Infectious Diseases

In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.

Courtesy NIH

In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.

For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).

Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.

Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.

In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.

“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.

The authors reported receiving funding from a number of pharmaceutical companies.

[email protected]

SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
 

In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.

Courtesy NIH

In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.

For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).

Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.

Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.

In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.

“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.

The authors reported receiving funding from a number of pharmaceutical companies.

[email protected]

SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
 

In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.

Courtesy NIH

In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.

For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).

Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.

Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.

In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.

“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.

The authors reported receiving funding from a number of pharmaceutical companies.

[email protected]

SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
 

A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.

©vchal/Thinkstock

The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.

The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.

The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).

“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.

The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.

[email protected]

SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.

A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.

©vchal/Thinkstock

The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.

The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.

The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).

“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.

The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.

[email protected]

SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.

A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.

©vchal/Thinkstock

The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.

The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.

The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).

“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.

The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.

[email protected]

SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.

Case Report

A 26-year-old woman with a medical history of newly diagnosed diabetes mellitus (DM), obesity, and asthma was evaluated as a hospital consultation with a vegetative plaque on the left lateral ankle of 13 months’ duration. The lesion first appeared as a red scaly rash that became purulent. The lesion had been treated with multiple rounds of topical antibiotics, oral antibiotics, topical antifungals, and corticosteroids without resolution. The patient denied pain or any decrease in ankle mobility. Review of systems was otherwise negative.

On physical examination, 3 large, pink, scaly, crusted plaques with surrounding erythema were observed (Figure 1A). On palpation, purulent drainage with a foul odor was noted in the area underlying the lesion. Initial punch biopsy demonstrated epidermal hyperplasia with neutrophil-rich sinus tracts consistent with pyoderma vegetans (PV)(Figure 2A). Tissue culture was positive for Staphylococcus aureus and Streptococcus anginosus. Cultures for both fungi and acid-fast bacilli were negative for growth.

The patient was treated with mupirocin ointment 2% and 3 months of cephalexin 250 mg twice daily, which cleared the purulent crust; however, serous drainage, ulceration, and erythema persisted. The patient needed an extended course of antibiotics, which had not been previously administered to clear the purulence. During this treatment regimen, the patient’s DM remained uncontrolled.

A second deeper punch biopsy revealed a layered granulomatous infiltrate with sclerosis throughout the dermis most consistent with necrobiosis lipoidica (NL)(Figure 2B). Direct immunofluorescence biopsy was negative. Once the PV was clear, betamethasone dipropionate ointment 0.05% was initiated to address the residual lesions (Figure 1B).

Physical examination combined with histopathologic findings and staphylococcal- and streptococcal-positive tissue cultures supported a diagnosis of NL with superimposed PV.

Comment

Necrobiosis lipoidica is a chronic granulomatous disease characterized by collagen degeneration, granulomatous formation, and endothelial wall thickening.¹ The condition is most commonly seen in association with insulin-dependent DM, though it also has been described in other inflammatory conditions. A case of NL in monozygotic twins has been reported, suggesting a genetic component in nondiabetic patients with NL.² Necrobiosis lipoidica affects females more often than males.

The pathogenesis of NL is not well understood but likely involves secondary microangiopathy because of glycoprotein deposition in vessel walls, leading to vascular thickening. Histopathology reveals palisading and necrobiotic granulomas comprising large confluent areas of necrobiosis throughout the dermis, giving a layered appearance.³

Clinically, NL presents with asymptomatic, well-circumscribed, violaceous papules and nodules that coalesce into plaques on the lower extremities, face, or trunk. The plaques have a central red-brown hue that progressively becomes more yellow and atrophic. The lesions can become eroded and ulcerated if left untreated.¹

Clinical diagnosis of NL can be challenging due to the similar clinical findings of other granulomatous lesions, such as granuloma annulare and cutaneous sarcoidosis. As reported by Pellicano and colleagues,⁴ dermoscopy has proved to be an excellent tool for differentiating these granulomatous skin lesions. Necrobiosis lipoidica demonstrates elongated serpentine telangiectases overlying a white structureless background, whereas granuloma annulare reveals orange-red structureless peripheral borders.⁵

Treatment of NL is difficult; patients often are refractory. Tight control of blood glucose alone has not been proven to cure NL. The mainstay of treatment is topical and intralesional corticosteroids at the active borders of the lesions. Tumor necrosis factor α inhibitors have shown some success, though recurrence has been reported.⁶ Other treatments, such as topical tretinoin and topical tacrolimus, may be of some benefit for atrophic NL lesions. Studies also have shown that skin grafting can be of surgical benefit in ulcerative NL with a low rate of recurrence.⁶ Control and management of DM plus lifestyle modifications may play a role in decreasing the severity of NL.⁷ Topical psoralen plus UVA light therapy and other experimental treatments, such as antiplatelet medications,⁸ also have been utilized.

The case of NL presented here was complicated by a superimposed suppurative infection consistent with PV, a rare chronic bacterial infection of the skin that presents with vegetative plaques. Pyoderma vegetans is most commonly observed in patients with underlying immunosuppression, likely secondary to DM in this case. Pyoderma vegetans is most often caused by S aureus and β-hemolytic streptococci. The clinical presentation of PV reveals verrucous vegetative plaques with pustules and abscesses. The borders of the lesions may be elevated and have a granulomatous appearance, thus complicating clinical diagnosis. There often is foul-smelling, purulent discharge within the plaques.⁹

Histopathology reveals pseudoepitheliomatous hyperplasia with abscesses and sinus tracts. An acute or chronic granulomatous inflammatory infiltrate may be observed. Basophilic fungus like granules are not seen within specimens of PV, which helps differentiate the disease from botryomycosis.¹⁰

There is no standardized treatment of PV; topical and systemic antibiotics are mainstays.¹⁰ One reported case of PV responded well to acitretin.⁹ Our patient responded well to 3 months of oral antibiotic therapy, followed by topical corticosteroids.

Case Report

A 26-year-old woman with a medical history of newly diagnosed diabetes mellitus (DM), obesity, and asthma was evaluated as a hospital consultation with a vegetative plaque on the left lateral ankle of 13 months’ duration. The lesion first appeared as a red scaly rash that became purulent. The lesion had been treated with multiple rounds of topical antibiotics, oral antibiotics, topical antifungals, and corticosteroids without resolution. The patient denied pain or any decrease in ankle mobility. Review of systems was otherwise negative.

On physical examination, 3 large, pink, scaly, crusted plaques with surrounding erythema were observed (Figure 1A). On palpation, purulent drainage with a foul odor was noted in the area underlying the lesion. Initial punch biopsy demonstrated epidermal hyperplasia with neutrophil-rich sinus tracts consistent with pyoderma vegetans (PV)(Figure 2A). Tissue culture was positive for Staphylococcus aureus and Streptococcus anginosus. Cultures for both fungi and acid-fast bacilli were negative for growth.

The patient was treated with mupirocin ointment 2% and 3 months of cephalexin 250 mg twice daily, which cleared the purulent crust; however, serous drainage, ulceration, and erythema persisted. The patient needed an extended course of antibiotics, which had not been previously administered to clear the purulence. During this treatment regimen, the patient’s DM remained uncontrolled.

A second deeper punch biopsy revealed a layered granulomatous infiltrate with sclerosis throughout the dermis most consistent with necrobiosis lipoidica (NL)(Figure 2B). Direct immunofluorescence biopsy was negative. Once the PV was clear, betamethasone dipropionate ointment 0.05% was initiated to address the residual lesions (Figure 1B).

Physical examination combined with histopathologic findings and staphylococcal- and streptococcal-positive tissue cultures supported a diagnosis of NL with superimposed PV.

Comment

Necrobiosis lipoidica is a chronic granulomatous disease characterized by collagen degeneration, granulomatous formation, and endothelial wall thickening.¹ The condition is most commonly seen in association with insulin-dependent DM, though it also has been described in other inflammatory conditions. A case of NL in monozygotic twins has been reported, suggesting a genetic component in nondiabetic patients with NL.² Necrobiosis lipoidica affects females more often than males.

The pathogenesis of NL is not well understood but likely involves secondary microangiopathy because of glycoprotein deposition in vessel walls, leading to vascular thickening. Histopathology reveals palisading and necrobiotic granulomas comprising large confluent areas of necrobiosis throughout the dermis, giving a layered appearance.³

Clinically, NL presents with asymptomatic, well-circumscribed, violaceous papules and nodules that coalesce into plaques on the lower extremities, face, or trunk. The plaques have a central red-brown hue that progressively becomes more yellow and atrophic. The lesions can become eroded and ulcerated if left untreated.¹

Clinical diagnosis of NL can be challenging due to the similar clinical findings of other granulomatous lesions, such as granuloma annulare and cutaneous sarcoidosis. As reported by Pellicano and colleagues,⁴ dermoscopy has proved to be an excellent tool for differentiating these granulomatous skin lesions. Necrobiosis lipoidica demonstrates elongated serpentine telangiectases overlying a white structureless background, whereas granuloma annulare reveals orange-red structureless peripheral borders.⁵

Treatment of NL is difficult; patients often are refractory. Tight control of blood glucose alone has not been proven to cure NL. The mainstay of treatment is topical and intralesional corticosteroids at the active borders of the lesions. Tumor necrosis factor α inhibitors have shown some success, though recurrence has been reported.⁶ Other treatments, such as topical tretinoin and topical tacrolimus, may be of some benefit for atrophic NL lesions. Studies also have shown that skin grafting can be of surgical benefit in ulcerative NL with a low rate of recurrence.⁶ Control and management of DM plus lifestyle modifications may play a role in decreasing the severity of NL.⁷ Topical psoralen plus UVA light therapy and other experimental treatments, such as antiplatelet medications,⁸ also have been utilized.

