NEW ORLEANS – An investigational hepatitis B vaccine known as Heplisav-B provided significantly better seroprotection among adults with type 2 diabetes than did a currently licensed vaccine, based on results from a randomized phase III trial.

A total of 321 patients received three doses of the Food and Drug Administration–approved vaccine Engerix-B at weeks 0, 4, and 24, while 640 patients received two doses of the investigational vaccine Heplisav-B at weeks 0 and 4 and a placebo injection at week 24. In both groups of patients, two-thirds of subjects had diabetes for 5 or more years, Randall N. Hyer, MD, reported in a poster at the annual scientific sessions of the American Diabetes Association.

Doug Brunk/Frontline Medical News

At 28 weeks, 90% of subjects in the Heplisav-B group and 65% in the Engerix-B group achieved seroprotection, defined as anti–hepatitis B titers of 10 mIU/mL or greater. The difference reached statistical significance. Among study participants aged 60-70 years, 85.8% of subjects in the Heplisav-B group achieved seroprotection, compared with 58.5% in the Engerix-B group. Among study participants with a body mass index of 30 kg/m², 89.5% of subjects in the Heplisav-B group achieved seroprotection, compared with 61.4% in the Engerix-B group, reported Dr. Hyer, who is vice president of medical affairs for Dynavax, the maker of Heplisav-B.

The safety profile, including the incidence of immune-mediated adverse events, was similar in both treatment groups. The most frequently reported local reaction was injection-site pain, while the most common systemic reactions were fatigue, headache, and malaise.

Dynavax submitted a biologics license application to the FDA in March 2016, and a decision on whether to approve Heplisav-B is expected by mid-December. “The Centers for Disease Control and Prevention does recommend that all adults with diabetes aged 19-59 be vaccinated against HBV [hepatitis B virus] as soon as feasible after diagnosis. For folks 60 and above, it’s at the discretion of the physician. People with type 2 diabetes are twice as likely to get HBV,” Dr. Hyer said in an interview.

Dynavax funded the study. Dr. Hyer is an employee of the company.

[email protected]

NEW ORLEANS – An investigational hepatitis B vaccine known as Heplisav-B provided significantly better seroprotection among adults with type 2 diabetes than did a currently licensed vaccine, based on results from a randomized phase III trial.

A total of 321 patients received three doses of the Food and Drug Administration–approved vaccine Engerix-B at weeks 0, 4, and 24, while 640 patients received two doses of the investigational vaccine Heplisav-B at weeks 0 and 4 and a placebo injection at week 24. In both groups of patients, two-thirds of subjects had diabetes for 5 or more years, Randall N. Hyer, MD, reported in a poster at the annual scientific sessions of the American Diabetes Association.

Doug Brunk/Frontline Medical News

At 28 weeks, 90% of subjects in the Heplisav-B group and 65% in the Engerix-B group achieved seroprotection, defined as anti–hepatitis B titers of 10 mIU/mL or greater. The difference reached statistical significance. Among study participants aged 60-70 years, 85.8% of subjects in the Heplisav-B group achieved seroprotection, compared with 58.5% in the Engerix-B group. Among study participants with a body mass index of 30 kg/m², 89.5% of subjects in the Heplisav-B group achieved seroprotection, compared with 61.4% in the Engerix-B group, reported Dr. Hyer, who is vice president of medical affairs for Dynavax, the maker of Heplisav-B.

The safety profile, including the incidence of immune-mediated adverse events, was similar in both treatment groups. The most frequently reported local reaction was injection-site pain, while the most common systemic reactions were fatigue, headache, and malaise.

Dynavax submitted a biologics license application to the FDA in March 2016, and a decision on whether to approve Heplisav-B is expected by mid-December. “The Centers for Disease Control and Prevention does recommend that all adults with diabetes aged 19-59 be vaccinated against HBV [hepatitis B virus] as soon as feasible after diagnosis. For folks 60 and above, it’s at the discretion of the physician. People with type 2 diabetes are twice as likely to get HBV,” Dr. Hyer said in an interview.

Dynavax funded the study. Dr. Hyer is an employee of the company.

[email protected]

NEW ORLEANS – An investigational hepatitis B vaccine known as Heplisav-B provided significantly better seroprotection among adults with type 2 diabetes than did a currently licensed vaccine, based on results from a randomized phase III trial.

A total of 321 patients received three doses of the Food and Drug Administration–approved vaccine Engerix-B at weeks 0, 4, and 24, while 640 patients received two doses of the investigational vaccine Heplisav-B at weeks 0 and 4 and a placebo injection at week 24. In both groups of patients, two-thirds of subjects had diabetes for 5 or more years, Randall N. Hyer, MD, reported in a poster at the annual scientific sessions of the American Diabetes Association.

Doug Brunk/Frontline Medical News

At 28 weeks, 90% of subjects in the Heplisav-B group and 65% in the Engerix-B group achieved seroprotection, defined as anti–hepatitis B titers of 10 mIU/mL or greater. The difference reached statistical significance. Among study participants aged 60-70 years, 85.8% of subjects in the Heplisav-B group achieved seroprotection, compared with 58.5% in the Engerix-B group. Among study participants with a body mass index of 30 kg/m², 89.5% of subjects in the Heplisav-B group achieved seroprotection, compared with 61.4% in the Engerix-B group, reported Dr. Hyer, who is vice president of medical affairs for Dynavax, the maker of Heplisav-B.

The safety profile, including the incidence of immune-mediated adverse events, was similar in both treatment groups. The most frequently reported local reaction was injection-site pain, while the most common systemic reactions were fatigue, headache, and malaise.

Dynavax submitted a biologics license application to the FDA in March 2016, and a decision on whether to approve Heplisav-B is expected by mid-December. “The Centers for Disease Control and Prevention does recommend that all adults with diabetes aged 19-59 be vaccinated against HBV [hepatitis B virus] as soon as feasible after diagnosis. For folks 60 and above, it’s at the discretion of the physician. People with type 2 diabetes are twice as likely to get HBV,” Dr. Hyer said in an interview.

Dynavax funded the study. Dr. Hyer is an employee of the company.

[email protected]

A biopsy was performed and direct immunofluorescence came back negative. This, along with the patient’s history of diabetes, led us to diagnose bullosis diabeticorum.

This condition, also known as bullous disease of diabetes, is characterized by abrupt development of noninflammatory bullae on acral areas in patients with diabetes. The skin appears normal except for the bullae. Bullosis diabeticorum occurs in just .5% of patients with diabetes and is twice as common in men as it is in women.

