ORLANDO, FLORIDA — Asthma is the most common cause of chronic cough in children, but it’s important to be aware of other differential diagnoses for those patients who have less common concerns, according to Rajeev Bhatia, MD, division chief of pulmonology at Phoenix Children’s in Phoenix, Arizona. Bhatia reviewed both the major causes of chronic cough as well as the rare zebras to watch out for in a presentation at the American Academy of Pediatrics (AAP) 2024 National Conference.

“When you see a patient for cough, the most important thing is, history, history, history,” Bhatia said. “There are many, many, many clues in the history, age of onset, and duration.” That includes starting at birth to ensure you don’t miss key details such as a preterm birth. It’s also important to discuss what the cough sounds like, how frequent it is, what makes it better, what makes it worse, and how it’s affecting the child and others around them — all of which can help narrow the diagnosis.

Jose Quijada, DO, a pediatrician with CommuniCare Pediatrics in San Antonio, found the session “incredibly useful” not only because of the specific pointers about each condition but also because of the realistic case studies he included throughout.

“Sometimes when you’re practicing, you focus on what’s most common,” Quijada said, so it was helpful to get a review of some of the key features and red flags that point to less common causes that may need to be considered. He particularly appreciated the discussion of habitual cough and potential treatments because those can be challenging patients and it can be tough to find a middle ground with how much workup to do.
 

Common Causes of Chronic Cough

The coughing from inadequately controlled asthma tends to be nonproductive and worse at night or in the early morning, Bhatia explained, and it’s often accompanied by wheezing, shortness of breath, and chest tightness. While fractional exhaled nitric oxide can be useful, “studies show that it is more useful for to monitor the symptoms rather than to diagnose the asthma,” Bhatia told attendees, but he also added that spirometry can be normal in patients with asthma. In young patients, the Asthma Predictive Index can be an invaluable tool, he also said.

Another common cause of chronic cough is a postinfectious cough, which lasts more than 3 weeks after resolution of acute upper respiratory infection. It occurs in about one in 10 children after a viral infection such as a rhinovirus or respiratory syncytial virus infection and results from extensive inflammation and disruption of the airway epithelial integrity. Chest x-rays are usually normal in these patients, and the cough will usually resolve on its own. Albuterol has not been shown to be any more effective than placebo for a postinfectious cough, and antibiotics similarly have no clinically useful role.

A wet cough that lasts for at least 4 weeks and appears to have no other specific cause may be protracted bacterial bronchitis (PBB). While the cause of PBB isn’t known, it could be due to frequent illnesses that cause airway inflammation and injury over time, thereby making it easier for bacteria to grow and cause infection. Risk factors include tracheomalacia/bronchomalacia and childcare attendance, and typical pathogens include Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis.

While an x-ray can be done, radiography is often normal in patients with PBB. Bronchoscopy will reveal purulent secretions. PBB should resolve with at least 2 weeks of antibiotics, including amoxicillin-clavulanate, but the course can be extended to 4 weeks if the cough persists. However, about 40% of patients will have recurrence, and those with recurrent PBB or with a chronic cough unresponsive to 4 weeks of antibiotics should be referred to a pediatric pulmonologist.

Upper airway cough syndrome is the updated name for postnasal drip, which can occur with both allergic and nonallergic rhinitis and chronic rhinosinusitis. This is often a dry, throat-clearing cough that can be accompanied by headaches, nasal congestion, and sinus or facial tenderness. An examination will reveal posterior pharynx cobblestoning, Bhatia said, and empirical use of intranasal steroids can be both diagnostic and therapeutic for upper airway cough syndrome. He also emphasized the importance of taking an environmental history and avoiding exposure of environmental triggers.
 

Uncommon Pulmonary Causes of Chronic Cough

After discussing frequent reasons patients may present with a chronic cough, Bhatia went on to discuss the less common things to consider if the provider has eliminated the other possibilities. These include both pulmonary causes as well as congenital malformations, gastrointestinal causes, and habit cough.

A child who presents with a sudden onset of cough or wheeze in the absence of an upper respiratory infection may have a retained foreign body. This cough can be mistaken for bronchiolitis, asthma, croup, and other infectious conditions, especially because a partial obstruction can make diagnosis confusing or challenging. Adding to the challenge is that most foreign bodies will be radiolucent. A decubitus chest x-ray could be useful, but bronchoscopy is necessary for diagnosis. Bhatia stressed that it’s easy to miss a foreign body in younger children and that the wheezing can be more prominent on one side or another.

Cystic fibrosis, another uncommon cause of chronic cough, is ideally diagnosed via newborn screening, but screening is imperfect and can involve missed diagnoses or false negatives. Over 75% of cystic fibrosis cases are diagnosed by age 2, but that means a substantial number of cases still are not diagnosed until older childhood or later. This cough will be a chronic productive/wet cough.

A family history of cystic fibrosis may be present but doesn’t have to be, so signs to look for include poor weight gain, sinusitis, nasal polyps, clubbing, and isolation of suspicious organisms from a respiratory culture, such as Pseudomonas aeruginosa or Burkholderia cepacia complex. Clubbing in the fingers is a particularly telltale symptom of undiagnosed cystic fibrosis, and bronchiectasis of unknown etiology will be present. Suspicion of cystic fibrosis should lead to a referral to a cystic fibrosis center for a sweat test.

Even rarer than cystic fibrosis is primary ciliary dyskinesia (PCD), an inherited autosomal recessive disease that occurs in about one in 20,000 live births and involves a structural or functional defect in the cilia. About half of all patients with PCD will have situs inversus — an arrangement of chest and abdominal organs that is a mirror image of typical human anatomical presentation — but most people with situs inversus do not have PCD. One type of PCD is Kartagener syndrome, identified by the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis.

Children with PCD present with a chronic productive cough and recurrent pneumonias, and nearly all patients will have rhinosinusitis. About 60% of patients will develop respiratory symptoms such as mild distress or cough in their first month, and recurrent otitis media is common in these patients. PCD diagnosis is based on a combination of genetic testing, nasal nitric oxide, and evaluation of ciliary motion and structure. Clinical suspicion of PCD should lead to a specialist referral.

Nearly all people with PCD will eventually develop bronchiectasis, where the priority should be airway clearance using antibiotics for acute exacerbations and chronic azithromycin therapy for recurrent exacerbations. Patients with chronic rhinosinusitis, chronic otitis media, and nasal polyposis should be referred to an ENT specialist.
 

Other Uncommon Causes of Chronic Cough

A non-pulmonary, uncommon cause of chronic cough is a vascular ring, a congenital anomaly in which blood vessels encircle and potentially constrict the esophagus and/or trachea. The most common type is a double aortic arch, but a right aortic arch or pulmonary artery sling is also possible. These coughs sound harsh and are usually accompanied by stridor, dyspnea and feeding problems. Workup includes an echocardiogram, a CT angiogram, and possibly a bronchoscopy to determine the extent of the airway narrowing. In symptomatic patients, surgery is indicated for correction.

Another congenital malformation that can cause chronic cough is a tracheoesophageal fistula, which occurs in about one in 3500 live births, commonly linked to trisomy disorders and VACTERL. Several types of tracheoesophageal fistula exist, and H-type fistula is associated with late onset symptoms. The cough can be wet or dry and sometimes sounds like barking because of the associated airway collapse. Patients often have recurrent pneumonia, bronchitis, and cough or cyanosis with feeding. Workup should include an upper gastrointestinal series but not with barium, Bhatia said, because that can cause pneumonitis. Instead, the series should be done with a thickened water-soluble contrast material, and a bronchoscopy may be indicated as well.

Though common as a condition in adults, gastroesophageal reflux disease (GERD) is a rare, but possible, cause of chronic cough in children. More often, the reflux is the result of the cough rather than the cause. The most sensitive tool for assessing GERD is esophageal 24-hour pH/impedance reflux monitoring. However, treatment of the reflux for cough is not recommended unless the patient has clinical features of GERD, including dystonic neck posturing in infants, heartburn, regurgitation, or other symptoms. If the patient has clinical symptoms, then treatment is acid suppressive therapy for 4-8 weeks, followed by a clinical reassessment.

An uncommon cause of chronic cough with no biological mechanism is habit cough. Habit cough is most easily distinguished from other coughs by its sounds, a “large, loud, honking noise,” Bhatia said. It also lacks a clear trigger and is usually absent during sleep, but it can be continuous during the day. Frustratingly, the patients themselves often don’t seem bothered by the cough, but “it’s very disruptive in the school and everywhere else,” Bhatia said. Families and/providers will often have tried multiple treatments and seen no improvement with habit cough.

The first thing to do with habit cough is reassure the family that there’s nothing serious going on because they are often worried by this point. Several non-pharmaceutical treatments can be effective, such as suggestion therapy or the “warm water technique,” in which the patient takes a sip of warm water every time they feel the urge to cough. “If they’re able to break the cycle, most of the time, they are fine,” Bhatia said. In rarer cases, more involved behavioral interventions may be indicated, such as a psychology referral if an underlying anxiety or other behavioral disorder is contributing.
 

Newer Causes of Cough

Two more recent causes of cough to watch for are long COVID and e-cigarette or vaping product–associated lung injury (EVALI), Bhatia said. The clearest sign of EVALI is a history of e-cigarette/vaping exposure, but clinical symptoms include a dry cough that occurs with dyspnea and chest pain. A chest x-ray may show diffuse, hazy, or consolidative opacities. Sometimes antibiotics or steroids can be helpful, but the evidence isn’t strong, and the most effective treatment is stopping e-cigarette use. Less commonly, passive exposure to vaping can also be associated with EVALI.

