Institutions participating in the American College of Surgeons (ACS) Transition to Practice (TTP) Program are now accepting applications for TTP Associates for the 2018−2019 academic year. Interested residents are encouraged to review the program profiles on the ACS website and submit an application to [email protected].

In addition, the TTP Steering Committee is accepting applications from institutions interested in establishing a new TTP Program site. Contact [email protected] for more information on the application process.

The ACS Division of Education launched the TTP Program in 2013 in response to the identified need for autonomous experience for general surgeons leaving residency. The program adds a layer of expertise between residency and independent practice. TTP Associates experience increasing autonomy throughout the year in a broad-based clinical setting, build their competence and confidence in general surgery, develop practice management skills, and gain practical experience for the next phase of their careers. Working closely with experienced surgeons, TTP Associates concentrate on specific areas within general surgery to refine operative skills based on their career goals.
 

Institutions participating in the American College of Surgeons (ACS) Transition to Practice (TTP) Program are now accepting applications for TTP Associates for the 2018−2019 academic year. Interested residents are encouraged to review the program profiles on the ACS website and submit an application to [email protected].

In addition, the TTP Steering Committee is accepting applications from institutions interested in establishing a new TTP Program site. Contact [email protected] for more information on the application process.

The ACS Division of Education launched the TTP Program in 2013 in response to the identified need for autonomous experience for general surgeons leaving residency. The program adds a layer of expertise between residency and independent practice. TTP Associates experience increasing autonomy throughout the year in a broad-based clinical setting, build their competence and confidence in general surgery, develop practice management skills, and gain practical experience for the next phase of their careers. Working closely with experienced surgeons, TTP Associates concentrate on specific areas within general surgery to refine operative skills based on their career goals.
 

Institutions participating in the American College of Surgeons (ACS) Transition to Practice (TTP) Program are now accepting applications for TTP Associates for the 2018−2019 academic year. Interested residents are encouraged to review the program profiles on the ACS website and submit an application to [email protected].

In addition, the TTP Steering Committee is accepting applications from institutions interested in establishing a new TTP Program site. Contact [email protected] for more information on the application process.

The ACS Division of Education launched the TTP Program in 2013 in response to the identified need for autonomous experience for general surgeons leaving residency. The program adds a layer of expertise between residency and independent practice. TTP Associates experience increasing autonomy throughout the year in a broad-based clinical setting, build their competence and confidence in general surgery, develop practice management skills, and gain practical experience for the next phase of their careers. Working closely with experienced surgeons, TTP Associates concentrate on specific areas within general surgery to refine operative skills based on their career goals.
 

Managing ocular rosacea often includes a combination of oral and topical treatments, and some patients find relief with natural strategies such as warm compresses and eyelid massage, Julie C. Harper, MD, said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Ocular rosacea can present in several forms, including sties on the eyelids, blepharitis with chalazia and telangiectasia, and “meibomian inspissation visible as pale streaks perpendicular to the lid margin,” according to a 2016 review article she cited (Clin Dermatol. 2016 Mar-Apr;34[2]:146-50).

[email protected]

Managing ocular rosacea often includes a combination of oral and topical treatments, and some patients find relief with natural strategies such as warm compresses and eyelid massage, Julie C. Harper, MD, said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Ocular rosacea can present in several forms, including sties on the eyelids, blepharitis with chalazia and telangiectasia, and “meibomian inspissation visible as pale streaks perpendicular to the lid margin,” according to a 2016 review article she cited (Clin Dermatol. 2016 Mar-Apr;34[2]:146-50).

[email protected]

Managing ocular rosacea often includes a combination of oral and topical treatments, and some patients find relief with natural strategies such as warm compresses and eyelid massage, Julie C. Harper, MD, said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Ocular rosacea can present in several forms, including sties on the eyelids, blepharitis with chalazia and telangiectasia, and “meibomian inspissation visible as pale streaks perpendicular to the lid margin,” according to a 2016 review article she cited (Clin Dermatol. 2016 Mar-Apr;34[2]:146-50).

[email protected]

Urinary tract infection (UTI) is one of the most common bacterial infections in young febrile infants, but doctors know that collecting a urine sample to diagnose or exclude UTI can be very challenging in practice.

Recently, researchers in Australia conducted a randomized controlled trial in a pediatric hospital emergency department to test a method that could stimulate voiding within 5 minutes. It’s called the Quick-Wee method, and the technique involves the clinician rubbing the suprapubic area of the child in a circular pattern with gauze soaked in cold saline held with disposable plastic forceps. In the trial, this was done until the sample was obtained or until 5 minutes passed.

Petro Feketa/iStockphoto

Reference

Kaufman J, Fitzpatrick P, Tosif S, et al. Faster clean catch urine collection (Quick-Wee method) from infants: randomised controlled trial. BMJ 2017;357:j1341. doi: 10.1136/bmj.j1341. Accessed June 12, 2017.

Urinary tract infection (UTI) is one of the most common bacterial infections in young febrile infants, but doctors know that collecting a urine sample to diagnose or exclude UTI can be very challenging in practice.

Recently, researchers in Australia conducted a randomized controlled trial in a pediatric hospital emergency department to test a method that could stimulate voiding within 5 minutes. It’s called the Quick-Wee method, and the technique involves the clinician rubbing the suprapubic area of the child in a circular pattern with gauze soaked in cold saline held with disposable plastic forceps. In the trial, this was done until the sample was obtained or until 5 minutes passed.

Petro Feketa/iStockphoto

Reference

Kaufman J, Fitzpatrick P, Tosif S, et al. Faster clean catch urine collection (Quick-Wee method) from infants: randomised controlled trial. BMJ 2017;357:j1341. doi: 10.1136/bmj.j1341. Accessed June 12, 2017.

Urinary tract infection (UTI) is one of the most common bacterial infections in young febrile infants, but doctors know that collecting a urine sample to diagnose or exclude UTI can be very challenging in practice.

Recently, researchers in Australia conducted a randomized controlled trial in a pediatric hospital emergency department to test a method that could stimulate voiding within 5 minutes. It’s called the Quick-Wee method, and the technique involves the clinician rubbing the suprapubic area of the child in a circular pattern with gauze soaked in cold saline held with disposable plastic forceps. In the trial, this was done until the sample was obtained or until 5 minutes passed.

Petro Feketa/iStockphoto

Reference

Kaufman J, Fitzpatrick P, Tosif S, et al. Faster clean catch urine collection (Quick-Wee method) from infants: randomised controlled trial. BMJ 2017;357:j1341. doi: 10.1136/bmj.j1341. Accessed June 12, 2017.

LAS VEGAS – Coprescribing isotretinoin and tetracycline antibiotics among dermatologists and nondermatologists was low, according to a study that analyzed 11 years of ambulatory medical data.

The findings were presented in a poster at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

“Patients with an inadequate response to tetracyclines or severe cases of acne may require isotretinoin,” wrote Brooke Vasicek, MD, of Loyola University Chicago in Maywood, Ill., and colleagues. However, since the combined use of tetracyclines and isotretinoin puts patients at risk of pseudotumor cerebri, which may lead to blindness, “concurrent use of these medications must be avoided,” they explained.

To assess the frequency of isotretinoin/tetracycline coprescribing, they reviewed data from the National Ambulatory Medical Care Survey collected during 2003-2013 and estimated the number of prescriptions for isotretinoin and/or tetracycline. The dataset included 51,980,042 visits to dermatologists for acne and 29,063,717 visits to nondermatologists.

Of the dermatologists in the survey data, 13.6% reported prescribing isotretinoin (compared with 1.6% of nondermatologists), 29.2% reported prescribing tetracycline (compared with 22.9% of nondermatologists), and 0.40% reported concurrently prescribing both medications (compared with .025% of nondermatologists).

Dermatologists were significantly more likely to mention isotretinoin than nondermatologists, but mention of tetracycline was not significantly different among specialties. “Acne severity and level of comfort because of specialty-based training may be at play in the isotretinoin prescribing pattern differences between dermatologists and nondermatologists,” the researchers noted. The increased pseudotumor cerebri risk associated with combining the medications “is well known among dermatologists, hence, patient exposure is likely very uncommon,” they added.

The results were limited by the cross-sectional nature of the study and possible sampling bias associated with the data collection source, they said.

The researchers had no financial conflicts to disclose.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Coprescribing isotretinoin and tetracycline antibiotics among dermatologists and nondermatologists was low, according to a study that analyzed 11 years of ambulatory medical data.

The findings were presented in a poster at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

“Patients with an inadequate response to tetracyclines or severe cases of acne may require isotretinoin,” wrote Brooke Vasicek, MD, of Loyola University Chicago in Maywood, Ill., and colleagues. However, since the combined use of tetracyclines and isotretinoin puts patients at risk of pseudotumor cerebri, which may lead to blindness, “concurrent use of these medications must be avoided,” they explained.

To assess the frequency of isotretinoin/tetracycline coprescribing, they reviewed data from the National Ambulatory Medical Care Survey collected during 2003-2013 and estimated the number of prescriptions for isotretinoin and/or tetracycline. The dataset included 51,980,042 visits to dermatologists for acne and 29,063,717 visits to nondermatologists.

Of the dermatologists in the survey data, 13.6% reported prescribing isotretinoin (compared with 1.6% of nondermatologists), 29.2% reported prescribing tetracycline (compared with 22.9% of nondermatologists), and 0.40% reported concurrently prescribing both medications (compared with .025% of nondermatologists).

Dermatologists were significantly more likely to mention isotretinoin than nondermatologists, but mention of tetracycline was not significantly different among specialties. “Acne severity and level of comfort because of specialty-based training may be at play in the isotretinoin prescribing pattern differences between dermatologists and nondermatologists,” the researchers noted. The increased pseudotumor cerebri risk associated with combining the medications “is well known among dermatologists, hence, patient exposure is likely very uncommon,” they added.

The results were limited by the cross-sectional nature of the study and possible sampling bias associated with the data collection source, they said.

The researchers had no financial conflicts to disclose.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Coprescribing isotretinoin and tetracycline antibiotics among dermatologists and nondermatologists was low, according to a study that analyzed 11 years of ambulatory medical data.

The findings were presented in a poster at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

“Patients with an inadequate response to tetracyclines or severe cases of acne may require isotretinoin,” wrote Brooke Vasicek, MD, of Loyola University Chicago in Maywood, Ill., and colleagues. However, since the combined use of tetracyclines and isotretinoin puts patients at risk of pseudotumor cerebri, which may lead to blindness, “concurrent use of these medications must be avoided,” they explained.

To assess the frequency of isotretinoin/tetracycline coprescribing, they reviewed data from the National Ambulatory Medical Care Survey collected during 2003-2013 and estimated the number of prescriptions for isotretinoin and/or tetracycline. The dataset included 51,980,042 visits to dermatologists for acne and 29,063,717 visits to nondermatologists.

Of the dermatologists in the survey data, 13.6% reported prescribing isotretinoin (compared with 1.6% of nondermatologists), 29.2% reported prescribing tetracycline (compared with 22.9% of nondermatologists), and 0.40% reported concurrently prescribing both medications (compared with .025% of nondermatologists).

