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Reducing Unnecessary Antibiotics for Conjunctivitis
TOPLINE:
More than two thirds of children with conjunctivitis received antibiotics within a day of their initial ambulatory care visit; however,
METHODOLOGY:
- Researchers evaluated the frequency of topical antibiotic treatment and its association with subsequent health care use among commercially insured children with acute infectious conjunctivitis in the United States.
- This cohort study analyzed data from the 2021 MarketScan Commercial Claims and Encounters Database, including 44,793 children with conjunctivitis (median age, 5 years; 47% girls) and ambulatory care encounters.
- The primary exposure was a topical antibiotic prescription dispensed within 1 day of an ambulatory care visit, with outcomes assessed 2-14 days after the visit.
- The primary outcomes were ambulatory care revisits for conjunctivitis and same-day dispensation of a new topical antibiotic, and secondary outcomes included emergency department revisits and hospitalizations.
TAKEAWAY:
- Topical antibiotics were dispensed within a day of an ambulatory care visit in 69% of the cases; however, they were less frequently dispensed following visits to eye clinics (34%), for children aged 6-11 years (66%), and for those with viral conjunctivitis (28%).
- Ambulatory care revisits for conjunctivitis within 2 weeks occurred in only 3.2% of children who had received antibiotics (adjusted odds ratio [aOR], 1.11; 95% CI, 0.99-1.25).
- Similarly, revisits with same-day dispensation of a new antibiotic were also rare (1.4%), with no significant association between antibiotic treatment and revisits (aOR, 1.10; 95% CI, 0.92-1.33).
- Hospitalizations for conjunctivitis occurred in 0.03% of cases, and emergency department revisits occurred in 0.12%, with no differences between children who received antibiotics and those who did not.
IN PRACTICE:
“Given that antibiotics may not be associated with improved outcomes or change in subsequent health care use and are associated with adverse effects and antibiotic resistance, efforts to reduce overtreatment of acute infectious conjunctivitis are warranted,” the authors wrote.
SOURCE:
The study was led by Daniel J. Shapiro, MD, MPH, of the Department of Emergency Medicine at the University of California, San Francisco, and published online on June 27, 2024, in JAMA Ophthalmology.
LIMITATIONS:
The major limitations of the study included the inability to distinguish scheduled visits from unscheduled revisits, incomplete clinical data such as rare complications of conjunctivitis, and the inability to confirm the accuracy of the coded diagnosis of infectious conjunctivitis, especially in children who did not receive a thorough eye examination.
DISCLOSURES:
This study did not declare receiving funding from any sources. One author reported receiving grants from several sources outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
More than two thirds of children with conjunctivitis received antibiotics within a day of their initial ambulatory care visit; however,
METHODOLOGY:
- Researchers evaluated the frequency of topical antibiotic treatment and its association with subsequent health care use among commercially insured children with acute infectious conjunctivitis in the United States.
- This cohort study analyzed data from the 2021 MarketScan Commercial Claims and Encounters Database, including 44,793 children with conjunctivitis (median age, 5 years; 47% girls) and ambulatory care encounters.
- The primary exposure was a topical antibiotic prescription dispensed within 1 day of an ambulatory care visit, with outcomes assessed 2-14 days after the visit.
- The primary outcomes were ambulatory care revisits for conjunctivitis and same-day dispensation of a new topical antibiotic, and secondary outcomes included emergency department revisits and hospitalizations.
TAKEAWAY:
- Topical antibiotics were dispensed within a day of an ambulatory care visit in 69% of the cases; however, they were less frequently dispensed following visits to eye clinics (34%), for children aged 6-11 years (66%), and for those with viral conjunctivitis (28%).
- Ambulatory care revisits for conjunctivitis within 2 weeks occurred in only 3.2% of children who had received antibiotics (adjusted odds ratio [aOR], 1.11; 95% CI, 0.99-1.25).
- Similarly, revisits with same-day dispensation of a new antibiotic were also rare (1.4%), with no significant association between antibiotic treatment and revisits (aOR, 1.10; 95% CI, 0.92-1.33).
- Hospitalizations for conjunctivitis occurred in 0.03% of cases, and emergency department revisits occurred in 0.12%, with no differences between children who received antibiotics and those who did not.
IN PRACTICE:
“Given that antibiotics may not be associated with improved outcomes or change in subsequent health care use and are associated with adverse effects and antibiotic resistance, efforts to reduce overtreatment of acute infectious conjunctivitis are warranted,” the authors wrote.
SOURCE:
The study was led by Daniel J. Shapiro, MD, MPH, of the Department of Emergency Medicine at the University of California, San Francisco, and published online on June 27, 2024, in JAMA Ophthalmology.
LIMITATIONS:
The major limitations of the study included the inability to distinguish scheduled visits from unscheduled revisits, incomplete clinical data such as rare complications of conjunctivitis, and the inability to confirm the accuracy of the coded diagnosis of infectious conjunctivitis, especially in children who did not receive a thorough eye examination.
DISCLOSURES:
This study did not declare receiving funding from any sources. One author reported receiving grants from several sources outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
More than two thirds of children with conjunctivitis received antibiotics within a day of their initial ambulatory care visit; however,
METHODOLOGY:
- Researchers evaluated the frequency of topical antibiotic treatment and its association with subsequent health care use among commercially insured children with acute infectious conjunctivitis in the United States.
- This cohort study analyzed data from the 2021 MarketScan Commercial Claims and Encounters Database, including 44,793 children with conjunctivitis (median age, 5 years; 47% girls) and ambulatory care encounters.
- The primary exposure was a topical antibiotic prescription dispensed within 1 day of an ambulatory care visit, with outcomes assessed 2-14 days after the visit.
- The primary outcomes were ambulatory care revisits for conjunctivitis and same-day dispensation of a new topical antibiotic, and secondary outcomes included emergency department revisits and hospitalizations.
TAKEAWAY:
- Topical antibiotics were dispensed within a day of an ambulatory care visit in 69% of the cases; however, they were less frequently dispensed following visits to eye clinics (34%), for children aged 6-11 years (66%), and for those with viral conjunctivitis (28%).
- Ambulatory care revisits for conjunctivitis within 2 weeks occurred in only 3.2% of children who had received antibiotics (adjusted odds ratio [aOR], 1.11; 95% CI, 0.99-1.25).
- Similarly, revisits with same-day dispensation of a new antibiotic were also rare (1.4%), with no significant association between antibiotic treatment and revisits (aOR, 1.10; 95% CI, 0.92-1.33).
- Hospitalizations for conjunctivitis occurred in 0.03% of cases, and emergency department revisits occurred in 0.12%, with no differences between children who received antibiotics and those who did not.
IN PRACTICE:
“Given that antibiotics may not be associated with improved outcomes or change in subsequent health care use and are associated with adverse effects and antibiotic resistance, efforts to reduce overtreatment of acute infectious conjunctivitis are warranted,” the authors wrote.
SOURCE:
The study was led by Daniel J. Shapiro, MD, MPH, of the Department of Emergency Medicine at the University of California, San Francisco, and published online on June 27, 2024, in JAMA Ophthalmology.
LIMITATIONS:
The major limitations of the study included the inability to distinguish scheduled visits from unscheduled revisits, incomplete clinical data such as rare complications of conjunctivitis, and the inability to confirm the accuracy of the coded diagnosis of infectious conjunctivitis, especially in children who did not receive a thorough eye examination.
DISCLOSURES:
This study did not declare receiving funding from any sources. One author reported receiving grants from several sources outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Dengue Surge in US Cases This Year
Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.
The global incidence of dengue in 2024 is the highest on record, reported the agency.
In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.
The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.
Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.
The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
Monitoring for Dengue
With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:
- Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
- Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
- Ensure timely reporting of dengue cases to public health authorities.
- Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.
Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.
Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
Disease Progression
Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.
One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.
Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.
“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.
The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.
The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.
A version of this article first appeared on Medscape.com.
Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.
The global incidence of dengue in 2024 is the highest on record, reported the agency.
In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.
The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.
Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.
The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
Monitoring for Dengue
With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:
- Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
- Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
- Ensure timely reporting of dengue cases to public health authorities.
- Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.
Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.
Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
Disease Progression
Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.
One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.
Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.
“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.
The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.
The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.
A version of this article first appeared on Medscape.com.
Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.
The global incidence of dengue in 2024 is the highest on record, reported the agency.
In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.
The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.
Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.
The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
Monitoring for Dengue
With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:
- Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
- Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
- Ensure timely reporting of dengue cases to public health authorities.
- Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.
Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.
Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
Disease Progression
Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.
One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.
Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.
“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.
The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.
The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.
A version of this article first appeared on Medscape.com.
Extensive Multidrug-Resistant Dermatophytosis From Trichophyton indotineae
To the Editor:
Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.1-5
Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.7 Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.8 We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.
An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.
Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.
The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 μg/mL (reference range, ≥0.6 μg/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8 μg/mL.
Approximately 1 month after the fungal isolate was sent to the reference laboratory, T indotineae was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 μg/mL), griseofulvin (2 μg/mL), itraconazole (≤0.03 μg/mL), posaconazole (≤0.03 μg/mL), terbinafine (≥2 μg/mL), and voriconazole (0.125 μg/mL).
Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred.
We report a unique case of T indotineae in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant T indotineae specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.9
Trichophyton indotineae dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.5 Previously called Trichophyton mentagrophytes genotype VIII when first isolated in 2017, the pathogen was renamed T indotineae in 2020 after important genetic differences were discovered between it and other T mentagrophytes species.5 The emergence of T indotineae has been attributed to concomitant use of topical steroids and antifungals,5,10 inappropriate prescribing of antifungals,5 and nonadherence to antifungal treatment.5
Likely risk factors for T indotineae infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.4 Transmission from family members appears common,5 especially when fomites are shared.4 A case reported in Pennsylvania likely was acquired through sexual contact.7 Travel to South Asia has been associated with acquisition of T indotineae infection,3,5-7 though our patient and some others had not traveled there.3,8 It is not clear whether immunosuppression and diabetes mellitus are associated with T indotineae infection.4,5,8Trichophyton indotineae also can affect animals,11 though zoonotic transmission has not been reported.4
Not all T indotineae isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.5 Terbinafine resistance in T indotineae is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.2,4,5,12 Although clinical cut-points for MIC obtained by AFST are not well established, T indotineae MICs for terbinafine of 0.5 μg/mL or more correlate with resistance.9 Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14α demethylase.4,12,13
Potassium hydroxide preparations and fungal cultures cannot differentiate T indotineae from other dermatophytes that typically cause tinea.5,14 Histopathologic findings in our case were no different than those of non–T indotineae dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm T indotineae infection. However, PCR assays and AFST are not available in many US laboratories.5 Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing T indotineae from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.15,16 Clinicians in the United States who want to test specimens from cases suspicious for T indotineae infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.3,5
Systemic treatment typically is necessary for T indotineae infection.5 Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.1,5,17-21
Itraconazole has emerged as the treatment of choice for T indotineae tinea, typically at 200 mg/d and often for courses of more than 3 months.5 Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.5 Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.5,22 Patients with T indotineae dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.4
Dermatologists who suspect T indotineae infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.5,23 Challenges to diagnosing and managing T indotineae infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant T indotineae infection is confirmed.
Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.
- Uhrlaß S, Verma SB, Gräser Y, al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757. doi:10.3390/jof8070757
- Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022;28:229-233. doi:10.3201/eid2801.210883
- Caplan AS, Chaturvedi S, Zhu Y, et al. Notes from the field. First reported U.S. cases of tinea caused by Trichophyton indotineae—New York City, December 2021-March 2023. MMWR Morb Mortal Wkly Rep. 2023;72:536-537. doi:10.15585/mmwr.mm7219a4
- Jabet A, Normand A-C, Brun S, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383
- Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. Am J Clin Dermatol. 2024;25:359-389. doi:10.1007/s40257-024-00848-1
- Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130. doi:10.1001/jamadermatol.2023.2645
- Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant Trichophyton indotineae. Emerg Infect Dis. 2024;30:807-809. doi:10.3201/eid3004.240115
- Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of Trichophyton indotineae. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126
- Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223. doi:10.1128/jcm.00562-23
- Gupta AK, Venkataraman M, Hall DC, et al. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857-861.
- Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance Trichophyton indotineae in a stray dog. Res Vet Sci. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105
- Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018;9:1108. doi:10.3389/fmicb.2018.01108
- Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;711:983. doi:10.3390/jof7110983
- Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. Diagnosis and Treatment of Human Mycoses. Humana Press; 2008:355-381.
- Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi (Basel). 2022;8:1103. doi:10.3390/jof8101103
- De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen Trichophyton indotineae. Mycopathologia. 2024;189:29. doi:10.1007/s11046-024-00835-4
- Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol. 2018;18:6. doi:10.1186/s12895-018-0073-1
- Verma SB, Panda S, Nenoff P, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options. Indian J Dermatol Venereol Leprol. 2021;87:468-482. doi:10.25259/IJDVL_303_20
- Shaw D, Singh S, Dogra S, et al. MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes–Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020;64:E01964-19. doi:10.1128/AAC.01964-19
- Burmester A, Hipler U-C, Uhrlaß S, et al. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses. 2020;63:1175-1180. doi:10.1111/myc.13150
- Khurana A, Agarwal A, Agrawal D, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269-1278. doi:10.1001/jamadermatol.2022.3745
- Itraconazole capsule. DailyMed [Internet]. Updated June 3, 2024. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d
- Bui TS, Katz KA. Resistant Trichophyton indotineae dermatophytosis—an emerging pandemic, now in the US. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1125
To the Editor:
Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.1-5
Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.7 Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.8 We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.
