Hair & Nails

Case Report

A 62-year-old black man presented for examination of a dark longitudinal streak located adjacent to the lateral nail fold on the third finger of the left hand. The lesion had been present for several months, during which time it had slowly expanded in size. The fingertip had recently become tender, which interfered with the patient’s ability to work. His past medical history was remarkable for end-stage renal disease secondary to glomerulonephritis with nephrotic syndrome of unclear etiology. He initially was treated by an outside physician using peritoneal dialysis for 3 years until he underwent renal transplantation in 2004 with a cadaveric organ. Other remarkable medical conditions included posttransplantation diabetes, hyperlipidemia, and gout. His multidrug regimen included 2 immunosuppressive medications: oral cyclosporine 125 mg twice daily and oral mycophenolate mofetil 250 mg twice daily.

A broad, irregular, black, pigmented, subungual band was noted on the left third finger. The lesion appeared to emanate from below the nail cuticle and traveled along the nail longitudinally toward the distal tip. The band appeared darker at the edge adjacent to the lateral nail fold and grew lighter near the middle of the nail where its free edge was noted to be irregular. A slightly thickened lateral nail fold with an irregular, small, sawtoothlike hyperkeratosis and hyperpigmentation also was noted (Figure 1).

Subungual melanoma, onychomycosis, squamous cell carcinoma (SCC), and a verruca copresenting with onychomycosis were considered in the differential diagnosis. The patient underwent nail avulsion and biopsy of the nail bed as well as the nail matrix. Histopathology was notable for malignant dyskeratosis with a lack of nuclear maturation, occasional mitoses, multinucleation, and individual cell keratinization (Figure 2). Immunostaining for S100 was negative, while staining for cytokeratins AE1/AE3 was positive. Deposition of melanin pigment in the malignant dyskeratotic cells was noted. Periodic acid–Schiff staining identified pseudohyphae without invasion of the nail plate. A diagnosis of pigmented SCC (pSCC) was made. The patient’s nail also was sent for fungal cultures that later grew Candida glabrata and Candida parapsilosis.

The patient underwent Mohs micrographic surgery for removal of the pSCC, which was found to be more extensive than originally suspected and required en bloc excision of the nail repaired with a full-thickness skin graft from the left forearm. The area healed well with some hyperpigmentation (Figure 3).

Comment

Among the various types of skin cancer, an estimated 700,000 patients are diagnosed with SCC annually, making it the second most common form of skin cancer in the United States.¹ Basal cell carcinoma (BCC) is the most common skin cancer among whites in the United States, while in contrast SCC is the most common skin cancer in patients with skin of color.² Only an estimated 2% to 5% of all SCCs are pigmented, and this variant is more commonly seen in patients with skin of color.^3-5 One analysis of 52 cases of pSCC showed that common features included a flat or slightly raised appearance and hyperpigmentation with varying levels of scaling.⁶ Studies have shown an altered presentation of pSCC in black skin with increased melanin production and thickness of the stratum corneum in contrast with cases seen in white patients.⁷ Other potential features include scaling, erosive changes, and sharply demarcated borders. Squamous cell carcinoma typically occurs in sun-exposed areas, reflecting its association with UV light damage; however, SCC in skin of color patients has been noted to occur in sun-protected areas and in areas of chronic scarring.⁸ Pigmented SCC also appears to follow this distribution, as affected areas are not necessarily in direct exposure to the sun. Pigmented SCCs have been associated with pruritus and/or burning pain, which also was seen in our case when our patient complained of tenderness at the site.

We describe the case of a subungual pSCC clinically presenting as longitudinal melanonychia. Pigmented SCC presenting as longitudinal melanonychia was first described by Baran and Simon in 1988.⁹ Since that time, it has been reported that approximately 10% of subungual pSCCs clinically present as longitudinal melanonychia.^10,11 A retrospective study reviewing 35 cases of SCC of the nail apparatus found that 5 (14.3%) cases presented as longitudinal melanonychia.¹⁰ Another retrospective study found that 6 of 51 (11.8%) cases of SCCs affecting the nail unit presented as the warty type of SCC in association with longitudinal melanonychia.¹² Cases of pSCC in situ appearing as longitudinal melanonychia also have been reported.^13,14

Risk factors for the development of pSCC include advanced age, male sex, presence of human papilloma virus, and use of immunosuppressants.¹⁵ Male predominance and advanced age at the time of diagnosis (mean age, 67 years) have been observed in pSCC cases.¹⁶ It is now well established that renal transplant recipients have an increased risk of SCC, with a reported incidence rate of 5% to 6%.¹⁶ When these patients develop an SCC, they typically follow a more aggressive course. Renal transplantation has a higher ratio than cardiac transplantation for SCC development (2.37:1), whereas cardiac transplantation is associated with a higher risk of BCC development.¹⁷ A study of 384 transplant recipients found that 96 (25.0%) had a postsurgical nonmelanoma skin cancer (NMSC), with a ratio of SCC to BCC of 1.2:1.¹⁶ The calculated incidence of NMSC at 10 and 20 years posttransplantation was 24.2% and 54.4%, respectively. Another study also determined that SCC rates (50.0%) in postrenal transplant recipients were approximately twice that of BCC (27.0%).¹⁸

A daily regimen of immunosuppressive medications such as cyclosporine and mycophenolate mofetil showed an increased risk for development of NMSC.¹⁵ Immunosuppressive medications play an important role in the pathogenesis of SCC due to a direct oncogenic effect as well as impairment of the immune system’s ability to fight precancerous developments.¹⁵ A 4-year study of 100 renal transplant recipients using mycophenolate mofetil as part of an immunosuppressive regimen reported 22% NMSC findings among 9 patients.¹⁹ On average, patients developed an NMSC approximately 61 months posttransplantation, with a wide range from 2 to 120 months.

Advanced age was another important risk factor, with each decade of life producing a 60% increase in instantaneous risk of SCC development for transplant recipients.¹⁵ A steady increase in risk was related to the length of time adhering to an immunosuppressive regimen, especially from 2 to 6 years, and then remaining constant in subsequent years. For older patients on immunosuppressant regimens for more than 8 years, the calculated relative risk was noted to be over 200 times greater than the normal population’s development of skin cancers.¹⁸

Conclusion

Although cases of pSCC presenting as longitudinal melanonychia have previously been reported,^9-14,20 our case is unique in that it describes pSCC in a renal transplant recipient. Our patient had many of the known risk factors for the development of pSCC including male sex, advanced age, skin of color, history of renal transplantation, and immunosuppressive therapy. Although regular full-body skin examinations are an accepted part of renal transplantation follow-up due to SCC risk, our case emphasizes the need to remain vigilant due to possible atypical presentations among the immunosuppressed. The nail unit should not be overlooked during the clinical examination of renal transplant recipients as demonstrated by our patient’s rare presentation of pSCC in the nail.

Case Report

A 62-year-old black man presented for examination of a dark longitudinal streak located adjacent to the lateral nail fold on the third finger of the left hand. The lesion had been present for several months, during which time it had slowly expanded in size. The fingertip had recently become tender, which interfered with the patient’s ability to work. His past medical history was remarkable for end-stage renal disease secondary to glomerulonephritis with nephrotic syndrome of unclear etiology. He initially was treated by an outside physician using peritoneal dialysis for 3 years until he underwent renal transplantation in 2004 with a cadaveric organ. Other remarkable medical conditions included posttransplantation diabetes, hyperlipidemia, and gout. His multidrug regimen included 2 immunosuppressive medications: oral cyclosporine 125 mg twice daily and oral mycophenolate mofetil 250 mg twice daily.

A broad, irregular, black, pigmented, subungual band was noted on the left third finger. The lesion appeared to emanate from below the nail cuticle and traveled along the nail longitudinally toward the distal tip. The band appeared darker at the edge adjacent to the lateral nail fold and grew lighter near the middle of the nail where its free edge was noted to be irregular. A slightly thickened lateral nail fold with an irregular, small, sawtoothlike hyperkeratosis and hyperpigmentation also was noted (Figure 1).

Subungual melanoma, onychomycosis, squamous cell carcinoma (SCC), and a verruca copresenting with onychomycosis were considered in the differential diagnosis. The patient underwent nail avulsion and biopsy of the nail bed as well as the nail matrix. Histopathology was notable for malignant dyskeratosis with a lack of nuclear maturation, occasional mitoses, multinucleation, and individual cell keratinization (Figure 2). Immunostaining for S100 was negative, while staining for cytokeratins AE1/AE3 was positive. Deposition of melanin pigment in the malignant dyskeratotic cells was noted. Periodic acid–Schiff staining identified pseudohyphae without invasion of the nail plate. A diagnosis of pigmented SCC (pSCC) was made. The patient’s nail also was sent for fungal cultures that later grew Candida glabrata and Candida parapsilosis.

The patient underwent Mohs micrographic surgery for removal of the pSCC, which was found to be more extensive than originally suspected and required en bloc excision of the nail repaired with a full-thickness skin graft from the left forearm. The area healed well with some hyperpigmentation (Figure 3).

Comment

Among the various types of skin cancer, an estimated 700,000 patients are diagnosed with SCC annually, making it the second most common form of skin cancer in the United States.¹ Basal cell carcinoma (BCC) is the most common skin cancer among whites in the United States, while in contrast SCC is the most common skin cancer in patients with skin of color.² Only an estimated 2% to 5% of all SCCs are pigmented, and this variant is more commonly seen in patients with skin of color.^3-5 One analysis of 52 cases of pSCC showed that common features included a flat or slightly raised appearance and hyperpigmentation with varying levels of scaling.⁶ Studies have shown an altered presentation of pSCC in black skin with increased melanin production and thickness of the stratum corneum in contrast with cases seen in white patients.⁷ Other potential features include scaling, erosive changes, and sharply demarcated borders. Squamous cell carcinoma typically occurs in sun-exposed areas, reflecting its association with UV light damage; however, SCC in skin of color patients has been noted to occur in sun-protected areas and in areas of chronic scarring.⁸ Pigmented SCC also appears to follow this distribution, as affected areas are not necessarily in direct exposure to the sun. Pigmented SCCs have been associated with pruritus and/or burning pain, which also was seen in our case when our patient complained of tenderness at the site.

