Although new COVID-19 cases in children, as measured by the American Academy of Pediatrics and the Children’s Hospital Association, have remained fairly steady in recent months, data from the Centers for Diseases Control and Prevention suggest that weekly cases took a big jump in early January.

For the most recent week covered in the AAP/CHA weekly report, Jan. 20-26, there were over 36,000 child COVID cases reported in the United States, an increase of 8.8% from the week before (Jan. 13-19). New cases for the first 2 weeks of the year – 31,000 for the week of Dec. 30 to Jan. 5 and 26,000 during Jan. 6-12 – were consistent with the AAP/CHA assertion that “weekly reported child cases have plateaued at an average of about 32,000 cases ... over the past 4 months.”

The CDC data, however, show that new cases doubled during the week of Jan. 1-7 to over 65,000, compared with the end of December, and stayed at that level for Jan. 8-14, and since CDC figures are subject to a 6-week reporting delay, the final numbers are likely to be even higher. The composition by age changed somewhat between the 2 weeks, though, as those aged 0-4 years went from almost half of all cases in the first week down to 40% in the second, while cases rose for children aged 5-11 and 12-15, based on data from the COVID-19 response team.

Emergency department visits for January do not show a corresponding increase. ED visits among children aged 0-11 years with COVID-19, measured as a percentage of all ED visits, declined over the course of the month, as did visits for 16- and 17-year-olds, while those aged 12-15 started the month at 1.4% and were at 1.4% on Jan. 27, with a slight dip down to 1.2% in between, the CDC said on its COVID Data Tracker. Daily hospitalizations for children aged 0-17 also declined through mid-January and did not reflect the jump in new cases.

Meanwhile, vaccinated children are still in the minority: 57% of those under age 18 have received no COVID vaccine yet, the AAP said in a separate report. Just 7.4% of children under age 2 years had received at least one dose as of Jan. 25, as had 10.1% of those aged 2-4 years, 39.6% of 5- to 11-year-olds and 71.8% of those 12-17 years old, according to the CDC, with corresponding figures for completion of the primary series at 3.5%, 5.3%, 32.5%, and 61.5%.

Although new COVID-19 cases in children, as measured by the American Academy of Pediatrics and the Children’s Hospital Association, have remained fairly steady in recent months, data from the Centers for Diseases Control and Prevention suggest that weekly cases took a big jump in early January.

For the most recent week covered in the AAP/CHA weekly report, Jan. 20-26, there were over 36,000 child COVID cases reported in the United States, an increase of 8.8% from the week before (Jan. 13-19). New cases for the first 2 weeks of the year – 31,000 for the week of Dec. 30 to Jan. 5 and 26,000 during Jan. 6-12 – were consistent with the AAP/CHA assertion that “weekly reported child cases have plateaued at an average of about 32,000 cases ... over the past 4 months.”

The CDC data, however, show that new cases doubled during the week of Jan. 1-7 to over 65,000, compared with the end of December, and stayed at that level for Jan. 8-14, and since CDC figures are subject to a 6-week reporting delay, the final numbers are likely to be even higher. The composition by age changed somewhat between the 2 weeks, though, as those aged 0-4 years went from almost half of all cases in the first week down to 40% in the second, while cases rose for children aged 5-11 and 12-15, based on data from the COVID-19 response team.

Emergency department visits for January do not show a corresponding increase. ED visits among children aged 0-11 years with COVID-19, measured as a percentage of all ED visits, declined over the course of the month, as did visits for 16- and 17-year-olds, while those aged 12-15 started the month at 1.4% and were at 1.4% on Jan. 27, with a slight dip down to 1.2% in between, the CDC said on its COVID Data Tracker. Daily hospitalizations for children aged 0-17 also declined through mid-January and did not reflect the jump in new cases.

Meanwhile, vaccinated children are still in the minority: 57% of those under age 18 have received no COVID vaccine yet, the AAP said in a separate report. Just 7.4% of children under age 2 years had received at least one dose as of Jan. 25, as had 10.1% of those aged 2-4 years, 39.6% of 5- to 11-year-olds and 71.8% of those 12-17 years old, according to the CDC, with corresponding figures for completion of the primary series at 3.5%, 5.3%, 32.5%, and 61.5%.

Although new COVID-19 cases in children, as measured by the American Academy of Pediatrics and the Children’s Hospital Association, have remained fairly steady in recent months, data from the Centers for Diseases Control and Prevention suggest that weekly cases took a big jump in early January.

For the most recent week covered in the AAP/CHA weekly report, Jan. 20-26, there were over 36,000 child COVID cases reported in the United States, an increase of 8.8% from the week before (Jan. 13-19). New cases for the first 2 weeks of the year – 31,000 for the week of Dec. 30 to Jan. 5 and 26,000 during Jan. 6-12 – were consistent with the AAP/CHA assertion that “weekly reported child cases have plateaued at an average of about 32,000 cases ... over the past 4 months.”

The CDC data, however, show that new cases doubled during the week of Jan. 1-7 to over 65,000, compared with the end of December, and stayed at that level for Jan. 8-14, and since CDC figures are subject to a 6-week reporting delay, the final numbers are likely to be even higher. The composition by age changed somewhat between the 2 weeks, though, as those aged 0-4 years went from almost half of all cases in the first week down to 40% in the second, while cases rose for children aged 5-11 and 12-15, based on data from the COVID-19 response team.

Emergency department visits for January do not show a corresponding increase. ED visits among children aged 0-11 years with COVID-19, measured as a percentage of all ED visits, declined over the course of the month, as did visits for 16- and 17-year-olds, while those aged 12-15 started the month at 1.4% and were at 1.4% on Jan. 27, with a slight dip down to 1.2% in between, the CDC said on its COVID Data Tracker. Daily hospitalizations for children aged 0-17 also declined through mid-January and did not reflect the jump in new cases.

Meanwhile, vaccinated children are still in the minority: 57% of those under age 18 have received no COVID vaccine yet, the AAP said in a separate report. Just 7.4% of children under age 2 years had received at least one dose as of Jan. 25, as had 10.1% of those aged 2-4 years, 39.6% of 5- to 11-year-olds and 71.8% of those 12-17 years old, according to the CDC, with corresponding figures for completion of the primary series at 3.5%, 5.3%, 32.5%, and 61.5%.

The 18th Annual Skin of Color Society Scientific Symposium was held in March 2022 in Boston, Massachusetts. With a theme of Diversity in Action: Science, Healthcare & Society, researchers gathered to present new findings, share key insights, and discuss the continuing evolution of the field. Three awards were presented from the scientific posters at the symposium.

The Best Poster Presentation Award was presented to Brandyn M. White, BS, for “A Preliminary Analysis of the DDB1 Gene: Genome-Wide Association Studies in African and Admixed African American Populations—Is Our Skin Different?” authored by Brandyn M. White, BS; Chidubem A.V. Okeke, BS; Raveena Khanna, MD; Ginette A. Okoye, MD; Michael C. Campbell, PhD; and Angel S. Byrd, MD, PhD. Their research evaluated the association of variant DNA damage binding protein 1, DDB1, with African populations and highlighted the possible phenotypic variations between African and admixed African American populations. Further, it discussed the advantages of conducting future genome-wide association studies in the Washington metropolitan area to better understand dermatological diseases that disproportionately affect skin of color patients.

The Best Oral Presentation Award was presented to Erica Ogwumike, BA, for “Matching into Dermatology Residency: The Impact of Research Fellowships” authored by Erica Ogwumike, BA; Chine Chime, MS, MPH; and Rebecca Vasquez, MD. The aim of this study was to explore what variables were important for 2 events: taking a research fellowship and matching into dermatology. The authors analyzed Electronic Residency Application Service (ERAS) applications for all medical students applying to the UT Southwestern Dermatology Residency Program in the 2014-2015 cycle. They found that 1 of 5 students participated in a research fellowship prior to applying to dermatology residency, and it was not associated with increased odds of matching. They also discovered that students more likely to take a research fellowship were Latinx, attended a medical school ranked in the Top 25, and were not Alpha Omega Alpha members. Nevertheless, total publications did increase the odds of matching; therefore, the authors concluded that when looking for a research fellowship, applicants should look for one that allows productivity so that this measure can be achieved. Further investigation is needed to substantiate these results, but this study was a starting point to examine the characteristics involved in taking a research fellowship in dermatology. 

Finally, the Crowd Favorite Award was presented to Jennifer Cucalon, BS, for “Non-invasive, In-Vivo RCM Monitoring of Lentigines Treated With Cryotherapy to Establish Minimum Freeze Time in Seconds (Dose) in Skin of Color” authored by Jennifer Cucalon, BS, and Babar K. Rao, MD. This pilot study showed a minimum freezing time of 3 seconds to be effective in removing lentigines in darker skin; increasing the dose to 6 and 9 seconds had no added benefit. The authors also demonstrated reflectance confocal microscopy to be an appropriate, noninvasive, in vivo tool to visualize pigmentary changes and monitor the effectiveness of treatments for various skin conditions.

The 19th Annual Scientific Symposium will take place on March 16, 2023, in New Orleans, Louisiana. The theme will be Where Science, Innovation & Inclusion Meet. For more information, visit https://skinofcolorsociety.org/19th-annual-skin-of-color-society-scientific-symposium/.

The 18th Annual Skin of Color Society Scientific Symposium was held in March 2022 in Boston, Massachusetts. With a theme of Diversity in Action: Science, Healthcare & Society, researchers gathered to present new findings, share key insights, and discuss the continuing evolution of the field. Three awards were presented from the scientific posters at the symposium.

The Best Poster Presentation Award was presented to Brandyn M. White, BS, for “A Preliminary Analysis of the DDB1 Gene: Genome-Wide Association Studies in African and Admixed African American Populations—Is Our Skin Different?” authored by Brandyn M. White, BS; Chidubem A.V. Okeke, BS; Raveena Khanna, MD; Ginette A. Okoye, MD; Michael C. Campbell, PhD; and Angel S. Byrd, MD, PhD. Their research evaluated the association of variant DNA damage binding protein 1, DDB1, with African populations and highlighted the possible phenotypic variations between African and admixed African American populations. Further, it discussed the advantages of conducting future genome-wide association studies in the Washington metropolitan area to better understand dermatological diseases that disproportionately affect skin of color patients.

The Best Oral Presentation Award was presented to Erica Ogwumike, BA, for “Matching into Dermatology Residency: The Impact of Research Fellowships” authored by Erica Ogwumike, BA; Chine Chime, MS, MPH; and Rebecca Vasquez, MD. The aim of this study was to explore what variables were important for 2 events: taking a research fellowship and matching into dermatology. The authors analyzed Electronic Residency Application Service (ERAS) applications for all medical students applying to the UT Southwestern Dermatology Residency Program in the 2014-2015 cycle. They found that 1 of 5 students participated in a research fellowship prior to applying to dermatology residency, and it was not associated with increased odds of matching. They also discovered that students more likely to take a research fellowship were Latinx, attended a medical school ranked in the Top 25, and were not Alpha Omega Alpha members. Nevertheless, total publications did increase the odds of matching; therefore, the authors concluded that when looking for a research fellowship, applicants should look for one that allows productivity so that this measure can be achieved. Further investigation is needed to substantiate these results, but this study was a starting point to examine the characteristics involved in taking a research fellowship in dermatology. 