The case of NL presented here was complicated by a superimposed suppurative infection consistent with PV, a rare chronic bacterial infection of the skin that presents with vegetative plaques. Pyoderma vegetans is most commonly observed in patients with underlying immunosuppression, likely secondary to DM in this case. Pyoderma vegetans is most often caused by S aureus and β-hemolytic streptococci. The clinical presentation of PV reveals verrucous vegetative plaques with pustules and abscesses. The borders of the lesions may be elevated and have a granulomatous appearance, thus complicating clinical diagnosis. There often is foul-smelling, purulent discharge within the plaques.⁹

Histopathology reveals pseudoepitheliomatous hyperplasia with abscesses and sinus tracts. An acute or chronic granulomatous inflammatory infiltrate may be observed. Basophilic fungus like granules are not seen within specimens of PV, which helps differentiate the disease from botryomycosis.¹⁰

There is no standardized treatment of PV; topical and systemic antibiotics are mainstays.¹⁰ One reported case of PV responded well to acitretin.⁹ Our patient responded well to 3 months of oral antibiotic therapy, followed by topical corticosteroids.

Case Report

A 26-year-old woman with a medical history of newly diagnosed diabetes mellitus (DM), obesity, and asthma was evaluated as a hospital consultation with a vegetative plaque on the left lateral ankle of 13 months’ duration. The lesion first appeared as a red scaly rash that became purulent. The lesion had been treated with multiple rounds of topical antibiotics, oral antibiotics, topical antifungals, and corticosteroids without resolution. The patient denied pain or any decrease in ankle mobility. Review of systems was otherwise negative.

On physical examination, 3 large, pink, scaly, crusted plaques with surrounding erythema were observed (Figure 1A). On palpation, purulent drainage with a foul odor was noted in the area underlying the lesion. Initial punch biopsy demonstrated epidermal hyperplasia with neutrophil-rich sinus tracts consistent with pyoderma vegetans (PV)(Figure 2A). Tissue culture was positive for Staphylococcus aureus and Streptococcus anginosus. Cultures for both fungi and acid-fast bacilli were negative for growth.

The patient was treated with mupirocin ointment 2% and 3 months of cephalexin 250 mg twice daily, which cleared the purulent crust; however, serous drainage, ulceration, and erythema persisted. The patient needed an extended course of antibiotics, which had not been previously administered to clear the purulence. During this treatment regimen, the patient’s DM remained uncontrolled.

A second deeper punch biopsy revealed a layered granulomatous infiltrate with sclerosis throughout the dermis most consistent with necrobiosis lipoidica (NL)(Figure 2B). Direct immunofluorescence biopsy was negative. Once the PV was clear, betamethasone dipropionate ointment 0.05% was initiated to address the residual lesions (Figure 1B).

Physical examination combined with histopathologic findings and staphylococcal- and streptococcal-positive tissue cultures supported a diagnosis of NL with superimposed PV.

Comment

Necrobiosis lipoidica is a chronic granulomatous disease characterized by collagen degeneration, granulomatous formation, and endothelial wall thickening.¹ The condition is most commonly seen in association with insulin-dependent DM, though it also has been described in other inflammatory conditions. A case of NL in monozygotic twins has been reported, suggesting a genetic component in nondiabetic patients with NL.² Necrobiosis lipoidica affects females more often than males.

The pathogenesis of NL is not well understood but likely involves secondary microangiopathy because of glycoprotein deposition in vessel walls, leading to vascular thickening. Histopathology reveals palisading and necrobiotic granulomas comprising large confluent areas of necrobiosis throughout the dermis, giving a layered appearance.³

Clinically, NL presents with asymptomatic, well-circumscribed, violaceous papules and nodules that coalesce into plaques on the lower extremities, face, or trunk. The plaques have a central red-brown hue that progressively becomes more yellow and atrophic. The lesions can become eroded and ulcerated if left untreated.¹

Clinical diagnosis of NL can be challenging due to the similar clinical findings of other granulomatous lesions, such as granuloma annulare and cutaneous sarcoidosis. As reported by Pellicano and colleagues,⁴ dermoscopy has proved to be an excellent tool for differentiating these granulomatous skin lesions. Necrobiosis lipoidica demonstrates elongated serpentine telangiectases overlying a white structureless background, whereas granuloma annulare reveals orange-red structureless peripheral borders.⁵

Treatment of NL is difficult; patients often are refractory. Tight control of blood glucose alone has not been proven to cure NL. The mainstay of treatment is topical and intralesional corticosteroids at the active borders of the lesions. Tumor necrosis factor α inhibitors have shown some success, though recurrence has been reported.⁶ Other treatments, such as topical tretinoin and topical tacrolimus, may be of some benefit for atrophic NL lesions. Studies also have shown that skin grafting can be of surgical benefit in ulcerative NL with a low rate of recurrence.⁶ Control and management of DM plus lifestyle modifications may play a role in decreasing the severity of NL.⁷ Topical psoralen plus UVA light therapy and other experimental treatments, such as antiplatelet medications,⁸ also have been utilized.

The case of NL presented here was complicated by a superimposed suppurative infection consistent with PV, a rare chronic bacterial infection of the skin that presents with vegetative plaques. Pyoderma vegetans is most commonly observed in patients with underlying immunosuppression, likely secondary to DM in this case. Pyoderma vegetans is most often caused by S aureus and β-hemolytic streptococci. The clinical presentation of PV reveals verrucous vegetative plaques with pustules and abscesses. The borders of the lesions may be elevated and have a granulomatous appearance, thus complicating clinical diagnosis. There often is foul-smelling, purulent discharge within the plaques.⁹

Histopathology reveals pseudoepitheliomatous hyperplasia with abscesses and sinus tracts. An acute or chronic granulomatous inflammatory infiltrate may be observed. Basophilic fungus like granules are not seen within specimens of PV, which helps differentiate the disease from botryomycosis.¹⁰

There is no standardized treatment of PV; topical and systemic antibiotics are mainstays.¹⁰ One reported case of PV responded well to acitretin.⁹ Our patient responded well to 3 months of oral antibiotic therapy, followed by topical corticosteroids.

Bedbugs are common pests causing several health and economic consequences. With increased travel, pesticide resistance, and a lack of awareness about prevention, bedbugs have become even more difficult to control, especially within large population centers.¹ The US Environmental Protection Agency considers bedbugs to be a considerable public health issue.² Typically, they are found in private residences; however, there have been more reports of bedbugs discovered in the workplace within the last 20 years.^3-5 Herein, we present a case of bedbugs presenting in this unusual environment.

Case Report

A 42-year-old man presented to our dermatology clinic with intensely itchy bumps over the bilateral posterior arms of 3 months’ duration. He had no other skin, hair, or nail concerns. Over the last 3 months prior to dermatologic evaluation, he was treated by an outside physician with topical steroids, systemic antibiotics, topical antifungals, and even systemic steroids with no improvement of the lesions or symptoms. On clinical examination at the current presentation, 8 to 10 pink dermal papules coalescing into 10-cm round patches were noted on the bilateral posterior arms (Figure 1). A punch biopsy of the posterior right arm was performed, and histologic analysis showed a dense superficial and deep infiltrate and a perivascular infiltrate of lymphocytes and eosinophils (Figure 2). No notable epidermal changes were observed.

At this time, the patient was counseled that the most likely cause was some unknown arthropod exposure. Given the chronicity of the patient’s disease course, bedbugs were favored; however, an extensive search of the patient’s home failed to uncover any arthropods, let alone bedbugs. A few weeks later, the patient discovered insects emanating from the mesh backing of his office chair while at work (Figure 3). The location of the intruders corresponded exactly with the lesions on the posterior arms. The occupational health office at his workplace collected samples of the arthropods and confirmed they were bedbugs. The patient’s lesions resolved with topical clobetasol once eradication of the workplace was complete.

Morphology and Epidemiology
Bedbugs are wingless arthropods that have flat, oval-shaped, reddish brown bodies. They are approximately 4.5-mm long and 2.5-mm wide (Figure 4). The 2 most common species of bedbugs that infect humans are Cimex lectularius and Cimex hemipterus. Bedbugs are most commonly found in hotels, apartments, and residential households near sleep locations. They reside in crevices, cracks, mattresses, cushions, dressers, and other structures proximal to the bed. During the day they remain hidden, but at night they emerge for a blood meal. The average lifespan of a bedbug is 6 to 12 months.⁶ Females lay more than 200 eggs that hatch in approximately 6 to 10 days.⁷ Bedbugs progress through 5 nymph stages before becoming adults; several blood meals are required to advance each stage.⁶

Although commonly attributed to the home, bedbugs are being increasingly seen in the office setting.^3-5 In a survey given to pest management professionals in 2015, more than 45% reported that they were contracted by corporations for bedbug infestations in office settings, an increase from 18% in 2010 and 36% in 2013.³ Bedbugs are brought into offices through clothing, luggage, books, and other personal items. Unable to find hosts at night, bedbugs adapt to daytime hours and spread to more unpredictable locations, including chairs, office equipment, desks, and computers.⁴ Additionally, they frequently move around to find a suitable host.⁵ As a result, the growth rate of bedbugs in an office setting is much slower than in the home, with fewer insects. Our patient did not have bedbugs at home, but it is possible that other employees transported them to the office over time.

Clinical Manifestations
Bedbugs cause pruritic and nonpruritic skin rashes, often of the arms, legs, neck, and face. A common reaction is an erythematous papule with a hemorrhagic punctum caused by one bite.⁸ Other presentations include purpuric macules, bullae, and papular urticaria.^8-10 Although bedbugs are suspected to transmit infectious diseases, no reports have substantiated that claim.¹¹

Our patient had several coalescing dermal papules on the arms indicating multiple bites around the same area. Due to the stationary aspect of his job—with the arms resting on his chair while typing at his desk—our patient was an easy target for consistent blood meals.

Detection
Due to an overall smaller population of insects in an office setting, detection of bedbugs in the workplace can be difficult. Infestations can be primarily identified on visual inspection by pest control.¹² The mesh backing on our patient’s chair was one site where bedbugs resided. It is important to check areas where employees congregate, such as lounges, lunch areas, conference rooms, and printers.⁴ It also is essential to examine coatracks and locker rooms, as employees may leave personal items that can serve as a source of transmission of the bugs from home. Additional detection tools provided by pest management professionals include canines, as well as devices that emit pheromones, carbon dioxide, or heat to ensnare the insects.¹²

Treatment
Treatment of bedbug bites is quite variable. For some patients, lesions may resolve on their own. Pruritic maculopapular eruptions can be treated with topical pramoxine or doxepin.⁸ Patients who develop allergic urticaria can use oral antihistamines. Systemic reactions such as anaphylaxis can be treated with a combination of intramuscular epinephrine, antihistamines, and corticosteroids.⁸ The etiology of our patient’s condition initially was unknown, and thus he was given unnecessary systemic steroids and antifungals until the source of the rash was identified and eradicated. Topical clobetasol was subsequently administered and was sufficient to resolve his symptoms.