The etiology of bullosis diabeticorum is unknown. The acral location suggests that trauma may be a contributing factor. Although electron microscopy has suggested an abnormality in anchoring fibrils, this cellular change does not fully explain the development of multiple blisters at varying sites. Glycemic control is not thought to play a role.

The distribution of lesions and the presence—or absence—of systemic symptoms goes a long way toward narrowing the differential of blistering diseases. The presence of generalized blistering and systemic symptoms would suggest conditions related to medication exposure, such as Stevens-Johnson syndrome or toxic epidermal necrolysis; infectious etiologies (eg, staphylococcal scalded skin syndrome); autoimmune causes; or underlying malignancy. Generalized blistering in the absence of systemic symptoms would support diagnoses such as bullous impetigo and pemphigoid.

Lesion distribution provides important clues, too. Sun exposure-related causes typically leave lesions on the hands and forearms, not just the toes. A dermatomal distribution would suggest herpes zoster. A linear distribution of blisters argues for contact dermatitis.

A diagnosis of bullosis diabeticorum can be made when biopsy with immunofluorescence excludes other histologically similar entities such as epidermolysis bullosa, noninflammatory bullous pemphigoid, and porphyria cutanea tarda. And while immunofluorescence findings are typically negative, elevated levels of immunoglobulin M and C3 have, on occasion, been reported. Cultures are warranted only if a secondary infection is suspected.

The bullae of this condition spontaneously resolve over several weeks without treatment, but tend to recur. The lesions typically heal without significant scarring, although they may have a darker pigmentation after the first occurrence. Treatment may be warranted if a patient develops a secondary infection.

In our patient’s case, the bullae resolved within 2 weeks without treatment, although mild hyperpigmentation remained.

Adapted from: Mims L, Savage A, Chessman A. Blisters on an elderly woman's toes. J Fam Pract. 2014;63:273-274.

A biopsy was performed and direct immunofluorescence came back negative. This, along with the patient’s history of diabetes, led us to diagnose bullosis diabeticorum.

This condition, also known as bullous disease of diabetes, is characterized by abrupt development of noninflammatory bullae on acral areas in patients with diabetes. The skin appears normal except for the bullae. Bullosis diabeticorum occurs in just .5% of patients with diabetes and is twice as common in men as it is in women.

The etiology of bullosis diabeticorum is unknown. The acral location suggests that trauma may be a contributing factor. Although electron microscopy has suggested an abnormality in anchoring fibrils, this cellular change does not fully explain the development of multiple blisters at varying sites. Glycemic control is not thought to play a role.

The distribution of lesions and the presence—or absence—of systemic symptoms goes a long way toward narrowing the differential of blistering diseases. The presence of generalized blistering and systemic symptoms would suggest conditions related to medication exposure, such as Stevens-Johnson syndrome or toxic epidermal necrolysis; infectious etiologies (eg, staphylococcal scalded skin syndrome); autoimmune causes; or underlying malignancy. Generalized blistering in the absence of systemic symptoms would support diagnoses such as bullous impetigo and pemphigoid.

Lesion distribution provides important clues, too. Sun exposure-related causes typically leave lesions on the hands and forearms, not just the toes. A dermatomal distribution would suggest herpes zoster. A linear distribution of blisters argues for contact dermatitis.

A diagnosis of bullosis diabeticorum can be made when biopsy with immunofluorescence excludes other histologically similar entities such as epidermolysis bullosa, noninflammatory bullous pemphigoid, and porphyria cutanea tarda. And while immunofluorescence findings are typically negative, elevated levels of immunoglobulin M and C3 have, on occasion, been reported. Cultures are warranted only if a secondary infection is suspected.

The bullae of this condition spontaneously resolve over several weeks without treatment, but tend to recur. The lesions typically heal without significant scarring, although they may have a darker pigmentation after the first occurrence. Treatment may be warranted if a patient develops a secondary infection.

In our patient’s case, the bullae resolved within 2 weeks without treatment, although mild hyperpigmentation remained.

Adapted from: Mims L, Savage A, Chessman A. Blisters on an elderly woman's toes. J Fam Pract. 2014;63:273-274.

A biopsy was performed and direct immunofluorescence came back negative. This, along with the patient’s history of diabetes, led us to diagnose bullosis diabeticorum.

This condition, also known as bullous disease of diabetes, is characterized by abrupt development of noninflammatory bullae on acral areas in patients with diabetes. The skin appears normal except for the bullae. Bullosis diabeticorum occurs in just .5% of patients with diabetes and is twice as common in men as it is in women.

The etiology of bullosis diabeticorum is unknown. The acral location suggests that trauma may be a contributing factor. Although electron microscopy has suggested an abnormality in anchoring fibrils, this cellular change does not fully explain the development of multiple blisters at varying sites. Glycemic control is not thought to play a role.

The distribution of lesions and the presence—or absence—of systemic symptoms goes a long way toward narrowing the differential of blistering diseases. The presence of generalized blistering and systemic symptoms would suggest conditions related to medication exposure, such as Stevens-Johnson syndrome or toxic epidermal necrolysis; infectious etiologies (eg, staphylococcal scalded skin syndrome); autoimmune causes; or underlying malignancy. Generalized blistering in the absence of systemic symptoms would support diagnoses such as bullous impetigo and pemphigoid.

Lesion distribution provides important clues, too. Sun exposure-related causes typically leave lesions on the hands and forearms, not just the toes. A dermatomal distribution would suggest herpes zoster. A linear distribution of blisters argues for contact dermatitis.

A diagnosis of bullosis diabeticorum can be made when biopsy with immunofluorescence excludes other histologically similar entities such as epidermolysis bullosa, noninflammatory bullous pemphigoid, and porphyria cutanea tarda. And while immunofluorescence findings are typically negative, elevated levels of immunoglobulin M and C3 have, on occasion, been reported. Cultures are warranted only if a secondary infection is suspected.

The bullae of this condition spontaneously resolve over several weeks without treatment, but tend to recur. The lesions typically heal without significant scarring, although they may have a darker pigmentation after the first occurrence. Treatment may be warranted if a patient develops a secondary infection.

In our patient’s case, the bullae resolved within 2 weeks without treatment, although mild hyperpigmentation remained.

Adapted from: Mims L, Savage A, Chessman A. Blisters on an elderly woman's toes. J Fam Pract. 2014;63:273-274.

CMV infection

Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.

