Article

Buruli ulcer (BU) is a potentially disabling necrotizing skin and soft tissue disease caused by Mycobacterium ulcerans infection.^1,2 Buruli ulcer is most common in hot and humid climates and has caused considerable morbidity in Western African countries (Côte d’Ivoire, Ghana, and Benin account for 73% of annual cases) and the temperate areas of Australia (283 reported cases in 2017).^1-4 In fact, the first recognizable cases of BU were described in 6 Australian individuals living in a riverine area in 1948, although the term Buruli ulcer is derived from the increased number of cases reported from Buruli county in Uganda near the Nile River.^1,3,4

From 2002 to 2017, 66,000 cases of BU were reported in 33 countries.¹ While the focal distribution has been demonstrated in the tropical areas of Sri Lanka, Malaysia, Papua New Guinea, Peru, and Mexico,⁴ nontropical nations such as Japan also are affected. Since 1981, 66 cases have been reported in Japan with M ulcerans subspecies—primarily Shinshuense, which has adapted to higher latitudes.¹ Herein, we provide an overview of the pathogenesis, clinical presentation, and treatment of BU and highlight aquatic insects and mosquitoes as possible vectors of transmission.

Pathogenesis

Mycobacterium ulcerans is a nontuberculous mycobacterium and ubiquitous acid-fast gram-positive bacillus that can be cultured using a Lowenstein-Jensen agar and has a doubling rate of 48 hours.^1,5 It produces the small 174-kb plasmid pMUM001-encoded compound mycolactone, a pathogenic toxin that causes immunosuppression, analgesia, and cytotoxic-associated tissue necrosis.^1,5-9

Mycolactone is a polyketide macrolide with a 12-membrane lactone with 2 attached acyl side chains.^1,7 Mycolactone is synthesized by the giant polyketide synthetases of M ulcerans. Mycolactone post-transcriptionally inhibits the development of lipopolysaccharide-dependent proinflammatory mediators—specifically by blocking protein translocation from the cytosol into the endoplasmic reticulum by targeting the SEC61 translocon.^1,6 The lack of translocation of 30% to 50% of proteins leads to cellular stress and apoptosis mediated by Bim/Bcl2. A single point mutation in the SEC61 translocon subunit alpha 1 gene (SEC61A1) is associated with resistance to the cytotoxic effects of mycolactone.¹

There are divergent hypotheses regarding the relationship of mycolactone to the Wiskott-Aldrich syndrome protein, with some researchers suggesting that mycolactone can attach to this protein, leading to cell detachment and death.⁷ However, others have proposed that mycolactone inhibits mTOR, activating the Wiskott-Aldrich syndrome protein and leading to subsequent extensive cytoskeleton remodeling.¹ Mycolactone also can cause hypoesthesia, either by activating type 2 angiotensin II receptors and creating downstream neuron hyperpolarization or by killing Schwann cells.¹

Transmission

Buruli ulcer caused by M ulcerans has a poorly understood transmission mechanism, and further studies are required to understand the underlying pathophysiology to decrease transmission rates and associated morbidity. Buruli ulcer is widely accepted to be transmitted to humans via predominantly water-rich environments; most cases occur around slow-moving and still bodies of water such as swamps, ponds, and marshes.¹Mycobacterium ulcerans DNA has been found in fish, water insects, and snails.^1,4 It also has been present in samples from aquatic insects such as Hemiptera (water strider), Naucoridae (creeping water bugs and saucer bugs), and Belostomatidae (giant water bugs) in West Africa and also from Aulacodes feces and moss.¹

Variations in geographic climate may lead to different modes of transmission of BU. For example, mosquitoes have been studied as a potential vector for BU in the temperate climate of Australia.² However, more data are needed from other countries to support mosquitoes as possible vectors. Wallace et al¹⁰ performed a study that showed skin puncture from insect bites or other injuries increases the chance of transmitting M ulcerans in the environment to the skin.

Clinical Presentation

Buruli ulcer most often manifests in healthy children younger than 15 years.^1,8 Potential risk factors include residing near a contaminated water source, swimming in a river, and being bitten by an insect in a river during the rainy season. Lack of protective clothing and mosquito nets also have been proposed as considerable risk factors for BU.² Genetic polymorphism in the solute carrier family 11 member 1 gene (SLC11A1) may increase the risk for BU with M ulcerans transmission. It is essential to understand that infection with M ulcerans does not always lead to the development of BU.¹

Buruli ulcer often begins as a painless nodule or papule that patients may confuse with an insect bite. Within a couple of weeks, the induration will grow into ill-defined edematous plaques that gradually turn into necrotic skin, which will eventually slough off to create painless to mildly painful irregular skin ulceration (Figure).¹¹ The surrounding uninvolved skin often is edematous and pigmented. Unfortunately, deep ulcerations can lead to osteomyelitis with exposure of the underlying bone. A secondary bacterial infection may be involved if a foul smell accompanies the ulcer. The vast extension of the ulcer has been known to lead to amputations, contractures, or deformities.^1-5 The nodule progression to ulceration varies and can occur within 3 weeks to 1 year of the initial exposure.^1,8

The World Health Organization (WHO) classifies BU into 3 categories: category 1 includes ulcers less than 5 cm in diameter; category 2 involves ulcers that are 5 to 15 cm in diameter; and category 3 involves ulcers that are larger than 15 cm in diameter as well as those involving the breasts, genitals, eyes, bones, or joints.^4,8

Diagnosis

Cultures and microscopic examination of M ulcerans acid-fast bacilli can be used to confirm the diagnosis of BU. However, polymerase chain reaction (PCR) is the best confirmatory test, as the WHO reports that 70% of reported cases of BU are confirmed by PCR detection of DNA.^1,4 Unfortunately, many BU-endemic areas lack feasible access to perform confirmatory tests such as PCR. Antigen detection assays, loop-mediated isothermal amplification tests, and detection of mycolactone by thinlayer chromatography are being developed to create more rapid and sensitive testing for BU.¹²

The lack of diagnostic testing for BU means physicians must rely on clinical diagnosis.¹ However, the differential diagnosis is extensive and includes ulcers due to diabetes and arterial and venous insufficiency, cutaneous leishmaniasis, and Haemophilus ducreyi ulcers.⁵ Despite the broad differential, Eddyani et al¹² found that BU diagnosed clinically by physicians had a sensitivity of 92%.

Treatment

Surgery was the first-line treatment for BU before the introduction of antibiotics for this condition. Antibiotics have created better outcomes with increased cure rates and decreased amputation.⁴

Pharmacotherapy—In the early 2000s, the WHO recommended a treatment regimen of once-daily 10 mg/kg rifampin (oral) and 15 mg/kg streptomycin ( intramuscular) for 8 weeks. This treatment protocol is effective for lesions measuring less than 10 cm in diameter and has an average cure rate of 50%.⁵ Unfortunately, streptomycin is associated with ototoxicity and nephrotoxicity.^1,4 Clinicians should be aware that 1.9% to 26% of patients may have paradoxical worsening of BU early during antibiotic use due to increased host inflammatory response, but it subsides with continued treatment.^1,4

Researchers in Australia have begun testing and using rifampin plus oral clarithromycin, ciprofloxacin, or moxifloxacin for 3 months. A common combination is oncedaily 10 mg/kg rifampicin and 400 mg/kg moxifloxacin.¹ After multiple randomized controlled trials showed the efficacy of rifampicin in combination with clarithromycin, many physicians now recommend 10 mg/kg of rifampicin once daily and 7.5 mg/kg of clarithromycin twice daily.^1,5 When BU is severe, intravenous amikacin and oral rifampin can be used for 4 to 8 weeks.⁵

Wound Management and Surgical Considerations—Since BU can cause extensive widespread ulceration, daily wound care is recommended. Clinicians should note that patients often experience pain during wound dressing, as gauze impairs dermal regeneration and adheres to wounds. A second-line treatment to combat patients’ intolerance to gauze placement—especially for large BU lesions causing mobility issues—includes surgical debridement with wide margins and grafting 4 weeks after antibiotic therapy. This surgical procedure also can treat the releasing contractures that BU is known to cause.¹ Severe cases of BU also can be treated with physiotherapy to prevent further disability.⁵

If histologic analysis of the margins reveals the presence of acid-fast bacilli and granulomas, the probability of future recurrence is high. In those instances, antibiotic therapy is given for prevention. In Australia, the Consensus Council Conference has recommended the removal of not only necrotic tissue but also a small margin of normal tissue to prevent the spread leading to recurrence.^1,5,8

Prevention—Multiple prevention techniques have been suggested to combat BU. Long sleeves and pants should be worn outdoors along with insect repellents in BU-endemic areas. Comprehensive—but perhaps impractical—prevention measures include avoidance of swimming and aquatic activities such as boating and fishing in BU-endemic areas. In the event of a skin abrasion, the wound should be cleaned and covered promptly.

There is no vaccine currently available for BU. Bacillus Calmette—Guérin vaccination can provide minimal protection against disseminated BU but with a short-term response.⁵ Fortunately, M ulcerans–specific vaccines are being developed. Currently, tested vaccines target an enzyme called mycolyl transferase, which is essential for the stability of the mycobacterial cell wall and could have powerful implications in preventing these ulcers. These mycolyl transferase–directed vaccines need to be further explored in the plight against BU.^1,5,8

Final Thoughts

Buruli ulcer remains a considerable public health challenge in endemic regions, with substantial morbidity and potential long-term disability. Hence, continued research into its transmission mechanisms, treatment options, and preventive measures is crucial for reducing the impact of this disease on affected populations.

Buruli ulcer (BU) is a potentially disabling necrotizing skin and soft tissue disease caused by Mycobacterium ulcerans infection.^1,2 Buruli ulcer is most common in hot and humid climates and has caused considerable morbidity in Western African countries (Côte d’Ivoire, Ghana, and Benin account for 73% of annual cases) and the temperate areas of Australia (283 reported cases in 2017).^1-4 In fact, the first recognizable cases of BU were described in 6 Australian individuals living in a riverine area in 1948, although the term Buruli ulcer is derived from the increased number of cases reported from Buruli county in Uganda near the Nile River.^1,3,4

From 2002 to 2017, 66,000 cases of BU were reported in 33 countries.¹ While the focal distribution has been demonstrated in the tropical areas of Sri Lanka, Malaysia, Papua New Guinea, Peru, and Mexico,⁴ nontropical nations such as Japan also are affected. Since 1981, 66 cases have been reported in Japan with M ulcerans subspecies—primarily Shinshuense, which has adapted to higher latitudes.¹ Herein, we provide an overview of the pathogenesis, clinical presentation, and treatment of BU and highlight aquatic insects and mosquitoes as possible vectors of transmission.

Pathogenesis

Mycobacterium ulcerans is a nontuberculous mycobacterium and ubiquitous acid-fast gram-positive bacillus that can be cultured using a Lowenstein-Jensen agar and has a doubling rate of 48 hours.^1,5 It produces the small 174-kb plasmid pMUM001-encoded compound mycolactone, a pathogenic toxin that causes immunosuppression, analgesia, and cytotoxic-associated tissue necrosis.^1,5-9

Mycolactone is a polyketide macrolide with a 12-membrane lactone with 2 attached acyl side chains.^1,7 Mycolactone is synthesized by the giant polyketide synthetases of M ulcerans. Mycolactone post-transcriptionally inhibits the development of lipopolysaccharide-dependent proinflammatory mediators—specifically by blocking protein translocation from the cytosol into the endoplasmic reticulum by targeting the SEC61 translocon.^1,6 The lack of translocation of 30% to 50% of proteins leads to cellular stress and apoptosis mediated by Bim/Bcl2. A single point mutation in the SEC61 translocon subunit alpha 1 gene (SEC61A1) is associated with resistance to the cytotoxic effects of mycolactone.¹

There are divergent hypotheses regarding the relationship of mycolactone to the Wiskott-Aldrich syndrome protein, with some researchers suggesting that mycolactone can attach to this protein, leading to cell detachment and death.⁷ However, others have proposed that mycolactone inhibits mTOR, activating the Wiskott-Aldrich syndrome protein and leading to subsequent extensive cytoskeleton remodeling.¹ Mycolactone also can cause hypoesthesia, either by activating type 2 angiotensin II receptors and creating downstream neuron hyperpolarization or by killing Schwann cells.¹

Transmission

Buruli ulcer caused by M ulcerans has a poorly understood transmission mechanism, and further studies are required to understand the underlying pathophysiology to decrease transmission rates and associated morbidity. Buruli ulcer is widely accepted to be transmitted to humans via predominantly water-rich environments; most cases occur around slow-moving and still bodies of water such as swamps, ponds, and marshes.¹Mycobacterium ulcerans DNA has been found in fish, water insects, and snails.^1,4 It also has been present in samples from aquatic insects such as Hemiptera (water strider), Naucoridae (creeping water bugs and saucer bugs), and Belostomatidae (giant water bugs) in West Africa and also from Aulacodes feces and moss.¹

Variations in geographic climate may lead to different modes of transmission of BU. For example, mosquitoes have been studied as a potential vector for BU in the temperate climate of Australia.² However, more data are needed from other countries to support mosquitoes as possible vectors. Wallace et al¹⁰ performed a study that showed skin puncture from insect bites or other injuries increases the chance of transmitting M ulcerans in the environment to the skin.

Clinical Presentation

Buruli ulcer most often manifests in healthy children younger than 15 years.^1,8 Potential risk factors include residing near a contaminated water source, swimming in a river, and being bitten by an insect in a river during the rainy season. Lack of protective clothing and mosquito nets also have been proposed as considerable risk factors for BU.² Genetic polymorphism in the solute carrier family 11 member 1 gene (SLC11A1) may increase the risk for BU with M ulcerans transmission. It is essential to understand that infection with M ulcerans does not always lead to the development of BU.¹

Buruli ulcer often begins as a painless nodule or papule that patients may confuse with an insect bite. Within a couple of weeks, the induration will grow into ill-defined edematous plaques that gradually turn into necrotic skin, which will eventually slough off to create painless to mildly painful irregular skin ulceration (Figure).¹¹ The surrounding uninvolved skin often is edematous and pigmented. Unfortunately, deep ulcerations can lead to osteomyelitis with exposure of the underlying bone. A secondary bacterial infection may be involved if a foul smell accompanies the ulcer. The vast extension of the ulcer has been known to lead to amputations, contractures, or deformities.^1-5 The nodule progression to ulceration varies and can occur within 3 weeks to 1 year of the initial exposure.^1,8

The World Health Organization (WHO) classifies BU into 3 categories: category 1 includes ulcers less than 5 cm in diameter; category 2 involves ulcers that are 5 to 15 cm in diameter; and category 3 involves ulcers that are larger than 15 cm in diameter as well as those involving the breasts, genitals, eyes, bones, or joints.^4,8

Diagnosis

Cultures and microscopic examination of M ulcerans acid-fast bacilli can be used to confirm the diagnosis of BU. However, polymerase chain reaction (PCR) is the best confirmatory test, as the WHO reports that 70% of reported cases of BU are confirmed by PCR detection of DNA.^1,4 Unfortunately, many BU-endemic areas lack feasible access to perform confirmatory tests such as PCR. Antigen detection assays, loop-mediated isothermal amplification tests, and detection of mycolactone by thinlayer chromatography are being developed to create more rapid and sensitive testing for BU.¹²

The lack of diagnostic testing for BU means physicians must rely on clinical diagnosis.¹ However, the differential diagnosis is extensive and includes ulcers due to diabetes and arterial and venous insufficiency, cutaneous leishmaniasis, and Haemophilus ducreyi ulcers.⁵ Despite the broad differential, Eddyani et al¹² found that BU diagnosed clinically by physicians had a sensitivity of 92%.