An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.
Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.
The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 μg/mL (reference range, ≥0.6 μg/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8 μg/mL.
Approximately 1 month after the fungal isolate was sent to the reference laboratory, T indotineae was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 μg/mL), griseofulvin (2 μg/mL), itraconazole (≤0.03 μg/mL), posaconazole (≤0.03 μg/mL), terbinafine (≥2 μg/mL), and voriconazole (0.125 μg/mL).
Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred.
We report a unique case of T indotineae in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant T indotineae specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.9
Trichophyton indotineae dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.5 Previously called Trichophyton mentagrophytes genotype VIII when first isolated in 2017, the pathogen was renamed T indotineae in 2020 after important genetic differences were discovered between it and other T mentagrophytes species.5 The emergence of T indotineae has been attributed to concomitant use of topical steroids and antifungals,5,10 inappropriate prescribing of antifungals,5 and nonadherence to antifungal treatment.5
Likely risk factors for T indotineae infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.4 Transmission from family members appears common,5 especially when fomites are shared.4 A case reported in Pennsylvania likely was acquired through sexual contact.7 Travel to South Asia has been associated with acquisition of T indotineae infection,3,5-7 though our patient and some others had not traveled there.3,8 It is not clear whether immunosuppression and diabetes mellitus are associated with T indotineae infection.4,5,8Trichophyton indotineae also can affect animals,11 though zoonotic transmission has not been reported.4
Not all T indotineae isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.5 Terbinafine resistance in T indotineae is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.2,4,5,12 Although clinical cut-points for MIC obtained by AFST are not well established, T indotineae MICs for terbinafine of 0.5 μg/mL or more correlate with resistance.9 Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14α demethylase.4,12,13
Potassium hydroxide preparations and fungal cultures cannot differentiate T indotineae from other dermatophytes that typically cause tinea.5,14 Histopathologic findings in our case were no different than those of non–T indotineae dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm T indotineae infection. However, PCR assays and AFST are not available in many US laboratories.5 Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing T indotineae from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.15,16 Clinicians in the United States who want to test specimens from cases suspicious for T indotineae infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.3,5
Systemic treatment typically is necessary for T indotineae infection.5 Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.1,5,17-21
Itraconazole has emerged as the treatment of choice for T indotineae tinea, typically at 200 mg/d and often for courses of more than 3 months.5 Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.5 Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.5,22 Patients with T indotineae dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.4
Dermatologists who suspect T indotineae infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.5,23 Challenges to diagnosing and managing T indotineae infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant T indotineae infection is confirmed.
Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.
To the Editor:
Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.1-5
Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.7 Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.8 We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.
An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.
Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.
The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 μg/mL (reference range, ≥0.6 μg/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8 μg/mL.
Approximately 1 month after the fungal isolate was sent to the reference laboratory, T indotineae was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 μg/mL), griseofulvin (2 μg/mL), itraconazole (≤0.03 μg/mL), posaconazole (≤0.03 μg/mL), terbinafine (≥2 μg/mL), and voriconazole (0.125 μg/mL).
Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred.
We report a unique case of T indotineae in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant T indotineae specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.9
Trichophyton indotineae dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.5 Previously called Trichophyton mentagrophytes genotype VIII when first isolated in 2017, the pathogen was renamed T indotineae in 2020 after important genetic differences were discovered between it and other T mentagrophytes species.5 The emergence of T indotineae has been attributed to concomitant use of topical steroids and antifungals,5,10 inappropriate prescribing of antifungals,5 and nonadherence to antifungal treatment.5
Likely risk factors for T indotineae infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.4 Transmission from family members appears common,5 especially when fomites are shared.4 A case reported in Pennsylvania likely was acquired through sexual contact.7 Travel to South Asia has been associated with acquisition of T indotineae infection,3,5-7 though our patient and some others had not traveled there.3,8 It is not clear whether immunosuppression and diabetes mellitus are associated with T indotineae infection.4,5,8Trichophyton indotineae also can affect animals,11 though zoonotic transmission has not been reported.4
Not all T indotineae isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.5 Terbinafine resistance in T indotineae is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.2,4,5,12 Although clinical cut-points for MIC obtained by AFST are not well established, T indotineae MICs for terbinafine of 0.5 μg/mL or more correlate with resistance.9 Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14α demethylase.4,12,13
Potassium hydroxide preparations and fungal cultures cannot differentiate T indotineae from other dermatophytes that typically cause tinea.5,14 Histopathologic findings in our case were no different than those of non–T indotineae dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm T indotineae infection. However, PCR assays and AFST are not available in many US laboratories.5 Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing T indotineae from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.15,16 Clinicians in the United States who want to test specimens from cases suspicious for T indotineae infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.3,5
Systemic treatment typically is necessary for T indotineae infection.5 Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.1,5,17-21
Itraconazole has emerged as the treatment of choice for T indotineae tinea, typically at 200 mg/d and often for courses of more than 3 months.5 Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.5 Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.5,22 Patients with T indotineae dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.4
Dermatologists who suspect T indotineae infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.5,23 Challenges to diagnosing and managing T indotineae infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant T indotineae infection is confirmed.
Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.
- Uhrlaß S, Verma SB, Gräser Y, al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757. doi:10.3390/jof8070757
- Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022;28:229-233. doi:10.3201/eid2801.210883
- Caplan AS, Chaturvedi S, Zhu Y, et al. Notes from the field. First reported U.S. cases of tinea caused by Trichophyton indotineae—New York City, December 2021-March 2023. MMWR Morb Mortal Wkly Rep. 2023;72:536-537. doi:10.15585/mmwr.mm7219a4
- Jabet A, Normand A-C, Brun S, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383
- Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. Am J Clin Dermatol. 2024;25:359-389. doi:10.1007/s40257-024-00848-1
- Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130. doi:10.1001/jamadermatol.2023.2645
- Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant Trichophyton indotineae. Emerg Infect Dis. 2024;30:807-809. doi:10.3201/eid3004.240115
- Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of Trichophyton indotineae. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126
- Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223. doi:10.1128/jcm.00562-23
- Gupta AK, Venkataraman M, Hall DC, et al. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857-861.
- Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance Trichophyton indotineae in a stray dog. Res Vet Sci. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105
- Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018;9:1108. doi:10.3389/fmicb.2018.01108
- Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;711:983. doi:10.3390/jof7110983
- Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. Diagnosis and Treatment of Human Mycoses. Humana Press; 2008:355-381.
- Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi (Basel). 2022;8:1103. doi:10.3390/jof8101103
- De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen Trichophyton indotineae. Mycopathologia. 2024;189:29. doi:10.1007/s11046-024-00835-4
- Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol. 2018;18:6. doi:10.1186/s12895-018-0073-1
- Verma SB, Panda S, Nenoff P, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options. Indian J Dermatol Venereol Leprol. 2021;87:468-482. doi:10.25259/IJDVL_303_20
- Shaw D, Singh S, Dogra S, et al. MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes–Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020;64:E01964-19. doi:10.1128/AAC.01964-19
- Burmester A, Hipler U-C, Uhrlaß S, et al. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses. 2020;63:1175-1180. doi:10.1111/myc.13150
- Khurana A, Agarwal A, Agrawal D, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269-1278. doi:10.1001/jamadermatol.2022.3745
- Itraconazole capsule. DailyMed [Internet]. Updated June 3, 2024. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d
- Bui TS, Katz KA. Resistant Trichophyton indotineae dermatophytosis—an emerging pandemic, now in the US. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1125
- Uhrlaß S, Verma SB, Gräser Y, al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757. doi:10.3390/jof8070757
- Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022;28:229-233. doi:10.3201/eid2801.210883
- Caplan AS, Chaturvedi S, Zhu Y, et al. Notes from the field. First reported U.S. cases of tinea caused by Trichophyton indotineae—New York City, December 2021-March 2023. MMWR Morb Mortal Wkly Rep. 2023;72:536-537. doi:10.15585/mmwr.mm7219a4
- Jabet A, Normand A-C, Brun S, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383
- Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. Am J Clin Dermatol. 2024;25:359-389. doi:10.1007/s40257-024-00848-1
- Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130. doi:10.1001/jamadermatol.2023.2645
- Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant Trichophyton indotineae. Emerg Infect Dis. 2024;30:807-809. doi:10.3201/eid3004.240115
- Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of Trichophyton indotineae. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126
- Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223. doi:10.1128/jcm.00562-23
- Gupta AK, Venkataraman M, Hall DC, et al. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857-861.
- Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance Trichophyton indotineae in a stray dog. Res Vet Sci. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105
- Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018;9:1108. doi:10.3389/fmicb.2018.01108
- Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;711:983. doi:10.3390/jof7110983
- Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. Diagnosis and Treatment of Human Mycoses. Humana Press; 2008:355-381.
- Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi (Basel). 2022;8:1103. doi:10.3390/jof8101103
- De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen Trichophyton indotineae. Mycopathologia. 2024;189:29. doi:10.1007/s11046-024-00835-4
- Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol. 2018;18:6. doi:10.1186/s12895-018-0073-1
- Verma SB, Panda S, Nenoff P, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options. Indian J Dermatol Venereol Leprol. 2021;87:468-482. doi:10.25259/IJDVL_303_20
- Shaw D, Singh S, Dogra S, et al. MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes–Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020;64:E01964-19. doi:10.1128/AAC.01964-19
- Burmester A, Hipler U-C, Uhrlaß S, et al. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses. 2020;63:1175-1180. doi:10.1111/myc.13150
- Khurana A, Agarwal A, Agrawal D, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269-1278. doi:10.1001/jamadermatol.2022.3745
- Itraconazole capsule. DailyMed [Internet]. Updated June 3, 2024. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d
- Bui TS, Katz KA. Resistant Trichophyton indotineae dermatophytosis—an emerging pandemic, now in the US. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1125
Practice Points
- Trichophyton indotineae can cause extensive dermatophytosis that often is resistant to terbinafine and in some cases to other antifungals.
- Only molecular testing, which is not widely available, can distinguish T indotineae from other dermatophytes.
- Suspected or confirmed cases of T indotineae dermatophytosis should be reported to public health agencies to provide assistance with testing, as well as surveillance, prevention, and control of infection.
Online Diagnosis of Sexually Transmitted Infections? Ethicist Says We Are Nowhere Close
This transcript has been edited for clarity.
There has been a large amount of news lately about dating online and dating apps. Probably the most common way younger people find potential partners is to go online and see who’s there that they might want to meet.
Online dating is also notorious for being full of scammers. There are all kinds of people out there that you have to be careful of, who are trying to rip you off by saying, “Send me money, I’m in trouble,” or “Now that we have a relationship, will you support my particular entrepreneurial idea?” Certainly, dangers are there.
Another danger we don’t talk much about is meeting people who have sexually transmitted diseases. That’s been a problem before websites and before dating apps. I think the opportunity of meeting more people — strangers, people you don’t really know — who may not tell you the truth about their health, and particularly their sexual health, is really out there.
It’s always good medical advice to tell people to practice safe sex, and that often involves a man wearing a condom. It certainly is the case that we want to attend not just to the prevention of unwanted pregnancy but also to the transmission of diseases. I think it’s very important to tell women of reproductive age to get their HPV shot to try to reduce cancers in their reproductive systems, or sometimes in men — anal cancers, or even being a transmitter of disease.
Even then, certainly one wants to recommend that, in an age where some people are going to meet many partners that they don’t know well or don’t have much background with, it’s wise to try to prevent diseases using the vaccines we’ve got, using the contraceptive methods that will prevent disease transmission, and reminding people to ask about sex life.
I did come across a website that just startled me. It’s called HeHealth, and basically it says to men, if you are conscientious about your sex life, take a picture of your penis, send it to us, and we have doctors — I presume they’re US doctors but I don’t know — who will diagnose venereal diseases based on that picture. I presume women could also say, “Before we have sex, or now that we’re approaching that possibility, I want you to send a picture to this company on this website.”
Now, a couple of reminders. I think we all know this, but just because you’re not manifesting symptoms on your reproductive organs doesn’t mean you don’t have a sexual disease. It’s not a reliable measure. Yes, maybe you could have somebody say: “Oh, that looks nasty. I’m not sure you ought to have sex right now, and maybe you should go get some treatment.” This is going to miss many cases and is not a reliable indicator that your partner is safe in terms of not transmitting diseases to you.
It also isn’t clear what they do with these images. Do they keep them? Who can see them? Could they resell them? What sort of privacy protection have you got if you decide to use this?
There’s another issue here, which is, if they misdiagnose someone and you do catch a sexual disease, who’s liable? Can you go after them for using doctors who weren’t competent or transmitting images that weren’t really adequate because you didn’t know how to take that picture properly when you sent that off to them? There are many unknowns.
