Inappropriate Prescription of Proton Pump Inhibitors in the Setting of Steroid Use: A Teachable Moment

Masha G. Jones; Surafel Tsega; Hyung J. Cho

doi:10.1001/jamainternmed.2016.0603

Jones, Masha G.;Tsega, Surafel;Cho, Hyung J.

2016-05-01 00:00:00

Story From the Front Lines A woman in her 60s with no significant medical history presented to her internist with ear fullness and asymmetric hearing loss. She was referred to an otolaryngologist, who diagnosed idiopathic asymmetric hearing loss. Before ordering brain imaging, he prescribed prednisone, 60 mg daily, and valacyclovir for possible herpes zoster infection. He also directed the patient to purchase over-the-counter omeprazole for peptic ulcer prophylaxis in the setting of steroid use, all medications to be taken for 14 days. On day 6 of this regimen, the patient developed subjective fevers and chills and had several episodes of nonbloody emesis and diarrhea. She felt better on day 7, with no vomiting or diarrhea. On day 8, she developed a red, blotchy, intensely pruritic cutaneous eruption that emerged simultaneously throughout the body. The patient visited her dermatologist that day for the cutaneous eruption, who performed a biopsy of the skin lesions and instructed her to stop all 3 medications, which she had already taken that day. The patient felt weak and went home, unable to go to an outside location for the blood tests that her dermatologist had ordered. On the morning of day 9, the patient was taken by ambulance to the hospital, where she was found to have a temperature of 39°C, a pulse of 102 beats per minute, a respiratory rate of 18 breaths per minute, and dry mucous membranes. Her vital signs improved after a few hours on intravenous fluids. Physical examination revealed a blanching, macular cutaneous eruption with some papules involving the trunk and limbs and sparing the palms, soles, and mucous membranes. Given the patient’s clinical presentation and new medication regimen, drug reaction and viral exanthem were top on the list of differential diagnoses. Toxic shock syndrome was considered less likely owing to the rapid stabilization of the patient’s vital signs. Biopsy test results were consistent with interface and spongiotic dermatitis, suggestive of a dermatologic drug reaction. The distribution of the cutaneous eruption was consistent with the classic dermatologic drug reaction caused by a proton pump inhibitor (PPI). The dermatology department was consulted and confirmed PPI-related dermatologic drug reaction as the most likely etiology. Valacyclovir-related cutaneous eruption was considered to be unlikely given its classic involvement of symmetric intertriginous areas and absence of systemic signs or symptoms,1 whereas our patient exhibited systemic manifestations. She was treated with hydroxyzine, a topical ointment, and betamethasone. Her cutaneous eruption and pruritus improved and she was discharged after a 2-day hospitalization. Teachable Moment The prevalence of PPI use is considerable, with estimated expenditures totaling over $11 billion annually in the United States. However, over one-third of PPI prescriptions in the ambulatory setting may not be associated with an appropriate, documented indication for PPI treatment. Among hospitalized, nonintensive care unit patients, none of the 22% of patients who received stress ulcer prophylaxis with PPIs met evidence-based criteria for such prophylaxis.2 Another study2 found that only 10% of such patients received PPIs for an appropriate, symptom-based indication for antisecretory therapy, while 38% were given antisecretory therapy for stress ulcer prophylaxis or corticosteroid-associated prophylaxis. The case described herein reminds us to carefully consider indications for PPI treatment in the setting of steroid use. A recent literature search concluded that systemic corticosteroid therapy rarely causes peptic ulcers and thus there is no indication for PPI prophylaxis with short-term systemic corticosteroid use in the absence of concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).3 Nevertheless, corticosteroid users are commonly prescribed PPIs. This is particularly concerning given that higher doses of corticosteroids are thought to increase the risk of adverse events such as fractures and infection, which are also associated with PPI use. PPI-related hypersensitivity reactions include type 1 hypersensitivity reactions such as urticaria, angioedema, and anaphylaxis, as well as toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Cutaneous manifestations are most often mild, and include pruritus, urticaria, and maculopapular eruptions,4 such as those present in our patient. However, patients with DRESS may progress from these initial dermatologic symptoms to more extensive presentations with mucosal involvement and desquamation, as well as multiorgan involvement that may eventually lead to multiorgan failure and death. The literature suggests no benefit from PPI prophylaxis in patients taking systemic corticosteroids without concomitant NSAID use. Furthermore, PPIs have been linked to numerous adverse events. Studies5 show a 2- to 3-fold increase in renal disease such as acute kidney injury in PPI users compared with nonusers and a 74% higher risk of developing Clostridium difficile infection. In addition to these adverse effects, the case described herein highlights the dermatologic drug reactions that may stem from PPI use. In both the inpatient and outpatient settings, it is important for clinicians to consider indications for PPI use and possible adverse reactions ranging from a mild dermatologic drug reaction to DRESS progressing to multiorgan failure. Avoiding the prescription of PPIs when it is not medically indicated has the potential to spare individuals from unnecessary distress, and reduce avoidable hospitalizations and health care spending. Back to top Article Information Corresponding Author: Masha G. Jones, 1 Gustave L. Levy Place, Box 1086, New York, NY 10029 (jones.masha@gmail.com). Published Online: April 11, 2016. doi:10.1001/jamainternmed.2016.0603. Conflict of Interest Disclosures: None reported. Additional Contributions: We thank the patient for granting permission to publish this information. References 1. Thyssen JP, Maibach HI. Drug-elicited systemic allergic (contact) dermatitis—update and possible pathomechanisms. Contact Dermatitis. 2008;59(4):195-202.PubMedGoogle ScholarCrossref 2. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.PubMedGoogle ScholarCrossref 3. Dorlo TP, Jager NG, Beijnen JH, Schellens JH. Concomitant use of proton pump inhibitors and systemic corticosteroids. Ned Tijdschr Geneeskd. 2013;157(19):A5540-A5540.PubMedGoogle Scholar 4. Chang Y-S. Hypersensitivity reactions to proton pump inhibitors. Curr Opin Allergy Clin Immunol. 2012;12(4):348-353.PubMedGoogle ScholarCrossref 5. Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176(2):172-174.PubMedGoogle ScholarCrossref