Finally, the Crowd Favorite Award was presented to Jennifer Cucalon, BS, for “Non-invasive, In-Vivo RCM Monitoring of Lentigines Treated With Cryotherapy to Establish Minimum Freeze Time in Seconds (Dose) in Skin of Color” authored by Jennifer Cucalon, BS, and Babar K. Rao, MD. This pilot study showed a minimum freezing time of 3 seconds to be effective in removing lentigines in darker skin; increasing the dose to 6 and 9 seconds had no added benefit. The authors also demonstrated reflectance confocal microscopy to be an appropriate, noninvasive, in vivo tool to visualize pigmentary changes and monitor the effectiveness of treatments for various skin conditions.

The 19th Annual Scientific Symposium will take place on March 16, 2023, in New Orleans, Louisiana. The theme will be Where Science, Innovation & Inclusion Meet. For more information, visit https://skinofcolorsociety.org/19th-annual-skin-of-color-society-scientific-symposium/.

The 18th Annual Skin of Color Society Scientific Symposium was held in March 2022 in Boston, Massachusetts. With a theme of Diversity in Action: Science, Healthcare & Society, researchers gathered to present new findings, share key insights, and discuss the continuing evolution of the field. Three awards were presented from the scientific posters at the symposium.

The Best Poster Presentation Award was presented to Brandyn M. White, BS, for “A Preliminary Analysis of the DDB1 Gene: Genome-Wide Association Studies in African and Admixed African American Populations—Is Our Skin Different?” authored by Brandyn M. White, BS; Chidubem A.V. Okeke, BS; Raveena Khanna, MD; Ginette A. Okoye, MD; Michael C. Campbell, PhD; and Angel S. Byrd, MD, PhD. Their research evaluated the association of variant DNA damage binding protein 1, DDB1, with African populations and highlighted the possible phenotypic variations between African and admixed African American populations. Further, it discussed the advantages of conducting future genome-wide association studies in the Washington metropolitan area to better understand dermatological diseases that disproportionately affect skin of color patients.

The Best Oral Presentation Award was presented to Erica Ogwumike, BA, for “Matching into Dermatology Residency: The Impact of Research Fellowships” authored by Erica Ogwumike, BA; Chine Chime, MS, MPH; and Rebecca Vasquez, MD. The aim of this study was to explore what variables were important for 2 events: taking a research fellowship and matching into dermatology. The authors analyzed Electronic Residency Application Service (ERAS) applications for all medical students applying to the UT Southwestern Dermatology Residency Program in the 2014-2015 cycle. They found that 1 of 5 students participated in a research fellowship prior to applying to dermatology residency, and it was not associated with increased odds of matching. They also discovered that students more likely to take a research fellowship were Latinx, attended a medical school ranked in the Top 25, and were not Alpha Omega Alpha members. Nevertheless, total publications did increase the odds of matching; therefore, the authors concluded that when looking for a research fellowship, applicants should look for one that allows productivity so that this measure can be achieved. Further investigation is needed to substantiate these results, but this study was a starting point to examine the characteristics involved in taking a research fellowship in dermatology. 

Finally, the Crowd Favorite Award was presented to Jennifer Cucalon, BS, for “Non-invasive, In-Vivo RCM Monitoring of Lentigines Treated With Cryotherapy to Establish Minimum Freeze Time in Seconds (Dose) in Skin of Color” authored by Jennifer Cucalon, BS, and Babar K. Rao, MD. This pilot study showed a minimum freezing time of 3 seconds to be effective in removing lentigines in darker skin; increasing the dose to 6 and 9 seconds had no added benefit. The authors also demonstrated reflectance confocal microscopy to be an appropriate, noninvasive, in vivo tool to visualize pigmentary changes and monitor the effectiveness of treatments for various skin conditions.

The 19th Annual Scientific Symposium will take place on March 16, 2023, in New Orleans, Louisiana. The theme will be Where Science, Innovation & Inclusion Meet. For more information, visit https://skinofcolorsociety.org/19th-annual-skin-of-color-society-scientific-symposium/.

To the Editor:

A 44-year-old woman presented with a low-grade fever (temperature, 38.0 °C) and painful acral lesions of 1 week’s duration. She had a history of hepatitis C viral infection and intravenous (IV) drug use, as well as polymicrobial infective endocarditis that involved the tricuspid and aortic valves; pathogenic organisms were identified via blood culture as Enterococcus faecalis, Serratia species, Streptococcus viridans, and Candida albicans. The patient had received a mechanical aortic valve and bioprosthetic tricuspid valve replacement 5 months prior with warfarin therapy and had completed a postsurgical 6-week course of high-dose micafungin. She reported that she had developed painful, violaceous, thin papules on the plantar surface of the left foot 2 weeks prior to presentation. Her symptoms improved with a short systemic steroid taper; however, within a week she developed new tender, erythematous, thin papules on the plantar surface of the right foot and the palmar surface of the left hand with associated lower extremity swelling. She denied other symptoms, including fever, chills, neurologic symptoms, shortness of breath, chest pain, nausea, vomiting, hematuria, and hematochezia. Due to worsening cutaneous findings, the patient presented to the emergency department, prompting hospital admission for empiric antibacterial therapy with vancomycin and piperacillin-tazobactam for suspected infectious endocarditis. Dermatology was consulted after 1 day of antibacterial therapy without improvement to determine the etiology of the patient’s skin findings.

Physical examination revealed the patient was afebrile with partially blanching violaceous to purpuric, tender, edematous papules on the left fourth and fifth finger pads, as well as scattered, painful, purpuric patches with stellate borders on the right plantar foot (Figure 1). Laboratory test results revealed mild anemia (hemoglobin, 11.9 g/dL [reference range, 12.0–15.0 g/dL], mild neutrophilia (neutrophils, 8.4×10⁹/L [reference range, 1.9–7.9×10⁹/L], elevated acute-phase reactants (erythrocyte sedimentation rate, 71 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 5.7 mg/dL [reference range, 0.0–0.5 mg/dL]), and positive hepatitis C virus antibody with an undetectable viral load. At the time of dermatologic evaluation, admission blood cultures and transthoracic echocardiogram were negative. Additionally, a transesophageal echocardiogram, limited by artifact from the mechanical aortic valve, was equivocal for valvular pathology. Subsequent ophthalmologic evaluation was negative for lesions associated with endocarditis, such as retinal hemorrhages.

Punch biopsies of the left fourth finger pad were submitted for histopathologic analysis and tissue cultures. Histopathology demonstrated deep dermal perivascular neutrophilic inflammation with multiple intravascular thrombi, perivascular fibrin, and karyorrhectic debris (Figure 2). Periodic acid–Schiff and Grocott-Gomori methenamine-silver stains revealed fungal spores with rare pseudohyphae within the thrombosed vascular spaces and the perivascular dermis, consistent with fungal septic emboli (Figure 3).

Empiric systemic antifungal coverage composed of IV liposomal amphotericin B and oral flucytosine was initiated, and the patient’s tender acral papules rapidly improved. Within 48 hours of biopsy, skin tissue culture confirmed the presence of C albicans. Four days after the preliminary dermatopathology report, confirmatory blood cultures resulted with pansensitive C albicans. Final tissue and blood cultures were negative for bacteria including mycobacteria. In addition to a 6-week course of IV amphotericin B and flucytosine, repeat surgical intervention was considered, and lifelong suppressive antifungal oral therapy was recommended. Unfortunately, the patient did not present for follow-up. Three months later, she presented to the emergency department with peritonitis; in the operating room, she was found to have ischemia of the entirety of the small and large intestines and died shortly thereafter.

Fungal endocarditis is rare, tending to develop in patient populations with particular risk factors such as immune compromise, structural heart defects or prosthetic valves, and IV drug use. Candida infective endocarditis (CIE) represents less than 2% of infective endocarditis cases and carries a high mortality rate (30%–80%).^1-3 Diagnosis may be challenging, as the clinical presentation varies widely. Although some patients may present with classic features of infective endocarditis, including fever, cardiac murmurs, and positive blood cultures, many cases of infective endocarditis present with nonspecific symptoms, raising a broad clinical differential diagnosis. Delay in diagnosis, which is seen in 82% of patients with fungal endocarditis, may be attributed to the slow progression of symptoms, inconclusive cardiac imaging, or negative blood cultures seen in almost one-third of cases.^2,3 The feared complication of systemic embolization via infective endocarditis may occur in up to one-half of cases, with the highest rates associated with staphylococcal or fungal pathogens.² The risk for embolization in fungal endocarditis is independent of the size of the cardiac valve vegetations; accordingly, sequelae of embolic complications may arise despite negative cardiac imaging.⁴ Embolic complications, which typically are seen within the first 2 to 4 weeks of treatment, may serve as the presenting feature of endocarditis and may even occur after completion of antimicrobial therapy.

Detection of cutaneous manifestations of infective endocarditis, including Janeway lesions, Osler nodes, and splinter hemorrhages, may allow for earlier diagnosis. Despite eponymous recognition, Janeway lesions and Osler nodes are relatively uncommon manifestations of infective endocarditis and may be found in only 5% to 15% of cases.⁵ Biopsies of suspected Janeway lesions and Osler nodes may allow for recognition of relevant vascular pathology, identification of the causative pathogen, and strong support for the diagnosis of infective endocarditis.^4-7

The initial photomicrograph of corresponding Janeway lesion histopathology was published by Kerr in 1955 and revealed dermal microabscesses posited to be secondary to bacterial emboli.^8,9 Additional cases through the years have reported overlapping histopathologic features of Janeway lesions and Osler nodes, with the latter often defined by the presence of vasculitis.⁴ Although there appears to be ongoing debate and overlap between the 2 integumentary findings, a general consensus on differentiation takes into account both the clinical signs and symptoms as well as the histopathologic findings.^10,11

Osler nodes present as tender, violaceous, subcutaneous nodules on the acral surfaces, usually on the pads of the fingers and toes.⁵ The pathogenesis involves the deposition of immune complexes as a sequela of vascular occlusion by microthrombi classically seen in the late phase of subacute endocarditis. Janeway lesions present as nontender erythematous macules on the acral surfaces and are thought to represent microthrombi with dermal microabscesses, more common in acute endocarditis. Our patient demonstrated features of both Osler nodes and Janeway lesions. Despite the presence of fungal thrombi—a pathophysiology closer to that of Janeway lesions—the clinical presentation of painful acral nodules affecting finger pads and histologic features of vasculitis may be better characterized as Osler nodes. Regardless of pathogenesis, these cutaneous findings serve as a minor clinical criterion in the Duke criteria for the diagnosis of infective endocarditis when present.¹²

Candida infective endocarditis should be suspected in a patient with a history of valvular disease or prior infective endocarditis with fungemia, unexplained neurologic signs, or manifestations of peripheral embolization despite negative blood cultures.³ Particularly in the setting of negative cardiac imaging, recognition of CIE requires heightened diagnostic acumen and clinicopathologic correlation. Although culture and pathologic examination of valvular vegetations represents the gold standard for diagnosis of CIE, aspiration and culture of easily accessible septic emboli may provide rapid identification of the etiologic pathogen. In 1976, Alpert et al¹³ identified C albicans from an aspirated Osler node. Postmortem examination revealed extensive involvement of the homograft valve and aortic root with C albicans.¹³ Many other examples exist in the literature demonstrating matching pathogenic isolates from microbiologic cultures of skin and blood.^4,9,14,15 Thadepalli and Francis⁷ investigated 26 cases of endocarditis in heroin users in which the admitting diagnosis was endocarditis in only 4 cases. The etiologic pathogen was aspirated from secondary sites of localized infections secondary to emboli, including cutaneous lesions in 10 of the cases. Gram stain and culture revealed the causative organism leading to the ultimate diagnosis and management in 17 of 26 patients with endocarditis.⁷

The incidence of fungal endocarditis is increasing, with a reported 67% of cases caused by nosocomial infection.¹ Given the rising incidence of fungal endocarditis and its accompanying diagnostic difficulties, including frequently negative blood cultures and cardiac imaging, clinicians must perform careful skin examinations, employ judicious use of skin biopsy, and carefully correlate clinical and pathologic findings to improve recognition of this disease and guide patient care.

