DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.

“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.

Bruce Jancin/Frontline Medical News

Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.

EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.

Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.

Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.

Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.

“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.

EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.

[email protected]

DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.

“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.

Bruce Jancin/Frontline Medical News

Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.

EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.

Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.

Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.

Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.

“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.

EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.

[email protected]

DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.

“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.

Bruce Jancin/Frontline Medical News

Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.

EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.

Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.

Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.

Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.

“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.

EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.

[email protected]

Over half, 56% of adolescents aged 13-17 years in the United States had received at least one dose of HPV vaccine, based on 2015 data from the Centers for Disease Control and Prevention’s 2015 National Immunization Survey-Teen.

From 2014 to 2015, the percentage of boys who had received at least one dose of HPV vaccine increased from 42% to 50% and the percentage in girls increased from 60% to 63%. In 2015, 35% of all adolescents (28% of boys and 42% of girls) received at least three doses of HPV vaccine.

©jarun011/Thinkstock

Despite the increases, “coverage with at least one HPV vaccine dose was lower than coverage with Tdap and MenACWY,” wrote Dr. Sarah Reagan-Steiner of the CDC and colleagues. During the time of the study, vaccination with at least one dose of the quadrivalent meningococcal conjugate vaccine (MenACWY) increased from 79% to 81% for all adolescents.

“These gaps in coverage demonstrate ongoing missed opportunities for HPV vaccination at visits when other recommended vaccines are administered,” the researchers said. “Strong clinician recommendations for HPV vaccination, and coadministration of the first HPV vaccine dose with Tdap and MenACWY vaccine at age 11-12 years during the same visit would improve HPV coverage,” they added.

Clinician resources to promote conversations with parents and adolescents about vaccination are available on the CDC website.

The findings were published Aug. 25 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR 2016;65:850-8).

Over half, 56% of adolescents aged 13-17 years in the United States had received at least one dose of HPV vaccine, based on 2015 data from the Centers for Disease Control and Prevention’s 2015 National Immunization Survey-Teen.

From 2014 to 2015, the percentage of boys who had received at least one dose of HPV vaccine increased from 42% to 50% and the percentage in girls increased from 60% to 63%. In 2015, 35% of all adolescents (28% of boys and 42% of girls) received at least three doses of HPV vaccine.

©jarun011/Thinkstock

Despite the increases, “coverage with at least one HPV vaccine dose was lower than coverage with Tdap and MenACWY,” wrote Dr. Sarah Reagan-Steiner of the CDC and colleagues. During the time of the study, vaccination with at least one dose of the quadrivalent meningococcal conjugate vaccine (MenACWY) increased from 79% to 81% for all adolescents.

“These gaps in coverage demonstrate ongoing missed opportunities for HPV vaccination at visits when other recommended vaccines are administered,” the researchers said. “Strong clinician recommendations for HPV vaccination, and coadministration of the first HPV vaccine dose with Tdap and MenACWY vaccine at age 11-12 years during the same visit would improve HPV coverage,” they added.

Clinician resources to promote conversations with parents and adolescents about vaccination are available on the CDC website.

The findings were published Aug. 25 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR 2016;65:850-8).

Over half, 56% of adolescents aged 13-17 years in the United States had received at least one dose of HPV vaccine, based on 2015 data from the Centers for Disease Control and Prevention’s 2015 National Immunization Survey-Teen.

From 2014 to 2015, the percentage of boys who had received at least one dose of HPV vaccine increased from 42% to 50% and the percentage in girls increased from 60% to 63%. In 2015, 35% of all adolescents (28% of boys and 42% of girls) received at least three doses of HPV vaccine.

©jarun011/Thinkstock

Despite the increases, “coverage with at least one HPV vaccine dose was lower than coverage with Tdap and MenACWY,” wrote Dr. Sarah Reagan-Steiner of the CDC and colleagues. During the time of the study, vaccination with at least one dose of the quadrivalent meningococcal conjugate vaccine (MenACWY) increased from 79% to 81% for all adolescents.

“These gaps in coverage demonstrate ongoing missed opportunities for HPV vaccination at visits when other recommended vaccines are administered,” the researchers said. “Strong clinician recommendations for HPV vaccination, and coadministration of the first HPV vaccine dose with Tdap and MenACWY vaccine at age 11-12 years during the same visit would improve HPV coverage,” they added.

Clinician resources to promote conversations with parents and adolescents about vaccination are available on the CDC website.

The findings were published Aug. 25 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR 2016;65:850-8).

Boston – Patients with delusional infestation often resist referral to a psychiatrist and insist on treatment by a dermatologist, according to Mark D. P. Davis, MD.

Dermatologists, conversely, often don’t want to treat these challenging patients because they aren’t really sure how to manage them, Dr. Davis said during a “practice gaps” session at the American Academy of Dermatology summer meeting.

An important practice gap is the lack of a standard approach to the investigation and management of these patients, he said.

An audience poll showed that respondents were divided as to whether patients presenting with delusional infestation, also known as delusional parasitosis, should be confronted, referred to a psychiatrist, treated with an antipsychotic, or approached in some other way.

The condition, which involves the delusional belief that one’s skin is “infested” with parasites, fibers, or some other materials, can result from another cause, said Dr. Davis of the Mayo Clinic, Rochester, Minn, noting that anxiety, depression, and medications such as opioids or treatments for attention deficit/hyperactivity disorder can contribute to the delusions.

Skin diseases themselves can also cause the sensation of infestation.

A good history should assess medical comorbidities, electrolyte abnormalities, or medication use that might be contributing to the problem.

For dermatologists who are not well-versed in “picking up on psychiatric comorbidities,” validated measures can be useful. Tools such as the Personal Health Questionnaire (PHQ)-9 for depression and Generalized Anxiety Disorder (GAD)-7 can be useful, Dr. Davis said.