We describe the case of a subungual pSCC clinically presenting as longitudinal melanonychia. Pigmented SCC presenting as longitudinal melanonychia was first described by Baran and Simon in 1988.⁹ Since that time, it has been reported that approximately 10% of subungual pSCCs clinically present as longitudinal melanonychia.^10,11 A retrospective study reviewing 35 cases of SCC of the nail apparatus found that 5 (14.3%) cases presented as longitudinal melanonychia.¹⁰ Another retrospective study found that 6 of 51 (11.8%) cases of SCCs affecting the nail unit presented as the warty type of SCC in association with longitudinal melanonychia.¹² Cases of pSCC in situ appearing as longitudinal melanonychia also have been reported.^13,14

Risk factors for the development of pSCC include advanced age, male sex, presence of human papilloma virus, and use of immunosuppressants.¹⁵ Male predominance and advanced age at the time of diagnosis (mean age, 67 years) have been observed in pSCC cases.¹⁶ It is now well established that renal transplant recipients have an increased risk of SCC, with a reported incidence rate of 5% to 6%.¹⁶ When these patients develop an SCC, they typically follow a more aggressive course. Renal transplantation has a higher ratio than cardiac transplantation for SCC development (2.37:1), whereas cardiac transplantation is associated with a higher risk of BCC development.¹⁷ A study of 384 transplant recipients found that 96 (25.0%) had a postsurgical nonmelanoma skin cancer (NMSC), with a ratio of SCC to BCC of 1.2:1.¹⁶ The calculated incidence of NMSC at 10 and 20 years posttransplantation was 24.2% and 54.4%, respectively. Another study also determined that SCC rates (50.0%) in postrenal transplant recipients were approximately twice that of BCC (27.0%).¹⁸

A daily regimen of immunosuppressive medications such as cyclosporine and mycophenolate mofetil showed an increased risk for development of NMSC.¹⁵ Immunosuppressive medications play an important role in the pathogenesis of SCC due to a direct oncogenic effect as well as impairment of the immune system’s ability to fight precancerous developments.¹⁵ A 4-year study of 100 renal transplant recipients using mycophenolate mofetil as part of an immunosuppressive regimen reported 22% NMSC findings among 9 patients.¹⁹ On average, patients developed an NMSC approximately 61 months posttransplantation, with a wide range from 2 to 120 months.

Advanced age was another important risk factor, with each decade of life producing a 60% increase in instantaneous risk of SCC development for transplant recipients.¹⁵ A steady increase in risk was related to the length of time adhering to an immunosuppressive regimen, especially from 2 to 6 years, and then remaining constant in subsequent years. For older patients on immunosuppressant regimens for more than 8 years, the calculated relative risk was noted to be over 200 times greater than the normal population’s development of skin cancers.¹⁸

Conclusion

Although cases of pSCC presenting as longitudinal melanonychia have previously been reported,^9-14,20 our case is unique in that it describes pSCC in a renal transplant recipient. Our patient had many of the known risk factors for the development of pSCC including male sex, advanced age, skin of color, history of renal transplantation, and immunosuppressive therapy. Although regular full-body skin examinations are an accepted part of renal transplantation follow-up due to SCC risk, our case emphasizes the need to remain vigilant due to possible atypical presentations among the immunosuppressed. The nail unit should not be overlooked during the clinical examination of renal transplant recipients as demonstrated by our patient’s rare presentation of pSCC in the nail.

Case Report

A 62-year-old black man presented for examination of a dark longitudinal streak located adjacent to the lateral nail fold on the third finger of the left hand. The lesion had been present for several months, during which time it had slowly expanded in size. The fingertip had recently become tender, which interfered with the patient’s ability to work. His past medical history was remarkable for end-stage renal disease secondary to glomerulonephritis with nephrotic syndrome of unclear etiology. He initially was treated by an outside physician using peritoneal dialysis for 3 years until he underwent renal transplantation in 2004 with a cadaveric organ. Other remarkable medical conditions included posttransplantation diabetes, hyperlipidemia, and gout. His multidrug regimen included 2 immunosuppressive medications: oral cyclosporine 125 mg twice daily and oral mycophenolate mofetil 250 mg twice daily.

A broad, irregular, black, pigmented, subungual band was noted on the left third finger. The lesion appeared to emanate from below the nail cuticle and traveled along the nail longitudinally toward the distal tip. The band appeared darker at the edge adjacent to the lateral nail fold and grew lighter near the middle of the nail where its free edge was noted to be irregular. A slightly thickened lateral nail fold with an irregular, small, sawtoothlike hyperkeratosis and hyperpigmentation also was noted (Figure 1).

Subungual melanoma, onychomycosis, squamous cell carcinoma (SCC), and a verruca copresenting with onychomycosis were considered in the differential diagnosis. The patient underwent nail avulsion and biopsy of the nail bed as well as the nail matrix. Histopathology was notable for malignant dyskeratosis with a lack of nuclear maturation, occasional mitoses, multinucleation, and individual cell keratinization (Figure 2). Immunostaining for S100 was negative, while staining for cytokeratins AE1/AE3 was positive. Deposition of melanin pigment in the malignant dyskeratotic cells was noted. Periodic acid–Schiff staining identified pseudohyphae without invasion of the nail plate. A diagnosis of pigmented SCC (pSCC) was made. The patient’s nail also was sent for fungal cultures that later grew Candida glabrata and Candida parapsilosis.

The patient underwent Mohs micrographic surgery for removal of the pSCC, which was found to be more extensive than originally suspected and required en bloc excision of the nail repaired with a full-thickness skin graft from the left forearm. The area healed well with some hyperpigmentation (Figure 3).

Comment

Among the various types of skin cancer, an estimated 700,000 patients are diagnosed with SCC annually, making it the second most common form of skin cancer in the United States.¹ Basal cell carcinoma (BCC) is the most common skin cancer among whites in the United States, while in contrast SCC is the most common skin cancer in patients with skin of color.² Only an estimated 2% to 5% of all SCCs are pigmented, and this variant is more commonly seen in patients with skin of color.^3-5 One analysis of 52 cases of pSCC showed that common features included a flat or slightly raised appearance and hyperpigmentation with varying levels of scaling.⁶ Studies have shown an altered presentation of pSCC in black skin with increased melanin production and thickness of the stratum corneum in contrast with cases seen in white patients.⁷ Other potential features include scaling, erosive changes, and sharply demarcated borders. Squamous cell carcinoma typically occurs in sun-exposed areas, reflecting its association with UV light damage; however, SCC in skin of color patients has been noted to occur in sun-protected areas and in areas of chronic scarring.⁸ Pigmented SCC also appears to follow this distribution, as affected areas are not necessarily in direct exposure to the sun. Pigmented SCCs have been associated with pruritus and/or burning pain, which also was seen in our case when our patient complained of tenderness at the site.

We describe the case of a subungual pSCC clinically presenting as longitudinal melanonychia. Pigmented SCC presenting as longitudinal melanonychia was first described by Baran and Simon in 1988.⁹ Since that time, it has been reported that approximately 10% of subungual pSCCs clinically present as longitudinal melanonychia.^10,11 A retrospective study reviewing 35 cases of SCC of the nail apparatus found that 5 (14.3%) cases presented as longitudinal melanonychia.¹⁰ Another retrospective study found that 6 of 51 (11.8%) cases of SCCs affecting the nail unit presented as the warty type of SCC in association with longitudinal melanonychia.¹² Cases of pSCC in situ appearing as longitudinal melanonychia also have been reported.^13,14

Risk factors for the development of pSCC include advanced age, male sex, presence of human papilloma virus, and use of immunosuppressants.¹⁵ Male predominance and advanced age at the time of diagnosis (mean age, 67 years) have been observed in pSCC cases.¹⁶ It is now well established that renal transplant recipients have an increased risk of SCC, with a reported incidence rate of 5% to 6%.¹⁶ When these patients develop an SCC, they typically follow a more aggressive course. Renal transplantation has a higher ratio than cardiac transplantation for SCC development (2.37:1), whereas cardiac transplantation is associated with a higher risk of BCC development.¹⁷ A study of 384 transplant recipients found that 96 (25.0%) had a postsurgical nonmelanoma skin cancer (NMSC), with a ratio of SCC to BCC of 1.2:1.¹⁶ The calculated incidence of NMSC at 10 and 20 years posttransplantation was 24.2% and 54.4%, respectively. Another study also determined that SCC rates (50.0%) in postrenal transplant recipients were approximately twice that of BCC (27.0%).¹⁸

A daily regimen of immunosuppressive medications such as cyclosporine and mycophenolate mofetil showed an increased risk for development of NMSC.¹⁵ Immunosuppressive medications play an important role in the pathogenesis of SCC due to a direct oncogenic effect as well as impairment of the immune system’s ability to fight precancerous developments.¹⁵ A 4-year study of 100 renal transplant recipients using mycophenolate mofetil as part of an immunosuppressive regimen reported 22% NMSC findings among 9 patients.¹⁹ On average, patients developed an NMSC approximately 61 months posttransplantation, with a wide range from 2 to 120 months.

Advanced age was another important risk factor, with each decade of life producing a 60% increase in instantaneous risk of SCC development for transplant recipients.¹⁵ A steady increase in risk was related to the length of time adhering to an immunosuppressive regimen, especially from 2 to 6 years, and then remaining constant in subsequent years. For older patients on immunosuppressant regimens for more than 8 years, the calculated relative risk was noted to be over 200 times greater than the normal population’s development of skin cancers.¹⁸

Conclusion

Although cases of pSCC presenting as longitudinal melanonychia have previously been reported,^9-14,20 our case is unique in that it describes pSCC in a renal transplant recipient. Our patient had many of the known risk factors for the development of pSCC including male sex, advanced age, skin of color, history of renal transplantation, and immunosuppressive therapy. Although regular full-body skin examinations are an accepted part of renal transplantation follow-up due to SCC risk, our case emphasizes the need to remain vigilant due to possible atypical presentations among the immunosuppressed. The nail unit should not be overlooked during the clinical examination of renal transplant recipients as demonstrated by our patient’s rare presentation of pSCC in the nail.