However, a new study, based on data from about 9500 patients, suggests otherwise.

Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.

Researchers reported these findings in Blood.

“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.

“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”

For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.

The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).

The median time to initial CMV reactivation was 41 days (range, 1-362 days).

The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).

However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).

Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).

“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”

One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.

For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.

“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.

“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”

CMV infection

Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.

However, a new study, based on data from about 9500 patients, suggests otherwise.

Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.

Researchers reported these findings in Blood.

“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.

“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”

For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.

The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).

The median time to initial CMV reactivation was 41 days (range, 1-362 days).

The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).

However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).

Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).

“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”

One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.

For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.

“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.

“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”

CMV infection

Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.

However, a new study, based on data from about 9500 patients, suggests otherwise.

Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.

Researchers reported these findings in Blood.

“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.

“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”

For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.

The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).

The median time to initial CMV reactivation was 41 days (range, 1-362 days).

The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).

However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).

Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).

“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”

One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.

For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.

“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.

“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”

Jill Slater Waldman, MD, SFHM, loved math and science and working with people, so a career in medicine was always the logical choice. She just didn’t want to leave a hospital, literally. So when she was finishing her internal medicine residency in 1994 at Westchester Medical Center in Valhalla, N.Y., internal medicine (IM) suddenly appealed.

“I started seeking any job that would be ‘all in house,’ with no outpatient or clinic time,” Dr. Waldman says. “I was informed those jobs did not exist, so I joined the faculty of Albert Einstein College of Medicine with a dual appointment in emergency and internal medicine.”

Fast-forward through a few IM positions at New York State hospitals, and she landed the directorship of the adult hospitalist program at Nyack (N.Y.) Hospital. Two years later, she left for her current post, director of the adult hospital service at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y.

A crowded résumé got an extra line this year as Dr. Waldman is one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Tell us about your training years.

Answer: I initially matched in anesthesia but within two weeks realized the pre-ops and post-ops were my favorite visits. I went back to complete my IM residency, doing multiple extra months of ICU night float to avoid having to go to continuity of care clinic.

Q: Did you have a mentor during your training or early career? If so, who was the mentor, and what were the most important lessons you learned from him/her?

A: My mentor was undoubtedly my internship coordinator, who allowed me back to complete my IM training when I realized anesthesia was not for me. He is a special man, incredibly brilliant, and committed to the art and science of medicine. He taught his staff to always act like a physician, always have respect for yourself and the patients, and to take no shortcuts. He is the brightest physician I likely have ever met, and I am lucky to have been hired by him to run his hospital medicine program as a senior attending.

Q: Have you tried to mentor others?

A: I enjoy mentoring junior faculty, house staff, and students. I just returned from a medical mission during which I supervised three fantastic medical students—one of whom was my own daughter.

Q: What do you like most about working as a hospitalist?

A: The variety of patients we get to interact with and the variety of pathology we see.

Q: What do you dislike most?

A: Raw beets and egotistical consultants who treat hospitalists like house staff.

Q: How many Apple products do you interface with in a given week?

A: Two.

Q: What impact do you feel those devices and ones similar to them have had on HM and medicine in a broader sense?

A: I believe they have enabled channels of communication and allowed the public to become more knowledgeable medically.

Q: What’s the best advice you ever received?

A: Do unto others as you wish others to do unto you.

Q: What’s the worst advice you ever received?

A: “There’s no way you can be both a mother and a doctor. Pick one.”

Q: What’s the biggest change you’ve seen in HM in your career?

A: The evolution of HM as a true specialty, requiring a skill set of its own to be a hospitalist.

Q: What’s the biggest change you would like to see in HM?

A: More respect for the field and understanding of our skill set and knowledge base.

Q: As a group leader, why is it important for you to continue seeing patients?

A: As a director, I believe keeping my skill set current is important for myself as well as my partners. I have always said I would never ask them to do something I would not do, so I get to practice what I preach. I also think it enables me to keep perspective when discussing plans with administration or reviewing complaints.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: You are meeting a person on what is likely the worst day of their life. Trying to find the best approach for each individual is still a challenge.

Q: What aspect of patient care is most rewarding?

A: Seeing the relief on a patient’s face when you tell them they will get better and explain their treatment plan.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: Teaching in the 21st century is challenging with all the new regulations. We have a family physician residency at our hospital, and the blind dedication we had as residents is just not present in a group of physicians who have grown up with duty hour restrictions and protected time.

Q: What is your biggest professional reward?

A: Our group has virtually no attrition and has been intact for more than five years.

Q: You received your SFHM designation five years ago. What does that public recognition mean to you?

A: It was a mark of respect and recognition for expertise in this new field. A very proud moment.

Q: Where do you see yourself in 10 years?

A: Hopefully, working as a part-time nocturnist two nights per week and caring for some grandbabies and going on medical missions. TH

Richard Quinn is a freelance writer in New Jersey.

Jill Slater Waldman, MD, SFHM, loved math and science and working with people, so a career in medicine was always the logical choice. She just didn’t want to leave a hospital, literally. So when she was finishing her internal medicine residency in 1994 at Westchester Medical Center in Valhalla, N.Y., internal medicine (IM) suddenly appealed.

“I started seeking any job that would be ‘all in house,’ with no outpatient or clinic time,” Dr. Waldman says. “I was informed those jobs did not exist, so I joined the faculty of Albert Einstein College of Medicine with a dual appointment in emergency and internal medicine.”

Fast-forward through a few IM positions at New York State hospitals, and she landed the directorship of the adult hospitalist program at Nyack (N.Y.) Hospital. Two years later, she left for her current post, director of the adult hospital service at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y.

A crowded résumé got an extra line this year as Dr. Waldman is one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Tell us about your training years.

Answer: I initially matched in anesthesia but within two weeks realized the pre-ops and post-ops were my favorite visits. I went back to complete my IM residency, doing multiple extra months of ICU night float to avoid having to go to continuity of care clinic.

Q: Did you have a mentor during your training or early career? If so, who was the mentor, and what were the most important lessons you learned from him/her?

A: My mentor was undoubtedly my internship coordinator, who allowed me back to complete my IM training when I realized anesthesia was not for me. He is a special man, incredibly brilliant, and committed to the art and science of medicine. He taught his staff to always act like a physician, always have respect for yourself and the patients, and to take no shortcuts. He is the brightest physician I likely have ever met, and I am lucky to have been hired by him to run his hospital medicine program as a senior attending.

Q: Have you tried to mentor others?