However, delusions, by definition, are “fixed false beliefs.” Challenging a patient regarding their delusions is likely pointless, as the patients’ minds cannot be changed.

For cases of primary delusional infestation, the goal generally is to decrease the patient’s preoccupation with the delusion and to improve social and occupational functions. Treatment with antipsychotic drugs is usually helpful–if patients will comply with treatment. “I’ve been very unsuccessful” at getting patients to use antipsychotics, he said.

A good treatment option is risperidone, which has low cost and good efficacy and tolerability. Start with a daily dose of 1 mg/day and gradually increase up to 6 mg daily if necessary, he said.

Establishing a rapport over multiple visits may help with compliance. For example, take a history on the first visit, order laboratory tests at a second visit, perform a biopsy at a third, and then broach the subject of treatment at a subsequent visit, he suggested.

Getting the patient on board with taking risperidone or another antipsychotic may be easier if you ask the patient early on whether they would like treatment for their symptoms in the event a definitive cause for their symptoms can’t be identified, he said.

Dr. Davis reported having no disclosures.

[email protected]

Boston – Patients with delusional infestation often resist referral to a psychiatrist and insist on treatment by a dermatologist, according to Mark D. P. Davis, MD.

Dermatologists, conversely, often don’t want to treat these challenging patients because they aren’t really sure how to manage them, Dr. Davis said during a “practice gaps” session at the American Academy of Dermatology summer meeting.

An important practice gap is the lack of a standard approach to the investigation and management of these patients, he said.

An audience poll showed that respondents were divided as to whether patients presenting with delusional infestation, also known as delusional parasitosis, should be confronted, referred to a psychiatrist, treated with an antipsychotic, or approached in some other way.

The condition, which involves the delusional belief that one’s skin is “infested” with parasites, fibers, or some other materials, can result from another cause, said Dr. Davis of the Mayo Clinic, Rochester, Minn, noting that anxiety, depression, and medications such as opioids or treatments for attention deficit/hyperactivity disorder can contribute to the delusions.

Skin diseases themselves can also cause the sensation of infestation.

A good history should assess medical comorbidities, electrolyte abnormalities, or medication use that might be contributing to the problem.

For dermatologists who are not well-versed in “picking up on psychiatric comorbidities,” validated measures can be useful. Tools such as the Personal Health Questionnaire (PHQ)-9 for depression and Generalized Anxiety Disorder (GAD)-7 can be useful, Dr. Davis said.

However, delusions, by definition, are “fixed false beliefs.” Challenging a patient regarding their delusions is likely pointless, as the patients’ minds cannot be changed.

For cases of primary delusional infestation, the goal generally is to decrease the patient’s preoccupation with the delusion and to improve social and occupational functions. Treatment with antipsychotic drugs is usually helpful–if patients will comply with treatment. “I’ve been very unsuccessful” at getting patients to use antipsychotics, he said.

A good treatment option is risperidone, which has low cost and good efficacy and tolerability. Start with a daily dose of 1 mg/day and gradually increase up to 6 mg daily if necessary, he said.

Establishing a rapport over multiple visits may help with compliance. For example, take a history on the first visit, order laboratory tests at a second visit, perform a biopsy at a third, and then broach the subject of treatment at a subsequent visit, he suggested.

Getting the patient on board with taking risperidone or another antipsychotic may be easier if you ask the patient early on whether they would like treatment for their symptoms in the event a definitive cause for their symptoms can’t be identified, he said.

Dr. Davis reported having no disclosures.

[email protected]

Boston – Patients with delusional infestation often resist referral to a psychiatrist and insist on treatment by a dermatologist, according to Mark D. P. Davis, MD.

Dermatologists, conversely, often don’t want to treat these challenging patients because they aren’t really sure how to manage them, Dr. Davis said during a “practice gaps” session at the American Academy of Dermatology summer meeting.

An important practice gap is the lack of a standard approach to the investigation and management of these patients, he said.

An audience poll showed that respondents were divided as to whether patients presenting with delusional infestation, also known as delusional parasitosis, should be confronted, referred to a psychiatrist, treated with an antipsychotic, or approached in some other way.

The condition, which involves the delusional belief that one’s skin is “infested” with parasites, fibers, or some other materials, can result from another cause, said Dr. Davis of the Mayo Clinic, Rochester, Minn, noting that anxiety, depression, and medications such as opioids or treatments for attention deficit/hyperactivity disorder can contribute to the delusions.

Skin diseases themselves can also cause the sensation of infestation.

A good history should assess medical comorbidities, electrolyte abnormalities, or medication use that might be contributing to the problem.

For dermatologists who are not well-versed in “picking up on psychiatric comorbidities,” validated measures can be useful. Tools such as the Personal Health Questionnaire (PHQ)-9 for depression and Generalized Anxiety Disorder (GAD)-7 can be useful, Dr. Davis said.

However, delusions, by definition, are “fixed false beliefs.” Challenging a patient regarding their delusions is likely pointless, as the patients’ minds cannot be changed.

For cases of primary delusional infestation, the goal generally is to decrease the patient’s preoccupation with the delusion and to improve social and occupational functions. Treatment with antipsychotic drugs is usually helpful–if patients will comply with treatment. “I’ve been very unsuccessful” at getting patients to use antipsychotics, he said.

A good treatment option is risperidone, which has low cost and good efficacy and tolerability. Start with a daily dose of 1 mg/day and gradually increase up to 6 mg daily if necessary, he said.

Establishing a rapport over multiple visits may help with compliance. For example, take a history on the first visit, order laboratory tests at a second visit, perform a biopsy at a third, and then broach the subject of treatment at a subsequent visit, he suggested.