The most recent research on long COVID suggests that about 10-20% of children with acute COVID develop long COVID, and about a quarter of these patients develop a chronic dry cough. It’s often associated with fatigue and shortness of breath, which can be assessed with cardiopulmonary exercise testing. Sometimes a short trial of inhaled steroids can help.

Bhatia also mentioned a handful of other uncommon causes of chronic cough that most American pediatricians are unlikely to see: Childhood interstitial lung disease, tuberculosis, use of Angiotensin-Converting Enzyme inhibitors, and a build-up of ear wax via the Arnold’s nerve reflex.
 

Evaluation and Workup

Bhatia also discussed what to cover while taking a history and questions to ask. The history should include the type of cough, the onset timing (sudden vs gradual), associated symptoms, the cough trajectory, medications the patient is taking, and the patient’s past medical history and environmental exposures. Those attributes are included in this more comprehensive list of questions to consider during evaluation, adapted from a list provided in a 2019 article in Paediatric Respiratory Reviews:

• Age of onset and duration?
• Was the onset sudden or associate with an illness?
• Is the cough wet or dry?
• What does the cough sound like?
• How often does the cough occur?
• Is it progressive?
• Is it present during sleep?
• Are there any other associated symptoms, such as wheeze, dyspnea, vomiting, chest pain, etc?
• Are there any exacerbating factors or known triggers?
• Are there any relieving factors, including a trial of bronchodilators?
• Has there been exposure to auto-irritants, such as secondhand smoke?
• What is the cough’s effect on the child and on others around the child?
• Does the child have any other underlying conditions such as neuromuscular disease or asthma?
• What medications is the child taking or has recently taken?
• Is there a family history of atopy and/or respiratory disease?

Bhatia also recommended paying special attention to the following red flags or key features that may help more quickly narrow the diagnosis and often require a specialist referral:

• Digital clubbing, failure to thrive, or low tone
• An abnormal cardiac exam
• Tachypnea, hypoxemia, chest retractions, or hemoptysis
• Abnormal breath sounds such as unilateral wheezing or coarse crackles
• Abnormal spirometry in those aged 5 and older showing reversible obstruction, which often indicates asthma
• An abnormal chest x-ray with, for example, bilateral infiltrates, hyperinflation, right middle lobe syndrome, situs inversus, unilateral hyperlucency, a right aortic arch, etc.

No external funding was used for the presentation. Bhatia and Quijada had no disclosures.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Asthma is the most common cause of chronic cough in children, but it’s important to be aware of other differential diagnoses for those patients who have less common concerns, according to Rajeev Bhatia, MD, division chief of pulmonology at Phoenix Children’s in Phoenix, Arizona. Bhatia reviewed both the major causes of chronic cough as well as the rare zebras to watch out for in a presentation at the American Academy of Pediatrics (AAP) 2024 National Conference.

“When you see a patient for cough, the most important thing is, history, history, history,” Bhatia said. “There are many, many, many clues in the history, age of onset, and duration.” That includes starting at birth to ensure you don’t miss key details such as a preterm birth. It’s also important to discuss what the cough sounds like, how frequent it is, what makes it better, what makes it worse, and how it’s affecting the child and others around them — all of which can help narrow the diagnosis.

Jose Quijada, DO, a pediatrician with CommuniCare Pediatrics in San Antonio, found the session “incredibly useful” not only because of the specific pointers about each condition but also because of the realistic case studies he included throughout.

“Sometimes when you’re practicing, you focus on what’s most common,” Quijada said, so it was helpful to get a review of some of the key features and red flags that point to less common causes that may need to be considered. He particularly appreciated the discussion of habitual cough and potential treatments because those can be challenging patients and it can be tough to find a middle ground with how much workup to do.
 

Common Causes of Chronic Cough

The coughing from inadequately controlled asthma tends to be nonproductive and worse at night or in the early morning, Bhatia explained, and it’s often accompanied by wheezing, shortness of breath, and chest tightness. While fractional exhaled nitric oxide can be useful, “studies show that it is more useful for to monitor the symptoms rather than to diagnose the asthma,” Bhatia told attendees, but he also added that spirometry can be normal in patients with asthma. In young patients, the Asthma Predictive Index can be an invaluable tool, he also said.

Another common cause of chronic cough is a postinfectious cough, which lasts more than 3 weeks after resolution of acute upper respiratory infection. It occurs in about one in 10 children after a viral infection such as a rhinovirus or respiratory syncytial virus infection and results from extensive inflammation and disruption of the airway epithelial integrity. Chest x-rays are usually normal in these patients, and the cough will usually resolve on its own. Albuterol has not been shown to be any more effective than placebo for a postinfectious cough, and antibiotics similarly have no clinically useful role.

A wet cough that lasts for at least 4 weeks and appears to have no other specific cause may be protracted bacterial bronchitis (PBB). While the cause of PBB isn’t known, it could be due to frequent illnesses that cause airway inflammation and injury over time, thereby making it easier for bacteria to grow and cause infection. Risk factors include tracheomalacia/bronchomalacia and childcare attendance, and typical pathogens include Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis.

While an x-ray can be done, radiography is often normal in patients with PBB. Bronchoscopy will reveal purulent secretions. PBB should resolve with at least 2 weeks of antibiotics, including amoxicillin-clavulanate, but the course can be extended to 4 weeks if the cough persists. However, about 40% of patients will have recurrence, and those with recurrent PBB or with a chronic cough unresponsive to 4 weeks of antibiotics should be referred to a pediatric pulmonologist.

Upper airway cough syndrome is the updated name for postnasal drip, which can occur with both allergic and nonallergic rhinitis and chronic rhinosinusitis. This is often a dry, throat-clearing cough that can be accompanied by headaches, nasal congestion, and sinus or facial tenderness. An examination will reveal posterior pharynx cobblestoning, Bhatia said, and empirical use of intranasal steroids can be both diagnostic and therapeutic for upper airway cough syndrome. He also emphasized the importance of taking an environmental history and avoiding exposure of environmental triggers.
 

Uncommon Pulmonary Causes of Chronic Cough

After discussing frequent reasons patients may present with a chronic cough, Bhatia went on to discuss the less common things to consider if the provider has eliminated the other possibilities. These include both pulmonary causes as well as congenital malformations, gastrointestinal causes, and habit cough.

A child who presents with a sudden onset of cough or wheeze in the absence of an upper respiratory infection may have a retained foreign body. This cough can be mistaken for bronchiolitis, asthma, croup, and other infectious conditions, especially because a partial obstruction can make diagnosis confusing or challenging. Adding to the challenge is that most foreign bodies will be radiolucent. A decubitus chest x-ray could be useful, but bronchoscopy is necessary for diagnosis. Bhatia stressed that it’s easy to miss a foreign body in younger children and that the wheezing can be more prominent on one side or another.

Cystic fibrosis, another uncommon cause of chronic cough, is ideally diagnosed via newborn screening, but screening is imperfect and can involve missed diagnoses or false negatives. Over 75% of cystic fibrosis cases are diagnosed by age 2, but that means a substantial number of cases still are not diagnosed until older childhood or later. This cough will be a chronic productive/wet cough.

A family history of cystic fibrosis may be present but doesn’t have to be, so signs to look for include poor weight gain, sinusitis, nasal polyps, clubbing, and isolation of suspicious organisms from a respiratory culture, such as Pseudomonas aeruginosa or Burkholderia cepacia complex. Clubbing in the fingers is a particularly telltale symptom of undiagnosed cystic fibrosis, and bronchiectasis of unknown etiology will be present. Suspicion of cystic fibrosis should lead to a referral to a cystic fibrosis center for a sweat test.

Even rarer than cystic fibrosis is primary ciliary dyskinesia (PCD), an inherited autosomal recessive disease that occurs in about one in 20,000 live births and involves a structural or functional defect in the cilia. About half of all patients with PCD will have situs inversus — an arrangement of chest and abdominal organs that is a mirror image of typical human anatomical presentation — but most people with situs inversus do not have PCD. One type of PCD is Kartagener syndrome, identified by the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis.

Children with PCD present with a chronic productive cough and recurrent pneumonias, and nearly all patients will have rhinosinusitis. About 60% of patients will develop respiratory symptoms such as mild distress or cough in their first month, and recurrent otitis media is common in these patients. PCD diagnosis is based on a combination of genetic testing, nasal nitric oxide, and evaluation of ciliary motion and structure. Clinical suspicion of PCD should lead to a specialist referral.

Nearly all people with PCD will eventually develop bronchiectasis, where the priority should be airway clearance using antibiotics for acute exacerbations and chronic azithromycin therapy for recurrent exacerbations. Patients with chronic rhinosinusitis, chronic otitis media, and nasal polyposis should be referred to an ENT specialist.
 

Other Uncommon Causes of Chronic Cough

A non-pulmonary, uncommon cause of chronic cough is a vascular ring, a congenital anomaly in which blood vessels encircle and potentially constrict the esophagus and/or trachea. The most common type is a double aortic arch, but a right aortic arch or pulmonary artery sling is also possible. These coughs sound harsh and are usually accompanied by stridor, dyspnea and feeding problems. Workup includes an echocardiogram, a CT angiogram, and possibly a bronchoscopy to determine the extent of the airway narrowing. In symptomatic patients, surgery is indicated for correction.

