- Email: [email protected]
Naltrexone (Contrave®)
The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–3, 2016 Published by Elsevier Inc. 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2016.11.034
Clinical Communications: Adult ACUTE GENERALIZED ERYTHRODERMIC PUSTULAR PSORIASIS ASSOCIATED WITH BUPROPION/NALTREXONE (CONTRAVEÒ) Priyanka A. Singh, PHARMD, BCPS,*† Kerry P. Cassel, MD,† Ronald M. Moscati, MD,† and David Eckersley, MD† *Department of Pharmaceutical Science, Erie County Medical Center, Buffalo, New York and †Department of Emergency Medicine, Erie County Medical Center, Buffalo, New York Reprint Address: Priyanka A. Singh, PHARMD, BCPS, Department of Pharmaceutical Science, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215
, Abstract—Background: We report a case of erythrodermic pustular psoriasis associated with initiation of bupropion/naltrexone (ContraveÒ; Orexigen Therapeutics, La Jolla, CA) in a patient with no history of psoriasis. Case Report: A 55-year-old woman was transferred to our tertiary medical center from a community hospital for possible Stevens-Johnson syndrome 3 weeks after initiation of bupropion/naltrexone. The patient was admitted to the burn unit for wound treatment and hydration. She received intravenous cyclosporine during the admission that resulted in acute kidney injury and the therapy was discontinued. The skin biopsy ruled out Stevens-Johnson syndrome and was more consistent with generalized pustular psoriasis. After discharge, the patient followed up with her dermatologist. She was diagnosed with acute generalized and erythrodermic psoriasis and the patient was restarted on cyclosporine 100 mg twice a day. Why Should an Emergency Physician Be Aware of This?: Few case reports of bupropion-induced generalized pustular psoriasis and erythrodermic psoriasis in patients with a history of psoriasis have been reported. To our knowledge, acute generalized erythrodermic pustular psoriasis associated with bupropion/naltrexone has not been reported in a patient without history of psoriasis. Due to increases in obesity and increases in prescribing of bupropion/naltrexone SR, health care providers should be aware of this possible severe adverse reaction. Published by Elsevier Inc.
INTRODUCTION In the United States, approximately 2% of the population is affected by psoriasis. Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. The morphology can range from small tearshaped papules to pustules with generalized erythema and scales. Generalized pustular psoriasis of von Zumbusch is rare and presents as an active, unstable disease with red, painful, inflamed skin with sterile pustules, which may coalesce to form sheets. This type of psoriasis frequently requires hospitalization for management (1). CASE REPORT A 55-year-old woman with a past medical history significant for gastroesophageal reflux disease and morbid obesity (body mass index 47.75 kg/m2) presented to our tertiary medical center after transfer from a community hospital with a presentation of body-wide rash 3 weeks after starting bupropion/naltrexone for higher level of care in skin/wound care. In the emergency department (ED) the patient denied any pain, pruritus, or mucosal involvement with the rash. She denied history of psoriasis. The patient had a previous adverse reaction to sulfa, which caused nausea and vomiting, but she denied any shortness of breath or rash with sulfa. Home medications
, Keywords—bupropion; drug eruption; psoriasis
RECEIVED: 26 April 2016; FINAL SUBMISSION RECEIVED: 12 November 2016; ACCEPTED: 28 November 2016 1
2
include bupropion/naltrexone ER (ContraveÒ; Orexigen Therapeutics, La Jolla, CA) 180 mg in the morning and 90 mg in the evening, esomeprazole 40 mg daily, cholecalciferol, and cyanocobalamin. The patient denied use of any new lotion, body wash, or detergent recently. She denied use of any herbal remedies. She reported the onset of the rash during the third week of dose titration of bupropion/naltrexone. The rash was described as a red, diffuse reaction on her chest. She stopped taking the medication and sought medical attention by a dermatologist. The patient was prescribed topical hydrocortisone cream and antihistamines, which failed to control the rash. Two weeks prior to initiating treatment with bupropion/naltrexone, the patient reported taking topiramate/phentermine (QysmiaÒ; VIVUS, Inc., Mountain View, CA). The topiramate/phentermine was discontinued because it caused the patient to have difficulty sleeping and body aches. When the patient presented in our ED, she had a generalized body-wide rash sparing her face, palms, and soles of her feet. The body-wide rash had a raised reddened area with minimal sloughing. The patient was initially admitted to the burn unit for possible Stevens-Johnson Syndrome (SJS), wound treatment, hydration, and discontinuation of bupropion/naltrexone. The next day, her rash progressed to form multiple, creamy-white pustules and increased erythema (see Figure 1). The patient also developed a hypersensitivity reaction to neomycin
Figure 1. Generalized erythema with minimal skin sloughing.