The bottom line is that we’re in a different world, I think, of romance. We’re in a world where some people are going to meet more partners. Some people are going to meet more strangers. One approach is to have us take pictures of ourselves, send them off to who knows where, and ask for a green light to go ahead and have sexual relations. I don’t think we’re anywhere close to being able to rely on that as a way to avoid the risks of unprotected sexual behavior.
We do know what to do in dealing with patients who are sexually active. First, we have to ask them. Then we’ve got to recommend available vaccinations to prevent the transmission of some cancers, the HPV vaccine. Then they need that reminder about safe sexual practices not only to protect against unwanted pregnancy, but still, in this day and age, to protect against syphilis, which is on the rise, plus HIV, gonorrhea, chlamydia, and other sexually transmissible diseases.
I’m not going to rely on the penis picture to make the world safe for sex. I think we have to still use the old-fashioned techniques of education and prevention to do the best we can.
Dr. Caplan is director of the Division of Medical Ethics at New York University Langone Medical Center, New York City. He reported conflicts of interest with Johnson & Johnson’s Panel for Compassionate Drug Use and Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
There has been a large amount of news lately about dating online and dating apps. Probably the most common way younger people find potential partners is to go online and see who’s there that they might want to meet.
Online dating is also notorious for being full of scammers. There are all kinds of people out there that you have to be careful of, who are trying to rip you off by saying, “Send me money, I’m in trouble,” or “Now that we have a relationship, will you support my particular entrepreneurial idea?” Certainly, dangers are there.
Another danger we don’t talk much about is meeting people who have sexually transmitted diseases. That’s been a problem before websites and before dating apps. I think the opportunity of meeting more people — strangers, people you don’t really know — who may not tell you the truth about their health, and particularly their sexual health, is really out there.
It’s always good medical advice to tell people to practice safe sex, and that often involves a man wearing a condom. It certainly is the case that we want to attend not just to the prevention of unwanted pregnancy but also to the transmission of diseases. I think it’s very important to tell women of reproductive age to get their HPV shot to try to reduce cancers in their reproductive systems, or sometimes in men — anal cancers, or even being a transmitter of disease.
Even then, certainly one wants to recommend that, in an age where some people are going to meet many partners that they don’t know well or don’t have much background with, it’s wise to try to prevent diseases using the vaccines we’ve got, using the contraceptive methods that will prevent disease transmission, and reminding people to ask about sex life.
I did come across a website that just startled me. It’s called HeHealth, and basically it says to men, if you are conscientious about your sex life, take a picture of your penis, send it to us, and we have doctors — I presume they’re US doctors but I don’t know — who will diagnose venereal diseases based on that picture. I presume women could also say, “Before we have sex, or now that we’re approaching that possibility, I want you to send a picture to this company on this website.”
Now, a couple of reminders. I think we all know this, but just because you’re not manifesting symptoms on your reproductive organs doesn’t mean you don’t have a sexual disease. It’s not a reliable measure. Yes, maybe you could have somebody say: “Oh, that looks nasty. I’m not sure you ought to have sex right now, and maybe you should go get some treatment.” This is going to miss many cases and is not a reliable indicator that your partner is safe in terms of not transmitting diseases to you.
It also isn’t clear what they do with these images. Do they keep them? Who can see them? Could they resell them? What sort of privacy protection have you got if you decide to use this?
There’s another issue here, which is, if they misdiagnose someone and you do catch a sexual disease, who’s liable? Can you go after them for using doctors who weren’t competent or transmitting images that weren’t really adequate because you didn’t know how to take that picture properly when you sent that off to them? There are many unknowns.
The bottom line is that we’re in a different world, I think, of romance. We’re in a world where some people are going to meet more partners. Some people are going to meet more strangers. One approach is to have us take pictures of ourselves, send them off to who knows where, and ask for a green light to go ahead and have sexual relations. I don’t think we’re anywhere close to being able to rely on that as a way to avoid the risks of unprotected sexual behavior.
We do know what to do in dealing with patients who are sexually active. First, we have to ask them. Then we’ve got to recommend available vaccinations to prevent the transmission of some cancers, the HPV vaccine. Then they need that reminder about safe sexual practices not only to protect against unwanted pregnancy, but still, in this day and age, to protect against syphilis, which is on the rise, plus HIV, gonorrhea, chlamydia, and other sexually transmissible diseases.
I’m not going to rely on the penis picture to make the world safe for sex. I think we have to still use the old-fashioned techniques of education and prevention to do the best we can.
Dr. Caplan is director of the Division of Medical Ethics at New York University Langone Medical Center, New York City. He reported conflicts of interest with Johnson & Johnson’s Panel for Compassionate Drug Use and Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
There has been a large amount of news lately about dating online and dating apps. Probably the most common way younger people find potential partners is to go online and see who’s there that they might want to meet.
Online dating is also notorious for being full of scammers. There are all kinds of people out there that you have to be careful of, who are trying to rip you off by saying, “Send me money, I’m in trouble,” or “Now that we have a relationship, will you support my particular entrepreneurial idea?” Certainly, dangers are there.
Another danger we don’t talk much about is meeting people who have sexually transmitted diseases. That’s been a problem before websites and before dating apps. I think the opportunity of meeting more people — strangers, people you don’t really know — who may not tell you the truth about their health, and particularly their sexual health, is really out there.
It’s always good medical advice to tell people to practice safe sex, and that often involves a man wearing a condom. It certainly is the case that we want to attend not just to the prevention of unwanted pregnancy but also to the transmission of diseases. I think it’s very important to tell women of reproductive age to get their HPV shot to try to reduce cancers in their reproductive systems, or sometimes in men — anal cancers, or even being a transmitter of disease.
Even then, certainly one wants to recommend that, in an age where some people are going to meet many partners that they don’t know well or don’t have much background with, it’s wise to try to prevent diseases using the vaccines we’ve got, using the contraceptive methods that will prevent disease transmission, and reminding people to ask about sex life.
I did come across a website that just startled me. It’s called HeHealth, and basically it says to men, if you are conscientious about your sex life, take a picture of your penis, send it to us, and we have doctors — I presume they’re US doctors but I don’t know — who will diagnose venereal diseases based on that picture. I presume women could also say, “Before we have sex, or now that we’re approaching that possibility, I want you to send a picture to this company on this website.”
Now, a couple of reminders. I think we all know this, but just because you’re not manifesting symptoms on your reproductive organs doesn’t mean you don’t have a sexual disease. It’s not a reliable measure. Yes, maybe you could have somebody say: “Oh, that looks nasty. I’m not sure you ought to have sex right now, and maybe you should go get some treatment.” This is going to miss many cases and is not a reliable indicator that your partner is safe in terms of not transmitting diseases to you.
It also isn’t clear what they do with these images. Do they keep them? Who can see them? Could they resell them? What sort of privacy protection have you got if you decide to use this?
There’s another issue here, which is, if they misdiagnose someone and you do catch a sexual disease, who’s liable? Can you go after them for using doctors who weren’t competent or transmitting images that weren’t really adequate because you didn’t know how to take that picture properly when you sent that off to them? There are many unknowns.
The bottom line is that we’re in a different world, I think, of romance. We’re in a world where some people are going to meet more partners. Some people are going to meet more strangers. One approach is to have us take pictures of ourselves, send them off to who knows where, and ask for a green light to go ahead and have sexual relations. I don’t think we’re anywhere close to being able to rely on that as a way to avoid the risks of unprotected sexual behavior.
We do know what to do in dealing with patients who are sexually active. First, we have to ask them. Then we’ve got to recommend available vaccinations to prevent the transmission of some cancers, the HPV vaccine. Then they need that reminder about safe sexual practices not only to protect against unwanted pregnancy, but still, in this day and age, to protect against syphilis, which is on the rise, plus HIV, gonorrhea, chlamydia, and other sexually transmissible diseases.
I’m not going to rely on the penis picture to make the world safe for sex. I think we have to still use the old-fashioned techniques of education and prevention to do the best we can.
Dr. Caplan is director of the Division of Medical Ethics at New York University Langone Medical Center, New York City. He reported conflicts of interest with Johnson & Johnson’s Panel for Compassionate Drug Use and Medscape.
A version of this article first appeared on Medscape.com.
Experts Expect New Human Cases of Avian Flu
With avian influenza spreading quickly around the globe, the virus has more opportunities to mutate and cause problems for people. By some calculations, H5N1 bird flu is still at least two mutations away from widespread human infections, but experts warn that new flu symptoms in individuals at high risk are likely to start turning up in health systems this summer.
Dr. Dugan is leading the team of CDC scientists that is working with partners from the US Department of Agriculture, the US Food and Drug Administration (FDA), and state and local health departments to track and respond to the H5N1 bird flu outbreak currently sweeping through the United States.
Since 2022, avian influenza A viruses have been detected in more than 9300 wild birds in 50 states and territories and in commercial and backyard flocks.
“It’s a bad situation,” said Florian Krammer, PhD, professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York. “Globally, we’ve seen tons of exposure in cities around the world and even in the birds here in New York City where I am.”
Birds shed the virus in their saliva, mucous, and feces, so people or other animals with close, unprotected contact with infected birds or their contaminated environments can be infected.
And for the first time in March 2024, H5N1 bird flu was reported in dairy cows. The US Department of Agriculture said that at last count, 101 dairy herds in 12 states had been infected, with several cases also found in dairy workers.
From Birds to Cattle and Farm Workers
The National Veterinary Services Laboratories confirmed the infections were highly pathogenic avian influenza H5N1 clade 2.3.4.4b of Eurasian lineage. Also known as the goose, Guangdong clade from China, phylogenetic analysis and epidemiology suggests a single introduction into cows followed by onward transmission.
“I was surprised when H5 was introduced to dairy cattle in this way,” Dr. Dugan said. “Influenza viruses are always surprising us and it reminds me to stay humble and keep an open mind when dealing with them.”
People rarely inhale or get sufficient virus in their eyes or mouth to get sick, Dr. Dugan said, but those in close contact with animals are still at risk for infection, which could lead to upper respiratory tract symptoms such as shortness of breath, cough, sore throat, or runny or stuffy nose.
Like with other viruses, people can also experience muscle or body aches, headache, fatigue, fever or, as was seen in farm workers, conjunctivitis.
But there are less-common symptoms too like diarrhea, nausea, and vomiting — and sometimes, even seizures.
The risk to the general public is still low, Dr. Dugan said, but authorities recommend that people working with animals wash their hands with soap and water and wear personal protective equipment that includes fluid-resistant coveralls, a waterproof apron, a safety-approved respirator, properly fitted goggles or face shield, a head or hair cover, gloves, and boots.
Dr. Dugan said that health care providers often don’t take a history of occupational exposures when a patient presents with flu. But with rising rates of bird flu in new animal hosts, “this will be an important next step.”
Asking Unusual Questions
This approach is not standardized on most electronic health records, so these are questions that clinicians will need to initiate themselves.
“Physicians should ask about work,” said Meghan Davis, PhD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “If it’s not already on the radar, asking about any direct contact with dairy cows, poultry, pigs, wild birds, or wild mammals is important.”
Dr. Davis says she’s worried about a new study tracking risk factors for farm-to-farm transmission because it shows that farms testing positive for avian influenza often have workers with a family member also employed on another farm. “This suggests that we might need to be on the lookout for possible transmission within families,” she said. Now, we have to ask “not just if the person with symptoms has contact with or works on a dairy farm, milk processing plant, or slaughterhouse, but also if any family member does.”
Dr. Davis said that it’s important to bear in mind when taking these histories that there may be younger workers on farms and in slaughter and processing facilities due to exemptions or illegal work.
What is important now is to get the situation under control this season in dairy cattle, Dr. Krammer said. “This will be easier to stop in cows than humans, so this is the time to stop moving dairy cattle and start vaccinating them.”
Spotting New Cases
Since April 2024, there have been three human cases of avian influenza after exposure to dairy cows reported. “And what we don’t want to see this summer is an unusual human cluster of influenza. It’s important we keep a close, watchful eye for this,” Dr. Krammer said.
“Influenza viruses do very interesting things and as we head into fall and winter flu season, we don’t want new human co-infections that could cause major problems for us,” he said.
If people become mixing vessels of a seasonal cocktail of multiple viruses, that could empower H5N1 to mutate again into something more dangerous, sparking a new pandemic.
“It wasn’t all that long ago that we were asking China difficult questions about the steps Chinese authorities took to protect human lives from SARS-CoV-2 in the COVID pandemic. Now, we must ask ourselves many of these questions,” Dr. Krammer said. “We are at a crucial crossroad where we will either elude a new pandemic or see one take off, risking 10 to 20 million lives.”
There is a precedent for safely evading more trouble, Dr. Krammer pointed out. Government agencies have already been working with the poultry industry for a couple of years now. “And here, we have successfully stopped H5N1 with new regulations and policies.”
But moving from poultry farms to cattle has not been an easy transition, Dr. Dugan said. Cattle farms have no experience with bird flu or tactics to contain it with regulations, and officials too are working in new, unfamiliar terrain.
