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Successful Treatment of Severe Dystrophic Nail Psoriasis With Deucravacitinib
Successful Treatment of Severe Dystrophic Nail Psoriasis With Deucravacitinib
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.
- Hwang JK, Grover C, Iorizzo M, et al. Nail psoriasis and nail lichen planus: updates on diagnosis and management. J Am Acad Dermatol. 2024;90:585-596. doi:10.1016/j.jaad.2023.11.024
- Ji C, Wang H, Bao C, et al. Challenge of nail psoriasis: an update review. Clin Rev Allergy Immunol. 2021;61:377-402. doi:10.1007/s12016-021-08896-9
- Muneer H, Sathe NC, Masood S. Nail psoriasis. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated March 1, 2024. Accessed October 24, 2024. https://www.ncbi.nlm.nih.gov/books/NBK559260/
- Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88:29-39. doi:10.1016/j.jaad.2022.07.002
- Strober B, Thaçi D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88:40-51. doi:10.1016/j.jaad.2022.08.061
- Sanchez DP, Sonthalia S. Koebner phenomenon. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated November 14, 2022. Accessed April 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK553108/
- Grover C, Kharghoria G, Bansal S. Triamcinolone acetonide injections in nail psoriasis: a pragmatic analysis. Skin Appendage Disord. 2024;10:50-59. doi:10.1159/000534699
- Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated August 16, 2023. Accessed April 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556114/
- Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2011:Cd008794. doi:10.1002/14651858.CD008794.pub2
- Thaçi D, Strober B, Gordon KB, et al. Deucravacitinib in moderate to severe psoriasis: clinical and quality-of-life outcomes in a phase 2 trial. Dermatol Ther (Heidelb). 2022;12:495-510. doi:10.1007/s13555-021-00649-y
- Week 0-16: demonstrated safety profile. Bristol-Myers Squibb. 2024. Accessed October 24, 2024. https://www.sotyktuhcp.com/safety-profile?cid=sem_2465603&gclid=CjwKCAiA9ourBhAVEiwA3L5RFnyYqmxbqkz1_zBNPz3dcyHKCSFf1XQ-7acznV0XbR5DDJHYkZcKJxoCWN0QAvD_BwE&gclsrc=aw.ds
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.
- Hwang JK, Grover C, Iorizzo M, et al. Nail psoriasis and nail lichen planus: updates on diagnosis and management. J Am Acad Dermatol. 2024;90:585-596. doi:10.1016/j.jaad.2023.11.024
- Ji C, Wang H, Bao C, et al. Challenge of nail psoriasis: an update review. Clin Rev Allergy Immunol. 2021;61:377-402. doi:10.1007/s12016-021-08896-9
- Muneer H, Sathe NC, Masood S. Nail psoriasis. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated March 1, 2024. Accessed October 24, 2024. https://www.ncbi.nlm.nih.gov/books/NBK559260/
- Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88:29-39. doi:10.1016/j.jaad.2022.07.002
- Strober B, Thaçi D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88:40-51. doi:10.1016/j.jaad.2022.08.061
- Sanchez DP, Sonthalia S. Koebner phenomenon. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated November 14, 2022. Accessed April 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK553108/
- Grover C, Kharghoria G, Bansal S. Triamcinolone acetonide injections in nail psoriasis: a pragmatic analysis. Skin Appendage Disord. 2024;10:50-59. doi:10.1159/000534699
- Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated August 16, 2023. Accessed April 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556114/
- Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2011:Cd008794. doi:10.1002/14651858.CD008794.pub2
- Thaçi D, Strober B, Gordon KB, et al. Deucravacitinib in moderate to severe psoriasis: clinical and quality-of-life outcomes in a phase 2 trial. Dermatol Ther (Heidelb). 2022;12:495-510. doi:10.1007/s13555-021-00649-y
- Week 0-16: demonstrated safety profile. Bristol-Myers Squibb. 2024. Accessed October 24, 2024. https://www.sotyktuhcp.com/safety-profile?cid=sem_2465603&gclid=CjwKCAiA9ourBhAVEiwA3L5RFnyYqmxbqkz1_zBNPz3dcyHKCSFf1XQ-7acznV0XbR5DDJHYkZcKJxoCWN0QAvD_BwE&gclsrc=aw.ds
- Hwang JK, Grover C, Iorizzo M, et al. Nail psoriasis and nail lichen planus: updates on diagnosis and management. J Am Acad Dermatol. 2024;90:585-596. doi:10.1016/j.jaad.2023.11.024
- Ji C, Wang H, Bao C, et al. Challenge of nail psoriasis: an update review. Clin Rev Allergy Immunol. 2021;61:377-402. doi:10.1007/s12016-021-08896-9