Getting the patient on board with taking risperidone or another antipsychotic may be easier if you ask the patient early on whether they would like treatment for their symptoms in the event a definitive cause for their symptoms can’t be identified, he said.

Dr. Davis reported having no disclosures.

[email protected]

DURBAN, SOUTH AFRICA – Maraviroc-containing regimens for daily oral pre-exposure prophylaxis in women at risk for HIV infection showed good safety and tolerability in a phase 2 study, the first randomized trial of PrEP ever conducted in U.S. women, Roy M. Gulick, MD, reported at the 21st International AIDS Conference.

No new HIV infections occurred in the 188 women who participated in the 48-week, randomized, double-blind, placebo-controlled study known as the HPTN 069/ACTG A5305 trial.

Bruce Jancin/Frontline Medical News

However, the results shouldn’t be taken as evidence of efficacy. The relatively low 2% incidence of new STIs diagnosed during 48 weeks of close followup – three cases of chlamydia, one of gonorrhea – suggests that the study population probably wasn’t at high risk for acquiring HIV. Further, the study wasn’t powered to determine efficacy. That determination will have to await a larger phase 3 trial, observed Dr. Gulick, professor of medicine at Cornell University in New York.

Maraviroc (Selzentry) is categorized as an HIV entry inhibitor. It’s an antagonist of the CCR5 receptor found on the surface of T cells, which is the route of HIV infection. The rationale for exploring the drug for HIV PrEP, according to Dr. Gulick, is that it concentrates in both the genital tract and rectum, doesn’t select for drug-resistant viral strains, is well tolerated, and it isn’t commonly used for treatment of HIV infection.

Additional options for oral daily HIV PrEP are clearly desirable, he added. The only approved agent is Truvada (tenofovir/emtricitabine), which is often used in HIV therapy as well, and there is concern it may select for drug resistance. Plus, it has renal, GI, and bone side effects.

Study participants were HIV-negative adult women who were born female and considered at risk for HIV acquisition because of a history of condomless vaginal or anal intercourse with at least one HIV-positive or unknown status man within the previous 90 days. The women were randomized to one of four study arms: maraviroc at the standard dose of 300 mg/day plus two placebo pills; maraviroc plus emtricitabine at the standard dose of 200 mg/day plus one placebo pill; maraviroc plus tenofovir at 300 mg/day plus a placebo pill, or a control regimen of fixed-dose Truvada (tenofovir 300 mg/emtricitabine 200 mg) plus two placebo pills. Thus, everyone took three pills once daily.

The three-pill regimen might help explain the less than stellar patient adherence. Study drugs were detectable – and not necessarily at therapeutic levels – in the plasma of 65% of subjects at 24 weeks and 60% at 48 weeks, with no differences between the study arms.

Maraviroc alone was associated with fewer grade 2-4 adverse events than the other regimens.

There were 11 grade 3 or 4 adverse events deemed by investigators to be related to study drugs. They included abnormal weight loss, depression, hypophosphatemia, a rise in LDL cholesterol, headache, vitamin D deficiency, back pain, two spontaneous abortions, and two dissimilar cases of congenital anomaly, with no obvious differences between the study groups in rate or pattern. Rates of specific renal and GI toxicities were comparable across the four study arms.

Earlier in 2016, Dr. Gulick presented the results of the men’s arm of HPTN 069/ACTG A5305, a parallel 48-week randomized trial in 406 men who have sex with men. Five men in the maraviroc monotherapy arm seroconverted during the 48-week study, for an incidence of 1.4%. All had no or low plasma drug concentrations, and all five were infected with HIV lacking antiretroviral drug resistance.

Dr. Gulick and coinvestigators plan to present the findings of an analysis of rectal and vaginal biopsies from 42 women in the trial, along with a bone mineral density substudy in 200 men and 200 women men in the trial, plus detailed quality-of-life, behavioral, and adherence data in the full men’s and women’s cohorts.

The trial was sponsored by the HIV Prevention Trials Network and the AIDS Clinical Trials Group with funding from the National Institute of Allergic and Infectious Diseases. Dr. Gulick reported having no financial conflicts of interest.

[email protected]

DURBAN, SOUTH AFRICA – Maraviroc-containing regimens for daily oral pre-exposure prophylaxis in women at risk for HIV infection showed good safety and tolerability in a phase 2 study, the first randomized trial of PrEP ever conducted in U.S. women, Roy M. Gulick, MD, reported at the 21st International AIDS Conference.

No new HIV infections occurred in the 188 women who participated in the 48-week, randomized, double-blind, placebo-controlled study known as the HPTN 069/ACTG A5305 trial.

Bruce Jancin/Frontline Medical News

However, the results shouldn’t be taken as evidence of efficacy. The relatively low 2% incidence of new STIs diagnosed during 48 weeks of close followup – three cases of chlamydia, one of gonorrhea – suggests that the study population probably wasn’t at high risk for acquiring HIV. Further, the study wasn’t powered to determine efficacy. That determination will have to await a larger phase 3 trial, observed Dr. Gulick, professor of medicine at Cornell University in New York.

Maraviroc (Selzentry) is categorized as an HIV entry inhibitor. It’s an antagonist of the CCR5 receptor found on the surface of T cells, which is the route of HIV infection. The rationale for exploring the drug for HIV PrEP, according to Dr. Gulick, is that it concentrates in both the genital tract and rectum, doesn’t select for drug-resistant viral strains, is well tolerated, and it isn’t commonly used for treatment of HIV infection.

Additional options for oral daily HIV PrEP are clearly desirable, he added. The only approved agent is Truvada (tenofovir/emtricitabine), which is often used in HIV therapy as well, and there is concern it may select for drug resistance. Plus, it has renal, GI, and bone side effects.