Final Thoughts

Bedbugs continue to remain a nuisance in the home. This case provides an example of bedbugs in the office, a location that is not commonly associated with bedbug infestations. Bedbugs pose numerous psychological, economic, and health consequences.² Productivity can be reduced, as patients with symptomatic lesions will be unable to work effectively, and those who are unaffected may be unwilling to work knowing their office environment poses a health risk. In addition, employees may worry about bringing the bedbugs home. It is important that employees be educated on the signs of a bedbug infestation and take preventive measures to stop spreading or introducing them to the office space. Due to the scattered habitation of bedbugs in offices, pest control managers need to be vigilant to identify sources of infestation and eradicate accordingly. Clinical manifestations can be nonspecific, resembling autoimmune disorders, fungal infections, or bites from other various arthropods; thus, treatment is highly dependent on the patient’s history and occupational exposure.

Bedbugs have successfully adapted to a new environment in the office space. Dermatologists and other health care professionals can no longer exclusively associate bedbugs with the home. When the clinical and histological presentation suggests an arthropod assault, we must counsel our patients to surveil their homes and work settings alike. If necessary, they should seek the assistance of occupational health professionals.

Bedbugs are common pests causing several health and economic consequences. With increased travel, pesticide resistance, and a lack of awareness about prevention, bedbugs have become even more difficult to control, especially within large population centers.¹ The US Environmental Protection Agency considers bedbugs to be a considerable public health issue.² Typically, they are found in private residences; however, there have been more reports of bedbugs discovered in the workplace within the last 20 years.^3-5 Herein, we present a case of bedbugs presenting in this unusual environment.

Case Report

A 42-year-old man presented to our dermatology clinic with intensely itchy bumps over the bilateral posterior arms of 3 months’ duration. He had no other skin, hair, or nail concerns. Over the last 3 months prior to dermatologic evaluation, he was treated by an outside physician with topical steroids, systemic antibiotics, topical antifungals, and even systemic steroids with no improvement of the lesions or symptoms. On clinical examination at the current presentation, 8 to 10 pink dermal papules coalescing into 10-cm round patches were noted on the bilateral posterior arms (Figure 1). A punch biopsy of the posterior right arm was performed, and histologic analysis showed a dense superficial and deep infiltrate and a perivascular infiltrate of lymphocytes and eosinophils (Figure 2). No notable epidermal changes were observed.

At this time, the patient was counseled that the most likely cause was some unknown arthropod exposure. Given the chronicity of the patient’s disease course, bedbugs were favored; however, an extensive search of the patient’s home failed to uncover any arthropods, let alone bedbugs. A few weeks later, the patient discovered insects emanating from the mesh backing of his office chair while at work (Figure 3). The location of the intruders corresponded exactly with the lesions on the posterior arms. The occupational health office at his workplace collected samples of the arthropods and confirmed they were bedbugs. The patient’s lesions resolved with topical clobetasol once eradication of the workplace was complete.

Morphology and Epidemiology
Bedbugs are wingless arthropods that have flat, oval-shaped, reddish brown bodies. They are approximately 4.5-mm long and 2.5-mm wide (Figure 4). The 2 most common species of bedbugs that infect humans are Cimex lectularius and Cimex hemipterus. Bedbugs are most commonly found in hotels, apartments, and residential households near sleep locations. They reside in crevices, cracks, mattresses, cushions, dressers, and other structures proximal to the bed. During the day they remain hidden, but at night they emerge for a blood meal. The average lifespan of a bedbug is 6 to 12 months.⁶ Females lay more than 200 eggs that hatch in approximately 6 to 10 days.⁷ Bedbugs progress through 5 nymph stages before becoming adults; several blood meals are required to advance each stage.⁶

Although commonly attributed to the home, bedbugs are being increasingly seen in the office setting.^3-5 In a survey given to pest management professionals in 2015, more than 45% reported that they were contracted by corporations for bedbug infestations in office settings, an increase from 18% in 2010 and 36% in 2013.³ Bedbugs are brought into offices through clothing, luggage, books, and other personal items. Unable to find hosts at night, bedbugs adapt to daytime hours and spread to more unpredictable locations, including chairs, office equipment, desks, and computers.⁴ Additionally, they frequently move around to find a suitable host.⁵ As a result, the growth rate of bedbugs in an office setting is much slower than in the home, with fewer insects. Our patient did not have bedbugs at home, but it is possible that other employees transported them to the office over time.

Clinical Manifestations
Bedbugs cause pruritic and nonpruritic skin rashes, often of the arms, legs, neck, and face. A common reaction is an erythematous papule with a hemorrhagic punctum caused by one bite.⁸ Other presentations include purpuric macules, bullae, and papular urticaria.^8-10 Although bedbugs are suspected to transmit infectious diseases, no reports have substantiated that claim.¹¹

Our patient had several coalescing dermal papules on the arms indicating multiple bites around the same area. Due to the stationary aspect of his job—with the arms resting on his chair while typing at his desk—our patient was an easy target for consistent blood meals.

Detection
Due to an overall smaller population of insects in an office setting, detection of bedbugs in the workplace can be difficult. Infestations can be primarily identified on visual inspection by pest control.¹² The mesh backing on our patient’s chair was one site where bedbugs resided. It is important to check areas where employees congregate, such as lounges, lunch areas, conference rooms, and printers.⁴ It also is essential to examine coatracks and locker rooms, as employees may leave personal items that can serve as a source of transmission of the bugs from home. Additional detection tools provided by pest management professionals include canines, as well as devices that emit pheromones, carbon dioxide, or heat to ensnare the insects.¹²

Treatment
Treatment of bedbug bites is quite variable. For some patients, lesions may resolve on their own. Pruritic maculopapular eruptions can be treated with topical pramoxine or doxepin.⁸ Patients who develop allergic urticaria can use oral antihistamines. Systemic reactions such as anaphylaxis can be treated with a combination of intramuscular epinephrine, antihistamines, and corticosteroids.⁸ The etiology of our patient’s condition initially was unknown, and thus he was given unnecessary systemic steroids and antifungals until the source of the rash was identified and eradicated. Topical clobetasol was subsequently administered and was sufficient to resolve his symptoms.

Final Thoughts

Bedbugs continue to remain a nuisance in the home. This case provides an example of bedbugs in the office, a location that is not commonly associated with bedbug infestations. Bedbugs pose numerous psychological, economic, and health consequences.² Productivity can be reduced, as patients with symptomatic lesions will be unable to work effectively, and those who are unaffected may be unwilling to work knowing their office environment poses a health risk. In addition, employees may worry about bringing the bedbugs home. It is important that employees be educated on the signs of a bedbug infestation and take preventive measures to stop spreading or introducing them to the office space. Due to the scattered habitation of bedbugs in offices, pest control managers need to be vigilant to identify sources of infestation and eradicate accordingly. Clinical manifestations can be nonspecific, resembling autoimmune disorders, fungal infections, or bites from other various arthropods; thus, treatment is highly dependent on the patient’s history and occupational exposure.

Bedbugs have successfully adapted to a new environment in the office space. Dermatologists and other health care professionals can no longer exclusively associate bedbugs with the home. When the clinical and histological presentation suggests an arthropod assault, we must counsel our patients to surveil their homes and work settings alike. If necessary, they should seek the assistance of occupational health professionals.

Bedbugs are common pests causing several health and economic consequences. With increased travel, pesticide resistance, and a lack of awareness about prevention, bedbugs have become even more difficult to control, especially within large population centers.¹ The US Environmental Protection Agency considers bedbugs to be a considerable public health issue.² Typically, they are found in private residences; however, there have been more reports of bedbugs discovered in the workplace within the last 20 years.^3-5 Herein, we present a case of bedbugs presenting in this unusual environment.

Case Report

A 42-year-old man presented to our dermatology clinic with intensely itchy bumps over the bilateral posterior arms of 3 months’ duration. He had no other skin, hair, or nail concerns. Over the last 3 months prior to dermatologic evaluation, he was treated by an outside physician with topical steroids, systemic antibiotics, topical antifungals, and even systemic steroids with no improvement of the lesions or symptoms. On clinical examination at the current presentation, 8 to 10 pink dermal papules coalescing into 10-cm round patches were noted on the bilateral posterior arms (Figure 1). A punch biopsy of the posterior right arm was performed, and histologic analysis showed a dense superficial and deep infiltrate and a perivascular infiltrate of lymphocytes and eosinophils (Figure 2). No notable epidermal changes were observed.

At this time, the patient was counseled that the most likely cause was some unknown arthropod exposure. Given the chronicity of the patient’s disease course, bedbugs were favored; however, an extensive search of the patient’s home failed to uncover any arthropods, let alone bedbugs. A few weeks later, the patient discovered insects emanating from the mesh backing of his office chair while at work (Figure 3). The location of the intruders corresponded exactly with the lesions on the posterior arms. The occupational health office at his workplace collected samples of the arthropods and confirmed they were bedbugs. The patient’s lesions resolved with topical clobetasol once eradication of the workplace was complete.

Morphology and Epidemiology
Bedbugs are wingless arthropods that have flat, oval-shaped, reddish brown bodies. They are approximately 4.5-mm long and 2.5-mm wide (Figure 4). The 2 most common species of bedbugs that infect humans are Cimex lectularius and Cimex hemipterus. Bedbugs are most commonly found in hotels, apartments, and residential households near sleep locations. They reside in crevices, cracks, mattresses, cushions, dressers, and other structures proximal to the bed. During the day they remain hidden, but at night they emerge for a blood meal. The average lifespan of a bedbug is 6 to 12 months.⁶ Females lay more than 200 eggs that hatch in approximately 6 to 10 days.⁷ Bedbugs progress through 5 nymph stages before becoming adults; several blood meals are required to advance each stage.⁶

Although commonly attributed to the home, bedbugs are being increasingly seen in the office setting.^3-5 In a survey given to pest management professionals in 2015, more than 45% reported that they were contracted by corporations for bedbug infestations in office settings, an increase from 18% in 2010 and 36% in 2013.³ Bedbugs are brought into offices through clothing, luggage, books, and other personal items. Unable to find hosts at night, bedbugs adapt to daytime hours and spread to more unpredictable locations, including chairs, office equipment, desks, and computers.⁴ Additionally, they frequently move around to find a suitable host.⁵ As a result, the growth rate of bedbugs in an office setting is much slower than in the home, with fewer insects. Our patient did not have bedbugs at home, but it is possible that other employees transported them to the office over time.