Treatment

Surgery was the first-line treatment for BU before the introduction of antibiotics for this condition. Antibiotics have created better outcomes with increased cure rates and decreased amputation.⁴

Pharmacotherapy—In the early 2000s, the WHO recommended a treatment regimen of once-daily 10 mg/kg rifampin (oral) and 15 mg/kg streptomycin ( intramuscular) for 8 weeks. This treatment protocol is effective for lesions measuring less than 10 cm in diameter and has an average cure rate of 50%.⁵ Unfortunately, streptomycin is associated with ototoxicity and nephrotoxicity.^1,4 Clinicians should be aware that 1.9% to 26% of patients may have paradoxical worsening of BU early during antibiotic use due to increased host inflammatory response, but it subsides with continued treatment.^1,4

Researchers in Australia have begun testing and using rifampin plus oral clarithromycin, ciprofloxacin, or moxifloxacin for 3 months. A common combination is oncedaily 10 mg/kg rifampicin and 400 mg/kg moxifloxacin.¹ After multiple randomized controlled trials showed the efficacy of rifampicin in combination with clarithromycin, many physicians now recommend 10 mg/kg of rifampicin once daily and 7.5 mg/kg of clarithromycin twice daily.^1,5 When BU is severe, intravenous amikacin and oral rifampin can be used for 4 to 8 weeks.⁵

Wound Management and Surgical Considerations—Since BU can cause extensive widespread ulceration, daily wound care is recommended. Clinicians should note that patients often experience pain during wound dressing, as gauze impairs dermal regeneration and adheres to wounds. A second-line treatment to combat patients’ intolerance to gauze placement—especially for large BU lesions causing mobility issues—includes surgical debridement with wide margins and grafting 4 weeks after antibiotic therapy. This surgical procedure also can treat the releasing contractures that BU is known to cause.¹ Severe cases of BU also can be treated with physiotherapy to prevent further disability.⁵

If histologic analysis of the margins reveals the presence of acid-fast bacilli and granulomas, the probability of future recurrence is high. In those instances, antibiotic therapy is given for prevention. In Australia, the Consensus Council Conference has recommended the removal of not only necrotic tissue but also a small margin of normal tissue to prevent the spread leading to recurrence.^1,5,8

Prevention—Multiple prevention techniques have been suggested to combat BU. Long sleeves and pants should be worn outdoors along with insect repellents in BU-endemic areas. Comprehensive—but perhaps impractical—prevention measures include avoidance of swimming and aquatic activities such as boating and fishing in BU-endemic areas. In the event of a skin abrasion, the wound should be cleaned and covered promptly.

There is no vaccine currently available for BU. Bacillus Calmette—Guérin vaccination can provide minimal protection against disseminated BU but with a short-term response.⁵ Fortunately, M ulcerans–specific vaccines are being developed. Currently, tested vaccines target an enzyme called mycolyl transferase, which is essential for the stability of the mycobacterial cell wall and could have powerful implications in preventing these ulcers. These mycolyl transferase–directed vaccines need to be further explored in the plight against BU.^1,5,8

Final Thoughts

Buruli ulcer remains a considerable public health challenge in endemic regions, with substantial morbidity and potential long-term disability. Hence, continued research into its transmission mechanisms, treatment options, and preventive measures is crucial for reducing the impact of this disease on affected populations.

Buruli ulcer (BU) is a potentially disabling necrotizing skin and soft tissue disease caused by Mycobacterium ulcerans infection.^1,2 Buruli ulcer is most common in hot and humid climates and has caused considerable morbidity in Western African countries (Côte d’Ivoire, Ghana, and Benin account for 73% of annual cases) and the temperate areas of Australia (283 reported cases in 2017).^1-4 In fact, the first recognizable cases of BU were described in 6 Australian individuals living in a riverine area in 1948, although the term Buruli ulcer is derived from the increased number of cases reported from Buruli county in Uganda near the Nile River.^1,3,4

From 2002 to 2017, 66,000 cases of BU were reported in 33 countries.¹ While the focal distribution has been demonstrated in the tropical areas of Sri Lanka, Malaysia, Papua New Guinea, Peru, and Mexico,⁴ nontropical nations such as Japan also are affected. Since 1981, 66 cases have been reported in Japan with M ulcerans subspecies—primarily Shinshuense, which has adapted to higher latitudes.¹ Herein, we provide an overview of the pathogenesis, clinical presentation, and treatment of BU and highlight aquatic insects and mosquitoes as possible vectors of transmission.

Pathogenesis

Mycobacterium ulcerans is a nontuberculous mycobacterium and ubiquitous acid-fast gram-positive bacillus that can be cultured using a Lowenstein-Jensen agar and has a doubling rate of 48 hours.^1,5 It produces the small 174-kb plasmid pMUM001-encoded compound mycolactone, a pathogenic toxin that causes immunosuppression, analgesia, and cytotoxic-associated tissue necrosis.^1,5-9

Mycolactone is a polyketide macrolide with a 12-membrane lactone with 2 attached acyl side chains.^1,7 Mycolactone is synthesized by the giant polyketide synthetases of M ulcerans. Mycolactone post-transcriptionally inhibits the development of lipopolysaccharide-dependent proinflammatory mediators—specifically by blocking protein translocation from the cytosol into the endoplasmic reticulum by targeting the SEC61 translocon.^1,6 The lack of translocation of 30% to 50% of proteins leads to cellular stress and apoptosis mediated by Bim/Bcl2. A single point mutation in the SEC61 translocon subunit alpha 1 gene (SEC61A1) is associated with resistance to the cytotoxic effects of mycolactone.¹

There are divergent hypotheses regarding the relationship of mycolactone to the Wiskott-Aldrich syndrome protein, with some researchers suggesting that mycolactone can attach to this protein, leading to cell detachment and death.⁷ However, others have proposed that mycolactone inhibits mTOR, activating the Wiskott-Aldrich syndrome protein and leading to subsequent extensive cytoskeleton remodeling.¹ Mycolactone also can cause hypoesthesia, either by activating type 2 angiotensin II receptors and creating downstream neuron hyperpolarization or by killing Schwann cells.¹

Transmission

Buruli ulcer caused by M ulcerans has a poorly understood transmission mechanism, and further studies are required to understand the underlying pathophysiology to decrease transmission rates and associated morbidity. Buruli ulcer is widely accepted to be transmitted to humans via predominantly water-rich environments; most cases occur around slow-moving and still bodies of water such as swamps, ponds, and marshes.¹Mycobacterium ulcerans DNA has been found in fish, water insects, and snails.^1,4 It also has been present in samples from aquatic insects such as Hemiptera (water strider), Naucoridae (creeping water bugs and saucer bugs), and Belostomatidae (giant water bugs) in West Africa and also from Aulacodes feces and moss.¹

Variations in geographic climate may lead to different modes of transmission of BU. For example, mosquitoes have been studied as a potential vector for BU in the temperate climate of Australia.² However, more data are needed from other countries to support mosquitoes as possible vectors. Wallace et al¹⁰ performed a study that showed skin puncture from insect bites or other injuries increases the chance of transmitting M ulcerans in the environment to the skin.

Clinical Presentation

Buruli ulcer most often manifests in healthy children younger than 15 years.^1,8 Potential risk factors include residing near a contaminated water source, swimming in a river, and being bitten by an insect in a river during the rainy season. Lack of protective clothing and mosquito nets also have been proposed as considerable risk factors for BU.² Genetic polymorphism in the solute carrier family 11 member 1 gene (SLC11A1) may increase the risk for BU with M ulcerans transmission. It is essential to understand that infection with M ulcerans does not always lead to the development of BU.¹

Buruli ulcer often begins as a painless nodule or papule that patients may confuse with an insect bite. Within a couple of weeks, the induration will grow into ill-defined edematous plaques that gradually turn into necrotic skin, which will eventually slough off to create painless to mildly painful irregular skin ulceration (Figure).¹¹ The surrounding uninvolved skin often is edematous and pigmented. Unfortunately, deep ulcerations can lead to osteomyelitis with exposure of the underlying bone. A secondary bacterial infection may be involved if a foul smell accompanies the ulcer. The vast extension of the ulcer has been known to lead to amputations, contractures, or deformities.^1-5 The nodule progression to ulceration varies and can occur within 3 weeks to 1 year of the initial exposure.^1,8

The World Health Organization (WHO) classifies BU into 3 categories: category 1 includes ulcers less than 5 cm in diameter; category 2 involves ulcers that are 5 to 15 cm in diameter; and category 3 involves ulcers that are larger than 15 cm in diameter as well as those involving the breasts, genitals, eyes, bones, or joints.^4,8

Diagnosis

Cultures and microscopic examination of M ulcerans acid-fast bacilli can be used to confirm the diagnosis of BU. However, polymerase chain reaction (PCR) is the best confirmatory test, as the WHO reports that 70% of reported cases of BU are confirmed by PCR detection of DNA.^1,4 Unfortunately, many BU-endemic areas lack feasible access to perform confirmatory tests such as PCR. Antigen detection assays, loop-mediated isothermal amplification tests, and detection of mycolactone by thinlayer chromatography are being developed to create more rapid and sensitive testing for BU.¹²

The lack of diagnostic testing for BU means physicians must rely on clinical diagnosis.¹ However, the differential diagnosis is extensive and includes ulcers due to diabetes and arterial and venous insufficiency, cutaneous leishmaniasis, and Haemophilus ducreyi ulcers.⁵ Despite the broad differential, Eddyani et al¹² found that BU diagnosed clinically by physicians had a sensitivity of 92%.

Treatment

Surgery was the first-line treatment for BU before the introduction of antibiotics for this condition. Antibiotics have created better outcomes with increased cure rates and decreased amputation.⁴

Pharmacotherapy—In the early 2000s, the WHO recommended a treatment regimen of once-daily 10 mg/kg rifampin (oral) and 15 mg/kg streptomycin ( intramuscular) for 8 weeks. This treatment protocol is effective for lesions measuring less than 10 cm in diameter and has an average cure rate of 50%.⁵ Unfortunately, streptomycin is associated with ototoxicity and nephrotoxicity.^1,4 Clinicians should be aware that 1.9% to 26% of patients may have paradoxical worsening of BU early during antibiotic use due to increased host inflammatory response, but it subsides with continued treatment.^1,4

Researchers in Australia have begun testing and using rifampin plus oral clarithromycin, ciprofloxacin, or moxifloxacin for 3 months. A common combination is oncedaily 10 mg/kg rifampicin and 400 mg/kg moxifloxacin.¹ After multiple randomized controlled trials showed the efficacy of rifampicin in combination with clarithromycin, many physicians now recommend 10 mg/kg of rifampicin once daily and 7.5 mg/kg of clarithromycin twice daily.^1,5 When BU is severe, intravenous amikacin and oral rifampin can be used for 4 to 8 weeks.⁵

Wound Management and Surgical Considerations—Since BU can cause extensive widespread ulceration, daily wound care is recommended. Clinicians should note that patients often experience pain during wound dressing, as gauze impairs dermal regeneration and adheres to wounds. A second-line treatment to combat patients’ intolerance to gauze placement—especially for large BU lesions causing mobility issues—includes surgical debridement with wide margins and grafting 4 weeks after antibiotic therapy. This surgical procedure also can treat the releasing contractures that BU is known to cause.¹ Severe cases of BU also can be treated with physiotherapy to prevent further disability.⁵

If histologic analysis of the margins reveals the presence of acid-fast bacilli and granulomas, the probability of future recurrence is high. In those instances, antibiotic therapy is given for prevention. In Australia, the Consensus Council Conference has recommended the removal of not only necrotic tissue but also a small margin of normal tissue to prevent the spread leading to recurrence.^1,5,8

Prevention—Multiple prevention techniques have been suggested to combat BU. Long sleeves and pants should be worn outdoors along with insect repellents in BU-endemic areas. Comprehensive—but perhaps impractical—prevention measures include avoidance of swimming and aquatic activities such as boating and fishing in BU-endemic areas. In the event of a skin abrasion, the wound should be cleaned and covered promptly.

There is no vaccine currently available for BU. Bacillus Calmette—Guérin vaccination can provide minimal protection against disseminated BU but with a short-term response.⁵ Fortunately, M ulcerans–specific vaccines are being developed. Currently, tested vaccines target an enzyme called mycolyl transferase, which is essential for the stability of the mycobacterial cell wall and could have powerful implications in preventing these ulcers. These mycolyl transferase–directed vaccines need to be further explored in the plight against BU.^1,5,8

Final Thoughts

Buruli ulcer remains a considerable public health challenge in endemic regions, with substantial morbidity and potential long-term disability. Hence, continued research into its transmission mechanisms, treatment options, and preventive measures is crucial for reducing the impact of this disease on affected populations.

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by firm hyperkeratotic nodules that develop when patients persistently scratch or rub intensely itchy areas of the skin. This potent itch-scratch cycle can be traced back to a dysfunctional interplay between cutaneous nerve fibers and the local immune environment.^1-3 Pruritis lasting at least 6 weeks is a hallmark symptom of PN and can be accompanied by pain and/or a burning sensation.⁴ The lesions are symmetrically distributed in areas that are easy to scratch (eg, arms, legs, trunk), typically sparing the face, palms, and soles; however, facial lesions have been reported in pediatric patients with PN, who also are more likely to have back, hand, and foot involvement.^5,6

Prurigo nodularis can greatly affect patients’ quality of life, leading to increased rates of depression and anxiety.^7-9 Patients with severe symptoms also report increased sleep disturbance, distraction from work, self-consciousness leading to social isolation, and missed days of work/school.⁹ In one study, patients with PN reported missing at least 1 day of work, school, training, or learning; giving up a leisure activity or sport; or refusing an invitation to dinner or a party in the past 3 months due to the disease.¹⁰

Epidemiology

Prurigo nodularis has a prevalence of 72 per 100,000 individuals in the United States,¹¹ most commonly affecting adults aged 51 to 65 years and disproportionately affecting African American and female patients.^12,13 Most patients with PN experience a 2-year delay in diagnosis after initial onset of symptoms.¹⁰ Adults with PN have an increased likelihood of having other dermatologic conditions, including atopic dermatitis (AD) and psoriasis.¹¹ Nearly two-thirds of pediatric patients with PN present with AD, and those with AD showed more resistance to first-line treatment options.⁵

Key Clinical Features

Compared to White patients, who typically present with lesions that appear erythematous or pink, patients with darker skin tones may present with hyperpigmented nodules that are larger and darker.¹² The pruritic nodules often show signs of scratching or picking (eg, excoriations, lichenification, and angulated erosions).⁴

Worth Noting

Diagnosis of PN is made clinically, but skin biopsy may be helpful to rule out alternative diseases. Histologically, the hairy palm sign may be present in addition to other histologic features commonly associated with excessive scratching or rubbing of the skin.

Patients with PN have a high risk for HIV, which is not suprising considering HIV is a known systemic cause of generalized chronic pruritus. Other associations include type 2 diabetes mellitus and thyroid, kidney, and liver disease.^11,13 Work-up for patients with PN should include a complete blood count with differential; liver and renal function testing; and testing for C-reactive protein, thyroid-stimulating hormone, and lactate dehydrogenase.^4,14 Hemoglobin A1c and HIV testing as well as a hepatitis panel also should be considered when appropriate. Because generalized pruritus may be a sign of malignancy, chest radiography and lymph node and abdominal ultrasonography should be performed in patients who have experienced itch for less than 1 year along with B symptoms (fever, night sweats, ≥10% weight loss over 6 months, fatigue).¹⁴ Frequent scratching can disrupt the skin barrier, contributing to the increased risk for skin infections.¹³ All patients with a suspected PN diagnosis also should undergo screening for depression and anxiety, as patients with PN are at an increased risk for these conditions.⁴

Treatment of PN starts with breaking the itch-scratch cycle by addressing the underlying cause of the pruritus. Therapies are focused on addressing the immunologic and neural components of the disease. Topical treatments include moderate to strong corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), capsaicin, and antipruritic emollients. Systemic agents include phototherapy (narrowband UVB or excimer laser), gabapentin, pregabalin, paroxetine, and amitriptyline to address the neural component of itch. Methotrexate or cyclosporine can be used to address the immunologic component of PN and diminish the itch. That said, methotrexate and cyclosporine often are inadequate to control pruritus.¹⁰ Of note, sedating antihistamines are not effective in treating itch in PN but can be used as an adjuvant therapy for sleep disturbances in these patients.¹⁵

The only drugs currently approved by the US Food and Drug Administration to treat PN are the biologics dupilumab (targeting the IL-4 receptor) approved in 2022 and nemolizumab (targeting the IL-31 receptor) approved in 2024.^16-18 The evidence that these injectable biologics work is heartening in a condition that has historically been very challenging to treat.^16,18 It should be noted that the high cost of these 2 medications can restrict access to care for patients who are uninsured or underinsured.