- Muneer H, Sathe NC, Masood S. Nail psoriasis. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated March 1, 2024. Accessed October 24, 2024. https://www.ncbi.nlm.nih.gov/books/NBK559260/
- Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88:29-39. doi:10.1016/j.jaad.2022.07.002
- Strober B, Thaçi D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88:40-51. doi:10.1016/j.jaad.2022.08.061
- Sanchez DP, Sonthalia S. Koebner phenomenon. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated November 14, 2022. Accessed April 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK553108/
- Grover C, Kharghoria G, Bansal S. Triamcinolone acetonide injections in nail psoriasis: a pragmatic analysis. Skin Appendage Disord. 2024;10:50-59. doi:10.1159/000534699
- Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet]. StatPearls Publishing; 2024 Jan-. Updated August 16, 2023. Accessed April 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556114/
- Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2011:Cd008794. doi:10.1002/14651858.CD008794.pub2
- Thaçi D, Strober B, Gordon KB, et al. Deucravacitinib in moderate to severe psoriasis: clinical and quality-of-life outcomes in a phase 2 trial. Dermatol Ther (Heidelb). 2022;12:495-510. doi:10.1007/s13555-021-00649-y
- Week 0-16: demonstrated safety profile. Bristol-Myers Squibb. 2024. Accessed October 24, 2024. https://www.sotyktuhcp.com/safety-profile?cid=sem_2465603&gclid=CjwKCAiA9ourBhAVEiwA3L5RFnyYqmxbqkz1_zBNPz3dcyHKCSFf1XQ-7acznV0XbR5DDJHYkZcKJxoCWN0QAvD_BwE&gclsrc=aw.ds
Successful Treatment of Severe Dystrophic Nail Psoriasis With Deucravacitinib
Successful Treatment of Severe Dystrophic Nail Psoriasis With Deucravacitinib
PRACTICE POINTS
- Nail psoriasis can masquerade as other dermatologic conditions, including squamous cell carcinoma of the nail bed and acrodermatitis continua of Hallopeau.
- Nail psoriasis can progress to permanent nail loss if not treated properly, making early recognition and treatment crucial.
- Deucravacitinib, an oral tyrosine kinase 2 inhibitor approved for the treatment of plaque psoriasis, has shown promise as an effective treatment for nail psoriasis in cases that are refractory to standard therapies.
Botulinum Toxin Injection for Treatment of Scleroderma-Related Anterior Neck Sclerosis
To the Editor:
Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.
A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated sclerosis with high tension.
The dermatologist (J.J.) discussed potential treatment options to help relax the tension in the skin of the anterior neck, including BTX injections. After receiving counsel on adverse effects, alternative treatments, and postprocedural care, the patient decided to proceed with the procedure. The anterior neck was cleansed with an alcohol swab and 37 units (range, 25–50 units) of incobotulinumtoxinA (reconstituted using 2.5-mL bacteriostatic normal saline per 100 units) was injected transdermally using a 9-point injection technique, with each injection placed approximately 1 cm apart. The approximate treatment area included the space between the sternocleidomastoid anterior edges and below the hyoid bone up to the cricothyroid membrane (anatomic zone II).
When the patient returned for follow-up 3 weeks later, she reported considerable improvement in the stiffness and appearance of the skin on the anterior neck. On physical examination, the skin of the neck appeared softened, and improved laxity was seen on pinching the skin compared to the initial presentation (Figure 2). The patient expressed satisfaction with the results and denied any adverse events following the procedure.
Mixed connective tissue disease manifests with a combination of features from various disorders—mainly lupus, scleroderma, polymyositis, and rheumatoid arthritis. It is most prevalent in females and often is diagnosed in the third decade of life.3 It is associated with positive antinuclear antibodies and human leukocyte antigen (HLA) II alleles (HLA-DR4, HLA-DR1, and HLA-DR2). Raynaud phenomenon (RP), one of the most common skin manifestations in both scleroderma and MCTD, is present in 75% to 90% of patients with MCTD.3
Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.4 Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4+ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.4 Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.5 Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).