P. A. Singh et al.
during her wound treatment, resulting in a medication change to mupirocin. A skin biopsy was performed at the outpatient dermatology office shortly after discharge. Results of the skin biopsy ruled out SJS and were consistent with generalized pustular psoriasis. Intravenous cyclosporine therapy was initiated, which resulted in kidney injury. The patient was discharged after a 2-week hospital stay and was instructed to follow up with her dermatologist. Her dermatologist diagnosed her rash as generalized and erythrodermic pustular psoriasis based on biopsy performed at the hospital and clinic. The results of skin biopsy revealed spongiform pustules, occasional eosinophils, and tortuous blood vessels within the papillary dermis. She was re-started on cyclosporine 100 mg twice a day with close monitoring of cyclosporine levels. DISCUSSION Our case was consistent with generalized and erythrodermic pustular psoriasis based on clinical presentation and pathology reports. Two skin biopsies performed at the dermatologist’s office revealed numerous neutrophils within the keratinizing layer and spongiform pustules, which is consistent with pustular psoriasis. Occasional eosinophils and necrotic keratinocytes raised a suspicion of acute generalized exanthematous pustulosis (AGEP). However, after the discontinuation of bupropion/ naltrexone, the reaction progressed; therefore, the dermatologist ruled out AGEP. Based on the Naranjo Scale, it scored a ‘‘possible’’ adverse drug reaction (2). The patient did develop a hypersensitivity to neomycin during admission, which may have prolonged the improvement of her rash. Erythrodermic psoriasis is a rare form of psoriasis, with a prevalence of 1–2.25% of patients with psoriasis. Due to its risks of complications such as superinfection, fever, and congestive heart failure, patients are usually hospitalized for hydration and supportive care. Due to the low incidence of disease, there is a lack of randomized, controlled studies on treatment options for erythrodermic psoriasis. Cyclosporine or infliximab is first-line therapy for unstable, erythrodermic psoriasis due to the drugs’ rapid onset (3). The patient did have a significant family history of psoriasis, which may have contributed to her development of erythrodermic pustular psoriasis shortly after medication was started. Bupropion can cause a number of skin reactions including angioedema, exfoliative dermatitis, serum sickness, and drug-induced rash with eosinophilia and systemic syndrome (4–6). There are a few reports of bupropion-induced psoriasis in patients with a history of psoriasis (7,8). There is one case report of bupropion-induced AGEP in a patient with no history
Erythrodermic Pustular Psoriasis Associated with Bupropion/Naltrexone
of psoriasis (9). Other medications such as beta-blockers, lithium, nonsteroidal antiinflammatory drugs, and tetracyclines also have been associated with triggering or aggravating psoriasis (10). However, the exact mechanism of how bupropion may trigger psoriasis is unknown. We report a case of generalized and erythrodermic pustular psoriasis that may have been triggered by bupropion/ naltrexone in a patient with no history of psoriasis.
3
providers should be aware of this possible severe adverse reaction. Acknowledgments—We would like to thank Angela Love and Heather Lindstrom for their assistance in preparing the case report.
