 minutes. Admission laboratory studies included white blood cell count, 6400/mm 3 ; hematocrit, 35.6%; platelet count, 149,000/mm 3 (150,000 to 450,000/mm 3 is normal); fibrinogen, 3S0 mg/dl (200 to 400 mg/dl is normal); and antithrombin III, 91% (S4% to 116% is normal). She was begun on a regimen of intravenous ritodrine hydrochloride at 100 /-Lg/min and contractions abated. Any attempt to change to a regimen of oral ritodrine or to decrease the amount of intravenous ritodrine resulted in return of contractions. On this medication regimen fibrinogen, hematocrit, and serum potassium level remained stable. She was continued on the regimen of intravenous ritodrine at 100 /-Lg/min for 5 weeks. At 34 weeks' gestation (5 weeks after admission) a nonpalpable, nonpruritic petechial rash appeared initially on the forearms and later extended to all extremities. She had no mucosal bleeding, hematuria, hematochezia, or palpable hepatosplenomegaly. Hematologic studies included white blood cell count, 5000/mm'; hematocrit, 34%; platelets, 125,000/mm 3 ; prothrombin time, 11.1 seconds (normal); partial thromboplastin time, 25.2 seconds (normal); fibrin degradation products, > 10