Another congenital malformation that can cause chronic cough is a tracheoesophageal fistula, which occurs in about one in 3500 live births, commonly linked to trisomy disorders and VACTERL. Several types of tracheoesophageal fistula exist, and H-type fistula is associated with late onset symptoms. The cough can be wet or dry and sometimes sounds like barking because of the associated airway collapse. Patients often have recurrent pneumonia, bronchitis, and cough or cyanosis with feeding. Workup should include an upper gastrointestinal series but not with barium, Bhatia said, because that can cause pneumonitis. Instead, the series should be done with a thickened water-soluble contrast material, and a bronchoscopy may be indicated as well.

Though common as a condition in adults, gastroesophageal reflux disease (GERD) is a rare, but possible, cause of chronic cough in children. More often, the reflux is the result of the cough rather than the cause. The most sensitive tool for assessing GERD is esophageal 24-hour pH/impedance reflux monitoring. However, treatment of the reflux for cough is not recommended unless the patient has clinical features of GERD, including dystonic neck posturing in infants, heartburn, regurgitation, or other symptoms. If the patient has clinical symptoms, then treatment is acid suppressive therapy for 4-8 weeks, followed by a clinical reassessment.

An uncommon cause of chronic cough with no biological mechanism is habit cough. Habit cough is most easily distinguished from other coughs by its sounds, a “large, loud, honking noise,” Bhatia said. It also lacks a clear trigger and is usually absent during sleep, but it can be continuous during the day. Frustratingly, the patients themselves often don’t seem bothered by the cough, but “it’s very disruptive in the school and everywhere else,” Bhatia said. Families and/providers will often have tried multiple treatments and seen no improvement with habit cough.

The first thing to do with habit cough is reassure the family that there’s nothing serious going on because they are often worried by this point. Several non-pharmaceutical treatments can be effective, such as suggestion therapy or the “warm water technique,” in which the patient takes a sip of warm water every time they feel the urge to cough. “If they’re able to break the cycle, most of the time, they are fine,” Bhatia said. In rarer cases, more involved behavioral interventions may be indicated, such as a psychology referral if an underlying anxiety or other behavioral disorder is contributing.
 

Newer Causes of Cough

Two more recent causes of cough to watch for are long COVID and e-cigarette or vaping product–associated lung injury (EVALI), Bhatia said. The clearest sign of EVALI is a history of e-cigarette/vaping exposure, but clinical symptoms include a dry cough that occurs with dyspnea and chest pain. A chest x-ray may show diffuse, hazy, or consolidative opacities. Sometimes antibiotics or steroids can be helpful, but the evidence isn’t strong, and the most effective treatment is stopping e-cigarette use. Less commonly, passive exposure to vaping can also be associated with EVALI.

The most recent research on long COVID suggests that about 10-20% of children with acute COVID develop long COVID, and about a quarter of these patients develop a chronic dry cough. It’s often associated with fatigue and shortness of breath, which can be assessed with cardiopulmonary exercise testing. Sometimes a short trial of inhaled steroids can help.

Bhatia also mentioned a handful of other uncommon causes of chronic cough that most American pediatricians are unlikely to see: Childhood interstitial lung disease, tuberculosis, use of Angiotensin-Converting Enzyme inhibitors, and a build-up of ear wax via the Arnold’s nerve reflex.
 

Evaluation and Workup

Bhatia also discussed what to cover while taking a history and questions to ask. The history should include the type of cough, the onset timing (sudden vs gradual), associated symptoms, the cough trajectory, medications the patient is taking, and the patient’s past medical history and environmental exposures. Those attributes are included in this more comprehensive list of questions to consider during evaluation, adapted from a list provided in a 2019 article in Paediatric Respiratory Reviews:

• Age of onset and duration?
• Was the onset sudden or associate with an illness?
• Is the cough wet or dry?
• What does the cough sound like?
• How often does the cough occur?
• Is it progressive?
• Is it present during sleep?
• Are there any other associated symptoms, such as wheeze, dyspnea, vomiting, chest pain, etc?
• Are there any exacerbating factors or known triggers?
• Are there any relieving factors, including a trial of bronchodilators?
• Has there been exposure to auto-irritants, such as secondhand smoke?
• What is the cough’s effect on the child and on others around the child?
• Does the child have any other underlying conditions such as neuromuscular disease or asthma?
• What medications is the child taking or has recently taken?
• Is there a family history of atopy and/or respiratory disease?

Bhatia also recommended paying special attention to the following red flags or key features that may help more quickly narrow the diagnosis and often require a specialist referral:

• Digital clubbing, failure to thrive, or low tone
• An abnormal cardiac exam
• Tachypnea, hypoxemia, chest retractions, or hemoptysis
• Abnormal breath sounds such as unilateral wheezing or coarse crackles
• Abnormal spirometry in those aged 5 and older showing reversible obstruction, which often indicates asthma
• An abnormal chest x-ray with, for example, bilateral infiltrates, hyperinflation, right middle lobe syndrome, situs inversus, unilateral hyperlucency, a right aortic arch, etc.

No external funding was used for the presentation. Bhatia and Quijada had no disclosures.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Asthma is the most common cause of chronic cough in children, but it’s important to be aware of other differential diagnoses for those patients who have less common concerns, according to Rajeev Bhatia, MD, division chief of pulmonology at Phoenix Children’s in Phoenix, Arizona. Bhatia reviewed both the major causes of chronic cough as well as the rare zebras to watch out for in a presentation at the American Academy of Pediatrics (AAP) 2024 National Conference.

“When you see a patient for cough, the most important thing is, history, history, history,” Bhatia said. “There are many, many, many clues in the history, age of onset, and duration.” That includes starting at birth to ensure you don’t miss key details such as a preterm birth. It’s also important to discuss what the cough sounds like, how frequent it is, what makes it better, what makes it worse, and how it’s affecting the child and others around them — all of which can help narrow the diagnosis.

Jose Quijada, DO, a pediatrician with CommuniCare Pediatrics in San Antonio, found the session “incredibly useful” not only because of the specific pointers about each condition but also because of the realistic case studies he included throughout.

“Sometimes when you’re practicing, you focus on what’s most common,” Quijada said, so it was helpful to get a review of some of the key features and red flags that point to less common causes that may need to be considered. He particularly appreciated the discussion of habitual cough and potential treatments because those can be challenging patients and it can be tough to find a middle ground with how much workup to do.
 

Common Causes of Chronic Cough

The coughing from inadequately controlled asthma tends to be nonproductive and worse at night or in the early morning, Bhatia explained, and it’s often accompanied by wheezing, shortness of breath, and chest tightness. While fractional exhaled nitric oxide can be useful, “studies show that it is more useful for to monitor the symptoms rather than to diagnose the asthma,” Bhatia told attendees, but he also added that spirometry can be normal in patients with asthma. In young patients, the Asthma Predictive Index can be an invaluable tool, he also said.

Another common cause of chronic cough is a postinfectious cough, which lasts more than 3 weeks after resolution of acute upper respiratory infection. It occurs in about one in 10 children after a viral infection such as a rhinovirus or respiratory syncytial virus infection and results from extensive inflammation and disruption of the airway epithelial integrity. Chest x-rays are usually normal in these patients, and the cough will usually resolve on its own. Albuterol has not been shown to be any more effective than placebo for a postinfectious cough, and antibiotics similarly have no clinically useful role.

A wet cough that lasts for at least 4 weeks and appears to have no other specific cause may be protracted bacterial bronchitis (PBB). While the cause of PBB isn’t known, it could be due to frequent illnesses that cause airway inflammation and injury over time, thereby making it easier for bacteria to grow and cause infection. Risk factors include tracheomalacia/bronchomalacia and childcare attendance, and typical pathogens include Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis.

While an x-ray can be done, radiography is often normal in patients with PBB. Bronchoscopy will reveal purulent secretions. PBB should resolve with at least 2 weeks of antibiotics, including amoxicillin-clavulanate, but the course can be extended to 4 weeks if the cough persists. However, about 40% of patients will have recurrence, and those with recurrent PBB or with a chronic cough unresponsive to 4 weeks of antibiotics should be referred to a pediatric pulmonologist.

Upper airway cough syndrome is the updated name for postnasal drip, which can occur with both allergic and nonallergic rhinitis and chronic rhinosinusitis. This is often a dry, throat-clearing cough that can be accompanied by headaches, nasal congestion, and sinus or facial tenderness. An examination will reveal posterior pharynx cobblestoning, Bhatia said, and empirical use of intranasal steroids can be both diagnostic and therapeutic for upper airway cough syndrome. He also emphasized the importance of taking an environmental history and avoiding exposure of environmental triggers.
 

Uncommon Pulmonary Causes of Chronic Cough

After discussing frequent reasons patients may present with a chronic cough, Bhatia went on to discuss the less common things to consider if the provider has eliminated the other possibilities. These include both pulmonary causes as well as congenital malformations, gastrointestinal causes, and habit cough.

A child who presents with a sudden onset of cough or wheeze in the absence of an upper respiratory infection may have a retained foreign body. This cough can be mistaken for bronchiolitis, asthma, croup, and other infectious conditions, especially because a partial obstruction can make diagnosis confusing or challenging. Adding to the challenge is that most foreign bodies will be radiolucent. A decubitus chest x-ray could be useful, but bronchoscopy is necessary for diagnosis. Bhatia stressed that it’s easy to miss a foreign body in younger children and that the wheezing can be more prominent on one side or another.