Clinical Manifestations
Bedbugs cause pruritic and nonpruritic skin rashes, often of the arms, legs, neck, and face. A common reaction is an erythematous papule with a hemorrhagic punctum caused by one bite.⁸ Other presentations include purpuric macules, bullae, and papular urticaria.^8-10 Although bedbugs are suspected to transmit infectious diseases, no reports have substantiated that claim.¹¹

Our patient had several coalescing dermal papules on the arms indicating multiple bites around the same area. Due to the stationary aspect of his job—with the arms resting on his chair while typing at his desk—our patient was an easy target for consistent blood meals.

Detection
Due to an overall smaller population of insects in an office setting, detection of bedbugs in the workplace can be difficult. Infestations can be primarily identified on visual inspection by pest control.¹² The mesh backing on our patient’s chair was one site where bedbugs resided. It is important to check areas where employees congregate, such as lounges, lunch areas, conference rooms, and printers.⁴ It also is essential to examine coatracks and locker rooms, as employees may leave personal items that can serve as a source of transmission of the bugs from home. Additional detection tools provided by pest management professionals include canines, as well as devices that emit pheromones, carbon dioxide, or heat to ensnare the insects.¹²

Treatment
Treatment of bedbug bites is quite variable. For some patients, lesions may resolve on their own. Pruritic maculopapular eruptions can be treated with topical pramoxine or doxepin.⁸ Patients who develop allergic urticaria can use oral antihistamines. Systemic reactions such as anaphylaxis can be treated with a combination of intramuscular epinephrine, antihistamines, and corticosteroids.⁸ The etiology of our patient’s condition initially was unknown, and thus he was given unnecessary systemic steroids and antifungals until the source of the rash was identified and eradicated. Topical clobetasol was subsequently administered and was sufficient to resolve his symptoms.

Final Thoughts

Bedbugs continue to remain a nuisance in the home. This case provides an example of bedbugs in the office, a location that is not commonly associated with bedbug infestations. Bedbugs pose numerous psychological, economic, and health consequences.² Productivity can be reduced, as patients with symptomatic lesions will be unable to work effectively, and those who are unaffected may be unwilling to work knowing their office environment poses a health risk. In addition, employees may worry about bringing the bedbugs home. It is important that employees be educated on the signs of a bedbug infestation and take preventive measures to stop spreading or introducing them to the office space. Due to the scattered habitation of bedbugs in offices, pest control managers need to be vigilant to identify sources of infestation and eradicate accordingly. Clinical manifestations can be nonspecific, resembling autoimmune disorders, fungal infections, or bites from other various arthropods; thus, treatment is highly dependent on the patient’s history and occupational exposure.

Bedbugs have successfully adapted to a new environment in the office space. Dermatologists and other health care professionals can no longer exclusively associate bedbugs with the home. When the clinical and histological presentation suggests an arthropod assault, we must counsel our patients to surveil their homes and work settings alike. If necessary, they should seek the assistance of occupational health professionals.

The definition of warts is variable, largely reflecting their manifold appearance, biologic potential, and public health concerns. One vernacular dictionary defines warts as:

Small, benign growths caused by a vital infection of the skin or mucous membrane. The virus infects the surface layer. The viruses that cause warts are members of the human papilloma virus (HPV) family. Warts are not cancerous but some strains of HPV, usually not associated with warts, have been linked with cancer formation. Warts are contagious from person to person and from one area of the body to another on the same person.¹

The World Health Organization defines warts by their structural components as:

Human papillomavirus (HPV) is a small, non-enveloped deoxyribonucleic acid (DNA) virus that infects skin or mucosal cells. The circular, double-stranded viral genome is approximately 8-kb in length. The genome encodes for 6 early proteins responsible for virus replication and 2 late proteins, L1 and L2, which are the viral structural proteins.²

In pediatric and adolescent dermatology, warts often are defined by their location and morphology; for example, facial warts typically are flat, minimally hyperkeratotic, or filiform, wherein the base is narrow and the lesion is tall, growing at a 90° angle to the surface of the skin. On the arms and legs, warts usually present as round to oval papules with overlying thick hyperkeratosis and/or callosity.^3,4 Common warts usually are flesh colored or lighter, and heavily pigmented lesions should be evaluated dermoscopically for a pigment network and biopsied when pigment is present.⁵

In this article, a successful paradigm for management of pediatric warts is provided with enhanced outcomes based on further insight into the disease course and patient selection.

Epidemiology of Pediatric Warts

There are more than 200 types of human papillomaviruses (HPV), with more than 100 oncogenic types. There is quite a bit of homology by species and genus that contributes to cross-immunity and similar behavior between certain types of HPV. The lifetime incidence of warts is very high. Approximately 30% of children develop a wart.⁶ A review of the 2007 National Health Interview Survey of 9417 children demonstrated a steady increase in prevalence of warts from 1 to 2 years of age to 7 to 8 years of age, with a peak at 9 to 10 years of age and a plateau at 11 to 17 years of age. Warts were most common in non-Hispanic white children and less common in black children.⁷ In an in-person survey of 12,370 individuals aged 18 to 74 years from 5 European countries, warts were the most common physician-diagnosed (27.3%) and self-reported (41.0%) dermatologic condition. Warts are more common in Northern countries (eg, Netherlands, Germany).⁸ Children with atopic dermatitis have a higher risk of developing warts and extracutaneous infections. In one study, children with warts and atopic dermatitis had a higher number of infections and food allergies and higher incidence of asthma and hay fever than either condition alone.⁹

Clinical Presentation of Warts

Warts usually present as common, palmoplantar, flat, or filiform in childhood, but variations by age are common (eFigure). The common and palmoplantar variants often are caused by HPV types 1 and 2.^4,5 In infancy, vertically transmitted HPV infections can cause juvenile-onset respiratory papillomatosis or vertically transmitted condyloma. Juvenile-onset respiratory papillomatosis refers to upper respiratory papillomas that are difficult to eliminate and has been associated with exfoliated cervical cell testing with 18.1% (13/72) typed HPV-positive, which allows neonates to be exposed to HPV in the upper respiratory tract in utero.¹⁰

Vertically transmitted condyloma is a difficult topic. Much data supports the vertical transmission of condyloma as the leading cause of condyloma in small children; however, a reasonable amount of caution is needed in this patient population. In cases suspicious for sexual abuse as well as those presenting in children 4 years and older, formal household evaluation by a sexual abuse clinic and mandatory reporting is needed. Anywhere from 2.6% to 32% of cases of genital warts in children have been reported to be caused by sexual abuse.^11-13 Therefore, most investigators have recommended careful review of the patient’s history and socioeconomic circumstances as well as a thorough physical examination. Mandatory reporting of suspected child sexual abuse is required in suspicious cases. Because HPV type 16 has been found in vertically transmitted cases, concern for long-term oncogenesis exists.^11-13

Adolescents generally present with lesions on the hands and feet. Plantar warts often are caused by HPV types from the alpha genus. Subtypes noted in plantar warts include HPV types 1a, 2, 27, 57, and 65.¹⁴ By 15 years of age, genital HPV becomes a common adolescent infection, persisting into adulthood.¹⁵ When studied, genital HPV often is subclinical or latent and often is preventable through vaccination. High-risk oncogenic alpha-genus HPV types can immortalize human keratinocytes. When HPV types 11, 16, 18, and 31 are compared, HPV-18 has the highest oncogenic potential based on colony-stimulating potential.¹⁶ Vaccination with the 9-valent HPV vaccine is recommended in adolescence due to the concern for exposures to both low-potential (HPV types 6 and 11) and high-potential (HPV types 16 and 18) oncogenic HPV types. Data strongly support the benefit of 9-valent HPV vaccination in the prevention of sexually transmitted HPV in both males and females.¹⁷

Contagion of HPV is easy due to its excellent survival of fomites on surfaces, which generally is how warts are transferred in gym or pool settings where individuals who walk barefoot in changing rooms are almost twice as likely to contract plantar warts (odds ratio, 1.97 [95% CI, 1.39%-2.79%]).¹⁸ In another case series, walking barefoot, using a swimming pool, and having a household contact with warts were the leading risk factors for contraction of warts in children younger than 13 years.¹⁹ Children often transfer warts from site to site as well as to siblings and other close contacts. Skin-to-skin contact is responsible for sexual transmission of warts, and surface transmission occurs via fomites. Entry of the virus often occurs through small breaks in the skin. Other modes of transmission include orogenital.²⁰

Therapeutic Options

Although the nuances of each available treatment for pediatric warts are beyond the scope of this article, the main core of therapy is 1 of 3 approaches: (1) observation, (2) over-the-counter salicylic acid therapy, and (3) in-office cryotherapy. Observation is an affirmed style of therapy for warts, as it is expected that two-thirds of warts will spontaneously resolve in 2 years and three-quarters will resolve in 3 years.^4,5 Condyloma in children has been responsive to therapies such as cryotherapy and imiquimod,¹³ but spontaneous clearance in 5 years has been noted in 76% of children,²¹ which is linked to development of spontaneous immune response in most individuals.

Therapies for pediatric warts are characterized according to 6 major categories: destructive; immune stimulating; immune modulating, including normalization of epithelial growth; irritant; vascular destructive; and nitric oxide releasing (eTable).