DALLAS – A picosecond 755-nm laser with focus lens array can serve as a safe, nonsurgical option for neck rejuvenation in patients with Fitzpatrick skin types I-III, especially for those who seek treatments with minimal downtime.

“It’s important to note that response was variable, but many patients were satisfied with the treatment,” Hana Jeon, MD said at the annual conference of the American Society for Laser Medicine and Surgery, Inc. “Further studies are needed to identify the clinical characteristics of neck laxity that would most benefit from this treatment.”

Hana Jeon, MD

Dr. Jeon reported that the average pain score during the procedure was 4.7 on a 10-point scale. Forced-air cooling was used for comfort, and on average, mild redness following the treatment lasted less than 1 day (a mean of 0.6 days, with a range of 0-5 days). Mild pain also lasted less than 1 day (a mean of 0.1 days, with a range of 0-2 days). No swelling, crusting, bruising, bleeding, infection, blistering, scarring, burn, or dyspigmentation occurred.

Hana Jeon, MD

At 3 months, 35% of patients said they would be “somewhat likely” to recommend the procedure, and 30% said they would be “extremely likely” to recommend it.

Dr. Jeon reported having no financial disclosures.

[email protected]

DALLAS – A picosecond 755-nm laser with focus lens array can serve as a safe, nonsurgical option for neck rejuvenation in patients with Fitzpatrick skin types I-III, especially for those who seek treatments with minimal downtime.

“It’s important to note that response was variable, but many patients were satisfied with the treatment,” Hana Jeon, MD said at the annual conference of the American Society for Laser Medicine and Surgery, Inc. “Further studies are needed to identify the clinical characteristics of neck laxity that would most benefit from this treatment.”

Hana Jeon, MD

Dr. Jeon reported that the average pain score during the procedure was 4.7 on a 10-point scale. Forced-air cooling was used for comfort, and on average, mild redness following the treatment lasted less than 1 day (a mean of 0.6 days, with a range of 0-5 days). Mild pain also lasted less than 1 day (a mean of 0.1 days, with a range of 0-2 days). No swelling, crusting, bruising, bleeding, infection, blistering, scarring, burn, or dyspigmentation occurred.

Hana Jeon, MD

At 3 months, 35% of patients said they would be “somewhat likely” to recommend the procedure, and 30% said they would be “extremely likely” to recommend it.

Dr. Jeon reported having no financial disclosures.

[email protected]

DALLAS – A picosecond 755-nm laser with focus lens array can serve as a safe, nonsurgical option for neck rejuvenation in patients with Fitzpatrick skin types I-III, especially for those who seek treatments with minimal downtime.

“It’s important to note that response was variable, but many patients were satisfied with the treatment,” Hana Jeon, MD said at the annual conference of the American Society for Laser Medicine and Surgery, Inc. “Further studies are needed to identify the clinical characteristics of neck laxity that would most benefit from this treatment.”

Hana Jeon, MD

Dr. Jeon reported that the average pain score during the procedure was 4.7 on a 10-point scale. Forced-air cooling was used for comfort, and on average, mild redness following the treatment lasted less than 1 day (a mean of 0.6 days, with a range of 0-5 days). Mild pain also lasted less than 1 day (a mean of 0.1 days, with a range of 0-2 days). No swelling, crusting, bruising, bleeding, infection, blistering, scarring, burn, or dyspigmentation occurred.

Hana Jeon, MD

At 3 months, 35% of patients said they would be “somewhat likely” to recommend the procedure, and 30% said they would be “extremely likely” to recommend it.

Dr. Jeon reported having no financial disclosures.

[email protected]

Hydroxychloroquine could be beneficial as a treatment option for children with alopecia areata (AA), according to Duri Yun, MD, of the University of Chicago Medicine, and associates.

In a retrospective review published in Pediatric Dermatology, nine children aged 6-16 years with AA and diverse ethnicities were treated with hydroxychloroquine between July 1, 2013, and July 1, 2015; all had failed multiple previous treatment modalities. In patient 1, hydroxychloroquine therapy was initiated, fine hair regrowth occurred after 5 months of therapy and was maintained, with dosage tapered to 200 mg once daily after 1 year. After 2 years of therapy, hair had nearly completely regrown. Similar results occurred in patient 2, who had nearly complete hair loss within 2 weeks of initiating hydroxychloroquine. Steady regrowth continued to near-complete regrowth after 1 year of treatment, when dosage was tapered to 200 mg once daily.

Abbassyma/Wikimedia Commons/Public Domain

[email protected]

SOURCE: Yun D et al., Pediatr Dermatol. 2018 Mar 25. doi: 10.1111/pde.13451.

Hydroxychloroquine could be beneficial as a treatment option for children with alopecia areata (AA), according to Duri Yun, MD, of the University of Chicago Medicine, and associates.

In a retrospective review published in Pediatric Dermatology, nine children aged 6-16 years with AA and diverse ethnicities were treated with hydroxychloroquine between July 1, 2013, and July 1, 2015; all had failed multiple previous treatment modalities. In patient 1, hydroxychloroquine therapy was initiated, fine hair regrowth occurred after 5 months of therapy and was maintained, with dosage tapered to 200 mg once daily after 1 year. After 2 years of therapy, hair had nearly completely regrown. Similar results occurred in patient 2, who had nearly complete hair loss within 2 weeks of initiating hydroxychloroquine. Steady regrowth continued to near-complete regrowth after 1 year of treatment, when dosage was tapered to 200 mg once daily.

Abbassyma/Wikimedia Commons/Public Domain

[email protected]

SOURCE: Yun D et al., Pediatr Dermatol. 2018 Mar 25. doi: 10.1111/pde.13451.

Hydroxychloroquine could be beneficial as a treatment option for children with alopecia areata (AA), according to Duri Yun, MD, of the University of Chicago Medicine, and associates.

In a retrospective review published in Pediatric Dermatology, nine children aged 6-16 years with AA and diverse ethnicities were treated with hydroxychloroquine between July 1, 2013, and July 1, 2015; all had failed multiple previous treatment modalities. In patient 1, hydroxychloroquine therapy was initiated, fine hair regrowth occurred after 5 months of therapy and was maintained, with dosage tapered to 200 mg once daily after 1 year. After 2 years of therapy, hair had nearly completely regrown. Similar results occurred in patient 2, who had nearly complete hair loss within 2 weeks of initiating hydroxychloroquine. Steady regrowth continued to near-complete regrowth after 1 year of treatment, when dosage was tapered to 200 mg once daily.

Abbassyma/Wikimedia Commons/Public Domain

[email protected]

SOURCE: Yun D et al., Pediatr Dermatol. 2018 Mar 25. doi: 10.1111/pde.13451.

Pediatric alopecia areata (AA) is more likely to affect girls, but boys are likely to have more severe types of the disorder, reported Iris Wohlmuth-Wieser, MD, of the department of dermatology, MD Anderson Cancer Center, Houston, and her associates, who conducted a large review of U.S. registry data.

Although it is the third most common dermatosis in children, there are not much data on AA in children, so the researchers used information from the National Alopecia Areata Registry, which was established in 2000. First, interested patients and parents were contacted and asked to fill out a web-based screening questionnaire. In the second phase, they were asked to fill out a more extensive survey and visit one of five U.S. sites for a clinical exam by a dermatologist.

Of the 2,218 children and teens who completed the initial questionnaire, the mean age at the time of the survey was 10 years, and their mean age of onset of AA was 6 years. The female to male ratio was 1.5:1; boys were significantly more likely to have severe types of AA (P = .009). Most patients (70%) were white, followed by mixed ethnicity (11%), Hispanic (3%), and then other ethnicities. About 3% of patients said they had a sibling with AA, 14% said that another first-degree relative had AA, and 8% said that at least three first-degree relatives had AA.

In terms of the degree of hair loss, 45% lost all scalp hair, 31% lost all body hair, and 14% lost all nails.

Concomitant diseases were reported by 47% of the responders, with atopic dermatitis, asthma, hay fever, and allergies the most common.

Of the 643 children and teens who completed a more detailed questionnaire and underwent clinical examination, 63% were female; 26% had at least one relative with AA and 8% had at least three first-degree relatives with AA. Almost 4% had congenital AA.

At the physical exam, there were data on the amount of hair loss in 617 children: Of these children, 37% had lost all scalp hair and 19% had lost up to three-quarters of their scalp hair. In 618 children (in whom information on body hair loss was obtained at the physical exam), 72% lost all or some of their body hair. Information on nails was available in 609 children; in this group, 44% had some nail involvement. More detailed information was available in 290 children; in this group, findings included pitting in 86%, dystrophy in 10%, onycholysis in 2%, ridging in 1%, and onychomycosis in 1%.

Commenting on the 25 children who presented with congenital AA, the authors wrote that this is “an extremely rare and infrequently reported form of AA.

“This is an interesting and important finding, because AA has traditionally been described as an acquired disease,” they added.

In their cohort overall, 25% had a family history of AA, with 8% having more than three first-degree relatives with AA. The researchers said that the percentage of children with AA and a positive family history ranges from 8% to 52% in the literature.

“The predominant presentation of AA types in our cohort (61.4%) was severe hair loss (76%-100% of scalp hair loss). This is comparable with a European study reporting a prevalence of 65%. Other studies on childhood AA conducted in Asian and Arab populations observed mainly mild cases,” they wrote.

Nail involvement, often reported with AA, was evident in 39% of patients who completed the questionnaire online and in 44% on physical exam. This agreed with the 26%-40% involvement reported in the literature.

There were no conflicts of interest or funding information reported.

SOURCE: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13387.

Pediatric alopecia areata (AA) is more likely to affect girls, but boys are likely to have more severe types of the disorder, reported Iris Wohlmuth-Wieser, MD, of the department of dermatology, MD Anderson Cancer Center, Houston, and her associates, who conducted a large review of U.S. registry data.

Although it is the third most common dermatosis in children, there are not much data on AA in children, so the researchers used information from the National Alopecia Areata Registry, which was established in 2000. First, interested patients and parents were contacted and asked to fill out a web-based screening questionnaire. In the second phase, they were asked to fill out a more extensive survey and visit one of five U.S. sites for a clinical exam by a dermatologist.