Resolution of a prurigo nodule may result in a hyperpigmented macule taking months to years to fade.

Health Disparity Highlight

Patients with PN have a considerable comorbidity burden, negative impact on quality of life, and increased health care utilization rates.¹² Prurigo nodularis is 3.4 times more common in Black patients than White patients.¹³ Black patients with PN have increased mortality, higher health care utilization rates, and increased systemic inflammation compared to White patients.^12,19,20

Social drivers of health (eg, socioeconomic challenges, education, access to high-quality health care) likely contribute to PN. Historically, there has been a paucity of research on PN, as with most conditions that disproportionately affect patients with skin of color. Several PN clinical trials currently are underway to explore additional therapeutic options.¹¹

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by firm hyperkeratotic nodules that develop when patients persistently scratch or rub intensely itchy areas of the skin. This potent itch-scratch cycle can be traced back to a dysfunctional interplay between cutaneous nerve fibers and the local immune environment.^1-3 Pruritis lasting at least 6 weeks is a hallmark symptom of PN and can be accompanied by pain and/or a burning sensation.⁴ The lesions are symmetrically distributed in areas that are easy to scratch (eg, arms, legs, trunk), typically sparing the face, palms, and soles; however, facial lesions have been reported in pediatric patients with PN, who also are more likely to have back, hand, and foot involvement.^5,6

Prurigo nodularis can greatly affect patients’ quality of life, leading to increased rates of depression and anxiety.^7-9 Patients with severe symptoms also report increased sleep disturbance, distraction from work, self-consciousness leading to social isolation, and missed days of work/school.⁹ In one study, patients with PN reported missing at least 1 day of work, school, training, or learning; giving up a leisure activity or sport; or refusing an invitation to dinner or a party in the past 3 months due to the disease.¹⁰

Epidemiology

Prurigo nodularis has a prevalence of 72 per 100,000 individuals in the United States,¹¹ most commonly affecting adults aged 51 to 65 years and disproportionately affecting African American and female patients.^12,13 Most patients with PN experience a 2-year delay in diagnosis after initial onset of symptoms.¹⁰ Adults with PN have an increased likelihood of having other dermatologic conditions, including atopic dermatitis (AD) and psoriasis.¹¹ Nearly two-thirds of pediatric patients with PN present with AD, and those with AD showed more resistance to first-line treatment options.⁵

Key Clinical Features

Compared to White patients, who typically present with lesions that appear erythematous or pink, patients with darker skin tones may present with hyperpigmented nodules that are larger and darker.¹² The pruritic nodules often show signs of scratching or picking (eg, excoriations, lichenification, and angulated erosions).⁴

Worth Noting

Diagnosis of PN is made clinically, but skin biopsy may be helpful to rule out alternative diseases. Histologically, the hairy palm sign may be present in addition to other histologic features commonly associated with excessive scratching or rubbing of the skin.

Patients with PN have a high risk for HIV, which is not suprising considering HIV is a known systemic cause of generalized chronic pruritus. Other associations include type 2 diabetes mellitus and thyroid, kidney, and liver disease.^11,13 Work-up for patients with PN should include a complete blood count with differential; liver and renal function testing; and testing for C-reactive protein, thyroid-stimulating hormone, and lactate dehydrogenase.^4,14 Hemoglobin A1c and HIV testing as well as a hepatitis panel also should be considered when appropriate. Because generalized pruritus may be a sign of malignancy, chest radiography and lymph node and abdominal ultrasonography should be performed in patients who have experienced itch for less than 1 year along with B symptoms (fever, night sweats, ≥10% weight loss over 6 months, fatigue).¹⁴ Frequent scratching can disrupt the skin barrier, contributing to the increased risk for skin infections.¹³ All patients with a suspected PN diagnosis also should undergo screening for depression and anxiety, as patients with PN are at an increased risk for these conditions.⁴

Treatment of PN starts with breaking the itch-scratch cycle by addressing the underlying cause of the pruritus. Therapies are focused on addressing the immunologic and neural components of the disease. Topical treatments include moderate to strong corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), capsaicin, and antipruritic emollients. Systemic agents include phototherapy (narrowband UVB or excimer laser), gabapentin, pregabalin, paroxetine, and amitriptyline to address the neural component of itch. Methotrexate or cyclosporine can be used to address the immunologic component of PN and diminish the itch. That said, methotrexate and cyclosporine often are inadequate to control pruritus.¹⁰ Of note, sedating antihistamines are not effective in treating itch in PN but can be used as an adjuvant therapy for sleep disturbances in these patients.¹⁵

The only drugs currently approved by the US Food and Drug Administration to treat PN are the biologics dupilumab (targeting the IL-4 receptor) approved in 2022 and nemolizumab (targeting the IL-31 receptor) approved in 2024.^16-18 The evidence that these injectable biologics work is heartening in a condition that has historically been very challenging to treat.^16,18 It should be noted that the high cost of these 2 medications can restrict access to care for patients who are uninsured or underinsured.

Resolution of a prurigo nodule may result in a hyperpigmented macule taking months to years to fade.

Health Disparity Highlight

Patients with PN have a considerable comorbidity burden, negative impact on quality of life, and increased health care utilization rates.¹² Prurigo nodularis is 3.4 times more common in Black patients than White patients.¹³ Black patients with PN have increased mortality, higher health care utilization rates, and increased systemic inflammation compared to White patients.^12,19,20

Social drivers of health (eg, socioeconomic challenges, education, access to high-quality health care) likely contribute to PN. Historically, there has been a paucity of research on PN, as with most conditions that disproportionately affect patients with skin of color. Several PN clinical trials currently are underway to explore additional therapeutic options.¹¹

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by firm hyperkeratotic nodules that develop when patients persistently scratch or rub intensely itchy areas of the skin. This potent itch-scratch cycle can be traced back to a dysfunctional interplay between cutaneous nerve fibers and the local immune environment.^1-3 Pruritis lasting at least 6 weeks is a hallmark symptom of PN and can be accompanied by pain and/or a burning sensation.⁴ The lesions are symmetrically distributed in areas that are easy to scratch (eg, arms, legs, trunk), typically sparing the face, palms, and soles; however, facial lesions have been reported in pediatric patients with PN, who also are more likely to have back, hand, and foot involvement.^5,6

Prurigo nodularis can greatly affect patients’ quality of life, leading to increased rates of depression and anxiety.^7-9 Patients with severe symptoms also report increased sleep disturbance, distraction from work, self-consciousness leading to social isolation, and missed days of work/school.⁹ In one study, patients with PN reported missing at least 1 day of work, school, training, or learning; giving up a leisure activity or sport; or refusing an invitation to dinner or a party in the past 3 months due to the disease.¹⁰

Epidemiology

Prurigo nodularis has a prevalence of 72 per 100,000 individuals in the United States,¹¹ most commonly affecting adults aged 51 to 65 years and disproportionately affecting African American and female patients.^12,13 Most patients with PN experience a 2-year delay in diagnosis after initial onset of symptoms.¹⁰ Adults with PN have an increased likelihood of having other dermatologic conditions, including atopic dermatitis (AD) and psoriasis.¹¹ Nearly two-thirds of pediatric patients with PN present with AD, and those with AD showed more resistance to first-line treatment options.⁵

Key Clinical Features

Compared to White patients, who typically present with lesions that appear erythematous or pink, patients with darker skin tones may present with hyperpigmented nodules that are larger and darker.¹² The pruritic nodules often show signs of scratching or picking (eg, excoriations, lichenification, and angulated erosions).⁴

Worth Noting

Diagnosis of PN is made clinically, but skin biopsy may be helpful to rule out alternative diseases. Histologically, the hairy palm sign may be present in addition to other histologic features commonly associated with excessive scratching or rubbing of the skin.

Patients with PN have a high risk for HIV, which is not suprising considering HIV is a known systemic cause of generalized chronic pruritus. Other associations include type 2 diabetes mellitus and thyroid, kidney, and liver disease.^11,13 Work-up for patients with PN should include a complete blood count with differential; liver and renal function testing; and testing for C-reactive protein, thyroid-stimulating hormone, and lactate dehydrogenase.^4,14 Hemoglobin A1c and HIV testing as well as a hepatitis panel also should be considered when appropriate. Because generalized pruritus may be a sign of malignancy, chest radiography and lymph node and abdominal ultrasonography should be performed in patients who have experienced itch for less than 1 year along with B symptoms (fever, night sweats, ≥10% weight loss over 6 months, fatigue).¹⁴ Frequent scratching can disrupt the skin barrier, contributing to the increased risk for skin infections.¹³ All patients with a suspected PN diagnosis also should undergo screening for depression and anxiety, as patients with PN are at an increased risk for these conditions.⁴

Treatment of PN starts with breaking the itch-scratch cycle by addressing the underlying cause of the pruritus. Therapies are focused on addressing the immunologic and neural components of the disease. Topical treatments include moderate to strong corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), capsaicin, and antipruritic emollients. Systemic agents include phototherapy (narrowband UVB or excimer laser), gabapentin, pregabalin, paroxetine, and amitriptyline to address the neural component of itch. Methotrexate or cyclosporine can be used to address the immunologic component of PN and diminish the itch. That said, methotrexate and cyclosporine often are inadequate to control pruritus.¹⁰ Of note, sedating antihistamines are not effective in treating itch in PN but can be used as an adjuvant therapy for sleep disturbances in these patients.¹⁵

The only drugs currently approved by the US Food and Drug Administration to treat PN are the biologics dupilumab (targeting the IL-4 receptor) approved in 2022 and nemolizumab (targeting the IL-31 receptor) approved in 2024.^16-18 The evidence that these injectable biologics work is heartening in a condition that has historically been very challenging to treat.^16,18 It should be noted that the high cost of these 2 medications can restrict access to care for patients who are uninsured or underinsured.

Resolution of a prurigo nodule may result in a hyperpigmented macule taking months to years to fade.

Health Disparity Highlight

Patients with PN have a considerable comorbidity burden, negative impact on quality of life, and increased health care utilization rates.¹² Prurigo nodularis is 3.4 times more common in Black patients than White patients.¹³ Black patients with PN have increased mortality, higher health care utilization rates, and increased systemic inflammation compared to White patients.^12,19,20

Social drivers of health (eg, socioeconomic challenges, education, access to high-quality health care) likely contribute to PN. Historically, there has been a paucity of research on PN, as with most conditions that disproportionately affect patients with skin of color. Several PN clinical trials currently are underway to explore additional therapeutic options.¹¹

Cyclosporine is a calcineurin inhibitor and immunosuppressive medication with several indications, including prevention of parenchymal organ and bone marrow transplant rejection as well as treatment of numerous dermatologic conditions (eg, psoriasis, atopic dermatitis). Although it is an effective medication, there are many known adverse effects including nephrotoxicity, hypertension, and gingival hyperplasia.¹ Addressing symptomatic cyclosporine-induced gingival hyperplasia can be challenging, especially if continued use of cyclosporine is necessary for adequate control of the underlying disease. We present a simplified approach for conservative management of cyclosporine-induced gingival hyperplasia that allows for continued use of cyclosporine.

Practice Gap

Cyclosporine-induced gingival hyperplasia is a fibrous overgrowth of the interdental papilla and labial gingiva that may lead to gum pain, difficulty eating, gingivitis, and/ or tooth decay or loss.² The condition usually occurs 3 to 6 months after starting cyclosporine but may occur as soon as 1 month later.^1,3 The pathophysiology of this adverse effect is incompletely understood, but several mechanisms have been implicated, including upregulation of the salivary proinflammatory cytokines IL-1α, IL-8, and IL-6.¹ Additionally, patients with cyclosporine-induced gingival hyperplasia have increased bacterial colonization with species such as Porphyromonas gingivalis.⁴ Risk factors for cyclosporine- induced gingival hyperplasia include higher serum concentrations (>400 ng/mL) of cyclosporine, history of gingival hyperplasia, concomitant use of calcium channel blockers, and insufficient oral hygiene.^2,3 A study by Seymour and Smith⁵ found that proper oral hygiene leads to less severe cases of cyclosporine-induced gingival hyperplasia but does not prevent gingival overgrowth. Treatment of cyclosporine-induced gingival hyperplasia traditionally involves targeting oral bacteria and reducing inflammation. Decreasing dental plaque through regular tooth-brushing and interdental cleaning may reduce symptoms such as bleeding and discomfort of the gums.

The intensity of cyclosporine-induced gingival hyperplasia can be reduced with chlorhexidine or azithromycin. Individually, each therapy has been shown to clinically improve cyclosporine-induced gingival hyperplasia; however, to our knowledge the combination of these treatments has not been reported.¹ We present a simplified approach to treating cyclosporine-induced gingival hyperplasia using both azithromycin and chlorhexidine. This conservative approach results in effective and sustained improvement of gingival hyperplasia while allowing patients to continue cyclosporine therapy to control underlying disease with minimal adverse effects.

Technique

Before initiating treatment, it is important to confirm that the etiology of gingival hyperplasia is due to cyclosporine use and rule out nutritional deficiencies and autoimmune conditions as potential causes. Be sure to inquire about nutritional intake, systemic symptoms, and family history of autoimmune conditions. Our approach includes the use of azithromycin 500 mg once daily for 7 days followed by chlorhexidine 0.12% oral solution 15 mL twice daily (swish undiluted for 30 seconds, then spit) for at least 3 months for optimal management of gingival hyperplasia. Chlorhexidine should be continued for at least 6 months to maintain symptom resolution. While cyclosporine therapy may be continued throughout the duration of this regimen, consider switching to other immunosuppressive medications that are not associated with gingival hyperplasia (eg, tacrolimus) if symptoms are severe and/or resistant to therapy.^1,6

We applied this technique to treat cyclosporine-induced gingival hyperplasia in a 28-year-old woman with a 3-year history of primary aplastic anemia. The patient initially presented with pain and bleeding of the gums of several months’ duration and reported experiencing gum pain when eating solid foods. Her medications included cyclosporine 225 mg daily for aplastic anemia and dapsone 100 mg daily for pneumocystis pneumonia prophylaxis, both of which were taken for the past 6 months. Oral examination revealed pink to bright red hyperplastic gingivae (Figure). She had no other symptoms associated with aplastic anemia and no signs of vitamin or nutritional deficiencies. She denied pre-existing periodontitis prior to starting cyclosporine and reported that the symptoms started several months after initiating cyclosporine therapy. Thus, the clinical diagnosis of cyclosporine-induced gingival hyperplasia was made, and treatment with azithromycin and chlorhexidine was initiated with marked reduction in symptoms.

Conservative management of gingival hyperplasia with oral hygiene including regular tooth-brushing and flossing and antimicrobial therapies was preferred in this patient to reduce gum pain and minimize the risk for tooth loss while also limiting the use of surgically invasive interventions. Due to limited therapeutic options for aplastic anemia, continued administration of cyclosporine was necessary in our patient to prevent further complications.

Practice Implications

The precise mechanism by which azithromycin treats gingival hyperplasia is unclear but may involve its antimicrobial and anti-inflammatory properties. Small concentrations of azithromycin have been shown to persist in macrophages and fibroblasts of the gingiva even with short-term administration of 3 to 5 days.⁷ Chlorhexidine is another antimicrobial agent often used in oral rinse solutions to decrease plaque formation and prevent gingivitis. Chlorhexidine can reduce cyclosporine-induced gingival overgrowth when used twice daily.⁸ After rinsing with chlorhexidine, saliva exhibits antibacterial activity for up to 5 hours; however, tooth and gum discoloration may occur.⁸

Recurrence of gingival hyperplasia is likely if cyclosporine is not discontinued or maintained with treatment.³ Conventional gingivectomy should be considered for cases in which conservative treatment is ineffective, aesthetic concerns arise, or gingival hyperplasia persists for more than 6 to 12 months after discontinuing cyclosporine.¹

We theorize that the microbial properties of azithromycin and chlorhexidine help reduce periodontal inflammation and bacterial overgrowth in patients with cyclosporine-induced gingival hyperplasia, which allows for restoration of gingival health. Our case highlights the efficacy of our treatment approach using a 7-day course of azithromycin followed by twice-daily use of chlorhexidine oral rinse in the treatment of cyclosporine-induced gingival hyperplasia with continued use of cyclosporine.