To the Editor:

A 44-year-old woman presented with a low-grade fever (temperature, 38.0 °C) and painful acral lesions of 1 week’s duration. She had a history of hepatitis C viral infection and intravenous (IV) drug use, as well as polymicrobial infective endocarditis that involved the tricuspid and aortic valves; pathogenic organisms were identified via blood culture as Enterococcus faecalis, Serratia species, Streptococcus viridans, and Candida albicans. The patient had received a mechanical aortic valve and bioprosthetic tricuspid valve replacement 5 months prior with warfarin therapy and had completed a postsurgical 6-week course of high-dose micafungin. She reported that she had developed painful, violaceous, thin papules on the plantar surface of the left foot 2 weeks prior to presentation. Her symptoms improved with a short systemic steroid taper; however, within a week she developed new tender, erythematous, thin papules on the plantar surface of the right foot and the palmar surface of the left hand with associated lower extremity swelling. She denied other symptoms, including fever, chills, neurologic symptoms, shortness of breath, chest pain, nausea, vomiting, hematuria, and hematochezia. Due to worsening cutaneous findings, the patient presented to the emergency department, prompting hospital admission for empiric antibacterial therapy with vancomycin and piperacillin-tazobactam for suspected infectious endocarditis. Dermatology was consulted after 1 day of antibacterial therapy without improvement to determine the etiology of the patient’s skin findings.

Physical examination revealed the patient was afebrile with partially blanching violaceous to purpuric, tender, edematous papules on the left fourth and fifth finger pads, as well as scattered, painful, purpuric patches with stellate borders on the right plantar foot (Figure 1). Laboratory test results revealed mild anemia (hemoglobin, 11.9 g/dL [reference range, 12.0–15.0 g/dL], mild neutrophilia (neutrophils, 8.4×10⁹/L [reference range, 1.9–7.9×10⁹/L], elevated acute-phase reactants (erythrocyte sedimentation rate, 71 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 5.7 mg/dL [reference range, 0.0–0.5 mg/dL]), and positive hepatitis C virus antibody with an undetectable viral load. At the time of dermatologic evaluation, admission blood cultures and transthoracic echocardiogram were negative. Additionally, a transesophageal echocardiogram, limited by artifact from the mechanical aortic valve, was equivocal for valvular pathology. Subsequent ophthalmologic evaluation was negative for lesions associated with endocarditis, such as retinal hemorrhages.

Punch biopsies of the left fourth finger pad were submitted for histopathologic analysis and tissue cultures. Histopathology demonstrated deep dermal perivascular neutrophilic inflammation with multiple intravascular thrombi, perivascular fibrin, and karyorrhectic debris (Figure 2). Periodic acid–Schiff and Grocott-Gomori methenamine-silver stains revealed fungal spores with rare pseudohyphae within the thrombosed vascular spaces and the perivascular dermis, consistent with fungal septic emboli (Figure 3).

Empiric systemic antifungal coverage composed of IV liposomal amphotericin B and oral flucytosine was initiated, and the patient’s tender acral papules rapidly improved. Within 48 hours of biopsy, skin tissue culture confirmed the presence of C albicans. Four days after the preliminary dermatopathology report, confirmatory blood cultures resulted with pansensitive C albicans. Final tissue and blood cultures were negative for bacteria including mycobacteria. In addition to a 6-week course of IV amphotericin B and flucytosine, repeat surgical intervention was considered, and lifelong suppressive antifungal oral therapy was recommended. Unfortunately, the patient did not present for follow-up. Three months later, she presented to the emergency department with peritonitis; in the operating room, she was found to have ischemia of the entirety of the small and large intestines and died shortly thereafter.

Fungal endocarditis is rare, tending to develop in patient populations with particular risk factors such as immune compromise, structural heart defects or prosthetic valves, and IV drug use. Candida infective endocarditis (CIE) represents less than 2% of infective endocarditis cases and carries a high mortality rate (30%–80%).^1-3 Diagnosis may be challenging, as the clinical presentation varies widely. Although some patients may present with classic features of infective endocarditis, including fever, cardiac murmurs, and positive blood cultures, many cases of infective endocarditis present with nonspecific symptoms, raising a broad clinical differential diagnosis. Delay in diagnosis, which is seen in 82% of patients with fungal endocarditis, may be attributed to the slow progression of symptoms, inconclusive cardiac imaging, or negative blood cultures seen in almost one-third of cases.^2,3 The feared complication of systemic embolization via infective endocarditis may occur in up to one-half of cases, with the highest rates associated with staphylococcal or fungal pathogens.² The risk for embolization in fungal endocarditis is independent of the size of the cardiac valve vegetations; accordingly, sequelae of embolic complications may arise despite negative cardiac imaging.⁴ Embolic complications, which typically are seen within the first 2 to 4 weeks of treatment, may serve as the presenting feature of endocarditis and may even occur after completion of antimicrobial therapy.

Detection of cutaneous manifestations of infective endocarditis, including Janeway lesions, Osler nodes, and splinter hemorrhages, may allow for earlier diagnosis. Despite eponymous recognition, Janeway lesions and Osler nodes are relatively uncommon manifestations of infective endocarditis and may be found in only 5% to 15% of cases.⁵ Biopsies of suspected Janeway lesions and Osler nodes may allow for recognition of relevant vascular pathology, identification of the causative pathogen, and strong support for the diagnosis of infective endocarditis.^4-7

The initial photomicrograph of corresponding Janeway lesion histopathology was published by Kerr in 1955 and revealed dermal microabscesses posited to be secondary to bacterial emboli.^8,9 Additional cases through the years have reported overlapping histopathologic features of Janeway lesions and Osler nodes, with the latter often defined by the presence of vasculitis.⁴ Although there appears to be ongoing debate and overlap between the 2 integumentary findings, a general consensus on differentiation takes into account both the clinical signs and symptoms as well as the histopathologic findings.^10,11

Osler nodes present as tender, violaceous, subcutaneous nodules on the acral surfaces, usually on the pads of the fingers and toes.⁵ The pathogenesis involves the deposition of immune complexes as a sequela of vascular occlusion by microthrombi classically seen in the late phase of subacute endocarditis. Janeway lesions present as nontender erythematous macules on the acral surfaces and are thought to represent microthrombi with dermal microabscesses, more common in acute endocarditis. Our patient demonstrated features of both Osler nodes and Janeway lesions. Despite the presence of fungal thrombi—a pathophysiology closer to that of Janeway lesions—the clinical presentation of painful acral nodules affecting finger pads and histologic features of vasculitis may be better characterized as Osler nodes. Regardless of pathogenesis, these cutaneous findings serve as a minor clinical criterion in the Duke criteria for the diagnosis of infective endocarditis when present.¹²

Candida infective endocarditis should be suspected in a patient with a history of valvular disease or prior infective endocarditis with fungemia, unexplained neurologic signs, or manifestations of peripheral embolization despite negative blood cultures.³ Particularly in the setting of negative cardiac imaging, recognition of CIE requires heightened diagnostic acumen and clinicopathologic correlation. Although culture and pathologic examination of valvular vegetations represents the gold standard for diagnosis of CIE, aspiration and culture of easily accessible septic emboli may provide rapid identification of the etiologic pathogen. In 1976, Alpert et al¹³ identified C albicans from an aspirated Osler node. Postmortem examination revealed extensive involvement of the homograft valve and aortic root with C albicans.¹³ Many other examples exist in the literature demonstrating matching pathogenic isolates from microbiologic cultures of skin and blood.^4,9,14,15 Thadepalli and Francis⁷ investigated 26 cases of endocarditis in heroin users in which the admitting diagnosis was endocarditis in only 4 cases. The etiologic pathogen was aspirated from secondary sites of localized infections secondary to emboli, including cutaneous lesions in 10 of the cases. Gram stain and culture revealed the causative organism leading to the ultimate diagnosis and management in 17 of 26 patients with endocarditis.⁷

The incidence of fungal endocarditis is increasing, with a reported 67% of cases caused by nosocomial infection.¹ Given the rising incidence of fungal endocarditis and its accompanying diagnostic difficulties, including frequently negative blood cultures and cardiac imaging, clinicians must perform careful skin examinations, employ judicious use of skin biopsy, and carefully correlate clinical and pathologic findings to improve recognition of this disease and guide patient care.

To the Editor:

A 44-year-old woman presented with a low-grade fever (temperature, 38.0 °C) and painful acral lesions of 1 week’s duration. She had a history of hepatitis C viral infection and intravenous (IV) drug use, as well as polymicrobial infective endocarditis that involved the tricuspid and aortic valves; pathogenic organisms were identified via blood culture as Enterococcus faecalis, Serratia species, Streptococcus viridans, and Candida albicans. The patient had received a mechanical aortic valve and bioprosthetic tricuspid valve replacement 5 months prior with warfarin therapy and had completed a postsurgical 6-week course of high-dose micafungin. She reported that she had developed painful, violaceous, thin papules on the plantar surface of the left foot 2 weeks prior to presentation. Her symptoms improved with a short systemic steroid taper; however, within a week she developed new tender, erythematous, thin papules on the plantar surface of the right foot and the palmar surface of the left hand with associated lower extremity swelling. She denied other symptoms, including fever, chills, neurologic symptoms, shortness of breath, chest pain, nausea, vomiting, hematuria, and hematochezia. Due to worsening cutaneous findings, the patient presented to the emergency department, prompting hospital admission for empiric antibacterial therapy with vancomycin and piperacillin-tazobactam for suspected infectious endocarditis. Dermatology was consulted after 1 day of antibacterial therapy without improvement to determine the etiology of the patient’s skin findings.

Physical examination revealed the patient was afebrile with partially blanching violaceous to purpuric, tender, edematous papules on the left fourth and fifth finger pads, as well as scattered, painful, purpuric patches with stellate borders on the right plantar foot (Figure 1). Laboratory test results revealed mild anemia (hemoglobin, 11.9 g/dL [reference range, 12.0–15.0 g/dL], mild neutrophilia (neutrophils, 8.4×10⁹/L [reference range, 1.9–7.9×10⁹/L], elevated acute-phase reactants (erythrocyte sedimentation rate, 71 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 5.7 mg/dL [reference range, 0.0–0.5 mg/dL]), and positive hepatitis C virus antibody with an undetectable viral load. At the time of dermatologic evaluation, admission blood cultures and transthoracic echocardiogram were negative. Additionally, a transesophageal echocardiogram, limited by artifact from the mechanical aortic valve, was equivocal for valvular pathology. Subsequent ophthalmologic evaluation was negative for lesions associated with endocarditis, such as retinal hemorrhages.

Punch biopsies of the left fourth finger pad were submitted for histopathologic analysis and tissue cultures. Histopathology demonstrated deep dermal perivascular neutrophilic inflammation with multiple intravascular thrombi, perivascular fibrin, and karyorrhectic debris (Figure 2). Periodic acid–Schiff and Grocott-Gomori methenamine-silver stains revealed fungal spores with rare pseudohyphae within the thrombosed vascular spaces and the perivascular dermis, consistent with fungal septic emboli (Figure 3).