Cystic fibrosis, another uncommon cause of chronic cough, is ideally diagnosed via newborn screening, but screening is imperfect and can involve missed diagnoses or false negatives. Over 75% of cystic fibrosis cases are diagnosed by age 2, but that means a substantial number of cases still are not diagnosed until older childhood or later. This cough will be a chronic productive/wet cough.

A family history of cystic fibrosis may be present but doesn’t have to be, so signs to look for include poor weight gain, sinusitis, nasal polyps, clubbing, and isolation of suspicious organisms from a respiratory culture, such as Pseudomonas aeruginosa or Burkholderia cepacia complex. Clubbing in the fingers is a particularly telltale symptom of undiagnosed cystic fibrosis, and bronchiectasis of unknown etiology will be present. Suspicion of cystic fibrosis should lead to a referral to a cystic fibrosis center for a sweat test.

Even rarer than cystic fibrosis is primary ciliary dyskinesia (PCD), an inherited autosomal recessive disease that occurs in about one in 20,000 live births and involves a structural or functional defect in the cilia. About half of all patients with PCD will have situs inversus — an arrangement of chest and abdominal organs that is a mirror image of typical human anatomical presentation — but most people with situs inversus do not have PCD. One type of PCD is Kartagener syndrome, identified by the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis.

Children with PCD present with a chronic productive cough and recurrent pneumonias, and nearly all patients will have rhinosinusitis. About 60% of patients will develop respiratory symptoms such as mild distress or cough in their first month, and recurrent otitis media is common in these patients. PCD diagnosis is based on a combination of genetic testing, nasal nitric oxide, and evaluation of ciliary motion and structure. Clinical suspicion of PCD should lead to a specialist referral.

Nearly all people with PCD will eventually develop bronchiectasis, where the priority should be airway clearance using antibiotics for acute exacerbations and chronic azithromycin therapy for recurrent exacerbations. Patients with chronic rhinosinusitis, chronic otitis media, and nasal polyposis should be referred to an ENT specialist.
 

Other Uncommon Causes of Chronic Cough

A non-pulmonary, uncommon cause of chronic cough is a vascular ring, a congenital anomaly in which blood vessels encircle and potentially constrict the esophagus and/or trachea. The most common type is a double aortic arch, but a right aortic arch or pulmonary artery sling is also possible. These coughs sound harsh and are usually accompanied by stridor, dyspnea and feeding problems. Workup includes an echocardiogram, a CT angiogram, and possibly a bronchoscopy to determine the extent of the airway narrowing. In symptomatic patients, surgery is indicated for correction.

Another congenital malformation that can cause chronic cough is a tracheoesophageal fistula, which occurs in about one in 3500 live births, commonly linked to trisomy disorders and VACTERL. Several types of tracheoesophageal fistula exist, and H-type fistula is associated with late onset symptoms. The cough can be wet or dry and sometimes sounds like barking because of the associated airway collapse. Patients often have recurrent pneumonia, bronchitis, and cough or cyanosis with feeding. Workup should include an upper gastrointestinal series but not with barium, Bhatia said, because that can cause pneumonitis. Instead, the series should be done with a thickened water-soluble contrast material, and a bronchoscopy may be indicated as well.

Though common as a condition in adults, gastroesophageal reflux disease (GERD) is a rare, but possible, cause of chronic cough in children. More often, the reflux is the result of the cough rather than the cause. The most sensitive tool for assessing GERD is esophageal 24-hour pH/impedance reflux monitoring. However, treatment of the reflux for cough is not recommended unless the patient has clinical features of GERD, including dystonic neck posturing in infants, heartburn, regurgitation, or other symptoms. If the patient has clinical symptoms, then treatment is acid suppressive therapy for 4-8 weeks, followed by a clinical reassessment.

An uncommon cause of chronic cough with no biological mechanism is habit cough. Habit cough is most easily distinguished from other coughs by its sounds, a “large, loud, honking noise,” Bhatia said. It also lacks a clear trigger and is usually absent during sleep, but it can be continuous during the day. Frustratingly, the patients themselves often don’t seem bothered by the cough, but “it’s very disruptive in the school and everywhere else,” Bhatia said. Families and/providers will often have tried multiple treatments and seen no improvement with habit cough.

The first thing to do with habit cough is reassure the family that there’s nothing serious going on because they are often worried by this point. Several non-pharmaceutical treatments can be effective, such as suggestion therapy or the “warm water technique,” in which the patient takes a sip of warm water every time they feel the urge to cough. “If they’re able to break the cycle, most of the time, they are fine,” Bhatia said. In rarer cases, more involved behavioral interventions may be indicated, such as a psychology referral if an underlying anxiety or other behavioral disorder is contributing.
 

Newer Causes of Cough

Two more recent causes of cough to watch for are long COVID and e-cigarette or vaping product–associated lung injury (EVALI), Bhatia said. The clearest sign of EVALI is a history of e-cigarette/vaping exposure, but clinical symptoms include a dry cough that occurs with dyspnea and chest pain. A chest x-ray may show diffuse, hazy, or consolidative opacities. Sometimes antibiotics or steroids can be helpful, but the evidence isn’t strong, and the most effective treatment is stopping e-cigarette use. Less commonly, passive exposure to vaping can also be associated with EVALI.

The most recent research on long COVID suggests that about 10-20% of children with acute COVID develop long COVID, and about a quarter of these patients develop a chronic dry cough. It’s often associated with fatigue and shortness of breath, which can be assessed with cardiopulmonary exercise testing. Sometimes a short trial of inhaled steroids can help.

Bhatia also mentioned a handful of other uncommon causes of chronic cough that most American pediatricians are unlikely to see: Childhood interstitial lung disease, tuberculosis, use of Angiotensin-Converting Enzyme inhibitors, and a build-up of ear wax via the Arnold’s nerve reflex.
 

Evaluation and Workup

Bhatia also discussed what to cover while taking a history and questions to ask. The history should include the type of cough, the onset timing (sudden vs gradual), associated symptoms, the cough trajectory, medications the patient is taking, and the patient’s past medical history and environmental exposures. Those attributes are included in this more comprehensive list of questions to consider during evaluation, adapted from a list provided in a 2019 article in Paediatric Respiratory Reviews:

• Age of onset and duration?
• Was the onset sudden or associate with an illness?
• Is the cough wet or dry?
• What does the cough sound like?
• How often does the cough occur?
• Is it progressive?
• Is it present during sleep?
• Are there any other associated symptoms, such as wheeze, dyspnea, vomiting, chest pain, etc?
• Are there any exacerbating factors or known triggers?
• Are there any relieving factors, including a trial of bronchodilators?
• Has there been exposure to auto-irritants, such as secondhand smoke?
• What is the cough’s effect on the child and on others around the child?
• Does the child have any other underlying conditions such as neuromuscular disease or asthma?
• What medications is the child taking or has recently taken?
• Is there a family history of atopy and/or respiratory disease?

Bhatia also recommended paying special attention to the following red flags or key features that may help more quickly narrow the diagnosis and often require a specialist referral:

• Digital clubbing, failure to thrive, or low tone
• An abnormal cardiac exam
• Tachypnea, hypoxemia, chest retractions, or hemoptysis
• Abnormal breath sounds such as unilateral wheezing or coarse crackles
• Abnormal spirometry in those aged 5 and older showing reversible obstruction, which often indicates asthma
• An abnormal chest x-ray with, for example, bilateral infiltrates, hyperinflation, right middle lobe syndrome, situs inversus, unilateral hyperlucency, a right aortic arch, etc.

No external funding was used for the presentation. Bhatia and Quijada had no disclosures.
 

A version of this article appeared on Medscape.com.

Noninvasive surveillance with multitarget stool DNA testing or fecal immunochemical testing (FIT) could potentially match colonoscopy for reducing long-term colorectal cancer (CRC) incidence and mortality. It might also reduce colonoscopies by an estimated 15%-41%.

The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.

In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.

“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.

Netherlands Cancer Institute

Stanford University

Study Details

The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.

For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.

A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.

Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:

• 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
• 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR 
• 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold 

Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.

“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.

In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”

He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”

The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.

This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.

Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.

Ladabaum disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Noninvasive surveillance with multitarget stool DNA testing or fecal immunochemical testing (FIT) could potentially match colonoscopy for reducing long-term colorectal cancer (CRC) incidence and mortality. It might also reduce colonoscopies by an estimated 15%-41%.

The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.

In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.

“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.

Netherlands Cancer Institute

Stanford University

Study Details

The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.

For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.

A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.

Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:

• 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
• 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR 
• 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold 

Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.

“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.

In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”

He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”

The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.

This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.

Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.

Ladabaum disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Noninvasive surveillance with multitarget stool DNA testing or fecal immunochemical testing (FIT) could potentially match colonoscopy for reducing long-term colorectal cancer (CRC) incidence and mortality. It might also reduce colonoscopies by an estimated 15%-41%.

The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.

In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.

“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.

Netherlands Cancer Institute

Stanford University

Study Details

The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.

For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.

A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.

Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:

• 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
• 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR 
• 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold 

Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.

“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.

In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”

He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”

The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.

This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.

Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.

Ladabaum disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Key clinical point: The presence of clinical or subclinical dactylitis represented a more active and severe form of psoriatic arthritis (PsA), characterized by increased disease activity, swollen joint counts (SJCs), and tender joint counts (TJCs).

Major finding: PsA with dactylitis (clinical or subclinical) vs without dactylitis was associated with higher median disease activity index in PsA (DAPSA) scores (25.5 vs 16.1; P < .01), SJCs (4 vs 2; P < .001), and TJCs (4 vs 3; P < .01). PsA with subclinical dactylitis vs without dactylitis was associated with even higher DAPSA scores (27.2 vs 16.1; P < .05), SJCs (4.5 vs 2; P < .01), and TJCs (5 vs 3; P < .05).