On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.5 Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.6 Similar to MCTD, scleroderma is most prevalent in middle-aged females,7 though it occurs at a higher rate and with a more severe disease course in Black patients.8
A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.9 Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.
While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.5 Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.5 However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.
Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.11 It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.12 Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.19 Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.20 In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.21
Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).22 Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.
- Lis-S´wie¸ty A, Skrzypek-Salamon A, Ranosz-Janicka I, et al. Health-related quality of life and its influencing factors in adult patients with localized scleroderma—a cross-sectional study. Health Qual Life Outcomes. 2020;18:133. doi:10.1186/s12955-020-01386-0
- Almeida C, Almeida I, Vasconcelos C. Quality of life in systemic sclerosis. Autoimmun Rev. 2015;14:1087-1096. doi:10.1016/j.autrev.2015.07.012
- Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2012;26:61-72. doi:10.1016/j.berh.2012.01.009
- Rongioletti F, Ferreli C, Atzori L, et al. Scleroderma with an update about clinico-pathological correlation. G Ital Dermatol Venereol. 2018;153:208-215. doi:10.23736/S0392-0488.18.05922-9
- Fett N. Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies. Clin Dermatol. 2013;31:432-437. doi:10.1016/j.clindermatol.2013.01.010
- Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol. 2015;90:62-73. doi:10.1590/abd1806-4841.20152890
- Calderon LM, Pope JE. Scleroderma epidemiology update. Curr Opin Rheumatol. 2021;33:122-127. doi:10.1097/BOR.0000000000000785
- Morgan ND, Gelber AC. African Americans and scleroderma: examining the root cause of the association. Arthritis Care Res (Hoboken). 2019;71:1151-1153. doi:10.1002/acr.23860
- Barnett AJ. The “neck sign” in scleroderma. Arthritis Rheum. 1989;32:209-211. doi:10.1002/anr.1780320215
- Barnett AJ, Miller M, Littlejohn GO. The diagnosis and classification of scleroderma (systemic sclerosis). Postgrad Med J. 1988;64:121-125. doi:10.1136/pgmj.64.748.121
- Rossetto O, Pirazzini M, Fabris F, et al. Botulinum neurotoxins: mechanism of action. Handb Exp Pharmacol. 2021;263:35-47.doi:10.1007/164_2020_355
- Ennis D, Ahmad Z, Anderson MA, et al. Botulinum toxin in the management of primary and secondary Raynaud’s phenomenon. Best Pract Res Clin Rheumatol. 2021;35:101684. doi:10.1016/j.berh.2021.101684
- Turkmani MG, Alnomair N. Enhancement of the aesthetic outcome of scleroderma en coup de sabre with botulinum toxin injection. JAAD Case Rep. 2018;4:579-581. doi:10.1016/j.jdcr.2018.03.023
- Le EN, Freischlag JA, Christo PJ, et al. Thoracic outlet syndrome secondary to localized scleroderma treated with botulinum toxin injection. Arthritis Care Res (Hoboken). 2010;62:430-433. doi:10.1002/acr.20099
- Mousty E, Rathat G, Rouleau C, et al. Botulinum toxin type A for treatment of dyspareunia caused by localized scleroderma. Acta Obstet Gynecol Scand. 2011;90:926-927. doi:10.1111/j.1600-0412.2011.01183.x
- Tang DM, Friedenberg FK. Gastroparesis: approach, diagnostic evaluation, and management. Dis Mon. 2011;57:74-101. doi:10.1016/j.disamonth.2010.12.007
- Katschinski M. [Diagnosis and treatment of esophageal motility disorders]. Ther Umsch. 2001;58:128-133. doi:10.1024/0040-5930.58.3.128
- Kim DJ, Odell ID. Improvement of pterygium inversum unguis and Raynaud phenomenon with interdigital botulinum toxin injections. JAAD Case Rep. 2022;26:79-81. doi:10.1016/j.jdcr.2022.06.009
- Baral H, Sekiguchi A, Uchiyama A, et al. Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress. J Dermatol. 2021;48:1052-1061. doi:10.1111/1346-8138.15888
- Jia C, Xing T, Shang Z, et al. Botulinum toxin A improves neurogenic bladder fibrosis by suppressing transforming growth factor β1 expression in rats. Transl Androl Urol. 2021;10:2000-2007. doi:10.21037/tau-21-62
- Hoverson K, Love T, Lam TK, et al. A novel treatment for limited mouth opening due to facial fibrosis: a case series. J Am Acad Dermatol. 2018;78:190-192. doi:10.1016/j.jaad.2017.07.006
- Kollewe K, Mohammadi B, Köhler S, et al. Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®. J Neural Transm (Vienna). 2015;122:427-431. doi:10.1007/s00702-014-1278-z
To the Editor:
Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.