“What we have now isn’t a science problem, it’s a policy issue, and it hasn’t always been clear who is in charge,” Dr. Krammer said.
“Agencies are working together at the state, federal, and global level,” said Dr. Dugan. “We are increasing our transparency and are working to share what we know, when we know it.”
The infrastructure built during the COVID pandemic has helped teams prepare for this new crisis, Dr. Dugan said. Year-round, layered monitoring has clinical labs reporting seasonal influenza and novel cases.
“Laboratories are ready to help with testing,” Dr. Dugan said.
Specimens should be collected as soon as possible from patients with flu symptoms. A nasopharyngeal swab is recommended with a nasal swab combined with an oropharyngeal swab. If a patient has conjunctivitis with or without respiratory symptoms, both a conjunctival swab and a nasopharyngeal swab should be collected.
People with severe respiratory disease should also have lower respiratory tract specimens collected.
Standard, contact, and airborne precautions are recommended for patients presenting for medical care who have illness consistent with influenza and recent exposure to birds or other animals.
Antiviral Drugs
There are four FDA-approved antivirals for influenza: Oseltamivir phosphate (available as a generic drug or by the trade name Tamiflu), zanamivir (Relenza), peramivir (Rapivab) , and baloxavir (Xofluza).
For people with suspected or confirmed avian influenza, treatment is recommended as soon as possible.
There are no clinical trials measuring the outcome of antivirals in people infected with avian influenza. However, data from animal models and human observational studies suggest a benefit.
“We can’t afford to wait this summer,” Dr. Krammer said. “We have an opportunity right now to stop this in cows before we risk infecting more people. I hope we do.”
A version of this article first appeared on Medscape.com.
With avian influenza spreading quickly around the globe, the virus has more opportunities to mutate and cause problems for people. By some calculations, H5N1 bird flu is still at least two mutations away from widespread human infections, but experts warn that new flu symptoms in individuals at high risk are likely to start turning up in health systems this summer.
Dr. Dugan is leading the team of CDC scientists that is working with partners from the US Department of Agriculture, the US Food and Drug Administration (FDA), and state and local health departments to track and respond to the H5N1 bird flu outbreak currently sweeping through the United States.
Since 2022, avian influenza A viruses have been detected in more than 9300 wild birds in 50 states and territories and in commercial and backyard flocks.
“It’s a bad situation,” said Florian Krammer, PhD, professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York. “Globally, we’ve seen tons of exposure in cities around the world and even in the birds here in New York City where I am.”
Birds shed the virus in their saliva, mucous, and feces, so people or other animals with close, unprotected contact with infected birds or their contaminated environments can be infected.
And for the first time in March 2024, H5N1 bird flu was reported in dairy cows. The US Department of Agriculture said that at last count, 101 dairy herds in 12 states had been infected, with several cases also found in dairy workers.
From Birds to Cattle and Farm Workers
The National Veterinary Services Laboratories confirmed the infections were highly pathogenic avian influenza H5N1 clade 2.3.4.4b of Eurasian lineage. Also known as the goose, Guangdong clade from China, phylogenetic analysis and epidemiology suggests a single introduction into cows followed by onward transmission.
“I was surprised when H5 was introduced to dairy cattle in this way,” Dr. Dugan said. “Influenza viruses are always surprising us and it reminds me to stay humble and keep an open mind when dealing with them.”
People rarely inhale or get sufficient virus in their eyes or mouth to get sick, Dr. Dugan said, but those in close contact with animals are still at risk for infection, which could lead to upper respiratory tract symptoms such as shortness of breath, cough, sore throat, or runny or stuffy nose.
Like with other viruses, people can also experience muscle or body aches, headache, fatigue, fever or, as was seen in farm workers, conjunctivitis.
But there are less-common symptoms too like diarrhea, nausea, and vomiting — and sometimes, even seizures.
The risk to the general public is still low, Dr. Dugan said, but authorities recommend that people working with animals wash their hands with soap and water and wear personal protective equipment that includes fluid-resistant coveralls, a waterproof apron, a safety-approved respirator, properly fitted goggles or face shield, a head or hair cover, gloves, and boots.
Dr. Dugan said that health care providers often don’t take a history of occupational exposures when a patient presents with flu. But with rising rates of bird flu in new animal hosts, “this will be an important next step.”
Asking Unusual Questions
This approach is not standardized on most electronic health records, so these are questions that clinicians will need to initiate themselves.
“Physicians should ask about work,” said Meghan Davis, PhD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “If it’s not already on the radar, asking about any direct contact with dairy cows, poultry, pigs, wild birds, or wild mammals is important.”
Dr. Davis says she’s worried about a new study tracking risk factors for farm-to-farm transmission because it shows that farms testing positive for avian influenza often have workers with a family member also employed on another farm. “This suggests that we might need to be on the lookout for possible transmission within families,” she said. Now, we have to ask “not just if the person with symptoms has contact with or works on a dairy farm, milk processing plant, or slaughterhouse, but also if any family member does.”
Dr. Davis said that it’s important to bear in mind when taking these histories that there may be younger workers on farms and in slaughter and processing facilities due to exemptions or illegal work.
What is important now is to get the situation under control this season in dairy cattle, Dr. Krammer said. “This will be easier to stop in cows than humans, so this is the time to stop moving dairy cattle and start vaccinating them.”
Spotting New Cases
Since April 2024, there have been three human cases of avian influenza after exposure to dairy cows reported. “And what we don’t want to see this summer is an unusual human cluster of influenza. It’s important we keep a close, watchful eye for this,” Dr. Krammer said.
“Influenza viruses do very interesting things and as we head into fall and winter flu season, we don’t want new human co-infections that could cause major problems for us,” he said.
If people become mixing vessels of a seasonal cocktail of multiple viruses, that could empower H5N1 to mutate again into something more dangerous, sparking a new pandemic.
“It wasn’t all that long ago that we were asking China difficult questions about the steps Chinese authorities took to protect human lives from SARS-CoV-2 in the COVID pandemic. Now, we must ask ourselves many of these questions,” Dr. Krammer said. “We are at a crucial crossroad where we will either elude a new pandemic or see one take off, risking 10 to 20 million lives.”
There is a precedent for safely evading more trouble, Dr. Krammer pointed out. Government agencies have already been working with the poultry industry for a couple of years now. “And here, we have successfully stopped H5N1 with new regulations and policies.”
But moving from poultry farms to cattle has not been an easy transition, Dr. Dugan said. Cattle farms have no experience with bird flu or tactics to contain it with regulations, and officials too are working in new, unfamiliar terrain.
“What we have now isn’t a science problem, it’s a policy issue, and it hasn’t always been clear who is in charge,” Dr. Krammer said.
“Agencies are working together at the state, federal, and global level,” said Dr. Dugan. “We are increasing our transparency and are working to share what we know, when we know it.”
The infrastructure built during the COVID pandemic has helped teams prepare for this new crisis, Dr. Dugan said. Year-round, layered monitoring has clinical labs reporting seasonal influenza and novel cases.
“Laboratories are ready to help with testing,” Dr. Dugan said.
Specimens should be collected as soon as possible from patients with flu symptoms. A nasopharyngeal swab is recommended with a nasal swab combined with an oropharyngeal swab. If a patient has conjunctivitis with or without respiratory symptoms, both a conjunctival swab and a nasopharyngeal swab should be collected.
People with severe respiratory disease should also have lower respiratory tract specimens collected.
Standard, contact, and airborne precautions are recommended for patients presenting for medical care who have illness consistent with influenza and recent exposure to birds or other animals.
Antiviral Drugs
There are four FDA-approved antivirals for influenza: Oseltamivir phosphate (available as a generic drug or by the trade name Tamiflu), zanamivir (Relenza), peramivir (Rapivab) , and baloxavir (Xofluza).
For people with suspected or confirmed avian influenza, treatment is recommended as soon as possible.
There are no clinical trials measuring the outcome of antivirals in people infected with avian influenza. However, data from animal models and human observational studies suggest a benefit.
“We can’t afford to wait this summer,” Dr. Krammer said. “We have an opportunity right now to stop this in cows before we risk infecting more people. I hope we do.”
A version of this article first appeared on Medscape.com.
With avian influenza spreading quickly around the globe, the virus has more opportunities to mutate and cause problems for people. By some calculations, H5N1 bird flu is still at least two mutations away from widespread human infections, but experts warn that new flu symptoms in individuals at high risk are likely to start turning up in health systems this summer.
Dr. Dugan is leading the team of CDC scientists that is working with partners from the US Department of Agriculture, the US Food and Drug Administration (FDA), and state and local health departments to track and respond to the H5N1 bird flu outbreak currently sweeping through the United States.
Since 2022, avian influenza A viruses have been detected in more than 9300 wild birds in 50 states and territories and in commercial and backyard flocks.
“It’s a bad situation,” said Florian Krammer, PhD, professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York. “Globally, we’ve seen tons of exposure in cities around the world and even in the birds here in New York City where I am.”
Birds shed the virus in their saliva, mucous, and feces, so people or other animals with close, unprotected contact with infected birds or their contaminated environments can be infected.
And for the first time in March 2024, H5N1 bird flu was reported in dairy cows. The US Department of Agriculture said that at last count, 101 dairy herds in 12 states had been infected, with several cases also found in dairy workers.
From Birds to Cattle and Farm Workers
The National Veterinary Services Laboratories confirmed the infections were highly pathogenic avian influenza H5N1 clade 2.3.4.4b of Eurasian lineage. Also known as the goose, Guangdong clade from China, phylogenetic analysis and epidemiology suggests a single introduction into cows followed by onward transmission.
“I was surprised when H5 was introduced to dairy cattle in this way,” Dr. Dugan said. “Influenza viruses are always surprising us and it reminds me to stay humble and keep an open mind when dealing with them.”
People rarely inhale or get sufficient virus in their eyes or mouth to get sick, Dr. Dugan said, but those in close contact with animals are still at risk for infection, which could lead to upper respiratory tract symptoms such as shortness of breath, cough, sore throat, or runny or stuffy nose.
Like with other viruses, people can also experience muscle or body aches, headache, fatigue, fever or, as was seen in farm workers, conjunctivitis.
But there are less-common symptoms too like diarrhea, nausea, and vomiting — and sometimes, even seizures.
The risk to the general public is still low, Dr. Dugan said, but authorities recommend that people working with animals wash their hands with soap and water and wear personal protective equipment that includes fluid-resistant coveralls, a waterproof apron, a safety-approved respirator, properly fitted goggles or face shield, a head or hair cover, gloves, and boots.
Dr. Dugan said that health care providers often don’t take a history of occupational exposures when a patient presents with flu. But with rising rates of bird flu in new animal hosts, “this will be an important next step.”
Asking Unusual Questions
This approach is not standardized on most electronic health records, so these are questions that clinicians will need to initiate themselves.
“Physicians should ask about work,” said Meghan Davis, PhD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “If it’s not already on the radar, asking about any direct contact with dairy cows, poultry, pigs, wild birds, or wild mammals is important.”
Dr. Davis says she’s worried about a new study tracking risk factors for farm-to-farm transmission because it shows that farms testing positive for avian influenza often have workers with a family member also employed on another farm. “This suggests that we might need to be on the lookout for possible transmission within families,” she said. Now, we have to ask “not just if the person with symptoms has contact with or works on a dairy farm, milk processing plant, or slaughterhouse, but also if any family member does.”
Dr. Davis said that it’s important to bear in mind when taking these histories that there may be younger workers on farms and in slaughter and processing facilities due to exemptions or illegal work.
What is important now is to get the situation under control this season in dairy cattle, Dr. Krammer said. “This will be easier to stop in cows than humans, so this is the time to stop moving dairy cattle and start vaccinating them.”
Spotting New Cases
Since April 2024, there have been three human cases of avian influenza after exposure to dairy cows reported. “And what we don’t want to see this summer is an unusual human cluster of influenza. It’s important we keep a close, watchful eye for this,” Dr. Krammer said.
“Influenza viruses do very interesting things and as we head into fall and winter flu season, we don’t want new human co-infections that could cause major problems for us,” he said.
If people become mixing vessels of a seasonal cocktail of multiple viruses, that could empower H5N1 to mutate again into something more dangerous, sparking a new pandemic.
“It wasn’t all that long ago that we were asking China difficult questions about the steps Chinese authorities took to protect human lives from SARS-CoV-2 in the COVID pandemic. Now, we must ask ourselves many of these questions,” Dr. Krammer said. “We are at a crucial crossroad where we will either elude a new pandemic or see one take off, risking 10 to 20 million lives.”
There is a precedent for safely evading more trouble, Dr. Krammer pointed out. Government agencies have already been working with the poultry industry for a couple of years now. “And here, we have successfully stopped H5N1 with new regulations and policies.”
But moving from poultry farms to cattle has not been an easy transition, Dr. Dugan said. Cattle farms have no experience with bird flu or tactics to contain it with regulations, and officials too are working in new, unfamiliar terrain.
“What we have now isn’t a science problem, it’s a policy issue, and it hasn’t always been clear who is in charge,” Dr. Krammer said.