Dermatologists were significantly more likely to mention isotretinoin than nondermatologists, but mention of tetracycline was not significantly different among specialties. “Acne severity and level of comfort because of specialty-based training may be at play in the isotretinoin prescribing pattern differences between dermatologists and nondermatologists,” the researchers noted. The increased pseudotumor cerebri risk associated with combining the medications “is well known among dermatologists, hence, patient exposure is likely very uncommon,” they added.

The results were limited by the cross-sectional nature of the study and possible sampling bias associated with the data collection source, they said.

The researchers had no financial conflicts to disclose.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Nondermatologists were 11 times more likely than dermatologists to prescribe nystatin for dermatophyte infections, according to a study that analyzed 12 years of ambulatory-care data in the United States.

The findings were presented in a poster at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

“Although it is effective for the treatment of cutaneous or mucocutaneous candidiasis, the topical polyene nystatin, however, is clinically ineffective in the treatment of dermatophyte infection,” wrote Jeave Reserva, MD, of the division of dermatology at Loyola University Health System in Illinois, and colleagues.

In their analysis, the researchers used 12 years of data from two separate surveys – the National Ambulatory Medical Care Surveys and the National Hospital Ambulatory Medical Care Survey–Emergency Department – collected between 2003 and 2014, as well as 9 years of data from the National Hospital Ambulatory Medical Care Survey–Outpatient Department collected between 2003 and 2011. They reviewed data from 48.4 million ambulatory-care visits for dermatophyte infections, including 1,459,184 visits in which nystatin was prescribed. Overall, nondermatologists were significantly more likely than dermatologists to prescribe nystatin. The researchers also found that, after controlling for race, gender, and insurance status, male or black patients were significantly more likely to have positive tinea infections.

Nondermatologists were 11.08 times more likely to prescribe nystatin for dermatophytosis, compared with dermatologists (P = .02), the researchers found.

Although the number of visits does not reflect disease prevalence, the results suggest that health care disparities affect patients presenting with dermatophytosis, the researchers said. “Nondermatologists may benefit from additional provider education on the diagnosis and appropriate treatment of dermatophyte infections,” they concluded.

The researchers had no financial conflicts to disclose; no funding source was listed.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Nondermatologists were 11 times more likely than dermatologists to prescribe nystatin for dermatophyte infections, according to a study that analyzed 12 years of ambulatory-care data in the United States.

The findings were presented in a poster at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

“Although it is effective for the treatment of cutaneous or mucocutaneous candidiasis, the topical polyene nystatin, however, is clinically ineffective in the treatment of dermatophyte infection,” wrote Jeave Reserva, MD, of the division of dermatology at Loyola University Health System in Illinois, and colleagues.

In their analysis, the researchers used 12 years of data from two separate surveys – the National Ambulatory Medical Care Surveys and the National Hospital Ambulatory Medical Care Survey–Emergency Department – collected between 2003 and 2014, as well as 9 years of data from the National Hospital Ambulatory Medical Care Survey–Outpatient Department collected between 2003 and 2011. They reviewed data from 48.4 million ambulatory-care visits for dermatophyte infections, including 1,459,184 visits in which nystatin was prescribed. Overall, nondermatologists were significantly more likely than dermatologists to prescribe nystatin. The researchers also found that, after controlling for race, gender, and insurance status, male or black patients were significantly more likely to have positive tinea infections.

Nondermatologists were 11.08 times more likely to prescribe nystatin for dermatophytosis, compared with dermatologists (P = .02), the researchers found.

Although the number of visits does not reflect disease prevalence, the results suggest that health care disparities affect patients presenting with dermatophytosis, the researchers said. “Nondermatologists may benefit from additional provider education on the diagnosis and appropriate treatment of dermatophyte infections,” they concluded.

The researchers had no financial conflicts to disclose; no funding source was listed.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Nondermatologists were 11 times more likely than dermatologists to prescribe nystatin for dermatophyte infections, according to a study that analyzed 12 years of ambulatory-care data in the United States.

The findings were presented in a poster at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

“Although it is effective for the treatment of cutaneous or mucocutaneous candidiasis, the topical polyene nystatin, however, is clinically ineffective in the treatment of dermatophyte infection,” wrote Jeave Reserva, MD, of the division of dermatology at Loyola University Health System in Illinois, and colleagues.

In their analysis, the researchers used 12 years of data from two separate surveys – the National Ambulatory Medical Care Surveys and the National Hospital Ambulatory Medical Care Survey–Emergency Department – collected between 2003 and 2014, as well as 9 years of data from the National Hospital Ambulatory Medical Care Survey–Outpatient Department collected between 2003 and 2011. They reviewed data from 48.4 million ambulatory-care visits for dermatophyte infections, including 1,459,184 visits in which nystatin was prescribed. Overall, nondermatologists were significantly more likely than dermatologists to prescribe nystatin. The researchers also found that, after controlling for race, gender, and insurance status, male or black patients were significantly more likely to have positive tinea infections.

Nondermatologists were 11.08 times more likely to prescribe nystatin for dermatophytosis, compared with dermatologists (P = .02), the researchers found.

Although the number of visits does not reflect disease prevalence, the results suggest that health care disparities affect patients presenting with dermatophytosis, the researchers said. “Nondermatologists may benefit from additional provider education on the diagnosis and appropriate treatment of dermatophyte infections,” they concluded.

The researchers had no financial conflicts to disclose; no funding source was listed.

SDEF and this news organization are owned by the same parent company.

Autoimmune encephalitis may be a potentially severe complication of immune checkpoint inhibitor therapy, a case report suggests.

The recently published report describes a 53-year-old man with B-cell non-Hodgkin lymphoma who presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with the immune checkpoint inhibitor nivolumab.

Neuropathologic examination of a biopsied brain lesion found on cranial MRI showed a T cell–dominated inflammatory process thought to be autoimmune in origin, according to Herwig Strik, MD, of the department of neurology at Philipps University of Marburg (Germany), and his colleagues (Eur J Cancer. 2017 Oct 16. doi: 10.1016/j.ejca.2017.09.026).

After the patient stopped taking nivolumab and the inflammatory process was treated, his “clinical neurological and radiological status remained stable but disabling with fluctuating dysarthria and ataxia,” Dr. Strik and his colleagues wrote.

“Since these novel anticancer agents are increasingly used, this severe complication should be recognized soon and treatment should be terminated to avoid chronification,” they said in the report.

Nivolumab and other checkpoint inhibitors are known to have autoimmune side effects in some cases that can affect the pulmonary, gastrointestinal, and endocrine systems, the authors said.

Several previous case reports have detailed encephalitis occurring in cancer patients receiving nivolumab, the combination of nivolumab plus the immune checkpoint inhibitor ipilimumab, or ipilimumab alone. The authors said they believe that this case report is the first to describe multifocal CNS inflammation following nivolumab treatment for systemic lymphoma.

The patient was diagnosed with B-cell non-Hodgkin lymphoma in 2005, according to the case report. He was first treated in 2009 with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), followed by stem cell apheresis, radioimmunotherapy, and rituximab; he then received R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) in August 2014, followed by autologous stem cell transplantation in October of that year. The patient started nivolumab maintenance therapy in February 2015 but started experiencing neurological symptoms that eventually led to ending nivolumab treatment in September 2015.

The patient’s lymphoma relapsed in June 2016. “The disabling neurological symptoms and his personal situation, however, worsened the patient’s depressive symptoms so severely that he went abroad to commit assisted suicide,” wrote Dr. Strik and his colleagues.

The authors proposed the term “immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD)” to describe the inflammatory condition described in the case report.

They declared no conflicts of interest related to the case report and did not receive grant support for conducting the research described in it.

Autoimmune encephalitis may be a potentially severe complication of immune checkpoint inhibitor therapy, a case report suggests.

The recently published report describes a 53-year-old man with B-cell non-Hodgkin lymphoma who presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with the immune checkpoint inhibitor nivolumab.

Neuropathologic examination of a biopsied brain lesion found on cranial MRI showed a T cell–dominated inflammatory process thought to be autoimmune in origin, according to Herwig Strik, MD, of the department of neurology at Philipps University of Marburg (Germany), and his colleagues (Eur J Cancer. 2017 Oct 16. doi: 10.1016/j.ejca.2017.09.026).

After the patient stopped taking nivolumab and the inflammatory process was treated, his “clinical neurological and radiological status remained stable but disabling with fluctuating dysarthria and ataxia,” Dr. Strik and his colleagues wrote.

“Since these novel anticancer agents are increasingly used, this severe complication should be recognized soon and treatment should be terminated to avoid chronification,” they said in the report.

Nivolumab and other checkpoint inhibitors are known to have autoimmune side effects in some cases that can affect the pulmonary, gastrointestinal, and endocrine systems, the authors said.

Several previous case reports have detailed encephalitis occurring in cancer patients receiving nivolumab, the combination of nivolumab plus the immune checkpoint inhibitor ipilimumab, or ipilimumab alone. The authors said they believe that this case report is the first to describe multifocal CNS inflammation following nivolumab treatment for systemic lymphoma.

The patient was diagnosed with B-cell non-Hodgkin lymphoma in 2005, according to the case report. He was first treated in 2009 with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), followed by stem cell apheresis, radioimmunotherapy, and rituximab; he then received R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) in August 2014, followed by autologous stem cell transplantation in October of that year. The patient started nivolumab maintenance therapy in February 2015 but started experiencing neurological symptoms that eventually led to ending nivolumab treatment in September 2015.

The patient’s lymphoma relapsed in June 2016. “The disabling neurological symptoms and his personal situation, however, worsened the patient’s depressive symptoms so severely that he went abroad to commit assisted suicide,” wrote Dr. Strik and his colleagues.

The authors proposed the term “immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD)” to describe the inflammatory condition described in the case report.

They declared no conflicts of interest related to the case report and did not receive grant support for conducting the research described in it.

Autoimmune encephalitis may be a potentially severe complication of immune checkpoint inhibitor therapy, a case report suggests.

The recently published report describes a 53-year-old man with B-cell non-Hodgkin lymphoma who presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with the immune checkpoint inhibitor nivolumab.

Neuropathologic examination of a biopsied brain lesion found on cranial MRI showed a T cell–dominated inflammatory process thought to be autoimmune in origin, according to Herwig Strik, MD, of the department of neurology at Philipps University of Marburg (Germany), and his colleagues (Eur J Cancer. 2017 Oct 16. doi: 10.1016/j.ejca.2017.09.026).

After the patient stopped taking nivolumab and the inflammatory process was treated, his “clinical neurological and radiological status remained stable but disabling with fluctuating dysarthria and ataxia,” Dr. Strik and his colleagues wrote.

“Since these novel anticancer agents are increasingly used, this severe complication should be recognized soon and treatment should be terminated to avoid chronification,” they said in the report.

Nivolumab and other checkpoint inhibitors are known to have autoimmune side effects in some cases that can affect the pulmonary, gastrointestinal, and endocrine systems, the authors said.

Several previous case reports have detailed encephalitis occurring in cancer patients receiving nivolumab, the combination of nivolumab plus the immune checkpoint inhibitor ipilimumab, or ipilimumab alone. The authors said they believe that this case report is the first to describe multifocal CNS inflammation following nivolumab treatment for systemic lymphoma.

The patient was diagnosed with B-cell non-Hodgkin lymphoma in 2005, according to the case report. He was first treated in 2009 with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), followed by stem cell apheresis, radioimmunotherapy, and rituximab; he then received R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) in August 2014, followed by autologous stem cell transplantation in October of that year. The patient started nivolumab maintenance therapy in February 2015 but started experiencing neurological symptoms that eventually led to ending nivolumab treatment in September 2015.