A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated sclerosis with high tension.
The dermatologist (J.J.) discussed potential treatment options to help relax the tension in the skin of the anterior neck, including BTX injections. After receiving counsel on adverse effects, alternative treatments, and postprocedural care, the patient decided to proceed with the procedure. The anterior neck was cleansed with an alcohol swab and 37 units (range, 25–50 units) of incobotulinumtoxinA (reconstituted using 2.5-mL bacteriostatic normal saline per 100 units) was injected transdermally using a 9-point injection technique, with each injection placed approximately 1 cm apart. The approximate treatment area included the space between the sternocleidomastoid anterior edges and below the hyoid bone up to the cricothyroid membrane (anatomic zone II).
When the patient returned for follow-up 3 weeks later, she reported considerable improvement in the stiffness and appearance of the skin on the anterior neck. On physical examination, the skin of the neck appeared softened, and improved laxity was seen on pinching the skin compared to the initial presentation (Figure 2). The patient expressed satisfaction with the results and denied any adverse events following the procedure.
Mixed connective tissue disease manifests with a combination of features from various disorders—mainly lupus, scleroderma, polymyositis, and rheumatoid arthritis. It is most prevalent in females and often is diagnosed in the third decade of life.3 It is associated with positive antinuclear antibodies and human leukocyte antigen (HLA) II alleles (HLA-DR4, HLA-DR1, and HLA-DR2). Raynaud phenomenon (RP), one of the most common skin manifestations in both scleroderma and MCTD, is present in 75% to 90% of patients with MCTD.3
Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.4 Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4+ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.4 Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.5 Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).
On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.5 Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.6 Similar to MCTD, scleroderma is most prevalent in middle-aged females,7 though it occurs at a higher rate and with a more severe disease course in Black patients.8
A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.9 Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.
While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.5 Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.5 However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.
Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.11 It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.12 Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.19 Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.20 In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.21
Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).22 Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.
To the Editor:
Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.
A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated sclerosis with high tension.
The dermatologist (J.J.) discussed potential treatment options to help relax the tension in the skin of the anterior neck, including BTX injections. After receiving counsel on adverse effects, alternative treatments, and postprocedural care, the patient decided to proceed with the procedure. The anterior neck was cleansed with an alcohol swab and 37 units (range, 25–50 units) of incobotulinumtoxinA (reconstituted using 2.5-mL bacteriostatic normal saline per 100 units) was injected transdermally using a 9-point injection technique, with each injection placed approximately 1 cm apart. The approximate treatment area included the space between the sternocleidomastoid anterior edges and below the hyoid bone up to the cricothyroid membrane (anatomic zone II).
When the patient returned for follow-up 3 weeks later, she reported considerable improvement in the stiffness and appearance of the skin on the anterior neck. On physical examination, the skin of the neck appeared softened, and improved laxity was seen on pinching the skin compared to the initial presentation (Figure 2). The patient expressed satisfaction with the results and denied any adverse events following the procedure.
Mixed connective tissue disease manifests with a combination of features from various disorders—mainly lupus, scleroderma, polymyositis, and rheumatoid arthritis. It is most prevalent in females and often is diagnosed in the third decade of life.3 It is associated with positive antinuclear antibodies and human leukocyte antigen (HLA) II alleles (HLA-DR4, HLA-DR1, and HLA-DR2). Raynaud phenomenon (RP), one of the most common skin manifestations in both scleroderma and MCTD, is present in 75% to 90% of patients with MCTD.3
Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.4 Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4+ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.4 Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.5 Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).
On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.5 Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.6 Similar to MCTD, scleroderma is most prevalent in middle-aged females,7 though it occurs at a higher rate and with a more severe disease course in Black patients.8
A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.9 Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.
While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.5 Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.5 However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.
Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.11 It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.12 Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.19 Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.20 In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.21
Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).22 Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.
