Jared Jagdeo, MD, MS

Visible light is part of the electromagnetic spectrum and is confined to a range of 400 to 700 nm. Visible light phototherapy can be delivered across various wavelengths within this spectrum, with most research focusing on blue light (BL)(400-500 nm) and red light (RL)(600-700 nm). Blue light commonly is used to treat acne as well as actinic keratosis and other inflammatory disorders,^1,2 while RL largely targets signs of skin aging and fibrosis.^2,3 Because of its shorter wavelength, the clinically meaningful skin penetration of BL reaches up to1 mm and is confined to the epidermis; in contrast, RL can access the dermal adnexa due to its penetration depth of more than 2 mm.⁴ Therapeutically, visible light can be utilized alone (eg, photobiomodulation [PBM]) or in combination with a photosensitizing agent (eg, photodynamic therapy [PDT]).^5,6

Our laboratory’s prior research has contributed to a greater understanding of the safety profile of visible light at various wavelengths.^1,3 Specifically, our work has shown that BL (417 nm [range, 412-422 nm]) and RL (633 nm [range, 627-639 nm]) demonstrated no evidence of DNA damage—via no formation of cyclobutane pyrimidine dimers and/or 6-4 photoproducts, the hallmark photolesions caused by UV exposure—in human dermal fibroblasts following visible light exposure at all fluences tested.^1,3 This evidence reinforces the safety of visible light at clinically relevant wavelengths, supporting its integration into dermatologic practice. In this editorial, we highlight the key clinical applications of PBM and PDT and outline safety considerations for visible light-based therapies in dermatologic practice.

Photobiomodulation

Photobiomodulation is a noninvasive treatment in which low-level lasers or light-emitting diodes deliver photons from a nonionizing light source to endogenous photoreceptors, primarily cytochrome C oxidase.^7-9 On the visible light spectrum, PBM primarily encompasses RL.^7-9 Photoactivation leads to production of reactive oxygen species as well as mitochondrial alterations, with resulting modulation of cellular activity.^7-9 Upregulation of cellular activity generally occurs at lower fluences (ie, energy delivered per unit area) of light, whereas higher fluences cause downregulation of cellular activity.⁵

Recent consensus guidelines, established with expert colleagues, define additional key parameters that are crucial to optimizing PBM treatment, including distance from the light source, area of the light beam, wavelength, length of treatment time, and number of treatments.⁵ Understanding the effects of different parameter combinations is essential for clinicians to select the best treatment regimen for each patient. Our laboratory has conducted National Institutes of Health–funded phase 1 and phase 2 clinical trials to determine the safety and efficacy of red-light PBM.^10-13 Additionally, we completed several pilot phase 2 clinical studies with commercially available light-emitting diode face masks using PBM technology, which demonstrated a favorable safety profile and high patient satisfaction across multiple self-reported measures.^14,15 These findings highlight PBM as a reliable and well-tolerated therapeutic approach that can be administered in clinical settings or by patients at home.

Adverse effects of PBM therapy generally are mild and transient, most commonly manifesting as slight irritation and erythema.⁵ Overall, PBM is widely regarded as safe with a favorable and nontoxic profile across treatment settings. Growing evidence supports the role of PBM in managing wound healing, acne, alopecia, and skin aging, among other dermatologic concerns.⁸

Photodynamic Therapy

Photodynamic therapy is a noninvasive procedure during which a photosensitizer—typically 5-aminolevulinic acid (5-ALA) or a derivative, methyl aminolevulinate—reacts with a light source and oxygen, resulting in reactive oxygen species.^6,16 This reaction ultimately triggers targeted cellular destruction of the intended lesional skin but with negligible effects on adjacent nonlesional tissue.⁶ The efficacy of PDT is determined by several parameters, including composition and concentration of the photosensitizer, photosensitizer incubation temperature, and incubation time with the photosensitizer. Methyl aminolevulinate is a lipophilic molecule and may promote greater skin penetration and cellular uptake than 5-ALA, which is a hydrophilic molecule.⁶

Our research further demonstrated that apoptosis increases in a dose- and temperature-dependent manner following 5-ALA exposure, both in cutaneous and mucosal squamous cell carcinoma cells and in human dermal fibroblasts.^17,18 Our mechanistic insights have clinical relevance, as evidenced by an independent pilot study demonstrating that temperature-modulated PDT significantly improved actinic keratosis lesion clearance rates (P<.0001).¹⁹ Additionally, we determined that even short periods of incubation with 5-ALA (ie, 15-30 minutes) result in statistically significant increases in apoptosis (P<.05).²⁰ Thus, these findings highlight that the choice of photosensitizing agent and the administration parameters are critical in determining PDT efficacy as well as the need to optimize clinical protocols.