A: I enjoy mentoring junior faculty, house staff, and students. I just returned from a medical mission during which I supervised three fantastic medical students—one of whom was my own daughter.

Q: What do you like most about working as a hospitalist?

A: The variety of patients we get to interact with and the variety of pathology we see.

Q: What do you dislike most?

A: Raw beets and egotistical consultants who treat hospitalists like house staff.

Q: How many Apple products do you interface with in a given week?

A: Two.

Q: What impact do you feel those devices and ones similar to them have had on HM and medicine in a broader sense?

A: I believe they have enabled channels of communication and allowed the public to become more knowledgeable medically.

Q: What’s the best advice you ever received?

A: Do unto others as you wish others to do unto you.

Q: What’s the worst advice you ever received?

A: “There’s no way you can be both a mother and a doctor. Pick one.”

Q: What’s the biggest change you’ve seen in HM in your career?

A: The evolution of HM as a true specialty, requiring a skill set of its own to be a hospitalist.

Q: What’s the biggest change you would like to see in HM?

A: More respect for the field and understanding of our skill set and knowledge base.

Q: As a group leader, why is it important for you to continue seeing patients?

A: As a director, I believe keeping my skill set current is important for myself as well as my partners. I have always said I would never ask them to do something I would not do, so I get to practice what I preach. I also think it enables me to keep perspective when discussing plans with administration or reviewing complaints.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: You are meeting a person on what is likely the worst day of their life. Trying to find the best approach for each individual is still a challenge.

Q: What aspect of patient care is most rewarding?

A: Seeing the relief on a patient’s face when you tell them they will get better and explain their treatment plan.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: Teaching in the 21st century is challenging with all the new regulations. We have a family physician residency at our hospital, and the blind dedication we had as residents is just not present in a group of physicians who have grown up with duty hour restrictions and protected time.

Q: What is your biggest professional reward?

A: Our group has virtually no attrition and has been intact for more than five years.

Q: You received your SFHM designation five years ago. What does that public recognition mean to you?

A: It was a mark of respect and recognition for expertise in this new field. A very proud moment.

Q: Where do you see yourself in 10 years?

A: Hopefully, working as a part-time nocturnist two nights per week and caring for some grandbabies and going on medical missions. TH

Richard Quinn is a freelance writer in New Jersey.

Jill Slater Waldman, MD, SFHM, loved math and science and working with people, so a career in medicine was always the logical choice. She just didn’t want to leave a hospital, literally. So when she was finishing her internal medicine residency in 1994 at Westchester Medical Center in Valhalla, N.Y., internal medicine (IM) suddenly appealed.

“I started seeking any job that would be ‘all in house,’ with no outpatient or clinic time,” Dr. Waldman says. “I was informed those jobs did not exist, so I joined the faculty of Albert Einstein College of Medicine with a dual appointment in emergency and internal medicine.”

Fast-forward through a few IM positions at New York State hospitals, and she landed the directorship of the adult hospitalist program at Nyack (N.Y.) Hospital. Two years later, she left for her current post, director of the adult hospital service at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y.

A crowded résumé got an extra line this year as Dr. Waldman is one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Tell us about your training years.

Answer: I initially matched in anesthesia but within two weeks realized the pre-ops and post-ops were my favorite visits. I went back to complete my IM residency, doing multiple extra months of ICU night float to avoid having to go to continuity of care clinic.

Q: Did you have a mentor during your training or early career? If so, who was the mentor, and what were the most important lessons you learned from him/her?

A: My mentor was undoubtedly my internship coordinator, who allowed me back to complete my IM training when I realized anesthesia was not for me. He is a special man, incredibly brilliant, and committed to the art and science of medicine. He taught his staff to always act like a physician, always have respect for yourself and the patients, and to take no shortcuts. He is the brightest physician I likely have ever met, and I am lucky to have been hired by him to run his hospital medicine program as a senior attending.

Q: Have you tried to mentor others?

A: I enjoy mentoring junior faculty, house staff, and students. I just returned from a medical mission during which I supervised three fantastic medical students—one of whom was my own daughter.

Q: What do you like most about working as a hospitalist?

A: The variety of patients we get to interact with and the variety of pathology we see.

Q: What do you dislike most?

A: Raw beets and egotistical consultants who treat hospitalists like house staff.

Q: How many Apple products do you interface with in a given week?

A: Two.

Q: What impact do you feel those devices and ones similar to them have had on HM and medicine in a broader sense?

A: I believe they have enabled channels of communication and allowed the public to become more knowledgeable medically.

Q: What’s the best advice you ever received?

A: Do unto others as you wish others to do unto you.

Q: What’s the worst advice you ever received?

A: “There’s no way you can be both a mother and a doctor. Pick one.”

Q: What’s the biggest change you’ve seen in HM in your career?

A: The evolution of HM as a true specialty, requiring a skill set of its own to be a hospitalist.

Q: What’s the biggest change you would like to see in HM?

A: More respect for the field and understanding of our skill set and knowledge base.

Q: As a group leader, why is it important for you to continue seeing patients?

A: As a director, I believe keeping my skill set current is important for myself as well as my partners. I have always said I would never ask them to do something I would not do, so I get to practice what I preach. I also think it enables me to keep perspective when discussing plans with administration or reviewing complaints.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: You are meeting a person on what is likely the worst day of their life. Trying to find the best approach for each individual is still a challenge.

Q: What aspect of patient care is most rewarding?

A: Seeing the relief on a patient’s face when you tell them they will get better and explain their treatment plan.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: Teaching in the 21st century is challenging with all the new regulations. We have a family physician residency at our hospital, and the blind dedication we had as residents is just not present in a group of physicians who have grown up with duty hour restrictions and protected time.

Q: What is your biggest professional reward?

A: Our group has virtually no attrition and has been intact for more than five years.

Q: You received your SFHM designation five years ago. What does that public recognition mean to you?

A: It was a mark of respect and recognition for expertise in this new field. A very proud moment.

Q: Where do you see yourself in 10 years?

A: Hopefully, working as a part-time nocturnist two nights per week and caring for some grandbabies and going on medical missions. TH

Richard Quinn is a freelance writer in New Jersey.

Blood for transfusion

Photo by Elise Amendola

Results of a large, retrospective study suggest that neurological diseases are not transmitted via blood transfusion.

Previous studies have shown that such diseases can be induced in healthy laboratory animals through the injection of diseased brain tissue from humans.

This has caused concern that neurological diseases might be transmitted from human to human via blood transfusions.