Cyclosporine is a calcineurin inhibitor and immunosuppressive medication with several indications, including prevention of parenchymal organ and bone marrow transplant rejection as well as treatment of numerous dermatologic conditions (eg, psoriasis, atopic dermatitis). Although it is an effective medication, there are many known adverse effects including nephrotoxicity, hypertension, and gingival hyperplasia.¹ Addressing symptomatic cyclosporine-induced gingival hyperplasia can be challenging, especially if continued use of cyclosporine is necessary for adequate control of the underlying disease. We present a simplified approach for conservative management of cyclosporine-induced gingival hyperplasia that allows for continued use of cyclosporine.

Practice Gap

Cyclosporine-induced gingival hyperplasia is a fibrous overgrowth of the interdental papilla and labial gingiva that may lead to gum pain, difficulty eating, gingivitis, and/ or tooth decay or loss.² The condition usually occurs 3 to 6 months after starting cyclosporine but may occur as soon as 1 month later.^1,3 The pathophysiology of this adverse effect is incompletely understood, but several mechanisms have been implicated, including upregulation of the salivary proinflammatory cytokines IL-1α, IL-8, and IL-6.¹ Additionally, patients with cyclosporine-induced gingival hyperplasia have increased bacterial colonization with species such as Porphyromonas gingivalis.⁴ Risk factors for cyclosporine- induced gingival hyperplasia include higher serum concentrations (>400 ng/mL) of cyclosporine, history of gingival hyperplasia, concomitant use of calcium channel blockers, and insufficient oral hygiene.^2,3 A study by Seymour and Smith⁵ found that proper oral hygiene leads to less severe cases of cyclosporine-induced gingival hyperplasia but does not prevent gingival overgrowth. Treatment of cyclosporine-induced gingival hyperplasia traditionally involves targeting oral bacteria and reducing inflammation. Decreasing dental plaque through regular tooth-brushing and interdental cleaning may reduce symptoms such as bleeding and discomfort of the gums.

The intensity of cyclosporine-induced gingival hyperplasia can be reduced with chlorhexidine or azithromycin. Individually, each therapy has been shown to clinically improve cyclosporine-induced gingival hyperplasia; however, to our knowledge the combination of these treatments has not been reported.¹ We present a simplified approach to treating cyclosporine-induced gingival hyperplasia using both azithromycin and chlorhexidine. This conservative approach results in effective and sustained improvement of gingival hyperplasia while allowing patients to continue cyclosporine therapy to control underlying disease with minimal adverse effects.

Technique

Before initiating treatment, it is important to confirm that the etiology of gingival hyperplasia is due to cyclosporine use and rule out nutritional deficiencies and autoimmune conditions as potential causes. Be sure to inquire about nutritional intake, systemic symptoms, and family history of autoimmune conditions. Our approach includes the use of azithromycin 500 mg once daily for 7 days followed by chlorhexidine 0.12% oral solution 15 mL twice daily (swish undiluted for 30 seconds, then spit) for at least 3 months for optimal management of gingival hyperplasia. Chlorhexidine should be continued for at least 6 months to maintain symptom resolution. While cyclosporine therapy may be continued throughout the duration of this regimen, consider switching to other immunosuppressive medications that are not associated with gingival hyperplasia (eg, tacrolimus) if symptoms are severe and/or resistant to therapy.^1,6

We applied this technique to treat cyclosporine-induced gingival hyperplasia in a 28-year-old woman with a 3-year history of primary aplastic anemia. The patient initially presented with pain and bleeding of the gums of several months’ duration and reported experiencing gum pain when eating solid foods. Her medications included cyclosporine 225 mg daily for aplastic anemia and dapsone 100 mg daily for pneumocystis pneumonia prophylaxis, both of which were taken for the past 6 months. Oral examination revealed pink to bright red hyperplastic gingivae (Figure). She had no other symptoms associated with aplastic anemia and no signs of vitamin or nutritional deficiencies. She denied pre-existing periodontitis prior to starting cyclosporine and reported that the symptoms started several months after initiating cyclosporine therapy. Thus, the clinical diagnosis of cyclosporine-induced gingival hyperplasia was made, and treatment with azithromycin and chlorhexidine was initiated with marked reduction in symptoms.

Conservative management of gingival hyperplasia with oral hygiene including regular tooth-brushing and flossing and antimicrobial therapies was preferred in this patient to reduce gum pain and minimize the risk for tooth loss while also limiting the use of surgically invasive interventions. Due to limited therapeutic options for aplastic anemia, continued administration of cyclosporine was necessary in our patient to prevent further complications.

Practice Implications

The precise mechanism by which azithromycin treats gingival hyperplasia is unclear but may involve its antimicrobial and anti-inflammatory properties. Small concentrations of azithromycin have been shown to persist in macrophages and fibroblasts of the gingiva even with short-term administration of 3 to 5 days.⁷ Chlorhexidine is another antimicrobial agent often used in oral rinse solutions to decrease plaque formation and prevent gingivitis. Chlorhexidine can reduce cyclosporine-induced gingival overgrowth when used twice daily.⁸ After rinsing with chlorhexidine, saliva exhibits antibacterial activity for up to 5 hours; however, tooth and gum discoloration may occur.⁸

Recurrence of gingival hyperplasia is likely if cyclosporine is not discontinued or maintained with treatment.³ Conventional gingivectomy should be considered for cases in which conservative treatment is ineffective, aesthetic concerns arise, or gingival hyperplasia persists for more than 6 to 12 months after discontinuing cyclosporine.¹

We theorize that the microbial properties of azithromycin and chlorhexidine help reduce periodontal inflammation and bacterial overgrowth in patients with cyclosporine-induced gingival hyperplasia, which allows for restoration of gingival health. Our case highlights the efficacy of our treatment approach using a 7-day course of azithromycin followed by twice-daily use of chlorhexidine oral rinse in the treatment of cyclosporine-induced gingival hyperplasia with continued use of cyclosporine.

Cyclosporine is a calcineurin inhibitor and immunosuppressive medication with several indications, including prevention of parenchymal organ and bone marrow transplant rejection as well as treatment of numerous dermatologic conditions (eg, psoriasis, atopic dermatitis). Although it is an effective medication, there are many known adverse effects including nephrotoxicity, hypertension, and gingival hyperplasia.¹ Addressing symptomatic cyclosporine-induced gingival hyperplasia can be challenging, especially if continued use of cyclosporine is necessary for adequate control of the underlying disease. We present a simplified approach for conservative management of cyclosporine-induced gingival hyperplasia that allows for continued use of cyclosporine.

Practice Gap

Cyclosporine-induced gingival hyperplasia is a fibrous overgrowth of the interdental papilla and labial gingiva that may lead to gum pain, difficulty eating, gingivitis, and/ or tooth decay or loss.² The condition usually occurs 3 to 6 months after starting cyclosporine but may occur as soon as 1 month later.^1,3 The pathophysiology of this adverse effect is incompletely understood, but several mechanisms have been implicated, including upregulation of the salivary proinflammatory cytokines IL-1α, IL-8, and IL-6.¹ Additionally, patients with cyclosporine-induced gingival hyperplasia have increased bacterial colonization with species such as Porphyromonas gingivalis.⁴ Risk factors for cyclosporine- induced gingival hyperplasia include higher serum concentrations (>400 ng/mL) of cyclosporine, history of gingival hyperplasia, concomitant use of calcium channel blockers, and insufficient oral hygiene.^2,3 A study by Seymour and Smith⁵ found that proper oral hygiene leads to less severe cases of cyclosporine-induced gingival hyperplasia but does not prevent gingival overgrowth. Treatment of cyclosporine-induced gingival hyperplasia traditionally involves targeting oral bacteria and reducing inflammation. Decreasing dental plaque through regular tooth-brushing and interdental cleaning may reduce symptoms such as bleeding and discomfort of the gums.

The intensity of cyclosporine-induced gingival hyperplasia can be reduced with chlorhexidine or azithromycin. Individually, each therapy has been shown to clinically improve cyclosporine-induced gingival hyperplasia; however, to our knowledge the combination of these treatments has not been reported.¹ We present a simplified approach to treating cyclosporine-induced gingival hyperplasia using both azithromycin and chlorhexidine. This conservative approach results in effective and sustained improvement of gingival hyperplasia while allowing patients to continue cyclosporine therapy to control underlying disease with minimal adverse effects.

Technique

Before initiating treatment, it is important to confirm that the etiology of gingival hyperplasia is due to cyclosporine use and rule out nutritional deficiencies and autoimmune conditions as potential causes. Be sure to inquire about nutritional intake, systemic symptoms, and family history of autoimmune conditions. Our approach includes the use of azithromycin 500 mg once daily for 7 days followed by chlorhexidine 0.12% oral solution 15 mL twice daily (swish undiluted for 30 seconds, then spit) for at least 3 months for optimal management of gingival hyperplasia. Chlorhexidine should be continued for at least 6 months to maintain symptom resolution. While cyclosporine therapy may be continued throughout the duration of this regimen, consider switching to other immunosuppressive medications that are not associated with gingival hyperplasia (eg, tacrolimus) if symptoms are severe and/or resistant to therapy.^1,6

We applied this technique to treat cyclosporine-induced gingival hyperplasia in a 28-year-old woman with a 3-year history of primary aplastic anemia. The patient initially presented with pain and bleeding of the gums of several months’ duration and reported experiencing gum pain when eating solid foods. Her medications included cyclosporine 225 mg daily for aplastic anemia and dapsone 100 mg daily for pneumocystis pneumonia prophylaxis, both of which were taken for the past 6 months. Oral examination revealed pink to bright red hyperplastic gingivae (Figure). She had no other symptoms associated with aplastic anemia and no signs of vitamin or nutritional deficiencies. She denied pre-existing periodontitis prior to starting cyclosporine and reported that the symptoms started several months after initiating cyclosporine therapy. Thus, the clinical diagnosis of cyclosporine-induced gingival hyperplasia was made, and treatment with azithromycin and chlorhexidine was initiated with marked reduction in symptoms.

Conservative management of gingival hyperplasia with oral hygiene including regular tooth-brushing and flossing and antimicrobial therapies was preferred in this patient to reduce gum pain and minimize the risk for tooth loss while also limiting the use of surgically invasive interventions. Due to limited therapeutic options for aplastic anemia, continued administration of cyclosporine was necessary in our patient to prevent further complications.

Practice Implications

The precise mechanism by which azithromycin treats gingival hyperplasia is unclear but may involve its antimicrobial and anti-inflammatory properties. Small concentrations of azithromycin have been shown to persist in macrophages and fibroblasts of the gingiva even with short-term administration of 3 to 5 days.⁷ Chlorhexidine is another antimicrobial agent often used in oral rinse solutions to decrease plaque formation and prevent gingivitis. Chlorhexidine can reduce cyclosporine-induced gingival overgrowth when used twice daily.⁸ After rinsing with chlorhexidine, saliva exhibits antibacterial activity for up to 5 hours; however, tooth and gum discoloration may occur.⁸

Recurrence of gingival hyperplasia is likely if cyclosporine is not discontinued or maintained with treatment.³ Conventional gingivectomy should be considered for cases in which conservative treatment is ineffective, aesthetic concerns arise, or gingival hyperplasia persists for more than 6 to 12 months after discontinuing cyclosporine.¹

We theorize that the microbial properties of azithromycin and chlorhexidine help reduce periodontal inflammation and bacterial overgrowth in patients with cyclosporine-induced gingival hyperplasia, which allows for restoration of gingival health. Our case highlights the efficacy of our treatment approach using a 7-day course of azithromycin followed by twice-daily use of chlorhexidine oral rinse in the treatment of cyclosporine-induced gingival hyperplasia with continued use of cyclosporine.

The recent Supreme Court ruling that struck down affirmative action¹ has caused many initiatives aimed at promoting diversity, equity, and inclusion (DEI) to fall under scrutiny; however, the American Academy of Dermatology (AAD) published a statement of intent in 2022 recognizing and committing to DEI as a priority in the specialty.² In this study, we used a formal survey to investigate the perceptions of dermatology program directors (PDs) on DEI programming from the AAD and how DEI is integrated into the resident selection process at varying institutions.

Methods

We conducted a cross-sectional study of dermatology PDs across the United States from April 2024 to July 2024. Program directors were contacted via the Association of Professors of Dermatology PD listserve, which includes all 103 PDs who are members of the organization. Personalized survey links were created and sent individually to each PD’s email address. Thirty responses were received. All survey responses were captured anonymously. The survey consisted of 17 questions focusing on dermatology PD demographics and opinions on DEI initiatives in the AAD and in the dermatology resident selection process. Data were collected using Qualtrics survey tools and analyzed using Qualtrics reports.

Results

Demographics—A total of 30 completed surveys were received. Thirty-three percent (10/30) of respondents were from the Midwest, and 23% (7/30) were from the Northeast. The next most represented region was the West, with 20% (6/30) of respondents. The Southeast and Southwest were the least represented regions captured in our survey, accounting for 13% (4/30) and 10% (3/30) of respondents, respectively. After answering this initial demographic question, 1 respondent stopped the survey, bringing our new total to 29 respondents.

Most (66% [19/29]) of the survey respondents had served as PDs for 5 years or less. Sixty-nine percent (20/29) identified as female, while 31% (9/29) identified as male. Seventy-two percent (21/29) identified as White, 17% (5/29) identified as Asian, 3% (1/29) identified as Black/African American, 3% (1/29) identified as Hispanic or Latinx, and 3% (1/29) identified as mixed race.

Opinions on DEI Initiatives—When asked about their satisfaction level with the current amount of DEI efforts within the AAD, 17% (5/29) of respondents said they were very satisfied, 59% (17/29) said they were satisfied, 17% (5/29) said they were neutral, and 7% (2/29) said they were dissatisfied. Given that none of the questions were mandatory to answer before proceeding with the survey, there were variable response rates to each of the remaining questions, which may have caused respondents to answer only questions they felt strongly about.

Twenty respondents answered when prompted to further classify their level of satisfaction: 70% (14/20) said there should be more DEI efforts through the AAD providing financial support, and 50% (10/20) wanted more nonfinancial support. When given the opportunity to specify which DEI initiatives should be enhanced, the majority (67% [14/21]) of PDs chose the AAD’s health disparities curriculum, followed by the Diversity Mentorship Program (52% [11/21]), AAD Diversity Toolkit (43% [9/21]), and the Skin of Color Curriculum (43% [9/21]). Thiry-three percent (7/30) of PDs wanted enhancement of Medicine Without Barriers: Overcoming Unintended Bias in Practice (an AAD educational resource), and 19% (4/21) of respondents did not think any of the AAD’s DEI initiatives needed to be enhanced. There were 14 responses to a question about choosing which DEI initiatives to reduce with singular votes (7% [1/14] each) to reduce Medicine Without Barriers: Overcoming Unintended Bias in Practice and the Skin of Color Curriculum.

Our survey also invited PDs to introduce ideas for new DEI initiatives or programs. The following were suggestions offered by respondents: education for senior members of the AAD on the importance of DEI in dermatology, professional development resources directed toward academic faculty members to prepare them for interacting with and teaching residents from different backgrounds, and more advertisements and support for the AAD’s Diversity Champion Workshop.

DEI in Resident Selection—When asked about the role that DEI plays in how programs develop their match lists for residency, 13% (3/23) of PDs responded that it plays a very large role, 52% (12/23) stated that it plays a large role, 26% (6/23) responded that it plays somewhat of a role, 4% (1/23) stated that it plays a small role, and 4% (1/23) stated that it plays no role. Twenty-four percent (4/17) of respondents were PDs in states that have legislation limiting or defunding DEI initiatives at institutions of higher education. Another 12% (2/17) were from states where such legislation was pending a vote, while 59% (10/17) of respondents indicated that their state had not introduced such legislation. Four percent (1/17) indicated that they were from a state that had introduced legislation to limit or defund DEI initiatives that failed to pass. Only 17 respondents answered this question, which may be due to a lack of awareness among respondents of state-specific legislation on limiting or defunding DEI initiatives.