Photodynamic therapy also has demonstrated general clinical and genotoxic safety, with the most common potential adverse events limited to temporary inflammation, erythema, and discomfort.²¹ A study in murine skin and human keratinocytes revealed that 5-ALA PDT had a photoprotective effect against previous irradiation with UVB (a known inducer of DNA damage) via removal of cyclobutane pyrimidine dimers.²² Thus, PDT has been recognized as a safe and effective therapeutic modality with broad applications in dermatology, including treatment of actinic keratosis and nonmelanoma skin cancers.¹⁶

Clinical Safety, Photoprotection, and Precautions

While visible light has shown substantial therapeutic potential in dermatology, there are several safety measures and precautions to be aware of. Visible light constitutes approximately 44% of the solar output; therefore, precautions against both UV and visible light are recommended for the general population.²³ Cumulative exposure to visible light has been shown to trigger melanogenesis, resulting in persistent erythema, hyperpigmentation, and uneven skin tones across all Fitzpatrick skin types.²⁴ Individuals with skin of color are more photosensitive to visible light due to increased baseline melanin levels.²⁴ Similarly, patients with pigmentary conditions such as melasma and postinflammatory hyperpigmentation may experience worsening of their dermatologic symptoms due to underlying visible light photosensitivity.²⁵

Patients undergoing PBM or PDT could benefit from visible light protection. The primary form of photoprotection against visible light is tinted sunscreen, which contains iron oxides and titanium dioxide.²⁶ Iron (III) oxide is capable of blocking nearly all visible light damage.²⁶ Use of physical barriers such as wavelength-specific sunglasses and wide-brimmed hats also is important for preventing photodamage from visible light.²⁶

Final Thoughts

Visible light has a role in the treatment of a variety of skin conditions, including actinic keratosis, nonmelanoma skin cancers, acne, wound healing, skin fibrosis, and photodamage. Photobiomodulation and PDT represent 2 noninvasive phototherapeutic options that utilize visible light to enact cellular changes necessary to improve skin health. Integrating visible light phototherapy into standard clinical practice is important for enhancing patient outcomes. Clinicians should remain mindful of the rare pigmentary risks associated with visible light therapy devices. Future research should prioritize optimization of standardized protocols and expansion of clinical indications for visible light phototherapy.

Visible light is part of the electromagnetic spectrum and is confined to a range of 400 to 700 nm. Visible light phototherapy can be delivered across various wavelengths within this spectrum, with most research focusing on blue light (BL)(400-500 nm) and red light (RL)(600-700 nm). Blue light commonly is used to treat acne as well as actinic keratosis and other inflammatory disorders,^1,2 while RL largely targets signs of skin aging and fibrosis.^2,3 Because of its shorter wavelength, the clinically meaningful skin penetration of BL reaches up to1 mm and is confined to the epidermis; in contrast, RL can access the dermal adnexa due to its penetration depth of more than 2 mm.⁴ Therapeutically, visible light can be utilized alone (eg, photobiomodulation [PBM]) or in combination with a photosensitizing agent (eg, photodynamic therapy [PDT]).^5,6

Our laboratory’s prior research has contributed to a greater understanding of the safety profile of visible light at various wavelengths.^1,3 Specifically, our work has shown that BL (417 nm [range, 412-422 nm]) and RL (633 nm [range, 627-639 nm]) demonstrated no evidence of DNA damage—via no formation of cyclobutane pyrimidine dimers and/or 6-4 photoproducts, the hallmark photolesions caused by UV exposure—in human dermal fibroblasts following visible light exposure at all fluences tested.^1,3 This evidence reinforces the safety of visible light at clinically relevant wavelengths, supporting its integration into dermatologic practice. In this editorial, we highlight the key clinical applications of PBM and PDT and outline safety considerations for visible light-based therapies in dermatologic practice.