Immune-Stimulating Therapies                                                                                                                                                                                                                         
Immune stimulants often are used to treat warts in children and adolescents who have many lesions, a prolonged disease course, disfigurement, and/or subungual localizations, as well as in those who have been treated with multiple destructive methods without success. Topical imiquimod and oral cimetidine are readily available, while squaric acid (at-home or in-office therapy) and intralesional candida antigen can be used in offices that carry these agents. Topical imiquimod has been reported to achieve success in genital warts in children,¹³ with good efficacy in recalcitrant, periungual, and subungual warts when used for up to 16 weeks.³¹ In one randomized clinical trial, imiquimod cream 5% combined with salicylic acid 15% was applied to warts for 6 to 10 hours for 5 consecutive days per week versus cryotherapy with liquid nitrogen every 2 weeks for a maximum of 3 months. At the end of the study period, 81.1% (30/37) of participants treated with imiquimod and salicylic acid showed clearance of their warts versus 67.3% (33/49) of those treated with cryotherapy.³²

Oral cimetidine has been reported to be successful in treating recalcitrant warts in more than 80% of children when dosed at 30 to 40 mg/kg 3 times daily, requiring 6 to 12 weeks to achieve clearance. Side effects of oral cimetidine include many cytochrome P450 interactions; gynecomastia, which limits usage in teenaged males; and stomach upset.³⁰

Treatment of recalcitrant pediatric warts with intralesional candida antigen has been associated with side effects consistent with delayed-type hypersensitivity reactions. Injections should be administered once monthly, with a minimum of 3 cycles if not effective and up to 6 cycles where partial efficacy is noted. In a retrospective review of 220 cases, 70.9% of children showed complete clearance and 16.8% had partial response.³³ However, the treatment may be limited in children by fear of needles.

Squaric acid dibutyl ester is a universal allergen that is not mutagenic on Ames testing and causes milder allergy symptoms than the mutagenic dinitrochlorobenzene and less erythema and pruritus than diphencyclopropenone. Squaric acid dibutyl ester home therapy was evaluated in 61 children with at least one nonfacial wart.³⁴ Application began with squaric acid dibutyl ester in acetone (SADBE) 2% sensitization on the arm followed by at-home application of SADBE 0.2% three to seven times weekly for a minimum of 2 months to determine benefit and for 3 to 4 months as needed; however, average response was 7 weeks. The average complete clearance was 58% and partial clearance was 18%. Side effects included erythema and mild itching as well as urticaria in one case.³⁴ In-office SADBE also has been evaluated in children. In a case series that included 29 children sensitized with SADBE 1% to 2% under occlusion followed by once monthly application of SADBE 0.5% to 5.0% to their warts, 69% clearance and 10% partial clearance was noted after a little more than 4 months of treatment.³⁵ One retrospective review compared combination SADBE, trichloroacetic acid (TCA), and cantharidin both alone and in combination as duos (eg, SADBE and TCA) or trios (SADBE, TCA, and cantharidin).²³ Of the 74 children whose medical charts were reviewed, the addition of pretreatment of warts with TCA 50% prior to in-office sensitization and monthly in-office application of SADBE increased treatment response to 100% with an average 2.45 months of therapy, whereas no enhancement was noted with cantharidin. Therefore, it appears that there may be enhanced immune reactivity when TCA pretreatment of warts is performed.²³

Immune-Modulating Therapies (Including Normalization of Epithelial Growth)
The most novel immunologic therapy for warts is plerixafor, an agent used to treat WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, which has been linked to heterozygous gain of function mutations in the chemokine receptor CXCR4 (located on 2q22). In WHIM syndrome, the mutated CXCR4 is more sensitive to CXCL12 activation. Plerixafor is a selective reversible antagonist that blocks the capacity of the chemokine CXCL12 to sustain the permanent activation of CXCR4.³⁷ Combination therapy with plerixafor and topical imiquimod has resulted in wart improvement in WHIM syndrome patients in a small series.³⁸

Oral isotretinoin has been described to be efficacious over placebo at a dosage of 30 mg daily for 12 weeks and can be used in teenagers but requires standard monitoring.³⁶

Nitric Oxide–Releasing Therapies                                                                                                                                                                                                                         
Nitric oxide release may increase local blood flow, thereby increasing immune response, or may have a primary mechanism of antimicrobial activity, which is why these agents have been investigated for wart treatment. Topical garlic has been described anecdotally as a therapy for thin childhood warts with the putative mechanism being nitric oxide release.⁴² A new investigational drug recently has had phase 2 data published. Berdazimer sodium plus carboxymethyl cellulose hydrogel has demonstrated benefit in adult warts, but data in children is lacking.⁴¹

Therapeutic Ladder for Childhood Warts

The therapeutic ladder (Table) for childhood warts starts with first doing no harm. Although many parents are disturbed by their child’s condition, the natural history of resolution is spontaneous and therefore no therapy is required in many cases. The child and his/her caregivers should be engaged to determine if he/she is emotionally disturbed or uncomfortable with their lesions and to address any fears and concerns that some children may experience (eg, contagion risk, pain with ambulation, ostracism). For example, children with hand warts may report that other children will not hold their hand while in line at school. Prominent facial lesions can be particularly problematic for children due to teasing and bullying.

Conclusion

Warts are a common infection in childhood caused by the ubiquitous HPV virus. Therapeutic options abound, but most cases are either ignored or treated with over-the-counter salicylic acid or in-office cryotherapy. The decision to employ alternative therapeutic options requires agreement by the child, his/her caregiver, and the treating physician and can be tailored to suit the desires and needs of the child. Whether or not therapy is offered, spontaneous clearance is frequently seen in common warts. On the other hand, genital warts are associated with later conversion to malignancies of the genital tract; therefore, encouragement of HPV vaccination is needed in the adolescent population to best ensure long-term genital health.

The definition of warts is variable, largely reflecting their manifold appearance, biologic potential, and public health concerns. One vernacular dictionary defines warts as:

Small, benign growths caused by a vital infection of the skin or mucous membrane. The virus infects the surface layer. The viruses that cause warts are members of the human papilloma virus (HPV) family. Warts are not cancerous but some strains of HPV, usually not associated with warts, have been linked with cancer formation. Warts are contagious from person to person and from one area of the body to another on the same person.¹

The World Health Organization defines warts by their structural components as:

Human papillomavirus (HPV) is a small, non-enveloped deoxyribonucleic acid (DNA) virus that infects skin or mucosal cells. The circular, double-stranded viral genome is approximately 8-kb in length. The genome encodes for 6 early proteins responsible for virus replication and 2 late proteins, L1 and L2, which are the viral structural proteins.²

In pediatric and adolescent dermatology, warts often are defined by their location and morphology; for example, facial warts typically are flat, minimally hyperkeratotic, or filiform, wherein the base is narrow and the lesion is tall, growing at a 90° angle to the surface of the skin. On the arms and legs, warts usually present as round to oval papules with overlying thick hyperkeratosis and/or callosity.^3,4 Common warts usually are flesh colored or lighter, and heavily pigmented lesions should be evaluated dermoscopically for a pigment network and biopsied when pigment is present.⁵

In this article, a successful paradigm for management of pediatric warts is provided with enhanced outcomes based on further insight into the disease course and patient selection.

Epidemiology of Pediatric Warts

There are more than 200 types of human papillomaviruses (HPV), with more than 100 oncogenic types. There is quite a bit of homology by species and genus that contributes to cross-immunity and similar behavior between certain types of HPV. The lifetime incidence of warts is very high. Approximately 30% of children develop a wart.⁶ A review of the 2007 National Health Interview Survey of 9417 children demonstrated a steady increase in prevalence of warts from 1 to 2 years of age to 7 to 8 years of age, with a peak at 9 to 10 years of age and a plateau at 11 to 17 years of age. Warts were most common in non-Hispanic white children and less common in black children.⁷ In an in-person survey of 12,370 individuals aged 18 to 74 years from 5 European countries, warts were the most common physician-diagnosed (27.3%) and self-reported (41.0%) dermatologic condition. Warts are more common in Northern countries (eg, Netherlands, Germany).⁸ Children with atopic dermatitis have a higher risk of developing warts and extracutaneous infections. In one study, children with warts and atopic dermatitis had a higher number of infections and food allergies and higher incidence of asthma and hay fever than either condition alone.⁹

Clinical Presentation of Warts

Warts usually present as common, palmoplantar, flat, or filiform in childhood, but variations by age are common (eFigure). The common and palmoplantar variants often are caused by HPV types 1 and 2.^4,5 In infancy, vertically transmitted HPV infections can cause juvenile-onset respiratory papillomatosis or vertically transmitted condyloma. Juvenile-onset respiratory papillomatosis refers to upper respiratory papillomas that are difficult to eliminate and has been associated with exfoliated cervical cell testing with 18.1% (13/72) typed HPV-positive, which allows neonates to be exposed to HPV in the upper respiratory tract in utero.¹⁰

Vertically transmitted condyloma is a difficult topic. Much data supports the vertical transmission of condyloma as the leading cause of condyloma in small children; however, a reasonable amount of caution is needed in this patient population. In cases suspicious for sexual abuse as well as those presenting in children 4 years and older, formal household evaluation by a sexual abuse clinic and mandatory reporting is needed. Anywhere from 2.6% to 32% of cases of genital warts in children have been reported to be caused by sexual abuse.^11-13 Therefore, most investigators have recommended careful review of the patient’s history and socioeconomic circumstances as well as a thorough physical examination. Mandatory reporting of suspected child sexual abuse is required in suspicious cases. Because HPV type 16 has been found in vertically transmitted cases, concern for long-term oncogenesis exists.^11-13

Adolescents generally present with lesions on the hands and feet. Plantar warts often are caused by HPV types from the alpha genus. Subtypes noted in plantar warts include HPV types 1a, 2, 27, 57, and 65.¹⁴ By 15 years of age, genital HPV becomes a common adolescent infection, persisting into adulthood.¹⁵ When studied, genital HPV often is subclinical or latent and often is preventable through vaccination. High-risk oncogenic alpha-genus HPV types can immortalize human keratinocytes. When HPV types 11, 16, 18, and 31 are compared, HPV-18 has the highest oncogenic potential based on colony-stimulating potential.¹⁶ Vaccination with the 9-valent HPV vaccine is recommended in adolescence due to the concern for exposures to both low-potential (HPV types 6 and 11) and high-potential (HPV types 16 and 18) oncogenic HPV types. Data strongly support the benefit of 9-valent HPV vaccination in the prevention of sexually transmitted HPV in both males and females.¹⁷

Contagion of HPV is easy due to its excellent survival of fomites on surfaces, which generally is how warts are transferred in gym or pool settings where individuals who walk barefoot in changing rooms are almost twice as likely to contract plantar warts (odds ratio, 1.97 [95% CI, 1.39%-2.79%]).¹⁸ In another case series, walking barefoot, using a swimming pool, and having a household contact with warts were the leading risk factors for contraction of warts in children younger than 13 years.¹⁹ Children often transfer warts from site to site as well as to siblings and other close contacts. Skin-to-skin contact is responsible for sexual transmission of warts, and surface transmission occurs via fomites. Entry of the virus often occurs through small breaks in the skin. Other modes of transmission include orogenital.²⁰

Therapeutic Options

Although the nuances of each available treatment for pediatric warts are beyond the scope of this article, the main core of therapy is 1 of 3 approaches: (1) observation, (2) over-the-counter salicylic acid therapy, and (3) in-office cryotherapy. Observation is an affirmed style of therapy for warts, as it is expected that two-thirds of warts will spontaneously resolve in 2 years and three-quarters will resolve in 3 years.^4,5 Condyloma in children has been responsive to therapies such as cryotherapy and imiquimod,¹³ but spontaneous clearance in 5 years has been noted in 76% of children,²¹ which is linked to development of spontaneous immune response in most individuals.