Resident Selection Factors—Ninety-six percent (22/23) of PDs stated that their residency program uses a holistic review that takes into account factors such as experiences (eg, volunteer work, research endeavors), personal attributes, and metrics in a balanced manner. No PDs offered United States Medical Licensing Examination Step score cutoffs or medical school clerkship cutoff grades. When asked to rank the importance placed on individual factors in the residency application, the following were ranked from most to least important in the process: performance on clerkships/rotations, performance on interviews, letters of recommendation, clerkship grades, United States Medical Licensing Examination Step scores, research content/ quality, race/ethnicity, history of teaching and mentorship, volunteering, and research amount. When asked to indicate the most pertinent factors used to incorporate DEI in resident selection, the most popular factor was lived experience/life, which was chosen by 90% (18/20) of PDs followed by 75% (15/20) of respondents incorporating underrepresented in medicine (URM) status (including Black, Latinx, and Native American applicants) and 70% (4/20) incorporating socioeconomic status. Sexual orientation and geographic ties of the applicant to the region of the residency program was incorporated by 45% (9/20) of respondents, and other characteristics of race and sex each were incorporated by 30% (6/20) of respondents. Religion was the least incorporated, with 10% (2/20) of PDs selecting this classification. In considering URM status when choosing dermatology residents, 100% (11/11) of respondents indicated that their institution promotes diversity as a part of the recruitment process. Eighty-two percent (9/11) of respondents try to recruit URM applicants to reflect their patient population, 82% (9/11) try as part of a belief that a diverse group benefits everyone in their program, and 45% (5/11) try in order to address societal inequities and as a broader mission to diversify the health care workforce. Seventy-three percent (8/11) indicated that they pay attention to URM status throughout the application process.

Comment

Diversity in the US population is steadily increasing. Within the past decade, the diversity index (the probability that 2 people chosen at random will be from different racial and ethnic groups) has grown from 54.9% in 2010 to 61.1% in 2020.³ There was a 24.9% increase in population groups other than non-Hispanic Whites from 2010 to 2020, an increase in diversity that was present in every region of the United States.⁴ The field of dermatology already does not reflect the racial distribution of the nation,⁴ with Black individuals accounting for 13.7% of the nation’s population but only 3% of dermatologists; similarly, Hispanic individuals account for 19.5% of the population but only comprise 4.2% of dermatologists.^5,6 There is overwhelming evidence that patients prefer to be diagnosed and treated by physicians who reflect their own demographics.⁷ Furthermore, physicians who prescribe treatment plans that reflect and respect socioeconomic and religious beliefs of the populations they serve enable patients to meet treatment expectations and experience better outcomes.⁸ Direct action is required to ensure that the specialty more accurately represents the evolving demographics of the country. This can be accomplished in myriad ways, including but not limited to cultural humility training⁹ for current dermatologists and trainees and recruitment of a more diverse workforce. These measures can ultimately improve treatment approaches and outcomes for dermatologic conditions across various groups.¹⁰

There are efforts by various dermatologic organizations, including the AAD, Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance, Skin of Color Society, Women’s Dermatologic Society, and American Society for Dermatologic Surgery, that are focused on promoting DEI through research, education, and mentorship of potential future dermatologists.¹¹ However, the perceptions, opinions, and selection process instituted by PDs are most consequential in determining the diversity of the specialty, as PDs are at the forefront of establishing the next generation of dermatologists. Through this study, we have found that most PDs recognize the importance of diversity in residency education and recruitment without it being the only deciding factor.

The main limitation of this study was the small sample size, which may not adequately represent all dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education as a result of selection bias toward respondents who were more likely to participate in survey-based research on topics of DEI.

Conclusion

This study revealed that, among dermatology residency PDs, there is interest in modifying the resources and initiatives surrounding DEI in the field. It also revealed that DEI remains a consideration in the resident selection process despite the recent Supreme Court ruling. In conclusion, there is an eagerness among dermatology PDs to incorporate DEI into resident selection even though gaps in knowledge and awareness remain.

The recent Supreme Court ruling that struck down affirmative action¹ has caused many initiatives aimed at promoting diversity, equity, and inclusion (DEI) to fall under scrutiny; however, the American Academy of Dermatology (AAD) published a statement of intent in 2022 recognizing and committing to DEI as a priority in the specialty.² In this study, we used a formal survey to investigate the perceptions of dermatology program directors (PDs) on DEI programming from the AAD and how DEI is integrated into the resident selection process at varying institutions.

Methods

We conducted a cross-sectional study of dermatology PDs across the United States from April 2024 to July 2024. Program directors were contacted via the Association of Professors of Dermatology PD listserve, which includes all 103 PDs who are members of the organization. Personalized survey links were created and sent individually to each PD’s email address. Thirty responses were received. All survey responses were captured anonymously. The survey consisted of 17 questions focusing on dermatology PD demographics and opinions on DEI initiatives in the AAD and in the dermatology resident selection process. Data were collected using Qualtrics survey tools and analyzed using Qualtrics reports.

Results

Demographics—A total of 30 completed surveys were received. Thirty-three percent (10/30) of respondents were from the Midwest, and 23% (7/30) were from the Northeast. The next most represented region was the West, with 20% (6/30) of respondents. The Southeast and Southwest were the least represented regions captured in our survey, accounting for 13% (4/30) and 10% (3/30) of respondents, respectively. After answering this initial demographic question, 1 respondent stopped the survey, bringing our new total to 29 respondents.

Most (66% [19/29]) of the survey respondents had served as PDs for 5 years or less. Sixty-nine percent (20/29) identified as female, while 31% (9/29) identified as male. Seventy-two percent (21/29) identified as White, 17% (5/29) identified as Asian, 3% (1/29) identified as Black/African American, 3% (1/29) identified as Hispanic or Latinx, and 3% (1/29) identified as mixed race.

Opinions on DEI Initiatives—When asked about their satisfaction level with the current amount of DEI efforts within the AAD, 17% (5/29) of respondents said they were very satisfied, 59% (17/29) said they were satisfied, 17% (5/29) said they were neutral, and 7% (2/29) said they were dissatisfied. Given that none of the questions were mandatory to answer before proceeding with the survey, there were variable response rates to each of the remaining questions, which may have caused respondents to answer only questions they felt strongly about.

Twenty respondents answered when prompted to further classify their level of satisfaction: 70% (14/20) said there should be more DEI efforts through the AAD providing financial support, and 50% (10/20) wanted more nonfinancial support. When given the opportunity to specify which DEI initiatives should be enhanced, the majority (67% [14/21]) of PDs chose the AAD’s health disparities curriculum, followed by the Diversity Mentorship Program (52% [11/21]), AAD Diversity Toolkit (43% [9/21]), and the Skin of Color Curriculum (43% [9/21]). Thiry-three percent (7/30) of PDs wanted enhancement of Medicine Without Barriers: Overcoming Unintended Bias in Practice (an AAD educational resource), and 19% (4/21) of respondents did not think any of the AAD’s DEI initiatives needed to be enhanced. There were 14 responses to a question about choosing which DEI initiatives to reduce with singular votes (7% [1/14] each) to reduce Medicine Without Barriers: Overcoming Unintended Bias in Practice and the Skin of Color Curriculum.

Our survey also invited PDs to introduce ideas for new DEI initiatives or programs. The following were suggestions offered by respondents: education for senior members of the AAD on the importance of DEI in dermatology, professional development resources directed toward academic faculty members to prepare them for interacting with and teaching residents from different backgrounds, and more advertisements and support for the AAD’s Diversity Champion Workshop.

DEI in Resident Selection—When asked about the role that DEI plays in how programs develop their match lists for residency, 13% (3/23) of PDs responded that it plays a very large role, 52% (12/23) stated that it plays a large role, 26% (6/23) responded that it plays somewhat of a role, 4% (1/23) stated that it plays a small role, and 4% (1/23) stated that it plays no role. Twenty-four percent (4/17) of respondents were PDs in states that have legislation limiting or defunding DEI initiatives at institutions of higher education. Another 12% (2/17) were from states where such legislation was pending a vote, while 59% (10/17) of respondents indicated that their state had not introduced such legislation. Four percent (1/17) indicated that they were from a state that had introduced legislation to limit or defund DEI initiatives that failed to pass. Only 17 respondents answered this question, which may be due to a lack of awareness among respondents of state-specific legislation on limiting or defunding DEI initiatives.

Resident Selection Factors—Ninety-six percent (22/23) of PDs stated that their residency program uses a holistic review that takes into account factors such as experiences (eg, volunteer work, research endeavors), personal attributes, and metrics in a balanced manner. No PDs offered United States Medical Licensing Examination Step score cutoffs or medical school clerkship cutoff grades. When asked to rank the importance placed on individual factors in the residency application, the following were ranked from most to least important in the process: performance on clerkships/rotations, performance on interviews, letters of recommendation, clerkship grades, United States Medical Licensing Examination Step scores, research content/ quality, race/ethnicity, history of teaching and mentorship, volunteering, and research amount. When asked to indicate the most pertinent factors used to incorporate DEI in resident selection, the most popular factor was lived experience/life, which was chosen by 90% (18/20) of PDs followed by 75% (15/20) of respondents incorporating underrepresented in medicine (URM) status (including Black, Latinx, and Native American applicants) and 70% (4/20) incorporating socioeconomic status. Sexual orientation and geographic ties of the applicant to the region of the residency program was incorporated by 45% (9/20) of respondents, and other characteristics of race and sex each were incorporated by 30% (6/20) of respondents. Religion was the least incorporated, with 10% (2/20) of PDs selecting this classification. In considering URM status when choosing dermatology residents, 100% (11/11) of respondents indicated that their institution promotes diversity as a part of the recruitment process. Eighty-two percent (9/11) of respondents try to recruit URM applicants to reflect their patient population, 82% (9/11) try as part of a belief that a diverse group benefits everyone in their program, and 45% (5/11) try in order to address societal inequities and as a broader mission to diversify the health care workforce. Seventy-three percent (8/11) indicated that they pay attention to URM status throughout the application process.

Comment

Diversity in the US population is steadily increasing. Within the past decade, the diversity index (the probability that 2 people chosen at random will be from different racial and ethnic groups) has grown from 54.9% in 2010 to 61.1% in 2020.³ There was a 24.9% increase in population groups other than non-Hispanic Whites from 2010 to 2020, an increase in diversity that was present in every region of the United States.⁴ The field of dermatology already does not reflect the racial distribution of the nation,⁴ with Black individuals accounting for 13.7% of the nation’s population but only 3% of dermatologists; similarly, Hispanic individuals account for 19.5% of the population but only comprise 4.2% of dermatologists.^5,6 There is overwhelming evidence that patients prefer to be diagnosed and treated by physicians who reflect their own demographics.⁷ Furthermore, physicians who prescribe treatment plans that reflect and respect socioeconomic and religious beliefs of the populations they serve enable patients to meet treatment expectations and experience better outcomes.⁸ Direct action is required to ensure that the specialty more accurately represents the evolving demographics of the country. This can be accomplished in myriad ways, including but not limited to cultural humility training⁹ for current dermatologists and trainees and recruitment of a more diverse workforce. These measures can ultimately improve treatment approaches and outcomes for dermatologic conditions across various groups.¹⁰

There are efforts by various dermatologic organizations, including the AAD, Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance, Skin of Color Society, Women’s Dermatologic Society, and American Society for Dermatologic Surgery, that are focused on promoting DEI through research, education, and mentorship of potential future dermatologists.¹¹ However, the perceptions, opinions, and selection process instituted by PDs are most consequential in determining the diversity of the specialty, as PDs are at the forefront of establishing the next generation of dermatologists. Through this study, we have found that most PDs recognize the importance of diversity in residency education and recruitment without it being the only deciding factor.

The main limitation of this study was the small sample size, which may not adequately represent all dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education as a result of selection bias toward respondents who were more likely to participate in survey-based research on topics of DEI.

Conclusion

This study revealed that, among dermatology residency PDs, there is interest in modifying the resources and initiatives surrounding DEI in the field. It also revealed that DEI remains a consideration in the resident selection process despite the recent Supreme Court ruling. In conclusion, there is an eagerness among dermatology PDs to incorporate DEI into resident selection even though gaps in knowledge and awareness remain.

The recent Supreme Court ruling that struck down affirmative action¹ has caused many initiatives aimed at promoting diversity, equity, and inclusion (DEI) to fall under scrutiny; however, the American Academy of Dermatology (AAD) published a statement of intent in 2022 recognizing and committing to DEI as a priority in the specialty.² In this study, we used a formal survey to investigate the perceptions of dermatology program directors (PDs) on DEI programming from the AAD and how DEI is integrated into the resident selection process at varying institutions.

Methods

We conducted a cross-sectional study of dermatology PDs across the United States from April 2024 to July 2024. Program directors were contacted via the Association of Professors of Dermatology PD listserve, which includes all 103 PDs who are members of the organization. Personalized survey links were created and sent individually to each PD’s email address. Thirty responses were received. All survey responses were captured anonymously. The survey consisted of 17 questions focusing on dermatology PD demographics and opinions on DEI initiatives in the AAD and in the dermatology resident selection process. Data were collected using Qualtrics survey tools and analyzed using Qualtrics reports.

Results

Demographics—A total of 30 completed surveys were received. Thirty-three percent (10/30) of respondents were from the Midwest, and 23% (7/30) were from the Northeast. The next most represented region was the West, with 20% (6/30) of respondents. The Southeast and Southwest were the least represented regions captured in our survey, accounting for 13% (4/30) and 10% (3/30) of respondents, respectively. After answering this initial demographic question, 1 respondent stopped the survey, bringing our new total to 29 respondents.

Most (66% [19/29]) of the survey respondents had served as PDs for 5 years or less. Sixty-nine percent (20/29) identified as female, while 31% (9/29) identified as male. Seventy-two percent (21/29) identified as White, 17% (5/29) identified as Asian, 3% (1/29) identified as Black/African American, 3% (1/29) identified as Hispanic or Latinx, and 3% (1/29) identified as mixed race.

Opinions on DEI Initiatives—When asked about their satisfaction level with the current amount of DEI efforts within the AAD, 17% (5/29) of respondents said they were very satisfied, 59% (17/29) said they were satisfied, 17% (5/29) said they were neutral, and 7% (2/29) said they were dissatisfied. Given that none of the questions were mandatory to answer before proceeding with the survey, there were variable response rates to each of the remaining questions, which may have caused respondents to answer only questions they felt strongly about.

Twenty respondents answered when prompted to further classify their level of satisfaction: 70% (14/20) said there should be more DEI efforts through the AAD providing financial support, and 50% (10/20) wanted more nonfinancial support. When given the opportunity to specify which DEI initiatives should be enhanced, the majority (67% [14/21]) of PDs chose the AAD’s health disparities curriculum, followed by the Diversity Mentorship Program (52% [11/21]), AAD Diversity Toolkit (43% [9/21]), and the Skin of Color Curriculum (43% [9/21]). Thiry-three percent (7/30) of PDs wanted enhancement of Medicine Without Barriers: Overcoming Unintended Bias in Practice (an AAD educational resource), and 19% (4/21) of respondents did not think any of the AAD’s DEI initiatives needed to be enhanced. There were 14 responses to a question about choosing which DEI initiatives to reduce with singular votes (7% [1/14] each) to reduce Medicine Without Barriers: Overcoming Unintended Bias in Practice and the Skin of Color Curriculum.

Our survey also invited PDs to introduce ideas for new DEI initiatives or programs. The following were suggestions offered by respondents: education for senior members of the AAD on the importance of DEI in dermatology, professional development resources directed toward academic faculty members to prepare them for interacting with and teaching residents from different backgrounds, and more advertisements and support for the AAD’s Diversity Champion Workshop.

DEI in Resident Selection—When asked about the role that DEI plays in how programs develop their match lists for residency, 13% (3/23) of PDs responded that it plays a very large role, 52% (12/23) stated that it plays a large role, 26% (6/23) responded that it plays somewhat of a role, 4% (1/23) stated that it plays a small role, and 4% (1/23) stated that it plays no role. Twenty-four percent (4/17) of respondents were PDs in states that have legislation limiting or defunding DEI initiatives at institutions of higher education. Another 12% (2/17) were from states where such legislation was pending a vote, while 59% (10/17) of respondents indicated that their state had not introduced such legislation. Four percent (1/17) indicated that they were from a state that had introduced legislation to limit or defund DEI initiatives that failed to pass. Only 17 respondents answered this question, which may be due to a lack of awareness among respondents of state-specific legislation on limiting or defunding DEI initiatives.