The patient’s lymphoma relapsed in June 2016. “The disabling neurological symptoms and his personal situation, however, worsened the patient’s depressive symptoms so severely that he went abroad to commit assisted suicide,” wrote Dr. Strik and his colleagues.

The authors proposed the term “immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD)” to describe the inflammatory condition described in the case report.

They declared no conflicts of interest related to the case report and did not receive grant support for conducting the research described in it.

Well-known for its typical presentation, classic herpes zoster (HZ) presents as a dermatomal eruption of painful erythematous papules that evolve into grouped vesicles or bullae.^1,2 Thereafter, the lesions can become pustular or hemorrhagic.¹ Although the diagnosis most often is made clinically, confirmatory techniques for diagnosis include viral culture, direct fluorescent antibody testing, or polymerase chain reaction (PCR) assay.^1,3

The main risk factor for HZ is advanced age, most commonly affecting elderly patients.⁴ It is hypothesized that a physiological decline in varicella-zoster virus (VZV)–specific cell-mediated immunity among elderly individuals helps trigger reactivation of the virus within the dorsal root ganglion.^1,5 Similarly affected are immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection, due to suppression of T cells immune to VZV,^1,5 as well as immunosuppressed transplant recipients who have diminished VZV-specific cellular responses and VZV IgG antibody avidity.⁶

Secondary complications of VZV infection (eg, postherpetic neuralgia, bacterial superinfection progressing to cellulitis) lead to increased morbidity.^7,8 Disseminated cutaneous HZ is another grave complication of VZV infection and almost exclusively occurs with immunosuppression.^1,8 It manifests as an eruption of at least 20 widespread vesiculobullous lesions outside the primary and adjacent dermatomes.⁶ Immunocompromised patients also are at increased risk for visceral involvement of VZV infection, which may affect vital organs such as the brain, liver, or lungs.^7,8 Given the atypical presentation of VZV infection among some immunocompromised individuals, these patients are at increased risk for diagnostic delay and morbidity in the absence of high clinical suspicion for disseminated HZ.

Case Reports

Patient 1
A 52-year-old man developed a painless nonpruritic rash on the left leg of 4 days’ duration. It initially appeared as an erythematous maculopapular rash on the medial aspect of the left knee without any prodromal symptoms. Over the next 4 days, erythematous vesicles developed that progressed to pustules, and the rash spread both proximally and distally along the left leg. Shortly following hospital admission, he developed a fever (temperature, 38.4°C). His medical history included alcoholic liver cirrhosis and AIDS, with a CD4 count of 174 cells/µL (reference range, 500–1500 cells/µL). He had been taking antiretroviral therapy (abacavir-lamivudine and dolutegravir) and prophylaxis against opportunistic infections (dapsone and itraconazole).

Physical examination was remarkable for an extensive rash consisting of multiple 1-cm clusters of approximately 40 pustules each scattered in a nondermatomal distribution along the left leg (Figure 1). Many of the vesicles were confluent with an erythematous base and were in different stages of evolution with some crusted and others emanating a thin liquid exudate. The lesions were nontender and without notable induration. The leg was warm and edematous.

Clinically, the differential diagnosis included disseminated HZ with bacterial superinfection, Vibrio vulnificus infection, and herpes simplex virus (HSV) infection. The patient was treated with intravenous vancomycin, levofloxacin, and acyclovir, and no new lesions developed throughout the course of treatment. On this regimen, his fever resolved after 1 day, the active lesions began to crust, and the edema and erythema diminished. Results of bacterial cultures and plasma PCR and IgM for HSV types 1 and 2 were negative. Viral culture results were negative, but a PCR assay for VZV was positive, reflective of acute reactivation of VZV.

Patient 2
A 63-year-old man developed a pruritic burning rash involving the face, trunk, arms, and legs of 6 days’ duration. His medical history included a heart transplant 6 months prior to presentation, type 2 diabetes mellitus, and chronic kidney disease. He was taking antirejection therapy with mycophenolate mofetil (MMF), prednisone, and tacrolimus.

Physical examination was remarkable for an extensive rash consisting of clusters of 1- to 2-mm vesicles scattered in a nondermatomal pattern. Isolated vesicles involved the forehead, nose, and left ear, and diffuse vesicles with a relatively symmetric distribution were scattered across the back, chest, and proximal and distal arms and legs (Figure 2). Many of the vesicles had an associated overlying crust with hemorrhage. Some of the vesicles coalesced with central necrotic plaques.

Given a clinical suspicion for disseminated HZ, therapy with oral valacyclovir was initiated. Two punch biopsies were consistent with herpesvirus cytopathic changes. Multiple sections demonstrated ulceration as well as acantholysis and necrosis of keratinocytes with multinucleation and margination of chromatin. There was an intense lichenoid and perivascular lymphocytic infiltrate in the dermis. Immunohistochemistry staining was positive for VZV and negative for HSV, indicating acute reactivation of VZV (Figure 3). Upon completion of an antiviral regimen, the patient returned to clinic with healed crusted lesions.

Comment

Frequently, the clinical features of HZ in immunocompromised patients mirror those in immunocompetent hosts.⁸ However, each of our 2 patients developed an unusual presentation of atypical generalized HZ.⁷ In this clinical variant, lesions develop along a single dermatome, then a diffuse vesicular eruption subsequently develops without dermatomal localization. These lesions can be chronic, persisting for months or years.⁷

The classic clinical presentation of HZ is distinct and often is readily diagnosed by visual inspection.⁷ However, atypical presentations and their associated complications can pose diagnostic and therapeutic challenges.⁷ Painless HZ lesions in a nondermatomal pattern were described in a patient who also had AIDS.⁹ Interestingly, multiple reports have found that patients with a severe but painless rash are less likely to have experienced a viral prodrome consisting of hyperesthesia, paresthesia, or pruritus.^2,10 This observation suggests that lack of a prodrome, as in the case of patient 1 in our report, may aid in the recognition of painless HZ. Because of these atypical presentations, laboratory testing is even more important than in immunocompetent hosts, as diagnosis may be more difficult to establish on clinical presentation alone.

Several studies^11-32 have evaluated modalities for treatment and prophylaxis for disseminated HZ in immunocompromised hosts, given its increased risk and potentially fatal complications in this population. The current guidelines in patients with HIV/AIDS, solid organ transplantation (SOT), and hematopoietic stem cell transplantation (HSCT) are summarized in the eTable.

HIV/AIDS Patients
Given their efficacy and low rate of toxicity, oral acyclovir, valacyclovir, and famciclovir are recommended treatment options for HIV patients with localized, mild, dermatomal HZ.¹¹ Two exceptions include HZ ophthalmicus and Ramsay Hunt syndrome for which some experts recommend intravenous acyclovir given the risk for vision loss and facial palsy, respectively. Intravenous acyclovir often is the drug of choice for treating complicated, disseminated, or severe HZ in HIV-infected patients, though prospective efficacy data remain limited.¹¹

With regard to prevention of infection, a large randomized trial in 2016 found that acyclovir prophylaxis resulted in a 68% reduction in HZ over 2 years among HIV patients.¹² Despite data that acyclovir may be effective for this purpose, long-term antiviral prophylaxis is not routinely recommended for HZ,^11,13 as it has been linked to rare cases of acyclovir-resistant HZ in HIV patients.^14,15 However, antiviral prophylaxis against HSV type 2 reactivation in HIV patients also confers protection against VZV reactivation.^11,12

Solid Organ Transplantation
Localized, mild to moderately severe dermatomal HZ can be treated with oral acyclovir, valacyclovir, or famciclovir. As in HIV patients, SOT patients with severe, disseminated, or complicated HZ should receive IV acyclovir.¹¹ In the first 3 to 6 months following the procedure, SOT patients receive cytomegalovirus prophylaxis with ganciclovir or valgan-ciclovir, which also provides protection against HZ.^13-18 For patients not receiving cytomegalovirus prophylaxis, HSV prophylaxis with oral acyclovir or valacyclovir is given for at least the first month after transplantation, which also confers protection against HZ.^16,19 Antiviral therapy is critical during the early posttransplantation period when patients are most severely immunosuppressed and thus have the highest risk for VZV-associated complications.²⁰ Although immunosuppression is lifelong in most SOT recipients, there is insufficient evidence for extending prophylaxis beyond 6 months.^16,21

As a possible risk factor for HZ,²² MMF use is another consideration among SOT patients, similar to patient 2 in our report. A 2003 observational study supported withdrawal of MMF therapy during active VZV infection due to clinical observation of an association with HZ.²³ However, a multicenter, randomized, controlled trial reported no cases of HZ in renal transplant recipients on MMF.²⁴ Additionally, MMF has been observed to enhance the antiviral activity of acyclovir, at least in vitro.²⁵ Given the lack of evidence of MMF as a risk factor for HZ, there is insufficient evidence for cessation of use during VZVreactivation in SOT patients.

Hematopoietic Stem Cell Transplantation
The preferred agents for treatment of localized mild dermatomal HZ are oral acyclovir or valacyclovir, as data on the safety and efficacy of famciclovir among HSCT recipients are limited.^13,26 Patients should receive antiviral prophylaxis with one of these agents during the first year following allogeneic or autologous HSCT. This 1-year course has proven highly effective in reducing HZ in the first year following transplantation when most severe cases occur,^21,26-29 and it has been associated with a persistently decreased risk for HZ even after discontinuation.²¹ Prophylaxis may be continued beyond 1 year in allogeneic HSCT recipients experiencing graft-versus-host disease who should receive acyclovir until 6 months after the end of immunosuppressive therapy.^21,26

Vaccination remains a potential strategy to reduce the incidence of HZ in this patient population. A heat-inactivated vaccine administered within the first 3 months after the procedure has been shown to be safe among autologous and allogeneic HSCT patients.^30,31 The vaccine notably reduced the incidence of HZ in patients who underwent autologous HSCT,³² but no known data are available on its clinical efficacy in allogeneic HSCT patients. Accordingly, there are no known official recommendations to date regarding vaccine use in these patient populations.²⁶

Conclusion

It is incumbent upon clinicians to recognize the spectrum of atypical presentations of HZ and maintain a low threshold for performing appropriate diagnostic or confirmatory studies among at-risk patients with impaired immune function. Disseminated HZ can have potentially life-threatening visceral complications such as encephalitis, hepatitis, or pneumonitis.^7,8 As such, an understanding of prevention and treatment modalities for VZV infection among immunocompromised patients is critical. Because the morbidity associated with complications of VZV infection is substantial and the risks associated with antiviral agents are minimal, antiviral prophylaxis is recommended for 6 months following SOT or 1 year following HSCT, and prompt treatment is warranted in cases of reasonable clinical suspicion for HZ.

Acknowledgment
The authors gratefully acknowledge the generosity of our patients in permitting photography of their skin findings for the furthering of medical education.