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Inappropriate Prescription of Proton Pump Inhibitors in the Setting of Steroid Use: A Teachable Moment

$Story From the Front Lines A woman in her 60s with no significant medical history presented to her internist with ear fullness and asymmetric hearing loss. She was referred to an otolaryngologist, who diagnosed idiopathic asymmetric hearing loss. Before ordering brain imaging, he prescribed prednisone, 60 mg daily, and valacyclovir for possible herpes zoster infection. He also directed the patient to purchase over-the-counter omeprazole for peptic ulcer prophylaxis in the setting of steroid use, all medications to be taken for 14 days. On day 6 of this regimen, the patient developed subjective fevers and chills and had several episodes of nonbloody emesis and diarrhea. She felt better on day 7, with no vomiting or diarrhea. On day 8, she developed a red, blotchy, intensely pruritic cutaneous eruption that emerged simultaneously throughout the body. The patient visited her dermatologist that day for the cutaneous eruption, who performed a biopsy of the skin lesions and instructed her to stop all 3 medications, which she had already taken that day. The patient felt weak and went home, unable to go to an outside location for the blood tests that her dermatologist had ordered. On the morning of day 9, the patient was taken by ambulance to the hospital, where she was found to have a temperature of 39°C, a pulse of 102 beats per minute, a respiratory rate of 18 breaths per minute, and dry mucous membranes. Her vital signs improved after a few hours on intravenous fluids. Physical examination revealed a blanching, macular cutaneous eruption with some papules involving the trunk and limbs and sparing the palms, soles, and mucous membranes. Given the patient’s clinical presentation and new medication regimen, drug reaction and viral exanthem were top on the list of differential diagnoses. Toxic shock syndrome was considered less likely owing to the rapid stabilization of the patient’s vital signs. Biopsy test results were consistent with interface and spongiotic dermatitis, suggestive of a dermatologic drug reaction. The distribution of the cutaneous eruption was consistent with the classic dermatologic drug reaction caused by a proton pump inhibitor (PPI). The dermatology department was consulted and confirmed PPI-related dermatologic drug reaction as the most likely etiology. Valacyclovir-related cutaneous eruption was considered to be unlikely given its classic involvement of symmetric intertriginous areas and absence of systemic signs or symptoms,1 whereas our patient exhibited systemic manifestations. She was treated with hydroxyzine, a topical ointment, and betamethasone. Her cutaneous eruption and pruritus improved and she was discharged after a 2-day hospitalization. Teachable Moment The prevalence of PPI use is considerable, with estimated expenditures totaling over $11 billion annually in the United States. However, over one-third of PPI prescriptions in the ambulatory setting may not be associated with an appropriate, documented indication for PPI treatment. Among hospitalized, nonintensive care unit patients, none of the 22% of patients who received stress ulcer prophylaxis with PPIs met evidence-based criteria for such prophylaxis.2 Another study2 found that only 10% of such patients received PPIs for an appropriate, symptom-based indication for antisecretory therapy, while 38% were given antisecretory therapy for stress ulcer prophylaxis or corticosteroid-associated prophylaxis. The case described herein reminds us to carefully consider indications for PPI