REFERENCES WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? In the United States, more than one-third of adults are obese (11). In 2008, the annual medical cost of obesity in the United States was $147 billion due to obesityrelated conditions like heart disease, stroke, diabetes, hypertension, and certain types of cancer (12). The U.S. Food and Drug Administration recently approved bupropion/naltrexone extended release (Contrave) in September 2014 for chronic weight management along with physical activity and reduced calorie intake. Bupropion is a dopamine and norepinephrine reuptake inhibitor that stimulates pro-opiomelanocortin neurons, which then activate a-melanocortin-stimulating hormone, resulting in decreased food intake. Naltrexone inhibits the auto-inhibitory mechanism of pro-opiomelanocortinproducing neurons, thereby increasing the efficacy of bupropion. In clinical studies, bupropion SR/naltrexone SR resulted in 3–5% more weight loss than each agent separately (13). Previously, case reports of generalized and erythrodermic psoriasis have been reported in patients with a previous history of psoriasis after initiation of bupropion. To our knowledge, we report the first case of erythrodermic psoriasis that may be associated with initiation of bupropion SR/naltrexone SR in a patient without a history of psoriasis. Due to increases in obesity and increases in prescribing of bupropion/naltrexone SR, health care
1. Langley RGB, Krueger GG, Griffiths CEM. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis 2005; 64:ii18–23. 2. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30:239–45. 3. Rosenbach M, Hsu S, Korman NJ, et al. Treatment of erythrodermic psoriasis: from medical board of the National Psoriasis Foundation. J Am Acad Dermatol 2010;62:655–62. 4. Tackett AE, Smith KM. Bupropion-induced angioedemia. Am J Health Syst Pharm 2008;65:1627–30. 5. Bagshaw SM, Cload B, Gilmour J, Leung ST, Bowen TJ. Druginduced rash with eosinophilia and systemic symptoms with bupropion administration. Ann Allergy Asthma Immunol 2003;90: 572–5. 6. McCollom RA, Elbe DH, Ritchie AH. Bupropion-induced serum sickness-like reaction. Ann Pharmacother 2000;34:471–3. 7. Cox NH, Gordon PM, Dodd H. Generalized pustular and erythrodermic psoriasis associated with bupropion treatment. Br J Dermatol 2002;146:1061–3. 8. Go´mez-Ferna´ndez C, Herranz Pinto P, Casado Verrier B, Sendagorta Cudo´s E, Beato-Merino MJ, Jime´nez MC. Drug eruption and exacerbation of psoriasis related to bupropion. Eur J Dermatol 2011;21:120–1. 9. Ray AK, Wall GC. Bupropion-induced acute generalized exanthematous pustulosis. Pharmacotherapy 2011;31:621. 10. Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug induced or drug aggravated? J Clin Aesthetic Dermatol 2010;3:32–8. 11. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 2014;311:806–14. 12. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer and service-specific estimates. Health Aff (Millwood) 2009;28:w822–31. 13. Aprovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015;100:342–62.
http://dx.doi.org/10.1016/j.jemermed.2016.11.034
Clinical Communications: Adult ACUTE GENERALIZED ERYTHRODERMIC PUSTULAR PSORIASIS ASSOCIATED WITH BUPROPION/NALTREXONE (CONTRAVEÒ) Priyanka A. Singh, PHARMD, BCPS,*† Kerry P. Cassel, MD,† Ronald M. Moscati, MD,† and David Eckersley, MD† *Department of Pharmaceutical Science, Erie County Medical Center, Buffalo, New York and †Department of Emergency Medicine, Erie County Medical Center, Buffalo, New York Reprint Address: Priyanka A. Singh, PHARMD, BCPS, Department of Pharmaceutical Science, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215
, Abstract—Background: We report a case of erythrodermic pustular psoriasis associated with initiation of bupropion/naltrexone (ContraveÒ; Orexigen Therapeutics, La Jolla, CA) in a patient with no history of psoriasis. Case Report: A 55-year-old woman was transferred to our tertiary medical center from a community hospital for possible Stevens-Johnson syndrome 3 weeks after initiation of bupropion/naltrexone. The patient was admitted to the burn unit for wound treatment and hydration. She received intravenous cyclosporine during the admission that resulted in acute kidney injury and the therapy was discontinued. The skin biopsy ruled out Stevens-Johnson syndrome and was more consistent with generalized pustular psoriasis. After discharge, the patient followed up with her dermatologist. She was diagnosed with acute generalized and erythrodermic psoriasis and the patient was restarted on cyclosporine 100 mg twice a day. Why Should an Emergency Physician Be Aware of This?: Few case reports of bupropion-induced generalized pustular psoriasis and erythrodermic psoriasis in patients with a history of psoriasis have been reported. To our knowledge, acute generalized erythrodermic pustular psoriasis associated with bupropion/naltrexone has not been reported in a patient without history of psoriasis. Due to increases in obesity and increases in prescribing of bupropion/naltrexone SR, health care providers should be aware of this possible severe adverse reaction. Published by Elsevier Inc.