Study details: This case-control study included 223 patients with PsA who were stratified on the basis of the presence of dactylitis (clinical or subclinical) or its absence at baseline.

Disclosures: This study was supported by the Youth Clinical Research Project of Peking University First Hospital and other sources. No conflicts of interest were reported.

Source: Song Z, Geng Y, Zhang X, Deng X, Zhang Z. Subclinical dactylitis represents a more active phenotype of psoriatic arthritis. Joint Bone Spine. Published online September 24, 2024. Source

Key clinical point: The presence of clinical or subclinical dactylitis represented a more active and severe form of psoriatic arthritis (PsA), characterized by increased disease activity, swollen joint counts (SJCs), and tender joint counts (TJCs).

Major finding: PsA with dactylitis (clinical or subclinical) vs without dactylitis was associated with higher median disease activity index in PsA (DAPSA) scores (25.5 vs 16.1; P < .01), SJCs (4 vs 2; P < .001), and TJCs (4 vs 3; P < .01). PsA with subclinical dactylitis vs without dactylitis was associated with even higher DAPSA scores (27.2 vs 16.1; P < .05), SJCs (4.5 vs 2; P < .01), and TJCs (5 vs 3; P < .05).

Study details: This case-control study included 223 patients with PsA who were stratified on the basis of the presence of dactylitis (clinical or subclinical) or its absence at baseline.

Disclosures: This study was supported by the Youth Clinical Research Project of Peking University First Hospital and other sources. No conflicts of interest were reported.

Source: Song Z, Geng Y, Zhang X, Deng X, Zhang Z. Subclinical dactylitis represents a more active phenotype of psoriatic arthritis. Joint Bone Spine. Published online September 24, 2024. Source

Key clinical point: The presence of clinical or subclinical dactylitis represented a more active and severe form of psoriatic arthritis (PsA), characterized by increased disease activity, swollen joint counts (SJCs), and tender joint counts (TJCs).

Major finding: PsA with dactylitis (clinical or subclinical) vs without dactylitis was associated with higher median disease activity index in PsA (DAPSA) scores (25.5 vs 16.1; P < .01), SJCs (4 vs 2; P < .001), and TJCs (4 vs 3; P < .01). PsA with subclinical dactylitis vs without dactylitis was associated with even higher DAPSA scores (27.2 vs 16.1; P < .05), SJCs (4.5 vs 2; P < .01), and TJCs (5 vs 3; P < .05).

Study details: This case-control study included 223 patients with PsA who were stratified on the basis of the presence of dactylitis (clinical or subclinical) or its absence at baseline.

Disclosures: This study was supported by the Youth Clinical Research Project of Peking University First Hospital and other sources. No conflicts of interest were reported.

Source: Song Z, Geng Y, Zhang X, Deng X, Zhang Z. Subclinical dactylitis represents a more active phenotype of psoriatic arthritis. Joint Bone Spine. Published online September 24, 2024. Source

Key clinical point: Guselkumab administered every 4 weeks (Q4W) or every 8 weeks (Q8W) yielded better clinical outcomes than placebo in patients with psoriatic arthritis (PsA), without any new safety concerns.

Major findings: At week 24, a higher proportion of patients receiving guselkumab Q4W (60%) and Q8W (51%) vs placebo (30%) achieved a ≥ 20% improvement in the American College of Rheumatology (ACR)20 response. The response rates increased through week 52 (69%-78) and were consistent at week 100 (76%-80%) across all the groups. Similar trends were observed for ACR50, with no new safety signals.

Study details: This post hoc analysis of the phase 3 trials DISCOVER-1 and DISCOVER-2 included 1002 biologic-naive patients with PsA who received 100 mg guselkumab Q4W, 100 mg guselkumab at weeks 0 and 4 and then Q8W, or placebo through week 24 with crossover to 100 mg guselkumab Q4W.

Disclosure: The study was sponsored by Janssen-Cilag Ltd. Four authors were employees of Johnson & Johnson. Several authors received research grants, consulting fees, or had ties with various sources.

Source: Mease P, Korotaeva T, Shesternya P, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis in Russia: A post hoc analysis of the DISCOVER-1 and -2 randomized clinical trials. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: Guselkumab administered every 4 weeks (Q4W) or every 8 weeks (Q8W) yielded better clinical outcomes than placebo in patients with psoriatic arthritis (PsA), without any new safety concerns.

Major findings: At week 24, a higher proportion of patients receiving guselkumab Q4W (60%) and Q8W (51%) vs placebo (30%) achieved a ≥ 20% improvement in the American College of Rheumatology (ACR)20 response. The response rates increased through week 52 (69%-78) and were consistent at week 100 (76%-80%) across all the groups. Similar trends were observed for ACR50, with no new safety signals.

Study details: This post hoc analysis of the phase 3 trials DISCOVER-1 and DISCOVER-2 included 1002 biologic-naive patients with PsA who received 100 mg guselkumab Q4W, 100 mg guselkumab at weeks 0 and 4 and then Q8W, or placebo through week 24 with crossover to 100 mg guselkumab Q4W.

Disclosure: The study was sponsored by Janssen-Cilag Ltd. Four authors were employees of Johnson & Johnson. Several authors received research grants, consulting fees, or had ties with various sources.

Source: Mease P, Korotaeva T, Shesternya P, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis in Russia: A post hoc analysis of the DISCOVER-1 and -2 randomized clinical trials. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: Guselkumab administered every 4 weeks (Q4W) or every 8 weeks (Q8W) yielded better clinical outcomes than placebo in patients with psoriatic arthritis (PsA), without any new safety concerns.

Major findings: At week 24, a higher proportion of patients receiving guselkumab Q4W (60%) and Q8W (51%) vs placebo (30%) achieved a ≥ 20% improvement in the American College of Rheumatology (ACR)20 response. The response rates increased through week 52 (69%-78) and were consistent at week 100 (76%-80%) across all the groups. Similar trends were observed for ACR50, with no new safety signals.

Study details: This post hoc analysis of the phase 3 trials DISCOVER-1 and DISCOVER-2 included 1002 biologic-naive patients with PsA who received 100 mg guselkumab Q4W, 100 mg guselkumab at weeks 0 and 4 and then Q8W, or placebo through week 24 with crossover to 100 mg guselkumab Q4W.

Disclosure: The study was sponsored by Janssen-Cilag Ltd. Four authors were employees of Johnson & Johnson. Several authors received research grants, consulting fees, or had ties with various sources.

Source: Mease P, Korotaeva T, Shesternya P, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis in Russia: A post hoc analysis of the DISCOVER-1 and -2 randomized clinical trials. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: In patients with psoriatic arthritis (PsA), tofacitinib demonstrated higher efficacy than placebo, regardless of smoking status; however, current or past smokers experienced increased rates of adverse events.

Major finding: At 3 months, 10 mg tofacitinib showed higher rates of a ≥ 50% improvement in the American College of Rheumatology response than placebo in current or past smokers (odds ratio [OR], 3.01; 95% CI, 1.43-6.33) and never smokers (OR, 6.53; 95% CI, 3.46-12.33). The incidence rates of treatment-emergent adverse events were higher in current or past smokers vs never smokers (adjusted incidence rate, 263.2 vs 208.9); 5 mg tofacitinib had comparable outcomes.

Study details: This post hoc analysis pooled data from phase 2 and 3 trials and a long-term extension study, involving 914 patients with PsA and 372 patients with ankylosing spondylitis who received tofacitinib (5 or 10 mg twice daily) or placebo, while considering their smoking status.

Disclosures: This study was sponsored by Pfizer. Four authors declared being current or former employees or shareholders of Pfizer. Other authors declared having ties with various sources.

Source: Ogdie A, Kristensen LE, Soriano ER, et al. Efficacy and safety of tofacitinib in patients with psoriatic arthritis or ankylosing spondylitis by cigarette smoking status. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: In patients with psoriatic arthritis (PsA), tofacitinib demonstrated higher efficacy than placebo, regardless of smoking status; however, current or past smokers experienced increased rates of adverse events.

Major finding: At 3 months, 10 mg tofacitinib showed higher rates of a ≥ 50% improvement in the American College of Rheumatology response than placebo in current or past smokers (odds ratio [OR], 3.01; 95% CI, 1.43-6.33) and never smokers (OR, 6.53; 95% CI, 3.46-12.33). The incidence rates of treatment-emergent adverse events were higher in current or past smokers vs never smokers (adjusted incidence rate, 263.2 vs 208.9); 5 mg tofacitinib had comparable outcomes.

Study details: This post hoc analysis pooled data from phase 2 and 3 trials and a long-term extension study, involving 914 patients with PsA and 372 patients with ankylosing spondylitis who received tofacitinib (5 or 10 mg twice daily) or placebo, while considering their smoking status.

Disclosures: This study was sponsored by Pfizer. Four authors declared being current or former employees or shareholders of Pfizer. Other authors declared having ties with various sources.

Source: Ogdie A, Kristensen LE, Soriano ER, et al. Efficacy and safety of tofacitinib in patients with psoriatic arthritis or ankylosing spondylitis by cigarette smoking status. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: In patients with psoriatic arthritis (PsA), tofacitinib demonstrated higher efficacy than placebo, regardless of smoking status; however, current or past smokers experienced increased rates of adverse events.