Photobiomodulation

Photobiomodulation is a noninvasive treatment in which low-level lasers or light-emitting diodes deliver photons from a nonionizing light source to endogenous photoreceptors, primarily cytochrome C oxidase.^7-9 On the visible light spectrum, PBM primarily encompasses RL.^7-9 Photoactivation leads to production of reactive oxygen species as well as mitochondrial alterations, with resulting modulation of cellular activity.^7-9 Upregulation of cellular activity generally occurs at lower fluences (ie, energy delivered per unit area) of light, whereas higher fluences cause downregulation of cellular activity.⁵

Recent consensus guidelines, established with expert colleagues, define additional key parameters that are crucial to optimizing PBM treatment, including distance from the light source, area of the light beam, wavelength, length of treatment time, and number of treatments.⁵ Understanding the effects of different parameter combinations is essential for clinicians to select the best treatment regimen for each patient. Our laboratory has conducted National Institutes of Health–funded phase 1 and phase 2 clinical trials to determine the safety and efficacy of red-light PBM.^10-13 Additionally, we completed several pilot phase 2 clinical studies with commercially available light-emitting diode face masks using PBM technology, which demonstrated a favorable safety profile and high patient satisfaction across multiple self-reported measures.^14,15 These findings highlight PBM as a reliable and well-tolerated therapeutic approach that can be administered in clinical settings or by patients at home.

Adverse effects of PBM therapy generally are mild and transient, most commonly manifesting as slight irritation and erythema.⁵ Overall, PBM is widely regarded as safe with a favorable and nontoxic profile across treatment settings. Growing evidence supports the role of PBM in managing wound healing, acne, alopecia, and skin aging, among other dermatologic concerns.⁸

Photodynamic Therapy

Photodynamic therapy is a noninvasive procedure during which a photosensitizer—typically 5-aminolevulinic acid (5-ALA) or a derivative, methyl aminolevulinate—reacts with a light source and oxygen, resulting in reactive oxygen species.^6,16 This reaction ultimately triggers targeted cellular destruction of the intended lesional skin but with negligible effects on adjacent nonlesional tissue.⁶ The efficacy of PDT is determined by several parameters, including composition and concentration of the photosensitizer, photosensitizer incubation temperature, and incubation time with the photosensitizer. Methyl aminolevulinate is a lipophilic molecule and may promote greater skin penetration and cellular uptake than 5-ALA, which is a hydrophilic molecule.⁶

Our research further demonstrated that apoptosis increases in a dose- and temperature-dependent manner following 5-ALA exposure, both in cutaneous and mucosal squamous cell carcinoma cells and in human dermal fibroblasts.^17,18 Our mechanistic insights have clinical relevance, as evidenced by an independent pilot study demonstrating that temperature-modulated PDT significantly improved actinic keratosis lesion clearance rates (P<.0001).¹⁹ Additionally, we determined that even short periods of incubation with 5-ALA (ie, 15-30 minutes) result in statistically significant increases in apoptosis (P<.05).²⁰ Thus, these findings highlight that the choice of photosensitizing agent and the administration parameters are critical in determining PDT efficacy as well as the need to optimize clinical protocols.

Photodynamic therapy also has demonstrated general clinical and genotoxic safety, with the most common potential adverse events limited to temporary inflammation, erythema, and discomfort.²¹ A study in murine skin and human keratinocytes revealed that 5-ALA PDT had a photoprotective effect against previous irradiation with UVB (a known inducer of DNA damage) via removal of cyclobutane pyrimidine dimers.²² Thus, PDT has been recognized as a safe and effective therapeutic modality with broad applications in dermatology, including treatment of actinic keratosis and nonmelanoma skin cancers.¹⁶