Resident Selection Factors—Ninety-six percent (22/23) of PDs stated that their residency program uses a holistic review that takes into account factors such as experiences (eg, volunteer work, research endeavors), personal attributes, and metrics in a balanced manner. No PDs offered United States Medical Licensing Examination Step score cutoffs or medical school clerkship cutoff grades. When asked to rank the importance placed on individual factors in the residency application, the following were ranked from most to least important in the process: performance on clerkships/rotations, performance on interviews, letters of recommendation, clerkship grades, United States Medical Licensing Examination Step scores, research content/ quality, race/ethnicity, history of teaching and mentorship, volunteering, and research amount. When asked to indicate the most pertinent factors used to incorporate DEI in resident selection, the most popular factor was lived experience/life, which was chosen by 90% (18/20) of PDs followed by 75% (15/20) of respondents incorporating underrepresented in medicine (URM) status (including Black, Latinx, and Native American applicants) and 70% (4/20) incorporating socioeconomic status. Sexual orientation and geographic ties of the applicant to the region of the residency program was incorporated by 45% (9/20) of respondents, and other characteristics of race and sex each were incorporated by 30% (6/20) of respondents. Religion was the least incorporated, with 10% (2/20) of PDs selecting this classification. In considering URM status when choosing dermatology residents, 100% (11/11) of respondents indicated that their institution promotes diversity as a part of the recruitment process. Eighty-two percent (9/11) of respondents try to recruit URM applicants to reflect their patient population, 82% (9/11) try as part of a belief that a diverse group benefits everyone in their program, and 45% (5/11) try in order to address societal inequities and as a broader mission to diversify the health care workforce. Seventy-three percent (8/11) indicated that they pay attention to URM status throughout the application process.

Comment

Diversity in the US population is steadily increasing. Within the past decade, the diversity index (the probability that 2 people chosen at random will be from different racial and ethnic groups) has grown from 54.9% in 2010 to 61.1% in 2020.³ There was a 24.9% increase in population groups other than non-Hispanic Whites from 2010 to 2020, an increase in diversity that was present in every region of the United States.⁴ The field of dermatology already does not reflect the racial distribution of the nation,⁴ with Black individuals accounting for 13.7% of the nation’s population but only 3% of dermatologists; similarly, Hispanic individuals account for 19.5% of the population but only comprise 4.2% of dermatologists.^5,6 There is overwhelming evidence that patients prefer to be diagnosed and treated by physicians who reflect their own demographics.⁷ Furthermore, physicians who prescribe treatment plans that reflect and respect socioeconomic and religious beliefs of the populations they serve enable patients to meet treatment expectations and experience better outcomes.⁸ Direct action is required to ensure that the specialty more accurately represents the evolving demographics of the country. This can be accomplished in myriad ways, including but not limited to cultural humility training⁹ for current dermatologists and trainees and recruitment of a more diverse workforce. These measures can ultimately improve treatment approaches and outcomes for dermatologic conditions across various groups.¹⁰

There are efforts by various dermatologic organizations, including the AAD, Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance, Skin of Color Society, Women’s Dermatologic Society, and American Society for Dermatologic Surgery, that are focused on promoting DEI through research, education, and mentorship of potential future dermatologists.¹¹ However, the perceptions, opinions, and selection process instituted by PDs are most consequential in determining the diversity of the specialty, as PDs are at the forefront of establishing the next generation of dermatologists. Through this study, we have found that most PDs recognize the importance of diversity in residency education and recruitment without it being the only deciding factor.

The main limitation of this study was the small sample size, which may not adequately represent all dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education as a result of selection bias toward respondents who were more likely to participate in survey-based research on topics of DEI.

Conclusion

This study revealed that, among dermatology residency PDs, there is interest in modifying the resources and initiatives surrounding DEI in the field. It also revealed that DEI remains a consideration in the resident selection process despite the recent Supreme Court ruling. In conclusion, there is an eagerness among dermatology PDs to incorporate DEI into resident selection even though gaps in knowledge and awareness remain.

To the Editor:
Psoriasis is a chronic inflammatory skin condition that commonly affects the nail matrix and/or nail bed.¹ Nail involvement is present in up to 50% of patients with cutaneous psoriasis and 80% of patients with psoriatic arthritis.¹ Approximately 5% to 10% of patients with psoriasis demonstrate isolated nail involvement with no skin or joint manifestations.¹ Nail psoriasis can cause severe pain and psychological distress, and extreme cases may cause considerable morbidity and functional impairment.^2,3 Treatment often requires a long duration and may not result in complete recovery due to the slow rate of nail growth. Patients can progress to permanent nail loss if not treated properly, making early recognition and treatment crucial.^1,2 Despite the availability of various treatment options, many cases remain refractory to standard interventions, which underscores the need for novel therapeutic approaches. Herein, we present a severe case of refractory isolated nail psoriasis that was successfully treated with deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor.

A 59-year-old woman presented with a progressive, yellow, hyperkeratotic lesion on the left thumbnail of 2 years’ duration. The patient noted initial discoloration and peeling at the distal end of the nail. Over time, the discoloration progressed to encompass the entire nail. Previous treatments performed by outside physicians including topical corticosteroids, calcineurin inhibitors, and 2 surgeries to remove the nail plate and nail bed all were unsuccessful. The patient also reported severe left thumbnail pain and pruritus that considerably impaired her ability to work. The rest of the nails were unaffected, and she had no personal or family history of psoriasis. Her medical history was notable for hypertension, gastroesophageal reflux disease, and osteomyelitis of the right thumb without nail involvement. Drug allergies included penicillin G benzathine, sulfonamides, amoxicillin, and ciprofloxacin.

Physical examination of the left thumbnail revealed severe yellow, hyperkeratotic, dystrophic changes with a large, yellow, crumbling hyperkeratotic plaque that extended from approximately 1 cm beyond the nail plate to the proximal end of the distal interphalangeal joint, to and along the lateral nail folds, with extensive distal onycholysis. The proximal and lateral nail folds demonstrated erythema as well as maceration that was extremely tender to minimal palpation (Figure 1). No cutaneous lesions were noted elsewhere on the body. The patient had no tenderness, swelling, or stiffness in any of the joints. The differential diagnosis at the time included squamous cell carcinoma of the nail bed and acrodermatitis continua of Hallopeau.

Radiography of the left thumb revealed irregular swelling and nonspecific soft tissue enlargement at the tip of the digit. A nail clipping from the left thumbnail and 3-mm punch biopsies of the lateral and proximal nail folds as well as the horn of the proximal nail fold (Figure 2) were negative for fungus and confirmed psoriasiform dermatitis of the nail.

The patient was started on vinegar soaks (1:1 ratio of vinegar to water) every other day as well as urea cream 10%, ammonium lactate 15%, and petrolatum twice daily for 2 months without considerable improvement. Due to lack of improvement during this 2-month period, the patient subsequently was started on oral deucravacitinib 6 mg/d along with continued use of petrolatum twice daily and vinegar soaks every other day. We selected a trial of deucravacitinib for our patient because of its convenient daily oral dosing and promising clinical evidence.^4,5 After 2 months of treatment with deucravacitinib, the patient reported substantial improvement and satisfaction with the treatment results. Physical examination of the left thumbnail after 2 months of deucravacitinib treatment revealed mildly hyperkeratotic, yellow, dystrophic changes of the nail with notable improvement of the yellow hyperkeratotic plaque on the distal thumbnail. Normal-appearing nail growth was noted at the proximal nail fold, demonstrating considerable improvement from the initial presentation (Figure 3). However, the patient had developed multiple oral ulcers, generalized pruritus, and an annular urticarial plaque on the left arm. As such, deucravacitinib was discontinued after 2 months of treatment. These symptoms resolved within a week of discontinuing deucravacitinib.

While the etiology of nail psoriasis remains unclear, it is believed to be due to a combination of immunologic, genetic, and environmental factors.³ Classical clinical features include nail pitting, leukonychia, onycholysis, nail bed hyperkeratosis, and splinter hemorrhages.^1,3 Our patient exhibited a severe form of nail psoriasis, encompassing the entire nail matrix and bed and extending to the distal interphalangeal joint and lateral nail folds. Previous surgical interventions may have triggered the Koebner phenomenon—which commonly is associated with psoriasis—and resulted in new skin lesions as a secondary response to the surgical trauma.⁶ The severity of the condition profoundly impacted her quality of life and considerably hindered her ability to work.

Treatment for nail psoriasis includes topical or systemic therapies such as corticosteroids, vitamin D analogs, tacrolimus, and tumor necrosis factor α inhibitors.^1,3 Topical treatment is challenging because it is difficult to deliver medication effectively to the nail bed and nail matrix, and patient adherence may be poor.² Although it has been shown to be effective, intralesional triamcinolone can be associated with pain as the most common adverse effect.⁷ Systemic medications such as oral methotrexate also may be effective but are contraindicated in pregnant patients and are associated with potential adverse events (AEs), including hepatotoxicity and acute kidney injury.⁸ The use of biologics may be challenging due to potential AEs and patient reluctance toward injection-based treatments.⁹

Deucravacitinib is a TYK2 inhibitor approved for treatment of plaque psoriasis.¹⁰ Tyrosine kinase 2 is an intracellular kinase that mediates the signaling of IL-23 and other cytokines involved in psoriasis pathogenesis.¹⁰ Deucravacitinib selectively binds to the regulatory domain of TYK2, leading to targeted allosteric inhibition of TYK2-mediated IL-23 and type I interferon signaling.^4,5,10 Compared with biologics, deucravacitinib is advantageous because it can be administered as a daily oral pill, encouraging high patient compliance.

In the POETYK PSO-1 and PSO-2 phase 3 randomized controlled trials, 20.9% (n=332) and 20.3% (n=510) of deucravacitinib-treated patients with moderate to severe nail involvement achieved a Physician’s Global Assessment of Fingernail score of 0/1 compared with 8.8% (n=165) and 7.9% (n=254) of patients in the placebo group, respectively. All patients in these trials had a diagnosis of plaque psoriasis with at least 10% body surface area involvement; none of the patients had isolated nail psoriasis.^4,5

The phase 3 POETYK PSO-1 and PSO-2 trials demonstrated deucravacitinib to be safe and well tolerated with minimal AEs.^4,5 However, the development of AEs in our patient, including oral ulcers and generalized pruritus, underscores the need for close monitoring and consideration of potential risks of treatment. Common AEs associated with deucravacitinib include upper respiratory infections (19.2% [n=840]), increased blood creatine phosphokinase levels (2.7% [n=840]), herpes simplex virus (2.0% [n=840]), and mouth ulcers (1.9% [n=840]).¹¹

Patient education also is a crucial component in the treatment of nail psoriasis. Physicians should emphasize the slow growth of nails and need for prolonged treatment. Clear communication and realistic expectations are essential for ensuring patient adherence to treatment.

Our case highlights the potential efficacy and safety of deucravacitinib for treatment of nail psoriasis, potentially laying the groundwork for future clinical studies. Our patient had a severe case of nail psoriasis that involved the entire nail bed and nail plate, resulting in extreme pain, pruritus, and functional impairment. Her case was unique because involvement was isolated to the nail without any accompanying skin or joint manifestations. She showed a favorable response to deucravacitinib within only 2 months of treatment and exhibited considerable improvement of nail psoriasis, with a reported high level of satisfaction with the treatment. We plan to continue to monitor the patient for long-term results. Future randomized clinical trials with longer follow-up periods are crucial to further establish the efficacy and safety of deucravacitinib for treatment of nail psoriasis.

To the Editor:
Psoriasis is a chronic inflammatory skin condition that commonly affects the nail matrix and/or nail bed.¹ Nail involvement is present in up to 50% of patients with cutaneous psoriasis and 80% of patients with psoriatic arthritis.¹ Approximately 5% to 10% of patients with psoriasis demonstrate isolated nail involvement with no skin or joint manifestations.¹ Nail psoriasis can cause severe pain and psychological distress, and extreme cases may cause considerable morbidity and functional impairment.^2,3 Treatment often requires a long duration and may not result in complete recovery due to the slow rate of nail growth. Patients can progress to permanent nail loss if not treated properly, making early recognition and treatment crucial.^1,2 Despite the availability of various treatment options, many cases remain refractory to standard interventions, which underscores the need for novel therapeutic approaches. Herein, we present a severe case of refractory isolated nail psoriasis that was successfully treated with deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor.

A 59-year-old woman presented with a progressive, yellow, hyperkeratotic lesion on the left thumbnail of 2 years’ duration. The patient noted initial discoloration and peeling at the distal end of the nail. Over time, the discoloration progressed to encompass the entire nail. Previous treatments performed by outside physicians including topical corticosteroids, calcineurin inhibitors, and 2 surgeries to remove the nail plate and nail bed all were unsuccessful. The patient also reported severe left thumbnail pain and pruritus that considerably impaired her ability to work. The rest of the nails were unaffected, and she had no personal or family history of psoriasis. Her medical history was notable for hypertension, gastroesophageal reflux disease, and osteomyelitis of the right thumb without nail involvement. Drug allergies included penicillin G benzathine, sulfonamides, amoxicillin, and ciprofloxacin.

Physical examination of the left thumbnail revealed severe yellow, hyperkeratotic, dystrophic changes with a large, yellow, crumbling hyperkeratotic plaque that extended from approximately 1 cm beyond the nail plate to the proximal end of the distal interphalangeal joint, to and along the lateral nail folds, with extensive distal onycholysis. The proximal and lateral nail folds demonstrated erythema as well as maceration that was extremely tender to minimal palpation (Figure 1). No cutaneous lesions were noted elsewhere on the body. The patient had no tenderness, swelling, or stiffness in any of the joints. The differential diagnosis at the time included squamous cell carcinoma of the nail bed and acrodermatitis continua of Hallopeau.

Radiography of the left thumb revealed irregular swelling and nonspecific soft tissue enlargement at the tip of the digit. A nail clipping from the left thumbnail and 3-mm punch biopsies of the lateral and proximal nail folds as well as the horn of the proximal nail fold (Figure 2) were negative for fungus and confirmed psoriasiform dermatitis of the nail.

The patient was started on vinegar soaks (1:1 ratio of vinegar to water) every other day as well as urea cream 10%, ammonium lactate 15%, and petrolatum twice daily for 2 months without considerable improvement. Due to lack of improvement during this 2-month period, the patient subsequently was started on oral deucravacitinib 6 mg/d along with continued use of petrolatum twice daily and vinegar soaks every other day. We selected a trial of deucravacitinib for our patient because of its convenient daily oral dosing and promising clinical evidence.^4,5 After 2 months of treatment with deucravacitinib, the patient reported substantial improvement and satisfaction with the treatment results. Physical examination of the left thumbnail after 2 months of deucravacitinib treatment revealed mildly hyperkeratotic, yellow, dystrophic changes of the nail with notable improvement of the yellow hyperkeratotic plaque on the distal thumbnail. Normal-appearing nail growth was noted at the proximal nail fold, demonstrating considerable improvement from the initial presentation (Figure 3). However, the patient had developed multiple oral ulcers, generalized pruritus, and an annular urticarial plaque on the left arm. As such, deucravacitinib was discontinued after 2 months of treatment. These symptoms resolved within a week of discontinuing deucravacitinib.

While the etiology of nail psoriasis remains unclear, it is believed to be due to a combination of immunologic, genetic, and environmental factors.³ Classical clinical features include nail pitting, leukonychia, onycholysis, nail bed hyperkeratosis, and splinter hemorrhages.^1,3 Our patient exhibited a severe form of nail psoriasis, encompassing the entire nail matrix and bed and extending to the distal interphalangeal joint and lateral nail folds. Previous surgical interventions may have triggered the Koebner phenomenon—which commonly is associated with psoriasis—and resulted in new skin lesions as a secondary response to the surgical trauma.⁶ The severity of the condition profoundly impacted her quality of life and considerably hindered her ability to work.