Empiric systemic antifungal coverage composed of IV liposomal amphotericin B and oral flucytosine was initiated, and the patient’s tender acral papules rapidly improved. Within 48 hours of biopsy, skin tissue culture confirmed the presence of C albicans. Four days after the preliminary dermatopathology report, confirmatory blood cultures resulted with pansensitive C albicans. Final tissue and blood cultures were negative for bacteria including mycobacteria. In addition to a 6-week course of IV amphotericin B and flucytosine, repeat surgical intervention was considered, and lifelong suppressive antifungal oral therapy was recommended. Unfortunately, the patient did not present for follow-up. Three months later, she presented to the emergency department with peritonitis; in the operating room, she was found to have ischemia of the entirety of the small and large intestines and died shortly thereafter.

Fungal endocarditis is rare, tending to develop in patient populations with particular risk factors such as immune compromise, structural heart defects or prosthetic valves, and IV drug use. Candida infective endocarditis (CIE) represents less than 2% of infective endocarditis cases and carries a high mortality rate (30%–80%).^1-3 Diagnosis may be challenging, as the clinical presentation varies widely. Although some patients may present with classic features of infective endocarditis, including fever, cardiac murmurs, and positive blood cultures, many cases of infective endocarditis present with nonspecific symptoms, raising a broad clinical differential diagnosis. Delay in diagnosis, which is seen in 82% of patients with fungal endocarditis, may be attributed to the slow progression of symptoms, inconclusive cardiac imaging, or negative blood cultures seen in almost one-third of cases.^2,3 The feared complication of systemic embolization via infective endocarditis may occur in up to one-half of cases, with the highest rates associated with staphylococcal or fungal pathogens.² The risk for embolization in fungal endocarditis is independent of the size of the cardiac valve vegetations; accordingly, sequelae of embolic complications may arise despite negative cardiac imaging.⁴ Embolic complications, which typically are seen within the first 2 to 4 weeks of treatment, may serve as the presenting feature of endocarditis and may even occur after completion of antimicrobial therapy.

Detection of cutaneous manifestations of infective endocarditis, including Janeway lesions, Osler nodes, and splinter hemorrhages, may allow for earlier diagnosis. Despite eponymous recognition, Janeway lesions and Osler nodes are relatively uncommon manifestations of infective endocarditis and may be found in only 5% to 15% of cases.⁵ Biopsies of suspected Janeway lesions and Osler nodes may allow for recognition of relevant vascular pathology, identification of the causative pathogen, and strong support for the diagnosis of infective endocarditis.^4-7

The initial photomicrograph of corresponding Janeway lesion histopathology was published by Kerr in 1955 and revealed dermal microabscesses posited to be secondary to bacterial emboli.^8,9 Additional cases through the years have reported overlapping histopathologic features of Janeway lesions and Osler nodes, with the latter often defined by the presence of vasculitis.⁴ Although there appears to be ongoing debate and overlap between the 2 integumentary findings, a general consensus on differentiation takes into account both the clinical signs and symptoms as well as the histopathologic findings.^10,11

Osler nodes present as tender, violaceous, subcutaneous nodules on the acral surfaces, usually on the pads of the fingers and toes.⁵ The pathogenesis involves the deposition of immune complexes as a sequela of vascular occlusion by microthrombi classically seen in the late phase of subacute endocarditis. Janeway lesions present as nontender erythematous macules on the acral surfaces and are thought to represent microthrombi with dermal microabscesses, more common in acute endocarditis. Our patient demonstrated features of both Osler nodes and Janeway lesions. Despite the presence of fungal thrombi—a pathophysiology closer to that of Janeway lesions—the clinical presentation of painful acral nodules affecting finger pads and histologic features of vasculitis may be better characterized as Osler nodes. Regardless of pathogenesis, these cutaneous findings serve as a minor clinical criterion in the Duke criteria for the diagnosis of infective endocarditis when present.¹²

Candida infective endocarditis should be suspected in a patient with a history of valvular disease or prior infective endocarditis with fungemia, unexplained neurologic signs, or manifestations of peripheral embolization despite negative blood cultures.³ Particularly in the setting of negative cardiac imaging, recognition of CIE requires heightened diagnostic acumen and clinicopathologic correlation. Although culture and pathologic examination of valvular vegetations represents the gold standard for diagnosis of CIE, aspiration and culture of easily accessible septic emboli may provide rapid identification of the etiologic pathogen. In 1976, Alpert et al¹³ identified C albicans from an aspirated Osler node. Postmortem examination revealed extensive involvement of the homograft valve and aortic root with C albicans.¹³ Many other examples exist in the literature demonstrating matching pathogenic isolates from microbiologic cultures of skin and blood.^4,9,14,15 Thadepalli and Francis⁷ investigated 26 cases of endocarditis in heroin users in which the admitting diagnosis was endocarditis in only 4 cases. The etiologic pathogen was aspirated from secondary sites of localized infections secondary to emboli, including cutaneous lesions in 10 of the cases. Gram stain and culture revealed the causative organism leading to the ultimate diagnosis and management in 17 of 26 patients with endocarditis.⁷

The incidence of fungal endocarditis is increasing, with a reported 67% of cases caused by nosocomial infection.¹ Given the rising incidence of fungal endocarditis and its accompanying diagnostic difficulties, including frequently negative blood cultures and cardiac imaging, clinicians must perform careful skin examinations, employ judicious use of skin biopsy, and carefully correlate clinical and pathologic findings to improve recognition of this disease and guide patient care.

The clinical features and inflammatory mediators of adult-onset asthma were associated with distinct endotype groups defined by eosinophil and neutrophil levels, based on data from a real-life long term study of 203 patients.

Asthma is a chronic condition from lower respiratory tract inflammation composed of complex, heterogeneous endotypes with T2 helper cells being one way to distinguish between them. Endotypes have previously been suggested to have differing risks for asthma exacerbations and severity. However, clinical and biomarker information used for recognizing and targeting treatment is largely lacking in those subgroups other than eosinophilic asthma, according to Ella Flinkman, faculty of medicine and health technology, of Tampere University (Finland), and colleagues.

In a study published in The Journal of Allergy and Clinical Immunology: In Practice the researchers reported on their single-center 12-year follow-up phase II Seinäjoki Adult Asthma Study (SAAS). The included cohort of 203 patients had a median age of 58 years and 58% were women; all participants were originally diagnosed by a respiratory specialist physician as having new adult-onset asthma during the years 1999-2000 using asthma symptoms and objective lung function measurements.

To evaluate the association between clinical features and inflammation mediators to venous blood granulocytes this cohort was divided into paucigranulocytic (n = 108), neutrophilic (n = 60), eosinophilic (n = 21), and mixed granulocytic (n = 14) endotype subgroups based on eosinophil and neutrophil levels. Objective comparisons between groups were made using measurements from forced expiratory volume in 1 second (FEV₁), fraction of exhaled nitric oxide (FeNO), immunoglobin E (IgE), high-sensitivity C-reactive protein (hsCRP), IL-6, resistin, MMP-9, plasma soluble urokinase plasminogen activator receptor (suPAR), leptin, HMW adiponectin, and periostin tests. Asthma-related medications and disease exacerbation data were collected from medical records accumulated over the 12-year study period.

The neutrophilic group was defined by high (≥ 4.4×10^9/L) neutrophil but low (< 0.30×10⁹/L) eosinophil counts and conversely the eosinophilic group had low (< 4.4×10⁹/L) neutrophil but high (≥ 0.30×10⁹/L) eosinophil counts. The paucigranulocytic was low and the mixed granulocytic group was high for both eosinophil and neutrophil levels, respectively. Each group was associated with a unique profile of features related to asthma prognosis and treatment. The paucigranulocytic endotype was used as the base comparison group in regression analysis as it was the least likely to meet the definition of severe asthma. This was indicated by the lowest use of inhaled corticosteroid (ICS), antibiotics, and occurrence of unplanned respiratory visits. The other three groups were more likely to fulfill a severe asthma classification.

Negative binomial regression analysis showed significant association of increased incidence rate ratio (IRR) of unplanned respiratory visits, highest body mass index (BMI), and highest dispensed doses of ICS with neutrophilic asthma. Additional significantly associated factors included smoking history and gender. Adjustment for dispensed ICS 2 years prior to the 12-year follow-up visit resulted in a change from borderline to significant association of increased IRR for the eosinophilic group. Both the eosinophilic and neutrophilic groups were associated with the most antibiotic use over the 12-year follow-up period. The authors suggested their data may indicate that antibiotics are overprescribed for asthma and further investigation is required.

Multiple linear regression analysis showed a decline in lung function associated with the eosinophilic but not the neutrophilic group. Connections between specific blood endotypes and molecular features were also identified. Highest periostin and FeNO levels found in the eosinophilic group were consistent with other studies on patients specifically diagnosed with eosinophilic asthma.

The neutrophilic group was distinguished by the highest hsCRP, MMP-9, IL-6, leptin, and suPAR levels. Highest resistin levels were found in both the mixed granulocyte and neutrophilic groups.

This study was strengthened by its real life long-term nature and method for cohort selection, according to the authors, though the value of a larger population to raise numbers particularly in the smaller sized groups was noted.

The authors concluded: “Our study indicates that assays of blood eosinophil and neutrophil counts provide useful information for assessing and treating patients with adult-onset asthma. These granulocyte counts reflect the underlying inflammatory pattern and reveal important differences in asthma clinical features and outcomes.” Additional research “regarding biomarkers used to identify different endotypes of asthma” is needed.

The study was sponsored by a number of research foundations in Finland as well as hospital research center funds. Several of the authors disclosed associations with pharmaceutical companies, including Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, and Sanofi.

The clinical features and inflammatory mediators of adult-onset asthma were associated with distinct endotype groups defined by eosinophil and neutrophil levels, based on data from a real-life long term study of 203 patients.

Asthma is a chronic condition from lower respiratory tract inflammation composed of complex, heterogeneous endotypes with T2 helper cells being one way to distinguish between them. Endotypes have previously been suggested to have differing risks for asthma exacerbations and severity. However, clinical and biomarker information used for recognizing and targeting treatment is largely lacking in those subgroups other than eosinophilic asthma, according to Ella Flinkman, faculty of medicine and health technology, of Tampere University (Finland), and colleagues.

In a study published in The Journal of Allergy and Clinical Immunology: In Practice the researchers reported on their single-center 12-year follow-up phase II Seinäjoki Adult Asthma Study (SAAS). The included cohort of 203 patients had a median age of 58 years and 58% were women; all participants were originally diagnosed by a respiratory specialist physician as having new adult-onset asthma during the years 1999-2000 using asthma symptoms and objective lung function measurements.

To evaluate the association between clinical features and inflammation mediators to venous blood granulocytes this cohort was divided into paucigranulocytic (n = 108), neutrophilic (n = 60), eosinophilic (n = 21), and mixed granulocytic (n = 14) endotype subgroups based on eosinophil and neutrophil levels. Objective comparisons between groups were made using measurements from forced expiratory volume in 1 second (FEV₁), fraction of exhaled nitric oxide (FeNO), immunoglobin E (IgE), high-sensitivity C-reactive protein (hsCRP), IL-6, resistin, MMP-9, plasma soluble urokinase plasminogen activator receptor (suPAR), leptin, HMW adiponectin, and periostin tests. Asthma-related medications and disease exacerbation data were collected from medical records accumulated over the 12-year study period.