- Lis-S´wie¸ty A, Skrzypek-Salamon A, Ranosz-Janicka I, et al. Health-related quality of life and its influencing factors in adult patients with localized scleroderma—a cross-sectional study. Health Qual Life Outcomes. 2020;18:133. doi:10.1186/s12955-020-01386-0
- Almeida C, Almeida I, Vasconcelos C. Quality of life in systemic sclerosis. Autoimmun Rev. 2015;14:1087-1096. doi:10.1016/j.autrev.2015.07.012
- Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2012;26:61-72. doi:10.1016/j.berh.2012.01.009
- Rongioletti F, Ferreli C, Atzori L, et al. Scleroderma with an update about clinico-pathological correlation. G Ital Dermatol Venereol. 2018;153:208-215. doi:10.23736/S0392-0488.18.05922-9
- Fett N. Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies. Clin Dermatol. 2013;31:432-437. doi:10.1016/j.clindermatol.2013.01.010
- Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol. 2015;90:62-73. doi:10.1590/abd1806-4841.20152890
- Calderon LM, Pope JE. Scleroderma epidemiology update. Curr Opin Rheumatol. 2021;33:122-127. doi:10.1097/BOR.0000000000000785
- Morgan ND, Gelber AC. African Americans and scleroderma: examining the root cause of the association. Arthritis Care Res (Hoboken). 2019;71:1151-1153. doi:10.1002/acr.23860
- Barnett AJ. The “neck sign” in scleroderma. Arthritis Rheum. 1989;32:209-211. doi:10.1002/anr.1780320215
- Barnett AJ, Miller M, Littlejohn GO. The diagnosis and classification of scleroderma (systemic sclerosis). Postgrad Med J. 1988;64:121-125. doi:10.1136/pgmj.64.748.121
- Rossetto O, Pirazzini M, Fabris F, et al. Botulinum neurotoxins: mechanism of action. Handb Exp Pharmacol. 2021;263:35-47.doi:10.1007/164_2020_355
- Ennis D, Ahmad Z, Anderson MA, et al. Botulinum toxin in the management of primary and secondary Raynaud’s phenomenon. Best Pract Res Clin Rheumatol. 2021;35:101684. doi:10.1016/j.berh.2021.101684
- Turkmani MG, Alnomair N. Enhancement of the aesthetic outcome of scleroderma en coup de sabre with botulinum toxin injection. JAAD Case Rep. 2018;4:579-581. doi:10.1016/j.jdcr.2018.03.023
- Le EN, Freischlag JA, Christo PJ, et al. Thoracic outlet syndrome secondary to localized scleroderma treated with botulinum toxin injection. Arthritis Care Res (Hoboken). 2010;62:430-433. doi:10.1002/acr.20099
- Mousty E, Rathat G, Rouleau C, et al. Botulinum toxin type A for treatment of dyspareunia caused by localized scleroderma. Acta Obstet Gynecol Scand. 2011;90:926-927. doi:10.1111/j.1600-0412.2011.01183.x
- Tang DM, Friedenberg FK. Gastroparesis: approach, diagnostic evaluation, and management. Dis Mon. 2011;57:74-101. doi:10.1016/j.disamonth.2010.12.007
- Katschinski M. [Diagnosis and treatment of esophageal motility disorders]. Ther Umsch. 2001;58:128-133. doi:10.1024/0040-5930.58.3.128
- Kim DJ, Odell ID. Improvement of pterygium inversum unguis and Raynaud phenomenon with interdigital botulinum toxin injections. JAAD Case Rep. 2022;26:79-81. doi:10.1016/j.jdcr.2022.06.009
- Baral H, Sekiguchi A, Uchiyama A, et al. Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress. J Dermatol. 2021;48:1052-1061. doi:10.1111/1346-8138.15888
- Jia C, Xing T, Shang Z, et al. Botulinum toxin A improves neurogenic bladder fibrosis by suppressing transforming growth factor β1 expression in rats. Transl Androl Urol. 2021;10:2000-2007. doi:10.21037/tau-21-62
- Hoverson K, Love T, Lam TK, et al. A novel treatment for limited mouth opening due to facial fibrosis: a case series. J Am Acad Dermatol. 2018;78:190-192. doi:10.1016/j.jaad.2017.07.006
- Kollewe K, Mohammadi B, Köhler S, et al. Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®. J Neural Transm (Vienna). 2015;122:427-431. doi:10.1007/s00702-014-1278-z
- Lis-S´wie¸ty A, Skrzypek-Salamon A, Ranosz-Janicka I, et al. Health-related quality of life and its influencing factors in adult patients with localized scleroderma—a cross-sectional study. Health Qual Life Outcomes. 2020;18:133. doi:10.1186/s12955-020-01386-0