Study participants were HIV-negative adult women who were born female and considered at risk for HIV acquisition because of a history of condomless vaginal or anal intercourse with at least one HIV-positive or unknown status man within the previous 90 days. The women were randomized to one of four study arms: maraviroc at the standard dose of 300 mg/day plus two placebo pills; maraviroc plus emtricitabine at the standard dose of 200 mg/day plus one placebo pill; maraviroc plus tenofovir at 300 mg/day plus a placebo pill, or a control regimen of fixed-dose Truvada (tenofovir 300 mg/emtricitabine 200 mg) plus two placebo pills. Thus, everyone took three pills once daily.

The three-pill regimen might help explain the less than stellar patient adherence. Study drugs were detectable – and not necessarily at therapeutic levels – in the plasma of 65% of subjects at 24 weeks and 60% at 48 weeks, with no differences between the study arms.

Maraviroc alone was associated with fewer grade 2-4 adverse events than the other regimens.

There were 11 grade 3 or 4 adverse events deemed by investigators to be related to study drugs. They included abnormal weight loss, depression, hypophosphatemia, a rise in LDL cholesterol, headache, vitamin D deficiency, back pain, two spontaneous abortions, and two dissimilar cases of congenital anomaly, with no obvious differences between the study groups in rate or pattern. Rates of specific renal and GI toxicities were comparable across the four study arms.

Earlier in 2016, Dr. Gulick presented the results of the men’s arm of HPTN 069/ACTG A5305, a parallel 48-week randomized trial in 406 men who have sex with men. Five men in the maraviroc monotherapy arm seroconverted during the 48-week study, for an incidence of 1.4%. All had no or low plasma drug concentrations, and all five were infected with HIV lacking antiretroviral drug resistance.

Dr. Gulick and coinvestigators plan to present the findings of an analysis of rectal and vaginal biopsies from 42 women in the trial, along with a bone mineral density substudy in 200 men and 200 women men in the trial, plus detailed quality-of-life, behavioral, and adherence data in the full men’s and women’s cohorts.

The trial was sponsored by the HIV Prevention Trials Network and the AIDS Clinical Trials Group with funding from the National Institute of Allergic and Infectious Diseases. Dr. Gulick reported having no financial conflicts of interest.

[email protected]

DURBAN, SOUTH AFRICA – Maraviroc-containing regimens for daily oral pre-exposure prophylaxis in women at risk for HIV infection showed good safety and tolerability in a phase 2 study, the first randomized trial of PrEP ever conducted in U.S. women, Roy M. Gulick, MD, reported at the 21st International AIDS Conference.

No new HIV infections occurred in the 188 women who participated in the 48-week, randomized, double-blind, placebo-controlled study known as the HPTN 069/ACTG A5305 trial.

Bruce Jancin/Frontline Medical News

However, the results shouldn’t be taken as evidence of efficacy. The relatively low 2% incidence of new STIs diagnosed during 48 weeks of close followup – three cases of chlamydia, one of gonorrhea – suggests that the study population probably wasn’t at high risk for acquiring HIV. Further, the study wasn’t powered to determine efficacy. That determination will have to await a larger phase 3 trial, observed Dr. Gulick, professor of medicine at Cornell University in New York.

Maraviroc (Selzentry) is categorized as an HIV entry inhibitor. It’s an antagonist of the CCR5 receptor found on the surface of T cells, which is the route of HIV infection. The rationale for exploring the drug for HIV PrEP, according to Dr. Gulick, is that it concentrates in both the genital tract and rectum, doesn’t select for drug-resistant viral strains, is well tolerated, and it isn’t commonly used for treatment of HIV infection.

Additional options for oral daily HIV PrEP are clearly desirable, he added. The only approved agent is Truvada (tenofovir/emtricitabine), which is often used in HIV therapy as well, and there is concern it may select for drug resistance. Plus, it has renal, GI, and bone side effects.

Study participants were HIV-negative adult women who were born female and considered at risk for HIV acquisition because of a history of condomless vaginal or anal intercourse with at least one HIV-positive or unknown status man within the previous 90 days. The women were randomized to one of four study arms: maraviroc at the standard dose of 300 mg/day plus two placebo pills; maraviroc plus emtricitabine at the standard dose of 200 mg/day plus one placebo pill; maraviroc plus tenofovir at 300 mg/day plus a placebo pill, or a control regimen of fixed-dose Truvada (tenofovir 300 mg/emtricitabine 200 mg) plus two placebo pills. Thus, everyone took three pills once daily.

The three-pill regimen might help explain the less than stellar patient adherence. Study drugs were detectable – and not necessarily at therapeutic levels – in the plasma of 65% of subjects at 24 weeks and 60% at 48 weeks, with no differences between the study arms.

Maraviroc alone was associated with fewer grade 2-4 adverse events than the other regimens.

There were 11 grade 3 or 4 adverse events deemed by investigators to be related to study drugs. They included abnormal weight loss, depression, hypophosphatemia, a rise in LDL cholesterol, headache, vitamin D deficiency, back pain, two spontaneous abortions, and two dissimilar cases of congenital anomaly, with no obvious differences between the study groups in rate or pattern. Rates of specific renal and GI toxicities were comparable across the four study arms.

Earlier in 2016, Dr. Gulick presented the results of the men’s arm of HPTN 069/ACTG A5305, a parallel 48-week randomized trial in 406 men who have sex with men. Five men in the maraviroc monotherapy arm seroconverted during the 48-week study, for an incidence of 1.4%. All had no or low plasma drug concentrations, and all five were infected with HIV lacking antiretroviral drug resistance.