Of the 2,218 children and teens who completed the initial questionnaire, the mean age at the time of the survey was 10 years, and their mean age of onset of AA was 6 years. The female to male ratio was 1.5:1; boys were significantly more likely to have severe types of AA (P = .009). Most patients (70%) were white, followed by mixed ethnicity (11%), Hispanic (3%), and then other ethnicities. About 3% of patients said they had a sibling with AA, 14% said that another first-degree relative had AA, and 8% said that at least three first-degree relatives had AA.

In terms of the degree of hair loss, 45% lost all scalp hair, 31% lost all body hair, and 14% lost all nails.

Concomitant diseases were reported by 47% of the responders, with atopic dermatitis, asthma, hay fever, and allergies the most common.

Of the 643 children and teens who completed a more detailed questionnaire and underwent clinical examination, 63% were female; 26% had at least one relative with AA and 8% had at least three first-degree relatives with AA. Almost 4% had congenital AA.

At the physical exam, there were data on the amount of hair loss in 617 children: Of these children, 37% had lost all scalp hair and 19% had lost up to three-quarters of their scalp hair. In 618 children (in whom information on body hair loss was obtained at the physical exam), 72% lost all or some of their body hair. Information on nails was available in 609 children; in this group, 44% had some nail involvement. More detailed information was available in 290 children; in this group, findings included pitting in 86%, dystrophy in 10%, onycholysis in 2%, ridging in 1%, and onychomycosis in 1%.

Commenting on the 25 children who presented with congenital AA, the authors wrote that this is “an extremely rare and infrequently reported form of AA.

“This is an interesting and important finding, because AA has traditionally been described as an acquired disease,” they added.

In their cohort overall, 25% had a family history of AA, with 8% having more than three first-degree relatives with AA. The researchers said that the percentage of children with AA and a positive family history ranges from 8% to 52% in the literature.

“The predominant presentation of AA types in our cohort (61.4%) was severe hair loss (76%-100% of scalp hair loss). This is comparable with a European study reporting a prevalence of 65%. Other studies on childhood AA conducted in Asian and Arab populations observed mainly mild cases,” they wrote.

Nail involvement, often reported with AA, was evident in 39% of patients who completed the questionnaire online and in 44% on physical exam. This agreed with the 26%-40% involvement reported in the literature.

There were no conflicts of interest or funding information reported.

SOURCE: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13387.

Pediatric alopecia areata (AA) is more likely to affect girls, but boys are likely to have more severe types of the disorder, reported Iris Wohlmuth-Wieser, MD, of the department of dermatology, MD Anderson Cancer Center, Houston, and her associates, who conducted a large review of U.S. registry data.

Although it is the third most common dermatosis in children, there are not much data on AA in children, so the researchers used information from the National Alopecia Areata Registry, which was established in 2000. First, interested patients and parents were contacted and asked to fill out a web-based screening questionnaire. In the second phase, they were asked to fill out a more extensive survey and visit one of five U.S. sites for a clinical exam by a dermatologist.

Of the 2,218 children and teens who completed the initial questionnaire, the mean age at the time of the survey was 10 years, and their mean age of onset of AA was 6 years. The female to male ratio was 1.5:1; boys were significantly more likely to have severe types of AA (P = .009). Most patients (70%) were white, followed by mixed ethnicity (11%), Hispanic (3%), and then other ethnicities. About 3% of patients said they had a sibling with AA, 14% said that another first-degree relative had AA, and 8% said that at least three first-degree relatives had AA.

In terms of the degree of hair loss, 45% lost all scalp hair, 31% lost all body hair, and 14% lost all nails.

Concomitant diseases were reported by 47% of the responders, with atopic dermatitis, asthma, hay fever, and allergies the most common.

Of the 643 children and teens who completed a more detailed questionnaire and underwent clinical examination, 63% were female; 26% had at least one relative with AA and 8% had at least three first-degree relatives with AA. Almost 4% had congenital AA.

At the physical exam, there were data on the amount of hair loss in 617 children: Of these children, 37% had lost all scalp hair and 19% had lost up to three-quarters of their scalp hair. In 618 children (in whom information on body hair loss was obtained at the physical exam), 72% lost all or some of their body hair. Information on nails was available in 609 children; in this group, 44% had some nail involvement. More detailed information was available in 290 children; in this group, findings included pitting in 86%, dystrophy in 10%, onycholysis in 2%, ridging in 1%, and onychomycosis in 1%.

Commenting on the 25 children who presented with congenital AA, the authors wrote that this is “an extremely rare and infrequently reported form of AA.

“This is an interesting and important finding, because AA has traditionally been described as an acquired disease,” they added.

In their cohort overall, 25% had a family history of AA, with 8% having more than three first-degree relatives with AA. The researchers said that the percentage of children with AA and a positive family history ranges from 8% to 52% in the literature.

“The predominant presentation of AA types in our cohort (61.4%) was severe hair loss (76%-100% of scalp hair loss). This is comparable with a European study reporting a prevalence of 65%. Other studies on childhood AA conducted in Asian and Arab populations observed mainly mild cases,” they wrote.

Nail involvement, often reported with AA, was evident in 39% of patients who completed the questionnaire online and in 44% on physical exam. This agreed with the 26%-40% involvement reported in the literature.

There were no conflicts of interest or funding information reported.

SOURCE: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13387.

When longitudinal melanonychia appears as a sharply demarcated pigment band of even width against normal nail in a child, Hutchinson’s sign with longitudinal brushy pigmentation may be a useful clinical pattern suggesting a diagnosis of nail matrix nevus rather than subungual melanoma, said Jae Ho Lee, MD, of Sungkyunkwan University, Seoul, South Korea, and associates.

In a study of biopsy-proven nail matrix nevi (NMN) in 20 children and 8 adults, average melanonychia width was 3.5 times greater in children than in adults, with 14 children having melanonychia greater than 20% the width of the nail, compared with 2 adults. Total melanonychia occurred just twice, in two children. A total of 12 children had nail dystrophy, while none of the adults did; nail dystrophy was more frequent in wider lesions.

Hutchinson’s sign was seen in seven pediatric patients, but no adult patients. In most cases, Hutchinson’s sign had hyponychial pigmentation, and on dermoscopy showed a pigment pattern presenting longitudinally and resembling a brush mark (longitudinal brushy pigmentation or LBP). LBP of nail matrix nevi is different from the Hutchinson’s sign that occurs in subungual melanoma (SUM), where it is typically a “haphazard pigmentation pattern involving periungual skin.

“We propose that Hutchinson’s sign occurs more commonly in pediatric NMN than in adult NMN, and that the presence of the LBP pattern can help distinguish pediatric NMN from SUM,” the investigators said.

Histologically, the biopsies of the NMN in this study showed some important differences from known SUM histology. All the study biopsies “showed a melanocytic proliferation exhibiting a predominantly nested growth pattern, with the nests mostly located at the dermoepithelial junction and with retraction artifact surrounding the nests. There were variable nuclear hyperchromatism, nuclear sizes, and cytologic atypia within the NMN biopsy specimens,” the researchers said. “In contrast, the histology of SUM demonstrates a predominance of atypical single melanocytes over nests, retraction artifacts around individual melanocytes, and uniform atypia of melanocytes throughout the biopsy specimen.”

SOURCE: Lee JH et al. J Am Acad Dermatol. 2018 Mar;78(3):479-89.

When longitudinal melanonychia appears as a sharply demarcated pigment band of even width against normal nail in a child, Hutchinson’s sign with longitudinal brushy pigmentation may be a useful clinical pattern suggesting a diagnosis of nail matrix nevus rather than subungual melanoma, said Jae Ho Lee, MD, of Sungkyunkwan University, Seoul, South Korea, and associates.

In a study of biopsy-proven nail matrix nevi (NMN) in 20 children and 8 adults, average melanonychia width was 3.5 times greater in children than in adults, with 14 children having melanonychia greater than 20% the width of the nail, compared with 2 adults. Total melanonychia occurred just twice, in two children. A total of 12 children had nail dystrophy, while none of the adults did; nail dystrophy was more frequent in wider lesions.

Hutchinson’s sign was seen in seven pediatric patients, but no adult patients. In most cases, Hutchinson’s sign had hyponychial pigmentation, and on dermoscopy showed a pigment pattern presenting longitudinally and resembling a brush mark (longitudinal brushy pigmentation or LBP). LBP of nail matrix nevi is different from the Hutchinson’s sign that occurs in subungual melanoma (SUM), where it is typically a “haphazard pigmentation pattern involving periungual skin.

“We propose that Hutchinson’s sign occurs more commonly in pediatric NMN than in adult NMN, and that the presence of the LBP pattern can help distinguish pediatric NMN from SUM,” the investigators said.

Histologically, the biopsies of the NMN in this study showed some important differences from known SUM histology. All the study biopsies “showed a melanocytic proliferation exhibiting a predominantly nested growth pattern, with the nests mostly located at the dermoepithelial junction and with retraction artifact surrounding the nests. There were variable nuclear hyperchromatism, nuclear sizes, and cytologic atypia within the NMN biopsy specimens,” the researchers said. “In contrast, the histology of SUM demonstrates a predominance of atypical single melanocytes over nests, retraction artifacts around individual melanocytes, and uniform atypia of melanocytes throughout the biopsy specimen.”

SOURCE: Lee JH et al. J Am Acad Dermatol. 2018 Mar;78(3):479-89.

When longitudinal melanonychia appears as a sharply demarcated pigment band of even width against normal nail in a child, Hutchinson’s sign with longitudinal brushy pigmentation may be a useful clinical pattern suggesting a diagnosis of nail matrix nevus rather than subungual melanoma, said Jae Ho Lee, MD, of Sungkyunkwan University, Seoul, South Korea, and associates.

In a study of biopsy-proven nail matrix nevi (NMN) in 20 children and 8 adults, average melanonychia width was 3.5 times greater in children than in adults, with 14 children having melanonychia greater than 20% the width of the nail, compared with 2 adults. Total melanonychia occurred just twice, in two children. A total of 12 children had nail dystrophy, while none of the adults did; nail dystrophy was more frequent in wider lesions.