Major finding: At 3 months, 10 mg tofacitinib showed higher rates of a ≥ 50% improvement in the American College of Rheumatology response than placebo in current or past smokers (odds ratio [OR], 3.01; 95% CI, 1.43-6.33) and never smokers (OR, 6.53; 95% CI, 3.46-12.33). The incidence rates of treatment-emergent adverse events were higher in current or past smokers vs never smokers (adjusted incidence rate, 263.2 vs 208.9); 5 mg tofacitinib had comparable outcomes.

Study details: This post hoc analysis pooled data from phase 2 and 3 trials and a long-term extension study, involving 914 patients with PsA and 372 patients with ankylosing spondylitis who received tofacitinib (5 or 10 mg twice daily) or placebo, while considering their smoking status.

Disclosures: This study was sponsored by Pfizer. Four authors declared being current or former employees or shareholders of Pfizer. Other authors declared having ties with various sources.

Source: Ogdie A, Kristensen LE, Soriano ER, et al. Efficacy and safety of tofacitinib in patients with psoriatic arthritis or ankylosing spondylitis by cigarette smoking status. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: In patients with active psoriatic arthritis (PsA), intravenous secukinumab every 4 weeks demonstrated rapid and sustained efficacy, along with a safety profile consistent with that of subcutaneous secukinumab.

Major finding: At week 16, intravenous secukinumab vs placebo significantly improved the American College of Rheumatology 50 response rate (31.4% vs 6.3%; adjusted P < .0001). Improvements were observed as early as week 4 (P < .0005) and were sustained through week 52, regardless of whether patients continued intravenous secukinumab (58.0%) or switched from placebo to intravenous secukinumab (64.0%). No new safety signals were reported.

Study details: In this phase 3 INVIGORATE-2 trial, 381 patients with active PsA and either plaque psoriasis or nail psoriasis were randomly assigned to receive intravenous secukinumab or placebo with crossover to intravenous secukinumab at week 16.

Disclosures: This study was supported by Novartis. Five authors declared being employees of and owning stocks in Novartis. Several authors declared having ties with various sources, including Novartis.

Source: Kivitz A, Sedova L, Churchill M, et al. Efficacy and safety of intravenous secukinumab for the treatment of active psoriatic arthritis: Results from the randomized, placebo-controlled phase III INVIGORATE-2 study. Arthritis Rheumatol. Published online September 19, 2024. Source

Key clinical point: In patients with active psoriatic arthritis (PsA), intravenous secukinumab every 4 weeks demonstrated rapid and sustained efficacy, along with a safety profile consistent with that of subcutaneous secukinumab.

Major finding: At week 16, intravenous secukinumab vs placebo significantly improved the American College of Rheumatology 50 response rate (31.4% vs 6.3%; adjusted P < .0001). Improvements were observed as early as week 4 (P < .0005) and were sustained through week 52, regardless of whether patients continued intravenous secukinumab (58.0%) or switched from placebo to intravenous secukinumab (64.0%). No new safety signals were reported.

Study details: In this phase 3 INVIGORATE-2 trial, 381 patients with active PsA and either plaque psoriasis or nail psoriasis were randomly assigned to receive intravenous secukinumab or placebo with crossover to intravenous secukinumab at week 16.

Disclosures: This study was supported by Novartis. Five authors declared being employees of and owning stocks in Novartis. Several authors declared having ties with various sources, including Novartis.

Source: Kivitz A, Sedova L, Churchill M, et al. Efficacy and safety of intravenous secukinumab for the treatment of active psoriatic arthritis: Results from the randomized, placebo-controlled phase III INVIGORATE-2 study. Arthritis Rheumatol. Published online September 19, 2024. Source

Key clinical point: In patients with active psoriatic arthritis (PsA), intravenous secukinumab every 4 weeks demonstrated rapid and sustained efficacy, along with a safety profile consistent with that of subcutaneous secukinumab.

Major finding: At week 16, intravenous secukinumab vs placebo significantly improved the American College of Rheumatology 50 response rate (31.4% vs 6.3%; adjusted P < .0001). Improvements were observed as early as week 4 (P < .0005) and were sustained through week 52, regardless of whether patients continued intravenous secukinumab (58.0%) or switched from placebo to intravenous secukinumab (64.0%). No new safety signals were reported.

Study details: In this phase 3 INVIGORATE-2 trial, 381 patients with active PsA and either plaque psoriasis or nail psoriasis were randomly assigned to receive intravenous secukinumab or placebo with crossover to intravenous secukinumab at week 16.

Disclosures: This study was supported by Novartis. Five authors declared being employees of and owning stocks in Novartis. Several authors declared having ties with various sources, including Novartis.

Source: Kivitz A, Sedova L, Churchill M, et al. Efficacy and safety of intravenous secukinumab for the treatment of active psoriatic arthritis: Results from the randomized, placebo-controlled phase III INVIGORATE-2 study. Arthritis Rheumatol. Published online September 19, 2024. Source

Key clinical point: In biologic-naive patients with active psoriatic arthritis (PsA), guselkumab administered every 8 weeks (Q8W) led to consistent patient-level improvements in joint disease activity, which persisted for 2 years.

Major finding: Guselkumab maintained high rates of minimal clinically important improvements (MCII) in the clinical Disease Activity Index for PsA (cDAPSA; 94%-99%), with improvements of ≥ 5.7 from baseline through week 52 with a dosing of 100 mg guselkumab Q8W. Among those achieving MCII by week 24, maintenance rates were 69.2% for the cDAPSA and 89.0% for the Psoriatic Arthritis Disease Activity Score at 100 weeks post-achievement.

Study details: This post hoc analysis of the phase 3 DISCOVER-2 trial included 248 biologic-naive patients with active PsA who received 100 mg guselkumab Q8W for 100 weeks.

Disclosures: This study was supported by Janssen Research & Development, LLC. Several authors disclosed holding stock or stock options; receiving grants, payment, honoraria, or consulting fees; or having other ties with various sources, including Janssen.

Source: Mease PJ, Baraliakos X, Chandran V, et al. Persistent patient-level effect of guselkumab at consecutive 8-week dosing visits and over time in patients with active psoriatic arthritis: Post hoc analysis of a 2-year, phase 3, randomized, controlled study. ACR Open Rheumatol. Published online October 4, 2024. Source

Key clinical point: In biologic-naive patients with active psoriatic arthritis (PsA), guselkumab administered every 8 weeks (Q8W) led to consistent patient-level improvements in joint disease activity, which persisted for 2 years.

Major finding: Guselkumab maintained high rates of minimal clinically important improvements (MCII) in the clinical Disease Activity Index for PsA (cDAPSA; 94%-99%), with improvements of ≥ 5.7 from baseline through week 52 with a dosing of 100 mg guselkumab Q8W. Among those achieving MCII by week 24, maintenance rates were 69.2% for the cDAPSA and 89.0% for the Psoriatic Arthritis Disease Activity Score at 100 weeks post-achievement.

Study details: This post hoc analysis of the phase 3 DISCOVER-2 trial included 248 biologic-naive patients with active PsA who received 100 mg guselkumab Q8W for 100 weeks.

Disclosures: This study was supported by Janssen Research & Development, LLC. Several authors disclosed holding stock or stock options; receiving grants, payment, honoraria, or consulting fees; or having other ties with various sources, including Janssen.

Source: Mease PJ, Baraliakos X, Chandran V, et al. Persistent patient-level effect of guselkumab at consecutive 8-week dosing visits and over time in patients with active psoriatic arthritis: Post hoc analysis of a 2-year, phase 3, randomized, controlled study. ACR Open Rheumatol. Published online October 4, 2024. Source

Key clinical point: In biologic-naive patients with active psoriatic arthritis (PsA), guselkumab administered every 8 weeks (Q8W) led to consistent patient-level improvements in joint disease activity, which persisted for 2 years.

Major finding: Guselkumab maintained high rates of minimal clinically important improvements (MCII) in the clinical Disease Activity Index for PsA (cDAPSA; 94%-99%), with improvements of ≥ 5.7 from baseline through week 52 with a dosing of 100 mg guselkumab Q8W. Among those achieving MCII by week 24, maintenance rates were 69.2% for the cDAPSA and 89.0% for the Psoriatic Arthritis Disease Activity Score at 100 weeks post-achievement.

Study details: This post hoc analysis of the phase 3 DISCOVER-2 trial included 248 biologic-naive patients with active PsA who received 100 mg guselkumab Q8W for 100 weeks.

Disclosures: This study was supported by Janssen Research & Development, LLC. Several authors disclosed holding stock or stock options; receiving grants, payment, honoraria, or consulting fees; or having other ties with various sources, including Janssen.

Source: Mease PJ, Baraliakos X, Chandran V, et al. Persistent patient-level effect of guselkumab at consecutive 8-week dosing visits and over time in patients with active psoriatic arthritis: Post hoc analysis of a 2-year, phase 3, randomized, controlled study. ACR Open Rheumatol. Published online October 4, 2024. Source

Key clinical point: Secukinumab led to clinical improvements across all psoriatic arthritis (PsA) domains, achieving minimal disease activity and demonstrating a favorable 4-year safety profile in biologic-naive patients, those with previous treatment failure, and those with or without comorbidities.

Major finding: During the 48-month follow-up, secukinumab significantly reduced the proportion of patients with active tender joints, swollen joints, enthesitis, and dactylitis (all P < .01). Overall, 50% of patients achieved remission or low disease activity in PsA, with higher rates of minimal disease activity in biologic-naive vs non-naive patients (76.9% vs 66.2%; P < .01) and in those without comorbidities vs those with over three comorbidities (78.8% vs 48.7%; P < .001). Only 5.9% of patients discontinued treatment due to adverse events.