The neutrophilic group was defined by high (≥ 4.4×10^9/L) neutrophil but low (< 0.30×10⁹/L) eosinophil counts and conversely the eosinophilic group had low (< 4.4×10⁹/L) neutrophil but high (≥ 0.30×10⁹/L) eosinophil counts. The paucigranulocytic was low and the mixed granulocytic group was high for both eosinophil and neutrophil levels, respectively. Each group was associated with a unique profile of features related to asthma prognosis and treatment. The paucigranulocytic endotype was used as the base comparison group in regression analysis as it was the least likely to meet the definition of severe asthma. This was indicated by the lowest use of inhaled corticosteroid (ICS), antibiotics, and occurrence of unplanned respiratory visits. The other three groups were more likely to fulfill a severe asthma classification.

Negative binomial regression analysis showed significant association of increased incidence rate ratio (IRR) of unplanned respiratory visits, highest body mass index (BMI), and highest dispensed doses of ICS with neutrophilic asthma. Additional significantly associated factors included smoking history and gender. Adjustment for dispensed ICS 2 years prior to the 12-year follow-up visit resulted in a change from borderline to significant association of increased IRR for the eosinophilic group. Both the eosinophilic and neutrophilic groups were associated with the most antibiotic use over the 12-year follow-up period. The authors suggested their data may indicate that antibiotics are overprescribed for asthma and further investigation is required.

Multiple linear regression analysis showed a decline in lung function associated with the eosinophilic but not the neutrophilic group. Connections between specific blood endotypes and molecular features were also identified. Highest periostin and FeNO levels found in the eosinophilic group were consistent with other studies on patients specifically diagnosed with eosinophilic asthma.

The neutrophilic group was distinguished by the highest hsCRP, MMP-9, IL-6, leptin, and suPAR levels. Highest resistin levels were found in both the mixed granulocyte and neutrophilic groups.

This study was strengthened by its real life long-term nature and method for cohort selection, according to the authors, though the value of a larger population to raise numbers particularly in the smaller sized groups was noted.

The authors concluded: “Our study indicates that assays of blood eosinophil and neutrophil counts provide useful information for assessing and treating patients with adult-onset asthma. These granulocyte counts reflect the underlying inflammatory pattern and reveal important differences in asthma clinical features and outcomes.” Additional research “regarding biomarkers used to identify different endotypes of asthma” is needed.

The study was sponsored by a number of research foundations in Finland as well as hospital research center funds. Several of the authors disclosed associations with pharmaceutical companies, including Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, and Sanofi.

The clinical features and inflammatory mediators of adult-onset asthma were associated with distinct endotype groups defined by eosinophil and neutrophil levels, based on data from a real-life long term study of 203 patients.

Asthma is a chronic condition from lower respiratory tract inflammation composed of complex, heterogeneous endotypes with T2 helper cells being one way to distinguish between them. Endotypes have previously been suggested to have differing risks for asthma exacerbations and severity. However, clinical and biomarker information used for recognizing and targeting treatment is largely lacking in those subgroups other than eosinophilic asthma, according to Ella Flinkman, faculty of medicine and health technology, of Tampere University (Finland), and colleagues.

In a study published in The Journal of Allergy and Clinical Immunology: In Practice the researchers reported on their single-center 12-year follow-up phase II Seinäjoki Adult Asthma Study (SAAS). The included cohort of 203 patients had a median age of 58 years and 58% were women; all participants were originally diagnosed by a respiratory specialist physician as having new adult-onset asthma during the years 1999-2000 using asthma symptoms and objective lung function measurements.

To evaluate the association between clinical features and inflammation mediators to venous blood granulocytes this cohort was divided into paucigranulocytic (n = 108), neutrophilic (n = 60), eosinophilic (n = 21), and mixed granulocytic (n = 14) endotype subgroups based on eosinophil and neutrophil levels. Objective comparisons between groups were made using measurements from forced expiratory volume in 1 second (FEV₁), fraction of exhaled nitric oxide (FeNO), immunoglobin E (IgE), high-sensitivity C-reactive protein (hsCRP), IL-6, resistin, MMP-9, plasma soluble urokinase plasminogen activator receptor (suPAR), leptin, HMW adiponectin, and periostin tests. Asthma-related medications and disease exacerbation data were collected from medical records accumulated over the 12-year study period.

The neutrophilic group was defined by high (≥ 4.4×10^9/L) neutrophil but low (< 0.30×10⁹/L) eosinophil counts and conversely the eosinophilic group had low (< 4.4×10⁹/L) neutrophil but high (≥ 0.30×10⁹/L) eosinophil counts. The paucigranulocytic was low and the mixed granulocytic group was high for both eosinophil and neutrophil levels, respectively. Each group was associated with a unique profile of features related to asthma prognosis and treatment. The paucigranulocytic endotype was used as the base comparison group in regression analysis as it was the least likely to meet the definition of severe asthma. This was indicated by the lowest use of inhaled corticosteroid (ICS), antibiotics, and occurrence of unplanned respiratory visits. The other three groups were more likely to fulfill a severe asthma classification.

Negative binomial regression analysis showed significant association of increased incidence rate ratio (IRR) of unplanned respiratory visits, highest body mass index (BMI), and highest dispensed doses of ICS with neutrophilic asthma. Additional significantly associated factors included smoking history and gender. Adjustment for dispensed ICS 2 years prior to the 12-year follow-up visit resulted in a change from borderline to significant association of increased IRR for the eosinophilic group. Both the eosinophilic and neutrophilic groups were associated with the most antibiotic use over the 12-year follow-up period. The authors suggested their data may indicate that antibiotics are overprescribed for asthma and further investigation is required.

Multiple linear regression analysis showed a decline in lung function associated with the eosinophilic but not the neutrophilic group. Connections between specific blood endotypes and molecular features were also identified. Highest periostin and FeNO levels found in the eosinophilic group were consistent with other studies on patients specifically diagnosed with eosinophilic asthma.

The neutrophilic group was distinguished by the highest hsCRP, MMP-9, IL-6, leptin, and suPAR levels. Highest resistin levels were found in both the mixed granulocyte and neutrophilic groups.

This study was strengthened by its real life long-term nature and method for cohort selection, according to the authors, though the value of a larger population to raise numbers particularly in the smaller sized groups was noted.

The authors concluded: “Our study indicates that assays of blood eosinophil and neutrophil counts provide useful information for assessing and treating patients with adult-onset asthma. These granulocyte counts reflect the underlying inflammatory pattern and reveal important differences in asthma clinical features and outcomes.” Additional research “regarding biomarkers used to identify different endotypes of asthma” is needed.

The study was sponsored by a number of research foundations in Finland as well as hospital research center funds. Several of the authors disclosed associations with pharmaceutical companies, including Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, and Sanofi.

It’s a common scenario. A patient, Agnes, with symptoms of an upper respiratory infection (URI), but what’s the cause? Is it COVID-19, flu, or even RSV? I recently described just such a patient, an obese woman with type 2 diabetes, presenting with fever, cough, myalgia, and fatigue. I asked readers whether they agreed with my management of this patient.

Thank you for your comments as we continue to react to high rates of URIs. Your comments highlight the importance of local resources and practice habits when managing patients with URI.

It was clear that readers value testing to distinguish between infections. However, access to testing is highly variable around the world and is likely to be routinely used only in high-income countries. The Kaiser Family Foundation performed a cost analysis of testing for SARS-CoV-2 in 2020 and found, not surprisingly, wide variability in the cost of testing. Medicare covers tests at rates of $36-$143 per test; a study of list prices for SARS-CoV-2 tests at 93 hospitals found a median cost of $148 per test. And this does not include collection or facility fees. About 20% of tests cost more than $300.

These costs are prohibitive for many health systems. However, more devices have been introduced since that analysis, and competition and evolving technology should drive down prices. Generally, multiplex polymerase chain reaction (PCR) testing for multiple pathogens is less expensive than ordering two or three separate molecular tests and is more convenient for patients and practices alike.

Other reader comments focused on the challenges of getting accurate data on viral epidemiology, and there is certainly a time lag between infection trends and public health reports. This is exacerbated by underreporting of symptoms and more testing at home using antigen tests.

But please do not give up on epidemiology! If a test such as PCR is 90% sensitive for identifying infection, the yield in terms of the number of individuals infected with a particular virus should be high, and that is true when infection is in broad circulation. If 20% of a population of 1,000 has an infection and the test sensitivity is 90%, the yield of testing is 180 true cases versus 20 false positives.

However, if just 2% of the population of 1,000 has the infection in this same scenario, then only 18 true cases are identified. The effect on public health is certainly less, and a lower prevalence rate means that confounding variables, such as how long an individual might shed viral particles and the method of sample collection, have an outsized effect on results. This reduces the validity of diagnostic tests.

Even trends on a national level can provide some insight regarding whom to test. Traditionally, our practice has been to not routinely test patients for influenza or RSV from late spring to early fall unless there was a compelling reason, such as recent travel to an area where these infections were more prevalent. The loss of temporality for these infections since 2020 has altered this approach and made us pay more attention to reports from public health organizations.

I also appreciate the discussion of how to treat Agnes’s symptoms as she waits to improve, and anyone who suffers with or treats a viral URI knows that there are few interventions effective for such symptoms as cough and congestion. A systematic review of 29 randomized controlled trials of over-the-counter medications for cough yielded mixed and largely negative results.

Antihistamines alone do not seem to work, and guaifenesin was successful in only one of three trials. Combinations of different drug classes appeared to be slightly more effective.

My personal favorite for the management of acute cough is something that kids generally love: honey. In a review of 14 studies, 9 of which were limited to pediatric patients, honey was associated with significant reductions in cough frequency, cough severity, and total symptom score. However, there was a moderate risk of bias in the included research, and evidence of honey’s benefit in placebo-controlled trials was limited. Honey used in this research came in a variety of forms, so the best dosage is uncertain.

Clearly, advancements are needed. Better symptom management in viral URI will almost certainly improve productivity across the population and will probably reduce the inappropriate use of antibiotics as well. I have said for years that the scientists who can solve the Gordian knot of pediatric mucus deserve three Nobel prizes. I look forward to that golden day.

Dr. Vega is a clinical professor of family medicine at the University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

A version of this article first appeared on Medscape.com.

It’s a common scenario. A patient, Agnes, with symptoms of an upper respiratory infection (URI), but what’s the cause? Is it COVID-19, flu, or even RSV? I recently described just such a patient, an obese woman with type 2 diabetes, presenting with fever, cough, myalgia, and fatigue. I asked readers whether they agreed with my management of this patient.

Thank you for your comments as we continue to react to high rates of URIs. Your comments highlight the importance of local resources and practice habits when managing patients with URI.

It was clear that readers value testing to distinguish between infections. However, access to testing is highly variable around the world and is likely to be routinely used only in high-income countries. The Kaiser Family Foundation performed a cost analysis of testing for SARS-CoV-2 in 2020 and found, not surprisingly, wide variability in the cost of testing. Medicare covers tests at rates of $36-$143 per test; a study of list prices for SARS-CoV-2 tests at 93 hospitals found a median cost of $148 per test. And this does not include collection or facility fees. About 20% of tests cost more than $300.

These costs are prohibitive for many health systems. However, more devices have been introduced since that analysis, and competition and evolving technology should drive down prices. Generally, multiplex polymerase chain reaction (PCR) testing for multiple pathogens is less expensive than ordering two or three separate molecular tests and is more convenient for patients and practices alike.

Other reader comments focused on the challenges of getting accurate data on viral epidemiology, and there is certainly a time lag between infection trends and public health reports. This is exacerbated by underreporting of symptoms and more testing at home using antigen tests.

But please do not give up on epidemiology! If a test such as PCR is 90% sensitive for identifying infection, the yield in terms of the number of individuals infected with a particular virus should be high, and that is true when infection is in broad circulation. If 20% of a population of 1,000 has an infection and the test sensitivity is 90%, the yield of testing is 180 true cases versus 20 false positives.