However, a study published in Annals of Internal Medicine suggests such transmission does not occur.

“The results are unusually clear for such a complicated subject as this,” said study author Gustaf Edgren, PhD, of Karolinska Institutet in Stockholm, Sweden.

“We’ve been working with this question for a long time now and have found no indication that these diseases can be transmitted via transfusions.”

Dr Edgren and his colleagues conducted this study by analyzing data from 1,465,845 patients who received blood transfusions in Sweden or Denmark between 1968 and 2012.

The team used multivariable Cox regression models (taking into account sex, age, place of residence, blood group, number of transfusions, and time since first transfusion) to estimate hazard ratios for dementia of any type, Alzheimer’s disease, and Parkinson’s disease in patients who received transfusions from donors who were later diagnosed with any of these diseases, compared to patients who received blood from healthy donors.

In all, 2.9% of patients received a transfusion from a donor diagnosed with one of the aforementioned neurological diseases. And there was no evidence of disease transmission via transfusion.

The hazard ratio for dementia in transfusion recipients whose donors were diagnosed with dementia, compared to recipients of blood from healthy donors, was 1.04 (95% CI, 0.99 to 1.09).

The hazard ratios for Alzheimer’s disease and Parkinson’s disease were 0.99 (95% CI, 0.85 to 1.15) and 0.94 (95% CI, 0.78 to 1.14), respectively.

“Blood transfusions are extremely safe in the Western world today, but, even so, we are working continuously and proactively on identifying any overlooked risks,” Dr Edgren said.

“The Swedish-Danish database that we have built up and used in many similar studies clearly demonstrates the value of our vast health registries. This kind of study would have simply been extremely difficult anywhere else in the world.”

Blood for transfusion

Photo by Elise Amendola

Results of a large, retrospective study suggest that neurological diseases are not transmitted via blood transfusion.

Previous studies have shown that such diseases can be induced in healthy laboratory animals through the injection of diseased brain tissue from humans.

This has caused concern that neurological diseases might be transmitted from human to human via blood transfusions.

However, a study published in Annals of Internal Medicine suggests such transmission does not occur.

“The results are unusually clear for such a complicated subject as this,” said study author Gustaf Edgren, PhD, of Karolinska Institutet in Stockholm, Sweden.

“We’ve been working with this question for a long time now and have found no indication that these diseases can be transmitted via transfusions.”

Dr Edgren and his colleagues conducted this study by analyzing data from 1,465,845 patients who received blood transfusions in Sweden or Denmark between 1968 and 2012.

The team used multivariable Cox regression models (taking into account sex, age, place of residence, blood group, number of transfusions, and time since first transfusion) to estimate hazard ratios for dementia of any type, Alzheimer’s disease, and Parkinson’s disease in patients who received transfusions from donors who were later diagnosed with any of these diseases, compared to patients who received blood from healthy donors.

In all, 2.9% of patients received a transfusion from a donor diagnosed with one of the aforementioned neurological diseases. And there was no evidence of disease transmission via transfusion.

The hazard ratio for dementia in transfusion recipients whose donors were diagnosed with dementia, compared to recipients of blood from healthy donors, was 1.04 (95% CI, 0.99 to 1.09).

The hazard ratios for Alzheimer’s disease and Parkinson’s disease were 0.99 (95% CI, 0.85 to 1.15) and 0.94 (95% CI, 0.78 to 1.14), respectively.

“Blood transfusions are extremely safe in the Western world today, but, even so, we are working continuously and proactively on identifying any overlooked risks,” Dr Edgren said.

“The Swedish-Danish database that we have built up and used in many similar studies clearly demonstrates the value of our vast health registries. This kind of study would have simply been extremely difficult anywhere else in the world.”

Blood for transfusion

Photo by Elise Amendola

Results of a large, retrospective study suggest that neurological diseases are not transmitted via blood transfusion.

Previous studies have shown that such diseases can be induced in healthy laboratory animals through the injection of diseased brain tissue from humans.

This has caused concern that neurological diseases might be transmitted from human to human via blood transfusions.

However, a study published in Annals of Internal Medicine suggests such transmission does not occur.

“The results are unusually clear for such a complicated subject as this,” said study author Gustaf Edgren, PhD, of Karolinska Institutet in Stockholm, Sweden.

“We’ve been working with this question for a long time now and have found no indication that these diseases can be transmitted via transfusions.”

Dr Edgren and his colleagues conducted this study by analyzing data from 1,465,845 patients who received blood transfusions in Sweden or Denmark between 1968 and 2012.

The team used multivariable Cox regression models (taking into account sex, age, place of residence, blood group, number of transfusions, and time since first transfusion) to estimate hazard ratios for dementia of any type, Alzheimer’s disease, and Parkinson’s disease in patients who received transfusions from donors who were later diagnosed with any of these diseases, compared to patients who received blood from healthy donors.

In all, 2.9% of patients received a transfusion from a donor diagnosed with one of the aforementioned neurological diseases. And there was no evidence of disease transmission via transfusion.

The hazard ratio for dementia in transfusion recipients whose donors were diagnosed with dementia, compared to recipients of blood from healthy donors, was 1.04 (95% CI, 0.99 to 1.09).

The hazard ratios for Alzheimer’s disease and Parkinson’s disease were 0.99 (95% CI, 0.85 to 1.15) and 0.94 (95% CI, 0.78 to 1.14), respectively.

“Blood transfusions are extremely safe in the Western world today, but, even so, we are working continuously and proactively on identifying any overlooked risks,” Dr Edgren said.

“The Swedish-Danish database that we have built up and used in many similar studies clearly demonstrates the value of our vast health registries. This kind of study would have simply been extremely difficult anywhere else in the world.”

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

The first global mapping of artemisinin resistance indicates that resistance to the drug, which is used to treat Plasmodium falciparum malaria, is confined to Southeast Asia and has not yet spread to sub-Saharan Africa.

Results of the effort, known as the KARMA study, were published in NEJM.

The study builds on the 2014 discovery that the K13 gene is the major determinant of P falciparum’s resistance to artemisinin.

Researchers studied the diversity of the K13 gene in 14,037 blood samples taken from P falciparum-infected patients in 59 malaria-endemic countries—72% in Africa, 19% in Asia, 8% in Latin America, and 1% in Oceania. All samples were collected after 2012.

The researchers identified 108 nonsynonymous K13 mutations. In Asia, 36.5% of the mutations were distributed within 2 areas—Cambodia-Vietnam-Laos and western Thailand-Myanmar-China—with no overlap.