Therapies for pediatric warts are characterized according to 6 major categories: destructive; immune stimulating; immune modulating, including normalization of epithelial growth; irritant; vascular destructive; and nitric oxide releasing (eTable).

Immune-Stimulating Therapies                                                                                                                                                                                                                         
Immune stimulants often are used to treat warts in children and adolescents who have many lesions, a prolonged disease course, disfigurement, and/or subungual localizations, as well as in those who have been treated with multiple destructive methods without success. Topical imiquimod and oral cimetidine are readily available, while squaric acid (at-home or in-office therapy) and intralesional candida antigen can be used in offices that carry these agents. Topical imiquimod has been reported to achieve success in genital warts in children,¹³ with good efficacy in recalcitrant, periungual, and subungual warts when used for up to 16 weeks.³¹ In one randomized clinical trial, imiquimod cream 5% combined with salicylic acid 15% was applied to warts for 6 to 10 hours for 5 consecutive days per week versus cryotherapy with liquid nitrogen every 2 weeks for a maximum of 3 months. At the end of the study period, 81.1% (30/37) of participants treated with imiquimod and salicylic acid showed clearance of their warts versus 67.3% (33/49) of those treated with cryotherapy.³²

Oral cimetidine has been reported to be successful in treating recalcitrant warts in more than 80% of children when dosed at 30 to 40 mg/kg 3 times daily, requiring 6 to 12 weeks to achieve clearance. Side effects of oral cimetidine include many cytochrome P450 interactions; gynecomastia, which limits usage in teenaged males; and stomach upset.³⁰

Treatment of recalcitrant pediatric warts with intralesional candida antigen has been associated with side effects consistent with delayed-type hypersensitivity reactions. Injections should be administered once monthly, with a minimum of 3 cycles if not effective and up to 6 cycles where partial efficacy is noted. In a retrospective review of 220 cases, 70.9% of children showed complete clearance and 16.8% had partial response.³³ However, the treatment may be limited in children by fear of needles.

Squaric acid dibutyl ester is a universal allergen that is not mutagenic on Ames testing and causes milder allergy symptoms than the mutagenic dinitrochlorobenzene and less erythema and pruritus than diphencyclopropenone. Squaric acid dibutyl ester home therapy was evaluated in 61 children with at least one nonfacial wart.³⁴ Application began with squaric acid dibutyl ester in acetone (SADBE) 2% sensitization on the arm followed by at-home application of SADBE 0.2% three to seven times weekly for a minimum of 2 months to determine benefit and for 3 to 4 months as needed; however, average response was 7 weeks. The average complete clearance was 58% and partial clearance was 18%. Side effects included erythema and mild itching as well as urticaria in one case.³⁴ In-office SADBE also has been evaluated in children. In a case series that included 29 children sensitized with SADBE 1% to 2% under occlusion followed by once monthly application of SADBE 0.5% to 5.0% to their warts, 69% clearance and 10% partial clearance was noted after a little more than 4 months of treatment.³⁵ One retrospective review compared combination SADBE, trichloroacetic acid (TCA), and cantharidin both alone and in combination as duos (eg, SADBE and TCA) or trios (SADBE, TCA, and cantharidin).²³ Of the 74 children whose medical charts were reviewed, the addition of pretreatment of warts with TCA 50% prior to in-office sensitization and monthly in-office application of SADBE increased treatment response to 100% with an average 2.45 months of therapy, whereas no enhancement was noted with cantharidin. Therefore, it appears that there may be enhanced immune reactivity when TCA pretreatment of warts is performed.²³

Immune-Modulating Therapies (Including Normalization of Epithelial Growth)
The most novel immunologic therapy for warts is plerixafor, an agent used to treat WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, which has been linked to heterozygous gain of function mutations in the chemokine receptor CXCR4 (located on 2q22). In WHIM syndrome, the mutated CXCR4 is more sensitive to CXCL12 activation. Plerixafor is a selective reversible antagonist that blocks the capacity of the chemokine CXCL12 to sustain the permanent activation of CXCR4.³⁷ Combination therapy with plerixafor and topical imiquimod has resulted in wart improvement in WHIM syndrome patients in a small series.³⁸

Oral isotretinoin has been described to be efficacious over placebo at a dosage of 30 mg daily for 12 weeks and can be used in teenagers but requires standard monitoring.³⁶

Nitric Oxide–Releasing Therapies                                                                                                                                                                                                                         
Nitric oxide release may increase local blood flow, thereby increasing immune response, or may have a primary mechanism of antimicrobial activity, which is why these agents have been investigated for wart treatment. Topical garlic has been described anecdotally as a therapy for thin childhood warts with the putative mechanism being nitric oxide release.⁴² A new investigational drug recently has had phase 2 data published. Berdazimer sodium plus carboxymethyl cellulose hydrogel has demonstrated benefit in adult warts, but data in children is lacking.⁴¹

Therapeutic Ladder for Childhood Warts

The therapeutic ladder (Table) for childhood warts starts with first doing no harm. Although many parents are disturbed by their child’s condition, the natural history of resolution is spontaneous and therefore no therapy is required in many cases. The child and his/her caregivers should be engaged to determine if he/she is emotionally disturbed or uncomfortable with their lesions and to address any fears and concerns that some children may experience (eg, contagion risk, pain with ambulation, ostracism). For example, children with hand warts may report that other children will not hold their hand while in line at school. Prominent facial lesions can be particularly problematic for children due to teasing and bullying.

Conclusion

Warts are a common infection in childhood caused by the ubiquitous HPV virus. Therapeutic options abound, but most cases are either ignored or treated with over-the-counter salicylic acid or in-office cryotherapy. The decision to employ alternative therapeutic options requires agreement by the child, his/her caregiver, and the treating physician and can be tailored to suit the desires and needs of the child. Whether or not therapy is offered, spontaneous clearance is frequently seen in common warts. On the other hand, genital warts are associated with later conversion to malignancies of the genital tract; therefore, encouragement of HPV vaccination is needed in the adolescent population to best ensure long-term genital health.

The definition of warts is variable, largely reflecting their manifold appearance, biologic potential, and public health concerns. One vernacular dictionary defines warts as:

Small, benign growths caused by a vital infection of the skin or mucous membrane. The virus infects the surface layer. The viruses that cause warts are members of the human papilloma virus (HPV) family. Warts are not cancerous but some strains of HPV, usually not associated with warts, have been linked with cancer formation. Warts are contagious from person to person and from one area of the body to another on the same person.¹

The World Health Organization defines warts by their structural components as:

Human papillomavirus (HPV) is a small, non-enveloped deoxyribonucleic acid (DNA) virus that infects skin or mucosal cells. The circular, double-stranded viral genome is approximately 8-kb in length. The genome encodes for 6 early proteins responsible for virus replication and 2 late proteins, L1 and L2, which are the viral structural proteins.²

In pediatric and adolescent dermatology, warts often are defined by their location and morphology; for example, facial warts typically are flat, minimally hyperkeratotic, or filiform, wherein the base is narrow and the lesion is tall, growing at a 90° angle to the surface of the skin. On the arms and legs, warts usually present as round to oval papules with overlying thick hyperkeratosis and/or callosity.^3,4 Common warts usually are flesh colored or lighter, and heavily pigmented lesions should be evaluated dermoscopically for a pigment network and biopsied when pigment is present.⁵

In this article, a successful paradigm for management of pediatric warts is provided with enhanced outcomes based on further insight into the disease course and patient selection.