However, if just 2% of the population of 1,000 has the infection in this same scenario, then only 18 true cases are identified. The effect on public health is certainly less, and a lower prevalence rate means that confounding variables, such as how long an individual might shed viral particles and the method of sample collection, have an outsized effect on results. This reduces the validity of diagnostic tests.

Even trends on a national level can provide some insight regarding whom to test. Traditionally, our practice has been to not routinely test patients for influenza or RSV from late spring to early fall unless there was a compelling reason, such as recent travel to an area where these infections were more prevalent. The loss of temporality for these infections since 2020 has altered this approach and made us pay more attention to reports from public health organizations.

I also appreciate the discussion of how to treat Agnes’s symptoms as she waits to improve, and anyone who suffers with or treats a viral URI knows that there are few interventions effective for such symptoms as cough and congestion. A systematic review of 29 randomized controlled trials of over-the-counter medications for cough yielded mixed and largely negative results.

Antihistamines alone do not seem to work, and guaifenesin was successful in only one of three trials. Combinations of different drug classes appeared to be slightly more effective.

My personal favorite for the management of acute cough is something that kids generally love: honey. In a review of 14 studies, 9 of which were limited to pediatric patients, honey was associated with significant reductions in cough frequency, cough severity, and total symptom score. However, there was a moderate risk of bias in the included research, and evidence of honey’s benefit in placebo-controlled trials was limited. Honey used in this research came in a variety of forms, so the best dosage is uncertain.

Clearly, advancements are needed. Better symptom management in viral URI will almost certainly improve productivity across the population and will probably reduce the inappropriate use of antibiotics as well. I have said for years that the scientists who can solve the Gordian knot of pediatric mucus deserve three Nobel prizes. I look forward to that golden day.

Dr. Vega is a clinical professor of family medicine at the University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

A version of this article first appeared on Medscape.com.

It’s a common scenario. A patient, Agnes, with symptoms of an upper respiratory infection (URI), but what’s the cause? Is it COVID-19, flu, or even RSV? I recently described just such a patient, an obese woman with type 2 diabetes, presenting with fever, cough, myalgia, and fatigue. I asked readers whether they agreed with my management of this patient.

Thank you for your comments as we continue to react to high rates of URIs. Your comments highlight the importance of local resources and practice habits when managing patients with URI.

It was clear that readers value testing to distinguish between infections. However, access to testing is highly variable around the world and is likely to be routinely used only in high-income countries. The Kaiser Family Foundation performed a cost analysis of testing for SARS-CoV-2 in 2020 and found, not surprisingly, wide variability in the cost of testing. Medicare covers tests at rates of $36-$143 per test; a study of list prices for SARS-CoV-2 tests at 93 hospitals found a median cost of $148 per test. And this does not include collection or facility fees. About 20% of tests cost more than $300.

These costs are prohibitive for many health systems. However, more devices have been introduced since that analysis, and competition and evolving technology should drive down prices. Generally, multiplex polymerase chain reaction (PCR) testing for multiple pathogens is less expensive than ordering two or three separate molecular tests and is more convenient for patients and practices alike.

Other reader comments focused on the challenges of getting accurate data on viral epidemiology, and there is certainly a time lag between infection trends and public health reports. This is exacerbated by underreporting of symptoms and more testing at home using antigen tests.

But please do not give up on epidemiology! If a test such as PCR is 90% sensitive for identifying infection, the yield in terms of the number of individuals infected with a particular virus should be high, and that is true when infection is in broad circulation. If 20% of a population of 1,000 has an infection and the test sensitivity is 90%, the yield of testing is 180 true cases versus 20 false positives.

However, if just 2% of the population of 1,000 has the infection in this same scenario, then only 18 true cases are identified. The effect on public health is certainly less, and a lower prevalence rate means that confounding variables, such as how long an individual might shed viral particles and the method of sample collection, have an outsized effect on results. This reduces the validity of diagnostic tests.

Even trends on a national level can provide some insight regarding whom to test. Traditionally, our practice has been to not routinely test patients for influenza or RSV from late spring to early fall unless there was a compelling reason, such as recent travel to an area where these infections were more prevalent. The loss of temporality for these infections since 2020 has altered this approach and made us pay more attention to reports from public health organizations.

I also appreciate the discussion of how to treat Agnes’s symptoms as she waits to improve, and anyone who suffers with or treats a viral URI knows that there are few interventions effective for such symptoms as cough and congestion. A systematic review of 29 randomized controlled trials of over-the-counter medications for cough yielded mixed and largely negative results.

Antihistamines alone do not seem to work, and guaifenesin was successful in only one of three trials. Combinations of different drug classes appeared to be slightly more effective.

My personal favorite for the management of acute cough is something that kids generally love: honey. In a review of 14 studies, 9 of which were limited to pediatric patients, honey was associated with significant reductions in cough frequency, cough severity, and total symptom score. However, there was a moderate risk of bias in the included research, and evidence of honey’s benefit in placebo-controlled trials was limited. Honey used in this research came in a variety of forms, so the best dosage is uncertain.

Clearly, advancements are needed. Better symptom management in viral URI will almost certainly improve productivity across the population and will probably reduce the inappropriate use of antibiotics as well. I have said for years that the scientists who can solve the Gordian knot of pediatric mucus deserve three Nobel prizes. I look forward to that golden day.

Dr. Vega is a clinical professor of family medicine at the University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A surgeon in Tulsa shot by a disgruntled patient. A doctor in India beaten by a group of bereaved family members. A general practitioner in the United Kingdom threatened with stabbing. The reality is grim: Health care workers across the globe experience violence while at work. A new study identifies this trend and finds that 25% of health care workers polled were willing to quit because of such violence.

“That was pretty appalling,” Rahul Kashyap, MD, MBA, MBBS, recalls. Dr. Kashyap is one of the leaders of the Violence Study of Healthcare Workers and Systems (ViSHWaS), which polled an international sample of physicians, nurses, and hospital staff. This study has worrying implications, Dr. Kashyap says. In a time when hospital staff are reporting burnout in record numbers, further deterrents may be the last thing our health care system needs. But Dr. Kashyap hopes that bringing awareness to these trends may allow physicians, policymakers, and the public to mobilize and intervene before it’s too late.

Previous studies have revealed similar trends. The rate of workplace violence directed at U.S. health care workers is five times that of workers in any other industry, according to the Bureau of Labor Statistics. The same study found that attacks had increased 63% from 2011 to 2018. Other polls that focus on the pandemic show that nearly half of U.S. nurses believe that violence increased since the world shut down. Well before the pandemic, however, a study from the Indian Medical Association found that 75% of doctors experienced workplace violence.

With this history in mind, perhaps it’s not surprising that the idea for the study came from the authors’ personal experiences. They had seen coworkers go through attacks, or they had endured attacks themselves, Dr. Kashyap says. But they couldn’t find any global data to back up these experiences. So Dr. Kashyap and his colleagues formed a web of volunteers dedicated to creating a cross-sectional study.

They got in touch with researchers from countries across Asia, the Middle East, South America, North America, and Africa. The initial group agreed to reach out to their contacts, casting a wide net. Researchers used WhatsApp, LinkedIn, and text messages to distribute the survey. Health care workers in each country completed the brief questionnaire, recalling their prepandemic world and evaluating their current one.

Within 2 months, they had reached health care workers in more than 100 countries. They concluded the study when they received about 5,000 results, according to Dr. Kashyap, and then began the process of stratifying the data. For this report, they focused on critical care, emergency medicine, and anesthesiology, which resulted in 598 responses from 69 countries. Of these, India and the United States had the highest number of participants.

In all, 73% of participants reported facing physical or verbal violence while in the hospital; 48% said they felt less motivated to work because of that violence; 39% of respondents believed that the amount of violence they experienced was the same as before the COVID-19 pandemic; and 36% of respondents believed that violence had increased. Even though they were trained on guidelines from the Occupational Safety and Health Administration, 20% of participants felt unprepared to face violence.

Although the study didn’t analyze the reasons workers felt this way, Dr. Kashyap speculates that it could be related to the medical distrust that grew during the pandemic or the stress patients and health care professionals experienced during its peak.

Regardless, the researchers say their study is a starting point. Now that the trend has been highlighted, it may be acted on.

Moving forward, Dr. Kashyap believes that controlling for different variables could determine whether factors like gender or shift time put a worker at higher risk for violence. He hopes it’s possible to interrupt these patterns and reestablish trust in the hospital environment. “It’s aspirational, but you’re hoping that through studies like ViSHWaS, which means trust in Hindi ... [we could restore] the trust and confidence among health care providers for the patients and family members.”

A version of this article first appeared on Medscape.com.

A surgeon in Tulsa shot by a disgruntled patient. A doctor in India beaten by a group of bereaved family members. A general practitioner in the United Kingdom threatened with stabbing. The reality is grim: Health care workers across the globe experience violence while at work. A new study identifies this trend and finds that 25% of health care workers polled were willing to quit because of such violence.

“That was pretty appalling,” Rahul Kashyap, MD, MBA, MBBS, recalls. Dr. Kashyap is one of the leaders of the Violence Study of Healthcare Workers and Systems (ViSHWaS), which polled an international sample of physicians, nurses, and hospital staff. This study has worrying implications, Dr. Kashyap says. In a time when hospital staff are reporting burnout in record numbers, further deterrents may be the last thing our health care system needs. But Dr. Kashyap hopes that bringing awareness to these trends may allow physicians, policymakers, and the public to mobilize and intervene before it’s too late.

Previous studies have revealed similar trends. The rate of workplace violence directed at U.S. health care workers is five times that of workers in any other industry, according to the Bureau of Labor Statistics. The same study found that attacks had increased 63% from 2011 to 2018. Other polls that focus on the pandemic show that nearly half of U.S. nurses believe that violence increased since the world shut down. Well before the pandemic, however, a study from the Indian Medical Association found that 75% of doctors experienced workplace violence.

With this history in mind, perhaps it’s not surprising that the idea for the study came from the authors’ personal experiences. They had seen coworkers go through attacks, or they had endured attacks themselves, Dr. Kashyap says. But they couldn’t find any global data to back up these experiences. So Dr. Kashyap and his colleagues formed a web of volunteers dedicated to creating a cross-sectional study.

They got in touch with researchers from countries across Asia, the Middle East, South America, North America, and Africa. The initial group agreed to reach out to their contacts, casting a wide net. Researchers used WhatsApp, LinkedIn, and text messages to distribute the survey. Health care workers in each country completed the brief questionnaire, recalling their prepandemic world and evaluating their current one.

Within 2 months, they had reached health care workers in more than 100 countries. They concluded the study when they received about 5,000 results, according to Dr. Kashyap, and then began the process of stratifying the data. For this report, they focused on critical care, emergency medicine, and anesthesiology, which resulted in 598 responses from 69 countries. Of these, India and the United States had the highest number of participants.

In all, 73% of participants reported facing physical or verbal violence while in the hospital; 48% said they felt less motivated to work because of that violence; 39% of respondents believed that the amount of violence they experienced was the same as before the COVID-19 pandemic; and 36% of respondents believed that violence had increased. Even though they were trained on guidelines from the Occupational Safety and Health Administration, 20% of participants felt unprepared to face violence.

Although the study didn’t analyze the reasons workers felt this way, Dr. Kashyap speculates that it could be related to the medical distrust that grew during the pandemic or the stress patients and health care professionals experienced during its peak.

Regardless, the researchers say their study is a starting point. Now that the trend has been highlighted, it may be acted on.