Hutchinson’s sign was seen in seven pediatric patients, but no adult patients. In most cases, Hutchinson’s sign had hyponychial pigmentation, and on dermoscopy showed a pigment pattern presenting longitudinally and resembling a brush mark (longitudinal brushy pigmentation or LBP). LBP of nail matrix nevi is different from the Hutchinson’s sign that occurs in subungual melanoma (SUM), where it is typically a “haphazard pigmentation pattern involving periungual skin.

“We propose that Hutchinson’s sign occurs more commonly in pediatric NMN than in adult NMN, and that the presence of the LBP pattern can help distinguish pediatric NMN from SUM,” the investigators said.

Histologically, the biopsies of the NMN in this study showed some important differences from known SUM histology. All the study biopsies “showed a melanocytic proliferation exhibiting a predominantly nested growth pattern, with the nests mostly located at the dermoepithelial junction and with retraction artifact surrounding the nests. There were variable nuclear hyperchromatism, nuclear sizes, and cytologic atypia within the NMN biopsy specimens,” the researchers said. “In contrast, the histology of SUM demonstrates a predominance of atypical single melanocytes over nests, retraction artifacts around individual melanocytes, and uniform atypia of melanocytes throughout the biopsy specimen.”

SOURCE: Lee JH et al. J Am Acad Dermatol. 2018 Mar;78(3):479-89.

REPORTING FROM AAD 18

SAN DIEGO – Several device-based therapies are currently being evaluated as treatments for onychomycosis.

These include photodynamic therapy, which has been studied in two clinical trials and case series, Shari Lipner, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she presented on this topic.

“Something that we’re looking at is plasma treatment of onychomycosis basically using ionized gas,” which has been shown to inhibit the growth of Trichophyton rubrum in vitro, added Dr. Lipner of the department of dermatology, Cornell University, New York.

In a pilot study of 19 patients with onychomycosis, she and her associates found that the clinical cure with nonthermal plasma was about 50% and the mycological cure rate was 15%, “and we’re now trying to improve efficacy using this device,” she said (Clin Exp Dermatol. 2017 Apr;42[3]:295-8). With a dielectric insulator, “nonthermal plasma is created by short pulses (about 10 ns) of strong (about 20 kV/mm peak) electric field that ionizes air molecules, creating ions and electrons, as well as ozone, hydroxyl radicals and nitric oxide,” according to the description in the study.

Other device-based therapies include iontophoresis, using electrical currents to increase drug delivery, and creating small punch biopsies or using a device to create “microholes” in the nails to increase delivery of topical medication across the nail, Dr. Lipner said.

Patients often ask about another device-based treatment, laser therapy, which she pointed out is not approved by the Food and Drug Administration for cure, but for a temporary increase in clear nail in patients with onychomycosis, “very different” than the criteria used for topical and systemic medications, making it difficult to compare efficacy data between lasers and medications, she noted.

Dr. Lipner reported receiving grants/research funding from MOE Medical Devices.

[email protected]

REPORTING FROM AAD 18

SAN DIEGO – Several device-based therapies are currently being evaluated as treatments for onychomycosis.

These include photodynamic therapy, which has been studied in two clinical trials and case series, Shari Lipner, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she presented on this topic.

“Something that we’re looking at is plasma treatment of onychomycosis basically using ionized gas,” which has been shown to inhibit the growth of Trichophyton rubrum in vitro, added Dr. Lipner of the department of dermatology, Cornell University, New York.

In a pilot study of 19 patients with onychomycosis, she and her associates found that the clinical cure with nonthermal plasma was about 50% and the mycological cure rate was 15%, “and we’re now trying to improve efficacy using this device,” she said (Clin Exp Dermatol. 2017 Apr;42[3]:295-8). With a dielectric insulator, “nonthermal plasma is created by short pulses (about 10 ns) of strong (about 20 kV/mm peak) electric field that ionizes air molecules, creating ions and electrons, as well as ozone, hydroxyl radicals and nitric oxide,” according to the description in the study.

Other device-based therapies include iontophoresis, using electrical currents to increase drug delivery, and creating small punch biopsies or using a device to create “microholes” in the nails to increase delivery of topical medication across the nail, Dr. Lipner said.

Patients often ask about another device-based treatment, laser therapy, which she pointed out is not approved by the Food and Drug Administration for cure, but for a temporary increase in clear nail in patients with onychomycosis, “very different” than the criteria used for topical and systemic medications, making it difficult to compare efficacy data between lasers and medications, she noted.

Dr. Lipner reported receiving grants/research funding from MOE Medical Devices.

[email protected]

REPORTING FROM AAD 18

SAN DIEGO – Several device-based therapies are currently being evaluated as treatments for onychomycosis.

These include photodynamic therapy, which has been studied in two clinical trials and case series, Shari Lipner, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she presented on this topic.

“Something that we’re looking at is plasma treatment of onychomycosis basically using ionized gas,” which has been shown to inhibit the growth of Trichophyton rubrum in vitro, added Dr. Lipner of the department of dermatology, Cornell University, New York.

In a pilot study of 19 patients with onychomycosis, she and her associates found that the clinical cure with nonthermal plasma was about 50% and the mycological cure rate was 15%, “and we’re now trying to improve efficacy using this device,” she said (Clin Exp Dermatol. 2017 Apr;42[3]:295-8). With a dielectric insulator, “nonthermal plasma is created by short pulses (about 10 ns) of strong (about 20 kV/mm peak) electric field that ionizes air molecules, creating ions and electrons, as well as ozone, hydroxyl radicals and nitric oxide,” according to the description in the study.

Other device-based therapies include iontophoresis, using electrical currents to increase drug delivery, and creating small punch biopsies or using a device to create “microholes” in the nails to increase delivery of topical medication across the nail, Dr. Lipner said.

Patients often ask about another device-based treatment, laser therapy, which she pointed out is not approved by the Food and Drug Administration for cure, but for a temporary increase in clear nail in patients with onychomycosis, “very different” than the criteria used for topical and systemic medications, making it difficult to compare efficacy data between lasers and medications, she noted.

Dr. Lipner reported receiving grants/research funding from MOE Medical Devices.

[email protected]

What does your patient need to know at the first visit?

Risk factors for onychomycosis include prior trauma, history of tinea pedis, sports activities, frequenting gyms and pools, hyperhidrosis, advancing age, diabetes mellitus, immunosuppression, smoking, and family history of onychomycosis. Toenails are involved more frequently than fingernails, and typical physical examination findings are distal and lateral nail plate onycholysis with subungual hyperkeratosis. In more severe cases, there may be nail plate thickening, crumbling, yellowing, and involvement of the nail matrix.

Because other nail conditions may resemble onychomycosis, it is imperative to confirm the diagnosis using histopathology, direct microscopy, fungal culture, and/or polymerase chain reaction on nail plate clippings or subungual debris. 

What are your go-to treatments? What are the side effects?

After laboratory confirmation, assess the patient for the severity of the infection based on the surface area of nail plate affected, nail plate thickness, involvement of the nail matrix, and number of nails affected. United States Food and Drug Administration-approved oral and topical antifungals are used first line for the treatment of onychomycosis. Devices such as lasers are approved by the US Food and Drug Administration for temporary cosmetic improvement in the appearance of the nail without eradicating the fungus.

Oral antifungals such as terbinafine, itraconazole, and fluconazole (off label) are indicated for patients with severe disease. Patients with mild to moderate disease may benefit from oral or topical antifungals such as efinaconazole, tavaborole, or ciclopirox.

I recommend terbinafine to many of my patients due to its high complete and mycological cure rates, short list of drug-drug interactions, and low incidence of side effects. Adverse reactions are uncommon, with the most common being gastrointestinal upset. While liver injury has been reported, it is exceedingly rare. Itraconazole has many important drug interactions and is contraindicated in patients with congestive heart failure. With topical antifungals, side effects are uncommon, but dermatitis, ingrown nails, and vesicles may occur.

How do you keep patients compliant with treatment?

Patients on a 3-month course of daily oral terbinafine or itraconazole for toenail onychomycosis are typically highly compliant. Compliance for patients on oral fluconazole (off label) is generally more challenging because it is dosed weekly until the nail grows out (1-1.5 years for toenails). To circumvent missed fluconazole doses, I recommend that the patient schedule quarterly visits with me and also to set a cell phone alarm as a weekly reminder to take the medication.

Because topical medications are prescribed for the toenails for a year-long course (with avoidance of nail polish during this period), I prescribe topical antifungals only to highly motivated patients. In addition, because topical antifungals are retained in the nail plate for at least several days after a month-long application, I tell my patients that if they have a big event to attend that they can take a vacation from the topical antifungal, get a pedicure, and then resume treatment after the event. 

What do you do if they refuse treatment?

In 2018, we have many options to treat onychomycosis effectively, and therapy is individualized based on the patient's severity of disease, infecting organism(s), comorbidities, concomitant medications, and preferences. If the patient's fungal nail infection is asymptomatic and not aesthetically bothersome, he/she may opt for observation rather than treatment. If the decision is observation, I recommend use of a topical antifungal on the feet and web spaces to prevent worsening of onychomycosis. 

Suggested Readings

Gupta AK, Versteeg SG. A critical review of improvement rates for laser therapy used to treat toenail onychomycosis. J Eur Acad Dermatol Venereol. 2017;31:1111-1118.

Lipner SR, Scher RK. Long-standing onychodystrophy in a young woman. JAMA. 2016;316:1915-1916.

Lipner SR, Scher RK. Onychomycosis--a small step for quality of care. Curr Med Res Opin. 2016;32:865-867.

Lipner SR, Scher RK. Onychomycosis: current and investigational therapies. Cutis. 2014;94:E21-E24.

What does your patient need to know at the first visit?