INTRODUCTION In the United States, approximately 2% of the population is affected by psoriasis. Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. The morphology can range from small tearshaped papules to pustules with generalized erythema and scales. Generalized pustular psoriasis of von Zumbusch is rare and presents as an active, unstable disease with red, painful, inflamed skin with sterile pustules, which may coalesce to form sheets. This type of psoriasis frequently requires hospitalization for management (1). CASE REPORT A 55-year-old woman with a past medical history significant for gastroesophageal reflux disease and morbid obesity (body mass index 47.75 kg/m2) presented to our tertiary medical center after transfer from a community hospital with a presentation of body-wide rash 3 weeks after starting bupropion/naltrexone for higher level of care in skin/wound care. In the emergency department (ED) the patient denied any pain, pruritus, or mucosal involvement with the rash. She denied history of psoriasis. The patient had a previous adverse reaction to sulfa, which caused nausea and vomiting, but she denied any shortness of breath or rash with sulfa. Home medications
, Keywords—bupropion; drug eruption; psoriasis
RECEIVED: 26 April 2016; FINAL SUBMISSION RECEIVED: 12 November 2016; ACCEPTED: 28 November 2016 1
2
include bupropion/naltrexone ER (ContraveÒ; Orexigen Therapeutics, La Jolla, CA) 180 mg in the morning and 90 mg in the evening, esomeprazole 40 mg daily, cholecalciferol, and cyanocobalamin. The patient denied use of any new lotion, body wash, or detergent recently. She denied use of any herbal remedies. She reported the onset of the rash during the third week of dose titration of bupropion/naltrexone. The rash was described as a red, diffuse reaction on her chest. She stopped taking the medication and sought medical attention by a dermatologist. The patient was prescribed topical hydrocortisone cream and antihistamines, which failed to control the rash. Two weeks prior to initiating treatment with bupropion/naltrexone, the patient reported taking topiramate/phentermine (QysmiaÒ; VIVUS, Inc., Mountain View, CA). The topiramate/phentermine was discontinued because it caused the patient to have difficulty sleeping and body aches. When the patient presented in our ED, she had a generalized body-wide rash sparing her face, palms, and soles of her feet. The body-wide rash had a raised reddened area with minimal sloughing. The patient was initially admitted to the burn unit for possible Stevens-Johnson Syndrome (SJS), wound treatment, hydration, and discontinuation of bupropion/naltrexone. The next day, her rash progressed to form multiple, creamy-white pustules and increased erythema (see Figure 1). The patient also developed a hypersensitivity reaction to neomycin
Figure 1. Generalized erythema with minimal skin sloughing.
P. A. Singh et al.
during her wound treatment, resulting in a medication change to mupirocin. A skin biopsy was performed at the outpatient dermatology office shortly after discharge. Results of the skin biopsy ruled out SJS and were consistent with generalized pustular psoriasis. Intravenous cyclosporine therapy was initiated, which resulted in kidney injury. The patient was discharged after a 2-week hospital stay and was instructed to follow up with her dermatologist. Her dermatologist diagnosed her rash as generalized and erythrodermic pustular psoriasis based on biopsy performed at the hospital and clinic. The results of skin biopsy revealed spongiform pustules, occasional eosinophils, and tortuous blood vessels within the papillary dermis. She was re-started on cyclosporine 100 mg twice a day with close monitoring of cyclosporine levels. DISCUSSION Our case was consistent with generalized and erythrodermic pustular psoriasis based on clinical presentation and pathology reports. Two skin biopsies performed at the dermatologist’s office revealed numerous neutrophils within the keratinizing layer and spongiform pustules, which is consistent with pustular psoriasis. Occasional eosinophils and necrotic keratinocytes raised a suspicion of acute generalized exanthematous pustulosis (AGEP). However, after the discontinuation of bupropion/ naltrexone, the reaction progressed; therefore, the dermatologist ruled out AGEP. Based on the Naranjo Scale, it scored a ‘‘possible’’ adverse drug reaction (2). The patient did develop a hypersensitivity to neomycin during admission, which may have prolonged the improvement of her rash. Erythrodermic psoriasis is a rare form of psoriasis, with a prevalence of 1–2.25% of patients with psoriasis. Due to its risks of complications such as superinfection, fever, and congestive heart failure, patients are usually hospitalized for hydration and supportive care. Due to the low incidence of disease, there is a lack of randomized, controlled studies on treatment options for erythrodermic psoriasis. Cyclosporine or infliximab is first-line therapy for unstable, erythrodermic psoriasis due to the drugs’ rapid onset (3). The patient did have a significant family history of psoriasis, which may have contributed to her development of erythrodermic pustular psoriasis shortly after medication was started. Bupropion can cause a number of skin reactions including angioedema, exfoliative dermatitis, serum sickness, and drug-induced rash with eosinophilia and systemic syndrome (4–6). There are a few reports of bupropion-induced psoriasis in patients with a history of psoriasis (7,8). There is one case report of bupropion-induced AGEP in a patient with no history
Erythrodermic Pustular Psoriasis Associated with Bupropion/Naltrexone
of psoriasis (9). Other medications such as beta-blockers, lithium, nonsteroidal antiinflammatory drugs, and tetracyclines also have been associated with triggering or aggravating psoriasis (10). However, the exact mechanism of how bupropion may trigger psoriasis is unknown. We report a case of generalized and erythrodermic pustular psoriasis that may have been triggered by bupropion/ naltrexone in a patient with no history of psoriasis.