Dr. Gulick and coinvestigators plan to present the findings of an analysis of rectal and vaginal biopsies from 42 women in the trial, along with a bone mineral density substudy in 200 men and 200 women men in the trial, plus detailed quality-of-life, behavioral, and adherence data in the full men’s and women’s cohorts.

The trial was sponsored by the HIV Prevention Trials Network and the AIDS Clinical Trials Group with funding from the National Institute of Allergic and Infectious Diseases. Dr. Gulick reported having no financial conflicts of interest.

[email protected]

ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.

Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.

Mitchel L. Zoler/Frontline Medical News

As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.

The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.

He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.

“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.

“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”

DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).

The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).

The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.

Mitchel L. Zoler/Frontline Medical News

The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.

The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.

“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.

[email protected]

On Twitter @mitchelzoler

ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.

Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.

Mitchel L. Zoler/Frontline Medical News

As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.

The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.

He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.

“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.

“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”

DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).

The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).

The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.

Mitchel L. Zoler/Frontline Medical News

The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.

The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.

“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.

[email protected]

On Twitter @mitchelzoler

ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.

Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.

Mitchel L. Zoler/Frontline Medical News

As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.

The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.

He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.

“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.

“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”

DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).

The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).

The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.

Mitchel L. Zoler/Frontline Medical News

The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.

The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.

“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.

[email protected]

On Twitter @mitchelzoler

ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.

The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.

Bruce Jancin/Frontline Medical News

NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.

All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.

Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.

Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.

In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.

A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.

The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.

Bruce Jancin/Frontline Medical News

John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.

“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.

Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.

“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.

It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.

“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.

Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.

Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.

The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.

[email protected]

ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.

The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.

Bruce Jancin/Frontline Medical News

NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.

All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.

Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.

Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.

In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.

A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.

The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.

Bruce Jancin/Frontline Medical News

John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.

“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.

Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.

“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.

It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.

“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.

Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.

Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.

The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.

[email protected]

ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.

The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.

Bruce Jancin/Frontline Medical News

NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.

All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.

Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.

Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.

In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.

A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.

The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.

Bruce Jancin/Frontline Medical News

John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.

“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.

Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.

“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.

It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.

“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.

Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.

Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.

The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.

[email protected]

Dr. Tunc's literature review and retrospective review of headache clinic data provide food for thought with regard to chronic daily headache (CDH) in younger children. The rate of CDH in the papers reviewed ranged from 8% to 30%. I think this range represents the differences in nature between the pediatric headache clinics included in the sample. In some areas, the local primary care providers refer all children with headache to headache clinics. In other areas, the primary care providers hold on to "easy" headache patients and refer only the "tough cases." For that reason, it is hard to generalize from Dr. Tunc's finding. Suffice it to say that tertiary pediatric headache clinics do see some younger children with CDH. The Cleveland Clinic experience showed a prevalence of 58%, so that clinic sees the harder cases.

Dr. Tunc did not find MRI to be useful in children with CDH. I just want to caution readers to order MRIs when patients have systemic signs (eg, growth failure or secondary amenorrhea), neurologic signs (eg, ataxia, slurred speech, one-sided weakness, or facial asymmetry), abrupt onset of headache (think of ruptured aneurysm), or a new change in headache pattern. We must be careful with conclusions drawn from retrospective studies because we can't control for any factors. Although no MRIs were positive, we don't know about patients who came to the neurosurgeon through other pathways besides the headache clinic.

Dr. Tunc mentioned that younger patients had a longer duration of illness before seeking tertiary care, and she speculated as to why. Further clarification is needed to develop a plausible explanation. How was the time measured? Was it measured from the first headache until the tertiary care visit, or from onset of CDH until the tertiary care visit? If the former is true, then I might reach a different conclusion. Perhaps it takes longer for younger children to chronify than older children. If, on the other hand, time was measured from the onset of CDH until presentation, then the authors' explanations may indeed be sound.

In summary, this is a great study that shows that small children presenting to a tertiary care center do get CDH at a higher rate than we thought. It would be terrific to poll other pediatric headache programs to compare and contrast with the findings of this study.

—Jack Gladstein, MD
Professor of Pediatrics and Neurology
Director of the Pediatric Headache Clinic
University of Maryland School of Medicine
Baltimore

Dr. Tunc's literature review and retrospective review of headache clinic data provide food for thought with regard to chronic daily headache (CDH) in younger children. The rate of CDH in the papers reviewed ranged from 8% to 30%. I think this range represents the differences in nature between the pediatric headache clinics included in the sample. In some areas, the local primary care providers refer all children with headache to headache clinics. In other areas, the primary care providers hold on to "easy" headache patients and refer only the "tough cases." For that reason, it is hard to generalize from Dr. Tunc's finding. Suffice it to say that tertiary pediatric headache clinics do see some younger children with CDH. The Cleveland Clinic experience showed a prevalence of 58%, so that clinic sees the harder cases.

Dr. Tunc did not find MRI to be useful in children with CDH. I just want to caution readers to order MRIs when patients have systemic signs (eg, growth failure or secondary amenorrhea), neurologic signs (eg, ataxia, slurred speech, one-sided weakness, or facial asymmetry), abrupt onset of headache (think of ruptured aneurysm), or a new change in headache pattern. We must be careful with conclusions drawn from retrospective studies because we can't control for any factors. Although no MRIs were positive, we don't know about patients who came to the neurosurgeon through other pathways besides the headache clinic.

Dr. Tunc mentioned that younger patients had a longer duration of illness before seeking tertiary care, and she speculated as to why. Further clarification is needed to develop a plausible explanation. How was the time measured? Was it measured from the first headache until the tertiary care visit, or from onset of CDH until the tertiary care visit? If the former is true, then I might reach a different conclusion. Perhaps it takes longer for younger children to chronify than older children. If, on the other hand, time was measured from the onset of CDH until presentation, then the authors' explanations may indeed be sound.