Risk factors for onychomycosis include prior trauma, history of tinea pedis, sports activities, frequenting gyms and pools, hyperhidrosis, advancing age, diabetes mellitus, immunosuppression, smoking, and family history of onychomycosis. Toenails are involved more frequently than fingernails, and typical physical examination findings are distal and lateral nail plate onycholysis with subungual hyperkeratosis. In more severe cases, there may be nail plate thickening, crumbling, yellowing, and involvement of the nail matrix.

Because other nail conditions may resemble onychomycosis, it is imperative to confirm the diagnosis using histopathology, direct microscopy, fungal culture, and/or polymerase chain reaction on nail plate clippings or subungual debris. 

What are your go-to treatments? What are the side effects?

After laboratory confirmation, assess the patient for the severity of the infection based on the surface area of nail plate affected, nail plate thickness, involvement of the nail matrix, and number of nails affected. United States Food and Drug Administration-approved oral and topical antifungals are used first line for the treatment of onychomycosis. Devices such as lasers are approved by the US Food and Drug Administration for temporary cosmetic improvement in the appearance of the nail without eradicating the fungus.

Oral antifungals such as terbinafine, itraconazole, and fluconazole (off label) are indicated for patients with severe disease. Patients with mild to moderate disease may benefit from oral or topical antifungals such as efinaconazole, tavaborole, or ciclopirox.

I recommend terbinafine to many of my patients due to its high complete and mycological cure rates, short list of drug-drug interactions, and low incidence of side effects. Adverse reactions are uncommon, with the most common being gastrointestinal upset. While liver injury has been reported, it is exceedingly rare. Itraconazole has many important drug interactions and is contraindicated in patients with congestive heart failure. With topical antifungals, side effects are uncommon, but dermatitis, ingrown nails, and vesicles may occur.

How do you keep patients compliant with treatment?

Patients on a 3-month course of daily oral terbinafine or itraconazole for toenail onychomycosis are typically highly compliant. Compliance for patients on oral fluconazole (off label) is generally more challenging because it is dosed weekly until the nail grows out (1-1.5 years for toenails). To circumvent missed fluconazole doses, I recommend that the patient schedule quarterly visits with me and also to set a cell phone alarm as a weekly reminder to take the medication.

Because topical medications are prescribed for the toenails for a year-long course (with avoidance of nail polish during this period), I prescribe topical antifungals only to highly motivated patients. In addition, because topical antifungals are retained in the nail plate for at least several days after a month-long application, I tell my patients that if they have a big event to attend that they can take a vacation from the topical antifungal, get a pedicure, and then resume treatment after the event. 

What do you do if they refuse treatment?

In 2018, we have many options to treat onychomycosis effectively, and therapy is individualized based on the patient's severity of disease, infecting organism(s), comorbidities, concomitant medications, and preferences. If the patient's fungal nail infection is asymptomatic and not aesthetically bothersome, he/she may opt for observation rather than treatment. If the decision is observation, I recommend use of a topical antifungal on the feet and web spaces to prevent worsening of onychomycosis. 

Suggested Readings

Gupta AK, Versteeg SG. A critical review of improvement rates for laser therapy used to treat toenail onychomycosis. J Eur Acad Dermatol Venereol. 2017;31:1111-1118.

Lipner SR, Scher RK. Long-standing onychodystrophy in a young woman. JAMA. 2016;316:1915-1916.

Lipner SR, Scher RK. Onychomycosis--a small step for quality of care. Curr Med Res Opin. 2016;32:865-867.

Lipner SR, Scher RK. Onychomycosis: current and investigational therapies. Cutis. 2014;94:E21-E24.

What does your patient need to know at the first visit?

Risk factors for onychomycosis include prior trauma, history of tinea pedis, sports activities, frequenting gyms and pools, hyperhidrosis, advancing age, diabetes mellitus, immunosuppression, smoking, and family history of onychomycosis. Toenails are involved more frequently than fingernails, and typical physical examination findings are distal and lateral nail plate onycholysis with subungual hyperkeratosis. In more severe cases, there may be nail plate thickening, crumbling, yellowing, and involvement of the nail matrix.

Because other nail conditions may resemble onychomycosis, it is imperative to confirm the diagnosis using histopathology, direct microscopy, fungal culture, and/or polymerase chain reaction on nail plate clippings or subungual debris. 

What are your go-to treatments? What are the side effects?

After laboratory confirmation, assess the patient for the severity of the infection based on the surface area of nail plate affected, nail plate thickness, involvement of the nail matrix, and number of nails affected. United States Food and Drug Administration-approved oral and topical antifungals are used first line for the treatment of onychomycosis. Devices such as lasers are approved by the US Food and Drug Administration for temporary cosmetic improvement in the appearance of the nail without eradicating the fungus.

Oral antifungals such as terbinafine, itraconazole, and fluconazole (off label) are indicated for patients with severe disease. Patients with mild to moderate disease may benefit from oral or topical antifungals such as efinaconazole, tavaborole, or ciclopirox.

I recommend terbinafine to many of my patients due to its high complete and mycological cure rates, short list of drug-drug interactions, and low incidence of side effects. Adverse reactions are uncommon, with the most common being gastrointestinal upset. While liver injury has been reported, it is exceedingly rare. Itraconazole has many important drug interactions and is contraindicated in patients with congestive heart failure. With topical antifungals, side effects are uncommon, but dermatitis, ingrown nails, and vesicles may occur.

How do you keep patients compliant with treatment?

Patients on a 3-month course of daily oral terbinafine or itraconazole for toenail onychomycosis are typically highly compliant. Compliance for patients on oral fluconazole (off label) is generally more challenging because it is dosed weekly until the nail grows out (1-1.5 years for toenails). To circumvent missed fluconazole doses, I recommend that the patient schedule quarterly visits with me and also to set a cell phone alarm as a weekly reminder to take the medication.

Because topical medications are prescribed for the toenails for a year-long course (with avoidance of nail polish during this period), I prescribe topical antifungals only to highly motivated patients. In addition, because topical antifungals are retained in the nail plate for at least several days after a month-long application, I tell my patients that if they have a big event to attend that they can take a vacation from the topical antifungal, get a pedicure, and then resume treatment after the event. 

What do you do if they refuse treatment?

In 2018, we have many options to treat onychomycosis effectively, and therapy is individualized based on the patient's severity of disease, infecting organism(s), comorbidities, concomitant medications, and preferences. If the patient's fungal nail infection is asymptomatic and not aesthetically bothersome, he/she may opt for observation rather than treatment. If the decision is observation, I recommend use of a topical antifungal on the feet and web spaces to prevent worsening of onychomycosis. 

Suggested Readings

Gupta AK, Versteeg SG. A critical review of improvement rates for laser therapy used to treat toenail onychomycosis. J Eur Acad Dermatol Venereol. 2017;31:1111-1118.

Lipner SR, Scher RK. Long-standing onychodystrophy in a young woman. JAMA. 2016;316:1915-1916.

Lipner SR, Scher RK. Onychomycosis--a small step for quality of care. Curr Med Res Opin. 2016;32:865-867.

Lipner SR, Scher RK. Onychomycosis: current and investigational therapies. Cutis. 2014;94:E21-E24.

KAUAI, HAWAII – A topical halobetasol/tazarotene fixed-combination lotion for moderate to severe psoriasis hit all of its efficacy and safety endpoints in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.

Bruce Jancin/Frontline Medical News

[email protected]

KAUAI, HAWAII – A topical halobetasol/tazarotene fixed-combination lotion for moderate to severe psoriasis hit all of its efficacy and safety endpoints in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.

Bruce Jancin/Frontline Medical News

[email protected]

KAUAI, HAWAII – A topical halobetasol/tazarotene fixed-combination lotion for moderate to severe psoriasis hit all of its efficacy and safety endpoints in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.

Bruce Jancin/Frontline Medical News

[email protected]

SAN DIEGO – Treatment with a Janus kinase inhibitor such as tofacitinib is a reasonable option for patients with refractory alopecia who seek resolution of their hair loss and understand the adverse event risk from using this drug class, John E. Harris, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Using a Janus kinase (JAK) inhibitor to treat alopecia areata or totalis is a “highly successful, emerging therapy,” with efficacy rates for good responses of about a third or higher in a handful of published reports with experiences in more than 150 patients, said Dr. Harris, an associate professor of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School in Worcester.

Image

Mitchel L. Zoler/Frontline Medical News

“Some clinicians may say ‘I’d never prescribe a JAK inhibitor for hair loss, it’s too dangerous,’ but several hundred alopecia patients have now received this with no serious adverse effects,” said Dr. Harris. He acknowledged, however, that eventually some patients treated this way will have serious adverse effects. He said that he is treating with tofacitinib a “handful” of alopecia patients who have been unresponsive to other treatments, are eager for an intervention that might regrow their hair, and who understand and accept the risk for developing an infection, shingles, or myelosuppression (with ruxolitinib treatment).

Roughly half of the alopecia patients prescribed tofacitinib (Xeljanz) by Dr. Harris have had their drug cost covered by health insurance, with the others paying for it themselves. Arranging for insurance coverage has usually involved filing an appeal, Dr. Harris said in an interview. The reported successful dosages have been 5 mg bid, with a boost to 10 mg bid for patients who don’t initially respond.

Insurance companies have not yet paid for treatment with ruxolitinib (Jakafi), which has been described in case reports in far fewer patients and which costs about $120,000 a year, he noted.

Dr. Harris said that JAK inhibitors also have great potential for treating vitiligo, a disorder he thinks shares many features in common with alopecia ( J Allergy Clin Immunol. 2017 Sept;140[3]:654-62). 

“I think [JAK inhibitors] will have the same efficacy in vitiligo,” he predicted. He is particularly enthused about the possibility of administering ruxolitinib topically to patients with alopecia or vitiligo. Ruxolitinib is well suited to topical administration because of its good skin penetration, Dr. Harris said. Several trials now in progress are further studying JAK inhibitors for alopecia using oral or topical formulations.

Dr. Harris has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib (Xeljanz). He has also been a consultant to a dozen other companies, and has also received research support from Aclaris Therapeutics, Celgene, Dermavant, Genzyme, Sanofi, and Stiefel/GlaxoSmithKline.