Epidemiology of Pediatric Warts

There are more than 200 types of human papillomaviruses (HPV), with more than 100 oncogenic types. There is quite a bit of homology by species and genus that contributes to cross-immunity and similar behavior between certain types of HPV. The lifetime incidence of warts is very high. Approximately 30% of children develop a wart.⁶ A review of the 2007 National Health Interview Survey of 9417 children demonstrated a steady increase in prevalence of warts from 1 to 2 years of age to 7 to 8 years of age, with a peak at 9 to 10 years of age and a plateau at 11 to 17 years of age. Warts were most common in non-Hispanic white children and less common in black children.⁷ In an in-person survey of 12,370 individuals aged 18 to 74 years from 5 European countries, warts were the most common physician-diagnosed (27.3%) and self-reported (41.0%) dermatologic condition. Warts are more common in Northern countries (eg, Netherlands, Germany).⁸ Children with atopic dermatitis have a higher risk of developing warts and extracutaneous infections. In one study, children with warts and atopic dermatitis had a higher number of infections and food allergies and higher incidence of asthma and hay fever than either condition alone.⁹

Clinical Presentation of Warts

Warts usually present as common, palmoplantar, flat, or filiform in childhood, but variations by age are common (eFigure). The common and palmoplantar variants often are caused by HPV types 1 and 2.^4,5 In infancy, vertically transmitted HPV infections can cause juvenile-onset respiratory papillomatosis or vertically transmitted condyloma. Juvenile-onset respiratory papillomatosis refers to upper respiratory papillomas that are difficult to eliminate and has been associated with exfoliated cervical cell testing with 18.1% (13/72) typed HPV-positive, which allows neonates to be exposed to HPV in the upper respiratory tract in utero.¹⁰

Vertically transmitted condyloma is a difficult topic. Much data supports the vertical transmission of condyloma as the leading cause of condyloma in small children; however, a reasonable amount of caution is needed in this patient population. In cases suspicious for sexual abuse as well as those presenting in children 4 years and older, formal household evaluation by a sexual abuse clinic and mandatory reporting is needed. Anywhere from 2.6% to 32% of cases of genital warts in children have been reported to be caused by sexual abuse.^11-13 Therefore, most investigators have recommended careful review of the patient’s history and socioeconomic circumstances as well as a thorough physical examination. Mandatory reporting of suspected child sexual abuse is required in suspicious cases. Because HPV type 16 has been found in vertically transmitted cases, concern for long-term oncogenesis exists.^11-13

Adolescents generally present with lesions on the hands and feet. Plantar warts often are caused by HPV types from the alpha genus. Subtypes noted in plantar warts include HPV types 1a, 2, 27, 57, and 65.¹⁴ By 15 years of age, genital HPV becomes a common adolescent infection, persisting into adulthood.¹⁵ When studied, genital HPV often is subclinical or latent and often is preventable through vaccination. High-risk oncogenic alpha-genus HPV types can immortalize human keratinocytes. When HPV types 11, 16, 18, and 31 are compared, HPV-18 has the highest oncogenic potential based on colony-stimulating potential.¹⁶ Vaccination with the 9-valent HPV vaccine is recommended in adolescence due to the concern for exposures to both low-potential (HPV types 6 and 11) and high-potential (HPV types 16 and 18) oncogenic HPV types. Data strongly support the benefit of 9-valent HPV vaccination in the prevention of sexually transmitted HPV in both males and females.¹⁷

Contagion of HPV is easy due to its excellent survival of fomites on surfaces, which generally is how warts are transferred in gym or pool settings where individuals who walk barefoot in changing rooms are almost twice as likely to contract plantar warts (odds ratio, 1.97 [95% CI, 1.39%-2.79%]).¹⁸ In another case series, walking barefoot, using a swimming pool, and having a household contact with warts were the leading risk factors for contraction of warts in children younger than 13 years.¹⁹ Children often transfer warts from site to site as well as to siblings and other close contacts. Skin-to-skin contact is responsible for sexual transmission of warts, and surface transmission occurs via fomites. Entry of the virus often occurs through small breaks in the skin. Other modes of transmission include orogenital.²⁰

Therapeutic Options

Although the nuances of each available treatment for pediatric warts are beyond the scope of this article, the main core of therapy is 1 of 3 approaches: (1) observation, (2) over-the-counter salicylic acid therapy, and (3) in-office cryotherapy. Observation is an affirmed style of therapy for warts, as it is expected that two-thirds of warts will spontaneously resolve in 2 years and three-quarters will resolve in 3 years.^4,5 Condyloma in children has been responsive to therapies such as cryotherapy and imiquimod,¹³ but spontaneous clearance in 5 years has been noted in 76% of children,²¹ which is linked to development of spontaneous immune response in most individuals.

Therapies for pediatric warts are characterized according to 6 major categories: destructive; immune stimulating; immune modulating, including normalization of epithelial growth; irritant; vascular destructive; and nitric oxide releasing (eTable).

Immune-Stimulating Therapies                                                                                                                                                                                                                         
Immune stimulants often are used to treat warts in children and adolescents who have many lesions, a prolonged disease course, disfigurement, and/or subungual localizations, as well as in those who have been treated with multiple destructive methods without success. Topical imiquimod and oral cimetidine are readily available, while squaric acid (at-home or in-office therapy) and intralesional candida antigen can be used in offices that carry these agents. Topical imiquimod has been reported to achieve success in genital warts in children,¹³ with good efficacy in recalcitrant, periungual, and subungual warts when used for up to 16 weeks.³¹ In one randomized clinical trial, imiquimod cream 5% combined with salicylic acid 15% was applied to warts for 6 to 10 hours for 5 consecutive days per week versus cryotherapy with liquid nitrogen every 2 weeks for a maximum of 3 months. At the end of the study period, 81.1% (30/37) of participants treated with imiquimod and salicylic acid showed clearance of their warts versus 67.3% (33/49) of those treated with cryotherapy.³²

Oral cimetidine has been reported to be successful in treating recalcitrant warts in more than 80% of children when dosed at 30 to 40 mg/kg 3 times daily, requiring 6 to 12 weeks to achieve clearance. Side effects of oral cimetidine include many cytochrome P450 interactions; gynecomastia, which limits usage in teenaged males; and stomach upset.³⁰

Treatment of recalcitrant pediatric warts with intralesional candida antigen has been associated with side effects consistent with delayed-type hypersensitivity reactions. Injections should be administered once monthly, with a minimum of 3 cycles if not effective and up to 6 cycles where partial efficacy is noted. In a retrospective review of 220 cases, 70.9% of children showed complete clearance and 16.8% had partial response.³³ However, the treatment may be limited in children by fear of needles.

Squaric acid dibutyl ester is a universal allergen that is not mutagenic on Ames testing and causes milder allergy symptoms than the mutagenic dinitrochlorobenzene and less erythema and pruritus than diphencyclopropenone. Squaric acid dibutyl ester home therapy was evaluated in 61 children with at least one nonfacial wart.³⁴ Application began with squaric acid dibutyl ester in acetone (SADBE) 2% sensitization on the arm followed by at-home application of SADBE 0.2% three to seven times weekly for a minimum of 2 months to determine benefit and for 3 to 4 months as needed; however, average response was 7 weeks. The average complete clearance was 58% and partial clearance was 18%. Side effects included erythema and mild itching as well as urticaria in one case.³⁴ In-office SADBE also has been evaluated in children. In a case series that included 29 children sensitized with SADBE 1% to 2% under occlusion followed by once monthly application of SADBE 0.5% to 5.0% to their warts, 69% clearance and 10% partial clearance was noted after a little more than 4 months of treatment.³⁵ One retrospective review compared combination SADBE, trichloroacetic acid (TCA), and cantharidin both alone and in combination as duos (eg, SADBE and TCA) or trios (SADBE, TCA, and cantharidin).²³ Of the 74 children whose medical charts were reviewed, the addition of pretreatment of warts with TCA 50% prior to in-office sensitization and monthly in-office application of SADBE increased treatment response to 100% with an average 2.45 months of therapy, whereas no enhancement was noted with cantharidin. Therefore, it appears that there may be enhanced immune reactivity when TCA pretreatment of warts is performed.²³

Immune-Modulating Therapies (Including Normalization of Epithelial Growth)
The most novel immunologic therapy for warts is plerixafor, an agent used to treat WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, which has been linked to heterozygous gain of function mutations in the chemokine receptor CXCR4 (located on 2q22). In WHIM syndrome, the mutated CXCR4 is more sensitive to CXCL12 activation. Plerixafor is a selective reversible antagonist that blocks the capacity of the chemokine CXCL12 to sustain the permanent activation of CXCR4.³⁷ Combination therapy with plerixafor and topical imiquimod has resulted in wart improvement in WHIM syndrome patients in a small series.³⁸

Oral isotretinoin has been described to be efficacious over placebo at a dosage of 30 mg daily for 12 weeks and can be used in teenagers but requires standard monitoring.³⁶

Nitric Oxide–Releasing Therapies                                                                                                                                                                                                                         
Nitric oxide release may increase local blood flow, thereby increasing immune response, or may have a primary mechanism of antimicrobial activity, which is why these agents have been investigated for wart treatment. Topical garlic has been described anecdotally as a therapy for thin childhood warts with the putative mechanism being nitric oxide release.⁴² A new investigational drug recently has had phase 2 data published. Berdazimer sodium plus carboxymethyl cellulose hydrogel has demonstrated benefit in adult warts, but data in children is lacking.⁴¹

Therapeutic Ladder for Childhood Warts

The therapeutic ladder (Table) for childhood warts starts with first doing no harm. Although many parents are disturbed by their child’s condition, the natural history of resolution is spontaneous and therefore no therapy is required in many cases. The child and his/her caregivers should be engaged to determine if he/she is emotionally disturbed or uncomfortable with their lesions and to address any fears and concerns that some children may experience (eg, contagion risk, pain with ambulation, ostracism). For example, children with hand warts may report that other children will not hold their hand while in line at school. Prominent facial lesions can be particularly problematic for children due to teasing and bullying.

Conclusion

Warts are a common infection in childhood caused by the ubiquitous HPV virus. Therapeutic options abound, but most cases are either ignored or treated with over-the-counter salicylic acid or in-office cryotherapy. The decision to employ alternative therapeutic options requires agreement by the child, his/her caregiver, and the treating physician and can be tailored to suit the desires and needs of the child. Whether or not therapy is offered, spontaneous clearance is frequently seen in common warts. On the other hand, genital warts are associated with later conversion to malignancies of the genital tract; therefore, encouragement of HPV vaccination is needed in the adolescent population to best ensure long-term genital health.

A large proportion of laboring febrile women are not meeting proposed criteria for intrauterine inflammation or infection or both (triple I), but still may be at risk, according to an analysis of expert recommendations for clinical diagnosis published in Obstetrics & Gynecology.

©Cameron Whitman/Thinkstock

“Our data suggest caution in universal implementation of the triple I criteria to guide clinical management of febrile women in the intrapartum period,” according to lead author Samsiya Ona, MD, of Brigham and Women’s Hospital in Boston, and her coauthors.

In early 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established criteria for diagnosing triple I in an effort to “decrease overtreatment of intrapartum women and low-risk newborns.” To assess the validity of those criteria, Dr. Ona and her colleagues analyzed 339 women with a temperature taken of 100.4°F or greater (38.0°C) during labor or within 1 hour post partum from June 2015 to September 2017.