In samples from Africa, the researchers identified nonsynonymous K13 mutations that were not associated with artemisinin resistance, including the most frequent mutation found in Africa, A578S.

“We suspect that only a small number of mutations appear to be associated with resistance, which should facilitate global monitoring of resistance to artemisinin,” said study author Odile Mercereau-Puijalon, PhD, of the Institut Pasteur in Paris, France.

“Until now, scientists have not had the tools to be properly informed about the nature of resistance to antimalarial drugs in key affected regions such as sub-Saharan Africa,” added Didier Ménard, PhD, of the Institut Pasteur in Phnom Penh, Cambodia.

“We now have the capacity, thanks to molecular markers, to be able to trace—at a global level and virtually in real-time—resistance to antimalarial drugs. We must ensure that we use this technology to keep us a step ahead of the parasite.”

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

The first global mapping of artemisinin resistance indicates that resistance to the drug, which is used to treat Plasmodium falciparum malaria, is confined to Southeast Asia and has not yet spread to sub-Saharan Africa.

Results of the effort, known as the KARMA study, were published in NEJM.

The study builds on the 2014 discovery that the K13 gene is the major determinant of P falciparum’s resistance to artemisinin.

Researchers studied the diversity of the K13 gene in 14,037 blood samples taken from P falciparum-infected patients in 59 malaria-endemic countries—72% in Africa, 19% in Asia, 8% in Latin America, and 1% in Oceania. All samples were collected after 2012.

The researchers identified 108 nonsynonymous K13 mutations. In Asia, 36.5% of the mutations were distributed within 2 areas—Cambodia-Vietnam-Laos and western Thailand-Myanmar-China—with no overlap.

In samples from Africa, the researchers identified nonsynonymous K13 mutations that were not associated with artemisinin resistance, including the most frequent mutation found in Africa, A578S.

“We suspect that only a small number of mutations appear to be associated with resistance, which should facilitate global monitoring of resistance to artemisinin,” said study author Odile Mercereau-Puijalon, PhD, of the Institut Pasteur in Paris, France.

“Until now, scientists have not had the tools to be properly informed about the nature of resistance to antimalarial drugs in key affected regions such as sub-Saharan Africa,” added Didier Ménard, PhD, of the Institut Pasteur in Phnom Penh, Cambodia.

“We now have the capacity, thanks to molecular markers, to be able to trace—at a global level and virtually in real-time—resistance to antimalarial drugs. We must ensure that we use this technology to keep us a step ahead of the parasite.”

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

The first global mapping of artemisinin resistance indicates that resistance to the drug, which is used to treat Plasmodium falciparum malaria, is confined to Southeast Asia and has not yet spread to sub-Saharan Africa.

Results of the effort, known as the KARMA study, were published in NEJM.

The study builds on the 2014 discovery that the K13 gene is the major determinant of P falciparum’s resistance to artemisinin.

Researchers studied the diversity of the K13 gene in 14,037 blood samples taken from P falciparum-infected patients in 59 malaria-endemic countries—72% in Africa, 19% in Asia, 8% in Latin America, and 1% in Oceania. All samples were collected after 2012.

The researchers identified 108 nonsynonymous K13 mutations. In Asia, 36.5% of the mutations were distributed within 2 areas—Cambodia-Vietnam-Laos and western Thailand-Myanmar-China—with no overlap.

In samples from Africa, the researchers identified nonsynonymous K13 mutations that were not associated with artemisinin resistance, including the most frequent mutation found in Africa, A578S.

“We suspect that only a small number of mutations appear to be associated with resistance, which should facilitate global monitoring of resistance to artemisinin,” said study author Odile Mercereau-Puijalon, PhD, of the Institut Pasteur in Paris, France.

“Until now, scientists have not had the tools to be properly informed about the nature of resistance to antimalarial drugs in key affected regions such as sub-Saharan Africa,” added Didier Ménard, PhD, of the Institut Pasteur in Phnom Penh, Cambodia.

“We now have the capacity, thanks to molecular markers, to be able to trace—at a global level and virtually in real-time—resistance to antimalarial drugs. We must ensure that we use this technology to keep us a step ahead of the parasite.”

Preparing drug capsules

for a clinical trial

Photo by Esther Dyson

Publication agreements between industry and academic investigators involved in clinical trials are not often reported in the publications themselves, according to a study published in PLOS Medicine.

In most of the agreements studied, industry had the right to reject or review manuscripts before publication.

Therefore, according to researchers, publication agreements may compromise the scientific evidence base established by randomized clinical trials.

Matthias Briel, MD, of the University Hospital Basel in Switzerland, and his colleagues sought to understand how publication agreements might constrain the publication of trial results.

The researchers examined publication agreements in 647 randomized trial protocols approved from 2000 to 2003 by 6 research ethics committees in Switzerland, Canada, and Germany, as well as the 388 corresponding journal publications.

The team found that 71% of protocols mentioned an agreement on publication rights between industry and academic investigators.

In 86% of those agreements, industry retained the right to disapprove or at least review manuscripts before publication.

And 74% of the agreements documented in protocols were not mentioned in corresponding journal articles.

The researchers noted that half of the included journal articles were published before 2008, leaving open the possibility that these findings do not reflect current practice.

Nonetheless, the team said the findings suggest that more transparency on publication constraints is warranted.

Preparing drug capsules

for a clinical trial

Photo by Esther Dyson

Publication agreements between industry and academic investigators involved in clinical trials are not often reported in the publications themselves, according to a study published in PLOS Medicine.

In most of the agreements studied, industry had the right to reject or review manuscripts before publication.

Therefore, according to researchers, publication agreements may compromise the scientific evidence base established by randomized clinical trials.

Matthias Briel, MD, of the University Hospital Basel in Switzerland, and his colleagues sought to understand how publication agreements might constrain the publication of trial results.

The researchers examined publication agreements in 647 randomized trial protocols approved from 2000 to 2003 by 6 research ethics committees in Switzerland, Canada, and Germany, as well as the 388 corresponding journal publications.

The team found that 71% of protocols mentioned an agreement on publication rights between industry and academic investigators.

In 86% of those agreements, industry retained the right to disapprove or at least review manuscripts before publication.

And 74% of the agreements documented in protocols were not mentioned in corresponding journal articles.

The researchers noted that half of the included journal articles were published before 2008, leaving open the possibility that these findings do not reflect current practice.

Nonetheless, the team said the findings suggest that more transparency on publication constraints is warranted.