Well-known for its typical presentation, classic herpes zoster (HZ) presents as a dermatomal eruption of painful erythematous papules that evolve into grouped vesicles or bullae.^1,2 Thereafter, the lesions can become pustular or hemorrhagic.¹ Although the diagnosis most often is made clinically, confirmatory techniques for diagnosis include viral culture, direct fluorescent antibody testing, or polymerase chain reaction (PCR) assay.^1,3

The main risk factor for HZ is advanced age, most commonly affecting elderly patients.⁴ It is hypothesized that a physiological decline in varicella-zoster virus (VZV)–specific cell-mediated immunity among elderly individuals helps trigger reactivation of the virus within the dorsal root ganglion.^1,5 Similarly affected are immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection, due to suppression of T cells immune to VZV,^1,5 as well as immunosuppressed transplant recipients who have diminished VZV-specific cellular responses and VZV IgG antibody avidity.⁶

Secondary complications of VZV infection (eg, postherpetic neuralgia, bacterial superinfection progressing to cellulitis) lead to increased morbidity.^7,8 Disseminated cutaneous HZ is another grave complication of VZV infection and almost exclusively occurs with immunosuppression.^1,8 It manifests as an eruption of at least 20 widespread vesiculobullous lesions outside the primary and adjacent dermatomes.⁶ Immunocompromised patients also are at increased risk for visceral involvement of VZV infection, which may affect vital organs such as the brain, liver, or lungs.^7,8 Given the atypical presentation of VZV infection among some immunocompromised individuals, these patients are at increased risk for diagnostic delay and morbidity in the absence of high clinical suspicion for disseminated HZ.

Case Reports

Patient 1
A 52-year-old man developed a painless nonpruritic rash on the left leg of 4 days’ duration. It initially appeared as an erythematous maculopapular rash on the medial aspect of the left knee without any prodromal symptoms. Over the next 4 days, erythematous vesicles developed that progressed to pustules, and the rash spread both proximally and distally along the left leg. Shortly following hospital admission, he developed a fever (temperature, 38.4°C). His medical history included alcoholic liver cirrhosis and AIDS, with a CD4 count of 174 cells/µL (reference range, 500–1500 cells/µL). He had been taking antiretroviral therapy (abacavir-lamivudine and dolutegravir) and prophylaxis against opportunistic infections (dapsone and itraconazole).

Physical examination was remarkable for an extensive rash consisting of multiple 1-cm clusters of approximately 40 pustules each scattered in a nondermatomal distribution along the left leg (Figure 1). Many of the vesicles were confluent with an erythematous base and were in different stages of evolution with some crusted and others emanating a thin liquid exudate. The lesions were nontender and without notable induration. The leg was warm and edematous.

Clinically, the differential diagnosis included disseminated HZ with bacterial superinfection, Vibrio vulnificus infection, and herpes simplex virus (HSV) infection. The patient was treated with intravenous vancomycin, levofloxacin, and acyclovir, and no new lesions developed throughout the course of treatment. On this regimen, his fever resolved after 1 day, the active lesions began to crust, and the edema and erythema diminished. Results of bacterial cultures and plasma PCR and IgM for HSV types 1 and 2 were negative. Viral culture results were negative, but a PCR assay for VZV was positive, reflective of acute reactivation of VZV.

Patient 2
A 63-year-old man developed a pruritic burning rash involving the face, trunk, arms, and legs of 6 days’ duration. His medical history included a heart transplant 6 months prior to presentation, type 2 diabetes mellitus, and chronic kidney disease. He was taking antirejection therapy with mycophenolate mofetil (MMF), prednisone, and tacrolimus.

Physical examination was remarkable for an extensive rash consisting of clusters of 1- to 2-mm vesicles scattered in a nondermatomal pattern. Isolated vesicles involved the forehead, nose, and left ear, and diffuse vesicles with a relatively symmetric distribution were scattered across the back, chest, and proximal and distal arms and legs (Figure 2). Many of the vesicles had an associated overlying crust with hemorrhage. Some of the vesicles coalesced with central necrotic plaques.

Given a clinical suspicion for disseminated HZ, therapy with oral valacyclovir was initiated. Two punch biopsies were consistent with herpesvirus cytopathic changes. Multiple sections demonstrated ulceration as well as acantholysis and necrosis of keratinocytes with multinucleation and margination of chromatin. There was an intense lichenoid and perivascular lymphocytic infiltrate in the dermis. Immunohistochemistry staining was positive for VZV and negative for HSV, indicating acute reactivation of VZV (Figure 3). Upon completion of an antiviral regimen, the patient returned to clinic with healed crusted lesions.

Comment

Frequently, the clinical features of HZ in immunocompromised patients mirror those in immunocompetent hosts.⁸ However, each of our 2 patients developed an unusual presentation of atypical generalized HZ.⁷ In this clinical variant, lesions develop along a single dermatome, then a diffuse vesicular eruption subsequently develops without dermatomal localization. These lesions can be chronic, persisting for months or years.⁷

The classic clinical presentation of HZ is distinct and often is readily diagnosed by visual inspection.⁷ However, atypical presentations and their associated complications can pose diagnostic and therapeutic challenges.⁷ Painless HZ lesions in a nondermatomal pattern were described in a patient who also had AIDS.⁹ Interestingly, multiple reports have found that patients with a severe but painless rash are less likely to have experienced a viral prodrome consisting of hyperesthesia, paresthesia, or pruritus.^2,10 This observation suggests that lack of a prodrome, as in the case of patient 1 in our report, may aid in the recognition of painless HZ. Because of these atypical presentations, laboratory testing is even more important than in immunocompetent hosts, as diagnosis may be more difficult to establish on clinical presentation alone.

Several studies^11-32 have evaluated modalities for treatment and prophylaxis for disseminated HZ in immunocompromised hosts, given its increased risk and potentially fatal complications in this population. The current guidelines in patients with HIV/AIDS, solid organ transplantation (SOT), and hematopoietic stem cell transplantation (HSCT) are summarized in the eTable.

HIV/AIDS Patients
Given their efficacy and low rate of toxicity, oral acyclovir, valacyclovir, and famciclovir are recommended treatment options for HIV patients with localized, mild, dermatomal HZ.¹¹ Two exceptions include HZ ophthalmicus and Ramsay Hunt syndrome for which some experts recommend intravenous acyclovir given the risk for vision loss and facial palsy, respectively. Intravenous acyclovir often is the drug of choice for treating complicated, disseminated, or severe HZ in HIV-infected patients, though prospective efficacy data remain limited.¹¹

With regard to prevention of infection, a large randomized trial in 2016 found that acyclovir prophylaxis resulted in a 68% reduction in HZ over 2 years among HIV patients.¹² Despite data that acyclovir may be effective for this purpose, long-term antiviral prophylaxis is not routinely recommended for HZ,^11,13 as it has been linked to rare cases of acyclovir-resistant HZ in HIV patients.^14,15 However, antiviral prophylaxis against HSV type 2 reactivation in HIV patients also confers protection against VZV reactivation.^11,12

Solid Organ Transplantation
Localized, mild to moderately severe dermatomal HZ can be treated with oral acyclovir, valacyclovir, or famciclovir. As in HIV patients, SOT patients with severe, disseminated, or complicated HZ should receive IV acyclovir.¹¹ In the first 3 to 6 months following the procedure, SOT patients receive cytomegalovirus prophylaxis with ganciclovir or valgan-ciclovir, which also provides protection against HZ.^13-18 For patients not receiving cytomegalovirus prophylaxis, HSV prophylaxis with oral acyclovir or valacyclovir is given for at least the first month after transplantation, which also confers protection against HZ.^16,19 Antiviral therapy is critical during the early posttransplantation period when patients are most severely immunosuppressed and thus have the highest risk for VZV-associated complications.²⁰ Although immunosuppression is lifelong in most SOT recipients, there is insufficient evidence for extending prophylaxis beyond 6 months.^16,21

As a possible risk factor for HZ,²² MMF use is another consideration among SOT patients, similar to patient 2 in our report. A 2003 observational study supported withdrawal of MMF therapy during active VZV infection due to clinical observation of an association with HZ.²³ However, a multicenter, randomized, controlled trial reported no cases of HZ in renal transplant recipients on MMF.²⁴ Additionally, MMF has been observed to enhance the antiviral activity of acyclovir, at least in vitro.²⁵ Given the lack of evidence of MMF as a risk factor for HZ, there is insufficient evidence for cessation of use during VZVreactivation in SOT patients.

Hematopoietic Stem Cell Transplantation
The preferred agents for treatment of localized mild dermatomal HZ are oral acyclovir or valacyclovir, as data on the safety and efficacy of famciclovir among HSCT recipients are limited.^13,26 Patients should receive antiviral prophylaxis with one of these agents during the first year following allogeneic or autologous HSCT. This 1-year course has proven highly effective in reducing HZ in the first year following transplantation when most severe cases occur,^21,26-29 and it has been associated with a persistently decreased risk for HZ even after discontinuation.²¹ Prophylaxis may be continued beyond 1 year in allogeneic HSCT recipients experiencing graft-versus-host disease who should receive acyclovir until 6 months after the end of immunosuppressive therapy.^21,26

Vaccination remains a potential strategy to reduce the incidence of HZ in this patient population. A heat-inactivated vaccine administered within the first 3 months after the procedure has been shown to be safe among autologous and allogeneic HSCT patients.^30,31 The vaccine notably reduced the incidence of HZ in patients who underwent autologous HSCT,³² but no known data are available on its clinical efficacy in allogeneic HSCT patients. Accordingly, there are no known official recommendations to date regarding vaccine use in these patient populations.²⁶

Conclusion

It is incumbent upon clinicians to recognize the spectrum of atypical presentations of HZ and maintain a low threshold for performing appropriate diagnostic or confirmatory studies among at-risk patients with impaired immune function. Disseminated HZ can have potentially life-threatening visceral complications such as encephalitis, hepatitis, or pneumonitis.^7,8 As such, an understanding of prevention and treatment modalities for VZV infection among immunocompromised patients is critical. Because the morbidity associated with complications of VZV infection is substantial and the risks associated with antiviral agents are minimal, antiviral prophylaxis is recommended for 6 months following SOT or 1 year following HSCT, and prompt treatment is warranted in cases of reasonable clinical suspicion for HZ.

Acknowledgment
The authors gratefully acknowledge the generosity of our patients in permitting photography of their skin findings for the furthering of medical education.

Well-known for its typical presentation, classic herpes zoster (HZ) presents as a dermatomal eruption of painful erythematous papules that evolve into grouped vesicles or bullae.^1,2 Thereafter, the lesions can become pustular or hemorrhagic.¹ Although the diagnosis most often is made clinically, confirmatory techniques for diagnosis include viral culture, direct fluorescent antibody testing, or polymerase chain reaction (PCR) assay.^1,3

The main risk factor for HZ is advanced age, most commonly affecting elderly patients.⁴ It is hypothesized that a physiological decline in varicella-zoster virus (VZV)–specific cell-mediated immunity among elderly individuals helps trigger reactivation of the virus within the dorsal root ganglion.^1,5 Similarly affected are immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection, due to suppression of T cells immune to VZV,^1,5 as well as immunosuppressed transplant recipients who have diminished VZV-specific cellular responses and VZV IgG antibody avidity.⁶

Secondary complications of VZV infection (eg, postherpetic neuralgia, bacterial superinfection progressing to cellulitis) lead to increased morbidity.^7,8 Disseminated cutaneous HZ is another grave complication of VZV infection and almost exclusively occurs with immunosuppression.^1,8 It manifests as an eruption of at least 20 widespread vesiculobullous lesions outside the primary and adjacent dermatomes.⁶ Immunocompromised patients also are at increased risk for visceral involvement of VZV infection, which may affect vital organs such as the brain, liver, or lungs.^7,8 Given the atypical presentation of VZV infection among some immunocompromised individuals, these patients are at increased risk for diagnostic delay and morbidity in the absence of high clinical suspicion for disseminated HZ.