In summary, this is a great study that shows that small children presenting to a tertiary care center do get CDH at a higher rate than we thought. It would be terrific to poll other pediatric headache programs to compare and contrast with the findings of this study.

—Jack Gladstein, MD
Professor of Pediatrics and Neurology
Director of the Pediatric Headache Clinic
University of Maryland School of Medicine
Baltimore

Dr. Tunc's literature review and retrospective review of headache clinic data provide food for thought with regard to chronic daily headache (CDH) in younger children. The rate of CDH in the papers reviewed ranged from 8% to 30%. I think this range represents the differences in nature between the pediatric headache clinics included in the sample. In some areas, the local primary care providers refer all children with headache to headache clinics. In other areas, the primary care providers hold on to "easy" headache patients and refer only the "tough cases." For that reason, it is hard to generalize from Dr. Tunc's finding. Suffice it to say that tertiary pediatric headache clinics do see some younger children with CDH. The Cleveland Clinic experience showed a prevalence of 58%, so that clinic sees the harder cases.

Dr. Tunc did not find MRI to be useful in children with CDH. I just want to caution readers to order MRIs when patients have systemic signs (eg, growth failure or secondary amenorrhea), neurologic signs (eg, ataxia, slurred speech, one-sided weakness, or facial asymmetry), abrupt onset of headache (think of ruptured aneurysm), or a new change in headache pattern. We must be careful with conclusions drawn from retrospective studies because we can't control for any factors. Although no MRIs were positive, we don't know about patients who came to the neurosurgeon through other pathways besides the headache clinic.

Dr. Tunc mentioned that younger patients had a longer duration of illness before seeking tertiary care, and she speculated as to why. Further clarification is needed to develop a plausible explanation. How was the time measured? Was it measured from the first headache until the tertiary care visit, or from onset of CDH until the tertiary care visit? If the former is true, then I might reach a different conclusion. Perhaps it takes longer for younger children to chronify than older children. If, on the other hand, time was measured from the onset of CDH until presentation, then the authors' explanations may indeed be sound.

In summary, this is a great study that shows that small children presenting to a tertiary care center do get CDH at a higher rate than we thought. It would be terrific to poll other pediatric headache programs to compare and contrast with the findings of this study.

—Jack Gladstein, MD
Professor of Pediatrics and Neurology
Director of the Pediatric Headache Clinic
University of Maryland School of Medicine
Baltimore

A 19-year-old man presented to our clinic with erythematous, pruritic, lightly-scaled, and annular patches on his dorsal wrists. The rash had first appeared 3 weeks earlier on the patient’s left wrist, which is where he’d been wearing a chrome-colored watch for a couple of years. After the rash appeared on his left wrist, the patient began wearing the watch on his right wrist. Soon after the switch, the rash appeared on his right wrist. The patient was otherwise healthy and denied any previous rashes, had no body piercings or allergies of any kind, and was not on any medications.

On physical exam, we noted 2 erythematous, scaly, annular, and slightly raised plaques on the distal dorsal aspects of both forearms/wrists with a few erythematous papular lesions (FIGURE). There was also scaling on the soles of the patient’s feet and white, moist scaling in the web space between his 4th and 5th toes bilaterally.

COURTESY OF STEPHEN E. HELMS, MD, FAAD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tinea corporis (ringworm)

The patient and physician initially considered the possibility of allergic contact dermatitis due to nickel because of the history of redness, scaling, and itching underneath the watch when it was worn on the left wrist, and then when it was worn on the right wrist. Nickel dermatitis is common and it is easy to attribute the cause of a condition like this to the most obvious diagnosis without considering a more complete differential diagnosis.¹

However, there were clues that prompted us to suspect tinea corporis (ringworm). The red, scaly rash spread centrifugally over several weeks, and fomites, such as a watch, can spread infectious diseases. Also, our patient had a few erythematous papular lesions, and the presence of papules in addition to scaling rings is typical of fungal infections involving hair follicles (Majocchi’s granuloma).

A positive potassium hydroxide (KOH) preparation confirmed the diagnosis and eliminated the need for nickel patch testing.²

Warmth and moisture could explain tinea on the wrists

Dermatophytes are fungi that can cause infections in the skin, hair, and nails. They are classified by where they are found—anthropophilic (humans), geophilic (soil), or zoophilic (animals). Anthropophilic and zoophilic dermatophytes from the genera Trichophyton, Microsporum, and Epidermophyton are primarily responsible for human fungal infections.³ It is estimated that superficial fungal infections affect up to a quarter of the world’s population.³

The wrists are not a common place for tinea corporis, but the condition can occur anywhere on the body.

Tinea corporis mainly occurs in prepubertal children, presenting as a red, annular, scaly, pruritic patch with central clearing and an active border.⁴ Tinea corporis includes all superficial dermatophyte infections of the glabrous skin and is particularly common in areas of excessive heat and moisture.⁵ Patients can pick up tinea corporis via fomites at the gym, through soil in the garden, or by touching a pet’s fur or a child’s scalp when either has the fungal infection.

The wrists are not a common place for tinea corporis, but the condition can occur anywhere on the body. This patient may well have contracted tinea from his own interdigital tinea pedis. Warmth and moisture under the watch could also explain the predilection for fungus to grow on the wrists.

Distinguish between contact dermatitis and tinea corporis

The differential diagnosis for tinea corporis includes allergic contact dermatitis, granuloma annulare, annular elastolytic granuloma, and erythema chronicum migrans.