Treatment for nail psoriasis includes topical or systemic therapies such as corticosteroids, vitamin D analogs, tacrolimus, and tumor necrosis factor α inhibitors.^1,3 Topical treatment is challenging because it is difficult to deliver medication effectively to the nail bed and nail matrix, and patient adherence may be poor.² Although it has been shown to be effective, intralesional triamcinolone can be associated with pain as the most common adverse effect.⁷ Systemic medications such as oral methotrexate also may be effective but are contraindicated in pregnant patients and are associated with potential adverse events (AEs), including hepatotoxicity and acute kidney injury.⁸ The use of biologics may be challenging due to potential AEs and patient reluctance toward injection-based treatments.⁹

Deucravacitinib is a TYK2 inhibitor approved for treatment of plaque psoriasis.¹⁰ Tyrosine kinase 2 is an intracellular kinase that mediates the signaling of IL-23 and other cytokines involved in psoriasis pathogenesis.¹⁰ Deucravacitinib selectively binds to the regulatory domain of TYK2, leading to targeted allosteric inhibition of TYK2-mediated IL-23 and type I interferon signaling.^4,5,10 Compared with biologics, deucravacitinib is advantageous because it can be administered as a daily oral pill, encouraging high patient compliance.

In the POETYK PSO-1 and PSO-2 phase 3 randomized controlled trials, 20.9% (n=332) and 20.3% (n=510) of deucravacitinib-treated patients with moderate to severe nail involvement achieved a Physician’s Global Assessment of Fingernail score of 0/1 compared with 8.8% (n=165) and 7.9% (n=254) of patients in the placebo group, respectively. All patients in these trials had a diagnosis of plaque psoriasis with at least 10% body surface area involvement; none of the patients had isolated nail psoriasis.^4,5

The phase 3 POETYK PSO-1 and PSO-2 trials demonstrated deucravacitinib to be safe and well tolerated with minimal AEs.^4,5 However, the development of AEs in our patient, including oral ulcers and generalized pruritus, underscores the need for close monitoring and consideration of potential risks of treatment. Common AEs associated with deucravacitinib include upper respiratory infections (19.2% [n=840]), increased blood creatine phosphokinase levels (2.7% [n=840]), herpes simplex virus (2.0% [n=840]), and mouth ulcers (1.9% [n=840]).¹¹

Patient education also is a crucial component in the treatment of nail psoriasis. Physicians should emphasize the slow growth of nails and need for prolonged treatment. Clear communication and realistic expectations are essential for ensuring patient adherence to treatment.

Our case highlights the potential efficacy and safety of deucravacitinib for treatment of nail psoriasis, potentially laying the groundwork for future clinical studies. Our patient had a severe case of nail psoriasis that involved the entire nail bed and nail plate, resulting in extreme pain, pruritus, and functional impairment. Her case was unique because involvement was isolated to the nail without any accompanying skin or joint manifestations. She showed a favorable response to deucravacitinib within only 2 months of treatment and exhibited considerable improvement of nail psoriasis, with a reported high level of satisfaction with the treatment. We plan to continue to monitor the patient for long-term results. Future randomized clinical trials with longer follow-up periods are crucial to further establish the efficacy and safety of deucravacitinib for treatment of nail psoriasis.

To the Editor:
Psoriasis is a chronic inflammatory skin condition that commonly affects the nail matrix and/or nail bed.¹ Nail involvement is present in up to 50% of patients with cutaneous psoriasis and 80% of patients with psoriatic arthritis.¹ Approximately 5% to 10% of patients with psoriasis demonstrate isolated nail involvement with no skin or joint manifestations.¹ Nail psoriasis can cause severe pain and psychological distress, and extreme cases may cause considerable morbidity and functional impairment.^2,3 Treatment often requires a long duration and may not result in complete recovery due to the slow rate of nail growth. Patients can progress to permanent nail loss if not treated properly, making early recognition and treatment crucial.^1,2 Despite the availability of various treatment options, many cases remain refractory to standard interventions, which underscores the need for novel therapeutic approaches. Herein, we present a severe case of refractory isolated nail psoriasis that was successfully treated with deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor.

A 59-year-old woman presented with a progressive, yellow, hyperkeratotic lesion on the left thumbnail of 2 years’ duration. The patient noted initial discoloration and peeling at the distal end of the nail. Over time, the discoloration progressed to encompass the entire nail. Previous treatments performed by outside physicians including topical corticosteroids, calcineurin inhibitors, and 2 surgeries to remove the nail plate and nail bed all were unsuccessful. The patient also reported severe left thumbnail pain and pruritus that considerably impaired her ability to work. The rest of the nails were unaffected, and she had no personal or family history of psoriasis. Her medical history was notable for hypertension, gastroesophageal reflux disease, and osteomyelitis of the right thumb without nail involvement. Drug allergies included penicillin G benzathine, sulfonamides, amoxicillin, and ciprofloxacin.

Physical examination of the left thumbnail revealed severe yellow, hyperkeratotic, dystrophic changes with a large, yellow, crumbling hyperkeratotic plaque that extended from approximately 1 cm beyond the nail plate to the proximal end of the distal interphalangeal joint, to and along the lateral nail folds, with extensive distal onycholysis. The proximal and lateral nail folds demonstrated erythema as well as maceration that was extremely tender to minimal palpation (Figure 1). No cutaneous lesions were noted elsewhere on the body. The patient had no tenderness, swelling, or stiffness in any of the joints. The differential diagnosis at the time included squamous cell carcinoma of the nail bed and acrodermatitis continua of Hallopeau.

Radiography of the left thumb revealed irregular swelling and nonspecific soft tissue enlargement at the tip of the digit. A nail clipping from the left thumbnail and 3-mm punch biopsies of the lateral and proximal nail folds as well as the horn of the proximal nail fold (Figure 2) were negative for fungus and confirmed psoriasiform dermatitis of the nail.

The patient was started on vinegar soaks (1:1 ratio of vinegar to water) every other day as well as urea cream 10%, ammonium lactate 15%, and petrolatum twice daily for 2 months without considerable improvement. Due to lack of improvement during this 2-month period, the patient subsequently was started on oral deucravacitinib 6 mg/d along with continued use of petrolatum twice daily and vinegar soaks every other day. We selected a trial of deucravacitinib for our patient because of its convenient daily oral dosing and promising clinical evidence.^4,5 After 2 months of treatment with deucravacitinib, the patient reported substantial improvement and satisfaction with the treatment results. Physical examination of the left thumbnail after 2 months of deucravacitinib treatment revealed mildly hyperkeratotic, yellow, dystrophic changes of the nail with notable improvement of the yellow hyperkeratotic plaque on the distal thumbnail. Normal-appearing nail growth was noted at the proximal nail fold, demonstrating considerable improvement from the initial presentation (Figure 3). However, the patient had developed multiple oral ulcers, generalized pruritus, and an annular urticarial plaque on the left arm. As such, deucravacitinib was discontinued after 2 months of treatment. These symptoms resolved within a week of discontinuing deucravacitinib.

While the etiology of nail psoriasis remains unclear, it is believed to be due to a combination of immunologic, genetic, and environmental factors.³ Classical clinical features include nail pitting, leukonychia, onycholysis, nail bed hyperkeratosis, and splinter hemorrhages.^1,3 Our patient exhibited a severe form of nail psoriasis, encompassing the entire nail matrix and bed and extending to the distal interphalangeal joint and lateral nail folds. Previous surgical interventions may have triggered the Koebner phenomenon—which commonly is associated with psoriasis—and resulted in new skin lesions as a secondary response to the surgical trauma.⁶ The severity of the condition profoundly impacted her quality of life and considerably hindered her ability to work.

Treatment for nail psoriasis includes topical or systemic therapies such as corticosteroids, vitamin D analogs, tacrolimus, and tumor necrosis factor α inhibitors.^1,3 Topical treatment is challenging because it is difficult to deliver medication effectively to the nail bed and nail matrix, and patient adherence may be poor.² Although it has been shown to be effective, intralesional triamcinolone can be associated with pain as the most common adverse effect.⁷ Systemic medications such as oral methotrexate also may be effective but are contraindicated in pregnant patients and are associated with potential adverse events (AEs), including hepatotoxicity and acute kidney injury.⁸ The use of biologics may be challenging due to potential AEs and patient reluctance toward injection-based treatments.⁹

Deucravacitinib is a TYK2 inhibitor approved for treatment of plaque psoriasis.¹⁰ Tyrosine kinase 2 is an intracellular kinase that mediates the signaling of IL-23 and other cytokines involved in psoriasis pathogenesis.¹⁰ Deucravacitinib selectively binds to the regulatory domain of TYK2, leading to targeted allosteric inhibition of TYK2-mediated IL-23 and type I interferon signaling.^4,5,10 Compared with biologics, deucravacitinib is advantageous because it can be administered as a daily oral pill, encouraging high patient compliance.

In the POETYK PSO-1 and PSO-2 phase 3 randomized controlled trials, 20.9% (n=332) and 20.3% (n=510) of deucravacitinib-treated patients with moderate to severe nail involvement achieved a Physician’s Global Assessment of Fingernail score of 0/1 compared with 8.8% (n=165) and 7.9% (n=254) of patients in the placebo group, respectively. All patients in these trials had a diagnosis of plaque psoriasis with at least 10% body surface area involvement; none of the patients had isolated nail psoriasis.^4,5

The phase 3 POETYK PSO-1 and PSO-2 trials demonstrated deucravacitinib to be safe and well tolerated with minimal AEs.^4,5 However, the development of AEs in our patient, including oral ulcers and generalized pruritus, underscores the need for close monitoring and consideration of potential risks of treatment. Common AEs associated with deucravacitinib include upper respiratory infections (19.2% [n=840]), increased blood creatine phosphokinase levels (2.7% [n=840]), herpes simplex virus (2.0% [n=840]), and mouth ulcers (1.9% [n=840]).¹¹

Patient education also is a crucial component in the treatment of nail psoriasis. Physicians should emphasize the slow growth of nails and need for prolonged treatment. Clear communication and realistic expectations are essential for ensuring patient adherence to treatment.

Our case highlights the potential efficacy and safety of deucravacitinib for treatment of nail psoriasis, potentially laying the groundwork for future clinical studies. Our patient had a severe case of nail psoriasis that involved the entire nail bed and nail plate, resulting in extreme pain, pruritus, and functional impairment. Her case was unique because involvement was isolated to the nail without any accompanying skin or joint manifestations. She showed a favorable response to deucravacitinib within only 2 months of treatment and exhibited considerable improvement of nail psoriasis, with a reported high level of satisfaction with the treatment. We plan to continue to monitor the patient for long-term results. Future randomized clinical trials with longer follow-up periods are crucial to further establish the efficacy and safety of deucravacitinib for treatment of nail psoriasis.

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The Diagnosis: Apocrine Hidrocystoma

Histopathology of the excised nodule revealed a partially collapsed, multiloculated dermal cyst lined with apocrine cells, which was consistent with a diagnosis of apocrine hidrocystoma. Apocrine hidrocystomas are cysts that range from flesh-colored to blue-black and most commonly manifest as solitary lesions on the face, particularly near the eyelids.^1,2 Apocrine hidrocystomas typically range from 1 to 10 mm in diameter and contain fluid that can be colorless, yellow-brown, or blue-black.^1,2 Apocrine hidrocystomas usually are reported between the ages of 30 and 70 years and have no sex predilection.³ 

Apocrine hidrocystomas are thought to develop from adenomatous growth of apocrine sweat gland coils.⁴ The term apocrine hidrocystoma has been used interchangeably with apocrine cystadenoma, though some investigators have recommended using the latter term only for lesions with true papillary projections.⁵ Definitive diagnosis is obtained through histopathology, which typically shows unilocular or multilocular cystic spaces in the dermis lined by an apocrine secretory epithelium. These secretory cells often demonstrate decapitation secretion and apical snouting. The cyst wall may send pseudopapillary projections into the cystic cavity.^1,2 While apocrine and eccrine hidrocystomas previously were recognized as separate entities, it has been suggested that so-called eccrine hidrocystomas are truly apocrine in nature, with a cyst wall that is compressed by the cyst contents.⁴ 

Apocrine hidrocystomas are benign and do not require treatment; however, they may be removed for cosmetic purposes, most commonly via surgical excision. Lesions treated with needle puncture as monotherapy frequently recur. Other successful methods for removal include cyst puncture followed by hypertonic glucose sclerotherapy, trichloroacetic acid injection, botulinum toxin A injection, or CO₂ laser treatment.^3,6 

Several clinical and histopathologic findings can distinguish between apocrine hidrocystomas and other diagnoses in the differential. Lipomas are common benign tumors composed of mature fat that typically manifest as solitary, painless, soft nodules with a normal overlying epidermis. They frequently are distributed on the neck, arms, legs, and buttocks. While the differential for our patient initially included lipoma, these lesions do not contain or release fluid, which was present in our patient. On histopathology, lipoma shows a uniform population of mature fat cells with small, uniform, and eccentric nuclei (Figure 1).⁷ 

Epidermal inclusion cysts are derived from the follicular infundibulum and commonly are found on the face and upper trunk. They manifest as flesh-colored dermal nodules and may have a visible punctum. As opposed to the cystic cavities lined with apocrine cells seen in apocrine hidrocystomas, epidermal inclusion cysts are lined with a stratified squamous epithelium, are filled with laminated keratin, and have a visible granular layer (Figure 2).⁸ 

Pilar cysts, also known as trichilemmal cysts, clinically resemble epidermal inclusion cysts but are derived from the outer root sheath of hair follicles, manifesting as flesh-colored dermal nodules almost always found on the scalp. On histopathology, pilar cysts are lined with stratified squamous epithelial cells without a visible granular layer and are filled with compact eosinophilic keratin (Figure 3).⁸ 

Tubular apocrine adenomas are benign neoplasms of the apocrine glands that manifest as smooth nodules. They are within the same spectrum as papillary eccrine adenomas, appearing more frequently on the legs and less frequently on the face and scalp.⁹ Histopathology generally demonstrates well-circumscribed lobules of tubular structures in the dermis. Similar to apocrine hidrocystomas, tubular apocrine adenomas will demonstrate an inner layer of columnar apocrine cells with decapitation secretion, but the tubular architecture helps differentiate it from other adnexal tumors (Figure 4).¹⁰ 

The clinical manifestation of the apocrine hidrocystoma in our patient was unusual due to its size and location. Apocrine hidrocystomas rarely are found on the scalp, with few other cases found in the literature. To our knowledge, this is the largest apocrine hidrocystoma found on the scalp to date, although there is at least 1 other published case of an apocrine hidrocystoma on the scalp measuring at least 3 cm in diameter.¹¹ Our case highlights the importance of recognizing atypical manifestations of apocrine hidrocystomas, as a lesion on the midline scalp that discharges a thin fluid might raise initial concern for an intracranial connection. Awareness of atypical manifestations of common lesions can expand dermatologists’ differential diagnoses and help them to reassure patients. 