Case Reports

Patient 1
A 52-year-old man developed a painless nonpruritic rash on the left leg of 4 days’ duration. It initially appeared as an erythematous maculopapular rash on the medial aspect of the left knee without any prodromal symptoms. Over the next 4 days, erythematous vesicles developed that progressed to pustules, and the rash spread both proximally and distally along the left leg. Shortly following hospital admission, he developed a fever (temperature, 38.4°C). His medical history included alcoholic liver cirrhosis and AIDS, with a CD4 count of 174 cells/µL (reference range, 500–1500 cells/µL). He had been taking antiretroviral therapy (abacavir-lamivudine and dolutegravir) and prophylaxis against opportunistic infections (dapsone and itraconazole).

Physical examination was remarkable for an extensive rash consisting of multiple 1-cm clusters of approximately 40 pustules each scattered in a nondermatomal distribution along the left leg (Figure 1). Many of the vesicles were confluent with an erythematous base and were in different stages of evolution with some crusted and others emanating a thin liquid exudate. The lesions were nontender and without notable induration. The leg was warm and edematous.

Clinically, the differential diagnosis included disseminated HZ with bacterial superinfection, Vibrio vulnificus infection, and herpes simplex virus (HSV) infection. The patient was treated with intravenous vancomycin, levofloxacin, and acyclovir, and no new lesions developed throughout the course of treatment. On this regimen, his fever resolved after 1 day, the active lesions began to crust, and the edema and erythema diminished. Results of bacterial cultures and plasma PCR and IgM for HSV types 1 and 2 were negative. Viral culture results were negative, but a PCR assay for VZV was positive, reflective of acute reactivation of VZV.

Patient 2
A 63-year-old man developed a pruritic burning rash involving the face, trunk, arms, and legs of 6 days’ duration. His medical history included a heart transplant 6 months prior to presentation, type 2 diabetes mellitus, and chronic kidney disease. He was taking antirejection therapy with mycophenolate mofetil (MMF), prednisone, and tacrolimus.

Physical examination was remarkable for an extensive rash consisting of clusters of 1- to 2-mm vesicles scattered in a nondermatomal pattern. Isolated vesicles involved the forehead, nose, and left ear, and diffuse vesicles with a relatively symmetric distribution were scattered across the back, chest, and proximal and distal arms and legs (Figure 2). Many of the vesicles had an associated overlying crust with hemorrhage. Some of the vesicles coalesced with central necrotic plaques.

Given a clinical suspicion for disseminated HZ, therapy with oral valacyclovir was initiated. Two punch biopsies were consistent with herpesvirus cytopathic changes. Multiple sections demonstrated ulceration as well as acantholysis and necrosis of keratinocytes with multinucleation and margination of chromatin. There was an intense lichenoid and perivascular lymphocytic infiltrate in the dermis. Immunohistochemistry staining was positive for VZV and negative for HSV, indicating acute reactivation of VZV (Figure 3). Upon completion of an antiviral regimen, the patient returned to clinic with healed crusted lesions.

Comment

Frequently, the clinical features of HZ in immunocompromised patients mirror those in immunocompetent hosts.⁸ However, each of our 2 patients developed an unusual presentation of atypical generalized HZ.⁷ In this clinical variant, lesions develop along a single dermatome, then a diffuse vesicular eruption subsequently develops without dermatomal localization. These lesions can be chronic, persisting for months or years.⁷

The classic clinical presentation of HZ is distinct and often is readily diagnosed by visual inspection.⁷ However, atypical presentations and their associated complications can pose diagnostic and therapeutic challenges.⁷ Painless HZ lesions in a nondermatomal pattern were described in a patient who also had AIDS.⁹ Interestingly, multiple reports have found that patients with a severe but painless rash are less likely to have experienced a viral prodrome consisting of hyperesthesia, paresthesia, or pruritus.^2,10 This observation suggests that lack of a prodrome, as in the case of patient 1 in our report, may aid in the recognition of painless HZ. Because of these atypical presentations, laboratory testing is even more important than in immunocompetent hosts, as diagnosis may be more difficult to establish on clinical presentation alone.

Several studies^11-32 have evaluated modalities for treatment and prophylaxis for disseminated HZ in immunocompromised hosts, given its increased risk and potentially fatal complications in this population. The current guidelines in patients with HIV/AIDS, solid organ transplantation (SOT), and hematopoietic stem cell transplantation (HSCT) are summarized in the eTable.

HIV/AIDS Patients
Given their efficacy and low rate of toxicity, oral acyclovir, valacyclovir, and famciclovir are recommended treatment options for HIV patients with localized, mild, dermatomal HZ.¹¹ Two exceptions include HZ ophthalmicus and Ramsay Hunt syndrome for which some experts recommend intravenous acyclovir given the risk for vision loss and facial palsy, respectively. Intravenous acyclovir often is the drug of choice for treating complicated, disseminated, or severe HZ in HIV-infected patients, though prospective efficacy data remain limited.¹¹

With regard to prevention of infection, a large randomized trial in 2016 found that acyclovir prophylaxis resulted in a 68% reduction in HZ over 2 years among HIV patients.¹² Despite data that acyclovir may be effective for this purpose, long-term antiviral prophylaxis is not routinely recommended for HZ,^11,13 as it has been linked to rare cases of acyclovir-resistant HZ in HIV patients.^14,15 However, antiviral prophylaxis against HSV type 2 reactivation in HIV patients also confers protection against VZV reactivation.^11,12

Solid Organ Transplantation
Localized, mild to moderately severe dermatomal HZ can be treated with oral acyclovir, valacyclovir, or famciclovir. As in HIV patients, SOT patients with severe, disseminated, or complicated HZ should receive IV acyclovir.¹¹ In the first 3 to 6 months following the procedure, SOT patients receive cytomegalovirus prophylaxis with ganciclovir or valgan-ciclovir, which also provides protection against HZ.^13-18 For patients not receiving cytomegalovirus prophylaxis, HSV prophylaxis with oral acyclovir or valacyclovir is given for at least the first month after transplantation, which also confers protection against HZ.^16,19 Antiviral therapy is critical during the early posttransplantation period when patients are most severely immunosuppressed and thus have the highest risk for VZV-associated complications.²⁰ Although immunosuppression is lifelong in most SOT recipients, there is insufficient evidence for extending prophylaxis beyond 6 months.^16,21

As a possible risk factor for HZ,²² MMF use is another consideration among SOT patients, similar to patient 2 in our report. A 2003 observational study supported withdrawal of MMF therapy during active VZV infection due to clinical observation of an association with HZ.²³ However, a multicenter, randomized, controlled trial reported no cases of HZ in renal transplant recipients on MMF.²⁴ Additionally, MMF has been observed to enhance the antiviral activity of acyclovir, at least in vitro.²⁵ Given the lack of evidence of MMF as a risk factor for HZ, there is insufficient evidence for cessation of use during VZVreactivation in SOT patients.

Hematopoietic Stem Cell Transplantation
The preferred agents for treatment of localized mild dermatomal HZ are oral acyclovir or valacyclovir, as data on the safety and efficacy of famciclovir among HSCT recipients are limited.^13,26 Patients should receive antiviral prophylaxis with one of these agents during the first year following allogeneic or autologous HSCT. This 1-year course has proven highly effective in reducing HZ in the first year following transplantation when most severe cases occur,^21,26-29 and it has been associated with a persistently decreased risk for HZ even after discontinuation.²¹ Prophylaxis may be continued beyond 1 year in allogeneic HSCT recipients experiencing graft-versus-host disease who should receive acyclovir until 6 months after the end of immunosuppressive therapy.^21,26

Vaccination remains a potential strategy to reduce the incidence of HZ in this patient population. A heat-inactivated vaccine administered within the first 3 months after the procedure has been shown to be safe among autologous and allogeneic HSCT patients.^30,31 The vaccine notably reduced the incidence of HZ in patients who underwent autologous HSCT,³² but no known data are available on its clinical efficacy in allogeneic HSCT patients. Accordingly, there are no known official recommendations to date regarding vaccine use in these patient populations.²⁶

Conclusion

It is incumbent upon clinicians to recognize the spectrum of atypical presentations of HZ and maintain a low threshold for performing appropriate diagnostic or confirmatory studies among at-risk patients with impaired immune function. Disseminated HZ can have potentially life-threatening visceral complications such as encephalitis, hepatitis, or pneumonitis.^7,8 As such, an understanding of prevention and treatment modalities for VZV infection among immunocompromised patients is critical. Because the morbidity associated with complications of VZV infection is substantial and the risks associated with antiviral agents are minimal, antiviral prophylaxis is recommended for 6 months following SOT or 1 year following HSCT, and prompt treatment is warranted in cases of reasonable clinical suspicion for HZ.

Acknowledgment
The authors gratefully acknowledge the generosity of our patients in permitting photography of their skin findings for the furthering of medical education.

An environmental pathogen, Mycobacterium marinum can cause cutaneous infection when traumatized skin is exposed to fresh, brackish, or salt water. Fishing, aquarium cleaning, and aquatic recreational activities are risk factors for infection.^1,2 Diagnosis often is delayed and is made several weeks or even months after initial symptoms appear.³ Due to the protracted clinical course, patients may not recall the initial exposure, contributing to the delay in diagnosis and initiation of appropriate treatment. It is not uncommon for patients with M marinum infection to be initially treated with antibiotics or antifungal drugs.

We present a review of 5 patients who were diagnosed with M marinum infection at our institution between January 2003 and March 2013.

Methods

This study was conducted at Henry Ford Hospital, a 900-bed tertiary care center in Detroit, Michigan. Patients who had cultures positive for M marinum between January 2003 and March 2013 were identified using the institution’s laboratory database. Medical records were reviewed, and relevant demographic, epidemiologic, and clinical data, including initial clinical presentation, alternative diagnoses, time between initial presentation and definitive diagnosis, and specific treatment, were recorded.

Results

We identified 5 patients who were diagnosed with culture-confirmed M marinum skin infections during the study period: 3 men and 2 women aged 43 to 72 years (Table 1). Two patients had diabetes mellitus and 1 had hepatitis C virus. None had classic immunosuppression. On repeated questioning after the diagnosis was established, all 5 patients reported that they kept a home aquarium, and all recalled mild trauma to the hand prior to the onset of symptoms; however, none of the patients initially linked the minor skin injury to the subsequent infection.

All 5 patients initially presented with erythema and swelling at the site of the injury, which evolved into inflammatory nodules that progressed proximally up to the arm despite empiric treatment with antibiotics active against streptococci and staphylococci (Figures 1 and 2). Three patients also received empiric antifungal therapy due to suspicion of sporotrichosis.