treatment in the setting of steroid use. A recent literature search concluded that systemic corticosteroid therapy rarely causes peptic ulcers and thus there is no indication for PPI prophylaxis with short-term systemic corticosteroid use in the absence of concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).3 Nevertheless, corticosteroid users are commonly prescribed PPIs. This is particularly concerning given that higher doses of corticosteroids are thought to increase the risk of adverse events such as fractures and infection, which are also associated with PPI use. PPI-related hypersensitivity reactions include type 1 hypersensitivity reactions such as urticaria, angioedema, and anaphylaxis, as well as toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Cutaneous manifestations are most often mild, and include pruritus, urticaria, and maculopapular eruptions,4 such as those present in our patient. However, patients with DRESS may progress from these initial dermatologic symptoms to more extensive presentations with mucosal involvement and desquamation, as well as multiorgan involvement that may eventually lead to multiorgan failure and death. The literature suggests no benefit from PPI prophylaxis in patients taking systemic corticosteroids without concomitant NSAID use. Furthermore, PPIs have been linked to numerous adverse events. Studies5 show a 2- to 3-fold increase in renal disease such as acute kidney injury in PPI users compared with nonusers and a 74% higher risk of developing Clostridium difficile infection. In addition to these adverse effects, the case described herein highlights the dermatologic drug reactions that may stem from PPI use. In both the inpatient and outpatient settings, it is important for clinicians to consider indications for PPI use and possible adverse reactions ranging from a mild dermatologic drug reaction to DRESS progressing to multiorgan failure. Avoiding the prescription of PPIs when it is not medically indicated has the potential to spare individuals from unnecessary distress, and reduce avoidable hospitalizations and health care spending. Back to top Article Information Corresponding Author: Masha G. Jones, 1 Gustave L. Levy Place, Box 1086, New York, NY 10029 (jones.masha@gmail.com). Published Online: April 11, 2016. doi:10.1001/jamainternmed.2016.0603. Conflict of Interest Disclosures: None reported. Additional Contributions: We thank the patient for granting permission to publish this information. References 1. Thyssen JP, Maibach HI. Drug-elicited systemic allergic (contact) dermatitis—update and possible pathomechanisms. Contact Dermatitis. 2008;59(4):195-202.PubMedGoogle ScholarCrossref 2. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.PubMedGoogle ScholarCrossref 3. Dorlo TP, Jager NG, Beijnen JH, Schellens JH. Concomitant use of proton pump inhibitors and systemic corticosteroids. Ned Tijdschr Geneeskd. 2013;157(19):A5540-A5540.PubMedGoogle Scholar 4. Chang Y-S. Hypersensitivity reactions to proton pump inhibitors. Curr Opin Allergy Clin Immunol. 2012;12(4):348-353.PubMedGoogle ScholarCrossref 5. Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176(2):172-174.PubMedGoogle ScholarCrossref$

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Inappropriate Prescription of Proton Pump Inhibitors in the Setting of Steroid Use: A Teachable Moment

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Inappropriate Prescription of Proton Pump Inhibitors in the Setting of Steroid Use: A Teachable Moment

Inappropriate Prescription of Proton Pump Inhibitors in the Setting of Steroid Use: A Teachable Moment

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