[email protected]

SAN DIEGO – Treatment with a Janus kinase inhibitor such as tofacitinib is a reasonable option for patients with refractory alopecia who seek resolution of their hair loss and understand the adverse event risk from using this drug class, John E. Harris, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Using a Janus kinase (JAK) inhibitor to treat alopecia areata or totalis is a “highly successful, emerging therapy,” with efficacy rates for good responses of about a third or higher in a handful of published reports with experiences in more than 150 patients, said Dr. Harris, an associate professor of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School in Worcester.

Image

Mitchel L. Zoler/Frontline Medical News

“Some clinicians may say ‘I’d never prescribe a JAK inhibitor for hair loss, it’s too dangerous,’ but several hundred alopecia patients have now received this with no serious adverse effects,” said Dr. Harris. He acknowledged, however, that eventually some patients treated this way will have serious adverse effects. He said that he is treating with tofacitinib a “handful” of alopecia patients who have been unresponsive to other treatments, are eager for an intervention that might regrow their hair, and who understand and accept the risk for developing an infection, shingles, or myelosuppression (with ruxolitinib treatment).

Roughly half of the alopecia patients prescribed tofacitinib (Xeljanz) by Dr. Harris have had their drug cost covered by health insurance, with the others paying for it themselves. Arranging for insurance coverage has usually involved filing an appeal, Dr. Harris said in an interview. The reported successful dosages have been 5 mg bid, with a boost to 10 mg bid for patients who don’t initially respond.

Insurance companies have not yet paid for treatment with ruxolitinib (Jakafi), which has been described in case reports in far fewer patients and which costs about $120,000 a year, he noted.

Dr. Harris said that JAK inhibitors also have great potential for treating vitiligo, a disorder he thinks shares many features in common with alopecia ( J Allergy Clin Immunol. 2017 Sept;140[3]:654-62). 

“I think [JAK inhibitors] will have the same efficacy in vitiligo,” he predicted. He is particularly enthused about the possibility of administering ruxolitinib topically to patients with alopecia or vitiligo. Ruxolitinib is well suited to topical administration because of its good skin penetration, Dr. Harris said. Several trials now in progress are further studying JAK inhibitors for alopecia using oral or topical formulations.

Dr. Harris has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib (Xeljanz). He has also been a consultant to a dozen other companies, and has also received research support from Aclaris Therapeutics, Celgene, Dermavant, Genzyme, Sanofi, and Stiefel/GlaxoSmithKline.

[email protected]

SAN DIEGO – Treatment with a Janus kinase inhibitor such as tofacitinib is a reasonable option for patients with refractory alopecia who seek resolution of their hair loss and understand the adverse event risk from using this drug class, John E. Harris, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Using a Janus kinase (JAK) inhibitor to treat alopecia areata or totalis is a “highly successful, emerging therapy,” with efficacy rates for good responses of about a third or higher in a handful of published reports with experiences in more than 150 patients, said Dr. Harris, an associate professor of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School in Worcester.

Image

Mitchel L. Zoler/Frontline Medical News

“Some clinicians may say ‘I’d never prescribe a JAK inhibitor for hair loss, it’s too dangerous,’ but several hundred alopecia patients have now received this with no serious adverse effects,” said Dr. Harris. He acknowledged, however, that eventually some patients treated this way will have serious adverse effects. He said that he is treating with tofacitinib a “handful” of alopecia patients who have been unresponsive to other treatments, are eager for an intervention that might regrow their hair, and who understand and accept the risk for developing an infection, shingles, or myelosuppression (with ruxolitinib treatment).

Roughly half of the alopecia patients prescribed tofacitinib (Xeljanz) by Dr. Harris have had their drug cost covered by health insurance, with the others paying for it themselves. Arranging for insurance coverage has usually involved filing an appeal, Dr. Harris said in an interview. The reported successful dosages have been 5 mg bid, with a boost to 10 mg bid for patients who don’t initially respond.

Insurance companies have not yet paid for treatment with ruxolitinib (Jakafi), which has been described in case reports in far fewer patients and which costs about $120,000 a year, he noted.

Dr. Harris said that JAK inhibitors also have great potential for treating vitiligo, a disorder he thinks shares many features in common with alopecia ( J Allergy Clin Immunol. 2017 Sept;140[3]:654-62). 

“I think [JAK inhibitors] will have the same efficacy in vitiligo,” he predicted. He is particularly enthused about the possibility of administering ruxolitinib topically to patients with alopecia or vitiligo. Ruxolitinib is well suited to topical administration because of its good skin penetration, Dr. Harris said. Several trials now in progress are further studying JAK inhibitors for alopecia using oral or topical formulations.

Dr. Harris has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib (Xeljanz). He has also been a consultant to a dozen other companies, and has also received research support from Aclaris Therapeutics, Celgene, Dermavant, Genzyme, Sanofi, and Stiefel/GlaxoSmithKline.

[email protected]

Nail-patella syndrome (NPS), also known as hereditary osteo-onychodysplasia syndrome, is a rare autosomal-dominant disorder with an estimated incidence of 1 per 50,000 individuals in the United States. Nail-patella syndrome presents due to a heterozygous loss-of-function mutation in the LIM homeobox transcription factor 1 beta gene, LMX1B, on chromosome 9q34.¹ LMX1B gene mutations are fully penetrant, but there is variable expressivity, even within families.²

Case Report

A 69-year-old man presented to the dermatology clinic for a routine skin cancer screening. The patient’s history was remarkable for dystrophic fingernails and toenails since birth. In his 20s he developed progressively worsening instability of the left knee and chronic back pain due to scoliosis, lumbar lordosis, and spinal disc herniation. Since then, he underwent knee surgery and 7 back surgeries for rheumatologic disease. His medical history also was remarkable for osteoporosis, hypertension, and glaucoma. Family history was notable for similar findings in the patient’s sister; mother; and maternal aunt, uncle, and grandmother, all with varying disease severity.

Physical examination was remarkable for bilateral fingernail hypoplasia that was most prominent on the thumb, with improvement in each nail on progression toward the fifth digit (Figure 1A). Triangular fingernail lunulae, longitudinal ridging, and nail splitting were present (Figure 1A and 1B). Hypoplastic crumbly toenails also were appreciated (Figure 1C). Skin creases over the distal interphalangeal joints of the fingers and toes were conspicuously absent. Limited range of motion was noted in multiple joints, with profound limitation of bilateral elbow extension. Review of prior imaging reports revealed bilateral iliac horns as well as left patellar absence and right patellar hypoplasia (Figure 2). Urinalysis was remarkable for proteinuria and microscopic hematuria. Given the constellation of examination findings and positive family history, a diagnosis of NPS was made.

Comment

Nail-patella syndrome is characterized by variable dermatologic, neurologic, nephrogenic, ophthalmologic, and orthopedic clinical manifestations.³ Almost all patients with NPS have bilateral and symmetric nail changes, including absent or hypoplastic nails with ridging, splitting, or discoloration and triangular-shaped lunulae.^1,4 Nail findings are the most consistent findings of NPS, as they are present in more than 98% of patients.⁵ The thumb often is the most severely affected nail, with improvement appreciated on progression toward the fifth digit, as seen in our patient (Figure 1A).⁵ Each individual nail usually is more severely affected on its ulnar side. When toenails are involved, the abnormalities tend to be less severe, and the little toenail is most commonly affected. Distal digital changes also are observed in almost all patients. Loss of dorsal creases in the skin overlying the distal interphalangeal joints can be considered as a diagnostic clue.^3,4

There are a variety of orthopedic manifestations of NPS. Hypoplastic or absent patellae leading to recurrent subluxations or dislocations is a common finding.⁴ Bilateral symmetric bone formations (horns) arising from the iliac crest are pathognomonic but only found on radiography 70% of the time.⁶ Occasionally these protuberances can be palpated on physical examination,⁵ though this finding was not appreciated in our patient. Dysplasia of the elbows may result in limited elbow extension and limited pronation and supination. Early degenerative arthritis, lumbar lordosis, and scoliosis also are not uncommon. In addition, skeletal integrity is compromised, leading to early osteoporosis and increased risk for fractures.⁵

Nephropathy develops in approximately 30% to 40% of patients and is a major determinant of mortality in these patients.² Mutations in the LMX1B gene lead to abnormal development of podocytes and reduction in collagen in the glomerular basement membrane. The first sign of renal involvement usually is proteinuria, with or without microscopic hematuria. As in our patient, many patients develop hypertension. Patients may progress to develop nephrotic syndrome and end-stage renal failure (5%–10%).⁷ Death from NPS-related nephropathy has occurred, even in childhood.^4,5

Primary open-angle glaucoma has been recognized as a feature of NPS.⁸ It is the most frequent ocular abnormality observed, followed by ocular hypertension and Lester sign of the iris.^3,5 These conditions also are more common in younger patients with NPS than in the general population.⁵ Important neurologic findings include epilepsy, peripheral neuropathy, attention deficit disorder, major depressive disorder, and vasomotor problems.⁹

Our case highlights the importance of recognizing this rare condition to provide a multidisciplinary approach to care that addresses all aspects of LMX1B-associated disease in affected individuals. Nail findings may be the first clue to the need for additional screenings in these patients. Nail-patella syndrome patients should undergo thorough ophthalmologic examinations every 2 years, including measurement of intraocular pressure, examination of the optic disc, and assessment of visual fields. Given the variability in severity of joint problems and the unpredictable anatomy of the joints, magnetic resonance imaging of the joints is recommended prior to orthopedic intervention. Most importantly, physicians should recognize this genodermatosis to implement periodic screenings for renal disease, as up to 40% of NPS patients develop kidney failure. Annual blood pressure measurements, urinalysis, and measurement of the protein to creatinine ratio in the urine are recommended. For patients with end-stage renal failure, renal transplantation results in cure of nephropathy and may even result in nail regrowth.¹⁰ Further, this case is notable in that it describes a patient with NPS who is older than most other individuals presenting with the condition, thereby revealing novel information about NPS in its more advanced stages.