Skin biopsies were performed on 4 patients, and incision and drainage of purulent material was performed on the fifth patient. Histopathologic examination revealed granulomatous inflammation in 3 patients. Stains for acid-fast bacilli were positive in all 5 patients. Definitive diagnosis of the organism was confirmed by growth of M marinum within 11 to 40 days from the tissue in 4 patients and purulent material in the fifth patient. Susceptibility testing was performed on only 1 of the 5 isolates and showed that the organism was susceptible to amikacin, clarithromycin, doxycycline, ethambutol, rifampin, and trimethoprim-sulfamethoxazole (TMP-SMX).

The mean time from initial presentation to initiation of appropriate therapy for M marinum infection was 91 days (range, 21–245 days). Several different treatment regimens were used. All patients received either doxycycline or minocycline with or without a macrolide. Two also received other agents (TMP-SMX or ethambutol). Treatment duration varied from 2 to 6 months in 4 patients, and all 4 had complete resolution of the lesions; 1 patient was lost to follow-up.

Comment

Diagnosing the Infection
Diagnosis of M marinum infection remains problematic. In the 5 patients included in this study, the time between initial onset of symptoms and diagnosis of M marinum infection was delayed, as has been noted in other reports.^4-7 Delays as long as 2 years before the diagnosis is made have been described.⁷ The clinical presentation of cutaneous infection with M marinum varies, which may delay diagnosis. Nodular lymphangitis is classic, but papules, pustules, ulcers, inflammatory plaques, and single nodules also can occur.^1,2 Lymphadenopathy may or may not be present.^4,8,9 The differential diagnosis is broad and includes infection by other nontuberculous mycobacteria such as Mycobacterium chelonae; Mycobacterium fortuitum; Nocardia species, especially Nocardia brasiliensis; Francisella tularensis; Sporothrix schenckii; and Leishmania species. It is not surprising that 4 patients in our study were initially treated for a gram-positive bacterial infection and 3 were treated for a fungal infection before the diagnosis of M marinum was made. Distinctive features that may help to differentiate these infections are summarized in Table 2.

We found that the main cause of delayed diagnosis was the failure of physicians to obtain a thorough history regarding patients’ recreational activities and animal exposure. Patients often do not associate a remote aquatic exposure with their symptoms and will not volunteer this information unless directly asked.^2,10 It was only after repeated questioning in all of these patients that they recounted prior trauma to the involved hand related to the aquarium.

Biopsy and Culture
Histopathologic examination of material from a biopsied lesion can give an early clue that a mycobacterial infection might be involved. Biopsy can reveal either noncaseating or necrotizing granulomas that have larger numbers of neutrophils in addition to lymphocytes and macrophages. Giant cells often are noted.^5,9,11 Organisms can be seen with the use of a tissue acid-fast stain, but species cannot be differentiated by acid-fast staining.¹² However, the sensitivity of acid-fast stains on biopsy material is low.^3,13,14

Culture of the involved tissue is crucial for establishing the diagnosis of this infection. However, the rate of growth of M marinum is slow. Temperature requirements for incubation and delay in transporting specimens to the laboratory can lead to bacterial overgrowth, resulting in the inability to recover M marinum from the culture.¹³Mycobacterium marinum grows preferentially between 28°C and 32°C, and growth is limited at temperatures above 33°C.^13,15,16 As illustrated in the cases presented, recovery of the organism may not be accomplished from the first culture performed, and additional biopsy material for culture may be needed. Liquid media generally is more sensitive and produces more rapid results than solid media (eg, Löwenstein-Jensen, Middlebrook 7H10/7H11 agar). However, solid media carry the advantage of allowing observation of morphology and estimation of the number of organisms.^12,17

Rapid Detection
Advancements in molecular methods have allowed for more definitive and rapid identification of M marinum, substantially reducing the delay in diagnosis. Commercial molecular assays utilize in-solution hybridization or solid-format reverse-hybridization assays to allow mycobacterial detection as soon as growth appears.¹⁸ Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can substantially shorten the time to species identification.^19,20 Nonculture-based tests that have been developed for the rapid detection of M marinum infection include polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction amplification of the 16S RNA gene.²¹ It should be noted, however, that M marinum and Mycobacterium ulcerans have a very homologous 16S ribosomal RNA gene sequence, differing by only 1 nucleotide; thus, distinguishing between M marinum and M ulcerans using this method may be challenging.^22,23

Management
Treatment depends on the extent of the disease. Generally, localized cutaneous disease can be treated with monotherapy with agents such as doxycycline, clarithromycin, or TMP-SMX. Extensive disease typically requires a combination of 2 antimycobacterial agents, typically clarithromycin-rifampin, clarithromycin-ethambutol, or rifampin-ethambutol.¹² Amikacin has been used in combination with other agents such as rifampin and clarithromycin in refractory cases.^22,24 The use of ciprofloxacin is not encouraged because some isolates are resistant; however, other fluoroquinolones, such as moxifloxacin, may be options for combination therapy. Isoniazid, pyrazinamide, and streptomycin are not effective to treat M marinum.

Susceptibility testing of M marinum usually is performed to guide antimicrobial therapy in cases of poor clinical response or intolerance to first-line antimicrobials such as macrolides.²⁵ The likelihood of M marinum developing resistance to the agents used for treatment appears to be low. Unfortunately, in vitro antimicrobial susceptibility tests do not correlate well with treatment efficiency.¹⁰

The duration of therapy is not standardized but usually is 5 to 6 months,^7,10,26 with therapy often continuing 1 to 2 months after lesions appear to have resolved.¹² However, in some cases (usually those who have more extensive disease), therapy has been extended to as long as 1 to 2 years.¹⁰ The ideal length of therapy in immunocompromised individuals has not been established²⁷; however, a treatment duration of 6 to 9 months was reported in one study.²⁸ Surgical debridement may be necessary in some patients who have involvement of deep structures of the hand or knee, those with persistent pain, or those who fail to respond to a prolonged period of medical therapy.²⁹ Successful use of less conventional therapeutic approaches, including cryotherapy, radiation therapy, electrodesiccation, photodynamic therapy, curettage, and local hyperthermic therapy has been reported.^30-32

Conclusion

Diagnosis and management of M marinum infection is difficult. Patients presenting with indolent nodular skin infections affecting the upper extremities should be asked about aquatic exposure. Tissue biopsy for histopathologic examination and culture is essential to establish an early diagnosis and promptly initiate appropriate therapy.

Acknowledgment
We would like to thank Carol A. Kauffman, MD (Ann Arbor, Michigan), for her thoughtful comments that greatly improved this manuscript.

An environmental pathogen, Mycobacterium marinum can cause cutaneous infection when traumatized skin is exposed to fresh, brackish, or salt water. Fishing, aquarium cleaning, and aquatic recreational activities are risk factors for infection.^1,2 Diagnosis often is delayed and is made several weeks or even months after initial symptoms appear.³ Due to the protracted clinical course, patients may not recall the initial exposure, contributing to the delay in diagnosis and initiation of appropriate treatment. It is not uncommon for patients with M marinum infection to be initially treated with antibiotics or antifungal drugs.

We present a review of 5 patients who were diagnosed with M marinum infection at our institution between January 2003 and March 2013.

Methods

This study was conducted at Henry Ford Hospital, a 900-bed tertiary care center in Detroit, Michigan. Patients who had cultures positive for M marinum between January 2003 and March 2013 were identified using the institution’s laboratory database. Medical records were reviewed, and relevant demographic, epidemiologic, and clinical data, including initial clinical presentation, alternative diagnoses, time between initial presentation and definitive diagnosis, and specific treatment, were recorded.

Results

We identified 5 patients who were diagnosed with culture-confirmed M marinum skin infections during the study period: 3 men and 2 women aged 43 to 72 years (Table 1). Two patients had diabetes mellitus and 1 had hepatitis C virus. None had classic immunosuppression. On repeated questioning after the diagnosis was established, all 5 patients reported that they kept a home aquarium, and all recalled mild trauma to the hand prior to the onset of symptoms; however, none of the patients initially linked the minor skin injury to the subsequent infection.

All 5 patients initially presented with erythema and swelling at the site of the injury, which evolved into inflammatory nodules that progressed proximally up to the arm despite empiric treatment with antibiotics active against streptococci and staphylococci (Figures 1 and 2). Three patients also received empiric antifungal therapy due to suspicion of sporotrichosis.

Skin biopsies were performed on 4 patients, and incision and drainage of purulent material was performed on the fifth patient. Histopathologic examination revealed granulomatous inflammation in 3 patients. Stains for acid-fast bacilli were positive in all 5 patients. Definitive diagnosis of the organism was confirmed by growth of M marinum within 11 to 40 days from the tissue in 4 patients and purulent material in the fifth patient. Susceptibility testing was performed on only 1 of the 5 isolates and showed that the organism was susceptible to amikacin, clarithromycin, doxycycline, ethambutol, rifampin, and trimethoprim-sulfamethoxazole (TMP-SMX).

The mean time from initial presentation to initiation of appropriate therapy for M marinum infection was 91 days (range, 21–245 days). Several different treatment regimens were used. All patients received either doxycycline or minocycline with or without a macrolide. Two also received other agents (TMP-SMX or ethambutol). Treatment duration varied from 2 to 6 months in 4 patients, and all 4 had complete resolution of the lesions; 1 patient was lost to follow-up.

Comment

Diagnosing the Infection
Diagnosis of M marinum infection remains problematic. In the 5 patients included in this study, the time between initial onset of symptoms and diagnosis of M marinum infection was delayed, as has been noted in other reports.^4-7 Delays as long as 2 years before the diagnosis is made have been described.⁷ The clinical presentation of cutaneous infection with M marinum varies, which may delay diagnosis. Nodular lymphangitis is classic, but papules, pustules, ulcers, inflammatory plaques, and single nodules also can occur.^1,2 Lymphadenopathy may or may not be present.^4,8,9 The differential diagnosis is broad and includes infection by other nontuberculous mycobacteria such as Mycobacterium chelonae; Mycobacterium fortuitum; Nocardia species, especially Nocardia brasiliensis; Francisella tularensis; Sporothrix schenckii; and Leishmania species. It is not surprising that 4 patients in our study were initially treated for a gram-positive bacterial infection and 3 were treated for a fungal infection before the diagnosis of M marinum was made. Distinctive features that may help to differentiate these infections are summarized in Table 2.

We found that the main cause of delayed diagnosis was the failure of physicians to obtain a thorough history regarding patients’ recreational activities and animal exposure. Patients often do not associate a remote aquatic exposure with their symptoms and will not volunteer this information unless directly asked.^2,10 It was only after repeated questioning in all of these patients that they recounted prior trauma to the involved hand related to the aquarium.