Moving forward, Dr. Kashyap believes that controlling for different variables could determine whether factors like gender or shift time put a worker at higher risk for violence. He hopes it’s possible to interrupt these patterns and reestablish trust in the hospital environment. “It’s aspirational, but you’re hoping that through studies like ViSHWaS, which means trust in Hindi ... [we could restore] the trust and confidence among health care providers for the patients and family members.”

A version of this article first appeared on Medscape.com.

A surgeon in Tulsa shot by a disgruntled patient. A doctor in India beaten by a group of bereaved family members. A general practitioner in the United Kingdom threatened with stabbing. The reality is grim: Health care workers across the globe experience violence while at work. A new study identifies this trend and finds that 25% of health care workers polled were willing to quit because of such violence.

“That was pretty appalling,” Rahul Kashyap, MD, MBA, MBBS, recalls. Dr. Kashyap is one of the leaders of the Violence Study of Healthcare Workers and Systems (ViSHWaS), which polled an international sample of physicians, nurses, and hospital staff. This study has worrying implications, Dr. Kashyap says. In a time when hospital staff are reporting burnout in record numbers, further deterrents may be the last thing our health care system needs. But Dr. Kashyap hopes that bringing awareness to these trends may allow physicians, policymakers, and the public to mobilize and intervene before it’s too late.

Previous studies have revealed similar trends. The rate of workplace violence directed at U.S. health care workers is five times that of workers in any other industry, according to the Bureau of Labor Statistics. The same study found that attacks had increased 63% from 2011 to 2018. Other polls that focus on the pandemic show that nearly half of U.S. nurses believe that violence increased since the world shut down. Well before the pandemic, however, a study from the Indian Medical Association found that 75% of doctors experienced workplace violence.

With this history in mind, perhaps it’s not surprising that the idea for the study came from the authors’ personal experiences. They had seen coworkers go through attacks, or they had endured attacks themselves, Dr. Kashyap says. But they couldn’t find any global data to back up these experiences. So Dr. Kashyap and his colleagues formed a web of volunteers dedicated to creating a cross-sectional study.

They got in touch with researchers from countries across Asia, the Middle East, South America, North America, and Africa. The initial group agreed to reach out to their contacts, casting a wide net. Researchers used WhatsApp, LinkedIn, and text messages to distribute the survey. Health care workers in each country completed the brief questionnaire, recalling their prepandemic world and evaluating their current one.

Within 2 months, they had reached health care workers in more than 100 countries. They concluded the study when they received about 5,000 results, according to Dr. Kashyap, and then began the process of stratifying the data. For this report, they focused on critical care, emergency medicine, and anesthesiology, which resulted in 598 responses from 69 countries. Of these, India and the United States had the highest number of participants.

In all, 73% of participants reported facing physical or verbal violence while in the hospital; 48% said they felt less motivated to work because of that violence; 39% of respondents believed that the amount of violence they experienced was the same as before the COVID-19 pandemic; and 36% of respondents believed that violence had increased. Even though they were trained on guidelines from the Occupational Safety and Health Administration, 20% of participants felt unprepared to face violence.

Although the study didn’t analyze the reasons workers felt this way, Dr. Kashyap speculates that it could be related to the medical distrust that grew during the pandemic or the stress patients and health care professionals experienced during its peak.

Regardless, the researchers say their study is a starting point. Now that the trend has been highlighted, it may be acted on.

Moving forward, Dr. Kashyap believes that controlling for different variables could determine whether factors like gender or shift time put a worker at higher risk for violence. He hopes it’s possible to interrupt these patterns and reestablish trust in the hospital environment. “It’s aspirational, but you’re hoping that through studies like ViSHWaS, which means trust in Hindi ... [we could restore] the trust and confidence among health care providers for the patients and family members.”

A version of this article first appeared on Medscape.com.

At least one state licensing agency is revoking nursing licenses allegedly obtained in a multistate fake diploma scheme.

The U.S. Department of Justice recently announced charges against 25 owners, operators, and employees of three Florida nursing schools in a fraud scheme in which they sold as many as 7,600 fake nursing degrees.

The purchasers in the diploma scheme paid $10,000 to $15,000 for degrees and transcripts and some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses (RNs) and licensed practice nurses/vocational nurses (LPN/VNs) around the country, according to The New York Times.

Many of the degree recipients went on to work at hospitals, nursing homes, and Veterans Affairs medical centers, according to the U.S. Attorney’s Office for the Southern District of Florida.

Several national nursing organizations cooperated with the investigation, and the Delaware Division of Professional Regulation already annulled 26 licenses, according to the Delaware Nurses Association. Fake licenses were issued in five states, according to federal reports.

“We are deeply unsettled by this egregious act,” DNA President Stephanie McClellan, MSN, RN, CMSRN, said in the group’s press statement. “We want all Delaware nurses to be aware of this active issue and to speak up if there is a concern regarding capacity to practice safely by a colleague/peer,” she said.

The Oregon State Board of Nursing is also investigating at least a dozen nurses who may have paid for their degrees, according to a Portland CBS affiliate.

The National Council of State Boards of Nursing said in a statement that it had helped authorities identify and monitor the individuals who allegedly provided the false degrees.
 

Nursing community reacts

News of the fraud scheme spread through the nursing community, including social media. “The recent report on falsified nursing school degrees is both heartbreaking and serves as an eye-opener,” tweeted Usha Menon, PhD, RN, FAAN, dean and health professor of the University of South Florida Health College of Nursing. “There was enough of a need that prompted these bad actors to develop a scheme that could’ve endangered dozens of lives.”

Jennifer Mensik Kennedy, PhD, MBA, RN, the new president of the American Nurses Association, also weighed in. “The accusation that personnel at once-accredited nursing schools allegedly participated in this scheme is simply deplorable. These unlawful and unethical acts disparage the reputation of actual nurses everywhere who have rightfully earned [their titles] through their education, hard work, dedication, and time.”

The false degrees and transcripts were issued by three once-accredited and now-shuttered nursing schools in South Florida: Palm Beach School of Nursing, Sacred Heart International Institute, and Sienna College.

The alleged co-conspirators reportedly made $114 million from the scheme, which dates back to 2016, according to several news reports. Each defendant faces up to 20 years in prison.

Most LPN programs charge $10,000 to $15,000 to complete a program, Robert Rosseter, a spokesperson for the American Association of Colleges of Nursing (AACN), told this news organization.

None were AACN members, and none were accredited by the Commission on Collegiate Nursing Education, which is AACN’s autonomous accrediting agency, Mr. Rosseter said. AACN membership is voluntary and is open to schools offering baccalaureate or higher degrees, he explained.

“What is disturbing about this investigation is that there are over 7,600 people around the country with fraudulent nursing credentials who are potentially in critical health care roles treating patients,” Chad Yarbrough, acting special agent in charge for the FBI in Miami, said in the federal justice department release.
 

‘Operation Nightingale’ based on tip

The federal action, dubbed “Operation Nightingale” after the nursing pioneer Florence Nightingale, began in 2019. It was based on a tip related to a case in Maryland, according to Nurse.org.

That case ensnared Palm Beach School of Nursing owner Johanah Napoleon, who reportedly was selling fake degrees for $6,000 to $18,000 each to two individuals in Maryland and Virginia. Ms. Napoleon was charged in 2021 and eventually pled guilty. The Florida Board of Nursing shut down the Palm Beach school in 2017 owing to its students’ low passing rate on the national licensing exam.

Two participants in the bigger scheme who had also worked with Ms. Napoleon – Geralda Adrien and Woosvelt Predestin – were indicted in 2021. Ms. Adrien owned private education companies for people who at aspired to be nurses, and Mr. Predestin was an employee. They were sentenced to 27 months in prison last year and helped the federal officials build the larger case.

The 25 individuals who were charged Jan. 25 operated in Delaware, New York, New Jersey, Texas, and Florida.
 

Schemes lured immigrants

In the scheme involving Siena College, some of the individuals acted as recruiters to direct nurses who were looking for employment to the school, where they allegedly would then pay for an RN or LPN/VN degree. The recipients of the false documents then used them to obtain jobs, including at a hospital in Georgia and a Veterans Affairs medical center in Maryland, according to one indictment. The president of Siena and her co-conspirators sold more than 2,000 fake diplomas, according to charging documents.

At the Palm Beach College of Nursing, individuals at various nursing prep and education programs allegedly helped others obtain fake degrees and transcripts, which were then used to pass RN and LPN/VN licensing exams in states that included Massachusetts, New Jersey, New York, and Ohio, according to the indictment.

Some individuals then secured employment with a nursing home in Ohio, a home health agency for pediatric patients in Massachusetts, and skilled nursing facilities in New York and New Jersey.

Prosecutors allege that the president of Sacred Heart International Institute and two other co-conspirators sold 588 fake diplomas.

The FBI said that some of the aspiring nurses who were talked into buying the degrees were LPNs who wanted to become RNs and that most of those lured into the scheme were from South Florida’s Haitian American immigrant community, Nurse.org reported.

A version of this article first appeared on Medscape.com.

At least one state licensing agency is revoking nursing licenses allegedly obtained in a multistate fake diploma scheme.

The U.S. Department of Justice recently announced charges against 25 owners, operators, and employees of three Florida nursing schools in a fraud scheme in which they sold as many as 7,600 fake nursing degrees.

The purchasers in the diploma scheme paid $10,000 to $15,000 for degrees and transcripts and some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses (RNs) and licensed practice nurses/vocational nurses (LPN/VNs) around the country, according to The New York Times.

Many of the degree recipients went on to work at hospitals, nursing homes, and Veterans Affairs medical centers, according to the U.S. Attorney’s Office for the Southern District of Florida.

Several national nursing organizations cooperated with the investigation, and the Delaware Division of Professional Regulation already annulled 26 licenses, according to the Delaware Nurses Association. Fake licenses were issued in five states, according to federal reports.

“We are deeply unsettled by this egregious act,” DNA President Stephanie McClellan, MSN, RN, CMSRN, said in the group’s press statement. “We want all Delaware nurses to be aware of this active issue and to speak up if there is a concern regarding capacity to practice safely by a colleague/peer,” she said.

The Oregon State Board of Nursing is also investigating at least a dozen nurses who may have paid for their degrees, according to a Portland CBS affiliate.

The National Council of State Boards of Nursing said in a statement that it had helped authorities identify and monitor the individuals who allegedly provided the false degrees.
 

Nursing community reacts

News of the fraud scheme spread through the nursing community, including social media. “The recent report on falsified nursing school degrees is both heartbreaking and serves as an eye-opener,” tweeted Usha Menon, PhD, RN, FAAN, dean and health professor of the University of South Florida Health College of Nursing. “There was enough of a need that prompted these bad actors to develop a scheme that could’ve endangered dozens of lives.”

Jennifer Mensik Kennedy, PhD, MBA, RN, the new president of the American Nurses Association, also weighed in. “The accusation that personnel at once-accredited nursing schools allegedly participated in this scheme is simply deplorable. These unlawful and unethical acts disparage the reputation of actual nurses everywhere who have rightfully earned [their titles] through their education, hard work, dedication, and time.”

The false degrees and transcripts were issued by three once-accredited and now-shuttered nursing schools in South Florida: Palm Beach School of Nursing, Sacred Heart International Institute, and Sienna College.

The alleged co-conspirators reportedly made $114 million from the scheme, which dates back to 2016, according to several news reports. Each defendant faces up to 20 years in prison.