3
providers should be aware of this possible severe adverse reaction. Acknowledgments—We would like to thank Angela Love and Heather Lindstrom for their assistance in preparing the case report.
REFERENCES WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? In the United States, more than one-third of adults are obese (11). In 2008, the annual medical cost of obesity in the United States was $147 billion due to obesityrelated conditions like heart disease, stroke, diabetes, hypertension, and certain types of cancer (12). The U.S. Food and Drug Administration recently approved bupropion/naltrexone extended release (Contrave) in September 2014 for chronic weight management along with physical activity and reduced calorie intake. Bupropion is a dopamine and norepinephrine reuptake inhibitor that stimulates pro-opiomelanocortin neurons, which then activate a-melanocortin-stimulating hormone, resulting in decreased food intake. Naltrexone inhibits the auto-inhibitory mechanism of pro-opiomelanocortinproducing neurons, thereby increasing the efficacy of bupropion. In clinical studies, bupropion SR/naltrexone SR resulted in 3–5% more weight loss than each agent separately (13). Previously, case reports of generalized and erythrodermic psoriasis have been reported in patients with a previous history of psoriasis after initiation of bupropion. To our knowledge, we report the first case of erythrodermic psoriasis that may be associated with initiation of bupropion SR/naltrexone SR in a patient without a history of psoriasis. Due to increases in obesity and increases in prescribing of bupropion/naltrexone SR, health care
1. Langley RGB, Krueger GG, Griffiths CEM. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis 2005; 64:ii18–23. 2. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30:239–45. 3. Rosenbach M, Hsu S, Korman NJ, et al. Treatment of erythrodermic psoriasis: from medical board of the National Psoriasis Foundation. J Am Acad Dermatol 2010;62:655–62. 4. Tackett AE, Smith KM. Bupropion-induced angioedemia. Am J Health Syst Pharm 2008;65:1627–30. 5. Bagshaw SM, Cload B, Gilmour J, Leung ST, Bowen TJ. Druginduced rash with eosinophilia and systemic symptoms with bupropion administration. Ann Allergy Asthma Immunol 2003;90: 572–5. 6. McCollom RA, Elbe DH, Ritchie AH. Bupropion-induced serum sickness-like reaction. Ann Pharmacother 2000;34:471–3. 7. Cox NH, Gordon PM, Dodd H. Generalized pustular and erythrodermic psoriasis associated with bupropion treatment. Br J Dermatol 2002;146:1061–3. 8. Go´mez-Ferna´ndez C, Herranz Pinto P, Casado Verrier B, Sendagorta Cudo´s E, Beato-Merino MJ, Jime´nez MC. Drug eruption and exacerbation of psoriasis related to bupropion. Eur J Dermatol 2011;21:120–1. 9. Ray AK, Wall GC. Bupropion-induced acute generalized exanthematous pustulosis. Pharmacotherapy 2011;31:621. 10. Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug induced or drug aggravated? J Clin Aesthetic Dermatol 2010;3:32–8. 11. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 2014;311:806–14. 12. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer and service-specific estimates. Health Aff (Millwood) 2009;28:w822–31. 13. Aprovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015;100:342–62.