Clinical Safety, Photoprotection, and Precautions

While visible light has shown substantial therapeutic potential in dermatology, there are several safety measures and precautions to be aware of. Visible light constitutes approximately 44% of the solar output; therefore, precautions against both UV and visible light are recommended for the general population.²³ Cumulative exposure to visible light has been shown to trigger melanogenesis, resulting in persistent erythema, hyperpigmentation, and uneven skin tones across all Fitzpatrick skin types.²⁴ Individuals with skin of color are more photosensitive to visible light due to increased baseline melanin levels.²⁴ Similarly, patients with pigmentary conditions such as melasma and postinflammatory hyperpigmentation may experience worsening of their dermatologic symptoms due to underlying visible light photosensitivity.²⁵

Patients undergoing PBM or PDT could benefit from visible light protection. The primary form of photoprotection against visible light is tinted sunscreen, which contains iron oxides and titanium dioxide.²⁶ Iron (III) oxide is capable of blocking nearly all visible light damage.²⁶ Use of physical barriers such as wavelength-specific sunglasses and wide-brimmed hats also is important for preventing photodamage from visible light.²⁶

Final Thoughts

Visible light has a role in the treatment of a variety of skin conditions, including actinic keratosis, nonmelanoma skin cancers, acne, wound healing, skin fibrosis, and photodamage. Photobiomodulation and PDT represent 2 noninvasive phototherapeutic options that utilize visible light to enact cellular changes necessary to improve skin health. Integrating visible light phototherapy into standard clinical practice is important for enhancing patient outcomes. Clinicians should remain mindful of the rare pigmentary risks associated with visible light therapy devices. Future research should prioritize optimization of standardized protocols and expansion of clinical indications for visible light phototherapy.

Visible light is part of the electromagnetic spectrum and is confined to a range of 400 to 700 nm. Visible light phototherapy can be delivered across various wavelengths within this spectrum, with most research focusing on blue light (BL)(400-500 nm) and red light (RL)(600-700 nm). Blue light commonly is used to treat acne as well as actinic keratosis and other inflammatory disorders,^1,2 while RL largely targets signs of skin aging and fibrosis.^2,3 Because of its shorter wavelength, the clinically meaningful skin penetration of BL reaches up to1 mm and is confined to the epidermis; in contrast, RL can access the dermal adnexa due to its penetration depth of more than 2 mm.⁴ Therapeutically, visible light can be utilized alone (eg, photobiomodulation [PBM]) or in combination with a photosensitizing agent (eg, photodynamic therapy [PDT]).^5,6

Our laboratory’s prior research has contributed to a greater understanding of the safety profile of visible light at various wavelengths.^1,3 Specifically, our work has shown that BL (417 nm [range, 412-422 nm]) and RL (633 nm [range, 627-639 nm]) demonstrated no evidence of DNA damage—via no formation of cyclobutane pyrimidine dimers and/or 6-4 photoproducts, the hallmark photolesions caused by UV exposure—in human dermal fibroblasts following visible light exposure at all fluences tested.^1,3 This evidence reinforces the safety of visible light at clinically relevant wavelengths, supporting its integration into dermatologic practice. In this editorial, we highlight the key clinical applications of PBM and PDT and outline safety considerations for visible light-based therapies in dermatologic practice.

Photobiomodulation

Photobiomodulation is a noninvasive treatment in which low-level lasers or light-emitting diodes deliver photons from a nonionizing light source to endogenous photoreceptors, primarily cytochrome C oxidase.^7-9 On the visible light spectrum, PBM primarily encompasses RL.^7-9 Photoactivation leads to production of reactive oxygen species as well as mitochondrial alterations, with resulting modulation of cellular activity.^7-9 Upregulation of cellular activity generally occurs at lower fluences (ie, energy delivered per unit area) of light, whereas higher fluences cause downregulation of cellular activity.⁵

Recent consensus guidelines, established with expert colleagues, define additional key parameters that are crucial to optimizing PBM treatment, including distance from the light source, area of the light beam, wavelength, length of treatment time, and number of treatments.⁵ Understanding the effects of different parameter combinations is essential for clinicians to select the best treatment regimen for each patient. Our laboratory has conducted National Institutes of Health–funded phase 1 and phase 2 clinical trials to determine the safety and efficacy of red-light PBM.^10-13 Additionally, we completed several pilot phase 2 clinical studies with commercially available light-emitting diode face masks using PBM technology, which demonstrated a favorable safety profile and high patient satisfaction across multiple self-reported measures.^14,15 These findings highlight PBM as a reliable and well-tolerated therapeutic approach that can be administered in clinical settings or by patients at home.