“Agencies are working together at the state, federal, and global level,” said Dr. Dugan. “We are increasing our transparency and are working to share what we know, when we know it.”
The infrastructure built during the COVID pandemic has helped teams prepare for this new crisis, Dr. Dugan said. Year-round, layered monitoring has clinical labs reporting seasonal influenza and novel cases.
“Laboratories are ready to help with testing,” Dr. Dugan said.
Specimens should be collected as soon as possible from patients with flu symptoms. A nasopharyngeal swab is recommended with a nasal swab combined with an oropharyngeal swab. If a patient has conjunctivitis with or without respiratory symptoms, both a conjunctival swab and a nasopharyngeal swab should be collected.
People with severe respiratory disease should also have lower respiratory tract specimens collected.
Standard, contact, and airborne precautions are recommended for patients presenting for medical care who have illness consistent with influenza and recent exposure to birds or other animals.
Antiviral Drugs
There are four FDA-approved antivirals for influenza: Oseltamivir phosphate (available as a generic drug or by the trade name Tamiflu), zanamivir (Relenza), peramivir (Rapivab) , and baloxavir (Xofluza).
For people with suspected or confirmed avian influenza, treatment is recommended as soon as possible.
There are no clinical trials measuring the outcome of antivirals in people infected with avian influenza. However, data from animal models and human observational studies suggest a benefit.
“We can’t afford to wait this summer,” Dr. Krammer said. “We have an opportunity right now to stop this in cows before we risk infecting more people. I hope we do.”
A version of this article first appeared on Medscape.com.
FDA Approves New Pneumococcal Vaccine
A new vaccine to prevent invasive pneumococcal disease and pneumococcal pneumonia in adults has been approved by the Food and Drug Administration.
The injectable drug, Capvaxive (Pneumococcal 21-valent Conjugate Vaccine), protects against 22 serotypes that cause invasive pneumococcal disease in adults, the company said in a news release. These strains account for about 84% of invasive pneumococcal disease cases among adults aged 50 years or older and about 85% of these cases in adults aged 65 years or older.
The drug company said about 150,000 adults in the United States are hospitalized annually because of pneumococcal pneumonia.
“Many cases of adult disease are caused by serotypes not included in other approved pneumococcal conjugate vaccines,” Walter Orenstein, MD, a professor emeritus of medicine, epidemiology, global health, and pediatrics at Emory University, Atlanta, Georgia, and a member of Merck’s Scientific Advisory Committee, said in the release.
A draft agenda shows a Centers for Disease Control and Prevention (CDC) advisory panel will meet on June 27 to discuss the vaccine. If the committee votes to approve Capvaxive, the CDC director will decide whether to make it available across the country.
Testing showed that Capvaxive was well tolerated by people it was tested on, with the main reports being pain where they got the shot, fatigue, headaches, and muscle aches, Merck said.
The eight unique serotypes included in CAPVAXIVE will protect against invasive pneumococcal disease and pneumococcal pneumonia, not just pneumonia.
According to Reuters, Merck said Capvaxive has a wholesale acquisition price of $287 per dose, but most people will probably have access to it at no cost if the drug receives a routine CDC recommendation. Capvaxive’s main competition is expected to be Pfizer’s shot, Prevnar 20, which was approved in 2021 for use in adults aged 18 years or older, Reuters reported.
A version of this article appeared on Medscape.com.
A new vaccine to prevent invasive pneumococcal disease and pneumococcal pneumonia in adults has been approved by the Food and Drug Administration.
The injectable drug, Capvaxive (Pneumococcal 21-valent Conjugate Vaccine), protects against 22 serotypes that cause invasive pneumococcal disease in adults, the company said in a news release. These strains account for about 84% of invasive pneumococcal disease cases among adults aged 50 years or older and about 85% of these cases in adults aged 65 years or older.
The drug company said about 150,000 adults in the United States are hospitalized annually because of pneumococcal pneumonia.
“Many cases of adult disease are caused by serotypes not included in other approved pneumococcal conjugate vaccines,” Walter Orenstein, MD, a professor emeritus of medicine, epidemiology, global health, and pediatrics at Emory University, Atlanta, Georgia, and a member of Merck’s Scientific Advisory Committee, said in the release.
A draft agenda shows a Centers for Disease Control and Prevention (CDC) advisory panel will meet on June 27 to discuss the vaccine. If the committee votes to approve Capvaxive, the CDC director will decide whether to make it available across the country.
Testing showed that Capvaxive was well tolerated by people it was tested on, with the main reports being pain where they got the shot, fatigue, headaches, and muscle aches, Merck said.
The eight unique serotypes included in CAPVAXIVE will protect against invasive pneumococcal disease and pneumococcal pneumonia, not just pneumonia.
According to Reuters, Merck said Capvaxive has a wholesale acquisition price of $287 per dose, but most people will probably have access to it at no cost if the drug receives a routine CDC recommendation. Capvaxive’s main competition is expected to be Pfizer’s shot, Prevnar 20, which was approved in 2021 for use in adults aged 18 years or older, Reuters reported.
A version of this article appeared on Medscape.com.
A new vaccine to prevent invasive pneumococcal disease and pneumococcal pneumonia in adults has been approved by the Food and Drug Administration.
The injectable drug, Capvaxive (Pneumococcal 21-valent Conjugate Vaccine), protects against 22 serotypes that cause invasive pneumococcal disease in adults, the company said in a news release. These strains account for about 84% of invasive pneumococcal disease cases among adults aged 50 years or older and about 85% of these cases in adults aged 65 years or older.
The drug company said about 150,000 adults in the United States are hospitalized annually because of pneumococcal pneumonia.
“Many cases of adult disease are caused by serotypes not included in other approved pneumococcal conjugate vaccines,” Walter Orenstein, MD, a professor emeritus of medicine, epidemiology, global health, and pediatrics at Emory University, Atlanta, Georgia, and a member of Merck’s Scientific Advisory Committee, said in the release.
A draft agenda shows a Centers for Disease Control and Prevention (CDC) advisory panel will meet on June 27 to discuss the vaccine. If the committee votes to approve Capvaxive, the CDC director will decide whether to make it available across the country.
Testing showed that Capvaxive was well tolerated by people it was tested on, with the main reports being pain where they got the shot, fatigue, headaches, and muscle aches, Merck said.
The eight unique serotypes included in CAPVAXIVE will protect against invasive pneumococcal disease and pneumococcal pneumonia, not just pneumonia.
According to Reuters, Merck said Capvaxive has a wholesale acquisition price of $287 per dose, but most people will probably have access to it at no cost if the drug receives a routine CDC recommendation. Capvaxive’s main competition is expected to be Pfizer’s shot, Prevnar 20, which was approved in 2021 for use in adults aged 18 years or older, Reuters reported.
A version of this article appeared on Medscape.com.
Acute Sore Throat in Primary Care: When to Reach for the Antibiotics
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
Flesh-Colored Pinpoint Papules With Fine White Spicules on the Upper Body
The Diagnosis: Trichodysplasia Spinulosa
A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.
Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.
Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.
The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8
Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11
Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.
Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16
- Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
- Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
- Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
- Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
- Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
- Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
- Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
- Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
- Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
- Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
- Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
- Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
- Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
- Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
- Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
- Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
The Diagnosis: Trichodysplasia Spinulosa
A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.
Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.
Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.
The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8
Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11
Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.
Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16
The Diagnosis: Trichodysplasia Spinulosa
A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.
Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.
Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.
The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8
Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11
Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.
Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16
- Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
- Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
- Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
- Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
- Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
- Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
- Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
- Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
- Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
- Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
- Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
- Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
- Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
- Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
- Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
- Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
- Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
- Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
- Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
- Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
- Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
- Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
- Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
- Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
- Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
- Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
- Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
- Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
- Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
- Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
- Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
- Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
A 54-year-old Black woman presented with a rash that developed 6 months after a renal transplant due to a history of systemic lupus erythematosus with lupus nephritis. She was started on mycophenolate mofetil and tacrolimus after the transplant but was switched to cyclosporine because of BK viremia. The rash developed 1 week after cyclosporine was initiated and consisted of pruritic papules that started on the face and spread to the trunk and arms. Physical examination revealed innumerable follicular-based, keratotic, flesh-colored, pinpoint papules with fine white spicules on the face (top), neck, chest, arms, and back. Leonine facies was seen along the glabella with madarosis of the lateral eyebrows (top) and ears (bottom).
Predicting and Understanding Vaccine Response Determinants
In this column, I recently discussed the impact of the microbiome on childhood vaccine responses. My group has been expanding our research on the topic of childhood vaccine response and its relationship to infection proneness. Therefore, I want to share new research findings.
Immune responsiveness to vaccines varies among children, leaving some susceptible to infections. We also have evidence that the immune deficiencies that contribute to poor vaccine responsiveness also manifest in children as respiratory infection proneness.
Predicting Vaccine Response in the Neonatal Period
The first 100 days of life is an amazing transition time in early life. During that time, the immune system is highly influenced by environmental factors that generate epigenetic changes affecting vaccine responsiveness. Some publications have used the term “window of opportunity,” because it is thought that interventions to change a negative trajectory to a positive one for vaccine responsiveness have a better potential to be effective. Predicting which children will be poorly responsive to vaccines would be desirable, so those children could be specifically identified for intervention. Doing so in the neonatal age time frame using easy-to-obtain clinical samples would be a bonus.
In our most recent study, we sought to identify cytokine biosignatures in the neonatal period, measured in convenient nasopharyngeal secretions, that predict vaccine responses, measured as antibody levels to various vaccines at 1 year of life. Secondly, we assessed the effect of antibiotic exposures on vaccine responses in the study cohort. Third, we tested for induction of CD4+ T-cell vaccine-specific immune memory at infant age 1 year. Fourth, we studied antigen presenting cells (APCs) at rest and in response to an adjuvant called R848, known to stimulate toll-like receptor (TLR) 7/8 agonist, to assess its effects on the immune cells of low vaccine responder children, compared with other children.1
The study population consisted of 101 infants recruited from two primary care pediatric practices in/near Rochester, New York. Children lived in suburban and rural environments. Enrollment and sampling occurred during 2017-2020. All participants received regularly scheduled childhood vaccinations according to the recommendations by US Centers for Disease Control. Nasopharyngeal swabs were used to collect nasal secretions. Antibody titers against six antigens were measured at approximately 1 year of age from all 72 available blood samples. The protective threshold of the corresponding vaccine antigen divided each vaccine-induced antibody level and the ratio considered a normalized titer. The normalized antibody titers were used to define vaccine responsiveness groups as Low Vaccine Responder (bottom 25th percentile of vaccine responders, n = 18 children), as Normal Vaccine Responder (25-75th percentile of vaccine responders, n = 36 children) and as High Vaccine Responder (top 25th percentile of vaccine responders, n = 18 children).
We found that specific nasal cytokine levels measured at newborn age 1 week old, 2 weeks old, and 3 weeks old were predictive of the vaccine response groupings measured at child age 1 year old, following their primary series of vaccinations. The P values varied between less than .05 to .001.
Five newborns had antibiotic exposure at/near the time of birth; 4 [80%] of the 5 were Low Vaccine Responders vs 1 [2%] of 60 Normal+High Vaccine Responder children, P = .006. Also, the cumulative days of antibiotic exposure up to 1 year was highly associated with low vaccine responders, compared with Normal+High Vaccine Responder children (P = 2 x 10-16).
We found that Low Vaccine Responder infants had reduced vaccine-specific T-helper memory cells producing INFg and IL-2 (Th1 cytokines) and IL-4 (Th2 cytokines), compared with Normal+High Vaccine Responder children. In the absence of sufficient numbers of antigen-specific memory CD4+ T-cells, a child would become unprotected from the target infection that the vaccines were intended to prevent after the antibody levels wane.
We found that Low Vaccine Responder antigen-presenting cells are different from those in normal vaccine responders and they can be distinguished when at rest and when stimulated by a specific adjuvant — R848. Our previous findings suggested that Low Vaccine Responder children have a prolonged neonatal-like immune profile (PNIP).2 Therefore, stimulating the immune system of a Low Vaccine Responder could shift their cellular immune responses to behave like cells of Normal+High Vaccine Responder children.
In summary, we identified cytokine biosignatures measured in nasopharyngeal secretions in the neonatal period that predicted vaccine response groups measured as antibody levels at 1 year of life. We showed that reduced vaccine responsiveness was associated with antibiotic exposure at/near birth and with cumulative exposure during the first year of life. We found that Low Vaccine Responder children at 1 year old have fewer vaccine-specific memory CD4+ Th1 and Th2-cells and that antigen-presenting cells at rest and in response to R848 antigen stimulation differ, compared with Normal+High Vaccine Responder children.
Future work by our group will focus on exploring early-life risk factors that influence differences in vaccine responsiveness and interventions that might shift a child’s responsiveness from low to normal or high.
Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (New York) General Hospital. He has no conflicts of interest to declare.
References
1. Pichichero ME et al. Variability of Vaccine Responsiveness in Young Children. J Infect Dis. 2023 Nov 22:jiad524. doi: 10.1093/infdis/jiad524.
2. Pichichero ME et al. Functional Immune Cell Differences Associated with Low Vaccine Responses in Infants. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.