Study details: This 4-year prospective observational study included 685 patients with PsA who received secukinumab; 32.9% were biologic-naive and 74.2% had at least one comorbidity.

Disclosures: This study did not receive financial support from any pharmaceutical company. The authors declared no conflicts of interest.

Source: Ramonda R, Lorenzin M, Chimenti MS, et al. Four-year effectiveness, safety and drug retention rate of secukinumab in psoriatic arthritis: A real-life Italian multicenter cohort. Arthritis Res Ther. 2024;26:172. Source

Key clinical point: Secukinumab led to clinical improvements across all psoriatic arthritis (PsA) domains, achieving minimal disease activity and demonstrating a favorable 4-year safety profile in biologic-naive patients, those with previous treatment failure, and those with or without comorbidities.

Major finding: During the 48-month follow-up, secukinumab significantly reduced the proportion of patients with active tender joints, swollen joints, enthesitis, and dactylitis (all P < .01). Overall, 50% of patients achieved remission or low disease activity in PsA, with higher rates of minimal disease activity in biologic-naive vs non-naive patients (76.9% vs 66.2%; P < .01) and in those without comorbidities vs those with over three comorbidities (78.8% vs 48.7%; P < .001). Only 5.9% of patients discontinued treatment due to adverse events.

Study details: This 4-year prospective observational study included 685 patients with PsA who received secukinumab; 32.9% were biologic-naive and 74.2% had at least one comorbidity.

Disclosures: This study did not receive financial support from any pharmaceutical company. The authors declared no conflicts of interest.

Source: Ramonda R, Lorenzin M, Chimenti MS, et al. Four-year effectiveness, safety and drug retention rate of secukinumab in psoriatic arthritis: A real-life Italian multicenter cohort. Arthritis Res Ther. 2024;26:172. Source

Key clinical point: Secukinumab led to clinical improvements across all psoriatic arthritis (PsA) domains, achieving minimal disease activity and demonstrating a favorable 4-year safety profile in biologic-naive patients, those with previous treatment failure, and those with or without comorbidities.

Major finding: During the 48-month follow-up, secukinumab significantly reduced the proportion of patients with active tender joints, swollen joints, enthesitis, and dactylitis (all P < .01). Overall, 50% of patients achieved remission or low disease activity in PsA, with higher rates of minimal disease activity in biologic-naive vs non-naive patients (76.9% vs 66.2%; P < .01) and in those without comorbidities vs those with over three comorbidities (78.8% vs 48.7%; P < .001). Only 5.9% of patients discontinued treatment due to adverse events.

Study details: This 4-year prospective observational study included 685 patients with PsA who received secukinumab; 32.9% were biologic-naive and 74.2% had at least one comorbidity.

Disclosures: This study did not receive financial support from any pharmaceutical company. The authors declared no conflicts of interest.

Source: Ramonda R, Lorenzin M, Chimenti MS, et al. Four-year effectiveness, safety and drug retention rate of secukinumab in psoriatic arthritis: A real-life Italian multicenter cohort. Arthritis Res Ther. 2024;26:172. Source

A new serum containing 2-mercaptonicotinoyl glycine (Melasyl) as its main ingredient was at least as good as, if not better than, cysteamine 5% cream in treating facial melasma in a randomized controlled study presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“Melasyl is a new potent melanogenesis inhibitor that exhibits a unique mode of action while preserving melanocyte integrity,” Mukta Sachdev, MD, head of the Department of Dermatology at Manipal Hospital in Bangalore, India, said at a late-breaking news session.

Both the serum and the cysteamine cream lightened participants’ skin to a similar extent, according to the modified Melasma Area and Severity Index (mMASI), with respective reductions of 4.19 and 3.81 points over a period of 4 months from baseline values of 11.15 and 10.93. 

Toa55/iStock/Getty Images

The mMASI score ranges from 0 to 24, with the lowest score representing the least and the highest score the most severe hyperpigmentation of the skin.

But the serum performed better than the cream by another measure. Judged by investigators blinded to which preparation study participants had been using, there was a significantly higher reduction in the Investigator Global Assessment (IGA) score from baseline among those treated with the serum than among those treated with the cream (−51.85% vs −39.06%; P = .0163). 

Moreover, after 4 months of treatment, there were significantly more participants with clear or almost clear skin with the serum than with the cream (17.46% vs 7.81%; P = .0163), Sachdev reported.

Other skin parameters relative to melasma, such as the brightness of skin tone and evenness of the improvement, improved more in the participants using the serum vs cream, she said. 

With “no side effects, no local skin reactions,” Sachdev said, “quality of life improved significantly and similarly, and almost all subjects in both groups were very satisfied with their treatment options.”
 

Active Ingredients

Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra, in Portugal, who co-chaired the late-breaking news session, commented: “It’s really nice to have new products to treat such a devastating disease.”

Session co-chair, Lidia Rudnicka, MD, head of the Department of Dermatology, Medical University of Warsaw, in Poland, and president of the Polish Dermatological Society, wanted to know more about the active ingredients of the serum and the study’s design. 

Sachdev replied that the serum also contains other ingredients that provide “antioxidant protection” and moisturization. These include retinyl palmitate, which works on the dermal-epidermal junction, and hyaluronic acid, as well as “soothing agents,” such as the medicinal herb Centella asiatica, she said.
 

Study Design

Conducted at a single center in India, the study involved 127 adults aged 20-50 years with melasma. For inclusion, the participants had to have facial epidermal or mixed melasma (phototypes III-V) for more than 1 year; those with dermal melasma were excluded. 

Participants were randomly allocated to receive either the serum, which was applied topically to the areas of interest twice a day in the morning and then at bedtime (n = 63), or cysteamine cream (n = 64), which was applied once a day in addition to a neutral moisturizer. Treatment was for 4 months, with an on-site visit every month. 

All participants were supplied with the same sunscreen/ultraviolet protector applied twice a day (once in the morning and again at midday) and a neutral hydrating cleanser that was used in the morning and evening. 
 

Practical Implications

Over 4 months, both products showed significant improvement in melasma without reaching a plateau, Sachdev reported, with the serum demonstrating superior efficacy and tolerability, as judged by the investigators. 

The study suggests that the serum is a promising non-hydroquinone treatment for melasma, she said. Hydroquinone-containing topical preparations are used to depigment the skin, but their long-term use can be limited for safety reasons. 

“When products like this demonstrate improvement, it is something for the dermatologist to think about because we now have newer ingredients, which are safer and well tolerated,” she continued, noting that there appeared to be no risk for exogenous ochronosis, which can occur with long-term application of hydroquinone.

“So, I think the armamentarium of non-hydroquinone products for the treatment of melasma is rapidly expanding, and there are studies now with clinically proven efficacy,” Sachdev concluded. 

The study was supported by L’Oréal France La Roche-Posay, which launched Melasyl in March 2024. Sachdev reported receipt of research support and honoraria from the company. Gonçalo and Rudnicka were not involved in the study and had no relevant conflicts of interest to report. 
 

A version of this article appeared on Medscape.com.

A new serum containing 2-mercaptonicotinoyl glycine (Melasyl) as its main ingredient was at least as good as, if not better than, cysteamine 5% cream in treating facial melasma in a randomized controlled study presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“Melasyl is a new potent melanogenesis inhibitor that exhibits a unique mode of action while preserving melanocyte integrity,” Mukta Sachdev, MD, head of the Department of Dermatology at Manipal Hospital in Bangalore, India, said at a late-breaking news session.

Both the serum and the cysteamine cream lightened participants’ skin to a similar extent, according to the modified Melasma Area and Severity Index (mMASI), with respective reductions of 4.19 and 3.81 points over a period of 4 months from baseline values of 11.15 and 10.93. 

Toa55/iStock/Getty Images

The mMASI score ranges from 0 to 24, with the lowest score representing the least and the highest score the most severe hyperpigmentation of the skin.

But the serum performed better than the cream by another measure. Judged by investigators blinded to which preparation study participants had been using, there was a significantly higher reduction in the Investigator Global Assessment (IGA) score from baseline among those treated with the serum than among those treated with the cream (−51.85% vs −39.06%; P = .0163). 

Moreover, after 4 months of treatment, there were significantly more participants with clear or almost clear skin with the serum than with the cream (17.46% vs 7.81%; P = .0163), Sachdev reported.

Other skin parameters relative to melasma, such as the brightness of skin tone and evenness of the improvement, improved more in the participants using the serum vs cream, she said. 

With “no side effects, no local skin reactions,” Sachdev said, “quality of life improved significantly and similarly, and almost all subjects in both groups were very satisfied with their treatment options.”
 

Active Ingredients

Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra, in Portugal, who co-chaired the late-breaking news session, commented: “It’s really nice to have new products to treat such a devastating disease.”

Session co-chair, Lidia Rudnicka, MD, head of the Department of Dermatology, Medical University of Warsaw, in Poland, and president of the Polish Dermatological Society, wanted to know more about the active ingredients of the serum and the study’s design. 

Sachdev replied that the serum also contains other ingredients that provide “antioxidant protection” and moisturization. These include retinyl palmitate, which works on the dermal-epidermal junction, and hyaluronic acid, as well as “soothing agents,” such as the medicinal herb Centella asiatica, she said.
 