Preparing drug capsules

for a clinical trial

Photo by Esther Dyson

Publication agreements between industry and academic investigators involved in clinical trials are not often reported in the publications themselves, according to a study published in PLOS Medicine.

In most of the agreements studied, industry had the right to reject or review manuscripts before publication.

Therefore, according to researchers, publication agreements may compromise the scientific evidence base established by randomized clinical trials.

Matthias Briel, MD, of the University Hospital Basel in Switzerland, and his colleagues sought to understand how publication agreements might constrain the publication of trial results.

The researchers examined publication agreements in 647 randomized trial protocols approved from 2000 to 2003 by 6 research ethics committees in Switzerland, Canada, and Germany, as well as the 388 corresponding journal publications.

The team found that 71% of protocols mentioned an agreement on publication rights between industry and academic investigators.

In 86% of those agreements, industry retained the right to disapprove or at least review manuscripts before publication.

And 74% of the agreements documented in protocols were not mentioned in corresponding journal articles.

The researchers noted that half of the included journal articles were published before 2008, leaving open the possibility that these findings do not reflect current practice.

Nonetheless, the team said the findings suggest that more transparency on publication constraints is warranted.

A 31-year-old incarcerated man sought care for one crusted ulcer and one adjacent open ulcer with granulation tissue on his left malleolus. The ulcers were caused by chronic venous insufficiency—the result of previous trauma to the ankle. Concerned that the ulcers would become infected, the physician prescribed one double-strength tablet twice a day of trimethoprim-sulfamethoxazole (TMP-SMX). The patient took 2 doses of the antibiotic and one dose of naproxen.

When the patient awoke the next morning, he had a generalized skin eruption on his chin, trunk, buttocks, glans penis, and extremities (FIGURE). The rash began as red edematous plaques that became itchy and painful with dark, violaceous dusky centers surrounded by redness. The patient was treated with topical hydrocortisone 2.5% twice a day and oral diphenhydramine 25 mg followed by 50 mg, but the rash didn’t improve.

The patient was transported to the local emergency department where physicians noted that the patient had about 30 to 40 well-demarcated papules and plaques of various sizes that were haphazardly located over the patient’s chin, chest, back, upper and lower extremities, and genitalia. There was one lesion on the chest with central vesiculation. There were no lesions on the mucous membranes of his eyes, ears, nose, mouth, or anus.

The patient, whose vital signs were within normal limits, was empirically treated with one dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. Lab work revealed no elevation in his white blood cell count, creatinine, liver function enzymes, or C-reactive protein.

The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. He noted that during the previous episode, the lesions were located on the exact same areas of his glans penis and chin.

Diagnosis: Disseminated fixed-drug eruption

The diagnosis was based on the morphologic characteristics of the eruption and the patient’s history of similar lesions that appeared in the exact same initial locations (chin and glans penis) following previous treatment with TMP-SMX.

A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with our patient).

The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.¹

The diagnosis is usually made based on a history of similar lesions recurring at the same location in response to a specific drug² and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. To confirm a fixed-drug eruption in the case of clinical equipoise, a skin biopsy may be performed.

Classic histologic findings of a fixed-drug eruption include:

• band-like lichenoid lymphocytic infiltrates with vacuolar changes at the dermoepidermal junction,
• mixed cellular infiltrates, including eosinophils, throughout the dermis and occasional superficial and deep mixed cellular perivascular infiltrates, and
• abundant melanophages suggesting pigment incontinence.

There are several reports of similar TMP-SMX–induced generalized fixed-drug eruptions in the literature.³ One study of 64 cases of fixed-drug eruption found that TMP-SMX was the most common offender, causing 75% of fixed-drug eruption cases; naproxen sodium came in second with 12.5%.³ Other common culprits include the antipyretic metamizole and other pyrazolone derivatives such as tetracycline, metronidazole, ciprofloxacin, and phenytoin sodium.⁴ There is evidence supporting a correlation between the offending drug and the subsequent site of reaction; TMP-SMX is associated with mucosal junction and genital involvement.^4,5 This finding may aid physicians in the investigation of provoking agents.

Distinguish fixed-drug eruptions from serious bullous diseases

Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches. Fixed-drug eruptions can be distinguished by the lack of simultaneous involvement of 2 mucosal surfaces, lack of generalized desquamation, and normal vital signs and lab values, including white blood cell count and erythrocyte sedimentation rate/C-reactive protein.

A subset of fixed-drug eruption, generalized bullous fixed-drug eruption (which has been defined as blistering on >10% of the body’s surface area at 3 different anatomic sites), may be particularly hard to distinguish from SJS and TEN. Generalized bullous fixed-drug eruption generally has a shorter latency period than SJS or TEN (usually <3 days compared to 7-10 days) and has less mucosal involvement.⁶

Symptomatic therapy includes antihistamines, glucocorticoid ointment

Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like our patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days. Be advised, however, that these therapies are based on case report level data.²

Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.

Our patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption.

He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.

CORRESPONDENCE
Jackie Bucher, MD, 7733 Louis Pasteur Drive Apt. 209, San Antonio, TX 78229; [email protected].

A 31-year-old incarcerated man sought care for one crusted ulcer and one adjacent open ulcer with granulation tissue on his left malleolus. The ulcers were caused by chronic venous insufficiency—the result of previous trauma to the ankle. Concerned that the ulcers would become infected, the physician prescribed one double-strength tablet twice a day of trimethoprim-sulfamethoxazole (TMP-SMX). The patient took 2 doses of the antibiotic and one dose of naproxen.

When the patient awoke the next morning, he had a generalized skin eruption on his chin, trunk, buttocks, glans penis, and extremities (FIGURE). The rash began as red edematous plaques that became itchy and painful with dark, violaceous dusky centers surrounded by redness. The patient was treated with topical hydrocortisone 2.5% twice a day and oral diphenhydramine 25 mg followed by 50 mg, but the rash didn’t improve.

The patient was transported to the local emergency department where physicians noted that the patient had about 30 to 40 well-demarcated papules and plaques of various sizes that were haphazardly located over the patient’s chin, chest, back, upper and lower extremities, and genitalia. There was one lesion on the chest with central vesiculation. There were no lesions on the mucous membranes of his eyes, ears, nose, mouth, or anus.

The patient, whose vital signs were within normal limits, was empirically treated with one dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. Lab work revealed no elevation in his white blood cell count, creatinine, liver function enzymes, or C-reactive protein.