The Diagnosis: Apocrine Hidrocystoma

Histopathology of the excised nodule revealed a partially collapsed, multiloculated dermal cyst lined with apocrine cells, which was consistent with a diagnosis of apocrine hidrocystoma. Apocrine hidrocystomas are cysts that range from flesh-colored to blue-black and most commonly manifest as solitary lesions on the face, particularly near the eyelids.^1,2 Apocrine hidrocystomas typically range from 1 to 10 mm in diameter and contain fluid that can be colorless, yellow-brown, or blue-black.^1,2 Apocrine hidrocystomas usually are reported between the ages of 30 and 70 years and have no sex predilection.³ 

Apocrine hidrocystomas are thought to develop from adenomatous growth of apocrine sweat gland coils.⁴ The term apocrine hidrocystoma has been used interchangeably with apocrine cystadenoma, though some investigators have recommended using the latter term only for lesions with true papillary projections.⁵ Definitive diagnosis is obtained through histopathology, which typically shows unilocular or multilocular cystic spaces in the dermis lined by an apocrine secretory epithelium. These secretory cells often demonstrate decapitation secretion and apical snouting. The cyst wall may send pseudopapillary projections into the cystic cavity.^1,2 While apocrine and eccrine hidrocystomas previously were recognized as separate entities, it has been suggested that so-called eccrine hidrocystomas are truly apocrine in nature, with a cyst wall that is compressed by the cyst contents.⁴ 

Apocrine hidrocystomas are benign and do not require treatment; however, they may be removed for cosmetic purposes, most commonly via surgical excision. Lesions treated with needle puncture as monotherapy frequently recur. Other successful methods for removal include cyst puncture followed by hypertonic glucose sclerotherapy, trichloroacetic acid injection, botulinum toxin A injection, or CO₂ laser treatment.^3,6 

Several clinical and histopathologic findings can distinguish between apocrine hidrocystomas and other diagnoses in the differential. Lipomas are common benign tumors composed of mature fat that typically manifest as solitary, painless, soft nodules with a normal overlying epidermis. They frequently are distributed on the neck, arms, legs, and buttocks. While the differential for our patient initially included lipoma, these lesions do not contain or release fluid, which was present in our patient. On histopathology, lipoma shows a uniform population of mature fat cells with small, uniform, and eccentric nuclei (Figure 1).⁷ 

Epidermal inclusion cysts are derived from the follicular infundibulum and commonly are found on the face and upper trunk. They manifest as flesh-colored dermal nodules and may have a visible punctum. As opposed to the cystic cavities lined with apocrine cells seen in apocrine hidrocystomas, epidermal inclusion cysts are lined with a stratified squamous epithelium, are filled with laminated keratin, and have a visible granular layer (Figure 2).⁸ 

Pilar cysts, also known as trichilemmal cysts, clinically resemble epidermal inclusion cysts but are derived from the outer root sheath of hair follicles, manifesting as flesh-colored dermal nodules almost always found on the scalp. On histopathology, pilar cysts are lined with stratified squamous epithelial cells without a visible granular layer and are filled with compact eosinophilic keratin (Figure 3).⁸ 

Tubular apocrine adenomas are benign neoplasms of the apocrine glands that manifest as smooth nodules. They are within the same spectrum as papillary eccrine adenomas, appearing more frequently on the legs and less frequently on the face and scalp.⁹ Histopathology generally demonstrates well-circumscribed lobules of tubular structures in the dermis. Similar to apocrine hidrocystomas, tubular apocrine adenomas will demonstrate an inner layer of columnar apocrine cells with decapitation secretion, but the tubular architecture helps differentiate it from other adnexal tumors (Figure 4).¹⁰ 

The clinical manifestation of the apocrine hidrocystoma in our patient was unusual due to its size and location. Apocrine hidrocystomas rarely are found on the scalp, with few other cases found in the literature. To our knowledge, this is the largest apocrine hidrocystoma found on the scalp to date, although there is at least 1 other published case of an apocrine hidrocystoma on the scalp measuring at least 3 cm in diameter.¹¹ Our case highlights the importance of recognizing atypical manifestations of apocrine hidrocystomas, as a lesion on the midline scalp that discharges a thin fluid might raise initial concern for an intracranial connection. Awareness of atypical manifestations of common lesions can expand dermatologists’ differential diagnoses and help them to reassure patients. 

The Diagnosis: Apocrine Hidrocystoma

Histopathology of the excised nodule revealed a partially collapsed, multiloculated dermal cyst lined with apocrine cells, which was consistent with a diagnosis of apocrine hidrocystoma. Apocrine hidrocystomas are cysts that range from flesh-colored to blue-black and most commonly manifest as solitary lesions on the face, particularly near the eyelids.^1,2 Apocrine hidrocystomas typically range from 1 to 10 mm in diameter and contain fluid that can be colorless, yellow-brown, or blue-black.^1,2 Apocrine hidrocystomas usually are reported between the ages of 30 and 70 years and have no sex predilection.³ 

Apocrine hidrocystomas are thought to develop from adenomatous growth of apocrine sweat gland coils.⁴ The term apocrine hidrocystoma has been used interchangeably with apocrine cystadenoma, though some investigators have recommended using the latter term only for lesions with true papillary projections.⁵ Definitive diagnosis is obtained through histopathology, which typically shows unilocular or multilocular cystic spaces in the dermis lined by an apocrine secretory epithelium. These secretory cells often demonstrate decapitation secretion and apical snouting. The cyst wall may send pseudopapillary projections into the cystic cavity.^1,2 While apocrine and eccrine hidrocystomas previously were recognized as separate entities, it has been suggested that so-called eccrine hidrocystomas are truly apocrine in nature, with a cyst wall that is compressed by the cyst contents.⁴ 

Apocrine hidrocystomas are benign and do not require treatment; however, they may be removed for cosmetic purposes, most commonly via surgical excision. Lesions treated with needle puncture as monotherapy frequently recur. Other successful methods for removal include cyst puncture followed by hypertonic glucose sclerotherapy, trichloroacetic acid injection, botulinum toxin A injection, or CO₂ laser treatment.^3,6 

Several clinical and histopathologic findings can distinguish between apocrine hidrocystomas and other diagnoses in the differential. Lipomas are common benign tumors composed of mature fat that typically manifest as solitary, painless, soft nodules with a normal overlying epidermis. They frequently are distributed on the neck, arms, legs, and buttocks. While the differential for our patient initially included lipoma, these lesions do not contain or release fluid, which was present in our patient. On histopathology, lipoma shows a uniform population of mature fat cells with small, uniform, and eccentric nuclei (Figure 1).⁷ 

Epidermal inclusion cysts are derived from the follicular infundibulum and commonly are found on the face and upper trunk. They manifest as flesh-colored dermal nodules and may have a visible punctum. As opposed to the cystic cavities lined with apocrine cells seen in apocrine hidrocystomas, epidermal inclusion cysts are lined with a stratified squamous epithelium, are filled with laminated keratin, and have a visible granular layer (Figure 2).⁸ 

Pilar cysts, also known as trichilemmal cysts, clinically resemble epidermal inclusion cysts but are derived from the outer root sheath of hair follicles, manifesting as flesh-colored dermal nodules almost always found on the scalp. On histopathology, pilar cysts are lined with stratified squamous epithelial cells without a visible granular layer and are filled with compact eosinophilic keratin (Figure 3).⁸ 

Tubular apocrine adenomas are benign neoplasms of the apocrine glands that manifest as smooth nodules. They are within the same spectrum as papillary eccrine adenomas, appearing more frequently on the legs and less frequently on the face and scalp.⁹ Histopathology generally demonstrates well-circumscribed lobules of tubular structures in the dermis. Similar to apocrine hidrocystomas, tubular apocrine adenomas will demonstrate an inner layer of columnar apocrine cells with decapitation secretion, but the tubular architecture helps differentiate it from other adnexal tumors (Figure 4).¹⁰ 

The clinical manifestation of the apocrine hidrocystoma in our patient was unusual due to its size and location. Apocrine hidrocystomas rarely are found on the scalp, with few other cases found in the literature. To our knowledge, this is the largest apocrine hidrocystoma found on the scalp to date, although there is at least 1 other published case of an apocrine hidrocystoma on the scalp measuring at least 3 cm in diameter.¹¹ Our case highlights the importance of recognizing atypical manifestations of apocrine hidrocystomas, as a lesion on the midline scalp that discharges a thin fluid might raise initial concern for an intracranial connection. Awareness of atypical manifestations of common lesions can expand dermatologists’ differential diagnoses and help them to reassure patients. 

Recently published clinical research in psoriatic arthritis (PsA) has continued to focus on the transition from psoriasis to PsA, comorbidities, and effects of treatments. Garcia-Salinas and colleagues reported results of a large study that investigated 1419 patients with joint pain who were carefully clinically evaluated with imaging (ultrasonography and MRI) and laboratory tests. They found that among patients with arthralgia, 8.4% were at risk of developing PsA (ie, had a personal or family history of psoriasis), with 29% of these patients progressing to PsA within 1 year. Significant predictors of progression included a family history of psoriasis, synovitis detected by power Doppler ultrasound, enthesopathy on ultrasonography, and a low tender joint count. Thus, more than one quarter of patients with psoriasis and joint pain developed PsA in 1 year. Patients with psoriasis and joint pain, especially those with findings on imaging, should be referred to rheumatologists and carefully followed up for early diagnosis of PsA and therefore better outcomes.

Chronic kidney disease (CKD) is a known comorbidity in psoriatic disease but is less well characterised. In a prospective observational cohort study that included 1336 patients with PsA, Kharouf and colleagues reported that 123 (9.2%) had CKD. They demonstrated that diabetes, kidney stones, joint damage, high uric acid levels, and daily use of nonsteroidal anti-inflammatory drugs were associated with development of CKD, whereas methotrexate use had a renoprotective effect. Thus, patients with severe PsA and comorbidities such as diabetes are at higher risk for CKD. Better management of PsA using disease-modifying antirheumatic drugs may reduce the risk. Replication of these findings, especially in terms of the renoprotective effect of methotrexate, is required.

Patients with PsA who do not respond to treatment with tumour necrosis factor (TNF) inhibitors are generally less likely to respond to subsequent therapy. Evaluating newer modes of action in this treatment-resistant PsA population is important. COSMOS was a phase 3b trial that included 285 patients with PsA who had inadequate response or intolerance to TNF inhibitors and were randomly assigned to receive 100 mg guselkumab (a monoclonal antibody targeting interleukin-23; n = 189) or placebo (n = 96). In a post hoc analysis, Gossec and colleagues showed that at week 24, a greater proportion of patients receiving guselkumab vs placebo achieved minimal disease activity (MDA) (14.8% vs 3.1%). Most of the patients who achieved MDA at week 24 maintained the response at week 48. Thus, guselkumab treatment led to sustained MDA over 1 year in patients with PsA who had inadequate response or intolerance to TNF inhibitors.

Achieving MDA was also evaluated in another novel drug for PsA. Deucravacitinib is an oral TYK2 inhibitor that is approved for the treatment of psoriasis and is currently being evaluated in phase 3 PsA trials. In a post hoc analysis of a phase 2 trial that included 203 adults with PsA who did not respond to or were intolerant to one or more prior therapies and were randomly assigned to receive 6 mg or 12 mg deucravacitinib or placebo, Kavanaugh and colleagues found that after 16 weeks, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved MDA (6 mg: 22.9% vs 7.6%; P = .01 and 12 mg: 23.9% vs 7.6%; P = .007). Achieving MDA reflects a state of low disease activity or remission; therefore, these results are very encouraging. Results from phase 3 trials and a formal comparison with other drugs will inform rheumatologists about the place of deucravacitinib in the management of PsA.

Recently published clinical research in psoriatic arthritis (PsA) has continued to focus on the transition from psoriasis to PsA, comorbidities, and effects of treatments. Garcia-Salinas and colleagues reported results of a large study that investigated 1419 patients with joint pain who were carefully clinically evaluated with imaging (ultrasonography and MRI) and laboratory tests. They found that among patients with arthralgia, 8.4% were at risk of developing PsA (ie, had a personal or family history of psoriasis), with 29% of these patients progressing to PsA within 1 year. Significant predictors of progression included a family history of psoriasis, synovitis detected by power Doppler ultrasound, enthesopathy on ultrasonography, and a low tender joint count. Thus, more than one quarter of patients with psoriasis and joint pain developed PsA in 1 year. Patients with psoriasis and joint pain, especially those with findings on imaging, should be referred to rheumatologists and carefully followed up for early diagnosis of PsA and therefore better outcomes.

Chronic kidney disease (CKD) is a known comorbidity in psoriatic disease but is less well characterised. In a prospective observational cohort study that included 1336 patients with PsA, Kharouf and colleagues reported that 123 (9.2%) had CKD. They demonstrated that diabetes, kidney stones, joint damage, high uric acid levels, and daily use of nonsteroidal anti-inflammatory drugs were associated with development of CKD, whereas methotrexate use had a renoprotective effect. Thus, patients with severe PsA and comorbidities such as diabetes are at higher risk for CKD. Better management of PsA using disease-modifying antirheumatic drugs may reduce the risk. Replication of these findings, especially in terms of the renoprotective effect of methotrexate, is required.

Patients with PsA who do not respond to treatment with tumour necrosis factor (TNF) inhibitors are generally less likely to respond to subsequent therapy. Evaluating newer modes of action in this treatment-resistant PsA population is important. COSMOS was a phase 3b trial that included 285 patients with PsA who had inadequate response or intolerance to TNF inhibitors and were randomly assigned to receive 100 mg guselkumab (a monoclonal antibody targeting interleukin-23; n = 189) or placebo (n = 96). In a post hoc analysis, Gossec and colleagues showed that at week 24, a greater proportion of patients receiving guselkumab vs placebo achieved minimal disease activity (MDA) (14.8% vs 3.1%). Most of the patients who achieved MDA at week 24 maintained the response at week 48. Thus, guselkumab treatment led to sustained MDA over 1 year in patients with PsA who had inadequate response or intolerance to TNF inhibitors.

Achieving MDA was also evaluated in another novel drug for PsA. Deucravacitinib is an oral TYK2 inhibitor that is approved for the treatment of psoriasis and is currently being evaluated in phase 3 PsA trials. In a post hoc analysis of a phase 2 trial that included 203 adults with PsA who did not respond to or were intolerant to one or more prior therapies and were randomly assigned to receive 6 mg or 12 mg deucravacitinib or placebo, Kavanaugh and colleagues found that after 16 weeks, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved MDA (6 mg: 22.9% vs 7.6%; P = .01 and 12 mg: 23.9% vs 7.6%; P = .007). Achieving MDA reflects a state of low disease activity or remission; therefore, these results are very encouraging. Results from phase 3 trials and a formal comparison with other drugs will inform rheumatologists about the place of deucravacitinib in the management of PsA.

Recently published clinical research in psoriatic arthritis (PsA) has continued to focus on the transition from psoriasis to PsA, comorbidities, and effects of treatments. Garcia-Salinas and colleagues reported results of a large study that investigated 1419 patients with joint pain who were carefully clinically evaluated with imaging (ultrasonography and MRI) and laboratory tests. They found that among patients with arthralgia, 8.4% were at risk of developing PsA (ie, had a personal or family history of psoriasis), with 29% of these patients progressing to PsA within 1 year. Significant predictors of progression included a family history of psoriasis, synovitis detected by power Doppler ultrasound, enthesopathy on ultrasonography, and a low tender joint count. Thus, more than one quarter of patients with psoriasis and joint pain developed PsA in 1 year. Patients with psoriasis and joint pain, especially those with findings on imaging, should be referred to rheumatologists and carefully followed up for early diagnosis of PsA and therefore better outcomes.

Chronic kidney disease (CKD) is a known comorbidity in psoriatic disease but is less well characterised. In a prospective observational cohort study that included 1336 patients with PsA, Kharouf and colleagues reported that 123 (9.2%) had CKD. They demonstrated that diabetes, kidney stones, joint damage, high uric acid levels, and daily use of nonsteroidal anti-inflammatory drugs were associated with development of CKD, whereas methotrexate use had a renoprotective effect. Thus, patients with severe PsA and comorbidities such as diabetes are at higher risk for CKD. Better management of PsA using disease-modifying antirheumatic drugs may reduce the risk. Replication of these findings, especially in terms of the renoprotective effect of methotrexate, is required.

Patients with PsA who do not respond to treatment with tumour necrosis factor (TNF) inhibitors are generally less likely to respond to subsequent therapy. Evaluating newer modes of action in this treatment-resistant PsA population is important. COSMOS was a phase 3b trial that included 285 patients with PsA who had inadequate response or intolerance to TNF inhibitors and were randomly assigned to receive 100 mg guselkumab (a monoclonal antibody targeting interleukin-23; n = 189) or placebo (n = 96). In a post hoc analysis, Gossec and colleagues showed that at week 24, a greater proportion of patients receiving guselkumab vs placebo achieved minimal disease activity (MDA) (14.8% vs 3.1%). Most of the patients who achieved MDA at week 24 maintained the response at week 48. Thus, guselkumab treatment led to sustained MDA over 1 year in patients with PsA who had inadequate response or intolerance to TNF inhibitors.

Achieving MDA was also evaluated in another novel drug for PsA. Deucravacitinib is an oral TYK2 inhibitor that is approved for the treatment of psoriasis and is currently being evaluated in phase 3 PsA trials. In a post hoc analysis of a phase 2 trial that included 203 adults with PsA who did not respond to or were intolerant to one or more prior therapies and were randomly assigned to receive 6 mg or 12 mg deucravacitinib or placebo, Kavanaugh and colleagues found that after 16 weeks, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved MDA (6 mg: 22.9% vs 7.6%; P = .01 and 12 mg: 23.9% vs 7.6%; P = .007). Achieving MDA reflects a state of low disease activity or remission; therefore, these results are very encouraging. Results from phase 3 trials and a formal comparison with other drugs will inform rheumatologists about the place of deucravacitinib in the management of PsA.