Study Design

Conducted at a single center in India, the study involved 127 adults aged 20-50 years with melasma. For inclusion, the participants had to have facial epidermal or mixed melasma (phototypes III-V) for more than 1 year; those with dermal melasma were excluded. 

Participants were randomly allocated to receive either the serum, which was applied topically to the areas of interest twice a day in the morning and then at bedtime (n = 63), or cysteamine cream (n = 64), which was applied once a day in addition to a neutral moisturizer. Treatment was for 4 months, with an on-site visit every month. 

All participants were supplied with the same sunscreen/ultraviolet protector applied twice a day (once in the morning and again at midday) and a neutral hydrating cleanser that was used in the morning and evening. 
 

Practical Implications

Over 4 months, both products showed significant improvement in melasma without reaching a plateau, Sachdev reported, with the serum demonstrating superior efficacy and tolerability, as judged by the investigators. 

The study suggests that the serum is a promising non-hydroquinone treatment for melasma, she said. Hydroquinone-containing topical preparations are used to depigment the skin, but their long-term use can be limited for safety reasons. 

“When products like this demonstrate improvement, it is something for the dermatologist to think about because we now have newer ingredients, which are safer and well tolerated,” she continued, noting that there appeared to be no risk for exogenous ochronosis, which can occur with long-term application of hydroquinone.

“So, I think the armamentarium of non-hydroquinone products for the treatment of melasma is rapidly expanding, and there are studies now with clinically proven efficacy,” Sachdev concluded. 

The study was supported by L’Oréal France La Roche-Posay, which launched Melasyl in March 2024. Sachdev reported receipt of research support and honoraria from the company. Gonçalo and Rudnicka were not involved in the study and had no relevant conflicts of interest to report. 
 

A version of this article appeared on Medscape.com.

A new serum containing 2-mercaptonicotinoyl glycine (Melasyl) as its main ingredient was at least as good as, if not better than, cysteamine 5% cream in treating facial melasma in a randomized controlled study presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“Melasyl is a new potent melanogenesis inhibitor that exhibits a unique mode of action while preserving melanocyte integrity,” Mukta Sachdev, MD, head of the Department of Dermatology at Manipal Hospital in Bangalore, India, said at a late-breaking news session.

Both the serum and the cysteamine cream lightened participants’ skin to a similar extent, according to the modified Melasma Area and Severity Index (mMASI), with respective reductions of 4.19 and 3.81 points over a period of 4 months from baseline values of 11.15 and 10.93. 

Toa55/iStock/Getty Images

The mMASI score ranges from 0 to 24, with the lowest score representing the least and the highest score the most severe hyperpigmentation of the skin.

But the serum performed better than the cream by another measure. Judged by investigators blinded to which preparation study participants had been using, there was a significantly higher reduction in the Investigator Global Assessment (IGA) score from baseline among those treated with the serum than among those treated with the cream (−51.85% vs −39.06%; P = .0163). 

Moreover, after 4 months of treatment, there were significantly more participants with clear or almost clear skin with the serum than with the cream (17.46% vs 7.81%; P = .0163), Sachdev reported.

Other skin parameters relative to melasma, such as the brightness of skin tone and evenness of the improvement, improved more in the participants using the serum vs cream, she said. 

With “no side effects, no local skin reactions,” Sachdev said, “quality of life improved significantly and similarly, and almost all subjects in both groups were very satisfied with their treatment options.”
 

Active Ingredients

Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra, in Portugal, who co-chaired the late-breaking news session, commented: “It’s really nice to have new products to treat such a devastating disease.”

Session co-chair, Lidia Rudnicka, MD, head of the Department of Dermatology, Medical University of Warsaw, in Poland, and president of the Polish Dermatological Society, wanted to know more about the active ingredients of the serum and the study’s design. 

Sachdev replied that the serum also contains other ingredients that provide “antioxidant protection” and moisturization. These include retinyl palmitate, which works on the dermal-epidermal junction, and hyaluronic acid, as well as “soothing agents,” such as the medicinal herb Centella asiatica, she said.
 

Study Design

Conducted at a single center in India, the study involved 127 adults aged 20-50 years with melasma. For inclusion, the participants had to have facial epidermal or mixed melasma (phototypes III-V) for more than 1 year; those with dermal melasma were excluded. 

Participants were randomly allocated to receive either the serum, which was applied topically to the areas of interest twice a day in the morning and then at bedtime (n = 63), or cysteamine cream (n = 64), which was applied once a day in addition to a neutral moisturizer. Treatment was for 4 months, with an on-site visit every month. 

All participants were supplied with the same sunscreen/ultraviolet protector applied twice a day (once in the morning and again at midday) and a neutral hydrating cleanser that was used in the morning and evening. 
 

Practical Implications

Over 4 months, both products showed significant improvement in melasma without reaching a plateau, Sachdev reported, with the serum demonstrating superior efficacy and tolerability, as judged by the investigators. 

The study suggests that the serum is a promising non-hydroquinone treatment for melasma, she said. Hydroquinone-containing topical preparations are used to depigment the skin, but their long-term use can be limited for safety reasons. 

“When products like this demonstrate improvement, it is something for the dermatologist to think about because we now have newer ingredients, which are safer and well tolerated,” she continued, noting that there appeared to be no risk for exogenous ochronosis, which can occur with long-term application of hydroquinone.

“So, I think the armamentarium of non-hydroquinone products for the treatment of melasma is rapidly expanding, and there are studies now with clinically proven efficacy,” Sachdev concluded. 

The study was supported by L’Oréal France La Roche-Posay, which launched Melasyl in March 2024. Sachdev reported receipt of research support and honoraria from the company. Gonçalo and Rudnicka were not involved in the study and had no relevant conflicts of interest to report. 
 

A version of this article appeared on Medscape.com.

Key clinical point: Adalimumab and secukinumab showed comparable efficacy in patients with psoriatic arthritis (PsA); however, secukinumab was more effective for skin improvement and adalimumab was superior in alleviating ultrasound-confirmed synovitis.

Major finding: At week 12, there was no significant difference between adalimumab and secukinumab in achieving a ≥ 20% improvement in the American College of Rheumatology response (odds ratio [OR], 0.59; P = .22). Secukinumab showed higher efficacy than adalimumab in achieving a 90% improvement in the Psoriasis Area and Severity Index (OR, 2.25; P = .03). At week 52, adalimumab achieved greater improvements in the ultrasound synovitis count (β, 0.94; P = .03) and synovitis power Doppler signal (β = 0.20; P = .02) than secukinumab.

Study details: This prospective real-world study included 116 patients with PsA (age, ≥ 18 years) who received secukinumab or adalimumab (both n = 58).

Disclosures: This study did not receive any specific funding. No conflicts of interest were reported.

Source: Wang Y, Xiao Y, Zhang L, et al. Superior effect of adalimumab versus secukinumab on ultrasound-confirmed synovitis in psoriatic arthritis: Comprehensive evidence from musculoskeletal ultrasound and clinical assessments. J Dermatolog Treat. 2024;35:2411849. Source

Key clinical point: Adalimumab and secukinumab showed comparable efficacy in patients with psoriatic arthritis (PsA); however, secukinumab was more effective for skin improvement and adalimumab was superior in alleviating ultrasound-confirmed synovitis.

Major finding: At week 12, there was no significant difference between adalimumab and secukinumab in achieving a ≥ 20% improvement in the American College of Rheumatology response (odds ratio [OR], 0.59; P = .22). Secukinumab showed higher efficacy than adalimumab in achieving a 90% improvement in the Psoriasis Area and Severity Index (OR, 2.25; P = .03). At week 52, adalimumab achieved greater improvements in the ultrasound synovitis count (β, 0.94; P = .03) and synovitis power Doppler signal (β = 0.20; P = .02) than secukinumab.

Study details: This prospective real-world study included 116 patients with PsA (age, ≥ 18 years) who received secukinumab or adalimumab (both n = 58).

Disclosures: This study did not receive any specific funding. No conflicts of interest were reported.

Source: Wang Y, Xiao Y, Zhang L, et al. Superior effect of adalimumab versus secukinumab on ultrasound-confirmed synovitis in psoriatic arthritis: Comprehensive evidence from musculoskeletal ultrasound and clinical assessments. J Dermatolog Treat. 2024;35:2411849. Source

Key clinical point: Adalimumab and secukinumab showed comparable efficacy in patients with psoriatic arthritis (PsA); however, secukinumab was more effective for skin improvement and adalimumab was superior in alleviating ultrasound-confirmed synovitis.

Major finding: At week 12, there was no significant difference between adalimumab and secukinumab in achieving a ≥ 20% improvement in the American College of Rheumatology response (odds ratio [OR], 0.59; P = .22). Secukinumab showed higher efficacy than adalimumab in achieving a 90% improvement in the Psoriasis Area and Severity Index (OR, 2.25; P = .03). At week 52, adalimumab achieved greater improvements in the ultrasound synovitis count (β, 0.94; P = .03) and synovitis power Doppler signal (β = 0.20; P = .02) than secukinumab.

Study details: This prospective real-world study included 116 patients with PsA (age, ≥ 18 years) who received secukinumab or adalimumab (both n = 58).

Disclosures: This study did not receive any specific funding. No conflicts of interest were reported.

Source: Wang Y, Xiao Y, Zhang L, et al. Superior effect of adalimumab versus secukinumab on ultrasound-confirmed synovitis in psoriatic arthritis: Comprehensive evidence from musculoskeletal ultrasound and clinical assessments. J Dermatolog Treat. 2024;35:2411849. Source