Nail-patella syndrome (NPS), also known as hereditary osteo-onychodysplasia syndrome, is a rare autosomal-dominant disorder with an estimated incidence of 1 per 50,000 individuals in the United States. Nail-patella syndrome presents due to a heterozygous loss-of-function mutation in the LIM homeobox transcription factor 1 beta gene, LMX1B, on chromosome 9q34.¹ LMX1B gene mutations are fully penetrant, but there is variable expressivity, even within families.²

Case Report

A 69-year-old man presented to the dermatology clinic for a routine skin cancer screening. The patient’s history was remarkable for dystrophic fingernails and toenails since birth. In his 20s he developed progressively worsening instability of the left knee and chronic back pain due to scoliosis, lumbar lordosis, and spinal disc herniation. Since then, he underwent knee surgery and 7 back surgeries for rheumatologic disease. His medical history also was remarkable for osteoporosis, hypertension, and glaucoma. Family history was notable for similar findings in the patient’s sister; mother; and maternal aunt, uncle, and grandmother, all with varying disease severity.

Physical examination was remarkable for bilateral fingernail hypoplasia that was most prominent on the thumb, with improvement in each nail on progression toward the fifth digit (Figure 1A). Triangular fingernail lunulae, longitudinal ridging, and nail splitting were present (Figure 1A and 1B). Hypoplastic crumbly toenails also were appreciated (Figure 1C). Skin creases over the distal interphalangeal joints of the fingers and toes were conspicuously absent. Limited range of motion was noted in multiple joints, with profound limitation of bilateral elbow extension. Review of prior imaging reports revealed bilateral iliac horns as well as left patellar absence and right patellar hypoplasia (Figure 2). Urinalysis was remarkable for proteinuria and microscopic hematuria. Given the constellation of examination findings and positive family history, a diagnosis of NPS was made.

Comment

Nail-patella syndrome is characterized by variable dermatologic, neurologic, nephrogenic, ophthalmologic, and orthopedic clinical manifestations.³ Almost all patients with NPS have bilateral and symmetric nail changes, including absent or hypoplastic nails with ridging, splitting, or discoloration and triangular-shaped lunulae.^1,4 Nail findings are the most consistent findings of NPS, as they are present in more than 98% of patients.⁵ The thumb often is the most severely affected nail, with improvement appreciated on progression toward the fifth digit, as seen in our patient (Figure 1A).⁵ Each individual nail usually is more severely affected on its ulnar side. When toenails are involved, the abnormalities tend to be less severe, and the little toenail is most commonly affected. Distal digital changes also are observed in almost all patients. Loss of dorsal creases in the skin overlying the distal interphalangeal joints can be considered as a diagnostic clue.^3,4

There are a variety of orthopedic manifestations of NPS. Hypoplastic or absent patellae leading to recurrent subluxations or dislocations is a common finding.⁴ Bilateral symmetric bone formations (horns) arising from the iliac crest are pathognomonic but only found on radiography 70% of the time.⁶ Occasionally these protuberances can be palpated on physical examination,⁵ though this finding was not appreciated in our patient. Dysplasia of the elbows may result in limited elbow extension and limited pronation and supination. Early degenerative arthritis, lumbar lordosis, and scoliosis also are not uncommon. In addition, skeletal integrity is compromised, leading to early osteoporosis and increased risk for fractures.⁵

Nephropathy develops in approximately 30% to 40% of patients and is a major determinant of mortality in these patients.² Mutations in the LMX1B gene lead to abnormal development of podocytes and reduction in collagen in the glomerular basement membrane. The first sign of renal involvement usually is proteinuria, with or without microscopic hematuria. As in our patient, many patients develop hypertension. Patients may progress to develop nephrotic syndrome and end-stage renal failure (5%–10%).⁷ Death from NPS-related nephropathy has occurred, even in childhood.^4,5

Primary open-angle glaucoma has been recognized as a feature of NPS.⁸ It is the most frequent ocular abnormality observed, followed by ocular hypertension and Lester sign of the iris.^3,5 These conditions also are more common in younger patients with NPS than in the general population.⁵ Important neurologic findings include epilepsy, peripheral neuropathy, attention deficit disorder, major depressive disorder, and vasomotor problems.⁹

Our case highlights the importance of recognizing this rare condition to provide a multidisciplinary approach to care that addresses all aspects of LMX1B-associated disease in affected individuals. Nail findings may be the first clue to the need for additional screenings in these patients. Nail-patella syndrome patients should undergo thorough ophthalmologic examinations every 2 years, including measurement of intraocular pressure, examination of the optic disc, and assessment of visual fields. Given the variability in severity of joint problems and the unpredictable anatomy of the joints, magnetic resonance imaging of the joints is recommended prior to orthopedic intervention. Most importantly, physicians should recognize this genodermatosis to implement periodic screenings for renal disease, as up to 40% of NPS patients develop kidney failure. Annual blood pressure measurements, urinalysis, and measurement of the protein to creatinine ratio in the urine are recommended. For patients with end-stage renal failure, renal transplantation results in cure of nephropathy and may even result in nail regrowth.¹⁰ Further, this case is notable in that it describes a patient with NPS who is older than most other individuals presenting with the condition, thereby revealing novel information about NPS in its more advanced stages.

Nail-patella syndrome (NPS), also known as hereditary osteo-onychodysplasia syndrome, is a rare autosomal-dominant disorder with an estimated incidence of 1 per 50,000 individuals in the United States. Nail-patella syndrome presents due to a heterozygous loss-of-function mutation in the LIM homeobox transcription factor 1 beta gene, LMX1B, on chromosome 9q34.¹ LMX1B gene mutations are fully penetrant, but there is variable expressivity, even within families.²

Case Report

A 69-year-old man presented to the dermatology clinic for a routine skin cancer screening. The patient’s history was remarkable for dystrophic fingernails and toenails since birth. In his 20s he developed progressively worsening instability of the left knee and chronic back pain due to scoliosis, lumbar lordosis, and spinal disc herniation. Since then, he underwent knee surgery and 7 back surgeries for rheumatologic disease. His medical history also was remarkable for osteoporosis, hypertension, and glaucoma. Family history was notable for similar findings in the patient’s sister; mother; and maternal aunt, uncle, and grandmother, all with varying disease severity.

Physical examination was remarkable for bilateral fingernail hypoplasia that was most prominent on the thumb, with improvement in each nail on progression toward the fifth digit (Figure 1A). Triangular fingernail lunulae, longitudinal ridging, and nail splitting were present (Figure 1A and 1B). Hypoplastic crumbly toenails also were appreciated (Figure 1C). Skin creases over the distal interphalangeal joints of the fingers and toes were conspicuously absent. Limited range of motion was noted in multiple joints, with profound limitation of bilateral elbow extension. Review of prior imaging reports revealed bilateral iliac horns as well as left patellar absence and right patellar hypoplasia (Figure 2). Urinalysis was remarkable for proteinuria and microscopic hematuria. Given the constellation of examination findings and positive family history, a diagnosis of NPS was made.

Comment

Nail-patella syndrome is characterized by variable dermatologic, neurologic, nephrogenic, ophthalmologic, and orthopedic clinical manifestations.³ Almost all patients with NPS have bilateral and symmetric nail changes, including absent or hypoplastic nails with ridging, splitting, or discoloration and triangular-shaped lunulae.^1,4 Nail findings are the most consistent findings of NPS, as they are present in more than 98% of patients.⁵ The thumb often is the most severely affected nail, with improvement appreciated on progression toward the fifth digit, as seen in our patient (Figure 1A).⁵ Each individual nail usually is more severely affected on its ulnar side. When toenails are involved, the abnormalities tend to be less severe, and the little toenail is most commonly affected. Distal digital changes also are observed in almost all patients. Loss of dorsal creases in the skin overlying the distal interphalangeal joints can be considered as a diagnostic clue.^3,4

There are a variety of orthopedic manifestations of NPS. Hypoplastic or absent patellae leading to recurrent subluxations or dislocations is a common finding.⁴ Bilateral symmetric bone formations (horns) arising from the iliac crest are pathognomonic but only found on radiography 70% of the time.⁶ Occasionally these protuberances can be palpated on physical examination,⁵ though this finding was not appreciated in our patient. Dysplasia of the elbows may result in limited elbow extension and limited pronation and supination. Early degenerative arthritis, lumbar lordosis, and scoliosis also are not uncommon. In addition, skeletal integrity is compromised, leading to early osteoporosis and increased risk for fractures.⁵

Nephropathy develops in approximately 30% to 40% of patients and is a major determinant of mortality in these patients.² Mutations in the LMX1B gene lead to abnormal development of podocytes and reduction in collagen in the glomerular basement membrane. The first sign of renal involvement usually is proteinuria, with or without microscopic hematuria. As in our patient, many patients develop hypertension. Patients may progress to develop nephrotic syndrome and end-stage renal failure (5%–10%).⁷ Death from NPS-related nephropathy has occurred, even in childhood.^4,5

Primary open-angle glaucoma has been recognized as a feature of NPS.⁸ It is the most frequent ocular abnormality observed, followed by ocular hypertension and Lester sign of the iris.^3,5 These conditions also are more common in younger patients with NPS than in the general population.⁵ Important neurologic findings include epilepsy, peripheral neuropathy, attention deficit disorder, major depressive disorder, and vasomotor problems.⁹

Our case highlights the importance of recognizing this rare condition to provide a multidisciplinary approach to care that addresses all aspects of LMX1B-associated disease in affected individuals. Nail findings may be the first clue to the need for additional screenings in these patients. Nail-patella syndrome patients should undergo thorough ophthalmologic examinations every 2 years, including measurement of intraocular pressure, examination of the optic disc, and assessment of visual fields. Given the variability in severity of joint problems and the unpredictable anatomy of the joints, magnetic resonance imaging of the joints is recommended prior to orthopedic intervention. Most importantly, physicians should recognize this genodermatosis to implement periodic screenings for renal disease, as up to 40% of NPS patients develop kidney failure. Annual blood pressure measurements, urinalysis, and measurement of the protein to creatinine ratio in the urine are recommended. For patients with end-stage renal failure, renal transplantation results in cure of nephropathy and may even result in nail regrowth.¹⁰ Further, this case is notable in that it describes a patient with NPS who is older than most other individuals presenting with the condition, thereby revealing novel information about NPS in its more advanced stages.