- Almeida C, Almeida I, Vasconcelos C. Quality of life in systemic sclerosis. Autoimmun Rev. 2015;14:1087-1096. doi:10.1016/j.autrev.2015.07.012
- Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2012;26:61-72. doi:10.1016/j.berh.2012.01.009
- Rongioletti F, Ferreli C, Atzori L, et al. Scleroderma with an update about clinico-pathological correlation. G Ital Dermatol Venereol. 2018;153:208-215. doi:10.23736/S0392-0488.18.05922-9
- Fett N. Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies. Clin Dermatol. 2013;31:432-437. doi:10.1016/j.clindermatol.2013.01.010
- Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol. 2015;90:62-73. doi:10.1590/abd1806-4841.20152890
- Calderon LM, Pope JE. Scleroderma epidemiology update. Curr Opin Rheumatol. 2021;33:122-127. doi:10.1097/BOR.0000000000000785
- Morgan ND, Gelber AC. African Americans and scleroderma: examining the root cause of the association. Arthritis Care Res (Hoboken). 2019;71:1151-1153. doi:10.1002/acr.23860
- Barnett AJ. The “neck sign” in scleroderma. Arthritis Rheum. 1989;32:209-211. doi:10.1002/anr.1780320215
- Barnett AJ, Miller M, Littlejohn GO. The diagnosis and classification of scleroderma (systemic sclerosis). Postgrad Med J. 1988;64:121-125. doi:10.1136/pgmj.64.748.121
- Rossetto O, Pirazzini M, Fabris F, et al. Botulinum neurotoxins: mechanism of action. Handb Exp Pharmacol. 2021;263:35-47.doi:10.1007/164_2020_355
- Ennis D, Ahmad Z, Anderson MA, et al. Botulinum toxin in the management of primary and secondary Raynaud’s phenomenon. Best Pract Res Clin Rheumatol. 2021;35:101684. doi:10.1016/j.berh.2021.101684
- Turkmani MG, Alnomair N. Enhancement of the aesthetic outcome of scleroderma en coup de sabre with botulinum toxin injection. JAAD Case Rep. 2018;4:579-581. doi:10.1016/j.jdcr.2018.03.023
- Le EN, Freischlag JA, Christo PJ, et al. Thoracic outlet syndrome secondary to localized scleroderma treated with botulinum toxin injection. Arthritis Care Res (Hoboken). 2010;62:430-433. doi:10.1002/acr.20099
- Mousty E, Rathat G, Rouleau C, et al. Botulinum toxin type A for treatment of dyspareunia caused by localized scleroderma. Acta Obstet Gynecol Scand. 2011;90:926-927. doi:10.1111/j.1600-0412.2011.01183.x
- Tang DM, Friedenberg FK. Gastroparesis: approach, diagnostic evaluation, and management. Dis Mon. 2011;57:74-101. doi:10.1016/j.disamonth.2010.12.007
- Katschinski M. [Diagnosis and treatment of esophageal motility disorders]. Ther Umsch. 2001;58:128-133. doi:10.1024/0040-5930.58.3.128
- Kim DJ, Odell ID. Improvement of pterygium inversum unguis and Raynaud phenomenon with interdigital botulinum toxin injections. JAAD Case Rep. 2022;26:79-81. doi:10.1016/j.jdcr.2022.06.009
- Baral H, Sekiguchi A, Uchiyama A, et al. Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress. J Dermatol. 2021;48:1052-1061. doi:10.1111/1346-8138.15888
- Jia C, Xing T, Shang Z, et al. Botulinum toxin A improves neurogenic bladder fibrosis by suppressing transforming growth factor β1 expression in rats. Transl Androl Urol. 2021;10:2000-2007. doi:10.21037/tau-21-62
- Hoverson K, Love T, Lam TK, et al. A novel treatment for limited mouth opening due to facial fibrosis: a case series. J Am Acad Dermatol. 2018;78:190-192. doi:10.1016/j.jaad.2017.07.006
- Kollewe K, Mohammadi B, Köhler S, et al. Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®. J Neural Transm (Vienna). 2015;122:427-431. doi:10.1007/s00702-014-1278-z
Practice Points
- Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body.
- Although there is no curative treatment for scleroderma, there are options to slow disease progression and improve quality of life.
- Botulinum toxin injection may be a preferred treatment option in patients with features of sclerosis or fibrosis related to scleroderma, particularly in the neck region.