Allergic contact dermatitis is caused by an allergy to a substance, such as the metal nickel. A preliminary diagnosis of contact dermatitis could easily be made in error if one were to assume that a patient was having a type IV hypersensitivity response to nickel from a watch.⁶

Granuloma annulare produces slowly expanding annular plaques that are not itchy and do not scale. This commonly occurs over the joints and is of unknown etiology.⁷

Annular elastolytic granuloma is a variant of granuloma annulare that occurs on skin that has been exposed to the sun. It presents with a red, ring-like pattern and is associated with little scaling or pruritus.⁸

Erythema chronicum migrans produces annular lesions at the site of a tick bite and is the primary sign of Lyme disease. The tick must be in place for 24 hours for infection to occur.⁹ (Our patient did not notice a tick attached at either site.)

In this case, a KOH preparation of skin scrapings identified septate hyphae, which supported our diagnosis of tinea corporis.² A history of red, scaly, itchy, and expanding round/oval patches or plaques and evidence of “athlete’s foot” can also help one to make the diagnosis.

Antifungal agents will clear the rash

Proper treatment of tinea corporis consists of antifungal creams containing ketoconazole, econazole, or naftifine on non-hair-bearing areas. The creams should be applied twice daily and rarely cause adverse effects. Bandages are not usually necessary, but may be used if contact with others is anticipated. For the scalp and other hair-bearing areas, systemic treatment with terbinafine 250 mg daily for one month in an adult is necessary. Oral agents will usually clear the rash within 4 to 6 weeks.^10,11

Because our patient had bilateral involvement and some papule formation indicating Majocchi’s granuloma, we prescribed oral terbinafine 250 mg daily for 2 weeks in addition to econazole cream. The patient was to apply the cream for a total of 4 weeks to ensure the rash did not recur.

CORRESPONDENCE
Stephen E. Helms, MD, Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; [email protected].

A 19-year-old man presented to our clinic with erythematous, pruritic, lightly-scaled, and annular patches on his dorsal wrists. The rash had first appeared 3 weeks earlier on the patient’s left wrist, which is where he’d been wearing a chrome-colored watch for a couple of years. After the rash appeared on his left wrist, the patient began wearing the watch on his right wrist. Soon after the switch, the rash appeared on his right wrist. The patient was otherwise healthy and denied any previous rashes, had no body piercings or allergies of any kind, and was not on any medications.

On physical exam, we noted 2 erythematous, scaly, annular, and slightly raised plaques on the distal dorsal aspects of both forearms/wrists with a few erythematous papular lesions (FIGURE). There was also scaling on the soles of the patient’s feet and white, moist scaling in the web space between his 4th and 5th toes bilaterally.

COURTESY OF STEPHEN E. HELMS, MD, FAAD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tinea corporis (ringworm)

The patient and physician initially considered the possibility of allergic contact dermatitis due to nickel because of the history of redness, scaling, and itching underneath the watch when it was worn on the left wrist, and then when it was worn on the right wrist. Nickel dermatitis is common and it is easy to attribute the cause of a condition like this to the most obvious diagnosis without considering a more complete differential diagnosis.¹

However, there were clues that prompted us to suspect tinea corporis (ringworm). The red, scaly rash spread centrifugally over several weeks, and fomites, such as a watch, can spread infectious diseases. Also, our patient had a few erythematous papular lesions, and the presence of papules in addition to scaling rings is typical of fungal infections involving hair follicles (Majocchi’s granuloma).

A positive potassium hydroxide (KOH) preparation confirmed the diagnosis and eliminated the need for nickel patch testing.²

Warmth and moisture could explain tinea on the wrists

Dermatophytes are fungi that can cause infections in the skin, hair, and nails. They are classified by where they are found—anthropophilic (humans), geophilic (soil), or zoophilic (animals). Anthropophilic and zoophilic dermatophytes from the genera Trichophyton, Microsporum, and Epidermophyton are primarily responsible for human fungal infections.³ It is estimated that superficial fungal infections affect up to a quarter of the world’s population.³

The wrists are not a common place for tinea corporis, but the condition can occur anywhere on the body.

Tinea corporis mainly occurs in prepubertal children, presenting as a red, annular, scaly, pruritic patch with central clearing and an active border.⁴ Tinea corporis includes all superficial dermatophyte infections of the glabrous skin and is particularly common in areas of excessive heat and moisture.⁵ Patients can pick up tinea corporis via fomites at the gym, through soil in the garden, or by touching a pet’s fur or a child’s scalp when either has the fungal infection.

The wrists are not a common place for tinea corporis, but the condition can occur anywhere on the body. This patient may well have contracted tinea from his own interdigital tinea pedis. Warmth and moisture under the watch could also explain the predilection for fungus to grow on the wrists.

Distinguish between contact dermatitis and tinea corporis

The differential diagnosis for tinea corporis includes allergic contact dermatitis, granuloma annulare, annular elastolytic granuloma, and erythema chronicum migrans.

Allergic contact dermatitis is caused by an allergy to a substance, such as the metal nickel. A preliminary diagnosis of contact dermatitis could easily be made in error if one were to assume that a patient was having a type IV hypersensitivity response to nickel from a watch.⁶

Granuloma annulare produces slowly expanding annular plaques that are not itchy and do not scale. This commonly occurs over the joints and is of unknown etiology.⁷

Annular elastolytic granuloma is a variant of granuloma annulare that occurs on skin that has been exposed to the sun. It presents with a red, ring-like pattern and is associated with little scaling or pruritus.⁸

Erythema chronicum migrans produces annular lesions at the site of a tick bite and is the primary sign of Lyme disease. The tick must be in place for 24 hours for infection to occur.⁹ (Our patient did not notice a tick attached at either site.)

In this case, a KOH preparation of skin scrapings identified septate hyphae, which supported our diagnosis of tinea corporis.² A history of red, scaly, itchy, and expanding round/oval patches or plaques and evidence of “athlete’s foot” can also help one to make the diagnosis.