The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. He noted that during the previous episode, the lesions were located on the exact same areas of his glans penis and chin.

Diagnosis: Disseminated fixed-drug eruption

The diagnosis was based on the morphologic characteristics of the eruption and the patient’s history of similar lesions that appeared in the exact same initial locations (chin and glans penis) following previous treatment with TMP-SMX.

A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with our patient).

The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.¹

The diagnosis is usually made based on a history of similar lesions recurring at the same location in response to a specific drug² and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. To confirm a fixed-drug eruption in the case of clinical equipoise, a skin biopsy may be performed.

Classic histologic findings of a fixed-drug eruption include:

• band-like lichenoid lymphocytic infiltrates with vacuolar changes at the dermoepidermal junction,
• mixed cellular infiltrates, including eosinophils, throughout the dermis and occasional superficial and deep mixed cellular perivascular infiltrates, and
• abundant melanophages suggesting pigment incontinence.

There are several reports of similar TMP-SMX–induced generalized fixed-drug eruptions in the literature.³ One study of 64 cases of fixed-drug eruption found that TMP-SMX was the most common offender, causing 75% of fixed-drug eruption cases; naproxen sodium came in second with 12.5%.³ Other common culprits include the antipyretic metamizole and other pyrazolone derivatives such as tetracycline, metronidazole, ciprofloxacin, and phenytoin sodium.⁴ There is evidence supporting a correlation between the offending drug and the subsequent site of reaction; TMP-SMX is associated with mucosal junction and genital involvement.^4,5 This finding may aid physicians in the investigation of provoking agents.

Distinguish fixed-drug eruptions from serious bullous diseases

Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches. Fixed-drug eruptions can be distinguished by the lack of simultaneous involvement of 2 mucosal surfaces, lack of generalized desquamation, and normal vital signs and lab values, including white blood cell count and erythrocyte sedimentation rate/C-reactive protein.

A subset of fixed-drug eruption, generalized bullous fixed-drug eruption (which has been defined as blistering on >10% of the body’s surface area at 3 different anatomic sites), may be particularly hard to distinguish from SJS and TEN. Generalized bullous fixed-drug eruption generally has a shorter latency period than SJS or TEN (usually <3 days compared to 7-10 days) and has less mucosal involvement.⁶

Symptomatic therapy includes antihistamines, glucocorticoid ointment

Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like our patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days. Be advised, however, that these therapies are based on case report level data.²

Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.

Our patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption.

He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.

CORRESPONDENCE
Jackie Bucher, MD, 7733 Louis Pasteur Drive Apt. 209, San Antonio, TX 78229; [email protected].

A 31-year-old incarcerated man sought care for one crusted ulcer and one adjacent open ulcer with granulation tissue on his left malleolus. The ulcers were caused by chronic venous insufficiency—the result of previous trauma to the ankle. Concerned that the ulcers would become infected, the physician prescribed one double-strength tablet twice a day of trimethoprim-sulfamethoxazole (TMP-SMX). The patient took 2 doses of the antibiotic and one dose of naproxen.

When the patient awoke the next morning, he had a generalized skin eruption on his chin, trunk, buttocks, glans penis, and extremities (FIGURE). The rash began as red edematous plaques that became itchy and painful with dark, violaceous dusky centers surrounded by redness. The patient was treated with topical hydrocortisone 2.5% twice a day and oral diphenhydramine 25 mg followed by 50 mg, but the rash didn’t improve.

The patient was transported to the local emergency department where physicians noted that the patient had about 30 to 40 well-demarcated papules and plaques of various sizes that were haphazardly located over the patient’s chin, chest, back, upper and lower extremities, and genitalia. There was one lesion on the chest with central vesiculation. There were no lesions on the mucous membranes of his eyes, ears, nose, mouth, or anus.

The patient, whose vital signs were within normal limits, was empirically treated with one dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. Lab work revealed no elevation in his white blood cell count, creatinine, liver function enzymes, or C-reactive protein.

The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. He noted that during the previous episode, the lesions were located on the exact same areas of his glans penis and chin.

Diagnosis: Disseminated fixed-drug eruption

The diagnosis was based on the morphologic characteristics of the eruption and the patient’s history of similar lesions that appeared in the exact same initial locations (chin and glans penis) following previous treatment with TMP-SMX.

A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with our patient).

The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.¹

The diagnosis is usually made based on a history of similar lesions recurring at the same location in response to a specific drug² and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. To confirm a fixed-drug eruption in the case of clinical equipoise, a skin biopsy may be performed.

Classic histologic findings of a fixed-drug eruption include:

• band-like lichenoid lymphocytic infiltrates with vacuolar changes at the dermoepidermal junction,
• mixed cellular infiltrates, including eosinophils, throughout the dermis and occasional superficial and deep mixed cellular perivascular infiltrates, and
• abundant melanophages suggesting pigment incontinence.

There are several reports of similar TMP-SMX–induced generalized fixed-drug eruptions in the literature.³ One study of 64 cases of fixed-drug eruption found that TMP-SMX was the most common offender, causing 75% of fixed-drug eruption cases; naproxen sodium came in second with 12.5%.³ Other common culprits include the antipyretic metamizole and other pyrazolone derivatives such as tetracycline, metronidazole, ciprofloxacin, and phenytoin sodium.⁴ There is evidence supporting a correlation between the offending drug and the subsequent site of reaction; TMP-SMX is associated with mucosal junction and genital involvement.^4,5 This finding may aid physicians in the investigation of provoking agents.

Distinguish fixed-drug eruptions from serious bullous diseases

Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches. Fixed-drug eruptions can be distinguished by the lack of simultaneous involvement of 2 mucosal surfaces, lack of generalized desquamation, and normal vital signs and lab values, including white blood cell count and erythrocyte sedimentation rate/C-reactive protein.

A subset of fixed-drug eruption, generalized bullous fixed-drug eruption (which has been defined as blistering on >10% of the body’s surface area at 3 different anatomic sites), may be particularly hard to distinguish from SJS and TEN. Generalized bullous fixed-drug eruption generally has a shorter latency period than SJS or TEN (usually <3 days compared to 7-10 days) and has less mucosal involvement.⁶

Symptomatic therapy includes antihistamines, glucocorticoid ointment

Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like our patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days. Be advised, however, that these therapies are based on case report level data.²

Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.

Our patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption.

He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.

CORRESPONDENCE
Jackie Bucher, MD, 7733 Louis Pasteur Drive Apt. 209, San Antonio, TX 78229; [email protected].