In this column, I recently discussed the impact of the microbiome on childhood vaccine responses. My group has been expanding our research on the topic of childhood vaccine response and its relationship to infection proneness. Therefore, I want to share new research findings.
Immune responsiveness to vaccines varies among children, leaving some susceptible to infections. We also have evidence that the immune deficiencies that contribute to poor vaccine responsiveness also manifest in children as respiratory infection proneness.
Predicting Vaccine Response in the Neonatal Period
The first 100 days of life is an amazing transition time in early life. During that time, the immune system is highly influenced by environmental factors that generate epigenetic changes affecting vaccine responsiveness. Some publications have used the term “window of opportunity,” because it is thought that interventions to change a negative trajectory to a positive one for vaccine responsiveness have a better potential to be effective. Predicting which children will be poorly responsive to vaccines would be desirable, so those children could be specifically identified for intervention. Doing so in the neonatal age time frame using easy-to-obtain clinical samples would be a bonus.
In our most recent study, we sought to identify cytokine biosignatures in the neonatal period, measured in convenient nasopharyngeal secretions, that predict vaccine responses, measured as antibody levels to various vaccines at 1 year of life. Secondly, we assessed the effect of antibiotic exposures on vaccine responses in the study cohort. Third, we tested for induction of CD4+ T-cell vaccine-specific immune memory at infant age 1 year. Fourth, we studied antigen presenting cells (APCs) at rest and in response to an adjuvant called R848, known to stimulate toll-like receptor (TLR) 7/8 agonist, to assess its effects on the immune cells of low vaccine responder children, compared with other children.1
The study population consisted of 101 infants recruited from two primary care pediatric practices in/near Rochester, New York. Children lived in suburban and rural environments. Enrollment and sampling occurred during 2017-2020. All participants received regularly scheduled childhood vaccinations according to the recommendations by US Centers for Disease Control. Nasopharyngeal swabs were used to collect nasal secretions. Antibody titers against six antigens were measured at approximately 1 year of age from all 72 available blood samples. The protective threshold of the corresponding vaccine antigen divided each vaccine-induced antibody level and the ratio considered a normalized titer. The normalized antibody titers were used to define vaccine responsiveness groups as Low Vaccine Responder (bottom 25th percentile of vaccine responders, n = 18 children), as Normal Vaccine Responder (25-75th percentile of vaccine responders, n = 36 children) and as High Vaccine Responder (top 25th percentile of vaccine responders, n = 18 children).
We found that specific nasal cytokine levels measured at newborn age 1 week old, 2 weeks old, and 3 weeks old were predictive of the vaccine response groupings measured at child age 1 year old, following their primary series of vaccinations. The P values varied between less than .05 to .001.
Five newborns had antibiotic exposure at/near the time of birth; 4 [80%] of the 5 were Low Vaccine Responders vs 1 [2%] of 60 Normal+High Vaccine Responder children, P = .006. Also, the cumulative days of antibiotic exposure up to 1 year was highly associated with low vaccine responders, compared with Normal+High Vaccine Responder children (P = 2 x 10-16).
We found that Low Vaccine Responder infants had reduced vaccine-specific T-helper memory cells producing INFg and IL-2 (Th1 cytokines) and IL-4 (Th2 cytokines), compared with Normal+High Vaccine Responder children. In the absence of sufficient numbers of antigen-specific memory CD4+ T-cells, a child would become unprotected from the target infection that the vaccines were intended to prevent after the antibody levels wane.
We found that Low Vaccine Responder antigen-presenting cells are different from those in normal vaccine responders and they can be distinguished when at rest and when stimulated by a specific adjuvant — R848. Our previous findings suggested that Low Vaccine Responder children have a prolonged neonatal-like immune profile (PNIP).2 Therefore, stimulating the immune system of a Low Vaccine Responder could shift their cellular immune responses to behave like cells of Normal+High Vaccine Responder children.
In summary, we identified cytokine biosignatures measured in nasopharyngeal secretions in the neonatal period that predicted vaccine response groups measured as antibody levels at 1 year of life. We showed that reduced vaccine responsiveness was associated with antibiotic exposure at/near birth and with cumulative exposure during the first year of life. We found that Low Vaccine Responder children at 1 year old have fewer vaccine-specific memory CD4+ Th1 and Th2-cells and that antigen-presenting cells at rest and in response to R848 antigen stimulation differ, compared with Normal+High Vaccine Responder children.
Future work by our group will focus on exploring early-life risk factors that influence differences in vaccine responsiveness and interventions that might shift a child’s responsiveness from low to normal or high.
Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (New York) General Hospital. He has no conflicts of interest to declare.
References
1. Pichichero ME et al. Variability of Vaccine Responsiveness in Young Children. J Infect Dis. 2023 Nov 22:jiad524. doi: 10.1093/infdis/jiad524.
2. Pichichero ME et al. Functional Immune Cell Differences Associated with Low Vaccine Responses in Infants. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.
In this column, I recently discussed the impact of the microbiome on childhood vaccine responses. My group has been expanding our research on the topic of childhood vaccine response and its relationship to infection proneness. Therefore, I want to share new research findings.
Immune responsiveness to vaccines varies among children, leaving some susceptible to infections. We also have evidence that the immune deficiencies that contribute to poor vaccine responsiveness also manifest in children as respiratory infection proneness.
Predicting Vaccine Response in the Neonatal Period
The first 100 days of life is an amazing transition time in early life. During that time, the immune system is highly influenced by environmental factors that generate epigenetic changes affecting vaccine responsiveness. Some publications have used the term “window of opportunity,” because it is thought that interventions to change a negative trajectory to a positive one for vaccine responsiveness have a better potential to be effective. Predicting which children will be poorly responsive to vaccines would be desirable, so those children could be specifically identified for intervention. Doing so in the neonatal age time frame using easy-to-obtain clinical samples would be a bonus.
In our most recent study, we sought to identify cytokine biosignatures in the neonatal period, measured in convenient nasopharyngeal secretions, that predict vaccine responses, measured as antibody levels to various vaccines at 1 year of life. Secondly, we assessed the effect of antibiotic exposures on vaccine responses in the study cohort. Third, we tested for induction of CD4+ T-cell vaccine-specific immune memory at infant age 1 year. Fourth, we studied antigen presenting cells (APCs) at rest and in response to an adjuvant called R848, known to stimulate toll-like receptor (TLR) 7/8 agonist, to assess its effects on the immune cells of low vaccine responder children, compared with other children.1
The study population consisted of 101 infants recruited from two primary care pediatric practices in/near Rochester, New York. Children lived in suburban and rural environments. Enrollment and sampling occurred during 2017-2020. All participants received regularly scheduled childhood vaccinations according to the recommendations by US Centers for Disease Control. Nasopharyngeal swabs were used to collect nasal secretions. Antibody titers against six antigens were measured at approximately 1 year of age from all 72 available blood samples. The protective threshold of the corresponding vaccine antigen divided each vaccine-induced antibody level and the ratio considered a normalized titer. The normalized antibody titers were used to define vaccine responsiveness groups as Low Vaccine Responder (bottom 25th percentile of vaccine responders, n = 18 children), as Normal Vaccine Responder (25-75th percentile of vaccine responders, n = 36 children) and as High Vaccine Responder (top 25th percentile of vaccine responders, n = 18 children).
We found that specific nasal cytokine levels measured at newborn age 1 week old, 2 weeks old, and 3 weeks old were predictive of the vaccine response groupings measured at child age 1 year old, following their primary series of vaccinations. The P values varied between less than .05 to .001.
Five newborns had antibiotic exposure at/near the time of birth; 4 [80%] of the 5 were Low Vaccine Responders vs 1 [2%] of 60 Normal+High Vaccine Responder children, P = .006. Also, the cumulative days of antibiotic exposure up to 1 year was highly associated with low vaccine responders, compared with Normal+High Vaccine Responder children (P = 2 x 10-16).
We found that Low Vaccine Responder infants had reduced vaccine-specific T-helper memory cells producing INFg and IL-2 (Th1 cytokines) and IL-4 (Th2 cytokines), compared with Normal+High Vaccine Responder children. In the absence of sufficient numbers of antigen-specific memory CD4+ T-cells, a child would become unprotected from the target infection that the vaccines were intended to prevent after the antibody levels wane.
We found that Low Vaccine Responder antigen-presenting cells are different from those in normal vaccine responders and they can be distinguished when at rest and when stimulated by a specific adjuvant — R848. Our previous findings suggested that Low Vaccine Responder children have a prolonged neonatal-like immune profile (PNIP).2 Therefore, stimulating the immune system of a Low Vaccine Responder could shift their cellular immune responses to behave like cells of Normal+High Vaccine Responder children.
In summary, we identified cytokine biosignatures measured in nasopharyngeal secretions in the neonatal period that predicted vaccine response groups measured as antibody levels at 1 year of life. We showed that reduced vaccine responsiveness was associated with antibiotic exposure at/near birth and with cumulative exposure during the first year of life. We found that Low Vaccine Responder children at 1 year old have fewer vaccine-specific memory CD4+ Th1 and Th2-cells and that antigen-presenting cells at rest and in response to R848 antigen stimulation differ, compared with Normal+High Vaccine Responder children.
Future work by our group will focus on exploring early-life risk factors that influence differences in vaccine responsiveness and interventions that might shift a child’s responsiveness from low to normal or high.
Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (New York) General Hospital. He has no conflicts of interest to declare.
References
1. Pichichero ME et al. Variability of Vaccine Responsiveness in Young Children. J Infect Dis. 2023 Nov 22:jiad524. doi: 10.1093/infdis/jiad524.
2. Pichichero ME et al. Functional Immune Cell Differences Associated with Low Vaccine Responses in Infants. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.
Latest Breakthroughs in Molluscum Contagiosum Therapy
Molluscum contagiosum (ie, molluscum) is a ubiquitous infection caused by the poxvirus molluscum contagiosum virus (MCV). Although skin deep, molluscum shares many factors with the more virulent poxviridae. Moisture and trauma can cause viral material to be released from the pearly papules through a small opening, which also allows entry of bacteria and medications into the lesion. The MCV is transmitted by direct contact with skin or via fomites.1
Molluscum can affect children of any age, with MCV type 1 peaking in toddlers and school-aged children and MCV type 2 after the sexual debut. The prevalence of molluscum has increased since the 1980s. It is stressful for children and caregivers and poses challenges in schools as well as sports such as swimming, wrestling, and karate.1,2
For the first time, we have US Food and Drug Administration (FDA)–approved products to treat MCV infections. Previously, only off-label agents were used. Therefore, we have to contemplate why treatment is important to our patients.
What type of care is required for molluscum?
Counseling is the first and only mandatory treatment, which consists of 3 parts: natural history, risk factors for spread, and options for therapy. The natural history of molluscum in children is early spread, contagion to oneself and others (as high as 60% of sibling co-bathers3), triggering of dermatitis, eventual onset of the beginning-of-the-end (BOTE) sign, and eventually clearance. The natural history in adults is poorly understood.
Early clearance is uncommon; reports have suggested 45.6% to 48.4% of affected patients are clear at 1 year and 69.5% to 72.6% at 1.5 years.4 For many children, especially those with atopic dermatitis (AD), lesions linger and often spread, with many experiencing disease for 3 to 4 years. Fomites such as towels, washcloths, and sponges can transfer the virus and spread lesions; therefore, I advise patients to gently pat their skin dry, wash towels frequently, and avoid sharing bathing equipment.1,3,5 Children and adults with immunosuppression may have a greater number of lesions and more prolonged course of disease, including those with HIV as well as DOC8 and CARD11 mutations.6 The American Academy of Pediatrics (AAP) emphasizes that children should not be excluded from attending child care/school or from swimming in public pools but lesions should be covered.6 Lesions, especially those in the antecubital region, can trigger new-onset AD or AD flares.3 In response, gentle skin care including fragrance-free cleansers and periodic application of moisturizers may ward off AD. Topical corticosteroids are preferred.
Dermatitis in MCV is a great mimicker and can resemble erythema multiforme, Gianotti-Crosti syndrome, impetigo, and AD.1 Superinfection recently has been reported; however, in a retrospective analysis of 56 patients with inflamed lesions secondary to molluscum infection, only 7 had positive bacterial cultures, which supports the idea of the swelling and redness of inflammation as a mimic for infection.7 When true infection does occur, tender, swollen, pus-filled lesions should be lanced and cultured.1,7,8
When should we consider therapy?
Therapy is highly dependent on the child, the caregiver, and the social circumstances.1 More than 80% of parents are anxious about molluscum, and countless children are embarrassed or ashamed.1 Ultimately, an unhappy child merits care. The AAP cites the following as reasons to treat: “(1) alleviate discomfort, including itching; (2) reduce autoinoculation; (3) limit transmission of the virus to close contacts; (4) reduce cosmetic concerns; and (5) prevent secondary infection.”6 For adults, we should consider limitations to intimacy and reduction of sexual transmission risk.6
Treatment can be based on the number of lesions. With a few lesions (<3), therapy is worthwhile if they are unsightly; appear on exposed skin causing embarrassment; and/or are itchy, uncomfortable, or large. In a report of 300 children with molluscum treated with cantharidin, most patients choosing therapy had 10 to 20 lesions, but this was over multiple visits.8 Looking at a 2018 data set of 50 patients (all-comers) with molluscum,3 the mean number of lesions was 10 (median, 7); 3 lesions were 1 SD below, while 14, 17, and 45 were 1, 2, and 3 SDs above, respectively. This data set shows that patients can develop more lesions rapidly, and most children have many visible lesions (N.B. Silverberg, MD, unpublished data).