Most LPN programs charge $10,000 to $15,000 to complete a program, Robert Rosseter, a spokesperson for the American Association of Colleges of Nursing (AACN), told this news organization.

None were AACN members, and none were accredited by the Commission on Collegiate Nursing Education, which is AACN’s autonomous accrediting agency, Mr. Rosseter said. AACN membership is voluntary and is open to schools offering baccalaureate or higher degrees, he explained.

“What is disturbing about this investigation is that there are over 7,600 people around the country with fraudulent nursing credentials who are potentially in critical health care roles treating patients,” Chad Yarbrough, acting special agent in charge for the FBI in Miami, said in the federal justice department release.
 

‘Operation Nightingale’ based on tip

The federal action, dubbed “Operation Nightingale” after the nursing pioneer Florence Nightingale, began in 2019. It was based on a tip related to a case in Maryland, according to Nurse.org.

That case ensnared Palm Beach School of Nursing owner Johanah Napoleon, who reportedly was selling fake degrees for $6,000 to $18,000 each to two individuals in Maryland and Virginia. Ms. Napoleon was charged in 2021 and eventually pled guilty. The Florida Board of Nursing shut down the Palm Beach school in 2017 owing to its students’ low passing rate on the national licensing exam.

Two participants in the bigger scheme who had also worked with Ms. Napoleon – Geralda Adrien and Woosvelt Predestin – were indicted in 2021. Ms. Adrien owned private education companies for people who at aspired to be nurses, and Mr. Predestin was an employee. They were sentenced to 27 months in prison last year and helped the federal officials build the larger case.

The 25 individuals who were charged Jan. 25 operated in Delaware, New York, New Jersey, Texas, and Florida.
 

Schemes lured immigrants

In the scheme involving Siena College, some of the individuals acted as recruiters to direct nurses who were looking for employment to the school, where they allegedly would then pay for an RN or LPN/VN degree. The recipients of the false documents then used them to obtain jobs, including at a hospital in Georgia and a Veterans Affairs medical center in Maryland, according to one indictment. The president of Siena and her co-conspirators sold more than 2,000 fake diplomas, according to charging documents.

At the Palm Beach College of Nursing, individuals at various nursing prep and education programs allegedly helped others obtain fake degrees and transcripts, which were then used to pass RN and LPN/VN licensing exams in states that included Massachusetts, New Jersey, New York, and Ohio, according to the indictment.

Some individuals then secured employment with a nursing home in Ohio, a home health agency for pediatric patients in Massachusetts, and skilled nursing facilities in New York and New Jersey.

Prosecutors allege that the president of Sacred Heart International Institute and two other co-conspirators sold 588 fake diplomas.

The FBI said that some of the aspiring nurses who were talked into buying the degrees were LPNs who wanted to become RNs and that most of those lured into the scheme were from South Florida’s Haitian American immigrant community, Nurse.org reported.

A version of this article first appeared on Medscape.com.

At least one state licensing agency is revoking nursing licenses allegedly obtained in a multistate fake diploma scheme.

The U.S. Department of Justice recently announced charges against 25 owners, operators, and employees of three Florida nursing schools in a fraud scheme in which they sold as many as 7,600 fake nursing degrees.

The purchasers in the diploma scheme paid $10,000 to $15,000 for degrees and transcripts and some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses (RNs) and licensed practice nurses/vocational nurses (LPN/VNs) around the country, according to The New York Times.

Many of the degree recipients went on to work at hospitals, nursing homes, and Veterans Affairs medical centers, according to the U.S. Attorney’s Office for the Southern District of Florida.

Several national nursing organizations cooperated with the investigation, and the Delaware Division of Professional Regulation already annulled 26 licenses, according to the Delaware Nurses Association. Fake licenses were issued in five states, according to federal reports.

“We are deeply unsettled by this egregious act,” DNA President Stephanie McClellan, MSN, RN, CMSRN, said in the group’s press statement. “We want all Delaware nurses to be aware of this active issue and to speak up if there is a concern regarding capacity to practice safely by a colleague/peer,” she said.

The Oregon State Board of Nursing is also investigating at least a dozen nurses who may have paid for their degrees, according to a Portland CBS affiliate.

The National Council of State Boards of Nursing said in a statement that it had helped authorities identify and monitor the individuals who allegedly provided the false degrees.
 

Nursing community reacts

News of the fraud scheme spread through the nursing community, including social media. “The recent report on falsified nursing school degrees is both heartbreaking and serves as an eye-opener,” tweeted Usha Menon, PhD, RN, FAAN, dean and health professor of the University of South Florida Health College of Nursing. “There was enough of a need that prompted these bad actors to develop a scheme that could’ve endangered dozens of lives.”

Jennifer Mensik Kennedy, PhD, MBA, RN, the new president of the American Nurses Association, also weighed in. “The accusation that personnel at once-accredited nursing schools allegedly participated in this scheme is simply deplorable. These unlawful and unethical acts disparage the reputation of actual nurses everywhere who have rightfully earned [their titles] through their education, hard work, dedication, and time.”

The false degrees and transcripts were issued by three once-accredited and now-shuttered nursing schools in South Florida: Palm Beach School of Nursing, Sacred Heart International Institute, and Sienna College.

The alleged co-conspirators reportedly made $114 million from the scheme, which dates back to 2016, according to several news reports. Each defendant faces up to 20 years in prison.

Most LPN programs charge $10,000 to $15,000 to complete a program, Robert Rosseter, a spokesperson for the American Association of Colleges of Nursing (AACN), told this news organization.

None were AACN members, and none were accredited by the Commission on Collegiate Nursing Education, which is AACN’s autonomous accrediting agency, Mr. Rosseter said. AACN membership is voluntary and is open to schools offering baccalaureate or higher degrees, he explained.

“What is disturbing about this investigation is that there are over 7,600 people around the country with fraudulent nursing credentials who are potentially in critical health care roles treating patients,” Chad Yarbrough, acting special agent in charge for the FBI in Miami, said in the federal justice department release.
 

‘Operation Nightingale’ based on tip

The federal action, dubbed “Operation Nightingale” after the nursing pioneer Florence Nightingale, began in 2019. It was based on a tip related to a case in Maryland, according to Nurse.org.

That case ensnared Palm Beach School of Nursing owner Johanah Napoleon, who reportedly was selling fake degrees for $6,000 to $18,000 each to two individuals in Maryland and Virginia. Ms. Napoleon was charged in 2021 and eventually pled guilty. The Florida Board of Nursing shut down the Palm Beach school in 2017 owing to its students’ low passing rate on the national licensing exam.

Two participants in the bigger scheme who had also worked with Ms. Napoleon – Geralda Adrien and Woosvelt Predestin – were indicted in 2021. Ms. Adrien owned private education companies for people who at aspired to be nurses, and Mr. Predestin was an employee. They were sentenced to 27 months in prison last year and helped the federal officials build the larger case.

The 25 individuals who were charged Jan. 25 operated in Delaware, New York, New Jersey, Texas, and Florida.
 

Schemes lured immigrants

In the scheme involving Siena College, some of the individuals acted as recruiters to direct nurses who were looking for employment to the school, where they allegedly would then pay for an RN or LPN/VN degree. The recipients of the false documents then used them to obtain jobs, including at a hospital in Georgia and a Veterans Affairs medical center in Maryland, according to one indictment. The president of Siena and her co-conspirators sold more than 2,000 fake diplomas, according to charging documents.

At the Palm Beach College of Nursing, individuals at various nursing prep and education programs allegedly helped others obtain fake degrees and transcripts, which were then used to pass RN and LPN/VN licensing exams in states that included Massachusetts, New Jersey, New York, and Ohio, according to the indictment.

Some individuals then secured employment with a nursing home in Ohio, a home health agency for pediatric patients in Massachusetts, and skilled nursing facilities in New York and New Jersey.

Prosecutors allege that the president of Sacred Heart International Institute and two other co-conspirators sold 588 fake diplomas.

The FBI said that some of the aspiring nurses who were talked into buying the degrees were LPNs who wanted to become RNs and that most of those lured into the scheme were from South Florida’s Haitian American immigrant community, Nurse.org reported.

A version of this article first appeared on Medscape.com.

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

A version of this article first appeared on WebMD.com.

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

A version of this article first appeared on WebMD.com.

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

A version of this article first appeared on WebMD.com.

To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.

Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.

The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.

They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.

Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).

Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.

Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.” 

Because they separately examined the association of demographic characteristics with the GWI phenotypes, the researchers also found that women, regardless of deployment status, had higher odds of meeting the GWI phenotypes compared with men.

Their findings will be used, the researchers say, “to understand how genetic variation is associated with the GWI phenotypes and to identify potential pathophysiologic underpinnings of GWI, pleiotropy with other traits, and gene by environment interactions.” With information from this large dataset of GW-era veterans, they will have a “powerful tool” for in-depth study of exposures and underlying genetic susceptibility to GWI—studies that could not be performed, they say, without the full description of the GWI phenotypes they have documented.

The study had several strengths, the researchers say. For example, unlike previous studies, this one had a sample size large enough to allow more representation of subpopulations, including age, sex, race, ethnicity, education, and military service. The researchers also collected data from surveys, especially data on veterans’ self-reported symptoms and other information “incompletely and infrequently documented in medical records.”

Finally, the data for the study were collected more than 27 years after the GW. It, therefore, gives an “updated, detailed description” of symptoms and conditions affecting GW-era veterans, decades after their return from service.

To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.

Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.

The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.

They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.

Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).

Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.

Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.” 

Because they separately examined the association of demographic characteristics with the GWI phenotypes, the researchers also found that women, regardless of deployment status, had higher odds of meeting the GWI phenotypes compared with men.

Their findings will be used, the researchers say, “to understand how genetic variation is associated with the GWI phenotypes and to identify potential pathophysiologic underpinnings of GWI, pleiotropy with other traits, and gene by environment interactions.” With information from this large dataset of GW-era veterans, they will have a “powerful tool” for in-depth study of exposures and underlying genetic susceptibility to GWI—studies that could not be performed, they say, without the full description of the GWI phenotypes they have documented.

The study had several strengths, the researchers say. For example, unlike previous studies, this one had a sample size large enough to allow more representation of subpopulations, including age, sex, race, ethnicity, education, and military service. The researchers also collected data from surveys, especially data on veterans’ self-reported symptoms and other information “incompletely and infrequently documented in medical records.”

Finally, the data for the study were collected more than 27 years after the GW. It, therefore, gives an “updated, detailed description” of symptoms and conditions affecting GW-era veterans, decades after their return from service.

To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.

Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.

The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.

They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.

Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).

Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.

Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.” 

Because they separately examined the association of demographic characteristics with the GWI phenotypes, the researchers also found that women, regardless of deployment status, had higher odds of meeting the GWI phenotypes compared with men.

Their findings will be used, the researchers say, “to understand how genetic variation is associated with the GWI phenotypes and to identify potential pathophysiologic underpinnings of GWI, pleiotropy with other traits, and gene by environment interactions.” With information from this large dataset of GW-era veterans, they will have a “powerful tool” for in-depth study of exposures and underlying genetic susceptibility to GWI—studies that could not be performed, they say, without the full description of the GWI phenotypes they have documented.

The study had several strengths, the researchers say. For example, unlike previous studies, this one had a sample size large enough to allow more representation of subpopulations, including age, sex, race, ethnicity, education, and military service. The researchers also collected data from surveys, especially data on veterans’ self-reported symptoms and other information “incompletely and infrequently documented in medical records.”

Finally, the data for the study were collected more than 27 years after the GW. It, therefore, gives an “updated, detailed description” of symptoms and conditions affecting GW-era veterans, decades after their return from service.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.