The women were split into two groups: 212 met criteria for suspected triple I (documented fever plus clinical signs of intrauterine infection such as maternal leukocytosis greater than 15,000 per mm³, fetal tachycardia greater than 160 beats per minute, and purulent amniotic fluid) and 127 met criteria for isolated maternal fever. Among the suspected triple I group, incidence of adverse clinical infectious outcomes was 12%, comparable with 10% in the isolated maternal fever group (P = .50). When it came to predicting confirmed triple I, the sensitivity and specificity of the suspected triple I criteria were 71% (95% confidence interval, 61.4%-80.1%) and 41% (95% CI, 33.6%-47.8%), respectively. For predicting adverse clinical infectious outcomes, the sensitivity and specificity of the suspected triple I criteria were 68% (95% CI, 50.2%-82.0%) and 38% (95% CI, 32.6%-43.8%).

The authors cited among study limitations their including only women who had blood cultures sent at initial fever and excluding women who did not have repeat febrile temperature taken within 45 minutes. However, they noted the benefits of working with “a unique, large database with physiologic, laboratory, and microbiological parameters” and emphasized the need for an improved method of diagnosis, suggesting “a simple bedside minimally invasive marker of infection may be ideal.”

The study was supported by an Expanding the Boundaries Faculty Grant from the department of obstetrics, gynecology, and reproductive biology at the Brigham and Women’s Hospital in Boston. No conflicts of interest were reported.

SOURCE: Ona S et al. Obstet Gynecol. 2019 Jan. doi: 10.1097/AOG.0000000000003008.

A large proportion of laboring febrile women are not meeting proposed criteria for intrauterine inflammation or infection or both (triple I), but still may be at risk, according to an analysis of expert recommendations for clinical diagnosis published in Obstetrics & Gynecology.

©Cameron Whitman/Thinkstock

“Our data suggest caution in universal implementation of the triple I criteria to guide clinical management of febrile women in the intrapartum period,” according to lead author Samsiya Ona, MD, of Brigham and Women’s Hospital in Boston, and her coauthors.

In early 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established criteria for diagnosing triple I in an effort to “decrease overtreatment of intrapartum women and low-risk newborns.” To assess the validity of those criteria, Dr. Ona and her colleagues analyzed 339 women with a temperature taken of 100.4°F or greater (38.0°C) during labor or within 1 hour post partum from June 2015 to September 2017.

The women were split into two groups: 212 met criteria for suspected triple I (documented fever plus clinical signs of intrauterine infection such as maternal leukocytosis greater than 15,000 per mm³, fetal tachycardia greater than 160 beats per minute, and purulent amniotic fluid) and 127 met criteria for isolated maternal fever. Among the suspected triple I group, incidence of adverse clinical infectious outcomes was 12%, comparable with 10% in the isolated maternal fever group (P = .50). When it came to predicting confirmed triple I, the sensitivity and specificity of the suspected triple I criteria were 71% (95% confidence interval, 61.4%-80.1%) and 41% (95% CI, 33.6%-47.8%), respectively. For predicting adverse clinical infectious outcomes, the sensitivity and specificity of the suspected triple I criteria were 68% (95% CI, 50.2%-82.0%) and 38% (95% CI, 32.6%-43.8%).

The authors cited among study limitations their including only women who had blood cultures sent at initial fever and excluding women who did not have repeat febrile temperature taken within 45 minutes. However, they noted the benefits of working with “a unique, large database with physiologic, laboratory, and microbiological parameters” and emphasized the need for an improved method of diagnosis, suggesting “a simple bedside minimally invasive marker of infection may be ideal.”

The study was supported by an Expanding the Boundaries Faculty Grant from the department of obstetrics, gynecology, and reproductive biology at the Brigham and Women’s Hospital in Boston. No conflicts of interest were reported.

SOURCE: Ona S et al. Obstet Gynecol. 2019 Jan. doi: 10.1097/AOG.0000000000003008.

A large proportion of laboring febrile women are not meeting proposed criteria for intrauterine inflammation or infection or both (triple I), but still may be at risk, according to an analysis of expert recommendations for clinical diagnosis published in Obstetrics & Gynecology.

©Cameron Whitman/Thinkstock

“Our data suggest caution in universal implementation of the triple I criteria to guide clinical management of febrile women in the intrapartum period,” according to lead author Samsiya Ona, MD, of Brigham and Women’s Hospital in Boston, and her coauthors.

In early 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established criteria for diagnosing triple I in an effort to “decrease overtreatment of intrapartum women and low-risk newborns.” To assess the validity of those criteria, Dr. Ona and her colleagues analyzed 339 women with a temperature taken of 100.4°F or greater (38.0°C) during labor or within 1 hour post partum from June 2015 to September 2017.

The women were split into two groups: 212 met criteria for suspected triple I (documented fever plus clinical signs of intrauterine infection such as maternal leukocytosis greater than 15,000 per mm³, fetal tachycardia greater than 160 beats per minute, and purulent amniotic fluid) and 127 met criteria for isolated maternal fever. Among the suspected triple I group, incidence of adverse clinical infectious outcomes was 12%, comparable with 10% in the isolated maternal fever group (P = .50). When it came to predicting confirmed triple I, the sensitivity and specificity of the suspected triple I criteria were 71% (95% confidence interval, 61.4%-80.1%) and 41% (95% CI, 33.6%-47.8%), respectively. For predicting adverse clinical infectious outcomes, the sensitivity and specificity of the suspected triple I criteria were 68% (95% CI, 50.2%-82.0%) and 38% (95% CI, 32.6%-43.8%).

The authors cited among study limitations their including only women who had blood cultures sent at initial fever and excluding women who did not have repeat febrile temperature taken within 45 minutes. However, they noted the benefits of working with “a unique, large database with physiologic, laboratory, and microbiological parameters” and emphasized the need for an improved method of diagnosis, suggesting “a simple bedside minimally invasive marker of infection may be ideal.”

The study was supported by an Expanding the Boundaries Faculty Grant from the department of obstetrics, gynecology, and reproductive biology at the Brigham and Women’s Hospital in Boston. No conflicts of interest were reported.

SOURCE: Ona S et al. Obstet Gynecol. 2019 Jan. doi: 10.1097/AOG.0000000000003008.

Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.

copyright/Dr. Daniel P. Perl/CDC

Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.

“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.

The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.

The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.

That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.

On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.

The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.

The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.

That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.

Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.

“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.

Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.

SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.

Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.

copyright/Dr. Daniel P. Perl/CDC

Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.

“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.

The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.

The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.

That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.

On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.

The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.

The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.

That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.

Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.

“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.

Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.

SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.

Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.

copyright/Dr. Daniel P. Perl/CDC

Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.

“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.

The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.

The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.

That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.

On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.

The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.

The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.

That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.

Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.

“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.

Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.

SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.

The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

Patients with hypertension who show substantial progression of cerebral small vessel disease have a sixfold higher odds of developing mild cognitive impairment compared with similar patients who do not have signs of progression. Also today, antidepressants are tied to greater hip fracture incidence, a hospital readmission reduction program may be doing more harm than good, and the flu season rages on with 19 states showing high activity in the final week of 2018.

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Patients with hypertension who show substantial progression of cerebral small vessel disease have a sixfold higher odds of developing mild cognitive impairment compared with similar patients who do not have signs of progression. Also today, antidepressants are tied to greater hip fracture incidence, a hospital readmission reduction program may be doing more harm than good, and the flu season rages on with 19 states showing high activity in the final week of 2018.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Patients with hypertension who show substantial progression of cerebral small vessel disease have a sixfold higher odds of developing mild cognitive impairment compared with similar patients who do not have signs of progression. Also today, antidepressants are tied to greater hip fracture incidence, a hospital readmission reduction program may be doing more harm than good, and the flu season rages on with 19 states showing high activity in the final week of 2018.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Here are 5 articles from the January issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Can ultrasound screening improve survival in ovarian cancer?

To take the posttest, go to: https://bit.ly/2Vtuc8F
Expires October 17, 2019

2. Higher BMI associated with greater loss of gray matter volume in MS

To take the posttest, go to: https://bit.ly/2ArvFDp
Expires October 29, 2019

3. Psoriasis adds to increased risk of cardiovascular procedures, surgery in patients with hypertension

To take the posttest, go to: https://bit.ly/2sbnkiS
Expires October 31, 2019

4. Fever, intestinal symptoms may delay diagnosis of Kawasaki disease in children

To take the posttest, go to: https://bit.ly/2RdPoBi
Expires October 31, 2019

5. Rate of STIs is rising, and many U.S. teens are sexually active

To take the posttest, go to: https://bit.ly/2CPuYFW
Expires November 8, 2019

Here are 5 articles from the January issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Can ultrasound screening improve survival in ovarian cancer?

To take the posttest, go to: https://bit.ly/2Vtuc8F
Expires October 17, 2019

2. Higher BMI associated with greater loss of gray matter volume in MS

To take the posttest, go to: https://bit.ly/2ArvFDp
Expires October 29, 2019

3. Psoriasis adds to increased risk of cardiovascular procedures, surgery in patients with hypertension

To take the posttest, go to: https://bit.ly/2sbnkiS
Expires October 31, 2019

4. Fever, intestinal symptoms may delay diagnosis of Kawasaki disease in children

To take the posttest, go to: https://bit.ly/2RdPoBi
Expires October 31, 2019

5. Rate of STIs is rising, and many U.S. teens are sexually active

To take the posttest, go to: https://bit.ly/2CPuYFW
Expires November 8, 2019

Here are 5 articles from the January issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Can ultrasound screening improve survival in ovarian cancer?

To take the posttest, go to: https://bit.ly/2Vtuc8F
Expires October 17, 2019

2. Higher BMI associated with greater loss of gray matter volume in MS

To take the posttest, go to: https://bit.ly/2ArvFDp
Expires October 29, 2019

3. Psoriasis adds to increased risk of cardiovascular procedures, surgery in patients with hypertension

To take the posttest, go to: https://bit.ly/2sbnkiS
Expires October 31, 2019

4. Fever, intestinal symptoms may delay diagnosis of Kawasaki disease in children

To take the posttest, go to: https://bit.ly/2RdPoBi
Expires October 31, 2019

5. Rate of STIs is rising, and many U.S. teens are sexually active

To take the posttest, go to: https://bit.ly/2CPuYFW
Expires November 8, 2019