Because each lesion contains infectious viral particles and patients scratch, more lesions are equated to greater autoinoculation and contagion. In addition to the AAP criteria, treatment can be considered for households with immunocompromised individuals, children at risk for new-onset AD, or those with AD at risk for flare. For patients with 45 lesions or more (3 SDs), clearance is harder to achieve with 2 sessions of in-office therapy, and multiple methods or the addition of immunomodulatory therapeutics should be considered.
Do we have to clear every lesion?
New molluscum lesions may arise until a patient achieves immunity, and they may appear more than a month after inoculation, making it difficult to keep up with the rapid spread. Latency between exposure and lesion development usually is 2 to 7 weeks but may be as long as 6 months, making it difficult to prevent spread.6 Therefore, when we treat, we should not promise full clearance to patients and parents. Rather, we should inform them that new lesions may develop later, and therapy is only effective on visible lesions. In a recent study, a 50% clearance of lesions was the satisfactory threshold for parents, demonstrating that satisfaction is possible with partial clearance.9
What is new in therapeutics for molluscum?
Molluscum therapies are either destructive, immunomodulatory, or antiviral. Two agents now are approved by the FDA for the treatment of molluscum infections.
Berdazimer gel 10.3% is approved for patients 1 year or older, but it is not yet available. This agent has both immunomodulatory and antiviral properties.10 It features a home therapy that is mixed on a small palette, then painted on by the patient or parent once daily for 12 weeks. Study outcomes demonstrated more than 50% lesional clearance.11,12 Complete clearance was achieved in at least 30% of patients.12A proprietary topical version of cantharidin 0.7% in flexible collodion is now FDA approved for patients 2 years and older. This vesicant-triggering iatrogenic is targeted at creating blisters overlying molluscum lesions. It is conceptually similar to older versions but with some enhanced features.5,13,14 This version was used for therapy every 3 weeks for up to 4 sessions in clinical trials. Safety is similar across all body sites treated (nonmucosal and not near the mucosal surfaces) but not for mucosa, the mid face, or eyelids.13 Complete lesion clearance was 46.3% to 54% and statistically greater than placebo (P<.001).14Both agents are well tolerated in children with AD; adverse effects include blistering with cantharidin and dermatitislike symptoms with berdazimer.15,16 These therapies have the advantage of being easy to use.
Final Thoughts
We have entered an era of high-quality molluscum therapy. Patient care involves developing a good knowledge of the agents, incorporating shared decision-making with patients and caregivers, and addressing therapy in the context of comorbid diseases such as AD.
- Silverberg NB. Pediatric molluscum: an update. Cutis. 2019;104:301-305, E1-E2.
- Thompson AJ, Matinpour K, Hardin J, et al. Molluscum gladiatorum. Dermatol Online J. 2014;20:13030/qt0nj121n1.
- Silverberg NB. Molluscum contagiosum virus infection can trigger atopic dermatitis disease onset or flare. Cutis. 2018;102:191-194.
- Basdag H, Rainer BM, Cohen BA. Molluscum contagiosum: to treat or not to treat? experience with 170 children in an outpatient clinic setting in the northeastern United States. Pediatr Dermatol. 2015;32:353-357. doi:10.1111/pde.12504
- Silverberg NB. Warts and molluscum in children. Adv Dermatol. 2004;20:23-73.
- Molluscum contagiosum. In: Kimberlin DW, Lynfield R, Barnett ED, et al (eds). Red Book: 2021–2024 Report of the Committee on Infectious Diseases. 32nd edition. American Academy of Pediatrics. May 26, 2021. Accessed May 20, 2024. https://publications.aap.org/redbook/book/347/chapter/5754264/Molluscum-Contagiosum
- Gross I, Ben Nachum N, Molho-Pessach V, et al. The molluscum contagiosum BOTE sign—infected or inflamed? Pediatr Dermatol. 2020;37:476-479. doi:10.1111/pde.14124
- Silverberg NB, Sidbury R, Mancini AJ. Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients. J Am Acad Dermatol. 2000;43:503-507. doi:10.1067/mjd.2000.106370
- Maeda-Chubachi T, McLeod L, Enloe C, et al. Defining clinically meaningful improvement in molluscum contagiosum. J Am Acad Dermatol. 2024;90:443-445. doi:10.1016/j.jaad.2023.10.033
- Guttman-Yassky E, Gallo RL, Pavel AB, et al. A nitric oxide-releasing topical medication as a potential treatment option for atopic dermatitis through antimicrobial and anti-inflammatory activity. J Invest Dermatol. 2020;140:2531-2535.e2. doi:10.1016/j.jid.2020.04.013
- Browning JC, Cartwright M, Thorla I Jr, et al. A patient-centered perspective of molluscum contagiosum as reported by B-SIMPLE4 Clinical Trial patients and caregivers: Global Impression of Change and Exit Interview substudy results. Am J Clin Dermatol. 2023;24:119-133. doi:10.1007/s40257-022-00733-9
- Sugarman JL, Hebert A, Browning JC, et al. Berdazimer gel for molluscum contagiosum: an integrated analysis of 3 randomized controlled trials. J Am Acad Dermatol. 2024;90:299-308. doi:10.1016/j.jaad.2023.09.066
- Eichenfield LF, Kwong P, Gonzalez ME, et al. Safety and efficacy of VP-102 (cantharidin, 0.7% w/v) in molluscum contagiosum by body region: post hoc pooled analyses from two phase III randomized trials. J Clin Aesthet Dermatol. 2021;14:42-47.
- Eichenfield LF, McFalda W, Brabec B, et al. Safety and efficacy of VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum: two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156:1315-1323. doi:10.1001/jamadermatol.2020.3238
- Paller AS, Green LJ, Silverberg N, et al. Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis. Pediatr Dermatol.Published online February 27, 2024. doi:10.1111/pde.15575
- Eichenfield L, Hebert A, Mancini A, et al. Therapeutic approaches and special considerations for treating molluscum contagiosum. J Drugs Dermatol. 2021;20:1185-1190. doi:10.36849/jdd.6383
Molluscum contagiosum (ie, molluscum) is a ubiquitous infection caused by the poxvirus molluscum contagiosum virus (MCV). Although skin deep, molluscum shares many factors with the more virulent poxviridae. Moisture and trauma can cause viral material to be released from the pearly papules through a small opening, which also allows entry of bacteria and medications into the lesion. The MCV is transmitted by direct contact with skin or via fomites.1
Molluscum can affect children of any age, with MCV type 1 peaking in toddlers and school-aged children and MCV type 2 after the sexual debut. The prevalence of molluscum has increased since the 1980s. It is stressful for children and caregivers and poses challenges in schools as well as sports such as swimming, wrestling, and karate.1,2
For the first time, we have US Food and Drug Administration (FDA)–approved products to treat MCV infections. Previously, only off-label agents were used. Therefore, we have to contemplate why treatment is important to our patients.
What type of care is required for molluscum?
Counseling is the first and only mandatory treatment, which consists of 3 parts: natural history, risk factors for spread, and options for therapy. The natural history of molluscum in children is early spread, contagion to oneself and others (as high as 60% of sibling co-bathers3), triggering of dermatitis, eventual onset of the beginning-of-the-end (BOTE) sign, and eventually clearance. The natural history in adults is poorly understood.
Early clearance is uncommon; reports have suggested 45.6% to 48.4% of affected patients are clear at 1 year and 69.5% to 72.6% at 1.5 years.4 For many children, especially those with atopic dermatitis (AD), lesions linger and often spread, with many experiencing disease for 3 to 4 years. Fomites such as towels, washcloths, and sponges can transfer the virus and spread lesions; therefore, I advise patients to gently pat their skin dry, wash towels frequently, and avoid sharing bathing equipment.1,3,5 Children and adults with immunosuppression may have a greater number of lesions and more prolonged course of disease, including those with HIV as well as DOC8 and CARD11 mutations.6 The American Academy of Pediatrics (AAP) emphasizes that children should not be excluded from attending child care/school or from swimming in public pools but lesions should be covered.6 Lesions, especially those in the antecubital region, can trigger new-onset AD or AD flares.3 In response, gentle skin care including fragrance-free cleansers and periodic application of moisturizers may ward off AD. Topical corticosteroids are preferred.
Dermatitis in MCV is a great mimicker and can resemble erythema multiforme, Gianotti-Crosti syndrome, impetigo, and AD.1 Superinfection recently has been reported; however, in a retrospective analysis of 56 patients with inflamed lesions secondary to molluscum infection, only 7 had positive bacterial cultures, which supports the idea of the swelling and redness of inflammation as a mimic for infection.7 When true infection does occur, tender, swollen, pus-filled lesions should be lanced and cultured.1,7,8
When should we consider therapy?
Therapy is highly dependent on the child, the caregiver, and the social circumstances.1 More than 80% of parents are anxious about molluscum, and countless children are embarrassed or ashamed.1 Ultimately, an unhappy child merits care. The AAP cites the following as reasons to treat: “(1) alleviate discomfort, including itching; (2) reduce autoinoculation; (3) limit transmission of the virus to close contacts; (4) reduce cosmetic concerns; and (5) prevent secondary infection.”6 For adults, we should consider limitations to intimacy and reduction of sexual transmission risk.6
Treatment can be based on the number of lesions. With a few lesions (<3), therapy is worthwhile if they are unsightly; appear on exposed skin causing embarrassment; and/or are itchy, uncomfortable, or large. In a report of 300 children with molluscum treated with cantharidin, most patients choosing therapy had 10 to 20 lesions, but this was over multiple visits.8 Looking at a 2018 data set of 50 patients (all-comers) with molluscum,3 the mean number of lesions was 10 (median, 7); 3 lesions were 1 SD below, while 14, 17, and 45 were 1, 2, and 3 SDs above, respectively. This data set shows that patients can develop more lesions rapidly, and most children have many visible lesions (N.B. Silverberg, MD, unpublished data).
Because each lesion contains infectious viral particles and patients scratch, more lesions are equated to greater autoinoculation and contagion. In addition to the AAP criteria, treatment can be considered for households with immunocompromised individuals, children at risk for new-onset AD, or those with AD at risk for flare. For patients with 45 lesions or more (3 SDs), clearance is harder to achieve with 2 sessions of in-office therapy, and multiple methods or the addition of immunomodulatory therapeutics should be considered.
Do we have to clear every lesion?
New molluscum lesions may arise until a patient achieves immunity, and they may appear more than a month after inoculation, making it difficult to keep up with the rapid spread. Latency between exposure and lesion development usually is 2 to 7 weeks but may be as long as 6 months, making it difficult to prevent spread.6 Therefore, when we treat, we should not promise full clearance to patients and parents. Rather, we should inform them that new lesions may develop later, and therapy is only effective on visible lesions. In a recent study, a 50% clearance of lesions was the satisfactory threshold for parents, demonstrating that satisfaction is possible with partial clearance.9
What is new in therapeutics for molluscum?
Molluscum therapies are either destructive, immunomodulatory, or antiviral. Two agents now are approved by the FDA for the treatment of molluscum infections.
Berdazimer gel 10.3% is approved for patients 1 year or older, but it is not yet available. This agent has both immunomodulatory and antiviral properties.10 It features a home therapy that is mixed on a small palette, then painted on by the patient or parent once daily for 12 weeks. Study outcomes demonstrated more than 50% lesional clearance.11,12 Complete clearance was achieved in at least 30% of patients.12A proprietary topical version of cantharidin 0.7% in flexible collodion is now FDA approved for patients 2 years and older. This vesicant-triggering iatrogenic is targeted at creating blisters overlying molluscum lesions. It is conceptually similar to older versions but with some enhanced features.5,13,14 This version was used for therapy every 3 weeks for up to 4 sessions in clinical trials. Safety is similar across all body sites treated (nonmucosal and not near the mucosal surfaces) but not for mucosa, the mid face, or eyelids.13 Complete lesion clearance was 46.3% to 54% and statistically greater than placebo (P<.001).14Both agents are well tolerated in children with AD; adverse effects include blistering with cantharidin and dermatitislike symptoms with berdazimer.15,16 These therapies have the advantage of being easy to use.
Final Thoughts
We have entered an era of high-quality molluscum therapy. Patient care involves developing a good knowledge of the agents, incorporating shared decision-making with patients and caregivers, and addressing therapy in the context of comorbid diseases such as AD.