Biopsy and Culture
Histopathologic examination of material from a biopsied lesion can give an early clue that a mycobacterial infection might be involved. Biopsy can reveal either noncaseating or necrotizing granulomas that have larger numbers of neutrophils in addition to lymphocytes and macrophages. Giant cells often are noted.^5,9,11 Organisms can be seen with the use of a tissue acid-fast stain, but species cannot be differentiated by acid-fast staining.¹² However, the sensitivity of acid-fast stains on biopsy material is low.^3,13,14

Culture of the involved tissue is crucial for establishing the diagnosis of this infection. However, the rate of growth of M marinum is slow. Temperature requirements for incubation and delay in transporting specimens to the laboratory can lead to bacterial overgrowth, resulting in the inability to recover M marinum from the culture.¹³Mycobacterium marinum grows preferentially between 28°C and 32°C, and growth is limited at temperatures above 33°C.^13,15,16 As illustrated in the cases presented, recovery of the organism may not be accomplished from the first culture performed, and additional biopsy material for culture may be needed. Liquid media generally is more sensitive and produces more rapid results than solid media (eg, Löwenstein-Jensen, Middlebrook 7H10/7H11 agar). However, solid media carry the advantage of allowing observation of morphology and estimation of the number of organisms.^12,17

Rapid Detection
Advancements in molecular methods have allowed for more definitive and rapid identification of M marinum, substantially reducing the delay in diagnosis. Commercial molecular assays utilize in-solution hybridization or solid-format reverse-hybridization assays to allow mycobacterial detection as soon as growth appears.¹⁸ Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can substantially shorten the time to species identification.^19,20 Nonculture-based tests that have been developed for the rapid detection of M marinum infection include polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction amplification of the 16S RNA gene.²¹ It should be noted, however, that M marinum and Mycobacterium ulcerans have a very homologous 16S ribosomal RNA gene sequence, differing by only 1 nucleotide; thus, distinguishing between M marinum and M ulcerans using this method may be challenging.^22,23

Management
Treatment depends on the extent of the disease. Generally, localized cutaneous disease can be treated with monotherapy with agents such as doxycycline, clarithromycin, or TMP-SMX. Extensive disease typically requires a combination of 2 antimycobacterial agents, typically clarithromycin-rifampin, clarithromycin-ethambutol, or rifampin-ethambutol.¹² Amikacin has been used in combination with other agents such as rifampin and clarithromycin in refractory cases.^22,24 The use of ciprofloxacin is not encouraged because some isolates are resistant; however, other fluoroquinolones, such as moxifloxacin, may be options for combination therapy. Isoniazid, pyrazinamide, and streptomycin are not effective to treat M marinum.

Susceptibility testing of M marinum usually is performed to guide antimicrobial therapy in cases of poor clinical response or intolerance to first-line antimicrobials such as macrolides.²⁵ The likelihood of M marinum developing resistance to the agents used for treatment appears to be low. Unfortunately, in vitro antimicrobial susceptibility tests do not correlate well with treatment efficiency.¹⁰

The duration of therapy is not standardized but usually is 5 to 6 months,^7,10,26 with therapy often continuing 1 to 2 months after lesions appear to have resolved.¹² However, in some cases (usually those who have more extensive disease), therapy has been extended to as long as 1 to 2 years.¹⁰ The ideal length of therapy in immunocompromised individuals has not been established²⁷; however, a treatment duration of 6 to 9 months was reported in one study.²⁸ Surgical debridement may be necessary in some patients who have involvement of deep structures of the hand or knee, those with persistent pain, or those who fail to respond to a prolonged period of medical therapy.²⁹ Successful use of less conventional therapeutic approaches, including cryotherapy, radiation therapy, electrodesiccation, photodynamic therapy, curettage, and local hyperthermic therapy has been reported.^30-32

Conclusion

Diagnosis and management of M marinum infection is difficult. Patients presenting with indolent nodular skin infections affecting the upper extremities should be asked about aquatic exposure. Tissue biopsy for histopathologic examination and culture is essential to establish an early diagnosis and promptly initiate appropriate therapy.

Acknowledgment
We would like to thank Carol A. Kauffman, MD (Ann Arbor, Michigan), for her thoughtful comments that greatly improved this manuscript.

An environmental pathogen, Mycobacterium marinum can cause cutaneous infection when traumatized skin is exposed to fresh, brackish, or salt water. Fishing, aquarium cleaning, and aquatic recreational activities are risk factors for infection.^1,2 Diagnosis often is delayed and is made several weeks or even months after initial symptoms appear.³ Due to the protracted clinical course, patients may not recall the initial exposure, contributing to the delay in diagnosis and initiation of appropriate treatment. It is not uncommon for patients with M marinum infection to be initially treated with antibiotics or antifungal drugs.

We present a review of 5 patients who were diagnosed with M marinum infection at our institution between January 2003 and March 2013.

Methods

This study was conducted at Henry Ford Hospital, a 900-bed tertiary care center in Detroit, Michigan. Patients who had cultures positive for M marinum between January 2003 and March 2013 were identified using the institution’s laboratory database. Medical records were reviewed, and relevant demographic, epidemiologic, and clinical data, including initial clinical presentation, alternative diagnoses, time between initial presentation and definitive diagnosis, and specific treatment, were recorded.

Results

We identified 5 patients who were diagnosed with culture-confirmed M marinum skin infections during the study period: 3 men and 2 women aged 43 to 72 years (Table 1). Two patients had diabetes mellitus and 1 had hepatitis C virus. None had classic immunosuppression. On repeated questioning after the diagnosis was established, all 5 patients reported that they kept a home aquarium, and all recalled mild trauma to the hand prior to the onset of symptoms; however, none of the patients initially linked the minor skin injury to the subsequent infection.

All 5 patients initially presented with erythema and swelling at the site of the injury, which evolved into inflammatory nodules that progressed proximally up to the arm despite empiric treatment with antibiotics active against streptococci and staphylococci (Figures 1 and 2). Three patients also received empiric antifungal therapy due to suspicion of sporotrichosis.

Skin biopsies were performed on 4 patients, and incision and drainage of purulent material was performed on the fifth patient. Histopathologic examination revealed granulomatous inflammation in 3 patients. Stains for acid-fast bacilli were positive in all 5 patients. Definitive diagnosis of the organism was confirmed by growth of M marinum within 11 to 40 days from the tissue in 4 patients and purulent material in the fifth patient. Susceptibility testing was performed on only 1 of the 5 isolates and showed that the organism was susceptible to amikacin, clarithromycin, doxycycline, ethambutol, rifampin, and trimethoprim-sulfamethoxazole (TMP-SMX).

The mean time from initial presentation to initiation of appropriate therapy for M marinum infection was 91 days (range, 21–245 days). Several different treatment regimens were used. All patients received either doxycycline or minocycline with or without a macrolide. Two also received other agents (TMP-SMX or ethambutol). Treatment duration varied from 2 to 6 months in 4 patients, and all 4 had complete resolution of the lesions; 1 patient was lost to follow-up.

Comment

Diagnosing the Infection
Diagnosis of M marinum infection remains problematic. In the 5 patients included in this study, the time between initial onset of symptoms and diagnosis of M marinum infection was delayed, as has been noted in other reports.^4-7 Delays as long as 2 years before the diagnosis is made have been described.⁷ The clinical presentation of cutaneous infection with M marinum varies, which may delay diagnosis. Nodular lymphangitis is classic, but papules, pustules, ulcers, inflammatory plaques, and single nodules also can occur.^1,2 Lymphadenopathy may or may not be present.^4,8,9 The differential diagnosis is broad and includes infection by other nontuberculous mycobacteria such as Mycobacterium chelonae; Mycobacterium fortuitum; Nocardia species, especially Nocardia brasiliensis; Francisella tularensis; Sporothrix schenckii; and Leishmania species. It is not surprising that 4 patients in our study were initially treated for a gram-positive bacterial infection and 3 were treated for a fungal infection before the diagnosis of M marinum was made. Distinctive features that may help to differentiate these infections are summarized in Table 2.

We found that the main cause of delayed diagnosis was the failure of physicians to obtain a thorough history regarding patients’ recreational activities and animal exposure. Patients often do not associate a remote aquatic exposure with their symptoms and will not volunteer this information unless directly asked.^2,10 It was only after repeated questioning in all of these patients that they recounted prior trauma to the involved hand related to the aquarium.

Biopsy and Culture
Histopathologic examination of material from a biopsied lesion can give an early clue that a mycobacterial infection might be involved. Biopsy can reveal either noncaseating or necrotizing granulomas that have larger numbers of neutrophils in addition to lymphocytes and macrophages. Giant cells often are noted.^5,9,11 Organisms can be seen with the use of a tissue acid-fast stain, but species cannot be differentiated by acid-fast staining.¹² However, the sensitivity of acid-fast stains on biopsy material is low.^3,13,14

Culture of the involved tissue is crucial for establishing the diagnosis of this infection. However, the rate of growth of M marinum is slow. Temperature requirements for incubation and delay in transporting specimens to the laboratory can lead to bacterial overgrowth, resulting in the inability to recover M marinum from the culture.¹³Mycobacterium marinum grows preferentially between 28°C and 32°C, and growth is limited at temperatures above 33°C.^13,15,16 As illustrated in the cases presented, recovery of the organism may not be accomplished from the first culture performed, and additional biopsy material for culture may be needed. Liquid media generally is more sensitive and produces more rapid results than solid media (eg, Löwenstein-Jensen, Middlebrook 7H10/7H11 agar). However, solid media carry the advantage of allowing observation of morphology and estimation of the number of organisms.^12,17

Rapid Detection
Advancements in molecular methods have allowed for more definitive and rapid identification of M marinum, substantially reducing the delay in diagnosis. Commercial molecular assays utilize in-solution hybridization or solid-format reverse-hybridization assays to allow mycobacterial detection as soon as growth appears.¹⁸ Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can substantially shorten the time to species identification.^19,20 Nonculture-based tests that have been developed for the rapid detection of M marinum infection include polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction amplification of the 16S RNA gene.²¹ It should be noted, however, that M marinum and Mycobacterium ulcerans have a very homologous 16S ribosomal RNA gene sequence, differing by only 1 nucleotide; thus, distinguishing between M marinum and M ulcerans using this method may be challenging.^22,23

Management
Treatment depends on the extent of the disease. Generally, localized cutaneous disease can be treated with monotherapy with agents such as doxycycline, clarithromycin, or TMP-SMX. Extensive disease typically requires a combination of 2 antimycobacterial agents, typically clarithromycin-rifampin, clarithromycin-ethambutol, or rifampin-ethambutol.¹² Amikacin has been used in combination with other agents such as rifampin and clarithromycin in refractory cases.^22,24 The use of ciprofloxacin is not encouraged because some isolates are resistant; however, other fluoroquinolones, such as moxifloxacin, may be options for combination therapy. Isoniazid, pyrazinamide, and streptomycin are not effective to treat M marinum.

Susceptibility testing of M marinum usually is performed to guide antimicrobial therapy in cases of poor clinical response or intolerance to first-line antimicrobials such as macrolides.²⁵ The likelihood of M marinum developing resistance to the agents used for treatment appears to be low. Unfortunately, in vitro antimicrobial susceptibility tests do not correlate well with treatment efficiency.¹⁰

The duration of therapy is not standardized but usually is 5 to 6 months,^7,10,26 with therapy often continuing 1 to 2 months after lesions appear to have resolved.¹² However, in some cases (usually those who have more extensive disease), therapy has been extended to as long as 1 to 2 years.¹⁰ The ideal length of therapy in immunocompromised individuals has not been established²⁷; however, a treatment duration of 6 to 9 months was reported in one study.²⁸ Surgical debridement may be necessary in some patients who have involvement of deep structures of the hand or knee, those with persistent pain, or those who fail to respond to a prolonged period of medical therapy.²⁹ Successful use of less conventional therapeutic approaches, including cryotherapy, radiation therapy, electrodesiccation, photodynamic therapy, curettage, and local hyperthermic therapy has been reported.^30-32

Conclusion

Diagnosis and management of M marinum infection is difficult. Patients presenting with indolent nodular skin infections affecting the upper extremities should be asked about aquatic exposure. Tissue biopsy for histopathologic examination and culture is essential to establish an early diagnosis and promptly initiate appropriate therapy.