Antifungal agents will clear the rash

Proper treatment of tinea corporis consists of antifungal creams containing ketoconazole, econazole, or naftifine on non-hair-bearing areas. The creams should be applied twice daily and rarely cause adverse effects. Bandages are not usually necessary, but may be used if contact with others is anticipated. For the scalp and other hair-bearing areas, systemic treatment with terbinafine 250 mg daily for one month in an adult is necessary. Oral agents will usually clear the rash within 4 to 6 weeks.^10,11

Because our patient had bilateral involvement and some papule formation indicating Majocchi’s granuloma, we prescribed oral terbinafine 250 mg daily for 2 weeks in addition to econazole cream. The patient was to apply the cream for a total of 4 weeks to ensure the rash did not recur.

CORRESPONDENCE
Stephen E. Helms, MD, Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; [email protected].

A 19-year-old man presented to our clinic with erythematous, pruritic, lightly-scaled, and annular patches on his dorsal wrists. The rash had first appeared 3 weeks earlier on the patient’s left wrist, which is where he’d been wearing a chrome-colored watch for a couple of years. After the rash appeared on his left wrist, the patient began wearing the watch on his right wrist. Soon after the switch, the rash appeared on his right wrist. The patient was otherwise healthy and denied any previous rashes, had no body piercings or allergies of any kind, and was not on any medications.

On physical exam, we noted 2 erythematous, scaly, annular, and slightly raised plaques on the distal dorsal aspects of both forearms/wrists with a few erythematous papular lesions (FIGURE). There was also scaling on the soles of the patient’s feet and white, moist scaling in the web space between his 4th and 5th toes bilaterally.

COURTESY OF STEPHEN E. HELMS, MD, FAAD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Tinea corporis (ringworm)

The patient and physician initially considered the possibility of allergic contact dermatitis due to nickel because of the history of redness, scaling, and itching underneath the watch when it was worn on the left wrist, and then when it was worn on the right wrist. Nickel dermatitis is common and it is easy to attribute the cause of a condition like this to the most obvious diagnosis without considering a more complete differential diagnosis.¹

However, there were clues that prompted us to suspect tinea corporis (ringworm). The red, scaly rash spread centrifugally over several weeks, and fomites, such as a watch, can spread infectious diseases. Also, our patient had a few erythematous papular lesions, and the presence of papules in addition to scaling rings is typical of fungal infections involving hair follicles (Majocchi’s granuloma).

A positive potassium hydroxide (KOH) preparation confirmed the diagnosis and eliminated the need for nickel patch testing.²

Warmth and moisture could explain tinea on the wrists

Dermatophytes are fungi that can cause infections in the skin, hair, and nails. They are classified by where they are found—anthropophilic (humans), geophilic (soil), or zoophilic (animals). Anthropophilic and zoophilic dermatophytes from the genera Trichophyton, Microsporum, and Epidermophyton are primarily responsible for human fungal infections.³ It is estimated that superficial fungal infections affect up to a quarter of the world’s population.³

The wrists are not a common place for tinea corporis, but the condition can occur anywhere on the body.

Tinea corporis mainly occurs in prepubertal children, presenting as a red, annular, scaly, pruritic patch with central clearing and an active border.⁴ Tinea corporis includes all superficial dermatophyte infections of the glabrous skin and is particularly common in areas of excessive heat and moisture.⁵ Patients can pick up tinea corporis via fomites at the gym, through soil in the garden, or by touching a pet’s fur or a child’s scalp when either has the fungal infection.

The wrists are not a common place for tinea corporis, but the condition can occur anywhere on the body. This patient may well have contracted tinea from his own interdigital tinea pedis. Warmth and moisture under the watch could also explain the predilection for fungus to grow on the wrists.

Distinguish between contact dermatitis and tinea corporis

The differential diagnosis for tinea corporis includes allergic contact dermatitis, granuloma annulare, annular elastolytic granuloma, and erythema chronicum migrans.

Allergic contact dermatitis is caused by an allergy to a substance, such as the metal nickel. A preliminary diagnosis of contact dermatitis could easily be made in error if one were to assume that a patient was having a type IV hypersensitivity response to nickel from a watch.⁶

Granuloma annulare produces slowly expanding annular plaques that are not itchy and do not scale. This commonly occurs over the joints and is of unknown etiology.⁷

Annular elastolytic granuloma is a variant of granuloma annulare that occurs on skin that has been exposed to the sun. It presents with a red, ring-like pattern and is associated with little scaling or pruritus.⁸

Erythema chronicum migrans produces annular lesions at the site of a tick bite and is the primary sign of Lyme disease. The tick must be in place for 24 hours for infection to occur.⁹ (Our patient did not notice a tick attached at either site.)

In this case, a KOH preparation of skin scrapings identified septate hyphae, which supported our diagnosis of tinea corporis.² A history of red, scaly, itchy, and expanding round/oval patches or plaques and evidence of “athlete’s foot” can also help one to make the diagnosis.

Antifungal agents will clear the rash

Proper treatment of tinea corporis consists of antifungal creams containing ketoconazole, econazole, or naftifine on non-hair-bearing areas. The creams should be applied twice daily and rarely cause adverse effects. Bandages are not usually necessary, but may be used if contact with others is anticipated. For the scalp and other hair-bearing areas, systemic treatment with terbinafine 250 mg daily for one month in an adult is necessary. Oral agents will usually clear the rash within 4 to 6 weeks.^10,11

Because our patient had bilateral involvement and some papule formation indicating Majocchi’s granuloma, we prescribed oral terbinafine 250 mg daily for 2 weeks in addition to econazole cream. The patient was to apply the cream for a total of 4 weeks to ensure the rash did not recur.

CORRESPONDENCE
Stephen E. Helms, MD, Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; [email protected].