Molluscum contagiosum (ie, molluscum) is a ubiquitous infection caused by the poxvirus molluscum contagiosum virus (MCV). Although skin deep, molluscum shares many factors with the more virulent poxviridae. Moisture and trauma can cause viral material to be released from the pearly papules through a small opening, which also allows entry of bacteria and medications into the lesion. The MCV is transmitted by direct contact with skin or via fomites.1
Molluscum can affect children of any age, with MCV type 1 peaking in toddlers and school-aged children and MCV type 2 after the sexual debut. The prevalence of molluscum has increased since the 1980s. It is stressful for children and caregivers and poses challenges in schools as well as sports such as swimming, wrestling, and karate.1,2
For the first time, we have US Food and Drug Administration (FDA)–approved products to treat MCV infections. Previously, only off-label agents were used. Therefore, we have to contemplate why treatment is important to our patients.
What type of care is required for molluscum?
Counseling is the first and only mandatory treatment, which consists of 3 parts: natural history, risk factors for spread, and options for therapy. The natural history of molluscum in children is early spread, contagion to oneself and others (as high as 60% of sibling co-bathers3), triggering of dermatitis, eventual onset of the beginning-of-the-end (BOTE) sign, and eventually clearance. The natural history in adults is poorly understood.
Early clearance is uncommon; reports have suggested 45.6% to 48.4% of affected patients are clear at 1 year and 69.5% to 72.6% at 1.5 years.4 For many children, especially those with atopic dermatitis (AD), lesions linger and often spread, with many experiencing disease for 3 to 4 years. Fomites such as towels, washcloths, and sponges can transfer the virus and spread lesions; therefore, I advise patients to gently pat their skin dry, wash towels frequently, and avoid sharing bathing equipment.1,3,5 Children and adults with immunosuppression may have a greater number of lesions and more prolonged course of disease, including those with HIV as well as DOC8 and CARD11 mutations.6 The American Academy of Pediatrics (AAP) emphasizes that children should not be excluded from attending child care/school or from swimming in public pools but lesions should be covered.6 Lesions, especially those in the antecubital region, can trigger new-onset AD or AD flares.3 In response, gentle skin care including fragrance-free cleansers and periodic application of moisturizers may ward off AD. Topical corticosteroids are preferred.
Dermatitis in MCV is a great mimicker and can resemble erythema multiforme, Gianotti-Crosti syndrome, impetigo, and AD.1 Superinfection recently has been reported; however, in a retrospective analysis of 56 patients with inflamed lesions secondary to molluscum infection, only 7 had positive bacterial cultures, which supports the idea of the swelling and redness of inflammation as a mimic for infection.7 When true infection does occur, tender, swollen, pus-filled lesions should be lanced and cultured.1,7,8
When should we consider therapy?
Therapy is highly dependent on the child, the caregiver, and the social circumstances.1 More than 80% of parents are anxious about molluscum, and countless children are embarrassed or ashamed.1 Ultimately, an unhappy child merits care. The AAP cites the following as reasons to treat: “(1) alleviate discomfort, including itching; (2) reduce autoinoculation; (3) limit transmission of the virus to close contacts; (4) reduce cosmetic concerns; and (5) prevent secondary infection.”6 For adults, we should consider limitations to intimacy and reduction of sexual transmission risk.6
Treatment can be based on the number of lesions. With a few lesions (<3), therapy is worthwhile if they are unsightly; appear on exposed skin causing embarrassment; and/or are itchy, uncomfortable, or large. In a report of 300 children with molluscum treated with cantharidin, most patients choosing therapy had 10 to 20 lesions, but this was over multiple visits.8 Looking at a 2018 data set of 50 patients (all-comers) with molluscum,3 the mean number of lesions was 10 (median, 7); 3 lesions were 1 SD below, while 14, 17, and 45 were 1, 2, and 3 SDs above, respectively. This data set shows that patients can develop more lesions rapidly, and most children have many visible lesions (N.B. Silverberg, MD, unpublished data).
Because each lesion contains infectious viral particles and patients scratch, more lesions are equated to greater autoinoculation and contagion. In addition to the AAP criteria, treatment can be considered for households with immunocompromised individuals, children at risk for new-onset AD, or those with AD at risk for flare. For patients with 45 lesions or more (3 SDs), clearance is harder to achieve with 2 sessions of in-office therapy, and multiple methods or the addition of immunomodulatory therapeutics should be considered.
Do we have to clear every lesion?
New molluscum lesions may arise until a patient achieves immunity, and they may appear more than a month after inoculation, making it difficult to keep up with the rapid spread. Latency between exposure and lesion development usually is 2 to 7 weeks but may be as long as 6 months, making it difficult to prevent spread.6 Therefore, when we treat, we should not promise full clearance to patients and parents. Rather, we should inform them that new lesions may develop later, and therapy is only effective on visible lesions. In a recent study, a 50% clearance of lesions was the satisfactory threshold for parents, demonstrating that satisfaction is possible with partial clearance.9
What is new in therapeutics for molluscum?
Molluscum therapies are either destructive, immunomodulatory, or antiviral. Two agents now are approved by the FDA for the treatment of molluscum infections.
Berdazimer gel 10.3% is approved for patients 1 year or older, but it is not yet available. This agent has both immunomodulatory and antiviral properties.10 It features a home therapy that is mixed on a small palette, then painted on by the patient or parent once daily for 12 weeks. Study outcomes demonstrated more than 50% lesional clearance.11,12 Complete clearance was achieved in at least 30% of patients.12A proprietary topical version of cantharidin 0.7% in flexible collodion is now FDA approved for patients 2 years and older. This vesicant-triggering iatrogenic is targeted at creating blisters overlying molluscum lesions. It is conceptually similar to older versions but with some enhanced features.5,13,14 This version was used for therapy every 3 weeks for up to 4 sessions in clinical trials. Safety is similar across all body sites treated (nonmucosal and not near the mucosal surfaces) but not for mucosa, the mid face, or eyelids.13 Complete lesion clearance was 46.3% to 54% and statistically greater than placebo (P<.001).14Both agents are well tolerated in children with AD; adverse effects include blistering with cantharidin and dermatitislike symptoms with berdazimer.15,16 These therapies have the advantage of being easy to use.
Final Thoughts
We have entered an era of high-quality molluscum therapy. Patient care involves developing a good knowledge of the agents, incorporating shared decision-making with patients and caregivers, and addressing therapy in the context of comorbid diseases such as AD.
- Silverberg NB. Pediatric molluscum: an update. Cutis. 2019;104:301-305, E1-E2.
- Thompson AJ, Matinpour K, Hardin J, et al. Molluscum gladiatorum. Dermatol Online J. 2014;20:13030/qt0nj121n1.
- Silverberg NB. Molluscum contagiosum virus infection can trigger atopic dermatitis disease onset or flare. Cutis. 2018;102:191-194.
- Basdag H, Rainer BM, Cohen BA. Molluscum contagiosum: to treat or not to treat? experience with 170 children in an outpatient clinic setting in the northeastern United States. Pediatr Dermatol. 2015;32:353-357. doi:10.1111/pde.12504
- Silverberg NB. Warts and molluscum in children. Adv Dermatol. 2004;20:23-73.
- Molluscum contagiosum. In: Kimberlin DW, Lynfield R, Barnett ED, et al (eds). Red Book: 2021–2024 Report of the Committee on Infectious Diseases. 32nd edition. American Academy of Pediatrics. May 26, 2021. Accessed May 20, 2024. https://publications.aap.org/redbook/book/347/chapter/5754264/Molluscum-Contagiosum
- Gross I, Ben Nachum N, Molho-Pessach V, et al. The molluscum contagiosum BOTE sign—infected or inflamed? Pediatr Dermatol. 2020;37:476-479. doi:10.1111/pde.14124
- Silverberg NB, Sidbury R, Mancini AJ. Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients. J Am Acad Dermatol. 2000;43:503-507. doi:10.1067/mjd.2000.106370
- Maeda-Chubachi T, McLeod L, Enloe C, et al. Defining clinically meaningful improvement in molluscum contagiosum. J Am Acad Dermatol. 2024;90:443-445. doi:10.1016/j.jaad.2023.10.033
- Guttman-Yassky E, Gallo RL, Pavel AB, et al. A nitric oxide-releasing topical medication as a potential treatment option for atopic dermatitis through antimicrobial and anti-inflammatory activity. J Invest Dermatol. 2020;140:2531-2535.e2. doi:10.1016/j.jid.2020.04.013
- Browning JC, Cartwright M, Thorla I Jr, et al. A patient-centered perspective of molluscum contagiosum as reported by B-SIMPLE4 Clinical Trial patients and caregivers: Global Impression of Change and Exit Interview substudy results. Am J Clin Dermatol. 2023;24:119-133. doi:10.1007/s40257-022-00733-9
- Sugarman JL, Hebert A, Browning JC, et al. Berdazimer gel for molluscum contagiosum: an integrated analysis of 3 randomized controlled trials. J Am Acad Dermatol. 2024;90:299-308. doi:10.1016/j.jaad.2023.09.066
- Eichenfield LF, Kwong P, Gonzalez ME, et al. Safety and efficacy of VP-102 (cantharidin, 0.7% w/v) in molluscum contagiosum by body region: post hoc pooled analyses from two phase III randomized trials. J Clin Aesthet Dermatol. 2021;14:42-47.
- Eichenfield LF, McFalda W, Brabec B, et al. Safety and efficacy of VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum: two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156:1315-1323. doi:10.1001/jamadermatol.2020.3238
- Paller AS, Green LJ, Silverberg N, et al. Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis. Pediatr Dermatol.Published online February 27, 2024. doi:10.1111/pde.15575
- Eichenfield L, Hebert A, Mancini A, et al. Therapeutic approaches and special considerations for treating molluscum contagiosum. J Drugs Dermatol. 2021;20:1185-1190. doi:10.36849/jdd.6383
- Silverberg NB. Pediatric molluscum: an update. Cutis. 2019;104:301-305, E1-E2.
- Thompson AJ, Matinpour K, Hardin J, et al. Molluscum gladiatorum. Dermatol Online J. 2014;20:13030/qt0nj121n1.
- Silverberg NB. Molluscum contagiosum virus infection can trigger atopic dermatitis disease onset or flare. Cutis. 2018;102:191-194.
- Basdag H, Rainer BM, Cohen BA. Molluscum contagiosum: to treat or not to treat? experience with 170 children in an outpatient clinic setting in the northeastern United States. Pediatr Dermatol. 2015;32:353-357. doi:10.1111/pde.12504
- Silverberg NB. Warts and molluscum in children. Adv Dermatol. 2004;20:23-73.
- Molluscum contagiosum. In: Kimberlin DW, Lynfield R, Barnett ED, et al (eds). Red Book: 2021–2024 Report of the Committee on Infectious Diseases. 32nd edition. American Academy of Pediatrics. May 26, 2021. Accessed May 20, 2024. https://publications.aap.org/redbook/book/347/chapter/5754264/Molluscum-Contagiosum
- Gross I, Ben Nachum N, Molho-Pessach V, et al. The molluscum contagiosum BOTE sign—infected or inflamed? Pediatr Dermatol. 2020;37:476-479. doi:10.1111/pde.14124
- Silverberg NB, Sidbury R, Mancini AJ. Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients. J Am Acad Dermatol. 2000;43:503-507. doi:10.1067/mjd.2000.106370
- Maeda-Chubachi T, McLeod L, Enloe C, et al. Defining clinically meaningful improvement in molluscum contagiosum. J Am Acad Dermatol. 2024;90:443-445. doi:10.1016/j.jaad.2023.10.033
- Guttman-Yassky E, Gallo RL, Pavel AB, et al. A nitric oxide-releasing topical medication as a potential treatment option for atopic dermatitis through antimicrobial and anti-inflammatory activity. J Invest Dermatol. 2020;140:2531-2535.e2. doi:10.1016/j.jid.2020.04.013
- Browning JC, Cartwright M, Thorla I Jr, et al. A patient-centered perspective of molluscum contagiosum as reported by B-SIMPLE4 Clinical Trial patients and caregivers: Global Impression of Change and Exit Interview substudy results. Am J Clin Dermatol. 2023;24:119-133. doi:10.1007/s40257-022-00733-9
- Sugarman JL, Hebert A, Browning JC, et al. Berdazimer gel for molluscum contagiosum: an integrated analysis of 3 randomized controlled trials. J Am Acad Dermatol. 2024;90:299-308. doi:10.1016/j.jaad.2023.09.066
- Eichenfield LF, Kwong P, Gonzalez ME, et al. Safety and efficacy of VP-102 (cantharidin, 0.7% w/v) in molluscum contagiosum by body region: post hoc pooled analyses from two phase III randomized trials. J Clin Aesthet Dermatol. 2021;14:42-47.
- Eichenfield LF, McFalda W, Brabec B, et al. Safety and efficacy of VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum: two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156:1315-1323. doi:10.1001/jamadermatol.2020.3238
- Paller AS, Green LJ, Silverberg N, et al. Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis. Pediatr Dermatol.Published online February 27, 2024. doi:10.1111/pde.15575
- Eichenfield L, Hebert A, Mancini A, et al. Therapeutic approaches and special considerations for treating molluscum contagiosum. J Drugs Dermatol. 2021;20:1185-1190. doi:10.36849/jdd.6383