Adverse effects of PBM therapy generally are mild and transient, most commonly manifesting as slight irritation and erythema.⁵ Overall, PBM is widely regarded as safe with a favorable and nontoxic profile across treatment settings. Growing evidence supports the role of PBM in managing wound healing, acne, alopecia, and skin aging, among other dermatologic concerns.⁸

Photodynamic Therapy

Photodynamic therapy is a noninvasive procedure during which a photosensitizer—typically 5-aminolevulinic acid (5-ALA) or a derivative, methyl aminolevulinate—reacts with a light source and oxygen, resulting in reactive oxygen species.^6,16 This reaction ultimately triggers targeted cellular destruction of the intended lesional skin but with negligible effects on adjacent nonlesional tissue.⁶ The efficacy of PDT is determined by several parameters, including composition and concentration of the photosensitizer, photosensitizer incubation temperature, and incubation time with the photosensitizer. Methyl aminolevulinate is a lipophilic molecule and may promote greater skin penetration and cellular uptake than 5-ALA, which is a hydrophilic molecule.⁶

Our research further demonstrated that apoptosis increases in a dose- and temperature-dependent manner following 5-ALA exposure, both in cutaneous and mucosal squamous cell carcinoma cells and in human dermal fibroblasts.^17,18 Our mechanistic insights have clinical relevance, as evidenced by an independent pilot study demonstrating that temperature-modulated PDT significantly improved actinic keratosis lesion clearance rates (P<.0001).¹⁹ Additionally, we determined that even short periods of incubation with 5-ALA (ie, 15-30 minutes) result in statistically significant increases in apoptosis (P<.05).²⁰ Thus, these findings highlight that the choice of photosensitizing agent and the administration parameters are critical in determining PDT efficacy as well as the need to optimize clinical protocols.

Photodynamic therapy also has demonstrated general clinical and genotoxic safety, with the most common potential adverse events limited to temporary inflammation, erythema, and discomfort.²¹ A study in murine skin and human keratinocytes revealed that 5-ALA PDT had a photoprotective effect against previous irradiation with UVB (a known inducer of DNA damage) via removal of cyclobutane pyrimidine dimers.²² Thus, PDT has been recognized as a safe and effective therapeutic modality with broad applications in dermatology, including treatment of actinic keratosis and nonmelanoma skin cancers.¹⁶

Clinical Safety, Photoprotection, and Precautions

While visible light has shown substantial therapeutic potential in dermatology, there are several safety measures and precautions to be aware of. Visible light constitutes approximately 44% of the solar output; therefore, precautions against both UV and visible light are recommended for the general population.²³ Cumulative exposure to visible light has been shown to trigger melanogenesis, resulting in persistent erythema, hyperpigmentation, and uneven skin tones across all Fitzpatrick skin types.²⁴ Individuals with skin of color are more photosensitive to visible light due to increased baseline melanin levels.²⁴ Similarly, patients with pigmentary conditions such as melasma and postinflammatory hyperpigmentation may experience worsening of their dermatologic symptoms due to underlying visible light photosensitivity.²⁵

Patients undergoing PBM or PDT could benefit from visible light protection. The primary form of photoprotection against visible light is tinted sunscreen, which contains iron oxides and titanium dioxide.²⁶ Iron (III) oxide is capable of blocking nearly all visible light damage.²⁶ Use of physical barriers such as wavelength-specific sunglasses and wide-brimmed hats also is important for preventing photodamage from visible light.²⁶

Final Thoughts

Visible light has a role in the treatment of a variety of skin conditions, including actinic keratosis, nonmelanoma skin cancers, acne, wound healing, skin fibrosis, and photodamage. Photobiomodulation and PDT represent 2 noninvasive phototherapeutic options that utilize visible light to enact cellular changes necessary to improve skin health. Integrating visible light phototherapy into standard clinical practice is important for enhancing patient outcomes. Clinicians should remain mindful of the rare pigmentary risks associated with visible light therapy devices. Future research should prioritize optimization of standardized protocols and expansion of clinical indications for visible light phototherapy.

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.