Acknowledgment
We would like to thank Carol A. Kauffman, MD (Ann Arbor, Michigan), for her thoughtful comments that greatly improved this manuscript.

Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.

I am currently working with my mentor, Dr. Ian Jenkins, an attending in the Division of Hospital Medicine at the University of California, San Diego, to start piloting data collection on our project to cut catheter-associated urinary tract infections (CAUTI). We have contacted a number of potential units to recruit for CAUTI prevention efforts, but we are hoping to do a preliminary trial of data collection to better estimate the amount of time it takes to gather data for an individual unit.

Victor Ekuta is a third-year medical student at UC San Diego.

Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.

I am currently working with my mentor, Dr. Ian Jenkins, an attending in the Division of Hospital Medicine at the University of California, San Diego, to start piloting data collection on our project to cut catheter-associated urinary tract infections (CAUTI). We have contacted a number of potential units to recruit for CAUTI prevention efforts, but we are hoping to do a preliminary trial of data collection to better estimate the amount of time it takes to gather data for an individual unit.

Victor Ekuta is a third-year medical student at UC San Diego.

Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.

I am currently working with my mentor, Dr. Ian Jenkins, an attending in the Division of Hospital Medicine at the University of California, San Diego, to start piloting data collection on our project to cut catheter-associated urinary tract infections (CAUTI). We have contacted a number of potential units to recruit for CAUTI prevention efforts, but we are hoping to do a preliminary trial of data collection to better estimate the amount of time it takes to gather data for an individual unit.

Victor Ekuta is a third-year medical student at UC San Diego.

As we head into the last few weeks of the first session of the 115th Congress, it is likely that several pieces of “must pass” legislation will move through the process of becoming law. This “must pass” legislation can serve as a vehicle onto which other bills are attached and thus, also move successfully through the process for passage. I have highlighted below three such bills from the Action Alert section of the SurgeonsVoice website (www.surgeonsvoice.com) which could, with less than 5 minutes of your time, develop enough forward momentum to so move.

Ensuring Access to General Surgery Act

Increasing evidence indicates a current and growing shortage of surgeons available to serve our nation’s population. A shortage of general surgeons is a critical component of the crisis in health care workforce because only surgeons are uniquely trained and qualified to provide certain necessary, lifesaving procedures. Accordingly, the American College of Surgeons (ACS) is urging policy makers to recognize, through the designation of a formal surgical shortage area, that surgeons are an essential component of a community based health care system.

Mission Zero Act

It has long been a priority of the ACS to establish and maintain high-quality and adequately-funded trauma systems throughout the U.S., including within the Armed Forces. The Mission Zero Act, introduced by Chairman of the House Energy and Commerce Health Subcommittee, Michael Burgess, MD (R-TX), Representatives Gene Green (D-TX), Richard Hudson (R-NC), and Kathy Castor (D-FL) in the House of Representatives and Senators Johnny Isakson (R-GA), John Cornyn (R-TX), and Tammy Duckworth (D-IL) in the Senate, would provide HHS grant funding to assist civilian trauma centers in partnering with military trauma professionals to establish a pathway to provide patients with the highest quality trauma care. As a result of these partnerships, military trauma care teams and providers will gain exposure treating critically injured patients and increase readiness for future deployments. Not only will this serve to maintain readiness among military providers, but it will facilitate the promulgation of the trauma lessons learned from the military theatres of conflict to the civilian world and potentially alleviate staffing shortages in civilian centers.

CHIP Funding

The Children’s Health Insurance Program (CHIP) is a joint federal and state program that provides health coverage to uninsured children from low-income families. In 2015, the CHIP program provided coverage to over 8 million children in the United States. In sum, CHIP ensures that these children have access to care. The ACS is very supportive of the CHIP program. The CHIP program ensures that a child’s health care concerns are addressed in a timely manner. Contrary to popular belief, many children currently covered by CHIP are not eligible to be covered under Medicaid and would therefore, be left uninsured if CHIP funding is not continued. The most recent reauthorization of this program extended funding for the CHIP program through Sept. 30, 2017, and funding for the program expired on that date. Urgent Congressional action is needed to reauthorize funding and thus, ensure that the children covered by CHIP continue to have access to the health care services they need.

The ACS strongly urges Congress to continue to make children’s health care a priority issue and accordingly, implores Congress to take action to reauthorize CHIP funding prior to concluding the business of the current session.

The SurgeonsVoice website provides an easy and efficient platform for surgeons to use to contact their senators and their representative to let them know of their support of these issues. Taking action on all three of these items would require the investment of less than 5 minutes of one’s valuable time. Our ability “to petition the government for a redress of grievances” is guaranteed by the First Amendment. I urge all Fellows to visit the SurgeonsVoice website and use it as a tool to exercise that right.

Until next month ….

Dr. Bailey is a pediatric surgeon and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, DC.

As we head into the last few weeks of the first session of the 115th Congress, it is likely that several pieces of “must pass” legislation will move through the process of becoming law. This “must pass” legislation can serve as a vehicle onto which other bills are attached and thus, also move successfully through the process for passage. I have highlighted below three such bills from the Action Alert section of the SurgeonsVoice website (www.surgeonsvoice.com) which could, with less than 5 minutes of your time, develop enough forward momentum to so move.

Ensuring Access to General Surgery Act

Increasing evidence indicates a current and growing shortage of surgeons available to serve our nation’s population. A shortage of general surgeons is a critical component of the crisis in health care workforce because only surgeons are uniquely trained and qualified to provide certain necessary, lifesaving procedures. Accordingly, the American College of Surgeons (ACS) is urging policy makers to recognize, through the designation of a formal surgical shortage area, that surgeons are an essential component of a community based health care system.

Mission Zero Act

It has long been a priority of the ACS to establish and maintain high-quality and adequately-funded trauma systems throughout the U.S., including within the Armed Forces. The Mission Zero Act, introduced by Chairman of the House Energy and Commerce Health Subcommittee, Michael Burgess, MD (R-TX), Representatives Gene Green (D-TX), Richard Hudson (R-NC), and Kathy Castor (D-FL) in the House of Representatives and Senators Johnny Isakson (R-GA), John Cornyn (R-TX), and Tammy Duckworth (D-IL) in the Senate, would provide HHS grant funding to assist civilian trauma centers in partnering with military trauma professionals to establish a pathway to provide patients with the highest quality trauma care. As a result of these partnerships, military trauma care teams and providers will gain exposure treating critically injured patients and increase readiness for future deployments. Not only will this serve to maintain readiness among military providers, but it will facilitate the promulgation of the trauma lessons learned from the military theatres of conflict to the civilian world and potentially alleviate staffing shortages in civilian centers.

CHIP Funding

The Children’s Health Insurance Program (CHIP) is a joint federal and state program that provides health coverage to uninsured children from low-income families. In 2015, the CHIP program provided coverage to over 8 million children in the United States. In sum, CHIP ensures that these children have access to care. The ACS is very supportive of the CHIP program. The CHIP program ensures that a child’s health care concerns are addressed in a timely manner. Contrary to popular belief, many children currently covered by CHIP are not eligible to be covered under Medicaid and would therefore, be left uninsured if CHIP funding is not continued. The most recent reauthorization of this program extended funding for the CHIP program through Sept. 30, 2017, and funding for the program expired on that date. Urgent Congressional action is needed to reauthorize funding and thus, ensure that the children covered by CHIP continue to have access to the health care services they need.

The ACS strongly urges Congress to continue to make children’s health care a priority issue and accordingly, implores Congress to take action to reauthorize CHIP funding prior to concluding the business of the current session.

The SurgeonsVoice website provides an easy and efficient platform for surgeons to use to contact their senators and their representative to let them know of their support of these issues. Taking action on all three of these items would require the investment of less than 5 minutes of one’s valuable time. Our ability “to petition the government for a redress of grievances” is guaranteed by the First Amendment. I urge all Fellows to visit the SurgeonsVoice website and use it as a tool to exercise that right.

Until next month ….

Dr. Bailey is a pediatric surgeon and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, DC.

As we head into the last few weeks of the first session of the 115th Congress, it is likely that several pieces of “must pass” legislation will move through the process of becoming law. This “must pass” legislation can serve as a vehicle onto which other bills are attached and thus, also move successfully through the process for passage. I have highlighted below three such bills from the Action Alert section of the SurgeonsVoice website (www.surgeonsvoice.com) which could, with less than 5 minutes of your time, develop enough forward momentum to so move.

Ensuring Access to General Surgery Act

Increasing evidence indicates a current and growing shortage of surgeons available to serve our nation’s population. A shortage of general surgeons is a critical component of the crisis in health care workforce because only surgeons are uniquely trained and qualified to provide certain necessary, lifesaving procedures. Accordingly, the American College of Surgeons (ACS) is urging policy makers to recognize, through the designation of a formal surgical shortage area, that surgeons are an essential component of a community based health care system.

Mission Zero Act

It has long been a priority of the ACS to establish and maintain high-quality and adequately-funded trauma systems throughout the U.S., including within the Armed Forces. The Mission Zero Act, introduced by Chairman of the House Energy and Commerce Health Subcommittee, Michael Burgess, MD (R-TX), Representatives Gene Green (D-TX), Richard Hudson (R-NC), and Kathy Castor (D-FL) in the House of Representatives and Senators Johnny Isakson (R-GA), John Cornyn (R-TX), and Tammy Duckworth (D-IL) in the Senate, would provide HHS grant funding to assist civilian trauma centers in partnering with military trauma professionals to establish a pathway to provide patients with the highest quality trauma care. As a result of these partnerships, military trauma care teams and providers will gain exposure treating critically injured patients and increase readiness for future deployments. Not only will this serve to maintain readiness among military providers, but it will facilitate the promulgation of the trauma lessons learned from the military theatres of conflict to the civilian world and potentially alleviate staffing shortages in civilian centers.

CHIP Funding

The Children’s Health Insurance Program (CHIP) is a joint federal and state program that provides health coverage to uninsured children from low-income families. In 2015, the CHIP program provided coverage to over 8 million children in the United States. In sum, CHIP ensures that these children have access to care. The ACS is very supportive of the CHIP program. The CHIP program ensures that a child’s health care concerns are addressed in a timely manner. Contrary to popular belief, many children currently covered by CHIP are not eligible to be covered under Medicaid and would therefore, be left uninsured if CHIP funding is not continued. The most recent reauthorization of this program extended funding for the CHIP program through Sept. 30, 2017, and funding for the program expired on that date. Urgent Congressional action is needed to reauthorize funding and thus, ensure that the children covered by CHIP continue to have access to the health care services they need.

The ACS strongly urges Congress to continue to make children’s health care a priority issue and accordingly, implores Congress to take action to reauthorize CHIP funding prior to concluding the business of the current session.

The SurgeonsVoice website provides an easy and efficient platform for surgeons to use to contact their senators and their representative to let them know of their support of these issues. Taking action on all three of these items would require the investment of less than 5 minutes of one’s valuable time. Our ability “to petition the government for a redress of grievances” is guaranteed by the First Amendment. I urge all Fellows to visit the SurgeonsVoice website and use it as a tool to exercise that right.

Until next month ….

Dr. Bailey is a pediatric surgeon and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, DC.